Alphaviruses, flaviviruses, measles viruses and rhabdoviruses are enveloped single-stranded RNA viruses, which have been engineered as expression vector systems for recombinant protein expression and vaccine development. Due to the presence of non-structural genes encoding the replicase complex, a 200,000-fold amplification of viral RNA occurs in the cytoplasm of infected cells providing extreme transgene expression levels, which is why they are named self-replicating RNA viruses. Expression of surface proteins of pathogens causing infectious disease and tumor antigens provide the basis for vaccine development against infectious diseases and cancer. The self-replicating RNA viral vectors can be administered as replicon RNA, recombinant viral particles, or layered DNA/RNA replicons. Self-replicating RNA viral vectors have been applied for vaccine development against influenza virus, HIV, hepatitis B virus, human papilloma virus, Ebola virus and recently coronaviruses, especially SARS-CoV-2 the causative agent of the COVID-19 pandemic. Measles virus and rhabdovirus vector-based SARS-CoV-2 vaccine candidates have been subjected to clinical trials. Moreover, RNA vaccine candidates based on self-amplifying alphaviruses have also been evaluated in clinical settings. Various cancers such as brain, breast, lung, ovarian, prostate cancer and melanoma have also been targeted for vaccine development. Robust immune responses and protection have been demonstrated in animal models. Clinical trials have shown good safety and target-specific immune responses. Ervebo, the VSV-based vaccine against Ebola virus disease has been approved for human use.

Breast Cancer (BC) is the second most common type of cancer worldwide and displays the highest cancer-related mortality among women worldwide. Targeted therapies have revolutionized the way BC has been treated in the last decades improving life expectancies of millions of women. Among the different molecular pathways that have been of interest for the development of targeted therapies are the Cyclin-Dependent Kinases (CDK). CDK inhibitors are a class of molecules that already exist in nature and those belonging to the INK4 protein family specifically inhibit the CDK4/6 proteins. CDK4/6 inhibitors specifically block the transition from the G1 to the S phase of the cell cycle by dephosphorylation of the retinoblastoma tumor suppressor protein. In the past four years CDK4/6 inhibitors palbociclib, ribociclib, and abemaciclib received their first FDA approval for the treatment of Hormone Receptor (HR)-positive and Human Epidermal growth factor Receptor 2 (HER2)-negative breast cancer after showing significant improvements in progression-free survival in the PALOMA-1, MONALEESA-2 and the MONARCH-2 randomized clinical trials, respectively. After the encouraging results from these clinical trials, CDK4/6 inhibitors have also been investigated in the other BC subtypes. In HER2-positive BC, combination of CDK4/6 inhibitors with HER2-targeted therapies showed promise in preclinical studies and their clinical evaluation is ongoing. Moreover, in triple-negative BC, CDK4/6 inhibitors efficacy has been investigated in combination with other targeted therapies or immunotherapies. This review summarizes the molecular background and clinical efficacy of CDK4/6 inhibitors as single agents or in combination with other targeted therapies for the treatment of BC. Future directions of ongoing clinical trials and predictive biomarkers will be further debated.

The consumption of sweet beverages, including sugar-sweetened beverages (SSB), artificially sweetened beverages (ASB) and fruit juices (FJ) is associated with the risk of different cardiometabolic diseases and probably with some tumors as well. We carried out a systematic review and meta-analysis of observational studies aimed at evaluating the association between sweet beverage intake and different types of cancer risk. Suitable papers published up to June 2020 were searched through PubMed, Web of Science and SCOPUS databases, using relevant keywords. Overall, 64 studies were identified for the systematic review, of which 27 were selected for the meta-analysis. This was performed by analyzing the multivariable-adjusted OR, RR or HR of the highest compared with the lowest sweet beverage intake categories. Random effects showed significant positive association between SSBs intake and breast (RR: 1.14, 95% CI: 1.01 – 1.30) and prostate cancer risk (RR: 1.18, 95% CI: 1.10 – 1.27), also between FJs and prostate cancer risk (RR: 1.03, 95% CI: 1.01 – 1.05). Associations between SSBs and colorectal and pancreatic cancer risk, FJs and breast, colorectal and pancreatic cancer risk, ASBs and pancreatic cancer risk tended to be positive but did not reach the statistically significant threshold. This study supports the recommendation to limit the consumption of SSBs and FJs for cancer prevention and proposes to further investigate the potential harmful role of ASBs intake in cancer risk.

1) Background: Studies indicate that caffeic acid (CA), caffeic acid phenethyl ester (CAPE) are compounds with potent chemopreventive effects. Breast cancer is a common cancer among women worldwide. The study shows comparison of caffeic acid and its ester activity in the cells of breast cancer line MDA-MB-231; 2) Methods: The cells of MDA-MB-231 were treated by CA and CAPE with doses from 10 to 100 µM in time 24 h and 48 h. Cytotoxicity MTT test, apoptosis by Annexin V and cell cycle with Dead Cell Assay were performed; 3) Results: The cytotoxic activity was greater for CAPE comparing to CA, in both incubation time (same dosage). IC50 values for CAPE were 27.84 (24h) and 15.83 (48h) and >10000 (24h) and >1000 (48h) for CA. Polyphenols induced apoptosis, higher apoptotic effect observed for CAPE (dose dependent). CAPE induced cell cycle arrest in S phase (time and dose dependent). Dose dependent decline G0/G1 phase (48h) and elimination of phase G2/M (100 µM of CAPE). For CA, only after 48 hours, small effect of cell cycle at phase S (however dose dependent), and slight decline of phase G0/G1 and G2/M only for highest doses (50 and 100 µM); 4) Conclusions: Comparing CA and CAPE activity, on the MDA-MB-231, we clearly see better activity of CAPE, with the same dosage and experiment time.

Results from the phase III Keynote-024 clinical trial have established Pembrolizumab monotherapy as the first-line standard of care for patients with metastatic NSCLC who have PD-L1 expression ≥ 50%, EGFR and ALK wild-type. However, given the differences between patients treated in routine clinical practice and within a clinical trial, real-world data are needed to confirm the treatment benefit in standard practice. Given the lack of data on large cohorts of patients with long follow-up, we designed a retrospective observational study of patients with NSCLC who were treated with Pembrolizumab, starting from its reimbursement eligibility until December 2020. The primary endpoints were to assess PFS and OS using the Kaplan-Meier method, treatment response and safety. We followed 880 patients (median follow-up: 35.1 months) until February 2022. Median PFS and OS were 8.6 months (95% CI: 7.6-10.0) and 25.5 months (95% CI: 21.8-31.6), respectively. We also found that ECOG PS, PD-L1 expression and smoking habit were prognostic factors for PFS, while age, sex, ECOG PS, smoking habit and histology had an impact on OS. Multivariable analysis confirms prognostic role of PD-L1 for PFS and ECOG for both PFS and OS. 39.9% of patients reported an adverse event, but only 6.3% of patients discontinued therapy due to toxicity. Our results suggest a long-term benefit of Pembrolizumab in the first-line setting as well as a safety profile consistent with the results of Keynote-042. Many collected variables appear to influence clinical outcome, but results from these exploratory unadjusted analyses should be interpreted with caution.

In Caucasians, basal cell carcinoma, a type of non-melanoma skin cancer, is most often found on the nose. This presents challenges for surgeons due to anatomical, functional, and aesthetic concerns. The study aimed to evaluate the distribution of tumor localization, size, morphological subtypes, surgical outcomes, radicality levels, and their correlation with recurrence rates. The research utilized data from the Hygiene Institute Health Information Centre. A retrospective analysis encompassed 343 cases of nasal skin cancer over a four-year period from January 1, 2019, to December 31, 2022. The research cohort comprised 252 female and 91 male participants, averaging 75,2 years old. Tumors were most found on the left sidewall of the nose (25.4%) and the dorsum (24.8%). The infiltrative morphological subtype was predominant (70.8%). Standard surgical excision with fasciocutaneous plastic was the preferred surgical procedure. Radical excision was achieved in 79.0% of lesions, while 16.9% were incompletely excised. Non-radically excised tumors exhibited a significantly higher recurrence rate (24.1%) compared to those with radical excision (6.3%). In nasal reconstruction, diverse surgical techniques are essential for precise adaptation based on factors like tumor characteristics and patient needs. Despite surgeons' careful adherence to excision guidelines, the potential for non-radical procedures cannot be entirely eliminated.

Background: Colorectal cancer (CRC) remains a leading cause of cancer-related morbidity and mortality in both sexes globally. This is not unconnected with the heterogeneity and plasticity of CRC stem cells (CRC-SCs) which stealthily exploit niche-related and (epi)genetic factors to facilitate metastasis, chemoresistance, tumor recurrence, and disease progression. Despite accumulating evidence of the role of dysregulated microRNAs in malignancies, the therapeutic efficacy of pharmacological-targeting of CRC-SC-associated microRNAs is relatively under-explored. Experimental approach: In this present study, we employed relatively new bioinformatics approaches, analyses of microarray data, western blot, RT-PCR, and functional assays to show that hsa-miR-324-5p expression is significantly suppressed in CRC cells, and inversely correlates with the aberrant expression of SOD2. Results: This converse hsa-miR-324-5p/SOD2 relationship is associated with enhanced oncogenicity, which is effectively inhibited by 4-AAQB as evidenced by inhibited cell viability and proliferation, as well as, attenuated migration, invasion and clonogenicity in 4-AAQB-treated DLD1 and HCT116 cells. We also showed that 4-AAQB-induced re-expression of hsa-miR-324-5p, akin to short-interfering RNA reduced SOD2 expression, correlates with the concurrent down-regulation of SOD2, N-cadherin, vimentin, c-Myc, and BcL-xL2, with concomitant up-regulation of E-cadherin and BAX2 proteins. Enhanced expression of hsa-miR-324-5p in the CRC cells suppressed their tumorigenicity in vitro and in vivo. Additionally, 4-AAQB synergistically potentiates FOLFOX anticancer effect by eliciting the re-expression of SOD2-suppressed hsa-miR-324 and inhibiting SOD2-mediated tumorigenicity. Conclusion: Our findings highlight the pre-clinical anti-CSC efficacy of 4-AAQB, with or without FOLFOX in CRC, and suggest a potential novel therapeutic strategy for CRC patients.

Background/Objectives: Head and neck free flap reconstructions are often required to treat tumors or extensive post-traumatic jaw defects. The facial artery is the standard receiving vessel for intraoral microvascular anastomoses. However, its use is associated with several disadvantages, such as lesions of buccal nerve branches or the parotid duct and variability in course and diameter. This study aims to investigate whether sublingual artery branches can be considered an alternative intraoral supply vessel to the facial artery to avoid these drawbacks. Methods: 12 formalin-fixed cadaveric heads with 24 sides were dissected. The sublingual artery's origin, course, branching pattern, and distribution were examined. In addition, the diameters of the branches of the sublingual artery were assessed to identify potential supply vessels for anastomoses. Results: In ten of the 24 cases (41.7 %), the sublingual artery originated from the lingual artery and nine cases (37.5 %) from the facial artery. The main trunk of the sublingual artery was present in the floor of the mouth in all cases (100 %) with a diameter of ≥ 0.9 mm in vitro (1 mm in vivo). In 15 of the 24 half heads (62.5 %), branches of the sublingual artery with ≥ 0.9 mm were identified in this space. Conclusions: The large diameter of the sublingual artery on the floor of the mandible suggests that this vessel or its branches could be considered alternative pedicles for intraoral anastomoses in mandibular microvascular free flap grafts.

The survival analysis of the Cancer Genome Atlas (TCGA) dataset is a well-known method to discover the gene expression-based prognostic biomarkers of head and neck squamous cell carcinoma (HNSCC). A cutoff point is usually used in survival analysis for the patients' dichotomization in the continuous gene expression. There is some optimization software for cutoff determination. However, the software's predetermined cutoffs are usually set at the median or quantiles of gene expression value to perform the analyses. There are also few clinicopathological features available on their pre-processed data sets. We applied an in-house workflow, including data retrieving and pre-processing, feature selection, sliding-window cutoff selection, Kaplan-Meier survival analysis, and Cox proportional hazard modeling for biomarker discovery. In our approach for the TCGA HNSCC cohort, we scanned human protein-coding genes to find optimal cutoff values. After adjustment with confounders, the clinical tumor stage and the surgical margin involvement are independent risk factors for patients' prognosis. According to the resulting tables with Bonferroni-adjusted P value under the optimal cutoff and the hazard ratio, three biomarker candidates, CAMK2N1, CALML5, and FCGBP, are significantly associated with the patients' overall survival. We validated this discovery by using the other independent HNSCC dataset (GSE65858). Thus, we suggest the transcriptomic analysis could help for biomarker discovery.

Management of multiple primary cancers, a not so infrequent event in oncology practice, is a critical issue due to the lack of literature . In this study, we reported the case of a patient with metachronous double metastatic non small cell lung cancer (NSCLC) and pancreatic ductal adenocarcinoma (PDAC) who received gefitinib in combination with gemcitabine plus nab-paclitaxel and with mFOLFOX6 in first and second line, respectively. She achieved a progression free survival and an overall survival (OS) of 28 months for NSCLC and PFS-1 and OS of 20 and 13 months, respectively for PDAC. Moreover, the combination of gefitinib and chemotherapies treatments displayed a good safety profile. Given the insignificant frequency of this case, we performed a molecular characterization of both neoplasms with the aim to investigate the existence of particular activated pathways and/or similar immunological mutations. it is interesting to note that two neoplasms shared a commune mutation of B7-H3 gene, with the consecutive impairment of its expressed protein. In both PDAC and NSCLC, the expression of this protein was associated with a worse survival. Since B7-H3 is an anti-apoptotic protein, the reduction of its expression or function should justify a pro-apoptotic activity with a putative justification of the long survival of the patient considered in this report.

Introduction. Self-sampling has the potential to increase cervical cancer screening (CCS) among women living with HIV (WLWH) in low and middle-income countries (LMICs). However, our understanding of how HPV self-collection studies have been conducted in WLWH is limited. The purpose of this scoping review was to examine the extent to which the HPV self-sampling has been applied among WLWH in LMICs. Method: We conducted multiple searches in several databases for articles published between 2000 and January 2022. With the combination of keywords relating to HPV self-sampling, LMICs, and WLWH, we retrieved over 9,000 articles. We used pre-defined inclusion and exclusion criteria to select relevant studies for this review. Once a study met the inclusion criteria, we created a table to extract each study’s characteristics and classified them under common themes. We used a qualitative descriptive approach to summarize the scoping results. Results: A total of 12 articles were included in the final review. Overall, 3,178 women were enrolled in those studies and 2,105 (66%) of them were WLWH. The self-sampling participation rate was 92.6%. The findings of our study show that 43% of the WLWH in 8 of the studies reviewed tested positive for high-risk HPV (hr-HPV) genotypes, indicating 4 out of 10 WLWH in the studies are at risk of cervical cancer. The prevalence of the hr-HPV in WLWH was 18% higher than that of HIV-negative women. Most women in the study found the self-sampling experience acceptable, easy to use, convenient, and comfortable. Self-sampling performance in detecting hr HPV genotypes is comparable to clinician-performed sampling. However, limited access (i.e., affordability, availability, transportation), limited knowledge about self-screening, doubts about the credibility of self-sampling results, and stigma remain barriers to wide acceptance and implementation of self-sampling. In conclusion, the findings of this review highlight that (a) cervical cancer is a threat to every sexually active woman but for WLWH the threat increases, (b) self-sampling laboratory performance is similar to clinician performed sampling, (c) self-sampling is associated with an increase in cervical cancer screening uptake and (d) WLWH reported a positive experience with self-sampling. However, personal, environmental, and structural barriers challenge the application of self-sampling in LMICs, and these need to be addressed. Keywords: keyword 1; keyword 2; keyword 3 (List three to ten pertinent keywords specific to the article yet reasonably common within the subject discipline.)

We aimed to directly compare the cost-effectiveness of the NELSON and NLST screening protocols, two trials influencing lung cancer screening implementation internationally. A decision-analytic model analyzing the cost-effectiveness of the NELSON protocols was manipulated to reflect the protocols of the NLST, while maintaining features specific to the Hungarian healthcare setting. In the NELSON protocol, there are three possible outcomes to the initial round of screening: positive, negative, or indeterminate, indicating an uncertain degree of suspicion for lung cancer. This pro-tocol differs from the NLST protocol, in which the only possible screening outcomes are positive or negative, with no indeterminate option. The NLST pathway for smokers aged 55-74 resulted in a 43 € increase in total average lifetime costs compared to the Hungarian screening pathway and re-sulted in a lifetime gain of 0.006 QALYs. The incremental costs and QALYs yield an ICER of 7875 €/QALY. Our results demonstrate that assigning any suspicious LDCT screen as a positive result (NLST protocol) rather than indeterminate (NELSON protocol) can yield a slight QALY gain that is worth the additional use of resources according to Hungary’s willingness to pay threshold. Our study provides insight on the cost-effectiveness, advantages, and disadvantages of various LDCT screening protocols for lung cancer and can assist other countries as they implement their screening programs.

Tumorigenesis is a complex and dynamic process involving cell-cell and cell-extracellular matrix (ECM) interactions that allow tumor cell growth, drug resistance and metastasis. This review provides an updated summary of the role played by the tumor microenvironment (TME) components and hypoxia in tumorigenesis and highlight various ways through which tumor cells reprogram normal cells including into phenotypes that are pro-tumorigenic including cancer associated- fibroblasts, -macrophages and -endothelial cells. Tumor cells secrete numerous factors leading to transformation of a previously anti-tumorigenic environment into a pro-tumorigenic environment. Once formed, solid tumors continue to interact with various stromal cells including local and infiltrating fibroblasts, macrophages, mesenchymal stem cells, endothelial cells, pericytes, and secreted factors and the ECM within the tumor microenvironment (TME). The TME is key to tumorigenesis, drug response and treatment outcome. Importantly, stromal cells and secreted factors can initially be anti-tumorigenic but over time promote tumorigenesis and induce therapy resistance. To counter hypoxia, increased angiogenesis leads to formation of new vascular networks in order to actively promote and sustain tumor growth via supply of oxygen and nutrients whilst removing metabolic waste. Angiogenic vascular network formation aid in tumor cell metastatic dissemination. Successful tumor treatment and novel drug development require the identification and therapeutic targeting of pro-tumorigenic components of the TME including cancer-associated- fibroblasts (CAFs) and -macrophages (CAMs), hypoxia, blocking ECM-receptor interactions, in addition to targeting of tumor cells. Re-programming of stromal cells and the immune response to be anti-tumorigenic is key to therapeutic success. Lastly, this review highlights potential TME- and hypoxia-centred therapies under investigations.

Intratumor heterogeneity (ITH) is associated with therapeutic resistance and poor prognosis in cancer patients, and attributed to genetic, epigenetic, and microenvironmental factors. We developed a new computational platform, GATHER, for geostatistical modeling of single cell RNA-seq data to synthesize high-resolution and continuous gene expression landscapes of a given tumor sample. Such landscapes allow GATHER to map the enriched regions of pathways of interest in the tumor space and identify genes that have spatial differential expressions at locations representing specific phenotypic contexts using measures based on optimal transport. GATHER provides new applications of spatial entropy measures for quantification and objective characterization of ITH. It includes new tools for insightful visualization of spatial transcriptomic phenomena. We illustrate the capabilities of GATHER using real data from breast cancer tumor to study hallmarks of cancer in the phenotypic contexts defined by cancer associated fibroblasts.

Ursolic and oleanolic acids are secondary plant metabolites that are known to be involved in the plant defence system against water loss and pathogens. Nowadays these triterpenoids are also regarded as potential pharmaceutical compounds and there is mounting experimental data that either purified compounds or triterpenoid-enriched plant extracts exert various beneficial effects, including anti-oxidative, anti-inflammatory and anticancer, on model systems of both human or animal origin. Some of those effects have been linked to the ability of ursolic and oleanolic acids to modulate intracellular antioxidant systems and also inflammation- and cell death-related pathways. Therefore, our aim was to review the current knowledge about the distribution of ursolic and oleanolic acids in plants, bioavailability and pharmacokinetic properties of these triterpenoids and their derivatives, and to discuss their neuromodulatory effects in vitro and in vivo.

Waddington’s epigenetic landscape, a famous metaphor in developmental biology, depicts how a stem cell progresses from an undifferentiated phenotype to a differentiated one. The concept of “landscape” in the context of dynamical system theory represents a high-dimensional cell state space, in which each cell phenotype is considered as an “attractor” that is determined by interactions among multiple variables (molecular players), and is buffered against environmental fluctuations. Further, biological noise is thought to play an important role during these cell-fate decisions and in fact controls transitions between different phenotypes. Here, we discuss these phenotypic transitions in cancer from a dynamical systems perspective and invoke the concept of “cancer attractors” – hidden stable states of the underlying regulatory network that are not occupied by normal cells. Using epithelial-to-mesenchymal transition (EMT), cancer stem-like properties, metabolic reprogramming and the emergence of drug/hormone resistance as examples, we illustrate how phenotypic plasticity in cancer cells enables them to acquire hybrid phenotypes (such as hybrid epithelial/mesenchymal and hybrid metabolic phenotypes) that tend to be more aggressive and notoriously resilient to drug/hormone treatment. Furthermore, we highlight multiple factors that may give rise to phenotypic plasticity in cancer cells, such as (a) multi-stability or oscillatory behaviors governed by underlying regulatory networks involved in cell-fate decisions in cancer cells, and (b) network rewiring due to conformational dynamics of intrinsically disordered proteins (IDPs) that are highly enriched in cancer cells. We conclude by discussing why a therapeutic approach that promotes ‘recanalization’, i.e. the exit from “cancer attractors” and re-entry into “normal attractors”, is more likely to succeed rather than a conventional approach that targets individual molecules/pathways.

Magnetic Fe3O4 nanoparticles (MNPs) functionalized with (3-aminopropylo)trietoksysilan (APTES) or N-carboxymethylchitosan (CMC) were proposed as nanocarriers of methotrexate (MTX) against ovarian cancer cell lines. The successful functionalization of the obtained nanostructures was confirmed by FT-IR spectroscopy. Nanoparticles were characterized by transmission electron spectroscopy (TEM) and dynamic light scattering (DLS) techniques. Their potential zeta, magnetization, and hyperthermic properties were also explored. MTX was conjugated with nanocarriers by ionic bonds or by amide bonds. For all three types of nanostructures, the drug release kinetics were examined at different pH and temperatures. The MTT assay showed no toxicity of MNPs[APTES] and MNPs[CMC]. Finally, the cytotoxicity of the nanostructures with MTX attached was measured towards the ovarian cancer cells model sensitivity and resistance to methotrexate in simplistic 2D and spheroid 3D conditions. The results of cytotoxicity tests of the tested nanostructures showed similar values for inhibiting the proliferation of ovarian cancer cells as methotrexate in its free form. Conjugating MTX with nanoparticles allows the drug to be directed to the target site using an external magnetic field, reducing overall toxicity. Combining this approach with hyperthermia could enhance the therapeutic effect in vivo compared to free MTX, though further research on advanced 3D models is needed.

The focus was on developing machine learning models to predict the IC50 values of the compound OTX015 using gene expression levels of cancer cell lines. Through regression-based machine learning models, particularly the SVM model, trained on pre-laboratory data, consistent and generalizable performance with low error scores was achieved. These models underwent enhancement via hyperparameter optimization and were tested on validation data. The results indicate the utility of machine learning in drug discovery processes and personalized medicine, offering rapid and cost-effective predictions of IC50 values. However, for enhanced reliability, further model development, data gathering, and evaluation with diverse compounds are recommended. In conclusion, this research demonstrates the potential of machine learning approaches to optimize experimental processes, reduce costs, and contribute to personalized treatments in healthcare by accurately predicting compound responses.

Aims. Bone metastases have an incidence of up to 75% in metastatic breast cancer, thanks to the evolution of imaging we can identify them in the oligometastatic phase. With the introduction of target therapies and increasingly effective conjugated antibodies, it is increasingly common to treat patients with radiotherapy although asymptomatic (if single or ≤5 bone lesions). Volumes and doses in this setting do not yet have a clear guidelines. In this study, the aim is to administer to the macroscopically evident disease an ablative dose that favors the local control of disease. Aim of this retrospective analysis is to evaluate the outcome of pts receiving SIB for treatment of bone metastases. Material and Methods. A retrospective analysis including mBC patients (pts) undergone RT on bone metastases was conducted for pts treated between January 2014 and January 2022. Primary endpoint was freedom from local progression (FFLP). Rate of disease progression after radiotherapy (DP-AR) and overall survival (OS) were secondary endpoints. Subgroup analysis (age, immunophenotype, line of therapy) were performed. Results. Among 954 mBC who underwent radiotherapy for metastases, 85 pts underwent SIB-IMRT with a boost on macroscopic lesion of 8-6 Gy in 5 fr. Mean follow up was 41 months (6-61.5 m). Nineteen pts had single bone metastase (22.4%), 20 pts were oligometastatic (23,5%), 46 pts were plurimetastatic (54,1%). FFLP was 17 months (95% CI 3.2-61.5 m). Only 6 pts (7%) had local relapse on SIB-IMRT site during follow up. DP-AR was 13,2 m (95% CI 3.1-56.9 m). OS was 82,7 m (95% CI 10.6-343 m). Local-relapse was not associated with age, immunophenotype or sistemic line ongoing. Among secondary outcomes, DP-AR resulted associated to immunophenotype (p 0.002). DP-AR and OS were not significantly associated with local relapse (respectively p 0.148 and p 0.4). Conclusions. Pts with breast tumor can be treated with SIB-IMRT on bone metastases with a 93% of local control at 17 months from radiotherapy. Further data are needed to individuate pts who can benefit of dose-escalation and also sinergic effect with systemic therapies to possibly increase DP-AR.

Driven by the importance of early detection for improving patient outcomes, this study investigates the effectiveness of various machine learning algorithms in predicting lung cancer based on clinical data. Lung cancer remains a significant global health concern, and this research seeks to contribute to advancements in early diagnosis through the application of machine learning techniques. The dataset consists of 385 training and 97 test samples, with a k-fold cross-validation approach (k=5) utilized to mitigate overfitting. Additionally, the ADASYN oversampling technique is employed to address class imbalance. Our analysis includes traditional algorithms such as Logistic Regression and Decision Trees, as well as ensemble methods like XGBoost, LGBM, and AdaBoost. Furthermore, we explore the effectiveness of deep learning models, particularly Deep Neural Networks (DNN). Results demonstrate promising accuracy rates across all models, with some outperforming others in terms of precision, recall, and F1-score. Our findings reveal that LGBM achieves the highest accuracy among all models, with an accuracy rate of 96.91%. It also exhibits superior performance in terms of precision, recall, and F1-score, particularly in classifying both positive and negative instances of lung cancer.

Hereditary cancer syndromes caused by germline mutations account for 5-10% of all cancers. The finding of a genetic mutation could have far-reaching consequences for pharmaceutical therapy, personalized prevention strategies, and cascade testing. According to the National Comprehensive Cancer Network’s (NCCN) and the Italian Association of Medical Oncology (AIOM) guidelines, unaffected family members should be tested only if the affected one is unavailable. This article explores whether germline genetic testing may be offered to high-risk families for hereditary cancer even if a living affected relative is missing. A retrospective study was carried out on 103 healthy subjects tested from 2017 to 2023. We enrolled all subjects with at least two first or second-degree relatives affected by breast, ovarian, pancreatic, gastric, prostate, or colorectal cancer. All subjects were tested by Next Generation Sequencing (NGS) multi-gene panel of 27 cancer-associated genes. In the study population, 5 (about 5%) pathogenic/likely pathogenic variants (PVs/LPVs) were found while 40 (42%) had a Variant of Uncertain Significance (VUS). This study highlights the importance of genetic testing for individuals with a strong family history of hereditary malignancies. This approach would allow women who tested positive to receive tailored treatment and prevention strategies based on their personal mutation status.

Breast cancer remains a major public health concern, and early detection can result in more treatment options, which are crucial for improving survival rates. Metabolomics offers the potential to develop blood-based screening and diagnostics tools that are less invasive and more cost-effective. However, the inherent complexity of metabolomic datasets makes identifying the most diagnostically relevant biomarkers a difficult task, with multiple studies demonstrating lim-ited agreement on the specific metabolites and pathways involved. This study aims to identify a set of biomarkers for early diagnosis of breast cancer using metabolomics data. Plasma samples from 185 breast cancer patients and 53 controls (CHTN) were analyzed. We utilized univariate Naïve Bayes, L2-regularized Support Vector Machines, and Principal Component Analysis (PCA), along with feature engineering techniques, to select the most informative features. Multiple ma-chine learning models, including Support Vector Machines, Multidimensional Scaling, Logistic Regression, and Ensemble Learning were utilized for classification. The best-performing feature set comprised 4 biomarkers and 2 demographic variables, achieving an accuracy of 98%, demon-strating the potential for a robust, cost-effective, non-invasive breast cancer screening and diagnostic tool.

In the last decade a group of Ca2+ channels called Piezo were discovered, demonstrating a decisive role in the cellular response to mechanical stimuli and being essential in the biological behaviour of cells regarding the extracellular compartment. Several investigations have suggested a potential role in carcinogenesis with a tumor supressor role in some cases, but increased expression in several high grade neoplasms. Regarding Piezo2 expression in mammary gland neoplasms, early results suggested a protective role of Piezo2, but posterior works resulted in a relationship between Piezo2 expression and the highly-aggressive triple negative phenotype of breast carcinoma. A cohort of 125 patients with clinical follow up was chosen to study Piezo2 expression and clarify its clinical implications, using the same immunohistochemical valuation performed for other breast carcinoma parameters. Fisher exact was chosen to identify potential relationships between the different variables. A significant association was found with the Ki67 proliferation index, but not with mitoses. The tendency of most proliferative tumors was to have a diminished score for Piezo2. A similar association was found between Piezo2 expression and perineurial invasion.

Introduction: Lung cancer remains a global health concern, with non-small cell lung cancer (NSCLC) comprising the majority of cases. Early detection of lung cancer has led to an increased number of cases identified in the earlier stages of NSCLC. This required the revaluation of the NSCLC treatment approaches for early-stage NSCLC. Methods: We conducted a comprehensive search using multiple databases to identify relevant studies on treatment modalities for early-stage NSCLC. Inclusion criteria prioritized but were not limited to, clinical trials and meta-analyses on surgical approaches to early-stage NSCLC conducted from 2021 onwards. Discussion: Minimally invasive approaches, such as VATS and RATS, along with lung resection techniques, including sublobar resection have emerged as treatments for early-stage NSCLC. Ground-glass opacities (GGOs) hve shown prognostic significance, especially when analyzing the consolidation-tumor ratio (CTR). There have also been updates on managing GGOs, including the non-surgical approaches, the extent of lung resection indicated, and the level of lymphadenectomy required. Conclusion: The management of early-stage NSCLC requires further assessment of treatment strategies. This includes understanding the required extent of surgical resection, interpreting the significance of GGOs (specifically GGOs with a high CTR), and evaluating the efficacy of alternative therapies. Customized treatment involving surgical and non-surgical interventions is essential for advancing patient care.

Despite significant advances in tumor biology and clinical therapeutics, metastasis remains the primary cause of cancer-related deaths. While RNA-seq technology has been used extensively to study metastatic cancer characteristics, challenges persist in acquiring adequate transcriptomic data. To overcome this challenge, we propose MetGen, a generative contrastive learning based on deep learning model. MetGen generates synthetic metastatic cancer expression profiles using primary cancer and normal tissue expression data. Our results demonstrate that MetGen generates comparable samples to actual metastatic cancer samples, and we discuss the learning mechanism of MetGen. Additionally, we demonstrate MetGen's interpretability using metastatic prostate cancer and metastatic breast cancer. MetGen has learned highly relevant signatures in cancer, tissue, and tumor microenvironment, such as immune response and the metastasis process, which potentially fosters a more comprehensive understanding of metastatic cancer biology. The development of MetGen represents a significant step toward the study of metastatic cancer biology by providing a generative model that identifies candidate therapeutic targets for the treatment of metastatic cancer.

Introduction Total pelvic exenteration (TPE) is a highly complex surgery associated with a high morbidity rate of 40% in reference units. It is performed for advanced or recurrences tumors in the pelvis with infiltration of multiple organs. Sometimes TPE is indicated in situations of palliation due to the side effects of radiotherapy or tumor progression. The aim of our study is to evaluate a single center experience in TPEs using a minimally invasive approach (LTPE) and compare the perioperative outcomes with the open technique (OTPE). Material and methods A prospective study of the TPE carried out in our unit between 2013-2023 was used. All anterior and posterior exenterations were discarded. Perioperative outcomes were evaluated. Results A total of 19 TPEs were analyzed, 9 LTPEs and 10 OTPEs. Most tumors originated from the colon and cervix. Hyperthermic intraperitoneal chemotherapy (HIPEC) was applied in one case of LTPE and intraoperative radiotherapy (IORT) in one case of OTPE. Cases with palliative intent were one in each group. Surgery time was 407 minutes for LTPE and 367 min for OPTE (p=0.38). Length of hospital stay was longer in the OPTE group at 21.6 days vs LTPE with 10.1 days, (p=0.23). The R0 rate excluding palliative cases was 88.9% for LTPE vs. 70% for OPTE (p=0.33). Major morbidity (grade III) was 45% in the LTPE group with no mortality and 40% (grade III/IV) in the OPTE group with one patient dying on admission. Survival was similar in both groups. Conclusion LTPE is a feasible and safe approach with similar perioperative outcomes and a trend toward shorter hospital stay.

In 2022, the new WHO Classification of Endocrine and Neuroendocrine Tumors, Fifth Edition (beta version) (WHO 5th) was published. The importance of understanding the molecular genetics of thyroid tumors as revealed by large-scale genomic analyses such as The Cancer Genome Atlas (TCGA). Consequently, the WHO 5th was fundamentally revised, resulting in a systematic classification based on tumor cell-of-origin and clinical risk. This paper outlines following critical points of the WHO 5th. 1. Genetic mutations in follicular cell-derived neoplasms (FDN) highlight the role of mutations in the MAP kinase pathway, including RET, RAS, and BRAF, as drivers of carcinogenesis. Differentiated thyroid cancers such as follicular thyroid carcinoma (FTC) and papillary thyroid carcinoma (PTC) have specific genetic alterations that correlate with morphological classifications: RAS-like tumors (RLTs) and BRAF p.V600E-like tumors (BLTs), respectively. 2. The Framework for benign lesions have revised. The WHO 5th introduces new categories such as "developmental abnormalities" and "thyroid follicular nodular disease" in benign FDN. 3. Low-Risk Tumors include NIFTP, TT-UMP, and HTT. 4. PTC histological variants are reclassified as "subtypes" in the WHO 5th. 5. The concept of high-grade carcinomas is introduced, encompassing poorly differentiated thyroid carcinoma (PDTC), differentiated high-grade thyroid carcinoma (DHGTC), and high-grade medullary thyroid carcinoma (MTC). 6. Squamous cell carcinoma is included in anaplastic thyroid carcinoma (ATC) in the WHO 5th due to shared genetic and prognostic features. 7. Hürthle cell adenoma/carcinoma is renamed oncocytic thyroid adenoma/carcinoma. 8. Other miscellaneous tumors are classified into salivary gland-type carcinomas of the thyroid, thyroid tumours of uncertain histogenesis, thymic tumours within the thyroid, and embryonal thyroid neoplasms. The WHO 5th thus emphasizes the importance of classifying tumors based on genetic abnormalities together with histomorphology, aiding in accurate pathological diagnosis and treatment selection, including molecular-targeted therapies.

Tumor infiltrating lymphocytes (TILs) are an emerging biomarker predictive of response to immunotherapy across a spectrum of solid organ malignancies. The characterization of TILs in gastric cancer (GC) treated with contemporary, multiagent neoadjuvant chemotherapy (NAC) is understudied. In this retrospective investigation, we analyzed the degree of infiltration, phenotype, and spatial distribution of TILs via immunohistochemistry within resected GC specimens treated with or without NAC at a Western center. We hypothesized that NAC executes immunostimulatory roles evidenced by an increased number of anti-tumor TILs in the tumor microenvironment. We found significantly elevated levels of conventional and memory CD8+ T cells, and total TILs (CD4+, CD8+, Treg, B cells) within chemotherapy-treated tumors compared to chemotherapy-naïve specimens. We also revealed important associations between survival and pathologic response with enhanced TIL infiltration. Taken together, our findings advocate for an immunostimulatory role of chemotherpy and underscore the potential synergistic effect of combining chemotherapy with immunotherapy in resectable gastric cancer.

TNF-related apoptosis-inducing ligand (TRAIL or Apo2 or TNFSF10) belongs to the TNF superfamily. When bound to its agonistic receptors, TRAIL can induce apoptosis in tumour cells, while sparing healthy cells. This tumour selectivity prompted, over the last three decades, many studies aiming at evaluating the anti-tumoral potential of TRAIL or its derivatives. Although most of these attempts have failed, so far, novel formulations are still being evaluated. Yet, emerging evidence indicates that TRAIL can also trigger, on the other hand, a non-canonical signal transduction pathway that is likely to be detrimental for its use in oncology. Likewise, increasing studies suggest that TRAIL can induce, through Death receptor 5 (DR5) in some circumstances, tumour cell motility, potentially leading to and contributing to tumour metastasis. While the pro-apoptotic signal transduction machinery of TRAIL is well known from a mechanistic point of view, that of the non-canonical pathway is less understood. We are reviewing here the current state of knowledge of TRAIL non-canonical signalling.

With the breakthroughs and innovative developments in nanotechnology, research on the application of nanomedicine in cancer therapy has so far seen tremendous expansion and success. Intelligent stimulus-responsive nanocarriers are an emerging field of research and have great interest in cancer therapy owing to the fascinating properties such as excellent targeting function, high drug loading capacity, and targeted on-demand release properties. Responsive nanomaterials can be designed and constructed according to the dosing context and therapeutic needs, at the same time, activated by internal bio-stimuli (pH, redox, and enzymes) and/or external stimuli (ultrasound, light, temperature, and magnetic), respectively. What’s more, smart nanocarriers are also utilized for the precise and controllable release of antitumor drugs from cancer tissues and cells to achieve efficient diagnosis and treatment of tumors. Deeply investigated, responsive nanocarriers have attracted considerable attention due to their ability to release precisely at tumor-specific sites. Herein, we review the recent advances of novel stimuli-responsive nanocarriers in the field of cancer therapy. Finally, the challenges and application prospects of smart nanocarriers are further elaborately discussed.

The receptor Tyrosine Kinase (RTK) pathway and the downstream related Mitogen Activated Protein Kinase (MAPK) cascades are crucial signal transduction pathways that preside over various cellular processes, including proliferation, differentiation, apoptosis, and responses to stressors. They are well described in solid malignancies, where many of the involved factors are used as prognostic molecular markers or targets for precision therapy. Germ cell tumors (GCTs) are relatively rare. However, they are the most diagnosed malignancies occurring in the testis (TGCT) among men aged between 15 and 40 years. Despite high aneuploidy and a paucity of somatic mutations, several genomic and transcriptomic assays have identified few significantly mutated somatic genes, primarily KIT and K-RAS, so affecting, at various levels, the KIT–RAS–RAF–MEK–ERK cascade. This review focuses on the most recent investigations about this signaling pathway in TGCTs concerning their development, natural history, response to standard chemotherapy protocols (i.e., cisplatin-based), and on the efforts being made to identify targetable markers for possible precision medicine approaches.

Pancreatic Ductal Adenocarcinoma (PDAC) is the most frequent infiltrating type of pancreatic cancer. The poor prognosis is due to the absence of specific biomarkers, aggressiveness and treatment resistance. PDAC is a deadly malignancy bearing distinct genetic alterations, the most common being those that cause cancer-causing versions of the KRAS gene. Cannabigerol (CBG) is a non-psychomimetic cannabinoid with anti-inflammatory property. Regarding CBG anticancer ef-fect, up to now there are only few evidence in human cancers. We investigated CBG effects on PDAC cell lines, PANC-1 and MIAPaCa-2. It was investigated CBG activity on cell viability, cell death and its effect of EGFR-RAS-associated signalling. Moreover, the potential synergistic effect of CBG in combination with gemcitabine (GEM) and paclitaxel (PTX) was investigated. MTT was applied to investigate CBG effect on PDAC cell lines viability. Annexin-V and Acridine Orange staining followed by cytofluorimetric analysis and Western blot were used to evaluate CBG effect on cell death. Modulation of EGFR-RAS-associated pathways was determined by Western Blot analysis and Milliplex multiplex assay. Moreover, by MTT data and Synergy finder software analysis the effect of the combination of CBG and chemotherapeutic drugs, was determined.

The persistent threat of cancer remains a significant hurdle for global health, prompting the exploration of innovative approaches in the quest for successful therapeutic interventions. Cyclin-dependent kinase 9 (CDK9), a central player in transcription regulation and cell cycle progression, has emerged as a promising target to combat cancer. Its pivotal role in oncogenic pathways and the pressing need for novel cancer treatments has propelled CDK9 into the spotlight of drug discovery efforts. This article presents a comprehensive study that connects a multidisciplinary approach, combining computational methodologies, experimental validation, and the transformative PROTAC (Proteolysis-Targeting Chimera) technology. By uniting these diverse techniques, we aim to identify, characterize, and optimize a new class of degraders targeting CDK9. We explore these compounds for kinase inhibitory properties and potential to induce targeted protein degradation, offering a novel and potentially more sustainable approach to cancer therapy. This cohesive strategy expresses the interface between computational predictions and experimental insights, with the ultimate goal of advancing the development of effective anticancer therapeutics targeting CDK9.

Cervical cancer remains a major public health problem. Despite the screening programs, cervical cancer is the second most commonly diagnosed cancer. Most of the cases occur in less developed countries, and it is the third leading cause of cancer death among females. In 2000–2007, the five-year relative survival rate for European women diagnosed with cervical cancer was 62%.[1] Standard treatment for locally advanced cervical cancer reveals external beam radiotherapy (EBRT) with concurrent chemotherapy followed by image-guided adaptive brachytherapy (IGABT) boost [2, 3]. In the last years, the Gynaecological (GYN) working group composed of Group Européen de Curiethérapie-European Society for Therapeutic Radiology and Oncology (GEC-ESTRO) has developed new recommendations for the treatment of cervical cancer based on IGABT. The treatment plan includes 3-dimensional (3D) imaging based on magnetic resonance imaging (MRI) or computed tomography (CT), adaptive to the target volume and organ at risk [4–6]. The brachytherapy insertion is made under anaesthesia. At the time of the application insertion, the ultrasound is used to guide the dilatation of the uterine canal and assess the depth of the uterine cavity. In this paper, we review the data available in international literature about the use of ultrasound (US) in brachytherapy treatment of cervical cancer.

ATP-binding cassette (ABC) transporters, acting as cellular "pumps," facilitate solutes translocation through membranes via ATP hydrolysis. Their overexpression is closely tied to multidrug resistance (MDR), a major obstacle in chemotherapy and neurological disorder treatment, hampering drug accumulation and delivery. Extensive research has delved into the intricate interplay between ABC transporter structure, function, and potential inhibition for MDR reversal. Cryo-electron microscopy has been instrumental in unveiling structural details of various MDR-causing ABC transporters, encompassing ABCB1, ABCC1, ABCG2, as well as recently revealed ABCC3 and ABCC4 structures. The newly obtained structural insight has deepened our understanding of substrate and drug binding, translocation mechanisms, and inhibitor interactions. Given the growing body of structural information available for human MDR transporters and their associated mechanisms, we believe it is timely to compile a comprehensive review of these transporters and compare their functional mechanisms in the context of multidrug resistance. Therefore, this review primarily focuses on the structural aspects of clinically significant human ABC transporters linked to MDR, with the aim of providing valuable insights to enhance the effectiveness of MDR reversal strategies in clinical therapies.

This study aimed to investigate the impact of the establishment of a nursing practice for micropigmentation of the nipple-areola complex at the San Cecilio University Hospital in Granada on women who have undergone unilateral or bilateral mastectomies. Micropigmentation is a procedure for decorating the human body by implanting pigments and dyes at the sub-epidermal level for a temporary duration of several months or years. Methodology: Retrospective descriptive study conducted in the micropigmentation clinic of HUSC-Granada (Spain). The sample consisted of 167 patients: 24 declined the treatment, 3 had second thoughts and cancelled the appointment, and 135 were accepted. Results: The mean age of the women was 53 years (range:35–75 years). Of the patients, 64.1% came from San Cecilio University Hospital in Granada, the rest from Virgen de las Nieves Hospital in Granada (19.6 %), hospitals in the province of Almería (7.2 %), and private hospitals and clinics (9.2 %). In the last two years, 36.4 % of the women had undergone surgery in the last 2 years. Complications arising from this technique are almost nonexistent. Conclusions: A very high number of women accepted the technique, with the highest proportion being those under 48 years of age. It is a technique that has not presented complications; therefore, it would be interesting to study how the application of the technique would affect women's self-esteem and quality of life

The purpose of this study was to identify subgroups of quality of life (QOL) changes in breast cancer survivors (BCS) and to determine factors associated with subgroups of consistently low or deteriorated QOL. We enrolled 101 women recently diagnosed with breast cancer in South Korea and asked them to complete a questionnaire at baseline (within 1 month of diagnosis), 1 year later (Year 1), 2 years later (Year 2), and 3 years later (Year 3). We assessed QOL using the global QOL subscale from the EORTC QLQ-C30. We defined low QOL as a global QOL score 10 points below the mean score of the general population. Based on low QOL as defined in this study, we identified subgroups of QOL changes over 3 years. We identified four subgroups of QOL changes: improved (47.4%), stable (30%), continuously low (8.8%), and deteriorated (13.8%) and considered the last two categories (22.6%) as poor QOL. Logistic regression analyses demonstrated that significant determinants of poor QOL were insomnia at Year 1, fatigue and anxiety at Year 2, and fatigue, depression, and comorbidity at Year 3. In conclusion, persistent symptoms of insomnia, fatigue, anxiety, depression, and comorbidity are potential risk factors for poor QOL in BCS.

In this paper, we introduce an innovative approach to distinguish Gliosarcoma (GSM) from Glioblastoma (GBM). Our method combines causal fuzzy logic rules with the Big Bird architecture, a Transformer-based Deep Learning algorithm. Unlike prior research, which often relied on statistical models to reduce dataset dimensions before causal analysis, our approach harnesses the complete dataset in tandem with our causal fuzzy Big Bird architecture. Additionally, we benchmark our results not only against previous Gliosarcoma/Glioblastoma studies but also against GPT-2 for a comprehensive evaluation.

In this study, we aimed to identify blood lymphocytes as a prognostic factor for survival in patients with locally advanced stage III non-small cell lung cancer (NSCLC) treated with concurrent chemoradiotherapy (CCRT). We conducted a secondary analysis of 196 patients enrolled in the Korean Radiation Oncology Group 0903 phase III clinical trial to evaluate the prognostic significance of circulating blood lymphocyte levels. The median total lymphocyte count (TLC) reduction ratio during CCRT was 0.74 (range: 0.29 – 0.97). In multivariate analysis, patient age (p = 0.014) and gross tumor volume (GTV, p = 0.031) were significant factors associated with overall survival, while TLC reduction (p = 0.018) and pretreatment neutrophil-to-lymphocyte ratio (NLR; p = 0.010) were associated with progression-free survival (PFS). In multivariate logistic regression analysis, pretreatment NLR, GTV, and heart V20 were significantly associated with TLC reduction. TLC reduction during CCRT is a significant prognostic factor for PFS, and heart V20 is significantly associated with TLC reduction. Thus, constraining the volume of the radiation dose to the whole heart must be prioritized to reduce TLC.

Understanding the molecular basis of cancer initiation and progression is critical to develop effective treatment strategies. Recently, mutations in genes encoding histone proteins have been identified that drive oncogenesis, converting these essential proteins into “oncohistones”. Understanding how oncohistone mutations, which are commonly missense mutations, subvert the normal function of histones to drive oncogenesis requires defining the functional consequences of such changes. Histones genes are present in multiple copies in the human genome with 15 genes encoding histone H3 isoforms, the histone for which the majority of oncohistone variants have been analyzed thus far. With so many histone genes, engineering human cell lines that assess changes induced by sole expression of the oncohistone variant is technically challenging. In contrast to humans, budding and fission yeast contain only two or three histone H3 genes, respectively. Furthermore, yeast histones share ~90% sequence identity with human H3 protein. The genetic simplicity and evolutionary conservation make yeast an excellent model for characterizing oncohistones. The power of genetic approaches can also be exploited in yeast models to define cellular signaling pathways that could serve as actionable therapeutic targets. In this review, we focus on the value of yeast models to serve as a discovery tool that can inform subsequent translational studies in humans.

CXCL14 is one of the most evolutionarily conserved members of the chemokine family and is constitutionally expressed in multiple organs, suggesting that it is involved in the homeostasis maintenance of the system. CXCL14 is highly expressed in colon epithelial cells and shows obvious gene silencing in clinical colon cancer samples, suggesting that its silencing is related to the immune escape of cancer cells. In this paper, we analyzed the expression profiles of multiple human clinical colon cancer datasets and mouse colon cancer models to reveal the variation trend of CXCL14 expression during colitis, colon polyps, primary colon cancer, and liver metastases. The relationship between CXCL14 gene silencing and promoter hypermethylation was revealed through the colorectal carcinoma methylation database. The results suggest that CXCL14 is a tumor suppressor gene in colorectal carcinoma, which is activated first and then silenced during the process of tumor occurrence and deterioration. Promoter hypermethylation is the main cause of CXCL14 silencing. The methylation level of CXCL14 is correlated with the anatomic site of tumor occurrence and positively correlated with patient age, and associated with prognosis. Reversing the hypermethylation of CXCL14 may be an epigenetic therapy for colon cancer.

Background: to assess the benefit of a deep inspiration breath hold (DIBH) over standard irradiation technique, and eventually to identify anatomical and/or treatment preplanning characteristics correlated with LAD dose. Methods: We retrospectively identified patients with left-sided breast cancer who underwent whole breast radiotherapy in DIBH. All patients had both plans in DIBH and free-breathing (FB). Receiving operating characteristics (ROC analysis) were performed to define the cut-off point of parameters to predict LAD maximum dose >10 Gy and LAD mean dose > 4 Gy. Areas under the curve (AUCs) were calculated for all variables. Post-test probability has been calculated to evaluate advantage for parameters combination. Results: One hundred ninety-seven patients were identified. LAD dose was significantly reduced in DIBH plans with maximum and mean dose reduced by 31.7% (mean value 3.5 Gy vs 4.8 Gy, p=<0.001) and 28.1% (mean value 8.2 Gy vs 12.8 Gy, p=<0.001) in DIBH plans compared to FB plans. The strongest predictor of LAD maximum dose > 10 Gy and a LAD mean dose > 4 Gy was the minimum distance of LAD from tangent open fields. Other parameters were lung volume and heart volume for LAD Dmax > 10 Gy and lung volume, heart volume and breast separation for LAD Dmean > 4 Gy. Conclusion: The dosimetric benefit of DIBH is valid for all patients and DIBH should be preferred for all left sided patients.

Breast cancer is the most common cancer in women. Cardiovascular diseases are common complications after chemotherapy due to the effect of the drug on lipid levels. This study aimed to explore the changes in lipid profiles in patients with breast cancer under chemotherapy. Methods: In this prospective study, 50 patients with breast cancer participated. Three biochemical-lipid hematological tests were performed: total cholesterol (TC), triglycerides (TG), High-Density Lipoprotein (HDL-C), and Low-Density Lipoprotein (LDL-C) before initiation (pre-chemotherapy), at the start (1st follow-up), and at the completion (2nd follow-up) of the first cycle of chemotherapy. Statistical significance was set at p&lt;0.05. Analyses were conducted using SPSS Statistical Software (version 22.0). Results: Mean TC values increased significantly at 2nd follow-up. TG values decreased significantly from 1st to 2nd follow-up. HDL-C was significantly lower at 1st follow-up compared to pre-chemotherapy and 2nd follow-up reaching similar to the initial levels. LDL-C values were significantly higher at 2nd follow-up compared to pre-chemotherapy measurement. Significantly positive correlations of BMI with pre-chemotherapy LDL-C, 1st follow-up TC, 1st follow-up LDL-C, 2nd follow-up TC, and 2nd follow-up LDL-C were found. Conclusions: There is a statistically significant increase in the levels of TC and LDL-C in breast cancer patients during chemotherapy. This study was not registered.

EGFR tyrosine kinase inhibitors (TKIs) are the preferred initial treatment for non-small cell lung cancer (NSCLC) patients harboring EGFR mutations. However, remission is transient, and no further effective treatment options are available for EGFR-TKI-advanced EGFR-mutant NSCLCs. Immunotherapy with immune checkpoint inhibitors (ICIs) induces sustained cancer remission in a subset of NSCLCs. However, ICI therapy exhibits limited activity in most EGFR-mutant NSCLCs. Mechanistically, the strong oncogenic EGFR signaling in EGFR-mutant NSCLCs contributes to the non-inflamed tumor immune microenvironment (TIME), characterized by a limited number of CD8+ T cell infiltration, a high number of regulatory CD4+ T cells and a high number of inactivated infiltrated T cells. Besides, EGFR-mutant NSCLC patients are generally non-smokers with low levels of PD-L1 expression and tumor mutation burden. However, current understanding only partially explains why a small population of EGFR-mutant NSCLCs durably respond to ICI therapy, resulting in many researchers actively working in this field. This review reviews the hope seen from pre-clinical studies and clinical trials which may be adopted to improve the outcome of ICI therapy in EGFR-mutant NSCLCs. Besides, the underlying mechanisms leading to the inferior clinical outcome of ICI therapy in EGFR-mutant NSCLCs are discussed.

The MET proto-oncogene encodes a pivotal tyrosine kinase receptor, binding the hepatocyte growth factor (HGF, also known as scatter factor, SF) and governing essential biological processes such as organogenesis, tissue repair, and angiogenesis. The pleiotropic physiological functions of MET explain its diverse role in cancer progression in a broad range of tumors; genetic/epigenetic alterations of MET drive tumor cell dissemination, metastasis, and acquired resistance to conventional and targeted therapies. Therefore, targeting MET emerged as a promising strategy, and many efforts were devoted to identifying the optimal way of hampering MET signaling. Despite encouraging results, however, the complexity of MET's functions in oncogenesis yields intriguing observations, fostering a humbler stance on our comprehension. This review explores recent discoveries concerning MET alterations in cancer, elucidating their biological repercussions, discussing therapeutic avenues, and outlining future directions. By contextualizing the research question and articulating the study's purpose, this work navigates MET biology's intricacies in cancer, offering a comprehensive perspective.

Breast cancer (BC) is the second leading cause of death in the United States in women. 1 in 8 women in their lifetime has a risk of developing breast cancer. With advances in omics technology, more data is available for diagnosis, treatment, and prognosis. The help of Machine Learning algorithms, a subdomain of Artificial Intelligence, would allow for a better clinical support tool. Machine Learning could be the key to answering a complex problem in BC. The methodology of this research question involves collecting and finding data such as RNA-Seq datasets, selecting and training appropriate machine learning algorithms, and evaluating the performance of the algorithms in predicting BC prognosis. Also, the study explores and tries to identify the most relevant genes and pathways through feature selection extraction and dimensionality reduction techniques. After applying feature extraction, the top 10 genes were extracted using the Univariate Feature Selection (UFS) method, precisely the SelectKBest technique. After employing different machine learning algorithms, such as Networks, Random Forest, Linear SVM, Logistic Regression, and Quadratic Discriminant Analysis (QDA), we found QDA was the best model in classifying the RNA-seq dataset with a 96% accuracy rate and 94% ROC AUC. This study suggests that AK2 and CD68 have a positive correlation with each other, and it could potentially be a biomarker and therapeutic target for BC.

Background: Pancreatic cancer (PC) is a disease with poor prognosis and survival rate. There is a pertinent need to identify the risk factors of this disease. The purpose of this study is to identify a subset of factors (a.k.a. features) as predictors of PC from the Prostate, Lung, Colorectal and Ovarian (PLCO) cancer dataset consisting of responses to 65 questions about demographics, cancer and health history, medication usage, and smoking habits from 154,897 participants. Method: There are two challenges to selecting the subset of features that predict PC with highest probability: the problem is computationally intractable, and the PLCO dataset is highly imbalanced. We use an innovative method to use the dataset in a balanced way, without involving up- or down-sampling. We use nine feature selection methods to select the optimal subset of features from the preprocessed and balanced dataset. Results: Our preprocessed dataset consists of 32 risk factors (8 demographics, 5 cancer history, 13 health history, 2 medication usage, 4 smoking habits). Risk factors belonging to cancer and health history, followed by smoking habits, were consistently chosen by the feature selection methods. We also discuss findings in the medical sciences literature that corroborate our findings. Conclusions: The study found that risk factors belonging to cancer and health history are the most prominent ones for PC. In particular, previously diagnosed with PC is chosen as the most prominent risk factor by majority of methods. While most of our findings are consistent with the literature, some of our findings shed light on novel factors that may not have received their due attention by the research community.

Neuroendocrine prostate cancer (NEPC) is a highly aggressive subtype of prostate cancer (PC) that commonly emerges through a transdifferentiation process from prostate adenocarcinoma and evades conventional therapies. Extensive molecular research has revealed factors that drive lineage plasticity, uncovering novel therapeutic targets to be explored. A diverse array of targeting agents is currently under evaluation in pre-clinical and clinical studies with promising results in suppressing or reversing the neuroendocrine phenotype and inhibiting tumor growth and metastasis. This new knowledge has the potential to contribute to development of novel therapeutic approaches that may enhance clinical management and prognosis of this lethal disease.

The role of upfront primary tumor resection (PTR) in patients with unresectable metastatic col-orectal cancer (CRC) without severe symptoms remains controversial. We retrospectively ana-lyzed the role of PTR in overall survival (OS) in different subgroups. Among 331 patients diag-nosed with synchronous metastatic CRC between 2010 and 2020, 223 were analyzed. The PTR group (n = 42) showed better performance (p = 0.038); higher frequencies of right-sided origin (p = 0.014), T4 stage (p = 0.005), M1a stage (p = 0.015), and <2 organ metastases (p = 0.002); and re-ceived fewer targeted agents (p < 0.001) than the chemotherapy group (n = 181). The PTR group showed longer OS (20.5 versus 14.0 months, p = 0.016), but PTR was marginally related to OS in multivariate analysis (p = 0.060). Male sex (p = 0.022), good performance status (p = 0.07), left-sided tumor (p = 0.069), low serum carcinoembryonic antigen level (p = 0.092), T3 stage (p = 0.029), M1a stage (p = 0.025), <2 organ metastases (p = 0.017), and administration of targeted agents, especially bevacizumab (p = 0.024), were related to survival benefit after PTR. Upfront PTR should be considered when selecting patients with favorable prognoses for bevacizumab administration.

Emerging evidence indicates that intracellular calcium (Ca2+) levels and their regulatory proteins play essential roles in normal stem cell proliferation and differentiation. Cancer stem-like cells (CSCs) are subpopulations of cancer cells that retain characteristics similar to stem cells and play an essential role in cancer progression. Recent studies have reported that the Orai3 calcium channel plays an oncogenic role in human cancer. However, its role in CSC remains underexplored. In this study, we explored the effects of Orai3 in the progression and stemness of oral/oropharyngeal squamous cell carcinoma (OSCC). Orai3 expression was increased in a stepwise manner during the progression of OSCC. In addition, Orai3 was highly enriched in CSC populations of OSCC. Ectopic Orai3 expression in non-tumorigenic immortalized oral epithelial cells increased intracellular Ca2+ levels, acquiring malignant growth and CSC properties. Conversely, silencing of endogenous Orai3 in OSCC cells suppressed CSC phenotype, indicating a pivotal role of Orai3 in CSC regulation. Moreover, Orai3 markedly increased the expression of inhibitor of DNA binding 1 (ID1), a stemness transcription factor. Orai3 and ID1 were highly expressed in CSCs compared to non-CSCs, implying the functional importance of the Orai3/ID1 axis in CSC regulation. Furthermore, suppression of ID1 abrogated CSC phenotype in the cell with ectopic Orai3 overexpression and OSCC. Our study reveals that Orai3 is a novel functional CSC regulator in OSCC and further suggests that Orai3 plays an oncogenic role in OSCC by promoting cancer stemness via ID1 upregulation.

Prostate cancer is a common cancer among men and typically progresses slowly for several decades before becoming aggressive and spreading to other organs, leaving few treatment options. While large animals have been studied, the dog's prostate is anatomically similar to humans and has been used to study spontaneous prostate cancer. However, most research currently focuses on the mouse as a model organism due to the ability to genetically modify their prostatic tissues for molecular analysis. One hallmark in this research was the identification of the prostate-specific promoter Probasin, allowing for prostate-specific expression of transgenes. This has led to generations of mice with aggressive prostatic tumors through overexpression of the SV40 oncogene. The Probasin promoter is also used to drive Cre expression and allow researcher to generated prostate specific loss-of-function studies. Another landmark in the process of modeling prostate cancer in mice was orthoptic delivery of viral particles. This technology allows selective overexpression of oncogenes from lentivirus or the use of CRISPR to generate complex loss of function studies. These genetic modified models are complemented by classical xenografts of human prostate tumor cells in immune deficient mice. Overall, pre-clinical models have provided a portfolio of model systems to study and address complex mechanisms in prostate cancer for improved treatment options. This review will focus on the advances of each technique.

Prostate cancer is the most common cancer among men in Poland. A significant proportion of prostate cancers can be cured, providing longer survival. Patients have the opportunity to undergo minimally invasive treatment methods like brachytherapy, while maintaining their previous quality of life. The disease itself, as well as treatment complications, primarily affect the functioning of the urinary and digestive systems and impact the sexual sphere. Aim: This study aims to assess the quality of life of patients after prostate brachytherapy. Methods: The research was conducted at the Lower Silesian Oncology Centre in Wroclaw. The study included fifty men aged between 51 and 85 years. The following questionnaires were used: EORTC QLQ-C30, QLQ-PR25. Scales: Katz, Mini-MAC, PSS-10. Moreover, the study used a self-designed survey covering socio-demographical factors. Results: Prostate brachytherapy has a significant impact on the degree of sexual dysfunction. Compared to sexually inactive individuals, sexually active individuals exhibit fewer negative psychological symptoms. Choosing a destructive coping strategy intensifies the occurrence of symptoms, lowers patients' level of independence, and negatively affects their quality of life. Conclusions: Brachytherapy contributes to worsening sexual function and temporarily affects urinary system function, which may lower the overall quality of life in patients.

Background: Music therapy (MT) is a non-pharmacological treatment increasingly used to reduce stress and anxiety in hospitalized children affected by cancers. The aim of this study was to eval-uate the impact of MT on quality of life of children with cancer. Methods: We have conducted a quasi-experimental study between April 1 and August 31, 2021 at Bechir Hamza children's Hos-pital in Tunis, including children treated for cancer. The child or the parent completed PedsQL Module Cancer french version 3.0 questionnaires before and after four weekly music therapy ses-sions. Child's respiratory and heart rate were measured before and after each session. Results: We included 20 children whose mean age was 7 ± 4.5 years [2-14]. The median value of the total questionnaire score increased from 57 [46; 70] to 72 [67; 85] (p < 10-3) with a significant reduction in pain (p = 0.02), nausea (p = 0.009), anxiety related to medical procedures (p = 0.009) and worry about the future (p = 0.005). We highlighted a significant decrease in respiratory and heart rate after MT (p<0,05). Conclusions: MT has positive impact of on quality of life of children with cancer.

Enzalutamide is a drug used to treat PC. Docetaxel is a drug for chemotherapy for different cancers including prostate cancer (PC). The effectiveness of these drugs in treating castration-resistant prostate cancer (CRPC) is not consistent and thus, CRPC is still an incurable disease. Recent evidence showed that the bio-inhibitor of FABP5, dmrFABP5, suppressed the tumorigenicity and metastasis of the CRPC cells. In this work, we studied the possible synergic effect of dmrFABP5 combined with either Enzalutamide or Docetaxel on suppressing tumorigenicity of the PC cells. A highly significant synergic effect was observed when dmrFABP5 was used in combination with Enzalutamide on the androgen-responsive PC cells 22RV1. A highly significant synergic effect was also observed when dmrFABP5 was combined with Docetaxel on 22RV1 cells and on the highly malignant, androgen-receptor (AR)-negative DU145 cells. These combined applications exhibited a highly significant inhibitory action on the viability, migration, invasion and colony formation abilities of both 22RV1and DU145 cells. However, dmrFABP5 did not produce any suppression effect when used on FABP5-negative cell line LNCaP, although Enzalutamide can significantly suppress LNCaP cells as a single agent. Further investigations suggested that these synergistic effects were produced by interrupting the FABP5-related signal transduction pathway in PC cells.

Background The nematode Caenorhabditis elegans (C. elegans) possesses a sophisticated sense of smell and is used for a novel cancer screening test that utilizes the chemotaxis index. We designed a single-institution, prospective study to confirm the ability of Nematode Nose (N-NOSE) to determine preoperative chemotherapy's efficacy for esophageal cancer patients. Patients and Methods We investigated the predictability of N-NOSE screening for the clinical effects of preoperative chemotherapy for esophageal cancer patients receiving radical surgery. The index reduction score (IRS) was calculated by chemotaxis of C. elegans at three points: before treatment, before surgery, and after surgery, and its clinical relevance was examined. Result Thirty-nine patients with esophageal cancer were enrolled from August 2020 to December 2021 and 30 patients receiving radical surgery were examined. Complete response or partial response was achieved in 23 cases (76.7%). When the target of the treatment effect was complete response only, the prediction accuracies of the IRS calculated by area under the curve was 0.85 (95% Confidence interval: 0.62-1) in clinically achieving complete response group, and the sensitivity and specificity were 1 and 0.63, respectively. Conclusion Index reduction score using N-NOSE screening may reflect the efficacy of chemotherapy for esophageal cancer patients. A large-scale prospective study at multiple centers is desired in the future.

Colorectal cancer (CRC) is one of the most common types of cancer worldwide. The KRAS mutation is present in 30-50% of CRC patients. This mutation confers resistance to treatment with anti-EGFR therapy. This article aims at proving that Computer Tomography (CT)-based Radiomics can predict the KRAS mutation in CRC patients. The piece is a retrospective study with 56 CRC patients from the Hospital of Santiago de Compostela, Spain. All patients had a confirmatory pathological analysis of the KRAS status. Radiomics features were obtained from the abdominal contrast enhancement CT (CECT), before applying any treatments. We used several classifiers, including adaboost, neural network, decision tree, support vector machine and random forest, to predict the presence or absence of KRAS mutation. The most reliable prediction was achieved using the adaboost ensemble on clinical patient data, with a kappa and accuracy of 53.7% and 76.8%, respectively. The sensitivity and specific were of 73.3% and 80.8%. Using texture descriptors, the best accuracy and kappa were 73.2% and 46%, respectively, with sensitivity and specificity of 76.7% and 69.2%, showing also a correlation between texture patterns on CT images and KRAS mutation. Radiomics could help manage CRC patients, and in the future, it could have a crucial role in diagnosing CRC patients ahead of invasive methods.

Current nutritional guidelines for stomach cancer survivors (SCS) mainly focus on the influence of surgical resection of the stomach, with limited guidance regarding a wider range of food options. We aimed to investigate the factors associated with healthier dietary changes in Korean adult SCS. This cross-sectional study assessed dietary pattern change after cancer treatment for 11 food categories, using a self-administered questionnaire. A ‘healthier dietary change’ was operationally defined as reduced consumption of red and processed meat, grains, salt, and burnt food, and increased consumption of poultry, fish, vegetables, fruits, legumes, and dairy products. Among a total of 624 SCS, approximately 60% of participants reported healthier directional dietary changes in three or more food categories, while 9.1% reported no changes. There was no significant difference in dietary habit changes between surgery types. Multivariable adjusted analysis showed that elderly and long-term survivors were inversely associated with a healthier dietary change. SCS with higher educational achievement and income were more likely to make healthier changes in their intake of processed meat, vegetables, fruits, burnt food, or salt. SCS with higher levels of fear of cancer recurrence, anxiety, or depression were more likely to follow healthier dietary changes for fish, meat, fruits, grains, or burnt food. Change in dietary pattern varied across different food items and was associated with various characteristics of SCS. It is crucial to repeatedly provide SCS with information about healthier dietary patterns, considering their sociodemographic, clinical, and psychological characteristics.

Venoms are a rich source of bioactive compounds, and among them is leberagin-C (Leb-C), a disintegrin-like protein derived from the venom Macrovipera lebetina transmediterrannea snakes. Leb-C has shown promising inhibitory effects on platelet aggregation. Previous studies have demonstrated that this SECD protein specifically targets α5β1, αvβ3 and αvβ6 integrins through a mimic mechanism of RGD disintegrins. In our current study, we focused on exploring the potential effects of Leb-C on metastatic breast cancer. Our findings revealed that Leb-C disrupted the adhesion, migration, and invasion capabilities of MDA-MB-231 breast cancer cells and its highly metastatic D3H2LN sub-population. Additionally, we observed significant suppression of adhesion, migration, and invasion of Human Umbilical Vein Endothelial Cells (HUVECs). Furthermore, Leb-C demonstrated a strong inhibitory effect on fibroblast growth factor 2-induced proliferation of HUVEC. We conducted in vivo experiments using nude mice and found that treatment with 2 µM of Leb-C resulted in a remarkable 73% reduction in D3H2LN xenograft tumor size. Additionally, quantification of intratumor microvessels revealed a 50 % reduction in tumor angiogenesis in xenograft after 21 days of twice-weekly treatment with 2 µM of Leb-C. Collectively, these findings suggest the potential utility of this dinsintegrin-like protein for inhibiting aggressive and resistant metastatic breast cancer.

Immune checkpoint inhibitors (ICIs) are a class of drug that produces durable and sustained anti-tumour responses in a wide variety of malignancies. The exponential rise in their use has been mirrored by a rise in immune-related adverse events (irAEs). Knowledge of such toxicities, as well as effective management algorithms for these toxicities, is essential to optimize clinical efficacy and safety. Currently, the guidelines for management of the irAEs are based largely on retrospective studies and case series. In this article, we review the current landscape of clinical trials investigating the management of irAEs with an aim to develop standardized, randomized controlled trial-based management algorithms for ICI-related toxicities.

Our recent studies showed that the treatment of human ovarian tumor cells with NCX4040 resulted in significant depletions of cellular glutathione, formation of reactive oxygen/nitrogen species and cell death. NCX4040 is also cytotoxic to several human colorectal cancer cells (CRC) in vitro and in vivo. Here, we have examined ferroptosis-dependent mechanism(s) of cytotoxicity of NCX4040 in HT-29 and K-RAS mutant HCT116 colon cell lines. Ferroptosis is characterized by accumulation of reactive oxygen species (ROS) within the cell, leading to an iron-dependent oxidative stress-mediated cell death. However, its relevance in the mechanism of NCX4040 cytotoxicity in CRC is not known. We found that NCX4040 generated ROS in CRC cells without any depletion of cellular GSH. Combinations of NCX4040 with erastin (ER) or RSL3 (RAS-selective lethal 3), known inducers of ferroptosis, enhanced CRC death. In contrast, ferrostatin-1, an inhibitor of ferroptosis, significantly inhibited NCX404-induced cell death. Treatment of CRC cells with NCX4040 resulted in induction of lipid peroxidation in a dose- and time-dependent manner. NCX4040 treatment induced several genes related to ferroptosis (e.g., CHAC1, GPX4 and NOX4) in both cell lines. Metabolomic studies also indicated significant increases in both lipid and energy metabolism following the drug treatment in HT-29 and HCT116 cells. These observations strongly suggest that NCX4040 causes ferroptosis-mediated cell death of CRC cells. Furthermore, combinations of NCX4040 and ER or RSL3 may contribute significantly for the treatment of CRC, including those that are difficult to treat due to the presence of Ras mutation in the clinic. NCX4040 induced ferroptosis may also be a dynamic form of cell death for the treatment of other cancers.

Energy is needed by cancer cells to stay alive and communicate with their surroundings. The primary organelles for cellular metabolism and energy synthesis are mitochondria. Researchers recently proved that cancer cells can steal immune cells' mitochondria using nanoscale tubes. This finding demonstrates the dependence of cancer cells on normal cells for their living and function. It also denotes the importance of mitochondria in cancer cells’ biology. Emerging evidence has demonstrated how mitochondria are essential for cancer cells to survive in the harsh tumor microenvironment, evade the immune system, obtain more aggressive features, and resist treatments. For instance, functional mitochondria can improve cancer resistance against radiotherapy by scavenging the released reactive oxygen species. Therefore, targeting mitochondria can potentially enhance oncological outcomes, according to this notion. The patients' reactions to radiation are varied, ranging from a complete response to even cancer progression during treatment. This concept illustrates how different levels of mitochondrial metabolism might contribute to this heterogeneity. Considering this notion can help to improve personalized oncological treatments. This article outlines the importance of mitochondrial metabolism in cancer biology and personalized treatments.

Background: Currently, many detection methods have high sensitivity to the diagnosis of lung cancer. However, some postoperative patients with pulmonary nodule were eventually diagnosed as benign nodules. The ideal evaluation of an individual with a pulmonary nodule would expedite therapy for a malignant nodule and minimize testing for those with a benign nodule.Methods: This case-control study is designed to explore the relationship between ACE1 rs4646994 polymorphism and the risk of lung cancer in patients with pulmonary nodules, 400 individuals with lung cancer and benign pulmonary nodules were included. A DNA extraction kit was used to extract plasm DNA from peripheral blood. The relationship between ACE1 rs4646994 and the risk of lung cancer in patients with pulmonary nodules was determined by chi-square test, logistic regression analysis and cross analysis. Results: The results showed that the DD genotype of ACE1 rs4646994 may increase the risk of lung cancer in patients with pulmonary nodules, and this correlation was more significant in the female subgroup. In the age stratification analysis, it was found that the risk of lung cancer was significantly increased in the DD genotype of ACE1 rs4646994 in the older subgroup (&gt; 45 years). In addition, the possibility of EGFR mutation in lung adenocarcinoma patients with ACE1 rs4646994 DD genotype was lower than that of II or ID genotype carriers. Conclusions: Our study indicated that ACE1 rs4646994 polymorphism increases the risk of lung cancer in patients with pulmonary nodules from China.

Growing evidence indicates the involvement of a genetic component for CaP susceptibility and clinical severity. Somatic mutations of TP53 have been associated with 50% of diverse human cancers. Studies have also reported the role of germ line mutations and single nucleotide poly-morphisms (SNPs) of TP53 as possible risk factors for cancer development. In this single De-partment of Defense institutional retrospective study, we identified common SNPs in the TP53 gene in AA and CA men and performed association analyses for functional TP53 SNPs with clinico-pathological features of CaP. The CPDR Oncoarray database on blood derived genomic DNA from 321 men treated by radical prostatectomy at WRNMMC were used to examine clini-co-pathological associations with TP53 SNPs. The SNP genotyping analysis on the final cohort of 308 patients (212 AA; 95 CA) identified 74 SNPs in the TP53 gene region with a minor allele fre-quency (MAF) of at least 1%. Two SNPs were non-synonymous in the exonic region of TP53: rs1800371 (Pro47Ser) and rs1042522 (Arg72Pro). The Pro47Ser variant, had a minor allele frequency of 0.01 in AA, however, was not detected in CA. Arg72Pro was the most common SNP with a minor allele frequency of 0.50 (0.41 in AA; 0.68 in CA). Additionally, Arg72Pro was associated with time to biochemical recurrence (BCR) after statistical adjustment for patient age at diagnosis, self-reported race, and Gleason score (p= 0.046; HR = 1.52). The present study demonstrated ancestral differences in allele frequencies of TP53 Arg72Pro and Pro47Ser SNPs in AA and CA CaP, providing a valuable framework for the interrogating CaP disparity among AA and CA men.

The tumor microenvironment (TME) plays a critical role in cancer progression and treatment outcomes. Despite advances in cancer research, many therapeutic strategies have failed to provide the desired clinical outcomes. In this integrated review, aimed to explore the role of TME in cancer biology and develop novel therapeutic strategies that target not only cancer cells but also the surrounding microenvironment. Study conducted a comprehensive literature search using PubMed, Embase, and Web of Science databases for articles published between 2016 and 2022. Inclusion of articles that discussed the impact of TME on cancer development and progression, as well as articles that proposed novel therapeutic strategies targeting the TME. The analysis of the literature revealed that the TME plays a crucial role in cancer development and progression by promoting cancer cell survival, angiogenesis, invasion, and metastasis, and by interfering with the efficacy of cancer therapies. The TME is composed of a complex network of non-cancerous cells, extracellular matrix components, and signaling molecules that interact with cancer cells. Several novel therapeutic strategies have been proposed based on the modulation of TME components. One of the most promising approaches is the use of immunotherapy, which aims to enhance the immune system's ability to recognize and attack cancer cells. Immunotherapy drugs such as checkpoint inhibitors, chimeric antigen receptor (CAR) T cells, and immune-stimulatory monoclonal antibodies have been approved for the treatment of different cancer types. These approaches have shown promising results in preclinical studies and clinical trials. The TME plays a critical role in cancer development and progression, and targeting its components represents a promising avenue for cancer therapy. Novel therapeutic strategies such as immunotherapy, extracellular matrix-targeting drugs, and nanoparticle-based therapies have shown promising results in preclinical studies and clinical trials. However, further research is needed to identify the most effective strategies and to overcome the challenges associated with TME targeting.

Hexokinases (HKs) convert hexose sugars to hexose-6-phosphate, thus trapping them inside cells to meet the synthetic and energetic demands. HKs participate in various standard and altered physiological processes, including cancer, primarily through the reprogramming of cellular metabolism. Four canonical HKs have been identified with different expression patterns across tissues. HKs 1-3 play a role in glucose utilization, whereas HK 4 (glucokinase, GCK) also acts as a glucose sensor. Recently, a novel 5^th HK, hexokinase domain containing 1 (HKDC1), has been identified, which plays a role in whole-body glucose utilization and insulin sensitivity. Beyond the metabolic functions, HKDC1 is differentially expressed in many forms of human cancer. This review focuses on the role of HKs, particularly HKDC1, in metabolic reprogramming and cancer progression.

In this study was found that these cancers were attributable to risk factors such as cigarette smoking, second-hand smoke, alcohol intake, excess body weight, diet, and six cancer-associated infections. Several databases were reviewed including PUBMED, Google scholar, and Web of Science. The facts suggest that a number of individuals present risk factors for cancer, which can be modifiable.

This study utilised an ensemble of pre-trained networks and digital mammograms to develop a supplementary diagnostic tool for radiologists. Digital mammograms and their associated information were collected from the department of radiology and pathology, Hospital Universiti Sains Malaysia. Thirteen pre-trained networks were selected and explored in this study. ResNet101V2 and ResNet152 had the highest mean PR-AUC, MobileNetV3Small and ResNet152 had the highest mean precision, ResNet101 had the highest mean F1 score, and ResNet152 and ResNet152V2 had the highest mean Youden J index. Subsequently, three ensemble models were developed using the top three pre-trained networks based on PR-AUC, precision, and F1 score. The final ensemble model had a mean precision, F1 score, and Youden J index of 0.82, 0.68, and 0.12, respectively. Additionally, the final model demonstrated a balanced performance across mammographic density. In conclusion, this study exhibited the good performance of the ensemble transfer learning on digital mammograms for the purpose of breast cancer risk estimation. This model can be utilised as a supplementary diagnostic tool for radiologists, thus, reducing their workloads.

Prostate cancer (PCa) is one of the most prevalent cancers among men in India. Although studies on PCa have dealt with the genetics, genomics, and the environmental influence in causality of PCa, not many studies employing the next generation sequencing (NGS) approaches of PCa have been carried out. In our previous study, we have identified some causal genes and mutations specific to Indian PCa using Whole-Exome Sequencing (WES). In the recent past, with the help of different cancer consortiums such as The Cancer Genome Atlas (TCGA), International Cancer Genome Consortium (ICGC), along with differentially expressed genes (DEGs), many cancer-associated novel non-coding RNAs have been identified as biomarkers. In this work, we attempt to identify DEGs as well as long non-coding RNAs (lncRNAs) associated with signature pathways from an Indian PCa cohort using RNA-sequencing (RNA-seq) approach. From a cohort of 60, we screened 6 patients who underwent prostatectomy; we performed a whole transcriptome shotgun sequencing (WTSS)/RNA-sequencing to decipher the DEGs. We further normalized the read counts using fragments per kilobase of transcript per million mapped reads (FPKM) and analyzed the DEGs using a cohort of downstream regulatory tools, viz. GeneMANIA Stringdb, Cytoscape-Cytohubba, cbioportal to map the inherent signatures associated with PCa. By comparing the RNA-seq data obtained from the pairs of normal and PCa tissue samples using our benchmarked in-house cuffdiff pipeline, we observed some important genes specific to PCa such as STEAP2, APP, PMEPA1, PABPC1, NFE2L2, HN1L and some other important genes known to be involved in different cancer pathways such as, COL6A1, DOK5, STX6, BCAS1, BACE1, BACE2, LMOD1, SNX9, CTNND1 etc. We also identified a few novel lncRNAs such as LINC01440, SOX2OT, ENSG00000232855, and ENST00000647843.1 that need to be characterized further. Deregulation of SOX2OT is observed in various tumors, including lung cancer, gastric cancer, esophageal cancer, breast cancer, hepatocellular carcinoma, ovarian cancer, pancreatic, laryngeal squamous cell carcinoma, osteosarcoma, nasopharyngeal carcinoma, and glioblastoma. It would be interesting to characterize its function in PCa as well. In comparison with publicly available datasets, we have identified characteristic DEGs and novel lncRNAs implicated in signature PCa pathways in an Indian PCa cohort which have perhaps not been reported. As a pilot study, this has set a precedent for us to validate further experimentally, and we firmly believe this will pave a way towards discovery of biomarkers and development of novel therapies.

Human cancers comprise an heterogeneous array of diseases with different progression patterns and responses to therapy. However, they all develop within a host context that constraints their natural history. As it occurs with the diversity of organisms, one can conjecture that there is order in the cancer multiverse. Is there a way to capture the broad range of tumor types within a space of the possible? Here we define the oncospace, a coordinate system that integrates the ecological, evolutionary and developmental components of cancer complexity. The spatial position of a tumor results from its departure from the healthy tissue along these three axes, and progression trajectories inform about the components driving malignancy across cancer subtypes. We postulate that the oncospace topology encodes new information regarding tumorigenic pathways, subtype prognosis and therapeutic opportunities: treatment design could benefit from considering how to nudge tumors towards empty evolutionary deserts in the oncospace.

In September 2021, the European Chemicals Agency evaluated a dossier for restricting polycyclic aromatic hydrocarbons (PAHs) in infant diapers and concluded that risks were not demonstrat-ed because of inconclusive exposure data. To fill this gap, we measured the 16 priority PAHs of the U.S. Environmental Protection Agency in the diaper core of four brands and in the sheets and fastening tapes of six brands of commercially available diapers. Health risks were conservatively assessed by assuming that dermally absorbed PAHs can cause both local (skin cancer) and sys-temic critical effects (neurobehavioral changes). Total concentrations of PAHs in diaper core and top sheet, the only significant contributors to skin exposure, averaged 34.5 μg/kg and 66.8 μg/kg, respectively. Excess skin cancer risks and hazard quotients for neurobehavioral effects calculated with the daily dose of total PAHs from combined diaper core and top sheet averaged 1.4 x 10-7 and 1.19 x 10-2, respectively. The median daily dose of total PAHs and of its ben-zo[a]pyrene-equivalent from breast milk estimated worldwide are 171 and 30 times greater than that from combined diaper core and top sheet, respectively. Altogether these findings indicate that trace levels of PAHs found in infant diapers are unlikely to pose health risks.

Cannabidiol (CBD) is an active diterpenoid compound that is extracted from the leaves and stem of Cannabis sativa. Previous studies show that CBD is a non-psychotropic compound with significant anti-cancer effects. This study determines its cytotoxic effect on oral cancer cells and OECM1 cells and compares the outcomes with a chemotherapeutic drug, cisplatin. This study determines the effect of CBD on the viability, apoptosis, morphology and migration of OECM1 cells. Electric cell-substrate impedance sensing (ECIS) is used to measure the change in cell impedance for cells that are treated with a series concentration of CBD for 24 hours. AlamarBlue and annexin V/7-AAD staining assays show that CBD has a cytotoxic effect on cell viability and induces cell apoptosis. ECIS analysis shows that CBD decreases the overall resistance and morphological parameters at 4 kHz in a concentration-dependent manner. There is a significant reduction in the wound-healing recovery rate for cells that are treated with 30 μM CBD. This study demonstrates that ECIS can be used for in vitro screening of anticancer drugs and is more sensitive, functional and comprehensive than traditional biochemical assays. CBD also increases cytotoxicity on cell survival and the migration of oral cancer cells, so it may be a therapeutic drug for oral cancer

Zinc (Zn) is a trace element crucial for oxidative stress, apoptosis, the immune response, and more globally for various processes involved in cellular homeostasis. In some cancers, Zn homeostasis is dysregulated. In this review, the role of Zn in cancer and all the components associated to Zn, the use of Zn and Zn -related proteins as biomarkers and Zn-based strategies for the treatment of tumors will be described. ZIP and ZnT are proteins related to Zn metabolism in normal conditions. In cancer, the level of expression of Zn related proteins is abnormal. These Zn proteins may act as prognostic or diagnostic biomarkers, and may be helpful for detecting early-stage cancers or monitoring the course of the disease. Additionally, Zn and its pathways may also be targeted to treat cancers. Indeed, the use of metals for binding Zn cations allows to regulate the biodistribution of Zn within cells, and will control several downstream signaling pathways. Zinc may also be directly used as a therapeutic substance to improve the prognosis of cancer patients, especially with the supplementation of zinc or the use of Zn oxide nanoparticles.

The recent approval of 177Lu PSMA-617 (Pluvicto®) by the United States Food and Drug Administration (FDA) is the culmination of decades of work in advancing the field of targeted radionuclide therapy for metastatic prostate cancer. 177Lu PSMA-617, along with the bone specific radiotherapeutic agent, 223RaCl2, are now commonly used in routine clinical care as a tertiary line of therapy for men with metastatic castrate resistant prostate cancer and for osseus metastatic disease respectively. While these radiopharmaceuticals are changing how metastatic prostate cancer is classified and treated, there is relatively little guidance to the practitioner and patient as to how best utilize these therapies, especially in conjunction with other more well-established regimens including hormonal, immunologic, and chemotherapeutic agents. This review article will go into detail about the mechanism and effectiveness of these radiopharmaceuticals and less well known classes of targeted radionuclide radiopharmaceuticals including alpha emitting prostate specific membrane antigen (PSMA) -, gastrin-releasing peptide receptor (GRPR) -, and somatostatin targeted radionuclide therapeutics. Additionally, a thorough discussion of the clinical approach of these agents is included and required futures studies.

In the post-PARP inhibitor era, potential changes in tumor biology after maintenance therapy have not been well investigated in recurrent ovarian cancer. We reported a case with alterations in the clinical and histological features of multiple relapsed disease associated with PARP inhibitor maintenance therapy. The patient with high-grade serous carcinoma exhibited BRCA wildtype and homologous recombination proficiency status, and suffered from three recurrences and surgeries accordingly. Olaparib maintenance had been used during the second-line therapy. We compared the differences in clinics and pathology among three recurrences and relapsed lesions. Disease-free survivals were dramatically decreased after the exposure to olaparib. At exploration of quaternary cytoreduction, the relapsed tumor was characterized by a carcinomatosis-like metastasis pattern and an easy tendency of bleeding. Tumor cytopathological changes and alterations were observed in both the tumoral and non-tumoral stroma, among relapsed tumor tissues derived from secondary, tertiary and quaternary cytoreduction. Histopathology indicated hemorrhage, necrosis, atypical tumor cells, massive angiogenesis, and decreased CD8+ tumor-infiltrating lymphocytes, particularly in the third relapsed disease. To our knowledge, this is the first report to show a unique metastatic pattern of angiogenic burst after PARP inhibitor maintenance therapy in ovarian cancer, which seemed to trigger invasive tumor growth and immune suppression. Further prospective studies and translational research focusing cytoreductive surgery after PARP inhibitor could progressively lead to an understanding of the biological behavior and metastatic patterns.

The purpose of this review is to summarize current knowledge on lymph node dissection (LND) in prostate cancer (PCa) patients undergoing radical prostatectomy (RP). Despite a growing body of evidence, utility, therapeutic and prognostic value of such approach as well as optimal extent of LND, remain unsolved issues. Although LND is the most accurate staging procedure, the direct therapeutic effect is still not evident from the current literature which limits the possibility of establishing clear recommendations. This indicates the need for further robust and adequately designed high quality clinical trials.

Liquid biopsy via isolation of circulating tumour cells (CTCs) represents a promising diagnostic tool capable of supplementing state-of-the-art for prostate cancer (PC) prognosis. Unfortunately, most of CTC technologies, such as AdnaTest or Cellsearch, critically rely on the Epithelial-Cell-Adhesion-Molecule (EpCAM) marker, limiting the possibility of detecting stem-like cells (CSCs) and mesenchymal-like cells (EMT-CTCs) that are present during PC progression. In this tontext, dielectrophoresis (DEP) is an epCAM independent, label-free, enrichment system, separating rare cells simply on the basis of their specific electrical properties. As compared to other technollgies, DEP represents a superior technique in terms of running costs, cells yield and specificity, but due to its higher complexity, requires still further technical as well as clinical development. Interestingly, DEP can be improved by the use of microfluid, nanostructured materials and fluoroimaging in order to increase its potential applications. In the context of PC, the utility of DEP can be translated in its capacity to detect CTC in the bloodstream in their epithelial, mesenchymal, or epithelial-mesenchymal phenotypes, which should be taken into account when choosing CTC enrichment and analysis methods for PC prognosis and early diagnosis.

Background: Risk of metastatic recurrence of breast cancer after initial diagnosis and treatment depends on the presence of a number of risk factors. Although most univariate risk factors have been identified using classical methods, machine-learning methods are also being conducted to tease out non-obvious contributors to a patient’s individual risk of developing late distant metastasis. Bayesian-network algorithms may predict not only risk factors but also interactions among these risks, which consequently lead to metastatic breast cancer. We proposed to apply a previously developed machine-learning method to predict risk factors of 5-, 10- and 15-year metastasis. Methods: We applied a previously validated algorithm named the Markov Blanket and Interactive risk factor Learner (MBIL) on the electronic health record (EHR)-based Lynn Sage database (LSDB) from the Lynn Sage Comprehensive Breast Cancer at Northwestern Memorial Hospital. This algorithm provided an output of both single and interactive risk factors of 5-, 10-, and 15-year metastasis from LSDB. We individually examined and interpreted the clinical relevance of these interactions based on years to metastasis and the reliance on interactivity between risk factors. Results: We found that with lower alpha values (low interactivity score), the prevalence of variables with an independent influence on long term metastasis was higher (i.e., HER2, TNEG). As the value of alpha increased to 480, stronger interactions were needed to define clusters of factors that increased the risk of metastasis (i.e., ER, smoking, race, alcohol usage). Conclusion: MBIL identified single and interacting risk factors of metastatic breast cancer, many of which were supported by clinical evidence. These results strongly recommend the development of further large data studies with different databases to validate the degree to which some of these variables impact metastatic breast cancer in the long term.

Being the predominant cause of disability, neurological diseases have received much attention from the global health community. Over a billion people suffer from one of the following neurological disorders: dementia, epilepsy, stroke, migraine, meningitis, Alzheimer's disease, Parkinson’s disease, multiple sclerosis, amyotrophic lateral sclerosis, Huntington’s disease, prion dis-ease, or brain tumors. Diagnosis and treatment options are limited for many of these diseases. Aptamers, being small and non-immunogenic nucleic acid molecules that are easy to chemically modify, offer potential diagnostic and theranostic applications to meet these needs. This review covers pioneer studies to apply aptamers, which show promise for future diagnostics and treatments of neurological disorders that pose increasingly dire worldwide health challenges.

Pancreatic cancer (PC) is one of the most lethal forms of cancers with 5-year mean survival rate of less than 10%. Most of the PC associated deaths are due to metastasis to secondary sites. Calcium (Ca²⁺) signaling plays a critical role in regulating hallmarks of cancer progression including cell proliferation, migration and apoptotic resistance. Store operated Ca²⁺ entry (SOCE) mediated by Orai1/2/3 channels is a highly regulated and ubiquitous pathway responsible for Ca²⁺ influx into non-excitable cells. In this study, we performed extensive bioinformatic analysis of publicly available datasets and observed that Orai3 expression is inversely associated with the mean survival time of PC patients. Orai3 expression analysis in a battery of PC cell lines corroborated its differential expression profile. We then carried out thorough Ca²⁺ imaging experiments in 6 PC cell lines and found that Orai3 forms a functional SOCE in PC cells. Our in vitro functional assays show that Orai3 regulates PC cell cycle progression, apoptosis and migration. Most importantly, our in vivo xenograft studies demonstrate a critical role of Orai3 in PC tumor growth and secondary metastasis. Mechanistically, Orai3 controls G₁ phase progression, matrix metalloproteinase expression and epithelial-mesenchymal transition in PC cells. Taken together, this study for the first time reports that Orai3 drives aggressive phenotypes of PC cells i.e. migration in vitro and metastasis in vivo. Considering that Orai3 expression is inversely associated with the PC patients survival time, it appears to be a highly attractive therapeutic target.

Accumulating evidences demonstrate that the host genome's epigenetic modificationsare essential for living organisms to adapt extreme conditions.DNA methylation, covalent modifications of histone, andinter-association of non-coding RNAs facilitate the cellular manifestation ofepigenetic changes in the genome. Out of various factors involved in the epigenetic programming of the host, miRNA (microRNA) and LncRNA (Long non-coding RNA) are new generationnon-coding molecules that influence a variety of cellular processes like immunity, cellular differentiation, and tumor development. During tumor development, temporal changes in miRNA/LncRNA rheostat influence sterile inflammatory responses accompanied by the changes in the carcinogenic signalling in the host. At the cellular level, this is manifested by the up-regulation of Inflammasome and inflammatory pathways, which promotes cancer-related inflammation. In view of this, we discuss the potential of lncRNA and miRNA directed interventions in regulating inflammation and tumor development in the host.

Cancer cachexia is a multifactorial syndrome that is identified by ongoing muscle atrophy, along with functional impairment, anorexia, weakness, fatigue, anemia, reduced tolerance to antitumor treatments. Thus, reducing the patients’ quality of life. Cachexia alone causes about 22-25% of cancer deaths. This review covers the symptoms, mediators, available treatment, and prospects of 3D bioprinting for cancer cachexia. Studies about cachexia have shown several factors that drive this disease – protein breakdown, inflammatory cytokines activation, and mitochondrial alteration. Even with proper nutrition, physical exercises, anti-inflammatory agents, chemotherapy, and grafting attempts, standard treatment has been unsuccessful for cachexia. But the use of 3D bioprinting shows much promise compared to conventional methods by attempting to fabricate 3D constructs mimicking the native muscle tissues. In this review, some 3D bioprinting techniques with their advantages and drawbacks, along with their achievements and challenges in in-vivo applications have been discussed. Constructs with neural integration or muscle-tendon units aim to repair muscle atrophy. But it is still difficult to properly bio-print these complex muscles. Although progress can be made by developing new bio-inks or 3D printers to fabricate high-resolution constructs. Using secondary data, this review study shows prospects of why 3D bioprinting can be a good alternate approach to fight cachexia.

Breast cancer, although the most frequently diagnosed malignant tumour in humans, has a less clear aetiology compared to other frequent cancer types. Mouse-mammary tumour virus (MMTV) is involved in breast cancer in mice and dogs and might play a role in the aetiology of some breast cancers in humans, since it has been identified in 20-40% of breast cancer samples in Western Europe, USA, Australia and some other parts of the world population. The purpose of our study was to identify MMTV DNA sequences in breast tissue samples from breast cancer patients operated in our regional centre from Romania. We have selected 75 patients with non-metastatic breast cancer treated with curative intent and searched with PCR the MMTV-like DNA sequence in the breast cancer tissue and normal breast tissue obtained from the same patients. Since none of the examined samples was positive for MMTV-like target sequences on PCR we could not prove that MMTV plays a role in the aetiology of breast cancer in our patient group. This finding is similar to publications of other geographically related research groups and might be due to the fact that only the Mus musculus domesticus mouse species was proven to carry infectious MMTV, but not the Mus musculus musculus species, which is specific to South-Eastern Europe (including Romania) and some parts of Asia.

Enhanced permeation retention (EPR) was a significant milestone discovery by Maeda et al. paving the road for the emerging nanomedicine as a powerful tool in the fight against cancer. Sildenafil is a potent inhibitor of phosphodiesterase 5 (PDE-5) used for treatment of erectile dysfunction (ED) through the relaxation of smooth muscles and the modulation of vascular endothelial permeability. Overexpression of PDE-5 was reported in lung, colon, metastatic breast cancers and bladder squamous carcinoma. Accordingly, there has been a growing interest in using sildenafil as monotherapy or chemoadjuvant in EPR augmentation and management of different types of cancer. Sildenafil had been reported to increase the sensitivity of tumor cells of different origins to the cytotoxic effect of chemotherapeutic agents with augmented apoptosis mediated through inducing the expression of Bad and Bax proapoptotic proteins. It was also reported that the use of sildenafil prior to the administration of Doxorubicin (DOX) increased its EPR-related concentration in breast cancer tissues by 2 folds. Further, a substantial reason of anticancer chemotherapeutic failure is due to multidrug resistance (MDR), exacerbated by the overexpression of ATP-binding cassette (ABC) transporters such as ABCB1 and ABCCs. Sildenafil has demonstrated inhibitory effects on the efflux activity of ABCC4, ABCC5, ABCB1, and ABCG2, ultimately reversing MDR caused by these transporters. In this review, we critically examine the overall potential of sildenafil in enhancing EPR-based anticancer drug delivery pointing up the outcome of the most important related preclinical and clinical studies.

The natural product elaiophylin is a macrodiolide with broad biological activities. However, no direct target of elaiophylin in eukaryotes has been described so far, which hinders a systematic explanation of its astonishing activity range. We recently showed that the related conglobatin A, a protein-protein interface inhibitor of the interaction between the N-terminus of Hsp90 and its cochaperone Cdc37, blocks cancer stem cell properties by selectively inhibiting K-Ras4B but not H-Ras. Here we elaborate that elaiophylin likewise disrupts the Hsp90/ Cdc37 interaction, without affecting the ATP-pocket of Hsp90. Similar to conglobatin A, elaiophylin decreased expression levels of the Hsp90 client HIF1⍺, a transcription factor with various downstream targets, including galectin-3. Galectin-3 is a nanocluster scaffold of K-Ras, which explains the K-Ras selectivity of Hsp90 inhibitors. In agreement with this K-Ras targeting and the potent effect on other Hsp90 clients, we observed with elaiophylin treatment a submicromolar IC50 for MDA-MB-231 3D spheroid formation. Finally, a strong inhibition of the same cells grown in the chorioallantoic membrane (CAM) microtumor model was determined. These results suggest that several other macrodiolides may have the Hsp90/ Cdc37 interface as a target site.

Cancer is one of the health concerns in modern societies. The application of nanotechnology in medical sciences has created new possibilities for the diagnosis, imaging and the treatment of tumors in humans. The present article reviews the application of marine-based gold nanoparticles in diagnosing and treating cancer. The main data were collected from research article on the application of different marine-based gold nanoparticles in detecting and imaging cancer cells as well as in drug delivery system in treatment of cancer. Chitosan is the most used marine natural compound used to fabricate gold nanocomposites and the most reported application of this type of nano-composites is related to drug delivery system. Despite the excellent anticancer potential of different marine natural products, less studies have been conducted on the use of their compositions with gold nanoparticles in cancer therapy than other materials. Moreover, most reports available in this filed are related to their application as a drug delivery system not anticancer drug. In general, there are still challenges and limitations to the use of nanoparticles in medicine, it is hoped that in the near future nanoparticles will create a dramatic revolution not only in oncology but also in medicine.

Proper and timely segregation of cellular genome is an important and a prime requirement of all cell division programmes. Mis-segregation of chromosomes and resulting aneuploidy leads to several clinical consequences. Over the years, shugoshin emerges as a key protein factor involved in the segregation of genetic material in dividing cells. Deletion or altered level of shugoshin is reported in several human malignancies, as a result, shugoshin now emerges as an important tumour associated gene and a possible target for cancer therapy. Apart from the role in cancer, recent studies also showed the involvement of shugoshin in several other clinical disorders. Through this review, we tried to highlight the clinical relevance of shugoshin.

Background: Our knowledge of prostate cancer (PCa) genomics mainly reflects European (EUR) and Asian (ASN) populations. Our understanding of the influence of Middle Eastern (ME) and African (AFR) ancestry on the mutational profiles of prostate cancer is limited. Design, setting and participants: To characterize genomic differences between ME, EUR, ASN and AFR ancestry, fluorescent in situ hybridization (FISH) studies for NKX3-1 deletions and MYC amplification was carried out on 42 tumors arising in individuals of ME ancestry. These were supplemented by analysis of copy number profiles of 401 tumors of all ancestries. Outcome measurement and statistical analysis: FISH results of NKX3-1 and MYC were assessed in the ME cohort and compared to other ancestries. Gene level copy number aberrations (CNAs) for each sample were statistically compared between ancestry groups. Results and Limitation: NKX3-1 deletions by FISH were observed in 17/42 (17.5%) prostate tumors arising in men of ME ancestry, while MYC amplifications were only observed in 1/42 (0.23%). Using CNAs called from arrays, the incidence of NKX3-1 deletions was significantly lower in ME vs. other ancestries (20% vs. 52%; p = 2.3 x 10-3). No differences in MYC amplifications was noted between the two cohorts using array-based CNAs. Across the genome, tumors arising in men of ME ancestry had fewer CNAs than those of other ancestries (p = 0.014). Additionally, the somatic amplification of 21 specific genes was more frequent in tumors arising in men of ME vs. EUR ancestry (Proportions test; Q < 0.05). Those included amplifications in the glutathione S-transferase family on chromosome 1 (GSTM1, GSTM2, GSTM5) and the IQ Motif Containing family on chromosome 3 (IQCF1, IQCF2, IQCF13, IQCF4, IQCF5, IQCF6). Conclusion: Significant differences in genetic background exists between different ancestries. The lower number of somatic CNAs observed in prostate cancer arising in men of ME ancestry may explain the relatively good prognosis in this population. Larger studies are warranted.

The exponential growth of biomedical data in recent years urged the application of numerous machine learning techniques to address emerging problems in biology and clinical research. By enabling automatic feature extraction, selection and generation of predictive models, these methods can be used to efficiently study complex biological systems. Machine learning techniques are frequently integrated with bioinformatic methods, as well as curated databases and biological networks, to enhance training and validation, identify the best interpretable features, and enable feature and model investigation. Here, we review recently developed methods that incorporate machine learning within the same framework with techniques from molecular evolution, protein structure analysis, systems biology and disease genomics. We outline the challenges posed for machine learning, and in particular, deep learning in biomedicine and suggest unique opportunities for machine learning techniques integrated with established bioinformatics approaches to overcome some of these challenges.

.Background: Prophylactic hyperthermic intraperitoneal chemotherapy (HIPEC) showed promising results in patients with colorectal carcinoma at high risk of recurrence but still without clinically and radiologically evident signs of peritoneal spread. This study aims to analyze the feasibility of this proactive, early phase, multimodality approach. Methods: A mono-institutional, prospective, parallel, two-stage phase II trial enrolled 49 patients to standard surgery or surgery plus intraoperative HIPEC. Before the procedure and during surgery, patients received intravenous fluorouracil (and leucovorin to potentiate oxaliplatin activity. Data analysis included length of hospital stay, surgery duration, type of surgery and chemotherapy-related complications risk score. Results: No significant difference was seen in the median time spent in the hospital with a median stay of 7 days in both groups (p=0.5720). The surgical procedure's median duration was longer in the HIPEC group than in the control one. Side-effects and surgical complications did not cross at any time the Pocock-type boundary for side/effect monitoring (p=0.80, N.S.). Conclusions: The present prospective study results demonstrate the feasibility and safety of the colorectal surgery plus HIPEC treatment in patients with colorectal cancer patients at high-risk for peritoneal invasion, although clinically and radiologically undetectable.

The overwhelming majority of bladder cancers are transitional cell carcinomas. Albeit mostly monotonous, carcinomas in the bladder may occasionally display a broad spectrum of histological features that should be recognized by pathologists because some of them represent a diagnostic problem and/or lead prognostic implications. Sometimes these features are focal in the context of conventional transitional cell carcinomas, but some others are generalized across the tumor making its recognition a challenge. For practical purposes, the review distributes the morphologic spectrum of changes in architectural and cytological. So, nested and large nested, micropapillary, myxoid stroma, small tubules and adenoma nephrogenic-like, microcystic, verrucous, and diffuse lymphoepithelioma-like, on one hand, and plasmacytoid, signet ring, basaloid-squamous, yolk-sac, trophoblastic, rhabdoid, lipid/lipoblastic, giant, clear, eosinophilic (oncocytoid), and sarcomatoid, on the other, are revisited. Key histological and immunohistochemical features useful in the differential diagnosis are mentioned. In selected cases, molecular data associated with the diagnosis, prognosis, and/or treatment are also included.

Background: Human papillomavirus (HPV) infection plays a key role in the development of cervical cancer that ranks as the third most common gynecological cancer in China. We attempt to investigate the age and genotype-specific prevalence of HPV DNA in western Chinese females. Methods: A total of 301,880 woman were recruited from 4 different regions of western China. Routine cervical samples were collected and HPV screening was performed using 21 HPV Genotyping test (Hybribio). The overall prevalence, age-specific prevalence, and genotype distribution were analyzed. Results: The overall prevalence of HPV was 18.01%. The high-risk HPV infection rate was 79.14%, the low-risk HPV infection rate was 12.56%, and the mixed HPV infection rate was 8.30%. The most common 4 HR HPV subtypes were HPV-52, 16, 58 and 53, which accounted for 20.49 %, 19.93 %, 14.54 % and 10.01 %. In LR HPV genotype, HPV-6 ranked the highest (28.17 %), followed by HPV-81 (9.09 %), HPV-11 (3.78 %). HPV genotype subgroup analysis also showed that single-type infections had the highest prevalence rate (77.26%) among HPV positive individuals. Among muti-infection genotype, double infection was most common with frequencies of 76.04%. Conclusion: This large report shows that the overall prevalence of HPV was high in China, whose distribution exhibits different patterns across different particular age and regions. Viral genotypes HPV53, 6 were are frequently detected in this population, which is worth of significant clinical attention.

This study aimed to rank cancers by the strength of relationship between comprehensive mRNA expression of the most harmful or protective genes and patient survival. Using TCGA dataset including RNA-SEQ and clinical data, we investigated not only gene specific prognostic availability, but also comprehensive prognostic availability of prognostic genes filtered by cox coefficient, and ranked cancers by specially designed prognostic indicator. Through Kaplan-Meier plots, we checked that cancers vary in the strength of influence of prognostic genes, and they follow as the rank. Developing treatment with method to reduce or increase expression of biomarkers for specific cancer which ranked bottom, it would be not efficient in high probability. The results of this study can be a scientific evidence for that.

The PI3K/AKT pathway is a key target in oncology where most efforts are focussed on phenotypes such as cell proliferation and survival. Comparatively little attention has been paid to PI3K in stemness regulation, despite the emerging link between acquisition of stem cell-like features and therapeutic failure in cancer. The aim of this review is to summarise current known and unknowns of PI3K-dependent stemness regulation, by integrating knowledge from the fields of developmental, signalling and cancer biology. Particular attention is given to the role of the PI3K pathway in pluripotent stem cells (PSCs) and the emerging parallels to dedifferentiated cancer cells with stem cell-like features. Compelling evidence suggests that PI3K/AKT signalling forms part of a ‘core molecular stemness programme’ in both mouse and human PSCs. In cancer, the oncogenic PIK3CA^H1047R variant causes constitutive activation of the PI3K pathway and has recently been linked to increased stemness in a dose-dependent manner, similar to observations in mouse PSCs with heterozygous versus homozygous Pten loss. There is also evidence that the stemness phenotype may become ‘locked’ and thus independent of the original PI3K activation, posing limitations for the success of PI3K monotherapy in cancer.Ongoing therapeutic developments for PI3K-associated cancers may therefore benefit from a better understanding of the pathway’s two-layered and highly context-dependent regulation of cell growth versus stemness.

Measurement of breast cancer burden and identification of its influencing factors help in the development of public health policy and strategy against the disease. This study aimed to examine the variability of the excess mortality of female breast cancer patients in the North East Region of Peninsular Malaysia. This retrospective cohort study was conducted using breast cancer data from the Kelantan Cancer Registry between 2007 and 2011, and Kelantan general population mortality data. The breast cancer cases were followed up for five years until 2016. Out of 598 cases, 549 cases met the study criteria and were included in the analysis. Modelling of excess mortality was conducted using Poisson regression. Excess mortality of breast cancer varied according to age group (50 years old and below vs above 50 years old, Adj. EHR: 1.47; 95% CI: 1.31, 4.09; P=0.004), ethnicity (Malay vs non-Malay, Adj. EHR: 2.31; 95% CI: 1.11, 1.96; P=0.008), and stage (stage III and IV vs. stage I and II, Adj. EHR: 5.75; 95% CI: 4.24, 7.81; P<0.001). In conclusion, public health policy and strategy aim to improve cancer survival should focus more on patients presented at age below 50 years old, Malay ethnicity, and at a later stage.

Brain cancer is the tenth leading cause of death in the U.S. Glioblastoma multiforme (GBM) is the most lethal primary malignant central nervous system tumor in adults. The present study employed samples from 1985-2014 to discover the difference in prognosis among glioblastoma subtypes after the evolution of treatment modalities over the past few years. The current study aims to find the differences between Glioblastoma multiforme (GBM) and giant cell glioblastoma (GCG) in terms of prognosis among adults and elderly patients in the U.S. This study is a historical cohort type of study and is conducted on adults and elderly individuals with GBM or GCG from the years 1985-2014 in the U.S. Data were collected from the Surveillance, Epidemiology, and End Results Program (SEER) database. The study exposure was GBM or GCG and the outcome was mortality. The potential confounders were age, sex, race, ethnicity, year of diagnosis, primary site, and surgery. A chi-square test was used for categorical data. A univariate analysis was used for variables having a p-value < 0.05. Potential confounders were selected and evaluated using multivariate logistic regression models to calculate the odds ratio with stepwise selection. The study sample was 25,117. The incidences of GBM and GCG were not similar in relation to age group. Also, Spanish-Hispanic ethnicity was independently protective of GBM and GCG as compared to Non-Spanish-Hispanic ethnicity patients with GBM have a higher mortality rate than do GCG patients. The mortality rate was higher among patients diagnosed before 2010. In conclusion, GCG was not statistically significant in association to reduced mortality. Non-Spanish-Hispanics with GBM or GCG had a higher mortality rate than did Spanish-Hispanics. Factors such as being female, being age >59, and having a year of diagnosis before 2010 were independently associated with increased mortality.

Cell division control 37 (CDC37) increases the stability of HSP90 client proteins and is thus essential for numerous intracellular oncogenic signaling pathways, playing a key role in prostate oncogenesis. Notably, elevated expression of CDC37 was found in prostate cancer cells, although the regulatory mechanisms through which CDC37 expression becomes increased are unknown. Here we show both positive and negative regulation of CDC37 gene transcription by two members of the SCAN transcription factor family- MZF1 and SCAND1, respectively. Consensus DNA-binding motifs for myeloid zinc finger 1 (MZF1 / ZSCAN6) were abundant in the CDC37 promoter region. MZF1 became bound to these regulatory sites and trans-activated the CDC37 gene whereas MZF1 depletion decreased CDC37 transcription and reduced tumorigenesis of prostate cancer cells. On the other hand, SCAND1, a zinc-fingerless SCAN box protein that potentially inhibits MZF1, accumulated at MZF1-binding sites in CDC37 gene, negatively regulated CDC37 gene and inhibited tumorigenesis. SCAND1 was abundantly expressed in normal prostate cells but was reduced in prostate cancer cells, suggesting a potential tumor suppressor role of SCAND1 in prostate cancer. These findings indicate that CDC37, a crucial protein in prostate cancer progression, is regulated reciprocally by MZF1 and SCAND1.

Bufadienolides-like chemicals, which mostly composed the active ingredient of Chansu, had been widely discovered to possess anti-inflammatory, tumor-suppressing and antipain activity, but the mechanisms of action were not clearly illuminated. In this research, in order to explore the potential mechanism of bufadienolides-like chemicals on breast cancer, a serious of bioinformatics analysis, included (1) differentially expressed genes identification combined with gene set variation analysis, (2) tissue specific co-expression network construction, (3) differentially regulated sub-networks detection with disease phenome, (4) hub gene selection and it’s relation to survival probability, and (5) similar small molecule detection were performed with gene expression profiles of bufadienolides-like chemicals. Results indicated bufadienolides-like chemicals had the most same target with valproic, estradiol and etc, could disturbed the pathways in RNA splicing, apoptotic process, cell migration, extracellular matrix organization, adherens junction organization, synaptic transmission, Wnt signaling, AK-STAT signaling, BMP signaling pathway and unfolded protein response, and had the potential ability to be used as anticancer, hormones and vasoprotectives agents.

Stereotactic radiosurgery (SRS) is considered the initial treatment for lung cancer patients with small-sized and limited number of brain metastases. The objective of this study was to assess clinical outcomes of SRS treatment using CyberKnife (CK) for recursive partitioning analysis (RPA) class II/III patients with one to three brain metastases from lung cancer and identify which patients in the high RPA class could benefit from SRS. A total of 48 lung cancer patients who received CK-based SRS for their metastatic brain lesions from 2010 to 2017 were retrospectively analyzed. Radiographic response was evaluated during follow-up period. Overall survival (OS) and intracranial progression-free survival (IPFS) were calculated and prognostic variables associated with OS and IPFS were evaluated. Median follow-up time was 6.6 months. Local control rates at 6 months and 1-year following SRS were 98% and 92%, respectively. The median OS of all patients was 8 months. One-year and 2-year OS rates were 40.8% and 20.9%, respectively. In multivariate analysis, uncontrolled primary disease (p = 0.008) and ECOG performance status of 2 or 3 (p = 0.001) were independent prognostic factors for inferior OS. These two factors were also significantly associated with inferior IPFS. In subgroup analysis according to RPA class, primary disease status was the only prognostic factor, showing statistically significant OS differences in both RPA class II and III (controlled vs. uncontrolled: 41.1 vs. 12.3 months in RPA class II, p = 0.031; 26.9 vs. 4.1 months in RPA class III, p = 0.011). Our results indicated that SRS could be an effective treatment option for RPA class II/III patients with brain metastases from lung cancer in the modern treatment era. SRS might be particularly considered for patients with controlled primary disease.

Cancer treatment with specific chemotherapeutic agents has been well documented to have an adverse impact on female fertility leading to premature ovarian failure (POF). The objective of this study was to investigate if chemotherapeutic induced POF can be reversed with an infusion of autologous nucleated peripheral blood cells (PBMC). To reach our goal, mice were treated with a single intraperitoneal injections of busulfan and cyclophosphamide to induce POF. This was followed by transfusion of PBMC. The ovarian morphology and functional parameters were monitored by radioimmunoassay, real-time PCR, immunofluorescence and immunohistochemistry analysis. Our study showed that chemotherapy (CTX) protracted estrous cycle period and repressed E2 production. CTX decreased the expressions of steroidogenesis markers- CYP-17 synthesis, StAR and Connexin-43 protein expression from the ovarian follicles. We also observed reduced numbers and sizes of the primordial and primary follicles in CTX-treated mice compared to untreated controls (P < 0.05). When both CTX and untreated –control groups were stimulated with gonadotrophin, the control group produced ten times more ova than the CTX group. Finally, the treatment of premature ovarian failure induced by CTX with autologous PBMC transfusion resulted in over-expression and a statistically significant increase in several stem cell markers and restoration of fertility. Infusion with PBMC in CTX further decreased the estrous cycle length by 2.5 times (P < 0.01). We found that transfusion of autologous PBMC to mice with chemotherapy induced POF was very effective at restoring fertility. These results are similar to other studies using bone marrow derived mesenchymal stem cells.

Background: Prostate cancer is a complex condition, in which both genetic and environmental factors concomitantly contribute to the tumor initiation and progression. Recently, HOXB13 has been proposed as a susceptibility gene for prostate cancer. Objective: So the current study was conducted to test the existence of potential variations in HOXB13 gene in Iranian men with prostate cancer (PCa) compared to benign prostatic hyperplasia (BPH) cases. Methods: The HOXB13 genetic status was screened in 51 samples, including 21 blood and tissue of PCa cases compared to 30 cases affected by BPH using PCR/sequencing. Then potential association between genomic DNA alterations in blood and tissue PCa specimens was investigated Results: Analysis of BPH tissues showed single nucleotide variations c.366C > T (rs) or c.513T > C (rs9900627) in exon 1, but not in exon 2. Evaluation of PCa tissues revealed two cases with both synonymous c.366C > T and c.513T > C variants and two cases with the synonymous c.366C > T variant in exon 1. The variants c.366C > T and c.513T > C simultaneously or separately were found blood samples of PCa patients. The novel variant c.127A > G in the exon 2 was detected in 1 PCa blood sample. Our analysis indicated a significant reciprocal correlation between HOXB13 mutation in tissue and blood in PCa cases (P=0.02). Conclusion: The variants in exon 2 of HOXB13 may influence the risk of prostate cancer. Also, evaluation of HOXB13 mutation may be considered as a novel marker for screening of PCa. Further investigations are warranted to evaluate the clinical significance of HOXB13 in Iranian population.