The increasing cancer burden is a major health concern in Arab countries with variations in cancer profiles. Given the limited oncology research output and scarce data on cancer trial participation in the Arab region, this study explored the therapeutic cancer trial landscape in Arab countries over the past 20 years. A bibliometric analysis of the PubMed database was conducted on primary publications of therapeutic trials with a participating Arab center. Arab countries participated in 320 published cancer-related therapeutic trials (2000‒2021). There was a consistent increase in the number of trials, sample size, multiregional site participation, and number of randomized trials. However, most trials were small, did not receive external funding, and included a single Arab site. Compared with Arab-only trials, trials with joint non-Arab sites were larger (p = .003) and more likely to be externally funded (p < .001). Citation numbers and journal impact factors were higher in trial publications with joint non-Arab authorship than those without (p < .001, for both). Despite improving conduct and publication records of oncology trials with Arab centers, cancer trial participation remains limited in Arab countries. Concerted efforts are required to encourage sponsorship and international collaboration in this region.

Polymeric hydrogels are promising polymeric functional materials that have been widely used in the biomedical field as an emerging carrier of various therapeutic agents. Polymeric hydrogels as a carrier of therapeutics can leverage therapeutically beneficial outcomes of drug delivery than systemic chemotherapy and can provide spatial and temporal control over the release of various therapeutic agents. Polymeric hydrogels are cross-linked three-dimensional networks constructed by hydrophilic polymers and they are capable of absorbing and re-taining a large amount of water. Polymeric hydrogels share many physiochemical features with natural tissues due to their water abundance, biomimetic microstructure, and intrinsic flexibility. Polymeric hydrogels have excellent biocompatibility, biodegradability, and lower toxicity. Polymeric hydrogels enhance the convenience and efficiency of drug delivery by assisting in situ gelation and controlling drug release by changing their volume and other properties when it encounters some stimuli (e.g., heat, pH, light, and ultrasound). This review aims to outline the overview of polymeric hydrogels, properties, types, advantage, disadvantages, characteri-zation, and their application with present status and future perspective used for the delivery of therapeutics in pharmaceutical and biomedical sciences.

Aberrant glycosylation affects cancer progression and immune evasion. Approximately 15% of colorectal cancers (CRCs) demonstrate microsatellite instability (MSI) and display major differences in outcomes and therapeutic responses as compared to corresponding microsatellite stable (MSS) tumors. We compared the N-glycan profiles of stage II and IV MSI CRC tumors, further subdivided into BRAFV600E wild-type and mutated subgroups (n=10 in each subgroup), with each other and with those of paired non-neoplastic mucosal samples using mass spectrometry. Further, the N-glycans of BRAFV600E wild-type stage II MSI tumors were compared to corresponding MSS tumors (n=9). Multiple differences in N-glycan profiles were identified between MSI CRCs and control tissues, as well as between stage II MSI and MSS samples. MSI CRC tumors showed a lower relative abundance of high-mannose N-glycans than the control tissues or the MSS CRCs. Among MSI CRC subgroups, acidic N-glycans showed tumor stage and BRAF mutation status dependent variation. Especially large, sulfated/phosphorylated, and putative terminal N-acetylhexosamine containing acidic N-glycans differed between the MSI CRC subgroups, showing opposite changes in stage II and IV, when comparing BRAF mutated and wild-type tumors. Our results show that molecular subgroups of CRC have characteristic glycan profiles that may explain certain carcinogenic properties of MSI tumors.

Cancers of the head and ne¬ck and their treatment can cause disfigurement and loss of functioning, with a profound negative impact on the person’s self-image and psychosocial wellbeing. This can lead to experiences of shame and stigma, which are important targets for psychosocial interventions. Accurate measurement and identification of these problems enables clinicians to offer appropriate interventions and monitor patients’ progress. This study aimed to validate the Canadian version of the Shame and Stigma Scale (SSS) among French and English speaking head and neck cancer patients. Data from 258 patients from two major Canadian hospitals was analysed. The existing 4-factor structure of the SSS was supported, with the following subscales: Shame with Appearance, Sense of Stigma, Regret, and Social/Speech Concerns. The Canadian SSS showed adequate convergent and divergent validity and test-retest reliability. Rasch analysis suggested scale improvement by removing two misfitting item and two items with differential functioning between French and English speaking patients. The final 16-item scale version had adequate fit to the Rasch model. The SSS provides more accurate measures for people with high levels of shame and stigma, and thus has utility in identifying patients with more severe symptoms who may be in need of psychosocial interventions.

Potato (Solanum tuberosum L) gradually becomes a stable food worldwide since it can be treated as practical nutritional supplement and antioxidant, as well as energy provider for human beings. Financially and nutritionally, cultivation and utility of potatoes is worthy enough attention of the world. To further explore functionality and maximize utilization of component parts, also to develop new products based on potato still be an ongoing issue. To maximize the benefits of potato and induce new high-value products while avoiding unfavorable properties of the crop has been a growing trend in food and medical areas. This review intends to summarize the factors that influence the changes in the key functional components of potatoes and discuss referred research focuses, then help further researchers to make efforts into. Afterwards, it summarizes the application of the latest commercial products and potential value of components existing in potato. Particularly, there are several main tasks for the next potato research: preparing starchy foods for special group of people and developing fiber-rich products to supply the dietary fiber intake as well as manufacturing bio-friendly and specific design films/coating in packaging industry; extracting bioactive proteins and potato protease inhibitors with high biological activity, and continue to build new commercial products based on potato protein and examine their health benefits. Noteworthy, the preservation methods play a key role in phytochemicals contents left in foods and potato performs superior to many common vegetables when meeting demand of mineral daily intake and alleviating mineral deficiencies.

Pancreatic ductal adenocarcinoma (PDAC) is still one of the deadliest cancers in Oncology be-cause of its increasing incidence and poor survival rate. More than 90% of PDAC patients are KRAS mutated (KRASmu), with KRASG12D and KRASG12V being the most common mutations. Despite this critical role, its characteristics have made direct targeting of the RAS protein ex-tremely difficult. KRAS regulates development, cell growth, Epigenetically-dysregulated differ-entiation, and survival in PDAC through activation of key downstream pathways, such as MAPK-ERK and PI3K-AKT-mammalian target of rapamycin (mTOR) signaling, in a KRAS-dependent manner. KRASmu induces the occurrence of Acinar-to-ductal metaplasia (ADM) and pancreatic intraepithelial neoplasia (PanIN) and leads to an immunosuppressive tumor microenvironment (TME). In this context, the oncogenic mutation of KRAS induces an epigenetic program that leads to the initiation of PDAC. Several studies have identified multiple direct and indirect inhibitors of KRAS signaling. Therefore, KRAS dependency is so essential in KRASmu PDAC that cancer cells have secured several compensatory escape mechanisms to counteract the efficacy of KRAS inhibitors, such as activation of MEK/ERK signaling or YAP1 upregulation. This review will provide insights into KRAS dependency in PDAC and analyze recent data on inhibitors of KRAS signaling, focusing on how cancer cells establish compensatory escape mechanisms.

Aim: to provide a comprehensive overview of the existing literature concerning the applications of positron emission tomography (PET)-radiomics in lung cancer patients candidates or undergoing immunotherapy. Materials and Methods: A systematic review was conducted on databases and web sources. English-language original articles were considered. The title and abstract were in-dependently reviewed to evaluate study inclusion. Papers duplicate, out-of-topic, review or edi-torials articles and letters to editors were excluded. For each study, the radiomics analysis was assessed based on the relies on radiomics quality score (RQS 2.0). The review was registered on the PROSPERO database with the number CRD42023402302. Results: 15 papers were included, 13 were qualified as conventional radiomics approaches, and two were as Deep Learning radiomics. The content of each study was different, indeed, 7 papers investigated the potential role of radiomics to predict PD-L1 expression and tumor microenvironment before starting immunotherapy. Moreo-ver, 2 were relative to the prediction of response and 4 investigated the utility of radiomics to predict the response to immunotherapy. Finally, 2 papers were relative to the prediction of adverse events due to the immunotherapy. Conclusions: radiomics is promising in the evaluation of TME and for the prediction of response to immunotherapy, but some limitations should be overpassed.

The identification of biomarkers is crucial for cancer diagnosis, understanding the underlying biological mechanisms, and developing targeted therapies. In this study we propose a machine learning approach to predict the outcome and platinum resistance status of ovarian cancer patients using public available gene expression data. Six classical machine learning algorithms are compared on their predictive performance. Those with the highest score are analyzed by their feature importance using the SHAP algorithm. We were able to select multiple genes that were correlating with the outcome and platinum resistance status of the patients and validated those using Kaplan-Meier plots. In comparison to similar approaches the performance of the models were higher and different genes using feature importance analysis were identified. The most promising identified genes that could be used as biomarkers are: TMEFF2, ACSM3, SLC4A1 and ALDH4A1.

Longer operating time in radical prostatectomy may escalate the risk of perioperative complications. Various factors like cancer extent, procedure’s level of difficulty, habitus and previous surgeries may lengthen robotic assisted radical prostatectomy (RARP) and therefor compromise outcomes. Objective: this study investigates the influence of operating time on outcomes after RARP in real life settings in a monocentric single surgeon study. Methods: 500 consecutive patients who underwent RARP between April 2019 and August 2022 were included. Patients were divided in three groups. Short (n=157; 31.4%) under or equal to 120 minutes, average (n=255; 51%) between 121 and 180 minutes, long (n=88; 17,6%) above 180 minutes console-time. Demographic, baseline and perioperative data were analyzed and compared between groups. Univariate logistic regression was completed to investigate the association between console-time and outcomes and to predict factors which may prolong surgery. Results: hospital stay and catheter days were significantly longer in group 3 with medians 6 and 7 days (p<0.001 and <0.001, respectively). Those findings were confirmed in univariate analysis, p=0.012 for Catheter days and p<0.001 for Hospital stay. Moreover, major complications were higher in patients with longer procedures p=0.008. Prostate volume was the only predictor for prolonged console time (p=0.005). Conclusion: RARP is a safe procedure and most patients will be discharged uneventfully. Yet longer console-time is associated with longer hospital stay, catheter days and major complications. Caution has to be taken in large prostate to avoid longer procedures, which may prevent postoperative advert events.

Resection of malignant lesions in the oral and maxillofacial area causes functional and morphological defects. To recover from these defects, reconstruction surgery is needed such as a primary closure or a flap. There are advantages and disadvantages to the method of using the primary closure and the flap, and the choice of procedure is entirely up to a surgeon. The purpose of this study is to evaluate availability of primary closure in patients. For 10 years from January 2010 to May 2020, patients who recovered using flaps after removing malignant lesions from the oral cavity and those who closed the lesion using primary closure were investigated. The investigation was conducted by searching the database of the hospital. There were 85 patients who removed malignant lesions in the oral and maxillofacial area, and among them 16 patients closed the soft tissue defects using primary closure. Operation time, histologic types, stages, wound status, and period of hospitalization according to the patients' medical records were investigated retrospectively. Between the staging and the primary closure, statistically significant differences were observed between stage I and stage II patients in 13 patients using the primary closure. (P=0.046). Statistically significant differences were identified between operation time and primary closure, with an average of 4.02 hours (P=0.015). The average period of hospitality for patients who underwent primary closure was 13.4 days, compared to 26.7 days for those who underwent flap surgery. This difference was statistically significant (P=0.0003). This study evaluated the use of primary closure in patients who underwent resection of malignant lesions in the oral and maxillofacial area. Although the majority of patients underwent reconstruction with flaps, our results showed that primary closure can be a viable option for certain patients with early-stage lesions. Therefore, oral and maxillofacial surgeons should carefully consider various evaluation criteria and select appropriate reconstruction methods to optimize functional and aesthetic outcomes for each patient.

Cancer is a major concern for people, and accurately predicting the probability of cancer incidence and mortality is an important research topic. With the development of big data and artificial intelligence technology, a new machine learning model has emerged. Using 72,591 pieces of data, including age, case count, population size, race, gender, site of onset, and year of discovery, we built a machine learning model. Through calculations, we found that the decision tree, random forest, logistic regression, support vector machine, and neural network achieved testing accuracies of 62.11%, 61.68%, 54.53%, 55.72%, and 63.10%, respectively. With the help of this model, scientists and policymakers can accurately predict future cancer incidence and mortality rates through databases, allowing them to make relevant policies (such as timely allocating doctors and medical resources) to better serve the people.

The mechanistic target of rapamycin (mTOR) kinase is one of the top drug targets for promoting health and lifespan extension. Besides rapamycin, only a few other mTOR inhibitors have been developed and shown their ability to slow aging. We used machine learning to predict novel small molecules targeting mTOR. We selected one small molecule, TKA001, based on in-silico predictions of a high on-target probability, low toxicity, favorable physicochemical properties, and preferable ADMET profile. We confirmed TKA001 binding in silico by molecular docking. TKA001 potently inhibits both TOR complex 1 and 2 downstream signaling in vitro. Furthermore, TKA001 inhibits human cancer cell proliferation in vitro and extended the lifespan of C. elegans, suggesting that TKA001 can slow aging in vivo.

Previous literature highlights the impact of COVID-19 on family functioning. Less is known about the impact of the pandemic on families of pediatric cancer patients. In order to determine universal and unique risk and resilience factors of these families during the pandemic, a qualitative analysis was conducted on families currently receiving cancer treatment at a midwestern hospital. Results of the data analysis depict ways in which these families have been impacted by and have adapted to COVID-19. These findings suggest that families of pediatric cancer patients have unique experiences in the context of COVID-19, in addition to universal experiences outlined in previous literature.

Ovarian cancers are curable by surgical resection when discovered early enough. Unfortunately, most ovarian cancers are diagnosed in the later stages. One strategy to identify early ovarian tumors is to screen women who have the highest risk scores. This mini review summarizes the accuracy of different methods used to assess the risk of developing ovarian cancer, including family history, BRCA genetic tests, and polygenic risk scores. The accuracy of these is compared to the maximum theoretical accuracy, revealing a substantial gap. We suggest that this gap, or missing heritability, could be caused by epistatic interactions between genes. An alternative approach to computing genetic risk scores, using chromosomal-scale length variation should incorporate epistatic interactions. Future research in this area should focus on this and other alternative methods of characterizing genomes.

Most head and neck cancers are diagnosed in advanced stages, when the curative interventions are no longer possible. The assessment and the multidisciplinary therapeutic approach of the locally advanced cases are difficult since the onset of the disease becomes a significant challenge for the whole attending team (including both the patient and his family) because they have to deal with to an extensive symptomatology (abundant secretions, refractory pain, mutilations predominantly in the cephalic area), with the cure of stomas (tracheostomy, gastrostomy) and with various post-therapeutic sequelae. The present paper reflects the impact of late diagnosis, the complexity of the multimodal specific oncological treatment (chemotherapy, radiotherapy, immunotherapy, pal-liative and terminal treatment), the adaptation of medical care to the psycho-emotional structure, having as an example the case of 54-year old patient (with his consent) diagnosed with pharyn-golaryngeal neoplasm who presented himself to “St. Luca” Chronic Disease Hospital, the Oncol-ogy-Palliative Care Department, in September 2021. In patients with locally advanced head and neck cancers, besides the specifically oncological therapeutic decisions, the empathic-emotional connection between the medical team with the patient and his family plays a key role in the ther-apeutic conduct.

(1) Background: Loss of weight is one of the practices which have been identified as key in reducing the risk of various forms of cancer. Therefore, this study is a systematic review and meta-analysis of studies related to the topic of loss of weight and risk of cancer and addresses the question, ‘does losing weight reduce the risk of cancer?’ Its purpose is to identify current high-quality evidence on such a question and synthesize such evidence before summarizing it given specific data attributes to improve decision-making processes on cancer management. (2) Methods: Research studies were identified from four main databases: PubMed, Science Direct, Google scholar, and Medline. A systematic review and meta-analysis of such studies were then conducted to reveal the most current evidence on the research topic. (3) Results: The studies showed that losing weight reduces cancer risk. Nonetheless, such intervention is not necessarily effective, especially in cases where patients may be at risk of developing cancer due to other risk factors. (4) Conclusions: The current study concludes that there is a need to implement effective interventions such as physical exercise, dietary restrictions, or both that can be effective in reducing weight to reduce the risk of cancer.

We attempted to understand the cervical cancer patient samples through Whole Exome Sequencing. We derived the variants from raw reads via our in-house benchmarked pipeline and validated the variants by IGV. This is the first cervical cancer exome data from the Indian cohort. Background: Cervical cancer (CC) is caused mainly by persistent infections of high-risk HPV, reduced parity, and factors like a decrease in average socioeconomic levels. We keep this because no cervical cancer exome data is available from the Indian cohort. Methods: The CC patient clinical samples were initially subjected to preparation using Qiagen DNA extraction, quantified, and the library preparation using the Agilent target enrichment system. Further, exome capture by Illumina platform (100X), quality check, alignment, and variant calling followed by the downstream analysis and finally visualized by IGV. Results: We observed a large number of SNVs or mutations from an Indian perspective, such as KMT2C, OR4M1, PDPR2P, EPHB1, FAS, OPCML, MGST1, C1QTNF9, HS6ST3, OR4K2, PRPSAP2, KCNJ12, FIGNL1, SFXN1, BAGE2, ARVCF, NAMPT variants of significance, unknown significance and possibly significant are reported. Conclusion: For the first time, KMT2C is observed as a novel potent mutation and pathogenic, showing the variant position at (7:152265091, T>A, SNV 62478356) from the Indian context in CC. Further, we visualized and validated the mutations using the Integrative Genomic Viewer (IGV) browser. Finally, we discuss the inherent challenges through KMT2C mutations.

A significant number of research studies have focused on determining whether BMI influences various types of cancer. The findings of these studies showed that people have to manage their BMIs to decrease their risk of developing various types of cancer, one of which is ovarian cancer. A PRISMA guideline for systematic review and meta-analysis was used to identify 20 research studies related to the topic to establish the truth or falsity of the findings. Later, their findings were synthesized. The synthesis of the findings of such research articles suggests that overweight and obesity increase an individual’s risk of developing ovarian cancer and experiencing severe symptoms of the disease. In such a manner, the current research study can conclude that effective management of BMI is necessary for decreasing the prevalence and mortality rates associated with ovarian cancer.

Australia and New Zealand have the highest incidence of skin cancer. Sport is a fundamental part of Australasian culture, beginning in childhood, often with life-long participation. Participating in outdoor sports can contribute significantly to the lifetime ultraviolet radiation (UVR) dose individuals receive and their risk of developing skin cancer. This systematic scoping review explores the use of sun-protection by outdoor sporting participants in Australasia and considers how sun-protection practices may be better evaluated and improved in the community. A search of electronic databases using the search strategy “sun protection” AND “sport” AND “Australia” yielded 17 studies published in English from January 1992 to August 2021. Study methods included using UV-dosimeters to measure individual UVR-exposure; remote estimates of clothing-adjusted UVR-exposure; direct observation of sun-protection practices; and self-reported sun-exposure and sun-protection. Despite 40-years of ‘Slip Slop Slap’ campaigns in Australia, the use of sun-protection in most outdoor sports is inadequate. The paucity of comparable data limited our analyses, demonstrating a need for standardized, objective evaluation tools. Such tools, if used across a range of sports, should inform the development of workable recommendations that sporting clubs could implement and adopt into policy, thus empowering them to better protect the health of their participants.

The epithelial cell adhesion molecule (EpCAM) is a stem cell and carcinoma antigen, which mediates cellular adhesion and proliferative signaling by the proteolytic cleavage. In contrast to low expression in normal epithelium, EpCAM is frequently overexpressed in various carcinomas, which correlates with poor prognosis. Therefore, EpCAM has been considered as a promising target for tumor diagnosis and therapy. Using the Cell-Based Immunization and Screening (CBIS) method, we previously established an anti‐EpCAM monoclonal antibody (EpMab-37; mouse IgG1, kappa). In this study, we investigated the antibody‐dependent cellular cytotoxicity (ADCC), complement‐dependent cytotoxicity (CDC), and an antitumor activity by a defucosylated mouse IgG2a-type of EpMab-37 (EpMab-37-mG2a-f) against an EpCAM‐expressing breast cancer cell line (BT-474). EpMab-37-mG2a-f recognized BT-474 cells with a moderate binding-affinity [a dissociation constant (KD): 2.9x10-8 M] by flow cytometry. EpMab-37-mG2a-f exhibited ADCC and CDC for BT-474 cells by murine splenocytes and complements, respectively. Furthermore, administration of EpMab-37-mG2a-f significantly suppressed the BT-474 xenograft tumor development compared with the control mouse IgG. These results indicated that EpMab-37-mG2a-f exerts antitumor activities against the BT-474 xenograft, and could provide valuable therapeutic regimen for the breast cancers.

Abstract Objectives: The purpose of this study was to determine whether breast cancer and diabetes status are related in adult Americans. Methods: We conducted a cross-sectional study of 7,599 individuals from the National Health and Nutrition Examination Survey (NHANES). Diabetes was classified as type 2 diabetes and pre-diabetes. Both prediabetes and diabetes were diagnosed according to ADA 2014 guidelines. Multiple logistic regression analysis was used to explore the relationship between diabetes status and breast cancer. Results: We found that prediabetes (OR = 0. 60, 95% CI:(0. 40, 0. 88), P= 0. 009613) and non-diabetes (OR = 0.05.3,95% CI: (0.34, 0.83), P = 0. 006014) were associated with a reduced risk of breast cancer in comparison to Type 2 diabetes (literature). Prediabetes in non-Hispanic blacks was associated with a reduced risk of breast cancer (OR=0. 55,95%CI:0. 40-0. 75, P<0. 001). Using two segmented linear regression models to fit the relationship between BMI and breast cancer, we found that the relationship between BMI and breast cancer was nonlinear, but there was a threshold effect. The threshold effect analysis found that BMI affcted breast cancer at an inflection point 26. 3 Kg/m2. Adjusted OR (95% CI) on both sides of the turning point was 1. 0799 ( 1. 0029, 1. 1629 ) and 0. 9873 ( 0. 9638, 1. 0115 ), respectively. Conclusions: Diabetes status is associated with the risk of breast cancer development. Moreover, the risk of developing breast cancer steadily increased from nondiabetes to prediabetes and type 2 diabetes. In addition, the prevalence of breast cancer showed a gradual increase withincreasing BMI up to 26. 3 Kg/m2 with the highest prevalence of breast cancer. There was an inverse U-shaped relationship between BMI and the breast cancer prevalence.

Esculetin is a coumarin compound, which belongs to the class of benzopyrone enriched in various plants such as Sonchus grandifolius, Aesculus turbinata, and many others. Glycosides and caffeic acid conjugates are the common forms of esculetin present in medicinal plants. Esculetin acts as an antioxidant, anti-inflammatory, anti-diabetic, anti-hepatic, and anti-cancer agent by inhibiting the production of free radicals, inflammatory mediators, and genes that cause liver diseases and cancer. It also aids in the regulation of blood sugar. Scientists developing pharmaceutical formulations require some rationale and preliminary studies for drug design, but a small number of clinical studies on humans containing esculetin limit its potential for use as a safe alternative drug. Therefore, in this review article, the published studies have been reviewed to identify the pathogenesis of cancer, oxidative stress, inflammation, arthritis, diabetes and fatty liver along with the discussion on potential therapeutic strategies of esculetin. Advancements in our understanding of these diseases will aid in the development of new and innovative medications for treating many ailments. In conclusion, esculetin has immense potential to be used as a safe drug against many diseases but requires further testing and confirmation through clinical trials.

The purpose of this review is to present the current knowledge about the diagnostic and treatment options in bladder cancer (BCa) patients with clinically positive lymph nodes (cN+). In this review compaction of CT and MRI performance in preoperative prediction of lymph node invasion (LNI) in BCa patients was presented, along with other diagnostic methods. Most scientific societies do not distinguish cN+ patients in their guidelines, recommendations concern muscle-invasive bladder cancer (MIBC) and differ between associations. Currently, the standard treatment of patients with MIBC is radical cystectomy (RC) with bilateral pelvic lymph node dis-section (PLND). The template of PLND and its therapeutic value remain debatable. Moreover, most guidelines recommend neoadjuvant chemotherapy (NAC). However, there is still lack of definitive evidence of the superiority of neoadjuvant chemotherapy over adjuvant chemotherapy. Nevertheless, the curative treatment that provides the best long-term survival in cN+ patients is a multimodal approach with a combination of chemotherapy and RC. Recent studies demonstrate the growing importance of immunotherapy. Special attention should be paid to cN+ BCa patients as the oncological outcomes are significantly worse for this group.

The high costs of cancer treatment and lack of investment in health care are significant obstacles to public health on the African continent. The objective of this study was to estimate the financial cost of treating children suffering from cancer in Africa. We conducted a systematic review and meta-analysis of expert opinions between March 2000 and March 2020. The key search terms included ‘cost’, ‘cancer’ and ‘child’; we selected articles that specifically addressed the financial costs of childhood cancer in African countries. Of the 103 articles found, 18 met the inclusion criteria. Cancer care was a heavy financial burden in most of the countries studied, although costs varied from country to country; the average expenditure on healthcare was US$1017.39 ± US$319.1 per year. In countries without a health insurance system, the highest proportion of cancer care costs, 46.6%, was indirect, whereas in countries with a cancer financing system, the direct cost of treatment was low, 53.4%. The cost of treating childhood cancer is high in Africa in relation to the standard of living of individuals residing in this region.

Histologically poor differentiation is associated with lymph node metastasis. Thus, pathological evaluation of biopsy specimens is crucial when treating stomach cancers. Deep learning of WSIs is challenging because the images are enormous. Given the computing limitations, patch-level supervised learning methods have been proposed. However, valuable information is lost when dividing WSIs into smaller patches. Another drawback is the need for pixel-level annotation by a pathologist. It is acceptable to differentiate, i.e., grade, gastric cancer at the holistic tissue level (i.e., under low magnification). We developed a weakly supervised learning technique for tissue-level gastric adenocarcinoma histological differentiation (well-to-moderately or poorly differentiated) and applied global reasoning to tissue-level features. The tissue-level AUROCs of the histological differentiation classifiers were 0.953, 0.969, and 0.943, respectively when data from five hospitals were subjected to threefold cross-validation. Comparison of the Grad-CAM heatmaps of the trained classifier and the pathologists’ annotations confirmed that our weakly supervised model exhibited performed well.

Background: Current strategies in circulating tumor cell (CTC) isolation in pancreatic cancer heavily rely on the EpCAM and cytokeratin cell status. EpCAM is generally not considered as a good marker given its transitory change during Epithelial to Mesenchymal Transition (EMT) or reverse EMT. There is a need to identify other surface markers to capture the complete repertoire of PDAC CTCs. The primary objective of the study is to characterize alternate surface bi-omarkers to EpCAM on CTCs that express low or negligible levels of surface EpCAM in pancre-atic cancer patients. Methods: Flow cytometry and surface mass spectrometry were used to iden-tify proteins expressed on the surface of PDAC CTCs in culture. CTCs were grown under condi-tions of attachment and in co-culture with naïve neutrophils. Putative biomarkers were then validated in GEMMs and patient samples. Results: Surface proteomic profiling of CTCs identi-fied several novel protein biomarkers. ALCAM was identified as a novel robust marker in GEMM models and in patient samples. Conclusions: We identified several novel surface bi-omarkers on CTCs expressed under differing conditions of culture. ALCAM was validated and identified as a novel alternate surface marker on EpCAMlow CTCs.

Breast cancer (BC) is a heterogeneous disease representing a substantial economic burden. In order to develop policies that successfully decrease this burden, the factors affecting costs need to be fully understood. Evidence suggests that early detection in Stage I has a lower cost than late detection. We aim to provide conservative estimates of BC's stage-wise medical costs from German healthcare and the payer's perspective. To this end, we conducted a literature review of articles evaluating stage-wise costs of BC in Germany through PubMed, Web of Science, and Econ Lit databases supplemented by Google Scholar. We developed a decision tree model to estimate BC related medical costs in Germany using available treatment and cost information. The review generated seven studies; none estimated the stage-wise costs of BC. The studies were classified into two groups: (1) case scenarios (five studies) and two studies based on administrative data. The first sickness funds data study (Gruber, Stock, et al. 2012) used 1999 information to approach BC attributable cost; their results suggest a range between €3,929 and €11,787 depending on age. The second study (Kreis, Plöthner, et al. 2020) used 2011-2014 data and suggested an initial phase incremental cost of €21,499, an intermediate phase cost of €2,620, and a terminal phase cost of €34,513 per incident case. Our decision tree model based BC stage-wise cost estimates were €21,523 for Stage I, €25,679 for Stage II, €30,156 for Stage III, €42,086 for Stage IV. Alternatively, the modeled cost estimates are €20,284 for the initial phase of care, €851 for the intermediate phase of care, and €34,963 for the terminal phase of care. Our estimates for phases of care are consistent with recent German estimates provided by Kreis and Plöthner et al. Furthermore, the data collected by sickness funds are collected primarily for reimbursement purposes, where the German ICD-10 classification system defines a cancer diagnosis. As a result, claims data lack the clinical information necessary to understand stage-wise BC costs. Our model-based estimates fill the gap and inform future economic evaluations of BC interventions.

The incidence and mortality rates of cervical cancer are rising among young women in Japan. In November 2021, the Japanese Ministry of Health, Labour and Welfare reinstated the active recommendation for the human papillomavirus (HPV) vaccine, which was discontinued in June 2013 due to reports of adverse reactions, including chronic pain and motor dysfunction, following vaccination. However, vaccine hesitancy among the younger generation remains, and it is essential to identify the barriers in vaccination uptake. Therefore, we aim to conduct a randomized study using different methods of providing educational contents to improve health literacy regarding cervical cancer and HPV vaccination among female students in Japan. Here, we present the results of our preliminary report and discuss current topics related to HPV vaccination in Japan. Data were collected from 27 female students—divided into three groups: no intervention, print-based intervention, and SNS-based intervention—using the Health Literacy Scale and Communicative and Critical Health Literacy scale. Our primary results indicate that participants’ knowledge and health literacy improved post intervention. Therefore, medical professionals must provide accurate scientific knowledge regarding routine HPV vaccination and the risk of cervical cancer to young women to improve their health literacy and subsequently increase the HPV vaccination rates.

Knowledge regarding the influence of the microbial community in cancer promotion or protection has expanded even more through the study of bacterial metabolic products and how they can modulate cancer risk, which represents an extremely challenging approach for the relationship between intestinal microbiota and colorectal cancer (CRC). This review discusses research pro-gresses in the effect of bacterial dysbiosis from a metabolic point of view, particularly on the bio-chemical mechanisms of butyrate, one of the main short chain fatty acids (SCFAs) with an-ti-inflammatory and anti-tumor properties in CRC. Increased daily intake of omega-3 polyun-saturated fatty acids (PUFAs) significantly increases the density of bacteria that are known to produce butyrate. Omega-3 PUFAs have been proposed as a treatment to prevent gut microbiota dysregulation and lower the risk or progression of CRC.

Lung cancer (LC) is one of the leading causes of cancer occurrence and mortality worldwide. Treatment of patients with advanced and metastatic LC presents a significant challenge as malignant cells use different mechanisms to resist chemotherapy. Drug resistance (DR) is a complex process that occurs due to a variety of genetic and acquired factors. Identifying the mechanisms underlying DR in LC patients and possible therapeutic alternatives for more efficient therapy is a central goal of LC research. Advances in nanotechnology resulted in the development of targeted and multifunctional nanoscale drug constructs. The possible modulation of the components of nanomedicine, their surface functionalization, and encapsulation of various active therapeutics provide promising tools to bypass crucial biological barriers. These attributes enhance the delivery of multiple therapeutic agents directly to the tumor microenvironment (TME), resulting in reversal of LC resistance to anticancer treatment. This review provides a broad framework for understanding the different molecular mechanisms of DR in lung cancer; presents novel nanomedicine therapeutics aimed to improve the efficacy of treatment of various forms of resistant LC; outlines current challenges in using nanotechnology for reversing DR; and discusses the future directions for clinical application of nanomedicine in management of LC resistance.

Malignant neoplasm is one of the most incurable diseases among inflammatory diseases. Researchers have been studying for decades to win over this lethal disease and provide the light of hope to humankind. The gastrointestinal bacteria of human hold a complex ecosystem and maintain homeostasis. One hundred trillion microbes are residing in the gastrointestinal tract of human. Disturbances in the microbiota of human’s gastrointestinal tract can create immune response against inflammation and also can develop diseases , including cancer. The bacteria of the gastrointestinal tract of human, can secrete a variety of metabolites and bioproducts which aid in the preservation of homeostasis in the host and gut. During pathogenic dysbiosis, on the other hand, numerous microbiota subpopulations may increase and create excessive levels of toxins, which can cause inflammation and cancer. Furthermore, the immune system of host and the epithelium cell can be influenced by gut microbiota. Probiotics, which are bacteria that live in the gut, have been protected against tumor formation. Probiotics are now studied to see if they can help fight dysbiosis in cancer patients undergoing chemotherapy or radiotherapy because of their capacity to maintain gut homeostasis. Countless numbers of gut bacteria have demonstrated anti-cancer efficiency in cancer treatment, prevention, and boosting the efficiency of immunotherapy. The review article has briefly explained the anti-cancer immunity of gut microbes and their application in treating a variety of cancer. This review paper also highlights the pre-clinical studies of probiotics against cancer and the completed and ongoing clinical trials on cancers with the two most common and highly effective probiotics Lactobacillus and Bacillus spp.

Familial colorectal cancer (CRC) is only partially explained by known germline predisposing genes. We performed whole genome sequencing in 15 Polish families of many affected individuals, without mutations in known CRC predisposing genes. We focused on loss-of-function variants and functionally characterized them. We identified a frameshift variant in the CYBA gene (c.246delC) in one family and a splice site variant in the TRPM4 gene (c.25-1 G>T) in another family. While both variants were absent or extremely rare in gene variant databases, we identified four additional Polish familial CRC cases and two healthy elderly individuals with the CYBA variant (odds ratio 2.46, 95% confidence interval 0.48-12.69). Both variants led to a premature stop codon and to a truncated protein. Functional characterization of the variants showed that knockdown of CYBA or TRPM4 depressed generation of reactive oxygen species (ROS) in LS174T and HT-29 cell lines. Knockdown of TRPM4 resulted in decreased MUC2 protein production. CYBA encodes a component in the NADPH oxidase system which generates ROS and controls, e.g., bacterial colonization in the gut. Germline CYBA variants are associated with early onset inflammatory bowel disease, supported with experimental evidence on loss of intestinal mucus barrier function due to ROS deficiency. TRPM4 encodes a calcium-activated ion channel, which in a human colonic cancer cell line controls calcium-mediated secretion of MUC2, a major component of intestinal mucus barrier. We suggest that the gene defects in CYBA and TRPM4 mechanistically involve intestinal barrier integrity through ROS and mucus biology, which converges in chronic bowel inflammation.

Glioblastoma (GB) is the most frequent malignant brain tumor among adults and currently there is no effective treatment. It is a very aggressive tumor that grows fast and spreads through the brain causing the death of patients in 15 months. GB cells mutate frequently and generate a heterogeneous population of tumoral cells genetically distinct. Thus, the contribution of genes and signaling pathways relevant for GB progression is of great relevance. We use a Drosophila model of GB that reproduces the features of human GB, and describe the upregulation of the circadian gene cry in GB patients and in a Drosophila GB model. We study the contribution of cry to the expansion of GB cells, to the neurodegeneration caused by GB, and to premature death and determine that cry is required for GB progression. Moreover, we analyze the mechanisms that regulate cry expression by the PI3K pathway. Finally, we conclude that cry is necessary and sufficient to regulate myc expression in GB. These results contribute to the understanding of the signals that impulse GB malignancy and lethality and open novel opportunities for the treatment of GB patients.

β-apopicropodophyllin (APP), a derivative of podophyllotoxin (PPT), has been identified as a potential anti-cancer drug. This study tested whether APP acts as an an-ti-cancer drug and can sensitize colorectal cancer (CRC) cells to radiation treatment. APP had an anti-cancer effect against the CRC cell lines HCT116, and DLD-1, SW480 and COLO320DM with IC50 values of 7.88 nM, and 8.22 nM, 9.84 nM and 7.757 nM, respec-tively induction of DNA damage. Colonogenic and cell counting assays indicated that the combined treatment of APP and γ-ionizing radiation (IR) showed greater retardation of cell growth than either alone, suggesting that APP sensitizes CRC cells to IR. Annexin V-propidium iodide (PI) assays and immunoblot analysis showed that the combined treatment of APP and IR increased apoptosis in CRC cells compared with either APP or IR alone. Results obtained from the xenograft experiments also indicated that the combination of APP and IR enhanced apoptosis in in vivo animal model. Apoptosis induction by the combined treatment of APP and IR resulted from reactive oxygen species (ROS). Inhibition of ROS by N-acetylcysteine (NAC) restored cell viability and decreased the induction of apoptosis by APP and IR in CRC cells. Taken together, these results indicate that a combined treatment of APP and IR might promote apoptosis by inducing ROS in CRC cells.

Background: Metastasis is a complex process that involves the spread of the tumor to distant parts of the body from its original site. Metastatic dissemination represents the main physiopathology of cancer. Soluble factors such as cytokines have been closely related to breast cancer (BC) metastasis. Bisphenol A (BPA) is an endocrine disrupting chemical compound with estrogenic properties, which exposure in the early stages of neonatal life leads to an increase in the size and weight of breast tumors and cellular changes in the tumoral immune microenvironment. Methods: Thus, we used female BALB/c mice that were exposed neonatally to a single dose of BPA. Once sexual maturity was reached, a mammary tumor was induced injecting 4T1 cells in situ. After 25 days of injection, we evaluated endocrine alterations, cytokine expression, tissue alterations denoted by macro and micro metastases in the lung, and metastasis-induced cell infiltration. Results: BPA neonatal treatment did not show significant endocrine alterations. Nevertheless, BPA induced a great rate of metastasis to the lung associated with higher intratumoral expression of IL-1b, IL-6, IFN-g, TNF-a and VEGF. Conclusions Our data suggest that cytokines are key players in BC metastasis induction, and that BPA is a risk factor to be considered. This knowledge must be considered with the aim of recognizing environmental pollution in the clinical history of patients to possibly counter BC metastases.

Background: Gastric cancer (GC) is one of the leading malignancy diseases worldwide, especially in Asian. CAST is a potential oncogene in GC carcinogenesis process. The character of macrophage infiltration in GC microenvironment was also unaddressed. Methods: We first applied machine searching in gene candidate evaluation of GC. CAST expression was analyzed via the Human Protein Atlas (HPA) and Gene Expression Profiling Interactive Analysis 2 (GEPIA2) database. Protein-protein interaction (PPI) network was downloaded from STRING. We investigated the impact of CAST on clinical prognosis using Kaplan-Meier plotter. The correlations between CAST and Lgr5 and macrophage infiltration in GC was surveyed via TIMER 2.0. Finally, GeneMANIA was also used to evaluate the possible functional linkage between genes. Results: After machine-assisted searching, CAST expression was found signicant difference in the overall survival of GC patients. STRING revealed CAST related proteomics and transcriptomics associations, mainly about CAPN family. Moreover, CAST significantly impacts the prognosis of GC from other datasets validation. Notably, high CAST expression was correlated with worse overall survival in GC patients (hazard ratio = 1.59; logrank P = 9.4 x 10-8). CAST and Lgr5 expressions were both positively correlated with WNT 2 and WNT 2B. Among GC patients in several datasets, CAST and macrophage infiltration evaluated together showed no obvious trend toward poor clinical overall survival. Conclusion: CAST plays an important role in GC clinical prognosis and is associated with WNT 2/WNT 2B/Lgr5. Our study denmostrated that CAST in GC overall survival is regulated by macrophage infiltration.

Background: About 10% of Wilms Tumor (WT) patients have a malformation or cancer predisposition syndrome (CPS) with causative germline genetic or epigenetic variants. Knowledge on CPS is essential for genetic counselling. Methods: This retrospective analysis focused on 2927 consecutive patients with WTs registered between 1989 and 2017 in the SIOP/GPOH studies. Results: (GU, N=66, 2,3%), Beckwith-Wiedemann spectrum (BWS, N=32, 1,1%), isolated hemihypertrophy (IHH, N=29, 1,0%), Denys-Drash syndrome (DDS, N=24, 0,8%) and WAGR syndrome (N=20, 0,7%) were reported most frequently. Compared to others, these patients were younger at WT diagnosis (median age 24,5 months vs. 39,0 months), had smaller tumors (334,8mL vs. 496,9mL), less often metastasis (8,2% vs. 18%), but more often nephroblastomatosis (12,9% vs. 1,9%). WT with IHH was associated with blastemal WT and DDS with stromal subtype. Bilateral WTs were common in WAGR (30%), DDS (29%) and BWS (31%). Chemotherapy induced reduction in tumor volume was poor in DDS (7,7% increase) and favorable in BWS (84,6% reduction). The event-free survival (EFS) of patients with BWS was significantly (p=0,002) worse than in others. Conclusions: CPS should be considered in WTs with specific clinical features resulting in referral to a geneticist. Their outcome was not always favorable.

Background: Zebrafish (Danio rerio) is a model organism emerged for the study of human cancer. Compared with the murine model, the zebrafish model has several properties ideal for personalized therapies. The transparency of the zebrafish embryos and the development of the pigment-deficient “casper” zebrafish line give the capacity to directly observe cancer formation and progression in the living animal. Automatic quantification of cellular proliferation in vivo is critical to the development of personalized medicine. Methods: A new methodology was defined to automatically quantify the cancer cellular evolution. ZFTool was developed to establish a base threshold that eliminates the embryo auto-fluorescence and automatically measures the area and intensity of GFP (green-fluorescent protein) marked cells and define a proliferation index. Results: Proliferation index automatically computed on different targets demonstrates the efficiency of ZFTool to provide a good automatic quantification of cancer cell evolution and dissemination. Conclusion: Our results demonstrate that ZFTool is a reliable tool for the automatic quantification of the proliferation index, being a measure of cancer mass evolution in zebrafish eliminating the influence of its autofluorescence.

Overexpression of BRF2, a selective subunit of RNA polymerase III, has been shown to be crucial in the development of several types of cancers, including breast cancer and lung squamous cell carcinoma . Predominately, BRF2 acts as a central redox-sensing transcription factor (TF) and is involved in rescuing oxidative stress (OS) -induced apoptosis. Here, we showed a novel link between BRF2 and DNA damage response. Due to the lack of BRF2 specific inhibitors, through virtual and molecular dynamics screening, we identified potential drug candidates that interfere with BRF2-TATA-binding Protein (TBP)-DNA complex interactions based on binding energy, intermolecular, and torsional energy parameters. We experimentally tested Bexarotene as a potential BRF2 inhibitor. We found that Bexarotene (Bex) treatment resulted in a dramatic decline in oxidative stress (Tert-butylhydroquinone (tBHQ))-induced levels of BRF2 and consequently, lead to a decrease in cellular proliferation of cancer cells which may in part be due to drug pretreatment induced reduction of ROS generated by the oxidizing agent. Our data thus, provide the first experimental evidence that BRF2 is a novel player in DNA damage response pathway and Bexarotene can be used as a potential inhibitor to treat cancers with the specific elevation of oxidative stress.

Cancer cells utilize a number of mechanisms to increase their survival and progression as well as their resistance to anticancer therapy: deregulation of growth regulatory pathways by acquiring grow factor independence, immune system suppression, reducing the expression of antigens activating T lymphocyte cells (mimicry), induction of anti-apoptotic signals to counter the action of drugs, activation of several DNA repair mechanisms and driving the active efflux of drugs from the cell cytoplasm and epigenetic regulation by microRNAs (miRNAs). Due to the fact that it is commonly diagnosed late, lung cancer remains a major malignancy with a low five-year survival rate; when diagnosed, the cancer is often highly advanced and the cancer cells may have acquired drug resistance. This review summarizes the main mechanisms involved in cisplatin resistance and in interactions between cisplatin-resistant cancer cells and the tumor microenvironment. It also analyses changes in the gene expression profile of cisplatin sensitive vs. cisplatin resistant non–small cell lung cancer (NSCLC) cellular model using the GSE108214 Gene Expression Omnibus database. It describes a protein-protein interaction network that indicates highly-dysregulated TP53, MDM2 and CDKN1A genes as they encodes the top networking proteins that may be involved in cisplatin tolerance, these all being upregulated in cisplatin-resistant cells. Furthermore, it illustrates the multifactorial nature of cisplatin resistance by examining the diversity of dysregulated pathways present in cisplatin-resistant NSCLC cells based on KEGG pathway analysis.

The use of multi-gene panels for germline testing in breast cancer enables the estimation of cancer risk and guides risk-reducing management options for tested individuals and their family members. We performed an analysis in our clinical database to identify breast cancer patients undergoing genetic testing with positive reports. We reviewed positive results with respect to the different levels of information provided in the reports; risk estimation and management, cascade family testing, information from secondary findings and actionable information for treatment decision-making. A total of 415 positive test reports were identified with 57.1%, 18.1%, 10.8% and 13.5% of individuals having pathogenic/likely pathogenic variants in high (BRCA1, BRCA2, PALB2, PTEN, TP53), moderate (ATM, CHEK2, NBN), low (BARD1, BRIP1, CHEK2, MLH1, MSH2, MSH6, NF1, RAD51C) and with insufficient evidence for breast cancer risk genes (FANCA, FANCM, NBN, MRE11, PMS2, RAD50, RAD51B, XRCC2, MUTYH), respectively. 6.7% of individuals were double heterozygotes with two pathogenic variants. Germline findings in 92% of individuals are linked to evidence-based treatment information and receive risk estimates for predisposition to breast and/or other cancer types. The use of germline findings for treatment decision making expands the indication of genetic testing to include individuals that could benefit from targeted treatments.

Due to the high effectiveness of cancer screening and therapies, the diagnosis of second primary cancers (SPCs) has increased in women with endometrial cancer (EC). However, there’s no previous literature mentioned about adequate evidence to support screening for SPCs in endometrial cancer. This study was aimed to develop effective risk prediction models of second primary endometrial cancer in women with obesity (Body-mass index; BMI > 25) and this study includes datasets of the incidence of SPCs and the other risks of SPCs in 4480 primary cancer survivors by a hospital-based cancer registry database. In our study, we found the obesity played a key role in SPCs. There’re 10 independent variables used as predicting variables, which corelated to obesity should be monitored for the early detection of SPCs in endometrial cancer. In conclusion, it is a promising SPCs prediction. The proposed scheme can support the important influence of obesity and clinical data representations in all cases after primary treatments. Our results suggested that obesity is still a crucial risk factor to SPCs in endometrial cancer.

The prominent cultivation of lemongrass relies on the pharmacological incentives of its essential oil. The lemongrass essential oil (LEO) has a significant amount of citral (mixture of geranial and neral), isoneral, isogeranial, geraniol, geranyl acetate, citronellal, citronellol, germacrene-D, and elemol in addition to numerous other bioactive compounds. These components confer various medicinal activities to LEO including antifungal, antibacterial, antiviral, anticancer, and antioxidant properties. These attributes are commercially exploited in pharmaceutical, cosmetics, and food preservations industries. Furthermore, the employment of LEO in the treatment of cancer opens a new vista in the field of therapeutics. Although different LEO components have shown promising anticancer activities in vitro, these effects have not been assessed yet in humans. Further studies on the anticancer mechanisms exerted by lemongrass components are required. The present review intends to provide a timely discussion on the relevance of lemongrass extracts in cancer and health treatment, and in food industry applications.

The PI3K/mTOR signalling pathway plays a central role in the governing of cell growth, survival and metabolism. As such, it must integrate and decode information from both external and internal sources to guide efficient decision-making by the cell. To facilitate this, the pathway have evolved an intricate web of complex regulatory mechanisms and elaborate crosstalk with neighbouring signalling pathways, making it a highly non-linear system. Here, we describe the mechanistic biological details that underpin these regulatory mechanisms, covering a multitude of negative and positive feedback loops, feed-forward loops, competing protein interactions, and crosstalk with major signalling pathways. Further, we highlight the non-linear and dynamic network behaviours that arise from these regulations, uncovered through both computational and experimental studies. Given the pivotal role of the PI3K/mTOR network in cellular homeostasis and its frequent dysregulation in pathologies including cancer and diabetes, a coherent and systems-level understanding of the complex regulation and consequential dynamic signalling behaviours within this network is imperative for advancing biology and development of new therapeutic approaches.

Breast cancer (BC) is the most common cancer diagnosed in women worldwide. Approximately 70% of BC patients have the luminal subtype, which expresses hormone receptors (HR+). Adjuvant endocrine treatments are the standard of care for HR+/HER2- BC patients. Over time, approximately 30% of those patients develop endocrine resistance and metastatic disease. Cyclin-dependent kinase inhibitors (CDKi) in combination with an aromatase inhibitor or fulvestrant have demonstrated superior efficacies in increasing progression-free survival, with a safe toxicity profile, in HR+/HER2- metastatic BC patients. CDKi blocks kinases 4/6, preventing G1/S cell cycle transition. However, not all patients respond to CDKi, and those who do respond ultimately develop resistance to the combined therapy. Studies in tumour tissues and cell lines have tried to elucidate the mechanisms underlying this progression, but there are still no conclusive data. Over the last few years, liquid biopsy has contributed relevant information. Circulating tumour materials are potential prognostic markers for determining patient prognosis in metastatic luminal BC, for monitoring disease and for treatment selection. This review outlines the different studies performed using liquid biopsy in patients with HR+ metastatic BC treated with CDKi plus endocrine therapy. We focus mainly on those studies that describe possible resistance mechanisms in circulating tumour-derived material.

Background: Breast cancer is the second type of cancer diagnosed in women and is the first cancer in women worldwide. Breast cancer also causes high morbidity and mortality in women and becomes a heavy burden due to the incidence of disability due to the disease. Purpose: This literature review aims to examine how social support affects anxiety, depression and quality of life in breast cancer sufferers. Method: The data were obtained by searching for reputable and trustworthy journals. have high quality criteria, namely Scopus, Proquest, Science Direct, Elsevier, Pubmed. Journals or articles used in this review literature are searched using keywords and Boolean operators (AND, OR NOT, or AND NOT). Keywords in this review literature are as follows: social support OR family support, quality of life OR Quality, anxiety OR depression, AND Cancer OR cancer treatment OR Chronic disease. Results: The results of this literature review show that there is a significant influence between the social support received by breast cancer patients on the improvement of their quality of life. The social support provided is also able to reduce anxiety and depression in breast cancer sufferersConclusion: Social support given to breast cancer patients is proven to have an effect on improving the quality of life, reducing anxiety and depression.

About 15% of colorectal cancer (CRC) patients have first-degree relatives affected by the same malignancy. However, for most families the cause of familial aggregation of CRC is unknown. In order to identify novel high-to-moderate penetrant germline variants underlying CRC susceptibility, we performed whole exome sequencing (WES) on four CRC cases and two unaffected family members of a Polish family without any mutation in known CRC predisposition genes. After WES, we used our in-house developed Familial Cancer Variant Prioritization Pipeline and identified two novel variants in the solute carrier family 15 member 4 (SLC15A4) gene. The heterozygous missense variant, p. Y444C, was predicted to affect the phylogenetically conserved PTR2/POT domain and to have a deleterious effect on the function of the encoded peptide/histidine transporter. The other variant was located in the upstream region of the same gene (GRCh37.p13, 12_129308531_C_T; 43bp upstream of transcription start site, ENST00000266771.5) and it was annotated to affect the promoter region of SLC15A4 as well as binding sites of 17 different transcription factors. Our findings of two distinct variants in the same gene may indicate a synergistic up-regulation of SLC15A4 as the underlying genetic cause and implicate this gene for the first time in genetic inheritance of familial CRC.

Nowadays, cervical cancer (CC) is treated as the leading cancer among women throughout the world. Despite effective vaccination and improved surgery and treatment, CC remains its fatality rate about half of the infected populations globally. The major screening biomarkers and therapeutic target identification have now become a global concern. The present study, we have employed systems biology approaches to retrieve the potential biomarkers and pathways from the transcriptomic profiling. Initially, we have identified 76 of each up-regulated and down-regulated gene from a total of 4,643 differentially expressed genes. The up-regulatory genes are mainly concentrating on immune-inflammatory response and the down-regulatory genes are on receptor binding and gamma-glutamyltransferase. The involved pathways associated with these genes were also assessed through pathway enrichment and they were mainly focused on different cancer pathways, immunoresponse, and cell cycle pathways. After the subsequent enrichment of these genes, we have identified 12 hub genes, which play a crucial role in CC. Furthermore, the survival of the hub genes was also assessed, and among them, finally, CXCR4 has identified as one of the most potential differentially expressed gene that might play a vital role to the survival of CC patients. Thus CXCR4 could be used as a prognostic biomarker and development of a drug target for CC.

Abstract: Background: Intensity modulated radiotherapy (IMRT) is still a standard of care for radiotherapy in locally advanced head and neck cancer (LA-HNSCC). Simultaneous integrated boost (SIB) and moderate hypofractionation offer an opportunity for individual dose painting and a reduction in overall treatment time. We present retrospective data on toxicity and locore-gional control of a patient cohort with LA-HNSCC treated with an IMRT-SIB concept in compar-ison to normofractionated 3D-conformal radiotherapy (3D-RT) after a long-term follow-up. Methods: Between 2012 and 2014, n=67 patients with HNSCC (stages III/IV without distant me-tastases) were treated with IMRT-SIB either definitively (single/total doses: 2.2/66 Gy, 2.08/62.4 Gy, 1.8/54 Gy in 30 fractions) or in the postoperative setting (2.08/62.4 Gy, 1.92/57.6 Gy, 1.8/54 Gy). These patients' clinical courses were matched (for sex, primary, and treatment concept) as part of a matched-pair analysis with patients treated before mid-2012 with normofractionated 3D-CRT (definitive: 2/50 Gy followed by a sequential boost up to 70 Gy; postoperative: 2/60-64 Gy). Chemotherapy/ immunotherapy was given concomitantly in both groups in the definitive situation (postoperative dependent on risk factors). The primary endpoints were acute and late toxicity; the secondary endpoint was locoregional control (LRC). Results: Sixty-seven patients treated with IMRT-SIB (n = 20 definitive, n = 47 adjuvant) were matched with 67 patients treated with 3D-RT. There were minor imbalances between the groups concerning nonmatching variables such as extracapsular extension (ECE) and chemotherapy in IMRT-SIB. Significantly less toxicity was found in favor of IMRT-SIB concerning dysphagia, ra-diation dermatitis, xerostomia, fibrosis, and lymphedema. After a median follow-up of 63 months, the median LRC was not reached (IMRT-SIB) vs. 69.5 months (3D-RT) (p=0.63). Conclusions: This moderately hypofractionated IMRT-SIB concept was shown to be feasible with less toxicity than conventional 3D-RT in this long-term follow-up observation.

Colorectal cancer (CRC) shows one of the largest proportions of familial cases among different malignancies, but only 5-10% of all CRC cases are linked to mutations in established predisposition genes. Thus, familial CRC constitutes a promising target for the identification of novel, high- to moderate-penetrance germline variants underlying cancer susceptibility by next generation sequencing. In this study, we performed whole genome sequencing on 3 members of a family with CRC aggregation. Subsequent integrative in silico analysis using our in-house developed variant prioritization pipeline resulted in the identification of a novel germline missense variant in SRC gene (V177M), a proto-oncogene highly upregulated in CRC. Functional validation experiments in HT-29 cells showed that introduction of SRCV177M resulted in increased cell proliferation and enhanced protein expression of phospho-SRC (Y419), a potential marker for SRC activity. Upregulation of paxillin, β-Catenin and STAT3 mRNA levels, increased levels of phospho-ERK, CREB and CCND1 proteins and downregulation of the tumor suppressor p53 further proposed the activation of several pathways due to the SRCV177M variant. The findings of our pedigree-based study contribute to the exploration of the genetic background of familial CRC and bring insights into the molecular basis of upregulated SRC activity and downstream pathways in colorectal carcinogenesis.

The emergence of three-dimensional human organoids has opened the door for development of patient-derived cancer organoid (PDO) models, which closely recapitulate parental tumor tissue. Mainstays of preclinical cancer modeling include in vitro cell lines and patient-derived xenografts, but these models lack the cellular heterogeneity seen in human tumors. Moreover, xenograft establishment is resource- and time-intensive, rendering these models difficult to use to inform clinical trials and decisions. PDOs, however, can be created efficiently and retain tumor-specific properties such as cellular heterogeneity, cell-cell and cell-stromal interactions, tumor microenvironment, and therapeutic responsiveness. PDO models and drug screening protocols have been described for several solid tumors and, more recently, for gliomas. Since PDOs can be developed in clinically relevant timeframes and share many characteristics of parent tumors, they may enhance the ability to provide precision oncologic care for patients. This review explores the current literature on cancer organoids, highlighting the history of PDO development, organoid models of glioma, and potential clinical applications of PDOs.

Breast cancer is the most commonly diagnosed cancer in women worldwide. Approximately, 70 % of breast cancer patients express hormone receptors (HR) (Luminal subtype). Adjuvant endocrine treatments are the standard of care in HR+/HER2- breast cancer. Over time, about 50% of those patients develop endocrine resistance and metastatic breast cancer. Cyclin-dependent kinase inhibitors (CDKi) in combination with an aromatase inhibitor or fulvestrant have demonstrated superior efficacy increasing progression-free survival, with a safe toxicity profile, in HR+/HER2- metastatic breast cancer patients. CDKi blocks kinases 4/6 ATP-binding domain preventing G1/S cell cycle transition. Despite this, not all patients respond to CDKi and those who respond, finally develop resistance to combination therapy. Different studies, in tumour tissue or cell lines, have tried to elucidate the mechanisms underlying this progression, but there are still no conclusive data. In the last few years, liquid biopsy has contributed relevant information to this knowledge. Liquid biopsy can be performed in real-time, non-invasively and be repeated whenever needed. Circulating tumour material are potential prognostic markers in metastatic luminal breast cancer to determine patient prognosis, monitor disease and treatment selection. The objective of this review is to outline the different studies carried out in HR+ metastatic breast cancer patients treated with CDKi plus endocrine therapy using liquid biopsy approaches looking for possible resistance mechanisms.

Several studies have suggested that pre and/or postdiagnosis physical activity can reduce the risk of recurrence in breast cancer patients, however its effect according to follow-up time has not yet been investigated. We analyzed recurrence and mortality dynamics in randomized clinical trials (RCTs) from Australia and Canada. The combined Australian RCTs evaluated, at median follow-up of 8.3 years, an 8-month pragmatic exercise intervention in 337 women with newly diagnosed breast cancer, while the Canadian RCT evaluated, at median follow-up of 7.4 years, supervised aerobic or resistance exercise during chemotherapy in 242 patients. For each RCT, the control arm consisted of patients undergoing usual care. We estimated the event dynamics by the discrete hazard function, through flexible regression of yearly conditional event probabilities with generalized additive models. In the considered RCTs, the recurrence and mortality risk of patients enrolled in the physical activity arm was stably reduced at medium/long term after five year of follow-up. In the Australian RCTs where patients were recruited by urban versus rural area, the latter group did not display benefit from physical activity. Estimated Odds Ratios (95% Confidence Intervals) for Disease Free Survival (DFS) in urban women were 0.63 (0.22-1.85); 0.27 (0.079-0.90); 0.11 (0.013-0.96) at the 3rd, 5th and 7th year of follow-up, respectively. For rural women, DFS patterns were overlapping with ORs approximating 1 at the different years of follow-up. Although not reaching statistical evidence, the estimates in the Canadian trial were in line with the results from the Australian urban women with ORs (95% CI) forDFS of 0.70 (0.33-1.50); 0.47 (0.19-1.18); 0.32 (0.077-1.29) at 3rd, 5th, 7th follow-up year, respectively. While we acknowledge that the analyzed RCTs were not designed for investigating disease recurrence over time, these results support the evidence that physical activity reduces the risk of developing medium/long-term metastases. Additional translational research is needed to clarify the mechanisms underlying these observations.

When the antioxidants in our immune system cannot neutralize or convert Reactive oxygen species into safe molecules at the rate at which it is produced then this imbalance is termed as “oxidative stress”. It is related with a wide array of diseases that includes cancer, diabetes, cardiovascular diseases, hypertension etc. These ROS species however are utmost essential for the proper functioning of human body which are produced as a consequence of partial oxidation of cellular metabolism performing essential functions such as protein phosphorylation, activation of several transcriptional factors, apoptosis, immunity, and differentiation. The sources by which these are produced can be broadly classified are intrinsic and extrinsic sources. There are variety of natural antioxidant enzymes of human body that combat against this oxidative stress. The extrinsic sources of ROS include the use of natural plants, extracted flavonoids and vitamins. In this review we will briefly explain how the sources of ROS, its essential function in human body, its elevation and associated damage to organs and effect on various diseases, and a hope of finding a way of how this oxidative stress can be exploited for therapeutic potential.

Single-stand selective monofunctional uracil DNA glycosylase 1 (SMUG1) works to remove uracil and certain oxidized bases from DNA during base excision repair (BER). This review provides a historical characterization of SMUG1 and 5-hydroxymethyl-2'-deoxyuridine (5-hmdU) one important substrate of this enzyme. Biochemical and structural analyses provide remarkable insight into the mechanism of this glycosylase revealing SMUG1 has a unique helical wedge which influences damage recognition during repair. Rodent studies suggest that, while SMUG1 shares substrate specificity with another uracil glycosylase UNG2, loss of SMUG1 can have unique cellular phenotypes. This review highlights the multiple roles SMUG1 may play in preserving genome stability, and how the loss of SMUG1 activity may promote cancer. Finally, we discuss recent studies indicating SMUG1 has moonlighting functions beyond BER, playing a critical role in RNA processing including the RNA component of telomerase.

In the present era, infertility is one of the major issues which restricts many couples to have their own kids. Infertility is the inability to achieve a clinical pregnancy after regular unprotected sexual intercourse for the period of one year or more. Various factors including defective male or female germ cell development, unhealthy and improper lifestyles, diseases like cancer and associated chemo-or-radiation therapies, congenital disorders etc. may be responsible for infertility. Therefore, it is highly important to understand the basic concepts of germ cell development including primordial germ cell (PGC) formation, specification, migration, entry to genital ridges and their molecular mechanisms, activated pathways, paracrine and autocrine signaling, along with possible alteration which can hamper germ cell development and can cause adversities like cancer progression and infertility. Knowing all these aspects in a proper way can be very much helpful in improving our understanding about gametogenesis and finding possible ways to cure related disorders. Here in this review, various aspects of gametogenesis especially female gametes and relevant factors causing functional impairment have been thoroughly discussed.

Biosensors are essential tools which have been traditionally used to monitor environmental pollution, detect the presence of toxic elements and biohazardous bacteria or virus in organic matter and biomolecules for clinical diagnostics. In the last couple of decades, the scientific community has witnessed their widespread application in the fields of military, health care, industrial process control, environmental monitoring, food-quality control, and microbiology. Biosensor technology has greatly evolved from the in vitro studies based on the biosensing ability of organic beings to the highly sophisticated world of nanofabrication enabled miniaturized biosensors. The incorporation of nanotechnology in the vast field of biosensing has led to the development of novel sensors and sensing mechanisms, as well as an increase in the sensitivity and performance of the existing biosensors. Additionally, the nanoscale dimension further assists the development of sensors for rapid and simple detection in vivo as well as the ability to probe single-biomolecules and obtain critical information for their detection and analysis. However, the major drawbacks of this include, but are not limited to potential toxicities associated with the unavoidable release of nanoparticles into the environment, miniaturization induced unreliability, lack of automation, and difficulty of integrating the nanostructured-based biosensors as well as unreliable transduction signals from these devices. Although the field of biosensors is vast, we intend to explore various nanotechnology enabled biosensors as part of this review article and provide a brief description of their fundamental working principles and potential applications.

Plasma medicine is a new field focusing on biomedical and clinical applications of cold physical plasmas, including their anticancer effects. Cold plasmas can be applied directly or indirectly as plasma activated liquids (PAL). The effect of plasma activated cell growth medium (PAM) and plasma activated phosphate buffered saline (PAPBS) were tested using a plasma pen generating streamer corona discharge in ambient air, on different cancer cell lines (melanoma A375, glioblastoma LN229 and pancreatic cancer MiaPaCa-2) and normal cells (human dermal fibroblasts HDFa). The viability reduction and apoptosis induction were detected in all cancer cells after incubation in PAL. In melanoma cells we focused on detailed insights to the apoptotic pathways. The anticancer effects depend on the plasma treatment time or PAL concentration. The first 30 minutes of incubation in PAL were enough to start processes leading to the cell death. In fibroblasts, no apoptosis induction was observed, only PAPBS, activated for longer time, slightly decreased their viability. Anticancer effects of PAM and PAPBS on cancer cells showed selectivity compared to normal fibroblasts, depended on correctly chosen activation time and PAL concentration. This selectivity, supported by optimum ratio of hydrogen peroxide and nitrites in PAL, is very promising for potential clinical applications.

Epidemiological studies have shown a strong association between high body mass index (BMI) and papillary thyroid cancer (PTC). We assessed the clinical and histopathological features of PTC in patients with a higher BMI and compared them to analogous parameters in PTC patients with a normal BMI. We retrospectively analyzed 5,021 medical records of patients admitted and surgically treated for thyroid tumors in one center between 2008 and 2018. Finally, we extracted data from 523 adult patients with PTC and stratified patients into two groups according to BMI: Group 1 with BMI < 25 kg/m² and Group 2 with BMI ≥25 kg/m². Data stratification was performed to estimate the association of overweight and obesity with clinical and histopathological features of PTC in both univariate and multivariate binary logistic regression analyses. Overall, compared to patients with a normal BMI, overweight and obese patients had a greater risk of minimal extrathyroidal extension (minimal ETE), multifocality and bilaterality of PTC (p<0.001 for all). Analysis did not show that BMI was significantly associated with more advanced tumor-node-metastasis (TNM) stage (p=0.894). Obesity and overweight were significantly associated with higher aggressiveness of PTC. When considering various management options for PTC patients, these findings regarding overweight and obesity should be taken into consideration during the decision-making process.

Ovarian cancer is the most frequent cause of deaths in gynecologic malignancies. Many possible mechanisms have been proposed via RNAseq and DNAseq technique recently. However, the driving factors are still obscure. The possible reasons are attributed to the incomplete human reference. This study integrated the canonical mapping-based and mapping-free protocols to extract reliable variations and novel events. We eventually obtained 450 reliable SNVs from the WES data and novel events from the RNAseq data, including 154 SNVs, 462 intron events, two repeats and six splice events. We identified six differentially expressed genes and six contigs that are significantly related to survival prognosis. The recurrent SNVs in significantly differentially expressed genes can be validated in an independent cohort of 20 Chinese ovarian cancer patients.

The imipramine ONC201 exerts a novel anti-proliferative activity over a wide spectrum of cancer cell types. ONC201 activates integrated stress response pathway that is associated with induction of Damage Inducible Transcript 3 (DDIT3, also known as C/EBP homologous protein or CHOP). We questioned whether the ONC201/CHOP crosstalk is regulated by diverse signaling pathways in non-metastatic versus metastatic cancer cell lines. Therefore, the Dukes' type B colorectal adenocarcinoma non-metastatic (SW480) and metastatic (LS-174T) cell lines were treated with ONC201. Cell proliferation and apoptosis were evaluated by MTT assay, flow cytometry analysis, gene expression was assessed by Affymetrix microarray, and key regulatory proteins were validated by Western blot assays. Unlike LS-174T cells, SW480 cells were resistant to ONC201 treatment. Gene ontology pathway enrichment analysis of differentially expressed genes revealed substantial differences between LS-174T and SW480 responsiveness to ONC201 treatment. In both cell lines, CHOP expression was upregulated in response to ONC201 treatment, however, its upstream regulatory mechanisms were not identical. Although, PERK, ATF6 and IRE1 ER-stress pathways were found to upregulated CHOP in both cell types, the BAK/BAX pathway was a notable regulator of CHOP in the metastatic LS-174T cells alone. In addition, CHOP RNA splicing profiles were varied between the two cell lines, which was further modified in response to ONC201 treatments. In conclusion, we delineated the signaling mechanisms regulating the expression of CHOP in non-metastatic versus metastatic colorectal cells in response to ONC201 treatment. The observed differences were related to cellular plasticity and metabolic reprogramming.

Background: In treatment-refractory cancers, tumor tissues damaged by therapy initiate the repair response; therefore, tumor tissues must be exposed to an additional burden before successful repair. We hypothesized that an agent recognizing a molecule that responds to anticancer treatment–induced tissue injury could deliver an additional antitumor agent including a radionuclide to damaged cancer tissues during repair. We selected the extracellular matrix glycoprotein tenascin-C (TNC) as such a molecule, and three antibodies recognizing human and murine TNC were employed to evaluate X-irradiation–induced changes in TNC uptake by subcutaneous tumors. Methods: TNC expression was assessed by immunohistochemical staining of BxPC-3 tumors treated with or without X-irradiation (30 Gy) for 7 days. Antibodies against TNC (3-6, 12-2-7, TDEAR) and a control antibody were radiolabeled with 111In and injected into nude mice having BxPC-3 tumors 7 days after X-irradiation, and temporal uptake was monitored for an additional 4 days by biodistribution and single-photon emission computed tomography with computed tomography (SPECT/CT) studies. Intratumoral distribution was analyzed by autoradiography. Results: The immunohistochemical signal for TNC expression was faint in nontreated tumors but increased and expanded with time until day 7 after X-irradiation. Biodistribution studies revealed increased tumor uptake of all three 111In-labeled antibodies and the control antibody. However, a statistically significant increase in uptake was evident only for 111In-labeled 3-6 (35%ID/g for 30 Gy vs. 15%ID/g for 0 Gy at day 1, P &lt; 0.01; ID, injected dose), whereas limited changes in 111In-labeled TDEAR2, 12-2-27, and control antibody were observed (several %ID/g for 0 and 30 Gy). Serial SPECT/CT imaging with 111In-labeled 3-6 or control antibody provided consistent results. Autoradiography revealed noticeably stronger signals in irradiated tumors injected with 111In-labeled 3-6 compared with each of nonirradiated tumors and the control antibody. The signals were observed in TNC-expressing stroma. Conclusion: Markedly increased uptake of 111In-labeled 3-6 in irradiated tumors supports our concept that an agent, such as an antibody, that recognizes a molecule, such as TNC, involved in tissue-injury repair could enhance drug delivery to therapy-experienced tumor tissues. The combination of antibody 3-6 coupled to a tumoricidal drug and conventional therapy has the potential to achieve better outcomes for patients with refractory cancer.

Ovarian cancer is the common cause of death among gynecological cancers. Although ovarian cancer initially responds to chemotherapy, the frequent recurrence in patients remains a therapeutic challenge. Pyruvate kinase M2 (PKM2) plays a pivotal role in regulating cancer cell survival. However, its therapeutic roles remain unclear. Here, we investigated the anticancer effects of compound 3K, a specific PKM2 inhibitor, on autophagic and apoptotic pathway regulation in SK-OV-3 (PKM2-overexpressing human ovarian adenocarcinoma cell line). The anticancer effect of compound 3K was examined using the MTT and colony formation assay in SK-OV-3. The results of tissue microarray showed that PKM2 expression positively correlated with the severity of the tumor. Moreover, the expression of pro-apoptotic proteins increased in SK-OV-3 following compound 3K treatment. Compound 3K induced AMPK activation, which was accompanied by the inhibition of mTOR. Additionally, this compound inhibited glycolysis, resulting in reduced proliferation in SK-OV-3. Compound 3K treatment suppressed tumor progression in vivo xenograft model. Our findings suggest that the inhibition of PKM2 by compound 3K affected Warburg effects and induced autophagic cell death. Therefore, the use of specific PKM2 inhibitors to block the glycolytic pathway and target cancer cell metabolism represents a promising therapeutic approach for treating PKM2-overexpressing ovarian cancer.

Targeted next-generation sequencing (NGS) technology detects specific mutations that can provide treatment opportunities for colorectal cancer (CRC) patients. We included 145 CRC patients who underwent surgery. We analyzed the mutation frequencies of common actionable genes and their association with clinicopathological characteristics and oncologic outcomes using targeted NGS. Approximately 97.9% (142) of patients showed somatic mutations. Frequent mutations were observed in TP53 (70%), KRAS (49%), and APC (47%). TP53 mutations were significantly linked to higher overall stage (p=0.038) and lower disease-free survival (DFS) (p=0.039). ATM mutation was significantly associated with higher tumor stage (p=0.012) and shorter overall survival (OS) (p=0.041). Stage 3 and 4 patients with ATM mutations (p=0.023) had shorter OS, and FBXW7 mutation was significantly associated with shorter DFS (p=0.002). In multivariate Cox regression analysis, ATM mutation was an independent biomarker for poor prognosis of OS (p=0.022). TP53 and FBXW7 mutations are independent biomarkers for poor prognosis of DFS (p=0.042 and 0.030, respectively). A comprehensive analysis of the molecular markers for CRC can provide insights into the mechanisms underlying disease progression and help optimize a personalized therapy.

The intracellular calcium concentration ([Ca2+]i) modulation plays a key role in the regulation of cellular growth and survival in normal cells and failure of [Ca2+]i homeostasis is involved in tumor initiation and progression. Here we show that inhibition of Furin by its naturally occurring inhibitor the prodomain ppFurin in the MDA-MB-231 breast cancer cells resulted in enhanced SOCE through TRPC6 activation that associated reduced cells malignant phenotype. Expression of ppFurin in a stable manner in MDA-MB-231 and the melanoma MDA-MB-435 cell lines inhibits Furin activity as assessed by in vitro digestion assays. Accordingly, cell transfection experiments, revealed that the ppFurin-expressing cells are unable to process adequately the PC substrates proVEGF-C and proIGF-1R. Compared to MDA-MB-435 cells, expression of ppFurin in MDA-MB-231 significantly induces Ca2+ entry which is impaired by silencing of TRPC6 expression. Analysis of TRPC6 activation revealed its up-regulated tyrosine phosphorylation in ppFurin-expressing MDA-MB-231 cells. The expression of ppFurin in MDA-MB-231 cells reduced their viability and ability to migrate and enhanced their sensitization to the apoptosis inducer hydrogen peroxide. These findings suggest that Furin inhibition by ppFurin may be a useful strategy to interfere with Ca2+ mobilization leading to breast cancer cells malignant phenotype repression and reduction of their resistance to treatments.

The standard care for metastatic breast cancer (MBC) is systemic therapies with imbrication of focal treatment for symptoms. Recently, thanks to implementation of radiological and metabolic exams and development of new target therapies, oligometastatic and oligoprogressive settings are even more common, paving the way to a paradigm change of focal treatments role. In fact, according to immunophenotype, radiotherapy can be considered with radical intent in these settings of patients. The aim of this literature review is to analyse available clinical data on prognosis of bone metastases from breast cancer and benefits of available treatments for developing a practical guide for clinicians.

Colorectal cancer (CRC) is the third most common cancer, with rising incidence due to lifestyle and diet. 40% of CRC cases are found to have KRAS mutations. In this study, we investigate the survival outcome of metastatic Colorectal cancer mCRC) patients in Brunei Darussalam restrospectively. Chi-squared test was used to compare the survival outcomes of mCRC patients, and Mann-Whitney U test was used to compare the median ages of both groups. Kaplan-Meier survival curves were drawn and logrank test was used to compare the survival outcome between two groups. There was a total of 105 patients with stage IV CRC being treated during the study period. 81.6% (n=62) of mCRC patients were found to have the primary tumours on the left side of the colon. 19 of these 26 (73.1%) mutant KRAS mCRC patients died, while 23 of 50 (46.0%) wild-type KRAS mCRC patients died at the end of the study period, contributing to death rates of 45.2% and 54.8%, correspondingly. 30.3% (n=23) of the study population had a single metastatic site detected (either liver, or lung or any other organs), while 69.7% (n=53) of the 76 mCRC patients had two (double) or more metastatic sites. 69.2% (n=18) and 30.8% (n=8) of the mutant KRAS mCRC patients had mutations within codons 12 and 13, respectively. To our knowledge, this is the first study in Brunei Darussalam to analyse both the survival outcomes of metastatic CRC patients and those of mutant KRAS mCRC patients. Chi-squared analysis showed a significant difference between the survival outcomes of wild-type KRAS and mutant KRAS mCRC patients (p-value = 0.024). There was a significant difference in the survival outcome between the mutant KRAS mCRC patients with RCC and mutant KRAS mCRC with LCC patients. There was no significant difference between the survival outcomes of mutant KRAS patients with mutations in either codon 12 or 13 of the KRAS gene (Table 3). However, there is a significant difference in the median survival periods between the mutant KRAS mCRC patients with mutations in codon 12 and those with mutation in codon 13 of the KRAS gene (p-value = 0.003). In conclusion, we found that mutant KRAS mCRC patients had a significantly poorer OS, which was shown to be worse when the primary tumours were found at the left side of the colon. Mutant KRAS mCRC patients with mutations in codon 12 were found to have shorter survival median periods than those with mutations within codon 13.

Lung cancer predominates in cancer-related deaths worldwide, with lung adenocarcinoma (LUAD) being a common histological subtype of lung cancer. The aim at this study was to search for biomarkers associated with the progression and prognosis of LUAD. We have integrated the expression profiles of 1174 lung cancer patients from five GEO datasets (GSE18842, GSE19804, GSE30219, GSE40791 and GSE68465) and identified a set of differentially expressed genes. Functional enrichment analysis showed that these genes are closely related to the progression of LUAD, such as cell cycle, mitosis and adhesion. Cytoscape software was used to establish a protein-protein interaction (PPI) network to analyze important modules using Molecular Complex Detection (MCODE), and finally CCNB1, BUB1B and TTK were selected for further study. The study found that compared with non-tumor lung tissue, CCNB1, BUB1B and TTK are highly expressed in LUAD. Kaplan-Meier analysis showed that CCNB1, BUB1B and TTK were negatively correlated with the overall survival and disease-free survival of patients. Gene set enrichment analysis (GSEA) demonstrated that for the samples of any hub gene highly expressed, most of the functional gene sets enriched in cell cycle. In summary, CCNB1, BUB1B and TTK can be used as biomarkers of poor prognosis of LUAD. The high expression of CCNB1, BUB1B and TTK can accelerate the progression of LUAD and lead to shorter survival, suggesting that they may be potential targets for treatment in LUAD.

Background: At present, the treatments for patients with advanced lung cancer focus on chemotherapy, targeted therapy, immunotherapy, or a combination of multiple treatments. Purpose: The main purpose of this study is to compare the various chemotherapy-based combination therapies and find the best one for patients with advanced lung cancer. Methods: Based on database (PubMed, EMBASE and Medline) for randomized controlled trials of advanced lung cancer with combination therapy from 2008 to 2020, we searched literatures with overall survival (OS), progression-free survival (PFS), objective response rate (ORR) and adverse as outcome indicators and established a Bayesian mesh meta-analysis for multiple treatment strategies. Then, we combined the results of four outcome indicators to find out the best chemotherapy-based combination therapy strategy for patients with advanced lung cancer, further, we tried to screen out the best drugs of which were commonly used now. Results: It contained a total of 51 studies, including five combination therapies: Chemotherapy/Chemotherapy plus placebo (CT), chemotherapy plus one targeted therapy drug (CT+T), chemotherapy plus two targeted therapy drugs (CT+T+T), chemotherapy combined with immunotherapy (CT+I) or chemotherapy combined with biotherapy (CT+B). In terms of four outcome indicators, CT+I showed the best therapeutic benefits. In the comparison of immunotherapy drugs, pembrolizumab showed the best effect. Conclusion: Our results showed that, among the multiple chemotherapy-based combination therapy strategies, chemotherapy combined with immunotherapy is the best choice for patients with advanced lung cancer, and pembrolizumab combined with chemotherapy has the best effect.

Stem cells are currently being used in many clinical trials for regenerative purposes. These are promising results for stem cells in the treatment of several diseases, including cancer. Nevertheless, there are still many variables which should be addressed before the application of stem cells for cancer treatment. One approach should be to establish well-characterized therapeutic stem cell banks to minimize the variation in results from different clinical trials and facilitate their effective use in basic and translational research.

Background: DSCAM-AS1 is a cancer-related long noncoding RNA with higher expression levels in Luminal A, B and HER2-positive Breast Cancer (BC), where its expression is strongly dependent on Estrogen Receptor Alpha (ERα). Methods: To decipher its function, DSCAM-AS1 expression was measured by qRT-PCR in tissue samples from 93 BC patients in addition to a meta-analysis of 30 gene expression datasets, together with the evaluation of its association with clinical data. By computational analyses of our RNA-Seq in MCF-7 cells, we investigated the DSCAM-AS1 knock-down effects at both gene and isoform levels. Results: We confirmed DSCAM-AS1 overexpression in high grade Luminal A, B and HER2+ BCs and found a significant correlation with disease relapse. 908 genes were regulated by DSCAM-AS1-silencing, primarily involved in cell cycle and inflammatory response. Noteworthy, the analysis of alternative splicing and isoform regulation revealed 2,085 splicing events regulated by DSCAM-AS1, enriched in differential polyadenylation sites and 3’UTR shortening events. Finally, the DSCAM-AS1-interacting splicing factor hnRNPL was predicted as the most enriched RBP for exon skipping and 3’UTR events. Conclusion: The relevance of DSCAM-AS1 overexpression in BC is confirmed by clinical data and further enhanced by its possible involvement in the regulation of RNA processing, which is emerging as one of the most important dysfunctions in cancer.

Cervical cancer is known as one of the most important cancers in women worldwide. Chemotherapy is a standard treatment for advanced/recurrent cervical cancer in which the prognosis of the disease is really poor and the 1-year survival chance in these patients is maximally 20%. However, resistance to anticancer drugs is a major problem in treating cancer. Cervical cancer stem cells are considered as a fundamental cause of chemo and radio-resistance and also relapse after primary successful treatment. Signaling pathways include a wide range of molecular mechanisms contribute to drug resistance. Recently, microRNAs (miRNAs) are announced as a group of molecular biomarkers involving in response to chemotherapy in cancer patients. As the miRNAs, there are some long non-coding RNAs (LncRNAs) which their aberrant expression is considered as a biomarker for monitoring chemoresistance. In this review, we summarized current reports about the involvement of signaling pathways during chemoresistance in cervical cancer. Then, genes that have been demonstrated their involvement during drug resistance in cervical cancer were tabulated. Further, miRNAs that have been reported as biomarkers during treatment are listed. By bioinformatic analysis, we predictedmiR-335-5p and miR-16-5p as the most potential biomarkers for monitoring resistance to chemotherapy. Finally, long non-coding RNAs that have been introduced in recent studies as novel biomarkers during the response to chemotherapy were mentioned.

The delivery of Cytochrome c (Cyt c) to the cytosol stimulates apoptosis in cells were its release from mitochondria and apoptosis induction is inhibited. We developed a drug delivery system consisting of Cyt c nanoparticles decorated with folate-poly(ethylene glycol)-poly(lactic-co-glycolic acid)-thiol (FA-PEG-PLGA-SH) to deliver Cyt c into cancer cells and test their targeting in the Lewis Lung Carcinoma (LLC) mouse model. Cyt c-PLGA-PEG-FA nanoparticles (NPs) of 253 ± 55 and 354 ± 11 nm were obtained by Cyt c nanoprecipitation, followed by surface decoration with the co-polymer SH-PLGA-PEG-FA, and compared to a nanoparticle-free formulation. Overexpression of FA in LLC cells and internalization of Cyt c-PLGA-PEG-FA nanoparticles (NPs) was confirmed by confocal microscopy. Caspase activation assays show NPs retain 88-96% Cyt c activity. The NP formulations were more efficient in decreasing LLC cell viability than the NP-free formulation, with IC50: 49.2 to 70.1 μg/ml versus 129.5 μg/ml, respectively. Our NP system is thrice as selective towards cancerous than normal cells. In-vivo studies using tagged nanoparticles show accumulation in mouse LLC tumor 5 min post-injection. In conclusion, our NP delivery system for Cyt c shows superiority over the NP-free formulation and reaches a folic acid-overexpressing tumor in an immune-competent animal model.

Endoplasmic reticulum (ER) stress perturbs cell homeostasis and induces the unfolded protein response (UPR). In breast cancer, this process is activated by oestrogen deprivation and is associated with tamoxifen resistance. We present evidence that the transcription factor SOX2 and the long noncoding RNA SOX2 overlapping transcript (SOX2OT) are up-regulated in oestrogen receptor-positive (ER+) breast cancer and in response to oestrogen deprivation. We examined the effect of the UPR on SOX2 and SOX2OT expression, and the effect of SOX2OT on UPR pathways in breast cancer cell lines. The induction of the UPR by thapsigargin or glucose deprivation up-regulates SOX2OT expression. This up-regulation is also shown with the anti-oestrogen 4OH-tamoxifen and mTOR inhibitor everolimus in ER + breast cancer cells that are sensitive to oestrogen deprivation or everolimus treatment. SOX2OT overexpression decreased BiP and PERK expression. This effect of SOX2OT overexpression was confirmed on BiP and PERK pathway by q-PCR. Our results show that a long noncoding RNA regulates the UPR and evince a new function of SOX2OT as a participant of ER stress reprogramming of breast cancer cells.

This study aims to evaluate the patient’s dose exposure from Computed Tomography Pulmonary Angiography (CTPA) examination and to estimates the cancer risk induced from the examinations based on the patient’s size. One hundred patients were recruited, and data information was collected retrospectively. A multi-detector (MDCT) (Philips Brilliance 128, USA) scanner were utilized for the CTPA examination, and dose data were obtained from the system. The effective diameter of each subjects’ image was measured for the Size-specific dose estimates (SSDEs). All subjects divided into Group 1 (19 – 25 cm), Group 2 (25-28 cm) and Group 3 (28-38 cm), where the association between gender were analysed. Effective dose (E), SSDE, organ dose and cancer risk of each group were evaluated and compared statistically using independent t-test and one-way ANOVA. The range of mean CTDI_vol, DLP and E values were (6.44 – 17.42 mGy), (239 – 631 mGy), (5.19 – 13.90 mSv), respectively. In respective with the patient’s effective diameter, the mean SSDE value for Group 1, Group 2 and Group 3 were 9.93 ± 3.89 mGy, 13.70 ± 9.04 mGy and 22.29 ± 7.35 mGy. The organ dose and cancer risk attained for breast, lung and liver were 17.05 ± 10.40 mGy (194 per one million procedure), 17.55 ± 10.86 mGy (192 per one million procedure) and 15.04 ± 9.75 mGy (53 per one million procedure), respectively. Lung and breast with more massive patient’s effective diameter received the highest dose exposure which increases the probability of the cancer risk. CTDI_vol was found to be underestimated, and SSDE provides more accurate in describing the radiation dose and cancer risk. Body effective diameter found to be significant on the estimation except for gender. Therefore, it is essential to apply optimised protocols in order to reduce patient’s exposure during CTPA examination.

Intratumoral heterogeneity is a major ongoing challenge in the effective therapeutic targeting of cancer. Accumulating evidence suggests that a fraction of cells within a tumor termed Cancer Stem Cells (CSCs) are primarily responsible for this diversity resulting in therapeutic resistance and metastasis. Adding to this complexity, recent studies have shown that there can be different subpopulations of CSCs with varying biochemical and biophysical traits resulting in varied dissemination and drug-resistance potential. Moreover, cancer cells can exhibit a high level of plasticity or the ability to dynamically switch between CSC and non-CSC states or among different subsets of CSCs. The molecular mechanisms underlying such plasticity has been under extensive investigation and the trans-differentiation process of Epithelial to Mesenchymal transition (EMT) has been identified as a major contributing factor. Besides genetic and epigenetic factors, CSC plasticity is also shaped by non-cell-autonomous effects such as the tumor microenvironment. In this review, we discuss the recent developments in understanding CSC plasticity in tumor progression at biochemical and biophysical levels, and the latest in silico approaches being taken for characterizing cancer cell plasticity with implications in improving existing therapeutic approaches.

Very hot (> 65 °C) beverages such as espresso were evaluated by the International Agency for Research on Cancer (IARC) as probably carcinogenic to humans. For this reason, research into lowering beverage temperature without compromising its quality or taste is important. For espresso, one obvious possibility consists in lowering the brewing temperature. In two sensory trials using ISO 4120:2004 triangle test methodology, brewing temperatures of 80°C vs. 128°C and 80° vs. 93°C were compared. From the tested levels, espresso brewed at the lowest temperature had the highest acceptance. However, most tasters were unable to distinguish between 80°C and 93°C. The results of these pilot experiments proof the possibility to decrease the health hazard of very hot beverages by lower brewing temperatures.

Background: Feasibility trials are preliminary trials that assess the viability and acceptability of intervention studies and the effects of the intervention on intermediate endpoints. Due to their short duration, they are unable to establish the effects of the intervention on long-term clinical outcomes. We propose a novel method that could transform the interpretation of feasibility trials using modified two-stage randomisation analyses. Methods In this two-stage process, we explored the effects of a 6-month feasibility factorial randomised controlled trial (RCT) of lycopene and green tea dietary interventions (ProDiet) on 159 serum metabolic traits in 133 men with raised PSA levels but prostate cancer (PCA) free. In the first stage, we conducted an intention-to-treat analysis, using linear regression to examine the effects of the interventions on metabolic traits, compared to the placebo group and instrumental variable analysis to assess the causal effect of the intervention on the outcomes. In the second stage, we used a two-sample Mendelian Randomization (MR) approach to assess the causal effect of metabolic traits altered by the interventions, on PCA risk, using summary statistics data from an international PCA consortium of 44,825 cancer cases and 27,904 controls. ResultsThe systemic effects of lycopene and green tea supplementation on serum metabolic profile were comparable to the effects of the respective dietary advice interventions (R2= 0.65 and 0.76 for lycopene and green tea respectively). Metabolites which were altered in response to lycopene supplementation were acetate (standard deviation difference versus placebo (β)): 0.69; 95% CI= 0.24, 1.15; p=0.003), valine (β: -0.62; -1.03, -0.02; p=0.004), pyruvate (β: -0.56; -0.95, -0.16; p=0.006), and docosahexaenoic acid (β: -0.50; -085, -0.14; p=0.006). The instrumental variable analysis showed there was no evidence that green tea altered the metabolome, but lycopene was associated with an increase in acetate (β=2.13; p=0.006) and decreases in pyruvate (β=-1.90; p=0.009), valine (β=-1.79; p=0.023), diacylglycerol (β=-1.81; p=0.026), alanine (β=-1.55; p=0.015) and DHA (p=0.097), where the regression coefficient represents the standard deviation (SD) difference in metabolite measures per unit change in lycopene (µmol/L) or EGCG (nM).Using MR, a genetically instrumented SD increase in pyruvate increased the odds of PCA by 1.29 (1.03, 1.62; p=0.027). Conclusion Using a two-stage randomization analysis in a feasibility RCT, we found that lycopene lowered levels of pyruvate, which our Mendelian randomization analysis suggests may be causally related to reduced PCA risk.

Patients with glioblastoma (GB), a highly aggressive brain tumor, have a median survival of 14.6 months following neurosurgical resection with adjuvant chemoradiotherapy. Quiescent GB cancer stem cells (CSCs) invariably cause local recurrence. These GB CSCs that can be identified by embryonic stem cell markers express components of the renin-angiotensin system and are associated with circulating CSCs. Despite the presence of circulating CSCs, GB rarely develops distant metastasis outside the central nervous system. This paper reviews the current literature on GB growth inhibition in relation to CSCs, circulating CSCs, the RAS and the novel therapeutic approach by repurposing drugs that target the renin-angiotensin system to improve overall symptom-free survival and maintain quality of life.

Objective: Pancreatic carcinoma (PANC) is one of the important aggressive cancers, with deficiency in effective therapeutics. Studies have unveiled that miR-139-5p expression is significantly downregulated in other types of cancers. However, the functions and mechanisms of miR-139-5p in PANC remain unclear. Methods: Bioinformatic analysis was performed to analyze the differentially expressed genes in the TCGA database. PANC cell line with overexpressed miR-139-5p and Solute Carrier Family 7, Member 11 (SLC7A11) was established, and has been used to detect cell proliferation, migration, invasion and colony formation in PANC. Subsequently, bioinformatic analysis and luciferase assay were performed to confirm that SLC7A11 was a target gene of miR-139-5p. Xenograft mouse model was used to investigate the role of miR-139-5p in PANC tumorigenicity. Results: Through bioinformatic analysis, miR-139-5p was predicted to regulate phosphatidylinositol signaling pathway by targeting SLC7A11. MiR-139-5p was found to be lowly expressed in PANC tissues, while SLC7A11 was highly expressed. Low expression of miR-139-5p and high expression of SLC7A11 were positively associated with poor clinical outcomes. PANC cell proliferation, migration, and invasion could be inhibited by miR-139-5p overexpression and could be promoted by SLC7A11 overexpression. MiR-139-5p could regulate the protein expression level of PI3K and Akt associated with phosphatidylinositol signaling pathway could be by inhibiting the expression of SLC7A11. MiR-139-5p overexpression could suppress PANC tumor growth and the expression of SLC7A11, p-PI3K, p-Akt in tumor tissues. Therefore, the inhibiting effect of miR-139-5p to PANC cell proliferation, invasion and migration, at least, was partly due to its inhibiting effect on SLC7A11 expression. Conclusion: These results demonstrated a novel role of miR-139-5p/SLC7A11 in PANC and provided potential prognostic predictors for PANC patients.

There are many species of endemic plants from Mexico, without food or commercial use, but with different applications in traditional medicine and valuable for their content of secondary metabolites. In this sense, we found two species of Cucurbitacea family plants natives of southeast and gulf of México, with traditionally use how soap and laundry agent, control of some pests, and it has also been used how infusion for the treatment of different types of dermatitis and stomachache. In the present work, we evaluate the antiproliferative activity in vitro, of six crude organic extracts, tested against six human tumor cell lines, A549 (lung), HBL-100 (breast), HeLa (cervix), SW1573 (lung), T-47D (breast) and WiDr (colon), the results indicated that at least three extracts from both species presents an interesting antiproliferative activity on five tumor cell lines.

Iodide is an essential micronutrient present in very small quantities in the human body, with a fundamental action for the adequate synthesis of thyroid hormones, which are critical for cell differentiation, growth and metabolism. In the form of iodide, iodine is widely distributed in the environment, although in an irregular manner, occurring in abundant amounts in the oceans and in coastal areas and scarcely found on islands and mountains. The diet is the main source of iodine, whose intake varies according to the amount present in soil and water and according to eating habits. Governmental policies have been adopted to satisfy and guarantee the necessary daily supply of iodine, such as fortification of industrialized salt for domestic iodine consumption or addition to the bread commonly consumed in a given region, or the offer of iodized oil to the population, or even iodine supplementation through medications. Iodide deficiency is the main avoidable cause of brain damage to fetuses and children, as well as retardation of psychomotor development. Thyroid hormones are almost universally involved in the development and proliferation of fetal neural tissue. Permanent lesions of the cerebral cortex, hippocampus and cerebellum may occur, with loss of, or damage to the brainstem or spinal cord, affecting cortical areas that integrate highly specialized stimuli, which become poorly defined on an anatomical basis, including silent areas of the associative cortex. One of the more significant metabolic problems due to dietary iodine deficiency is the presence of goiter (increased volume of the thyroid gland). Thyroid carcinoma is the most frequent endocrine neoplasia affecting the human species and plasma iodine concentration is related to the development of specific subtypes of this neoplasia. An increased prevalence of follicular carcinoma, a more aggressive tumor, has been observed in areas of iodine deficiency, while the correction of this deficiency is associated with a higher prevalence of papilliferous carcinoma, a less aggressive form. CONCLUSION: An ideal plasma iodide concentration is necessary to insure the proper mental development of fetuses and young children and to minimize the aggressiveness of thyroid cancer from follicular cells in humans.

This study analyzes oral supplement of molecular iodine (I2) alone and in combination with the neoadjuvant therapy 5-fluorouracil/epirubicin/cyclophosphamide or taxotere/epirubicin (FEC/TE) in women with Early (stage II) and Advanced (stage III) breast cancer. In the Early group, 30 women were treated with I2 (5 mg/day) or placebo (colored water) for 7–35 days before surgery. For the Advanced group, 30 patients received I2 or placebo along with FEC/TE treatment. After surgery, all patients received FEC/TE + I2 for 170 days. I2 supplementation showed a significant attenuation of the side effects and absence of tumor chemoresistance. Control, I2, FEC/TE, and FEC/TE+I2 groups exhibit response rate of 0, 33%, 73%, and 100%, respectively, and a pathologic complete response of 18%, and 36% in the last two groups. Five-year disease-free survival rate was significantly higher in patients with I2 supplement before and after surgery compared to those receiving the supplement only after surgery (82% vs. 46%). I2-treated tumors exhibit less invasive potential, and significant increases in apoptosis, estrogen receptor expression, and immune cell infiltration. Transcriptomic analysis indicated activation of the antitumoral immune response. The results led us to register a phase III clinical trial analyzing chemotherapy + I2 treatment for advanced breast cancer.

Although there is a several array of diagnostic and therapeutic choices for pancreatic cancer in recent years, a crucial medical approach for the refractory disease is still needed. Oligonucleotide therapeutics, such as those based on antisense RNAs, RNA interference, aptamers and decoys, are promising agents against pancreatic cancer because they identify a specific nucleotide sequence or protein and interfere with gene expression as molecular-targeted agents. Within just the past quarter-century, the diversity and feasibility of these drugs as diagnostic or therapeutic tools have dramatically increased. Actually, there have been several clinical and preclinical studies of oligonucleotides for patients with pancreatic cancer so far. To support the discovery of effective diagnostic or therapeutic options by using oligonucleotide-based strategies in the absence of satisfactory therapies for long-term survival and the rising trend of diseases, we summarize the current clinical trials of oligonucleotide therapeutics for pancreatic cancer patients with underlying preclinical or scientific data and focus on the possibility of oligonucleotides to target pancreatic cancer in clinical implications.

Owing to fascinating applications of ZnO in modern devices, it is interesting to explore its more features for future devices. Hence, herein, we have synthesized the high quality ZnO spherical nanoparticles (SNPs) through a facile green synthesis route and robust structural and biomedical studies are carried out. Hexagonal phase with 93.2% crystallinity was confirmed through XRD analysis. ZnO nanoparticles were tested for their bioactivities both in vivo (acute cytotoxicity test) and in vitro (Anti-cancer activities on liver (HepG2) and cervical (Hela) cancer cell lines, stimulatory/inhibitory effects on normal rat splenic cells and hemolytic effects on red blood cells). Results showed that ZnO SNPs has no cytotoxic effects on vital organ like liver and has no hemolytic action on red blood cells. ZnO SNPs showed inhibitory consequence on normal rat splenic cells growth at all tested concentrations. ZnO nanoparticles showed an inhibitory effect on HepG2 cell line. While showed stimulatory effect on Hela cell line. Current study presents the synthesized ZnO SNPs as highly applicable in bio-optoelectronics.

Direct intercellular communication, mediated by gap junctions formed by the connexin transmembrane protein family, is frequently dysregulated in cancer. Connexins have been described as tumour suppressors, but emerging evidence suggests that they can also act as tumour promoters. This feature is connexin- and tissue-specific and may be mediated by complex signalling pathways through gap junctions or hemichannels or by completely junction-independent events. Lung cancer is the number one cancer in terms of mortality worldwide, and novel biomarkers and therapeutic targets are urgently needed. Our objective was to gain a better understanding of connexins in this setting. We used several in silico tools to analyse TCGA data in order to compare connexin mRNA expression between healthy lung tissue and lung tumours and correlated these results with gene methylation patterns. Using Kaplan-Meier plotter tools, we analysed a microarray dataset and an RNA-seq dataset of non-small cell lung tumours in order to correlate connexin expression with patient prognosis. We found that connexin mRNA expression is frequently either upregulated or downregulated in lung tumours. This correlated with both good and poor prognosis (overall survival) in a clear connexin isoform-dependent manner. These associations were strongly influenced by the histological subtype (adenocarcinoma versus squamous cell carcinoma). We present an overview of all connexins but particularly focus on four isoforms implicated in lung cancer: Cx26, Cx30.3, Cx32 and Cx43. We further analysed the protein expression and localization of Cx43 in a series of 72 human lung tumours. We identified a subset of tumours that exhibited a unique strong nuclear Cx43 expression pattern that predicted worse overall survival (p=0.014). Upon sub-stratification, the prognostic value remained highly significant in the adenocarcinoma subtype (p=0.002) but not in the squamous carcinoma subtype (p=0.578). This finding highlights the importance of analysis of connexin expression at the protein level, particularly the subcellular localization. Elucidation of the underlying pathways regulating Cx43 localization may provide for novel therapeutic opportunities.

The incidence of human papillomavirus-related head and neck squamous cell carcinoma (HPV+HNSCC) has reached epidemic levels in the last decade. While prophylactic vaccines will prevent future HPV infections, there are currently no HPV-specific antiviral drugs to treat current HPV infections or HPV+HNSCC. HPV replication and transcription are promising targets for anti-HPV therapeutics, as modulation of these processes can alter expression levels of HPV E6 and E7, which are required for maintenance of the transformed phenotype. This is a particularly attractive target in in HPV+HNSCC where the majority of tumors have episomal genomes replicating in an E1-E2 dependent manner. Here, we describe a model system to study HPV16 E1-E2 mediated DNA replication and HPV16 E2-mediated transcriptional activation and repression in multiple HNSCC cell lines. Our results demonstrate that low levels of IFIT1 are required for HPV16 replication in HNSCC cell lines and HPV16 E1 interacts with IFIT1. Restoration of IFIT1 expression in HNSCC cell lines partially inhibits HPV16 E1-E2 mediated replication. This system can be used to study replication and transcription by HPV16 E1 and E2 in HNSCC as well as be utilized to screen potential anti-HPV therapeutics that target HPV16 replication and transcription.

Development of novel anti-cancer peptides requires a rapid screening process which can be accelerated by using appropriate in vitro tumor models. Breast carcinoma tissue is a three dimensional (3D) microenvironment, which contains a hypoxic center surrounded by dense proliferative tissue. Biochemical clues provided by such 3D cell mass cannot be recapitulated in conventional 2D culture systems. In this experiment, we evaluate the efficacy of the sandalwood peptide, cyclosaplin on established in vitro 3D silk breast cancer model using invasive MDA-MB-231 cell line. The anti-proliferative effect of the peptide on 3D silk tumor model is monitored by alamar blue assay, with conventional 2D culture as control. The proliferation rate, glucose consumed, LDH, and MMP-9 activity of Human breast cancer cells are higher in 3D constructs compared to 2D. A higher concentration of drug is required to achieve 50% cell death in 3D culture than 2D cultures. The cyclosaplin treated MDA-MB-231 cells showed significant decrease in MMP-9 activity in 3D constructs. Microscopic analysis revealed the formation of cell clusters evenly distributed in the scaffolds. The drug treated cells were less in number, smaller and showed unusual morphology. Overall, these findings indicate the role of cyclosaplin as a promising anti-cancer therapeutics.

Introduction: Novel robotic surgery systems (da Vinci Xi) are superior to classical open and laparoscopic techniques with its clear and three-dimensional view. We aimed to present the first case low anterior resection of rectal cancer and vaginal specimen extraction with Da Vinci Xi.Case: A 75-year-old female patient with rectum adenocarcinoma was undergone robotic-assisted low anterior resection (LAR) of the rectum, vaginal removal of the specimen, colorectal anastomosis and loop ileostomy. The operation time was 190 minutes. There were no postoperative complications. Pathological tumor stage was stage pT1N0 with negative proximal, distal and radial resection margins. The patient was discharged on the third postoperative day.Conclusion: Robot-assisted LAR, total mesorectal excision, vaginal removal of the specimen, colorectal anastomosis, and loop ileostomy can be performed easily and safely with Da Vinci Xi at early stage rectal cancer. And the vaginal extraction of the specimen avoids us from a traditional abdominal incision.

As part of our ongoing silybin project, this study aims to introduce a basic nitrogen-containing group to 7-OH of 3,5,20-O-trimethyl-2,3-dehydrosilybin or 3-OH of 5,7,20-O-trimethyl-2,3-dehydrosilybin via an appropriate linker for in vitro evaluation as potential anti-prostate cancer agents. The synthetic approaches to 7-O-substituted-3,5,20-O-trimethyl- 2,3-dehydrosilybins through a five-step procedure and to 3-O-substituted-5,7,20-O-trimethyl-2,3- dehydrosilybins via a four-step transformation have been developed. Thirty-two nitrogen-containing derivatives of silybin have been achieved through these synthetic methods for the evaluation of their antiproliferative activities towards both androgen-sensitive (LNCaP) and androgen-insensitive prostate cancer cell lines (PC-3 and DU145) using WST-1 cell proliferation assay. These derivatives exhibited greater in vitro antiproliferative potency than silybin. Among them, 11, 29, 31, 37, and 40 were identified as five optimal derivatives with IC50 values in the range of 1.40–3.06 µM, a 17- to 52-fold improvement in potency as compared with silybin. All these five optimal derivatives can arrest the PC-3 cell cycle in the G0/G1 phase and promote PC-3 cell apoptosis. Derivatives 11, 37, and 40 are more effective than 29 and 31 in activating PC-3 cell apoptosis.

Background: Cancer stem cells (CSCs) exhibit self-renewal activity and give rise to other cell types in tumors. Due to the infinite proliferative potential of CSCs, drugs targeting these cells are necessary to completely inhibit cancer development. beta-lapachone (bL) has been widely used to treat cancer development, but its effect on cancer stem cells remain elusive. Thus, we investigated the effect of bL on mammosphere formation using breast cancer stem cell (BCSC) marker positive cells, MDA-MB-231. Methods: MDA-MB-231 Cells, which is negative for NQO1 expression, was constructed to stably express NQO1(NQO1 stable cells) to see the effect of bL. The effect of bL on cells were evaluated by wound healing and Transwell cell culture chambers, and ALDEFLUOR assay. Results: Here, we show that bL inhibited the proliferative ability of mammosphere derived from BCSC marker-positive cells, MDA-MB-231, in an NQO1-dependent manner. bL treatment efficiently downregulated expression level of BCSC markers CD44, ALDH1A1, and DLGAP5 that recently identified as a stem cell proliferation marker in both cultured cells and mammosphered cells. Moreover, bL efficiently downregulates cell proliferation and migration activities. Conclusions: These results strongly suggest that bL could be a therapeutic agent targeting breast cancer stem cells with proper NQO1 expression.

Convenient labeling of proteins is important for observing its function under physiological conditions. In tissues particularly, heptamethine cyanine dyes (Cy-7) are valuable because they absorb in near infrared (NIR) region (750 – 900 nm) where light penetration is maximal. In this work, we found Cy-7 dyes with a meso-Cl functionality covalently binding to proteins with free Cys residues under physiological conditions (aqueous environments, at near neutral pH, and 37 °C). It transpired that the meso-Cl of the dye was displaced by free thiols in protein, while nucleophilic side-chains from amino acids like Tyr, Lys, and Ser did not react. This finding shows a new possibility for convenient and selective labeling of proteins with near-IR fluorescent probes.

Cancer is a leading cause of morbidity and mortality worldwide, yet much is still unknown about its mechanism of establishment and destruction. Recently, studies had shown that tumor cells cannot survive under the high temperature conditions. This treatment technique is called Hyperthermia. This report presents the case of radiative microwave heating of hyperthermia therapy on breast cancer in a porous medium. In this study, the steady state is solved analytically while unsteady state is solved using semi-implicit finite difference to get a more accurate prediction of blood temperature distributions within the breast tissues. A moderate temperature hyperthermia treatment is apply which results into cell death due to an increase in the level of cell sensitivity to radiation therapy and blood flow in tumor and oxygen. The results show that by applying metabolic heat generation rate of $3.97 X 10^{5}Wm^{-3}$, it takes upto 2 minutes for the tumor cells to get the require therapeutic temperature point.

Tumor dormancy, a clinically undetectable state of cancer, makes a major contribution to the development of multidrug resistance (MDR), minimum residual disease (MRD), tumor outgrowth, cancer relapse, and metastasis. Despite its high incidence, the whole picture of dormancy-regulated molecular programs is far from clear. That is, it is unknown when and which dormant cells will resume proliferation causing late relapse, and which will remain asymptomatic and harmless to their hosts. Thus, identification of dormancy-related culprits and understanding their roles can help predict cancer prognosis and may increase the probability of a timely therapeutic intervention for the desired outcome. Here, we provide a comprehensive review of the dormancy-dictated molecular mechanisms, including an angiogenic switch, immune escape, cancer stem cells, extra cellular matrix (ECM) remodeling, metabolic reprogramming, miRNAs, epigenetic modifications, and stress-induced-p38 signaling pathways. Further, we analyze the possibility of leveraging these dormancy-related molecular cues to outmaneuver cancer, and discuss the implications of such approaches in cancer treatment.

Tumor dormancy, a clinically undetectable state of cancer, makes a major contribution to the development of multidrug resistance (MDR), minimum residual disease (MRD), tumor outgrowth, cancer relapse, and metastasis. Despite its high incidence, the whole picture of dormancy-regulated molecular programs is far from clear. That is, it is unknown when and which dormant cells will resume proliferation causing late relapse, and which will remain asymptomatic and harmless to their hosts. Thus, identification of dormancy-related culprits and understanding their roles can help predict cancer prognosis and may increase the probability of a timely therapeutic intervention for the desired outcome. Here, we provide a comprehensive review of the dormancy-dictated molecular mechanisms, including an angiogenic switch, immune escape, cancer stem cells, extra cellular matrix (ECM) remodeling, metabolic reprogramming, miRNAs, epigenetic modifications, and stress-induced-p38 signaling pathways. Further, we analyze the possibility of leveraging these dormancy-related molecular cues to outmaneuver cancer, and discuss the implications of such approaches in cancer treatment.

In the present study, we have systematically examined the clinical significance of Nectin-4 (encoded by the PVRL-4 gene), a marker for breast cancer stem cells (CSCs), in cancer metastasis and angiogenesis using a variety of human specimens, including invasive duct carcinoma (IDC) with multiple grades, several types of primary tumors to local and distant relapses, lymph node metastases and circulating tumor cells (CTCs). Nectin-4 was overexpressed in more than 92% of samples with 65.2% Nectin-4 positive cells. The level of expression was increased with increasing tumor grade (GI-III) and size (T1-4) of IDC specimens. More induction of Nectin-4 was noted in relapsed samples from a variety of tumors (colon, tongue, liver, kidney, ovary, buccal mucosa) in comparison to primary tumors, while paired adjacent normal tissues do not express any Nectin-4. A high expression of Nectin-4 along with other representative markers in CTCs and lymph node metastasis was also observed in cancer specimens. An increased level of Nectin-4 along with representative metastatic (CD-44, Sca1, ALDH1, Nanog) and angiogenic (Ang-I, Ang-II, VEGF) markers was noted in metastatic tumors (local and distant) in comparison to primary tumors that were correlated with different grades of tumor progression. In addition, greater expression of Nectin-4 was observed in secondary tumors (distant metastasis, e.g., breast to liver or stomach to gallbladder) in comparison to primary tumors. Nectin-4 was overexpressed at all stages of metastasis and angiogenesis, thus appearing to play a major role in tumor relapse through the PI3K-Akt-NFκβ pathway.

Peripheral tissue metabolism of steroids (intracrinology) is now accepted as a key way in which tissues, such as the endometrium, can utilize inactive steroids present in the blood to respond to local physiological demands and ‘fine-tune’ the activation or inhibition of steroid hormone receptor-dependent processes. Expression of enzymes that play a critical role in activation and inactivation of bioactive oestrogens (E1, E2) and androgens (A4, T, DHT), as well as expression of steroid hormone receptors, has been detected in endometrial tissues and cells recovered during the menstrual cycle. There is robust evidence that increased expression of aromatase is important for creating a local microenvironment that can support a pregnancy. Measurement of intra-tissue concentrations of steroids using liquid chromatography–tandem mass spectrometry has been important in advancing our understanding of a role for androgens in the endometrium acting both as active ligands for the androgen receptor and as substrates for oestrogen biosynthesis. The emergence of intracrinology, associated with disordered expression of key enzymes such as aromatase, in the aetiology of common women’s health disorders such as endometriosis and endometrial cancer has prompted renewed interest in development of drugs targeting these pathways opening up new opportunities for targeted therapies and precision medicine.

Cyclin E2, a member of the cyclin family, is a key cell cycle-related protein. This protein plays essential roles in cancer progression, and as such, an inhibitor of cyclin E2 has been approved to treat several types of cancers. Even so, mechanisms underlying how to regulate cyclin E2 expression in cancer remain largely unknown. The current study found that miR-3687 is up-regulated in clinical bladder cancer (BC) tumor tissues, TCGA database and human BC cell lines. Inhibition of miR-3687 expression significantly reduces human BC cell proliferation in vitro and tumor growth in vivo, which are concurrently with the induction of G0/G1 cell cycle arrest and downregulation of cyclin E2 protein expression. Interestingly, overexpression of cyclin E2 reversed the inhibition of BC proliferation induced by miR-3687. Mechanistic studies suggest that miR-3687 could bind to the 3'-UTR of foxp1 mRNA, downregulates FOXP1 protein expression, and in turn promotes the transcription of cyclin E2, thereby promoting the growth of BC cells. Collectively, the current study not only establishes a novel regulatory axis of miR-3687/FOXP1 in regard to regulation of cyclin E2 expression in BC cells, but also provides strong suggestive evidence that miR-3687 and FOXP1 may be potentially promising targets in therapeutic strategies of human BC.

Owing to their unique physicochemical properties, nanoparticles are used in a variety of ways in the field of cancer treatment, including imaging, drug delivery, and photothermal and photodynamic therapies. The fascinating properties of nanoparticles are determined by their size, morphology, and constituent elements, and various synthetic methods and post-synthetic techniques have been applied to control these factors. Herein, we present examples of shape and composition control through galvanic replacement, a technique that exploits redox potential differences between elements to induce spontaneous ion-exchange and highlight its specific contributions to cancer treatment applications. The present article identifies the recent advances in nanoparticle formation techniques and discusses the future outlook of the field.

The licensing of talimogene laherparepvec (T-Vec) represented a landmark moment for oncolytic virotherapy, since it provided unequivocal evidence for the long-touted potential of genetically modified replicating viruses as anti-cancer agents. Whilst T-Vec is promising as a locally delivered virotherapy, especially in combination with immune-checkpoint inhibitors, the quest continues for a virus capable of specific tumour cell killing via systemic administration. One candidate is oncolytic adenovirus (Ad); it’s double stranded DNA genome is easily manipulated and a wide range of strategies and technologies have been employed to empower the vector with improved pharmacokinetics and tumour targeting ability. As well characterised clinical and experimental agents, we have detailed knowledge of adenoviruses’ mechanisms of pathogenicity, supported by detailed virological studies and in vivo interactions. In this review we highlight the strides made in the engineering of bespoke adenoviral vectors to specifically infect, replicate within, and destroy tumour cells. We discuss how mutations in genes regulating adenoviral replication after cell entry can be used to restrict replication to the tumour, and summarise how detailed knowledge of viral capsid interactions enable rational modification to eliminate native tropisms, and simultaneously promote active uptake by cancerous tissues. We argue that these designer-viruses, exploiting the viruses natural mechanisms and regulated at every level of replication, represent the ideal platforms for local overexpression of therapeutic transgenes such as immunomodulatory agents. Where T-Vec has paved the way, Ad-based vectors now follow. The era of designer oncolytic virotherapies looks decidedly as though it will soon become a reality.