Establishing a Prognostic Signature Based on Epithelial–Mesenchymal Transition-Related Genes for Endometrial Cancer Patients

BackgroundsEpithelial–mesenchymal transition (EMT) is a sequential process where tumor cells develop from the epithelial state to the mesenchymal state. EMT contributes to various tumor functions including initiation, propagating potential, and resistance to therapy, thus affecting the survival time of patients. The aim of this research is to set up an EMT-related prognostic signature for endometrial cancer (EC).MethodsEMT-related gene (ERG) expression and clinical data were acquired from The Cancer Genome Atlas (TCGA). The entire set was randomly divided into two sets, one for contributing the risk model (risk score) and the other for validating. Univariate and multivariate Cox proportional hazards regression analyses were applied to the training set to select the prognostic ERGs. The expression of 10 ERGs was confirmed by qRT-PCR in clinical samples. Then, we developed a nomogram predicting 1-/3-/5-year survival possibility combining the risk score and clinical factors. The entire set was stratified into the high- and low-risk groups, which was used to analyze the immune infiltrating, tumorigenesis pathways, and response to drugs.ResultsA total of 220 genes were screened out from 1,316 ERGs for their differential expression in tumor versus normal. Next, 10 genes were found to be associated with overall survival (OS) in EC, and the expression was validated by qRT-PCR using clinical samples, so we constructed a 10-ERG-based risk score to distinguish high-/low-risk patients and a nomogram to predict survival rate. The calibration plots proved the predictive value of our model. Gene Set Enrichment Analysis (GSEA) discovered that in the low-risk group, immune-related pathways were enriched; in the high-risk group, tumorigenesis pathways were enriched. The low-risk group showed more immune activities, higher tumor mutational burden (TMB), and higher CTAL4/PD1 expression, which was in line with a better response to immune checkpoint inhibitors. Nevertheless, response to chemotherapeutic drugs turned out better in the high-risk group. The high-risk group had higher N6-methyladenosine (m6A) RNA expression, microsatellite instability level, and stemness indices.ConclusionWe constructed the ERG-related signature model to predict the prognosis of EC patients. What is more, it might offer a reference for predicting individualized response to immune checkpoint inhibitors and chemotherapeutic drugs.

Ethanol Exposure During the Intravenous Administration of Chemotherapeutic Drugs: An Analysis of Clinical Practice and a Literature Review

PURPOSE: Injectable cytotoxics may be formulated with ethanol. This study sought to quantify the amount of ethanol exposure during chemotherapy infusions. MATERIALS AND METHODS: We first reviewed the antineoplastic drugs (Anatomical Therapeutic and Chemical code L01) and oncologic supportive care drugs (eg, antiemetics) currently available in France, to identify preparations containing ethanol. The amount of ethanol in the final chemotherapy preparation was calculated. Next, we performed a 2-year, single-center, retrospective analysis of injectable antineoplastic drug compounding in routine clinical practice in a French university medical center. Finally, we reviewed our results with regard to the literature data. RESULTS: Ten of the 60 cytotoxic products on the market contained ethanol at concentrations of up to 790 mg/mL, depending on the drug, formulation, and supplier. Several final preparations contained more than 3 g of ethanol per infusion (the maximum recommended by the European Medicines Agency); this was notably the case for gemcitabine, paclitaxel (up to 20 g ethanol per injection, for both), and etoposide (up to 50 g ethanol per infusion). The analysis of our compounding activity showed that 3,172 (4.99%) of the 63,613 chemotherapy preparations (notably paclitaxel) contained more than 3 g of ethanol. None of the oncologic supportive care drugs contained ethanol. CONCLUSION: Patients are exposed to ethanol during the infusion of antineoplastic drugs. With a view to better patient care, physicians and pharmacists should carefully evaluate the risk of ethanol exposure throughout the course of cytotoxic drug treatment.

The Role of Circular RNAs in the Drug Resistance of Cancers

Cancer is a major threat to human health and longevity. Chemotherapy is an effective approach to inhibit cancer cell proliferation, but a growing number of cancer patients are prone to develop resistance to various chemotherapeutics, including platinum, paclitaxel, adriamycin, and 5-fluorouracil, among others. Significant progress has been made in the research and development of chemotherapeutic drugs over the last few decades, including targeted therapy drugs and immune checkpoint inhibitors; however, drug resistance still severely limits the application and efficacy of these drugs in cancer treatment. Recently, emerging studies have emphasized the role of circular RNAs (circRNAs) in the proliferation, migration, invasion, and especially chemoresistance of cancer cells by regulating the expression of related miRNAs and targeted genes. In this review, we comprehensively summarized the potential roles and mechanisms of circRNAs in cancer drug resistance including the efflux of drugs, apoptosis, intervention with the TME (tumor microenvironment), autophagy, and dysfunction of DNA damage repair, among others. Furthermore, we highlighted the potential value of circRNAs as new therapeutic targets and prognostic biomarkers for cancer.

Ad-VT enhances the sensitivity of chemotherapy-resistant lung adenocarcinoma cells to gemcitabine and paclitaxel in vitro and in vivo

SummaryBackground One of the main challenges in the clinical treatment of lung cancer is resistance to chemotherapeutic drugs. P-glycoprotein (P-gp)-mediated drug resistance is the main obstacle to successfully implementing microtubule-targeted tumor chemotherapy. Purpose In this study, we explored the effect of Ad-hTERTp-E1a-Apoptin (Ad-VT) on drug-resistant cell lines and the molecular mechanism by which Ad-VT combined with chemotherapy affects drug-resistant cells and parental cells. Methods In vitro, cell proliferation, colony formation, resistance index (RI), apoptosis and autophagy assays were performed. Protein expression was analyzed by Western blotting. Finally, a xenograft tumor model in nude mice was used to detect tumor growth and evaluate histological characteristics. Results Our results showed that Ad-VT had an obvious killing effect on A549, A549/GEM and A549/Paclitaxel cancer cells, and the sensitivity of drug-resistant cell lines to Ad-VT was significantly higher than that of parental A549 cells. Compared with A549 cells, A549/GEM and A549/Paclitaxel cells had higher autophagy levels and higher viral replication ability. Ad-VT decreased the levels of p-PI3k, p-Akt and p-mTOR and the expression of P-gp. In vivo, Ad-VT combined with chemotherapy can effectively inhibit the growth of chemotherapy-resistant tumors and prolong the survival of mice. Conclusions Thus, the combination of Ad-VT and chemotherapeutic drugs will be a promising strategy to overcome chemoresistance.

Medicinal plants show remarkable antiproliferative potential in human cancer cell lines

Molecules isolated and identified from plant origin are used to manufacture most chemotherapeutic drugs for cancer treatment. We assumed that these plant extracts contain prolific bioactive compounds with potent antiproliferative activities and could be effective against different human cancer cells. Ethanolic extracts were prepared from Chelidonium majus, Myrica cerifera, Fumaria indica, Nigella sativa, and Silybum marianum, and the antiproliferative assay was performed in HepG2 and HeLa human cancer cell lines. All plants extract exhibited antiproliferative potential against studied cancer cell lines in the dose and time-dependent manner. Chelidonium majus and Silybum marianum have shown promising results against HepG2 and HeLa cells, respectively, followed by Myrica cerifera, Fumaria indica, and Nigella sativa. Results indicated that utilization of whole plant extract as anticancer compounds could be of great value in generating novel chemotherapeutic drugs.

Septilin, A Polyherbal Formulation Against the Immunosuppression Induced by Cyclophosphamide and Cisplatin in Swiss Albino Mice

Background: Septilin (Spt) is an ayurvedic drug formulation from Himalaya Drug Company and is well-known for its antibacterial, anti-inflammatory and immunomodulatory activities. Interest in the use of medicinal plants and herbal medicine as immunomodulators has currently been the subject of scientific investigation worldwide. Cyclophosphamide (CP) and Cisplatin (Csp) are widely used chemotherapeutic drugs and are known for their immunosuppressive effects. Methods: The present study evaluated the immune-stimulating activity of Spt (125, 250 and 500 mg/kg; PO/7 days) against CP (50 mg/kg) and Csp (10 mg/kg) induced immunosuppression in mice sensitized with sheep Red Blood Cells (RBC) by measuring Hemagglutination Antibody (HA) titre values and by determining the haematological parameters, such as Haemoglobin (Hb) content, White Blood Cells (WBC), RBC and platelet counts. Thymus index and differential counts of leukocytes were also determined. Results: Upon HA assay, the titre was significantly decreased in CP (59.40%) and Csp (62.16%) in the treatment groups (P<0.001). An increase in the HA titre value in Spt-treated mice showed the stimulation of humoral immune response (P<0.001). The results of haematological study in Spt-treated mice indicated stimulation of total leukocytes, RBC and platelet counts. Moreover, Spt treatment prior to the administration of CP and Csp prevented the loss of body weight and minimized their adverse effect on the mice thymus. Conclusion: Our experimental evidence suggests the immunostimulatory potency of Spt against the immunosuppression induced by chemotherapeutic drugs in mice. The study results are comparable with the immune-potentiating effects of standard immunomodulatory drug Levamisole (Lev). Hence, Spt may be used as an adjuvant to obviate the immune suppression induced by chemotherapeutic medications.

Clinical Theragnostic Relationship between Chemotherapeutic Resistance, and Sensitivity and miRNA Expressions in Head and Neck Cancers: A Systematic Review and Meta-Analysis Protocol

Background: The microRNAs (miRNAs) are small noncoding single-stranded RNAs typically 19–25 nucleotides long and regulated by cellular and epigenetic factors. These miRNAs plays important part in several pathways necessary for cancer development, an altered miRNA expression can be oncogenic or tumor-suppressive. Recent experimental results on miRNA have illuminated a different perspective of the molecular pathogenesis of head and neck cancers. Regulation of miRNA can have a detrimental effect on the efficacy of chemotherapeutic drugs in both neoadjuvant and adjuvant settings. This miRNA-induced chemoresistance can influence the prognosis and survival rate. The focus of the study is on how regulations of various miRNA levels contribute to chemoresistance in head and neck cancer (HNC). Recent findings suggest that up or down-regulation of miRNAs may lead to resistance towards various chemotherapeutic drugs, which may influence the prognosis. Methods: Studies on miRNA-specific chemoresistance in HNC were collected through literary (bibliographic) databases, including SCOPUS, PubMed, Nature, Elsevier, etc., and were systematically reviewed following PRISMA-P guidelines (Preferred Reporting Items for Systematic Review and Meta-analysis Protocol). We evaluated various miRNAs, their up and downregulation, the effect of altered regulation on the patient’s prognosis, resistant cell lines, etc. The data evaluated will be represented in the form of a review and meta-analysis. Discussion: This meta-analysis aims to explore the miRNA-induced chemoresistance in HNC and thus to aid further researches on this topic. PROSPERO registration: CRD42018104657.

Study on Role of In-patient Pharmacist in Prescribed Drug Handling, Mixing, Infusing and Spillage Handling of Chemotherapeutic Drug-Cisplatin in a Tertiary Hospital Pharmacy

The in-patient pharmacist in a cancer hospital plays a major role in patient care especially in patient taking chemotherapy and other narrow indexed drugs as a part of cancer treatment. The pharmacist works as one of the members of cancer treatment team along with physician, oncologist, nurse and other medical professionals. An oncology pharmacist has major role in chemotherapeutic drug handling, mixing, infusing and spillage handling in a disciplined manner. In order to get hands on training about ‘‘oncology-pharmacy’’, it is a mandatory novel pharmaceutical department where a hospital pharmacist who works in oncology will have to get training in handling of chemotherapeutic drugs. The pharmacists who are interested in cancer care will involve in various facets cancer care; from chemotherapeutic drug regimen preparation, mixing of dosage regimen, infusing and finally spillage handling. Hence, it is a mandatory criterion for a graduate pharmacist to get hands on training in specialty Centre to take the responsibility as oncology in-patient pharmacist. The inpatient pharmacist can also be a clinical investigator for various clinical trials involving chemotherapeutic medication usage in patients with cancer. Current study shows that an inpatient pharmacist can play a major role in handling, mixing, infusing and spillage handling of chemotherapeutic drugs in a cancer care centre. The pharmacists are also responsible for reducing drug waste, dealing with drug shortages and reducing exposure to hazardous cytotoxic drugs. The current study suggests that the pharmacist in a cancer care hospital should specially be trained for the handling of chemotherapeutic drugs, mixing and infusion, spillage handling and wastage handling in order to provide accurate treatment for patient and to avoid untoward damage to the person who is handling.

Galangin: A metabolite that suppresses anti-neoplastic activities through modulation of oncogenic targets

With the dramatic increase in cancer incidence all over the world in the last decades, studies on identifying novel efficient anti-cancer agents have been intensified. Historically, natural products have represented one of the most important sources of new lead compounds with a wide range of biological activities. In this article, the multifaceted anti-cancer action of propolis-derived flavonoid, galangin, is presented, discussing its antioxidant, anti-inflammatory, antiproliferative, pro-apoptotic, anti-angiogenic, and anti-metastatic effects in various cancer cells. In addition, co-effects with standard chemotherapeutic drugs as well as other natural compounds are also under discussion, besides highlighting modern nanotechnological advancements for overcoming the low bioavailability issue characteristic of galangin. Although further studies are needed for confirming the anti-cancer potential of galangin in vivo malignant systems, exploring this natural compound might open new perspectives in molecular oncology.