The futuristic applications of transition metal dichalcogenides for cancer therapy.

The second-most common cause of death resulting from genetic mutations in DNA sequences is cancer. The difficulty in the field of anticancer research is the application of the traditional methods, which also affects normal cells. Mutations, genetic replication alterations, and chromosomal abnormalities have a direct impact on the effectiveness of anticancer drugs at different stages. Presently, therapeutic techniques utilize nanotechnology, transition metal dichalcogenides (TMDCs), and robotics. TMDCs are being increasingly employed in tumor therapy and biosensing applications due to their biocompatibility, adjustable bandgap, versatile functionality, exceptional photoelectric properties, and wide range of applications. This study reports the advancement of nanoplatforms based on TMDCs that are specifically engineered for responsive and intelligent cancer therapy. This article offers a thorough examination of the current challenges, future possibilities for theranostic applications using TMDCs, and recent progress in employing TMDCs for cancer therapy. Currently, there is significant interest in two-dimensional (2D) TMDCs nanomaterials as ultrathin unique physicochemical properties. These materials have attracted attention in various fields, including biomedicine. Due to their inherent ability to absorb near-infrared light and their exceptionally large surface area, significant efforts are being made to prepare multifunctional nanoplatforms based on 2D TMDCs.

N-Hydroxyalkanamide Based Organo/hydrogels as Novel Scaffolds for pH-Dependent Metronidazole and Theophylline Release.

The traditional delivery of metronidazole and theophylline presents challenges like bitter taste, variable absorption, and side effects. However, gel-based systems offer advantages including enhanced targeted drug delivery, minimized side effects, and improved patient compliance, effectively addressing these challenges. Consequently, a cost-effective synthesis of N-hydroxyalkanamide gelators with varying alkyl chain lengths was achieved in a single-step reaction procedure. These gelators formed self-assembled aggregates in DMSO/water solvent system, resulting in organo/hydrogels at a minimum gelation concentration of 1.5 % w/v. Subsequently, metronidazole and theophylline were encapsulated within the gel core and released through gel-to-sol transition triggered by pH variation at 37 °C, while maintaining the structural-activity relationship. UV-vis spectroscopy was employed to observe the drug release behavior. Furthermore, in vitro cytotoxicity assays revealed cytotoxic effects against A549 lung adenocarcinoma cells, indicating anti-proliferative activity against human lung cancer cells. Specifically, the gel containing theophylline (16HAD+Th) exhibited cytotoxicity on cancerous A549 cells with IC50 values of 19.23±0.6 µg/mL, followed by the gel containing metronidazole (16HAD+Mz) with IC50 values of 23.75±0.7 µg/mL. Moreover, the system demonstrated comparable antibacterial activity against both gram-negative (E. coli) and gram-positive bacteria (S. aureus).

A Comprehensive Review of the Diverse Spectrum Activity of 1,2,3-Triazole-linked Isatin Hybrids.

Heterocyclic compounds containing 1,2,3-triazole and isatin as core structures have emerged as promising drug candidates due to their diverse biological activities such as anti-cancer, antifungal, antimicrobial, antitumor, anti-epileptic, antiviral, and more. The presence of 1,2,3-triazoles and isatin heterocycles in these hybrids, both individually known for their medicinal significance, has increasingly piqued the interest of drug discovery researchers, as they seek to delve deeper into their extensive pharmacological potential for enhancing therapeutic efficacy. Moreover, these hybrid compounds are synthetically accessible using readily available materials. Therefore, there is a pressing need to provide a comprehensive overview of the existing knowledge in this field, offering valuable insights to readers and paving the way for the discovery of novel 1,2,3-triazole-linked isatin hybrids with therapeutic potential.

Assessment of the USG Detection of Abdominal Pathologies in HIV and Aids and its Association with CD4 Counts - An Original Research.

Introduction: In individuals with acquired immunodeficiency syndrome (HIV/AIDS), abdominal pathologies rank second in frequency only to pulmonary illnesses. An essential imaging method for assessing abdominal diseases is ultrasonography (USG). In this study, abdominal pathologies in HIV/AIDS patients were evaluated using USG, and their relationship to CD4 count was further examined. Materials and Techniques: 400 HIV+ subjects with aberrant abdominal USG participated in the current investigation. The subjects were assessed and graded as per the CD4 counts. Later the comparisons were drawn between the USG, and its relationship to CD4 count using SPSS 16.0 software, and all data were examined using appropriate statistical tools. Results: Men were over 60% of the 400 subjects. The average age of these subjects was 35.6 years; the range for this age group was 6 to 63 years. Spleen involvement was found on ultrasonographic examination in 45.1% of subjects, while liver and lymph node involvement was seen in 43.6% of subjects. Substantial correlations between CD4 counts and findings such as periportal & mesenteric lymphadenopathy, localized pancreatic lesion, splenic microabscess, splenomegaly, and hepatomegaly were found. One percent of individuals had lymphoma, which affected the retroperitoneal lymph nodes, pancreas, and liver. Conclusion: Present research demonstrates the significance of abdominal ultrasonographic examination in HIV+ patients. CD4 counts have a big impact on how an HIV/AIDS patient's differential diagnosis is determined. The interpretation of USG results in relation to CD4 levels may aid in accurate diagnosis.

In-silico identification of small molecule benzofuran-1,2,3-triazole hybrids as potential inhibitors targeting EGFR in lung cancer via ligand-based pharmacophore modeling and molecular docking studies.

Lung cancer is one of the most common and deadly types of cancer worldwide, and the epidermal growth factor receptor (EGFR) has emerged as a promising therapeutic target for the treatment of this disease. In this study, we designed a library of 1840 benzofuran-1,2,3-triazole hybrids and conducted pharmacophore-based screening to identify potential EGFR inhibitors. The 20 identified compounds were further evaluated using molecular docking and molecular dynamics simulations to understand their binding interactions with the EGFR receptor. In-silico ADME and toxicity studies were also performed to assess their drug-likeness and safety profiles. The results of this study showed the benzofuran-1,2,3-triazole hybrids BENZ-0454, BENZ-0143, BENZ-1292, BENZ-0335, BENZ-0332, and BENZ-1070 dock score of - 10.2, - 10, - 9.9, - 9.8, - 9.7, - 9.6, while reference molecule - 7.9 kcal/mol for EGFR (PDB ID: 4HJO) respectively. The molecular docking and molecular dynamics simulations revealed that the identified compounds formed stable interactions with the active site of the receptor, indicating their potential as inhibitors. The in-silico ADME and toxicity studies suggested that the compounds had good pharmacokinetic and safety profiles, further supporting their potential as therapeutic agents. Finally, performed DFT studies on the best-selected ligands to gain further insights into their electronic properties. The findings of this study provide important insights into the potential of benzofuran-1,2,3-triazole hybrids as promising EGFR inhibitors for the treatment of lung cancer. Overall, this study provides a valuable starting point for the development of novel EGFR inhibitors with improved efficacy and safety profiles. Supplementary Information: The online version contains supplementary material available at 10.1007/s40203-023-00157-1.

Identification and exploration of quinazoline-1,2,3-triazole inhibitors targeting EGFR in lung cancer.

Epidermal growth factor receptor (EGFR) enhances lung cancer development, due to their inability to permeate the cell membrane, secreted growth factors work through specialized signal transduction pathways. The purpose of this study is to find out a novel anticancer agent that inhibits EGFR and reduces the chances of lung cancer. A series of triazole-substituted quinazoline hybrid compounds were designed by Chemdraw software and docked against five different crystallographic EGFR tyrosine kinase domain (TKD). For docking and visualization PyRx, Autodock vina, and Discovery studio visualizer were used. Molecule-14, Molecule-16, Molecule-19, Molecule-20, and Molecule-38 showed significant affinity but Molecule-19 showed excellent binding affinity (-12.4 kcal/mol) with crystallographic EGFR tyrosine kinase. The superimposition of the co-crystalized ligand with the hit compound shows similar conformation at the active site of EGFR (PDB ID: 4HJO) indicating excellent coupling and pharmaceutically active. The hit compound showed a good bioavailability score (0.55) with no sign of carcinogenesis, mutagenesis, or reproductive toxicity properties. MD simulation and MMGBSA represent good stability and binding free energy demonstrating that the hit (Molecule-19) may be used as a lead compound. Molecule-19 also showed good ADME properties, bioavailability scores, and synthetic accessibility with fewer signs of toxicity. It was observed that Molecule-19 may be a novel and potential inhibitor against EGFR with fewer side effects than the reference molecule. Additionally, the molecular dynamics simulation revealed the stable nature of protein-ligand interaction and provided information about the amino acid residues involved in binding. Overall, this study led to the identification of potential EGFR inhibitors with favorable pharmacokinetic properties. We believe that the outcome of this study can help to develop more potent drug-like molecules to tackle human lung cancer.

Challenges Faced by Cancer Patients in Receiving Health Services During the COVID-19 Pandemic in a Tertiary Care Hospital in Rajasthan.

BACKGROUND: Amidst the COVID-19 pandemic, cancer patients may have faced difficulty accessing health care. This study explored the challenges experienced by cancer patients in availing of healthcare during the pandemic, as well as the vaccination status and prevalence of COVID-19 infection among cancer patients in the year 2021. METHOD: A cross-sectional study was conducted in a tertiary care hospital in Jodhpur, Rajasthan, to interview 150 patients from the oncology department using convenience sampling. Face-to-face interviews lasted for 20-30 minutes. The first segment of the pretested semi-structured questionnaire was directed at obtaining the patient's socio-demographic characteristics, while the second segment focused on the problems that patients encountered during the pandemic in receiving cancer care. The data were analyzed using Statistical Packages for Social Sciences (SPSS) software (IBM Corp., Armonk, NY). RESULTS: Several constraints, such as a lack of transportation services, difficulty in availing outpatient department (OPD) and teleconsultation services, long waiting times, and deferred surgeries and therapies, have hampered cancer care. COVID-19 mitigation measures further imposed additional stress and financial burden on cancer patients. Moreover, there was low vaccination coverage among cancer patients, which increases their probability of acquiring an infection. CONCLUSION: Policy reforms must prioritize cancer care in India to maintain a continuum of care by ensuring medication, teleconsultation, uninterrupted treatment, and complete vaccination to decrease the risk of COVID-19 infection and facilitate patient compliance with the healthcare delivery system.

Deep learning techniques for cancer classification using microarray gene expression data.

Cancer is one of the top causes of death globally. Recently, microarray gene expression data has been used to aid in cancer's effective and early detection. The use of DNA microarray technology to uncover information from the expression levels of thousands of genes has enormous promise. The DNA microarray technique can determine the levels of thousands of genes simultaneously in a single experiment. The analysis of gene expression is critical in many disciplines of biological study to obtain the necessary information. This study analyses all the research studies focused on optimizing gene selection for cancer detection using artificial intelligence. One of the most challenging issues is figuring out how to extract meaningful information from massive databases. Deep Learning architectures have performed efficiently in numerous sectors and are used to diagnose many other chronic diseases and to assist physicians in making medical decisions. In this study, we have evaluated the results of different optimizers on a RNA sequence dataset. The Deep learning algorithm proposed in the study classifies five different forms of cancer, including kidney renal clear cell carcinoma (KIRC), Breast Invasive Carcinoma (BRCA), lung adenocarcinoma (LUAD), Prostate Adenocarcinoma (PRAD) and Colon Adenocarcinoma (COAD). The performance of different optimizers like Stochastic gradient descent (SGD), Root Mean Squared Propagation (RMSProp), Adaptive Gradient Optimizer (AdaGrad), and Adaptive Momentum (AdaM). The experimental results gathered on the dataset affirm that AdaGrad and Adam. Also, the performance analysis has been done using different learning rates and decay rates. This study discusses current advancements in deep learning-based gene expression data analysis using optimized feature selection methods.

Comprehensive Search for Novel Circulating miRNAs and Axon Guidance Pathway Proteins Associated with Risk of ESKD in Diabetes.

BACKGROUND: Mechanisms underlying the pro gression of diabetic kidney disease to ESKD are not fully understood. METHODS: We performed global microRNA (miRNA) analysis on plasma from two cohorts consisting of 375 individuals with type 1 and type 2 diabetes with late diabetic kidney disease, and targeted proteomics analysis on plasma from four cohorts consisting of 746 individuals with late and early diabetic kidney disease. We examined structural lesions in kidney biopsy specimens from the 105 individuals with early diabetic kidney disease. Human umbilical vein endothelial cells were used to assess the effects of miRNA mimics or inhibitors on regulation of candidate proteins. RESULTS: In the late diabetic kidney disease cohorts, we identified 17 circulating miRNAs, represented by four exemplars (miR-1287-5p, miR-197-5p, miR-339-5p, and miR-328-3p), that were strongly associated with 10-year risk of ESKD. These miRNAs targeted proteins in the axon guidance pathway. Circulating levels of six of these proteins-most notably, EFNA4 and EPHA2-were strongly associated with 10-year risk of ESKD in all cohorts. Furthermore, circulating levels of these proteins correlated with severity of structural lesions in kidney biopsy specimens. In contrast, expression levels of genes encoding these proteins had no apparent effects on the lesions. In in vitro experiments, mimics of miR-1287-5p and miR-197-5p and inhibitors of miR-339-5p and miR-328-3p upregulated concentrations of EPHA2 in either cell lysate, supernatant, or both. CONCLUSIONS: This study reveals novel mechanisms involved in progression to ESKD and points to the importance of systemic factors in the development of diabetic kidney disease. Some circulating miRNAs and axon guidance pathway proteins represent potential targets for new therapies to prevent and treat this condition.

Essential roles of insulin and IGF-1 receptors during embryonic lineage development.

The insulin and insulin-like growth factor-1 (IGF-1) receptors are important for the growth and development of embryonic tissues. To directly define their roles in the maintenance of pluripotency and differentiation of stem cells, we knocked out both receptors in induced pluripotent stem cells (iPSCs). iPSCs lacking both insulin and IGF-1 receptors (double knockout, DKO) exhibited preserved pluripotency potential despite decreased expression of transcription factors Lin28a and Tbx3 compared to control iPSCs. While embryoid body and teratoma assays revealed an intact ability of DKO iPSCs to form all three germ layers, the latter were composed of primitive neuroectodermal tumor-like cells in the DKO group. RNA-seq analyses of control vs DKO iPSCs revealed differential regulation of pluripotency, developmental, E2F1, and apoptosis pathways. Signaling analyses pointed to downregulation of the AKT/mTOR pathway and upregulation of the STAT3 pathway in DKO iPSCs in the basal state and following stimulation with insulin/IGF-1. Directed differentiation toward the three lineages was dysregulated in DKO iPSCs, with significant downregulation of key markers (Cebpα, Fas, Pparγ, and Fsp27) in adipocytes and transcription factors (Ngn3, Isl1, Pax6, and Neurod1) in pancreatic endocrine progenitors. Furthermore, differentiated pancreatic endocrine progenitor cells from DKO iPSCs showed increased apoptosis. We conclude that insulin and insulin-like growth factor-1 receptors are indispensable for normal lineage development and perturbations in the function and signaling of these receptors leads to upregulation of alternative compensatory pathways to maintain pluripotency.

A Prospective Observational Study Comparing Long-Course Conventional Neoadjuvant Chemoradiotherapy with Short-Course Radiotherapy Followed by Consolidation Chemotherapy with Delayed Surgery in Locally Advanced Rectal Cancer.

Background Polish and Australian randomized studies compared short-course radiotherapy (RT) with immediate surgery and long-course chemoradiotherapy (CRT) with delayed surgery. In these studies, similar long-term survival and local control have been reported for both these approaches, but pathological complete response (pCR) is not better with short-course RT. Moreover, studies have shown better tumor downstaging with delayed surgery. In this context, the use of short-course RT with delayed surgery may have some advantages and needs to be tested in clinical trials. Patients and Methods This was a two-arm, prospective, observational study, in which preoperative short-course RT followed by two cycles of chemotherapy was compared with the conventional neoadjuvant CRT in locally advanced rectal cancer. The primary end points were the rate of complete response and toxicity profile. The secondary end points were the rate of R0 resection, overall survival, and progression-free survival. The data obtained from the two arms were analyzed using Pearson's chi-square test to determine the statistical significance between the two treatment arms. Results The pCR rate was 6.7% in the study arm and 0 in the control arm ( p = 0.343). The RO resection rates were 92.8 and 92.3% in the study and control arms, respectively. The rates of grade 3and 4 acute toxicity in the study and control arms were 14.2 and 61.5%, respectively ( p = 0.011). The rates of grade 3 and 4 late toxicity in the study and control arms were 21.4 and 15.3%, respectively ( p = 0.686). Conclusions The pCR rates and the late toxicities in both arms are comparable. The major advantages of the 5 × 5 Gy regimen with chemotherapy in a neoadjuvant setting are a significant reduction in acute toxicities and better patient compliance along with similar efficacy as that of the standard regimen.

Leptin Receptor Signaling Regulates Protein Synthesis Pathways and Neuronal Differentiation in Pluripotent Stem Cells.

The role of leptin receptor (OB-R) signaling in linking pluripotency with growth and development and the consequences of dysfunctional leptin signaling on progression of metabolic disease is poorly understood. Using a global unbiased proteomics approach we report that embryonic fibroblasts (MEFs) carrying the db/db mutation exhibit metabolic abnormalities, while their reprogrammed induced pluripotent stem cells (iPSCs) show altered expression of proteins involved in embryonic development. An upregulation in expression of eukaryotic translation initiation factor 4e (Eif4e) and Stat3 binding to the Eif4e promoter was supported by enhanced protein synthesis in mutant iPSCs. Directed differentiation of db/db iPSCs toward the neuronal lineage showed defects. Gene editing to correct the point mutation in db/db iPSCs using CRISPR-Cas9, restored expression of neuronal markers and protein synthesis while reversing the metabolic defects. These data imply a direct role for OB-R in regulating metabolism in embryonic fibroblasts and key developmental pathways in iPSCs.

A comprehensive review of computational techniques for the prediction of drug side effects.

Drugs refer to the chemical compounds that are consumed by the human body and induce a change by interacting with the protein targets. The drugs may induce favorable or unfavorable changes in the human body. The unfavorable changes that are elicited by the drugs in the human body are known as drug side effects. These side effects range from minor reactions like headache to serious reactions such as cardiac arrest, cancer, or even death. The drugs are tested for their side effects based on laboratory experiments. However, these experiments are costly as well as prolonged. An alternative to the laboratory experiments is provided through the computational methods. Many computational techniques for identifying the drug side effects have been developed in the recent past. This review aims to summarize the important studies and contributions in the field of drug side effect prediction by computational techniques. A description of the data sets related to drug side effects and the metrics used for the evaluation of drug side effect prediction methods have also been explained. This article also highlights the future research that can be undertaken in this field. To the best of our knowledge, this is the first extensive review of the computational methods that have been developed for drug side effect prediction.

Curcumin - A Novel Therapeutic Agent in the Prevention of Colorectal Cancer.

BACKGROUND: Colorectal cancer is the third important cause of cancer-associated deaths across the world. Hence, there is an urgent need for understanding the complete mechanism associated with colorectal cancer, which in turn can be utilized toward early detection as well as the treatment of colorectal cancer in humans. Though colorectal cancer is a complex process and chemotherapy is the first step toward the treatment of colorectal cancer, recently several studies suggested that dietary phytochemicals may also aid significantly in reducing colorectal cancer risk in human. However, only few phytochemicals, specifically curcumin derived from the rhizomes of Curcuma longa, have better chemotherapeutic property, which might be because of its ability to regulate the activity of key factors associated with the initiation, promotion, as well as progression of tumors. OBJECTIVES: In the present review, the authors made an attempt to summarize the physiochemical properties of curcumin, which in turn prevent colorectal cancer via regulating numerous cell signaling as well as genetic pathways. CONCLUSION: Accumulated evidence suggested that curcumin suppresses tumour/colon cancer in various ways, (a) restricting cell cycle progression, or stimulating apoptosis, (b) restricting angiogenesis, anti-apoptotic proteins expression, cell survival signaling pathways & their cross-communication and (c) regulating immune responses. The information discussed in the present review will be useful in the drug discovery process as well as the treatment and prevention of colorectal cancer in humans.

Attenuation of PKCδ enhances metabolic activity and promotes expansion of blood progenitors.

A finely tuned balance of self-renewal, differentiation, proliferation, and survival governs the pool size and regenerative capacity of blood-forming hematopoietic stem and progenitor cells (HSPCs). Here, we report that protein kinase C delta (PKCδ) is a critical regulator of adult HSPC number and function that couples the proliferative and metabolic activities of HSPCs. PKCδ-deficient mice showed a pronounced increase in HSPC numbers, increased competence in reconstituting lethally irradiated recipients, enhanced long-term competitive advantage in serial transplantation studies, and an augmented HSPC recovery during stress. PKCδ-deficient HSPCs also showed accelerated proliferation and reduced apoptosis, but did not exhaust in serial transplant assays or induce leukemia. Using inducible knockout and transplantation models, we further found that PKCδ acts in a hematopoietic cell-intrinsic manner to restrict HSPC number and bone marrow regenerative function. Mechanistically, PKCδ regulates HSPC energy metabolism and coordinately governs multiple regulators within signaling pathways implicated in HSPC homeostasis. Together, these data identify PKCδ as a critical regulator of HSPC signaling and metabolism that acts to limit HSPC expansion in response to physiological and regenerative demands.

Insulin receptor-mediated signaling regulates pluripotency markers and lineage differentiation.

OBJECTIVES: Insulin receptor (IR)-mediated signaling is involved in the regulation of pluripotent stem cells; however, its direct effects on regulating the maintenance of pluripotency and lineage development are not fully understood. The main objective of this study is to understand the role of IR signaling in pluripotency and lineage development. METHODS: To explore the role of IR signaling, we generated IR knock-out (IRKO) mouse induced pluripotent stem cells (miPSCs) from E14.5 mouse embryonic fibroblasts (MEFs) of global IRKO mice using a cocktail of four reprogramming factors: Oct4, Sox2, Klf4, cMyc. We performed pluripotency characterization and directed the differentiation of control and IRKO iPSCs into neural progenitors (ectoderm), adipocyte progenitors (mesoderm), and pancreatic beta-like cells (endoderm). We mechanistically confirmed these findings via phosphoproteomics analyses of control and IRKO iPSCs. RESULTS: Interestingly, expression of pluripotency markers including Klf4, Lin28a, Tbx3, and cMyc were upregulated, while abundance of Oct4 and Nanog were enhanced by 4-fold and 3-fold, respectively, in IRKO iPSCs. Analyses of signaling pathways demonstrated downregulation of phospho-STAT3, p-mTor and p-Erk and an increase in the total mTor and Erk proteins in IRKO iPSCs in the basal unstimulated state. Stimulation with leukemia inhibitory factor (LIF) showed a ∼33% decrease of phospho-ERK in IRKO iPSCs. On the contrary, Erk phosphorylation was increased during in vitro spontaneous differentiation of iPSCs lacking IRs. Lineage-specific directed differentiation of the iPSCs revealed that cells lacking IR showed enhanced expression of neuronal lineage markers (Pax6, Tubb3, Ascl1 and Oligo2) while exhibiting a decrease in adipocyte (Fas, Acc, Pparγ, Fabp4, C/ebpα, and Fsp27) and pancreatic beta cell markers (Ngn3, Isl1, and Sox9). Further molecular characterization by phosphoproteomics confirmed the novel IR-mediated regulation of the global pluripotency network including several key proteins involved in diverse aspects of growth and embryonic development. CONCLUSION: We report, for the first time to our knowledge, the phosphoproteome of insulin, IGF1, and LIF stimulation in mouse iPSCs to reveal the importance of insulin receptor signaling for the maintenance of pluripotency and lineage determination.

Breast cancer risk factor evaluation in a Western Himalayan state: A case-control study and comparison with the Western World.

CONTEXT: Breast cancer incidence is increasing rapidly in India. The lifestyle, built, genetic makeup, reproductive and breastfeeding patterns are quite different in Indian females when compared to the Western population. Generalizing the Western data to the population residing in the Himalayan region would breed inaccuracies. AIM: The aim of our study was to identify risk factors in our own population in a Western Himalayan state of Himachal Pradesh, India. SUBJECTS AND METHODS: A case-control study with 377 cases of invasive breast cancer and 346 hospital-based controls was conducted for 1 year. The data were collected by interviewing the individuals during their visit to hospital using a questionnaire. The data were analyzed using standard statistical techniques using SPSS version 17 software. RESULTS: Factors found to have strong association with invasive breast cancer on multivariate analysis are late age at first childbirth >30 years, which is the strongest risk factor associated, late age of menopause > 50 years, high socioeconomic class, and age of female above 50 years. CONCLUSION: In our females, age >50 years, late age of menopause (>50 years), late age at first childbirth (>30 years), and high socioeconomic status were found to be major risk factors associated with breast cancer. Several factors implicated in the Western data were not found to be significant in our study. We need to identify such aspects in reproductive and breastfeeding patterns of women and spread awareness regarding the same.

Normal Tissue Complications following Hypofractionated Chest Wall Radiotherapy in Breast Cancer Patients and Their Correlation with Patient, Tumor, and Treatment Characteristics.

INTRODUCTION: Normal tissue complications following chest wall radiotherapy (RT) are inevitable, and the long-term data on hypofractionation are still limited. To quantify the late effects of hypofractionated RT on cardiac, pulmonary, brachial plexus, and regional lymphatics and their correlation with patient, tumor, and treatment characteristics is the main objective of this study. MATERIALS AND METHODS: Two hundred and sixteen breast cancer patients following mastectomy were treated with hypofractionated schedules either 40 Gy in 15 fractions or 42.5 Gy in 16 fractions. Common Toxicity Criteria version 3.0 was utilized to quantify the late effects of hypofractionation on cardiac, pulmonary, brachial plexus, and lymphedema at a maximum follow-up of 5 years. RESULTS: Median follow-up was 42 months. Median age was 49 years. 14.8% developed ≥Grade (Gr) 2 late cardiac toxicity. 10.2% developed ≥Gr2 late pulmonary toxicity. There were 28.7% patients who developed ≥Gr2 lymphedema. Sixty-seven out of 216 patients had symptomatic brachial plexopathy at 5-year follow-up. Variables found to increase the incidence of these adverse events included smoking, hypertension, diabetes mellitus, body mass index ≥25, extent of axillary dissection, and use of supraclavicular field. CONCLUSION: Hypofractionation leads to increased risk of normal tissue complications partly influenced by some patient- and treatment-related factors, but these were manageable and minimally disabling.

Can pure accelerated radiotherapy given as six fractions weekly be an option in locally advanced carcinoma cervix: Results of a prospective randomized phase III trial.

CONTEXT: Concurrent chemoradiation is presently the standard of care in locally advanced malignancy of the cervix uteri. But accelerated radiotherapy regimes have not been investigated much. AIMS: We conducted a randomized trial to compare the results of pure accelerated radiotherapy given as six fractions weekly to standard chemoradiotherapy in locally advanced carcinoma cervix patients. SETTINGS AND DESIGN: This was a prospective, phase III trial in which 106 patients of locally advanced (stage II and III) carcinoma cervix were randomized into two arms. SUBJECTS AND METHODS: The study arm (ART) received 50 Gy accelerated radiotherapy in 25 fractions, six fractions weekly; while control (CRT) arm was treated with concurrent chemoradiation 50 Gy in 25 fractions with weekly injection cisplatin. This was followed by intracavitary brachytherapy (ICBT; total dose of 85 Gy to point A) in both the arms. Fifty-one patients completed treatment in the ART arm and 50 patients in the CRT arm. In these patients, response to treatment, toxicity, and overall survival (OS) and disease-free survival (DFS) were compared between both the arms. STATISTICAL ANALYSIS USED: Survival analysis was done using Kaplan.Meier estimates, logrank test was used to compare differences, while proportions were compared using the Fisher's t-test. RESULTS: At a median follow.up of 36. months there was no difference between the two arms in terms of OS. (61 vs 62%,P = 0.9009) as well as DFS. (60 vs 64%,P = 0.6411) CONCLUSIONS: Accelerated radiotherapy given as six fractions per week is an effective alternative to concomitant chemoradiation in locally advanced carcinoma cervix and has shown lesser toxicities in our study.

Fat on sale: role of adipose-derived stem cells as anti-fibrosis agent in regenerative medicine.

The potential use of stem cells for cell-based tissue repair and regeneration offers alternative therapeutic strategies for various diseases. Adipose-derived stem cells (ADSCs) have emerged as a promising source of stem cells suitable for transplantation in regenerative medicine and wound repair. A recent publication in Stem Cell Research & Therapy by Zhang and colleagues reports a new finding about the anti-fibrosis role of ADSCs and conditioned media derived from them on hypertrophic scar formation in vivo.