Robust predictive control strategy of SCIG-based drive system.

This article presents a robust finite control set predictive scheme for a stand-alone squirrel cage induction generator (SCIG) drive. This technique is considered an alternative to the drive system due to the inclusion of system nonlinearities and fast dynamic response. The control objective in the distributed generation environment is to fix the output voltage to follow the stand-alone requirement. The strategy establishes optimized switching instants for cost function minimization for both source and load converter control and diminished cross-coupling amid active and reactive power during transient scenarios. The scheme is designed to achieve the minimal effect caused by the parameter uncertainties. During source and load changes, this work will also address the maintenance of dc-link voltage, machine, and load variables at the set value, supported by machine and load-end converter control to achieve stand-alone load objectives. In addition, the presented scheme is also tested with random variation of speed to check the efficacy of the control configuration. The drive performance is evaluated by simulation using MATLAB/Simulink environment. Comprehensive real-time findings obtained from a scaled laboratory test bench using dSPACE-1104 are provided to verify the feasibility of the predictive solution.

Effective seed cake extract of O. sanctum inducing the p53 dependent apoptotic pathway in oral cancer cells.

OBJECTIVE: Present study was to observe the therapeutic aspects of seed cake extracts of Ocimum sanctum against the oral cancer cell line with the activation of p53 apoptotic pathway. METHOD: Seed cake extracts were characterized using GC-MS analysis. Cytotoxic activity was observed on KB cells and L929 cell through MTT assay and scratch assay. Antioxidant activity on KB cells were determined using enzymatic and non enzyme content in the treated cells. Chick chorioallantoic membrane (CAM) was established to check the presence of blood vessel formation and neuvasculature pattern in the treated fertilized eggs. DNA fragmentation and gene expression studies were also determined in the treated cells to check the upregulation of apoptotic pathways. RESULTS: GC-MS analysis confirmed alkaloids, phenols, and many. The cytotoxic activity showed maximum antiproliferative potential with aqueous extract, whereas no cytotoxic effect was observed on L929 cells. The ethanolic and aqueous extract has shown a greater SI value. Scratch assay has signified that aqueous extract has a lower migration rate of KB cells. Aqueous extract showed maximum enzymatic activity and lower malondialdehyde content in cells treated with ethanolic extract. CAM model confirmed that eggs treated with aqueous extract has shown inhibition of vasculature pattern and dissolutions of blood vessels. DNA Fragmentation and Gene expression studies confirmed maximum fold in the KB cell treated with an aqueous extract of seed cake leading to activation of p53 dependent apoptotic pathway. CONCLUSION: The potent therapeutic properties of seed cake extracts have been proven, and they can be used as herbal treatments to prevent oral cancer.

Exploring the human microbiome - A step forward for precision medicine in breast cancer.

BACKGROUND: The second most frequent cancer in the world and the most common malignancy in women is breast cancer. Breast cancer is a significant health concern in India with a high mortality-to-incidence ratio and presentation at a younger age. RECENT FINDINGS: Recent studies have identified gut microbiota as a significant factor that can have an influence on the development, treatment, and prognosis of breast cancer. This review article aims to describe the influence of microbial dysbiosis on breast cancer occurrence and the possible interactions between oncobiome and specific breast cancer molecular subtypes. The review further also discusses the role of epigenetics and diet/nutrition in the regulation of the gut and breast microbiome and its association with breast cancer prevention, therapy, and recurrence. Additionally, the recent technological advances in microbiome research, including next-generation sequencing (NGS) technologies, genome sequencing, single-cell sequencing, and microbial metabolomics along with recent advances in artificial intelligence (AI) have also been reviewed. This is an attempt to present a comprehensive status of the microbiome as a key cancer biomarker. CONCLUSION: We believe that correlating microbiome and carcinogenesis is important as it can provide insights into the mechanisms by which microbial dysbiosis can influence cancer development and progression, leading to the potential use of the microbiome as a tool for prognostication and personalized therapy.

ΔNp63 overexpression promotes oral cancer cell migration through hyperactivated Activin A signaling.

Oral cancer is a common malignant tumor of the oral cavity that affects many countries with a prevalent distribution in the Indian subcontinent, with poor prognosis rate on account of locoregional metastases. Gain-of-function mutations in p53 and overexpression of its related transcription factor, p63 are both widely reported events in oral cancers. However, targeting these alterations remains a far-achieved aim due to lack of knowledge on their downstream signaling pathways. In the present study, we characterize the isoforms of p63 and using knockdown strategy, decipher the functions and oncogenic signaling of p63 in oral cancers. Using Microarray and Chromatin Immunoprecipitation experiments, we decipher a novel transcriptional regulatory axis between p63 and Activin A and establish its functional significance in migration of oral cancer cells. Using an orally bioavailable inhibitor of the Activin A pathway to attenuate oral cancer cell migration and invasion, we further demonstrate the targetability of this signaling axis. Our study highlights the oncogenic role of ΔNp63 - Activin A - SMAD2/3 signaling and provides a basis for targeting this oncogenic pathway in oral cancers.

Therapeutic mammoplasty: a "wise" oncoplastic choice-lessons from the largest single-center cohort from Asia.

Introduction: The majority of breast cancer patients from India usually present with advanced disease, limiting the scope of breast conservation surgery. Therapeutic mammoplasty (TM), an oncoplastic technique that permits larger excisions, is quite promising in such a scenario and well suited to breast cancer in medium-to-large-sized breasts with ptosis and in some cases of large or multifocal/multicentric tumors. Here, we describe our TM cohort of 205 (194 malignant and 11 benign) patients from 2012 to 2019 treated at a single surgeon center in India, the largest Asian dataset for TM. Methods: All patients underwent treatment after careful discussions by a multidisciplinary tumor board and patient counseling. We report the clinicopathological profiles and surgical, oncological, cosmetic, and patient-related outcomes with different TM procedures. Results: The median age of breast cancer patients was 49 years; that of benign disease patients was 41 years. The breast cancer cohort underwent simple (n = 84), complex (n = 71), or extreme (n = 44) TM surgeries. All resection margins were analyzed through intra-operative frozen-section assessment with stringent rad-path analysis protocols. The margin positivity rate was found to be 1.4%. A majority of the cohort was observed to have pT1-pT2 tumors, and the median resection volume was 180 cc. Low post-operative complication rates and good-to-excellent cosmetic scores were observed. The median follow-up was 39 months. We observed 2.07% local and 5.7% distal recurrences, and disease-specific mortality was 3.1%. At median follow-up, the overall survival was observed to be 95.9%, and disease-free survival was found to be 92.2%. The patient-reported outcome measures (PROMs) showed good-to-excellent scores for all types of TMs across BREAST-Q domains. Conclusion: We conclude that in India, a country where women present with large and locally advanced tumors, TM safely expands the indications for breast conservation surgery. Our results show oncological and cosmetic outcomes at acceptable levels. Most importantly, PROM scores suggest improved overall wellbeing and better satisfaction with the quality of life. For patients with macromastia, this technique not only focuses on cancer but also improves self-image and reduces associated physical discomfort often overlooked by women in the Indian setting. The popularization of this procedure will enable Indian patients with breast cancer to receive the benefits of breast conservation.

Proceedings of the 3rd Indian Cancer Genome Atlas Conference 2022: Biobanking to Omics: Collecting the Global Experience.

On January 13th and 14th 2022, the Center for Translational Cancer Research organized the virtual third Indian Cancer Genome Atlas (ICGA) Conference 2022 "Biobanking to Omics - Collecting the Global Experience." This conference was planned as the steppingstone to help ICGA understand the road ahead and the probable roadblocks in its preparatory phase as ICGA begins to streamline the tumor tissue biobanking and multi-omics efforts in the Indian subcontinent. The first day of the conference was dedicated to updates on the current status of ICGA, the future prospect, and the global understanding of multi-omics efforts. The key highlights included two keynote speeches by Dr Wui Jin Koh, Senior Vice President and Chief Medical Office, National Comprehensive Cancer Network, and by Dr Christina Curtis, Associate Professor, Stanford University School of Medicine. The first day ended with an intriguing panel discussion on "ICGA updates and Future Steps." The second day focused on biobanking practices across the globe and several aspects of biobank setup such as infrastructure, maintenance, quality control, patient consent, and lessons learned from established biobanking setups. The talk by Rosita Kammler, Head, Translational Research Coordination, International Breast Cancer Study Group, Switzerland, and Ruhul Amin, Director, Bangladesh Medical Research Council were the key highlights. The second day also ended with an engaging panel discussion on "Tumor tissue biobanking - national and international perspectives." Overall, the conference was well received and had good attendance from national and international students, researchers, and faculty from academia as well as industry.

Antiproliferative efficacy of the antioxidant bioactive compounds of defatted seeds of Azadirachta indica and Momordica charantia against the regulatory function of tumor suppressor gene inducing oral carcinoma.

The present study focuses on the antiproliferative activity of polyphenolic flavonoids found in defatted seeds of Azadirachta indica and Momordica charantia with the regulatory function of tumor suppressor genes inducing Oral Squamous Cell Carcinoma. Polyphenolic flavonoid in extracts was characterized using chromatographic analysis and has confirmed the presence of quercetin, rutin and tannic acid in the extracts of A. indica and M. charantia. According to DPPH assay and reducing power assays, free radical scavenging was found to be high in ethanolic extract of defatted seeds. Antiproliferative efficacies of defatted seed extracts against KB cell line (mouth) were studied by MTT assay and revealed that aqueous extract of defatted seeds of M. charantia has exhibited maximum antiproliferative activity against KB cells. Antioxidant activity of defatted seed extracts were observed on treated KB cells by determining enzymatic activity (SOD, Cat, and GST) and nonenzyme content (GSH and MDA Content). Using the AutoDock tool, quercetin, rutin and tannin acid revealed that mutant p53, TWIST related protein, TGF-ß and Snail I have the best binging energy results. MD simulation was observed on best docking results between the molecule and identified flavonoid by Desmond V 5.9 package . This leads to the conclusion that bioactive extracts with antiproliferative activity, antioxidant capacity and polyphenols with binding efficacy against tumor suppressor gene regulatory function could be used as a herbal remedy.Communicated by Ramaswamy H. Sarma.

Concomitant overexpression of Activin A and p63 is associated with poor outcome in oral cancer patients.

BACKGROUND: The present study aims to comprehensively analyze expression of Activin signaling components in oral cancer and to determine the predominant Activin expressed and its influence on prognosis. As our preliminary studies indicated regulation of Activin gene by p63, we also propose to assess its correlation with p63/p53 in oral tumors and its impact on outcome. METHODS: Expression of Activin subunits, receptors, and regulators was assessed by qRT-PCR and Western blotting. Correlation between Activin A and p63/p53 expression was evaluated in oral tumors by immunohistochemistry and their association with clinical outcome was determined by Kaplan-Meier curves and Cox regression. RESULTS: Activin ßA transcripts were upregulated (P = .013) in oral dysplastic and cancer cells compared with normal oral mucosa. Expression of Activin receptors and regulators was also altered. Activin ßA protein was significantly upregulated in oral tumors and adjacent normal tissues compared with normal oral mucosa (P < .0001). Expression of Activin ßA and p63 significantly correlated in oral tumors, correlation being stronger in tumors with high p53 (r = -.394, P = .005). Activin ßA overexpression was associated with advanced tumor stage (P = .021), positive nodes (P = .045), poor recurrence-free survival (P = .013), and overall survival (P = .024), while its concomitant overexpression with p63 was a better predictor of recurrence-free survival (HR = 10.66, CI: 1.41-80.19). CONCLUSIONS: Activin A overexpression is an early event in oral cancer pathogenesis and can independently predict survival. Moreover, in combination with p63 overexpression, it served as a better marker for poor prognosis. Activin A could thus be a promising target for improved outcome in oral cancer patients.

High expression of survivin and its splice variants survivin ΔEx3 and survivin 2 B in oral cancers.

OBJECTIVES: We have previously reported inactivation of p53 in 46% of Indian patients with oral cancer. Survivin, a p53 target gene and an inhibitor of apoptosis protein (IAP), is overexpressed in several cancers, including oral cancers. Studies assessing the role of survivin and its splice variants in oral cancers are, however, rare. MATERIALS AND METHODS: The expression of 6 survivin isoforms in 4 oral cancer cell lines (AW8507, AW13516, UPCI-SCC040, UPCI-SCC029 B), a dysplastic oral cell line (DOK), 75 paired oral tumor and adjacent normal tissues, and 12 normal oral tissue samples from healthy individuals was analyzed by real-time PCR. The expression was correlated with clinicopathologic parameters, which included age, sex, tumor-node-metastasis (TNM) staging, tobacco and/or alcohol consumption, site, and differentiation status of tumor. RESULTS: This is the first study to find overexpression of the 6 characterized survivin isoforms in oral cancers compared with normal tissues (P < .05). Additionally, a significant (P < .05) correlation among the fold changes of all 6 survivin isoforms was observed. Survivin wild type (wt) was the predominantly expressed isoform in oral cell lines and tumor tissues versus normal tissues (P < .05). Among the minor isoforms, survivin ΔEx3 and survivin 2 B were dominantly expressed, whereas survivin 2 α and survivin 3 α overexpression was found for the first time. Further high survivin 3 B expression exhibited a significant association (P < .05) with poorly differentiated tumors. Interestingly the combined expression of the antiapoptotic survivin isoforms, survivin wt, survivin ΔEx3, and survivin 3 B, exhibited a significant association with TNM staging of the tumor. CONCLUSIONS: Our studies thus indicate that oral cancers overexpress the antiapoptotic survivin variants, which exhibit an association with advanced tumor stage, implying a role for these variants in oral tumorigenesis.