Vikram Gota

Introduction: Docetaxel is widely used for advanced and metastatic solid tumours, but dose limiting toxicities, particularly haematological adverse events, often lead to treatment delays, dose reductions or discontinuation and impair quality of life. Tinospora cordifolia (Guduchi), long used in Ayurveda for its immunomodulatory and rejuvenating properties, has shown chemoprotective potential in experimental and early clinical studies, but robust randomized evidence is lacking. This trial evaluates whether adding an aqueous standardized extract of T. cordifolia(AsSET) to docetaxel-based chemotherapy reduces grade ≥2 adverse events and improves quality of life in patients with advanced or metastatic solid tumours. Methods and analysis: This randomized, double-blind, and placebo-controlled trial designed to evaluate the chemoprotective efficacy of an aqueous standardised extract of Tinospora cordifolia (AsSET) in patients with advanced, recurrent or metastatic solid tumors receiving docetaxel-based chemotherapy. A total of 81 eligible patients that have provided informed consent were recruited in the study. Participants were randomized 2:1 to AsSET or placebo using stratified permuted block randomization stratified by planned cumulative docetaxel dose (≤ 225 vs >225 mg/m ² ) except five participants enrolled before that date were allocated by minimization. All participants received standard intravenous docetaxel-based chemotherapy plus oral administration of either AsSET (two 300mg tablets, 600mg, twice daily) or matching placebo, from enrolment until completion of docetaxel-based therapy. Clinical, laboratory, imaging, and questionnaire based-assessment were performed at baseline, at scheduled interval during treatment and at the final visit. In consenting participants, blood samples for pharmacokinetics were collected once, at nine timepoints up to 24 hours, in any chemotherapy cycle from cycle 2 onwards. Adverse events were graded according to CTCAE version 5.0. The primary outcome is the proportion of patients experiencing grade ≥2 adverse events from first dose to study completion (up to 24 weeks). Secondary outcomes include quality of life measured by the EORTC QLQ-C30 and the disease-site-specific FACT scale, progression-free survival (PFS) per RECIST v1.1, haematological and biochemical parameters, and pharmacokinetic parameters. The database was locked on 17 September 2026 and the locked dataset was transferred to an independent statistician who remains blinded to treatment allocation. Unblinding has not yet been done and outcome analysis has not started. Ethics and dissemination: This study was approved by the Institutional Ethics Committee III (IEC) of the Advanced Centre for Treatment Research & Education in Cancer, Tata Memorial Centre, (ACTREC), Kharghar, Sector 22, Navi Mumbai (project approval no. 900950; first approved on 28 June 2023; this paper describes the most recently amended protocol, version 4.0 dated 24 February 2026; amendments are listed in Annexure 1). The trial is registered with the Clinical Trials Registry-India (CTRI/2023/08/056129) and is conducted in accordance with ICH Good Clinical Practice, the new drugs and Clinical Trials Rules 2019. All participants provided written informed consent, with an additional consent for pharmacokinetic sampling. Participants data are coded to protect confidentiality, and no participant will be identified in any publication without permission. The findings from this study will be presented at an academic conference and published in scholarly journals regardless of the findings. Trial registration: CTRI/2023/08/056129 Strengths and limitation of this study: □ Robust design in the form of randomized, double-blind, placebo-controlled trial with stratified block randomization provides good internal validity □ The study is adequately powered to demonstrate the treatment effect for the underlying assumptions □ Pharmacokinetic sampling in a subset of participants allows assessment of whether AsSET alters docetaxel exposure, an important concern for herb-drug interactions in integrative oncology. □ The study, being limited to docetaxel-based chemotherapy regimens at a single institution, may not be generalizable to other cytotoxic chemotherapy regimen. □ The inclusion of patients with multiple solid tumours receiving varied docetaxel-based regimens may lead to heterogeneity in the chemotherapy-related adverse events which could affect the interpretability of pooled results. □ The 2:1 allocation reduces statistical efficiency compared with equal allocation.

Introduction: Melphalan treatment can cause substantial gastrointestinal toxicity, yet the relationship between chemotherapy-induced epithelial injury, intestinal barrier dysfunction, and alterations in the gut metabolic environment remains incompletely understood. Here, we investigated whether nutritionally and mechanistically distinct interventions could attenuate melphalan-induced intestinal injury and associated metabolic perturbations. Methods: C57BL/6 mice were allocated to vehicle control, melphalan alone, melphalan plus fructo-oligosaccharides (FOS), melphalan plus a commercial probiotic preparation containing Lacticaseibacillus paracasei Shirota, or melphalan plus chlorophyllin ( n = per group). Interventions were administered orally for 3 days before and 3 days after a single oral dose of melphalan (10 mg/kg). Intestinal toxicity was characterized through physiological outcomes, circulating markers of epithelial injury and barrier dysfunction, intestinal protein expression, and targeted LC–MS/MS profiling of short-chain fatty acids, bile acids, and indole-derived metabolites. Results: Melphalan induced body-weight loss and shortening of the small intestine, accompanied by reduced plasma citrulline and increased circulating lipopolysaccharide and occludin, consistent with enterocyte loss and impaired intestinal barrier integrity. These alterations coincided with broad reductions across multiple metabolite classes, indicating substantial disruption of the intestinal metabolic environment. FOS, the commercial probiotic preparation, and chlorophyllin attenuated body-weight loss and restored small-intestinal length and plasma-marker levels toward vehicle-control values. FOS and the probiotic preparation significantly increased selected SCFAs and bile acids, whereas the probiotic preparation and chlorophyllin significantly increased selected tryptophan-derived metabolites. Chlorophyllin also significantly increased taurocholate relative to melphalan alone. Discussion: These findings support further investigation of gut-directed nutritional interventions as strategies to mitigate chemotherapy-associated intestinal injury, with the exploratory metabolite findings requiring confirmation in larger studies.

Introduction: Accurate identification and profiling of medicinal plants are essential for integrating traditional herbal medicine into mainstream healthcare. However, plant identification remains challenging due to morphological similarities among species and the declining availability of taxonomic expertise. Methods: We developed FloraMediX, an AI-enabled platform that combines deep learning‐based visual recognition with structured pharmacological knowledge retrieval. The system employs a Swin Transformer Base (Swin-B) architecture for medicinal plant classification, a human-in-the-loop curation pipeline for iterative model refinement, and integration with phytochemical, therapeutic, and geographical databases including IMPPAT and OSADHI. The model was trained on 166,684 images representing 75 Indian medicinal plant species from the PlantNet-300K dataset and evaluated on an independent test set of 20,880 images. Results: The Swin-B model achieved a Top-1 accuracy of 93.70%, Top-5 accuracy of 99.68%, Macro F1-score of 91.38%, and an AUC of 0.9987. Performance exceeded baseline architectures, including ResNet-CBAM (90.57%), ConvNeXt (92.22%), and CoAtNet (92.22%) on the same evaluation dataset. Discussion: FloraMediX provides a reliable and accurate framework for medicinal plant recognition while simultaneously delivering curated phytochemical, therapeutic, and geographical information. The integration of advanced deep learning, expert-guided curation, and knowledge databases supports applications in research, education, biodiversity conservation, and the preservation of India’s traditional medicinal plant knowledge.

PURPOSE: Abiraterone acetate (AA) is widely used for metastatic castration-resistant prostate cancer (mCRPC), but the standard dose (1000 mg fasting) imposes challenges in resource-constrained settings due to strict fasting requirements and financial toxicity. Pharmacokinetic (PK) studies suggest that low-dose AA (250 mg with a low-fat meal) may provide comparable drug exposure, although clinical evidence remains limited. This trial compared the clinical efficacy of low-dose versus standard-dose AA. MATERIALS AND METHODS: This multicenter, open-label, phase III, noninferiority trial randomly assigned patients with mCRPC, 1:1, to low-dose or standard-dose AA. The primary end point was prostate-specific antigen progression-free survival (PSA-PFS). Secondary/exploratory end points included PSA ₃₀ /PSA ₅₀ responses (% of patients with ≥30% or ≥50% reduction in PSA), radiographic PFS, overall PFS, overall survival (OS), quality of life (QoL), and PK. Planned sample size of 314 (on the basis of a noninferiority margin of hazard ratio, 1.37) was not achieved because of slow accrual, so the noninferiority hypothesis could not be tested. RESULTS: A total of 164 patients were enrolled between September 2020 and January 2025 (median age 65 years; 64.0% received prior docetaxel). PSA ₃₀ and PSA ₅₀ responses were 50.0% and 38.5% with low-dose AA versus 55.4% ( P = .505) and 45.9% ( P = .350) with standard-dose AA, respectively. Median follow-up was 17.5 months. Median PSA-PFS was 5.7 months with low-dose versus 3.8 months ( P = .830) with standard-dose AA. Median OS was 18.1 versus 15.8 months ( P = .976). Grade ≥3 toxicities occurred in 38.3% versus 30.0% ( P = .269), respectively. PK analyses demonstrated approximately 8-fold higher AA exposure with standard dose. QoL scores were comparable between arms. CONCLUSION: Although underpowered to prove noninferiority, low-dose AA with food yielded outcomes broadly similar to standard dosing, with maintained safety and QoL. This cost-conscious regimen may be a feasible alternative, supporting further confirmatory evaluation.

PURPOSE: The AKT pathway is upregulated in cervical cancer. This trial aimed to investigate whether the protease AKT pathway inhibitor (nelfinavir mesylate), in addition to chemoradiation (CRT) and image-guided brachytherapy (IGBT), could improve disease-free survival (DFS). METHODS: NELCER (ClinicalTrials.gov identifier: NCT03256916 ), a phase III adaptive trial, randomly assigned patients with stage III cervical cancer (International Federation of Gynecology and Obstetrics 2018) to CRT and IGBT (standard arm) or in combination with nelfinavir (test arm). Patients in the test arm received nelfinavir 1,250 mg twice a day starting 7-10 days before and during CRT. The primary end point was 3-year DFS. Secondary end points included locoregional control, overall survival, adverse events, and quality of life. Disease-specific survival (DSS) was also estimated. The study planned to randomly assign 348 patients to detect a hazard ratio (HR) of 0.66. Futility analysis was scheduled at 32 events. RESULTS: Ninety-two patients were recruited at the time of futility analysis. The stage was IIIA-B (43.5%), IIIC1 (48.9%), and IIIC2 (7.6%) patients. The median prescribed dose to high-risk clinical target volume was 88 Gy ₁₀ (IQR, 83.6-92 Gy ₁₀ ). At a median follow-up of 34.9 months (29-40.8), the 3-year DFS was 71% (95% CI, 0.58 to 0.86) in the standard arm and 56% in the nelfinavir arm (95% CI, 0.43 to 0.70; HR, 1.34 [0.66 to 2.7]; P = .40). The nelfinavir arm had a higher incidence of acute grade ≥ 3 (8.7% v 0%, P = .04) GI effects. The 3-year DSS was 82% (95% CI, 0.70 to 0.95) in the standard arm and 57% (95% CI, 0.43 to 0.75) in the nelfinavir arm (HR of 1.97 [0.87 to 4.4], P = .09). The z-value was 0.74. CONCLUSION: The 3-year DFS did not cross prespecified statistical boundary; however, on the basis of DSS and acute adverse events, nelfinavir was not considered clinically efficacious, and the trial was stopped at the first interim analysis.

Lung cancer remains the leading cause of cancer-related mortality worldwide. A major barrier to effective treatment is the development of drug resistance, which contributes to poor patient survival. One key mechanism underlying this resistance is the ability of cancer cells to evade apoptotic cell death. Thus, there is an urgent need for novel therapeutic strategies to overcome chemoresistance in lung cancer. The ultrastructural features of mitochondria and the endoplasmic reticulum (ER) were assessed using transmission electron microscopy (TEM). Transcriptomic profiling of A549 cells was carried out through whole-exome sequencing. Protein expression levels were validated by western blot analysis, while mitochondrial calcium content was quantified using flow cytometry. Our study utilized mitocurcumin (mitoC) to study an alternative form of cell death in NSCLC. Mitochondria and ER vacuolation and swelling were observed upon mitocurcumin treatment. MitoC treatment upregulated ER and mitochondria stress protein levels in A549 and A549R cells. However, the inhibition of intracellular ROS and JNK pathway abrogated mitoC-induced mitochondria and ER stress proteins. Moreover, we observed that mitoC treatment enhanced mitochondrial calcium uptake in A549 and A549R cells, which gets abrogated upon ROS/JNK signaling inhibition. MitoC exerted organellar stress related to paraptosis in A549 and A549R cells through activation of the ROS-mediated JNK signaling pathway and induced mitochondrial calcium uptake.

*Corresponding Author: Vikram Gota, MD (vikramgota@gmail.com). ^#Presenting Author: Amisha Joshi Keywords metastasis mitocurcumin mitochondrial dynamics Background: Despite only 0.01% of tumor cells successfully metastasizing, metastasis accounts for 90% of cancer deaths. Mitochondria have emerged as a promising therapeutic target, as mitochondrial dynamics are linked to key metastasis traits, including motility, invasion, microenvironment modulation, plasticity, and colonization. Mitocurcumin-1 (MiC), a curcumin derivative with two TPP moieties, selectively accumulates in cancer cell mitochondria. By inhibiting TrxR2 and modulating reactive oxygen species (ROS), MiC demonstrates potential anticancer activity. ROS in turn affects mt-dynamics, hence we aim to evaluate whether MiC modulates metastasis in lung cancer. Materials and Methods: A549, H1299, and LLC-1 lung cancer cell lines were studied. IBIDI inserts facilitated wound healing assays, while Boyden chamber assessed migration and invasion (Matrigel coated). Confocal microscopy analyzed mitochondrial and lysosomal structures, and Western blot evaluated protein levels. Frozen cell samples were sent to MedGenome for transcriptome analysis. Nonobese diabetic-severe combined immunodeficiency and C57BL/6 mice will be used for in vivo MiC evaluation. Results: MiC treatment delayed gap closure in wound healing assays and reduced cell migration and invasion in Boyden chamber experiments. Mesenchymal markers such as N-cadherin, vimentin, and Twist were downregulated. Mitochondria exhibited a more rounded structure, with increased colocalization of mitochondria and lysosomes. Transcriptome analysis further revealed modulation of metastasis-related gene expression in MiC-treated cells compared with controls. Conclusion: Lung cancer cells’ ability to migrate and invade reduces upon MiC treatment. MiC downregulates the early metastatic markers. MiC treatment leads to degradation of mitochondria via mitophagy in human nonsmall cell lung cancer cell lines (A549 and H1299). MiC treatment modulates migration-related genes Article published online: 15 December 2025 © 2025. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/) Thieme Medical and Scientific Publishers Pvt. Ltd. A-12, 2nd Floor, Sector 2, Noida-201301 UP, India