Selective Adjuvant Ayurvedic Treatment Modulates Immune Response and Oxidative Stress in a Patient with Carcinoma of the Pyriform Fossa, Undergoing Radiotherapy: A Case Study.

Introduction: Hypopharyngeal squamous cell carcinoma, stage III has poor prognosis with only 25% chance of 5 years of relative survival in such patients in spite of conventional treatment including radical surgery, radiotherapy, and concurrent chemotherapy.

Case Presentation: A chronic tobacco-betel nut chewer 62-year-old male patient had dysphagia with hoarseness of voice diagnosed with stage III, grade II malignant pyriform fossa. The patient underwent 9 cycles of neoadjuvant chemotherapy with Inj Paclitaxel 100 mg and Inj Cisplatin 40 mg.

Acellular scaffold-based approach for in situ genetic engineering of host T-cells in solid tumor immunotherapy.

Background: Targeted T-cell therapy has emerged as a promising strategy for the treatment of hematological malignancies. However, its application to solid tumors presents significant challenges due to the limited accessibility and heterogeneity. Localized delivery of tumor-specific T-cells using biomaterials has shown promise, however, procedures required for genetic modification and generation of a sufficient number of tumor-specific T-cells ex vivo remain major obstacles due to cost and time constraints.

Role of Curcumin in Reducing Toxicities Associated With Mucosal Injury Following Melphalan-Based Conditioning in Autologous Transplant Setting.

Mucositis is nearly inevitable following high-dose chemotherapy. Several pro-inflammatory cytokines play a role in pathogenesis of mucositis. Curcumin inhibits inflammatory cytokines through inhibition of nuclear factor kappa-β.

Transcriptome Signature of Vγ9Vδ2 T Cells Treated With Phosphoantigens and Notch Inhibitor Reveals Interplay Between TCR and Notch Signaling Pathways.

Gamma delta (γδ) T cells, especially the Vγ9Vδ2 subtype, have been implicated in cancer therapy and thus have earned the spotlight in the past decade. Although one of the most important properties of γδ T cells is their activation by phosphoantigens, which are intermediates of the Mevalonate and Rohmer pathway of isoprenoid biosynthesis, such as IPP and HDMAPP, respectively, the global effects of such treatments on Vγ9Vδ2 T cells remain elusive. Here, we used the high-throughput transcriptomics approach to elucidate the transcriptional changes in human Vγ9Vδ2 T cells upon HDMAPP, IPP, and anti-CD3 treatments in combination with interleukin 2 (IL2) cytokine stimulation.

CD26 expression on donor harvest as a risk predictive biomarker for developing graft-versus-host disease post-allogeneic hematopoietic stem cell transplantation: A ten-year follow-up study.

Background: Allogeneic hematopoietic stem cell transplantation (ASCT) is the preferred treatment option for patients with several hematologic disorders and immunodeficiency syndromes. Graft-versus-host disease (GVHD) is an immune mediated post-transplant complication which has a major impact on long-term transplant outcomes.

Objective: Current efforts are focused on identification of new markers that serve as potential predictors of GVHD and other post-transplant clinical outcomes.

Myeloid-derived suppressor cells impede T cell functionality and promote Th17 differentiation in oral squamous cell carcinoma.

Oral tumor microenvironment is characterized by chronic inflammation signified with infiltrating leukocytes and soluble mediators which cause immune suppression. However, how immunosuppressive cells like myeloid-derived suppressor cells (MDSCs) maintain the immunosuppressive tumor microenvironment and influence T cell function in oral squamous cell carcinoma (OSCC) patients remains poorly understood. In the present study, we found that percentages of MDSCs were higher in oral cancer patients compared to healthy individuals and correlated with cancer stage.

Hexane Fraction of Inhibits Intermediates of RANK-RANKL Signaling Pathway and Prevent Ovariectomy Induced Bone Loss.

Osteoporosis is a "silent disease" characterized by fragile and impaired bone quality. Bone fracture results in increased mortality and poor quality of life in aged people particularly in postmenopausal women. Bone is maintained through the delicate balance between osteoclast-mediated bone resorption and osteoblast-mediated bone formation.

Immunophenotype and function define TCRγδ + T-ALL as a distinct subgroup from TCRαβ + T-ALL patients.

We recently demonstrated TCRγδ + T-ALL as a distinct subgroup from TCRαβ + T-ALL at genomic level. TCRγδ + T-ALL subgroup possess significant survival advantage compared to TCRαβ + T-ALL. In the present study, functional level differences in these two subgroups of T-ALL were studied to understand the immune scenario contributing to survival benefit of TCRγδ + T-ALL subgroup.

The multifaceted role of Notch signal in regulating T cell fate.

Notch signaling pathway facilitates important cellular functions of the host. Notch signal is essential for the development of T cells, and the role of Notch in fine tuning of αβ versus γδ T cell lineage commitment is fundamentally different in mice and human. The Notch family of cell surface receptor likewise plays a critical role in regulating T cell activation, and influences T cell response both intrinsically and through the local environment.

Efficient in situ gene delivery via PEG diacrylate matrices.

For diseases related to genetic disorders or cancer, many cellular therapies rely on the ex vivo modification of cells for attaining a desired therapeutic effect. The efficacy of such therapies involving the genetic modification of cells relies on the extent of gene expression and subsequent persistence of modified cells when infused into the patient's body. In situ gene delivery implies the manipulation of cells in their in vivo niche such that the effectiveness can be improved by minimizing post manipulation effects like cell death, lack of persistence, etc.

Checkpoint Blockade Rescues the Repressive Effect of Histone Deacetylases Inhibitors on γδ T Cell Function.

Histone deacetylases (HDAC) are one of the key epigenetic modifiers that control chromatin accessibility and gene expression. Their role in tumorigenesis is well established and HDAC inhibitors have emerged as an effective treatment modality. HDAC inhibitors have been investigated for their specific antitumor activities and also clinically evaluated in treatment of various malignancies.

Study of stem cell homing & self-renewal marker gene profile of expanded human CD34 cells manipulated with a mixture of cytokines & stromal cell-derived factor 1.

Background & Objectives: Next generation transplantation medicine aims to develop stimulating cocktail for increased ex vivo expansion of primitive hematopoietic stem and progenitor cells (HSPC). The present study was done to evaluate the cocktail GF (Thrombopoietin + Stem Cell factor + Flt3-ligand) and homing-defining molecule Stromal cell-derived factor 1 (SDF1) for HSPC ex vivo expansion.

Methods: Peripheral blood stem cell (n=74) harvests were analysed for CD34hiCD45lo HSPC.

Inhibition of Notch signalling has ability to alter the proximal and distal TCR signalling events in human CD3 αβ T-cells.

The Notch signalling pathway is an important regulator of T cell function and is known to regulate the effector functions of T cells driven by T cell receptor (TCR). However, the mechanism integrating these pathways in human CD3 αβ T cells is not well understood. The present study was carried out to investigate how Notch and TCR driven signalling are synchronized in human αβ T cells.

Common genetic variation and risk of gallbladder cancer in India: a case-control genome-wide association study.

Background: Gallbladder cancer is highly lethal, with notable differences in incidence by geography and ethnic background. The aim of this study was to identify common genetic susceptibility alleles for gallbladder cancer.

Methods: In this case-control genome-wide association study (GWAS), we did a genome-wide scan of gallbladder cancer cases and hospital visitor controls, both of Indian descent, followed by imputation across the genome.

Next generation metronomic chemotherapy-report from the Fifth Biennial International Metronomic and Anti-angiogenic Therapy Meeting, 6-8 May 2016, Mumbai.

The 5 Biennial Metronomic and Anti-angiogenic Therapy Meeting was held on 6 - 8 May in the Indian city of Mumbai. The meeting brought together a wide range of clinicians and researchers interested in metronomic chemotherapy, anti-angiogenics, drug repurposing and combinations thereof. Clinical experiences, including many from India, were reported and discussed in three symposia covering breast cancer, head and neck cancers and paediatrics.

Galectin-3-induced cell spreading and motility relies on distinct signaling mechanisms compared to fibronectin.

Secreted galectin-3 often gets incorporated into extracellular matrix and is utilized by cancer cells for spreading, movement, and metastatic dissemination. Here we investigate molecular mechanisms by which galectin-3 brings about these effects and compare it with fibronectin. Imaging of cells spread on fibronectin showed stress fibers throughout cell body, however, galectin-3-induced formation of parallel actin bundles in the lamellipodial region resulting in unique morphological features.

Risk stratification of T-cell Acute Lymphoblastic Leukemia patients based on gene expression, mutations and copy number variation.

Gene expression, copy number variations (CNV), mutations and survival were studied to delineate TCRγδ+T-cell acute lymphoblastic leukemia (T-ALL) as a distinct subgroup from TCRαβ+T-ALL. Gene Ontology analysis showed that differential regulation of genes involved in pathways for leukemogenesis, apoptosis, cytokine-cytokine receptor interaction and antigen processing/presentation may offer a survival benefit to TCRγδ+T-ALL patients. Genes involved in disease biology and having equal expression in both the subgroups, were further analysed for mutations and CNV using droplet digital PCR.

IL17 producing γδT cells induce angiogenesis and are associated with poor survival in gallbladder cancer patients.

Despite conventional treatment modalities, gallbladder cancer (GBC) remains a highly lethal malignancy. Prognostic biomarkers and effective adjuvant immunotherapy for GBC are not available. In the recent past, immunotherapeutic approaches targeting tumor associated inflammation have gained importance but the mediators of inflammatory circuit remain unexplored in GBC patients.

Extracellular 2'5'-oligoadenylate synthetase 2 mediates T-cell receptor CD3-ζ chain down-regulation via caspase-3 activation in oral cancer.

Decreased expression of CD3-ζ chain, an adaptor protein associated with T-cell signalling, is well documented in patients with oral cancer, but the mechanistic justifications are fragmentary. Previous studies in patients with oral cancer have shown that decreased expression of CD3-ζ chain was associated with decreased responsiveness of T cells. Tumours are known to induce localized as well as systemic immune suppression.

Activation status of γδ T cells dictates their effect on osteoclast generation and bone resorption.

γδ T cells, a small subset of T cell population (5-10%), forms a bridge between innate and adaptive immunity. Although the role of γδ T cells in infectious diseases and antitumor immunity is well investigated, their role in bone biology needs to be explored. Aminobisphosphonates are used as a standard treatment modality for bone related disorders and are potent activators of γδ T cells.

Endogenous galectin-3 expression levels modulate immune responses in galectin-3 transgenic mice.

Galectin-3 (Gal-3), a β-galactoside-binding mammalian lectin, is involved in cancer progression and metastasis. However, there is an unmet need to identify the underlying mechanisms of cancer metastasis mediated by endogenous host galectin-3. Galectin-3 is also known to be an important regulator of immune responses.

Immunological & metabolic responses to a therapeutic course of Basti in obesity.

Background & Objectives: Basti (medicated enema) is a popular Ayurvedic intervention recommended for obesity. However, there are no data to show whether any physiological or biochemical changes occur following this treatment. This study was conducted to identify the immunological and metabolic changes in obese individuals after a therapeutic course of Basti.

N-glycans and metastasis in galectin-3 transgenic mice.

Poly-N-acetyl-lactosamine (polyLacNAc) on N-glycans facilitate lung specific metastasis of melanoma cells by serving as high affinity ligands for galectin-3, expressed in highest amounts in the lungs, on almost all its tissue compartments including on the surface of vascular endothelium. PolyLacNAc not only aids in initial arrest on the organ endothelium but in all the events of extravasation. Inhibition of polyLacNAc synthesis, or competitive inhibition of its interaction with galectin-3 all inhibited these processes and experimental metastasis.