Publications by authors named "Neyaz Alam"

Drug non-responsiveness is the major reason for the poor prognosis of hormonal receptor-positive breast cancer (ER/PR BCa), particularly the luminal A subtype. However, the underlying mechanism of drug non-responsiveness remains unknown. Flow cytometry and t-SNE analysis followed by ELISA validation of responder and non-responder unveiled lower secretion of IFN-γ, IL-12, and higher levels of IL-6 and TGF-β in CD4 T cells (P < 0.

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Complete eradication of aggressive head and neck squamous cell carcinoma (HNSCC) still remains a major challenging problem due to numerous resistance properties of cancer stem cells (CSC) which is crucially responsible for tumor recurrence and metastasis. This challenge causes a high demand for the emergence of novel targeted treatment modalities for improved therapeutic efficacies. Phytochemicals derived from plants proves to be a wide reservoir of important drug candidates which have the potential to impede multiple aspects of malignant growth and progression.

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Article Synopsis
  • This study focuses on understanding how hypoxia-inducible factor-1α (HIF1α) is activated in head-and-neck squamous cell carcinoma (HNSCC) and examines the roles of regulatory genes like VHL and LIMD1 along with the target gene VEGF in relation to HPV infection.
  • Analysis of public mRNA datasets and independent samples revealed that HIF1α and VEGF were highly expressed in HPV-positive tumors, while VHL and LIMD1 showed low expression regardless of HPV status.
  • Findings suggest that higher levels of HIF1α and VEGF, alongside lower levels of VHL and LIMD1, correlate with worse clinical outcomes in HNSCC, alongside changes in gene expression
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This study investigates the impact of Body Mass Index (BMI) on Quality of Life (QoL) and treatment outcomes in breast cancer (BC) patients, particularly focusing on underweight individuals with compromised nutritional status. A nonrandomized prospective study comprising 121 newly diagnosed patients across various BMI categories utilized FACT-B & FACIT-Sp-12 questionnaires. Follow-ups occurred at baseline, during (3rd and 6th), and after (12th month) anthracycline-taxane chemotherapy, either sequentially or concomitantly.

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Triple-negative breast cancer is characterized by high lethality attributed to factors such as chemoresistance, transcriptomic, and genomic heterogeneity, leading to a poor prognosis and limiting available targeted treatment options. While the identification of molecular targets remains pivotal for therapy involving chemo drugs, the current challenge lies in the poor response rates, low survival rates, and frequent relapses. Despite various clinical investigations exploring molecular targeted therapies in conjunction with conventional chemo treatment, the outcomes have been less than optimal.

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Triple-negative breast cancer (TNBC) is the most elusive subtype of breast cancer that encounters treatment dilemmas owing to the paucity of druggable targets. We found hyperactivation of c-MET and ephrin type-A receptor 2 (EphA2) in patients treated with 5FU driven chemotherapy which correlated with lower disease-free survival. However, silencing of both these genes resulted in a marked decrease in the invasive, migratory, and tumorigenic potential of TNBC cells, indicating that a dual target strategy is actionable.

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Cross-talk with TTEX CD8+ T cells mediated by the VEGFR2 axis induces aggressive properties in cancer stem cells to promote tumor progression.

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Vasculogenic mimicry (VM), defined as an endothelial cell independent alternative mechanism of blood and nutrient supply by dysregulated tumor cells, is associated with poor prognosis in oral squamous cell carcinoma (OSCC). Here we aim to investigate the underlying molecular mechanism of the synergistic effect of phytochemical Lupeol and standard microtubule inhibitor Paclitaxel in reversing the hypoxia induced VM formation in OSCC. The results demonstrated that the hypoxia induced upregulation of HIF-1α led to augmentation of signaling cascade associated with extracellular matrix remodeling and EMT phenotypes that are mechanistically linked to VM.

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Purpose: The study was aimed to understand the importance of the hedgehog signaling pathway in development of head and neck squamous cell carcinoma (HNSCC).

Methods: The molecular profiles of the key regulatory genes of the pathway were analysed in the adjacent normal epithelium and tumor samples. The findings were validated in HNSCC cell line.

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Vasculogenic mimicry (VM), an endothelial cell-independent alternative mechanism of blood supply to the malignant tumour, has long been considered as an adverse prognostic factor in many cancers. The correlation of VM with laminin-5γ2 and the assessment of their harmonized expression as an independent risk factor have not been elucidated yet in oral squamous cell carcinoma (OSCC). CD31/PAS staining stratified 116 clinically diagnosed OSCC specimens into VM+ and VM- cohorts.

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Article Synopsis
  • RGS5 is a protein linked to tumor growth and poor prognosis, known for promoting pericyte apoptosis in various cancers.
  • In the tumor microenvironment, TGFβ counteracts RGS5's harmful effects, allowing pericytes to survive and proliferate despite the presence of RGS5.
  • This study uncovers a new mechanism where TGFβ alters RGS5's signaling from promoting cell death to enhancing survival, which could inform future cancer treatment strategies.
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A high incidence of oral squamous cell carcinoma (OSCC) is observed in South-East Asian countries due to addictions such as chewing tobacco. Local invasion and distant metastases are primary causes of poor prognosis in OSCC. This study aimed to understand the alterations in metastasis biomarkers, such as stromal cell-derived factor-1α (SDF-1 or SDF1α) and its receptor C-X-C chemokine receptor type 4 (CXCR4), in OSCC patient samples that were stratified based on the history of addiction to chewing tobacco.

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The use of chewing tobacco is a severe risk factor for oral mucosa related diseases including cancer in India as well as USA, although its relationship with Oral Leukoplakia (OL) or related carcinogenicity is still not clear. This work chose two oncogenic pathway proteins- the Epidermal Growth Factor Receptor and the WNT pathway among leukoplakia patients and established their correlation with the individuals' tobacco chewing habit. 89 fresh patients with OL were selected for the work.

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The aim of this study is to understand the association of HPV infection and wnt-β-catenin self-renewal pathway in development of head and neck squamous cell carcinoma (HNSCC). For this reason, the molecular profiles (methylation/deletion/expression) of antagonists (SFRP1/2 and DKK1), agonists (FZD7 and LRP6) and effector protein β-catenin of the pathway were analyzed in HPV positive/negative oral epithelium at first, followed by its changes during development of the tumor along with correlations with different clinico-pathological parameters. HPV infection alone or in combination with tobacco habit could activate p- β-catenin expression in basal/parabasal layers of oral epithelium through high expression of FZD7 and significant down regulation of SFRP1/2 through promoter hypermethylation due to over expression of DNMT1 with ubiquitous down regulation of DKK1 and up-regulation of LRP6.

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Aberrant expression of mTOR signaling pathway is significantly associated with gastric cancer. However, the effect of smoking on mTOR expression and its downstream signaling molecules in gastric cancer has not been explored. Our study aims to investigate the effect of smoking on p-mTOR and its correlation with various downstream targets and survival of the smoker and never-smoker in advanced gastric cancer patients.

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Purpose: In approximately 30% of triple-negative breast cancer (TNBC) patients a complete pathological response is achieved. However, after neo-adjuvant chemotherapy treatment (NACT) residual tumour cells can be intrinsically resistant to chemotherapy. In this study, associations of the WNT/beta-catenin pathway with chemo-tolerance of NACT treated TNBC patients were compared to that of pre-treatment TNBC patients.

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Triple negative breast cancer (TNBC) originates from a less differentiated ductal cell of breast, which is less sensitive to chemotherapy. The chemotolerance mechanism of TNBC has not yet been studied in detail. For this reason, molecular profiles (expression/genetic/epigenetic) of Y654-p-β-catenin (active) and its kinase epidermal growth factor receptor (EGFR) along with SH3GL2 (regulator of EGFR homeostasis) were compared between neoadjuvant chemotherapy treated (NACT) and pretherapeutic TNBC samples.

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Purpose: The occurrence of vasculogenic mimicry (VM) and EphA2-mediated tumour progression are associated with poor prognosis in various solid tumours. Here, we aimed to investigate the prognostic implications of VM and its association with phosphorylated EphA2 receptor in invasive carcinoma of the breast.

Methods: The patients were stratified based on CD-31/PAS dual staining and subsequently the expression status of phospho-EphA2 (S897), FAK, phospho-ERK1/2 and Laminin 5Ƴ2 was analysed by immunohistochemistry.

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Background And Objectives: The aim of the study was to understand the importance of mismatch repair genes MLH1 and MSH2 in chemotolerance and prognosis of breast carcinoma (BC).

Methods: First, the alterations (deletion/methylation/expression) of MLH1 and MSH2 were analyzed in 45 neoadjuvant chemotherapy (NACT)-treated and 133 pretherapeutic BC samples. The chemotolerant BC cells were characterized by treating two BC cell lines MCF-7 and MDA MB 231 with two anthracycline antitumor antibiotics, doxorubicin and nogalamycin.

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The aim of the study was to understand the role of homologous recombination repair (HRR) pathway genes in development of chemotolerance in breast cancer (BC). For this purpose, chemotolerant BC cells were developed in MCF-7 and MDA MB 231 cell lines after treatment with two anthracycline anti-tumor antibiotics doxorubicin and nogalamycin at different concentrations for 48 h with differential cell viability. The drugs were more effective in MCF-7 (IC50: 0.

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Breast cancer is a leading cause of cancer-related mortality in women. Triple-negative breast cancer (TNBC; HER2-, ER-/PR-) is an aggressive subtype prone to drug resistance and metastasis, which is characterized by high intratumor microvascular density (iMVD) resulting from angiogenesis. However, the mechanisms contributing to the aggressive phenotypes of TNBC remain elusive.

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Aims: The cytotoxic response of an intermediate metabolite glyoxylate (Glx) on colon carcinoma has been evaluated in vitro.

Main Methods: The anti-proliferative effect of Glx was assessed on HT-29 and HCT-116 cells by performing MTT assay as well as beta-hexosaminidase assay. Evaluation of apoptotic event of Glx treated cells was measured by flow cytometry using annexin-V/PI staining.

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Head and neck squamous cell carcinoma (HNSCC) is a global disease and mortality burden, necessitating the elucidation of its molecular progression for effective disease management. The study aims to understand the molecular profile of three candidate cell cycle regulatory genes, RBSP3, LIMD1 and CDC25A in the basal/ parabasal versus spinous layer of normal oral epithelium and during head and neck tumorigenesis. Immunohistochemical expression and promoter methylation was used to determine the molecular signature in normal oral epithelium.

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