Mukund Sable

Introduction: Overexpression of Epidermal Growth Factor Receptor (EGFR) plays a critical role in the progression and high mortality of Non-Small Cell Lung Cancer (NSCLC). Although EGFR tyrosine kinase inhibitors (EGFR-TKIs) demonstrate promising efficacy as first-line therapy, acquired resistance remains a major clinical challenge. Increasing evidence suggests that microRNAs (miRNAs) regulate EGFR signaling pathways and may influence therapeutic response and the development of resistance. Methods: This study aimed to identify EGFR-targeting microRNAs (miRNAs) and evaluate their binding stability using in silico approaches. Experimentally validated EGFR-targeting miRNAs were retrieved from miRTarBase and subsequently screened using miRDB and TargetScan based on their expression in lung adenocarcinoma cell lines. The secondary structures of miRNA–EGFR duplexes and three-dimensional structures of the miRNA–EGFR complexes were gener-ated using RNAfold and RNAComposer, respectively. Binding affinity was evaluated using HNADOCK molecular docking. Further validation included survival and co-expression analyses using OncomiR and starBase, RNA-Binding Protein (RBP) interaction analysis using POSTAR3, and pathway enrichment analysis using DIANA-miRPath. results: The docking analysis predicted the good binding affinity of 3 miRNAs i.e., hsa-miR-7-5p, hsa-miR-133b and hsa-miR-302b-3p with EGFR. Followed by the resulted docking scores i.e., -340.80 kcal/moL, -473.46 kcal/moL, and -491.18 kcal/moL respectively of the best docked complexes were visualized using Discovery Studio Visualizer. Results: Three miRNAs—miR-7-5p, miR-133b, and miR-302b-3p were identified as potential regulators of EGFR. Molecular docking analysis demonstrated strong binding affinities, with docking scores of −339.30, −476.76, and −491.18 kcal/mol, respectively. Survival analysis re-vealed no significant association between the expression of these miRNAs and patient prognosis. In contrast, co-expression analysis demonstrated a significant correlation between miR-133b and EGFR expression. Several upregulated RNA- Binding Proteins (RBPs) that interact with EGFR were identified, suggesting enhanced post-transcriptional regulation that may contribute to the development of EGFR-TKI resistance. Pathway enrichment analysis further identified hsa-miR-7-5p as being significantly associated with EGFR-mediated PI3K–Akt signaling and the NSCLC pathway. Discussion: These findings highlight candidate miRNAs as potential regulators of EGFR signal-ing and possible biomarkers influencing targeted therapy response. Conclusion: Further experimental and clinical validation is required to confirm their therapeutic relevance in EGFR-TKI-resistant lung cancer.

Endobronchial hamartoma (EH) is a rare benign bronchial tumour that represents a small subset of pulmonary hamartomas. EH often presents with non‐specific symptoms and may mimic malignancy or chronic infections such as tuberculosis, leading to delayed diagnosis or inappropriate treatment. We report here a case of a 60‐year‐old man who presented with 6 months of progressive dyspnoea and productive cough, and 2 months of low‐grade fever. Flexible bronchoscopy showed an endobronchial mass, and forceps biopsies performed twice were reported as granulomatous inflammation. He received antitubercular treatment based on presumptive diagnosis of endobronchial tuberculosis. However, there was no clinical and radiological improvement despite 7 months of treatment. We performed rigid bronchoscopy and removed the endobronchial tumour using an electrocautery snare and cryoextraction. The excisional biopsy confirmed the diagnosis of EH. This case highlights the limitations of small biopsy specimens in diagnosing hamartoma and reemphasises the role of advanced pulmonary interventions, such as electrocautery snare and cryotherapy, as diagnostic‐cum‐therapeutic tools in such lesions.

Gastrointestinal stromal tumours (GIST) are rare mesenchymal neoplasms comprising less than 1% tumours. Originating from the interstitial cells of Cajal. These mostly affect the stomach, followed by the small intestine. Among the small intestine, jejunal involvement is particularly uncommon and rare. They are present in the older population and are small in size. Giant forms, female gender, young population, and jejunal involvement are a combination of exceptionally rare entities individually and combined. We report this rare combination wherein a young female, brought dead to the emergency with a protruded abdomen with a deluded diagnosis of pregnancy at first instance, was sent for medicolegal autopsy, revealing a giant, ruptured, aggressively progressive jejunal GIST. Despite undergoing a biopsy, a definitive diagnosis was not achieved, delaying appropriate diagnosis, which ultimately led to death.

Glioblastoma (GBM) is an aggressive CNS malignancy with extensive tumor growth and invasion. Highly proliferating cells require an increased intracellular iron concentration to maintain cell metabolism. We assessed the expression of transferrin receptor 1 (TFR1), the principal iron transporter, in GBM and ascertained its clinicopathological significance, implication in pathobiology, and therapeutic potential. Ninety‐four cases of adult‐type hemispheric GBM were included, along with 60 cases of IDH‐mutant astrocytic and oligodendroglial tumors (grade 2–4) for comparison. The protein and mRNA expression were assessed by immunohistochemistry and qRT‐PCR, respectively. We used U87MG and LN229 cell lines for in vitro analysis. TFR1 expression was significantly higher in GBM than in other IDH‐mutant/lower‐grade diffuse gliomas at mRNA and protein level. The non‐tumor brain was negative on immunohistochemistry, and strong immunoreactivity was present only in GBM, indicating its diagnostic significance. SiRNA‐mediated knockdown of TFR1 was associated with reduced cell survival, proliferation, migration, invasion, and increased apoptosis in vitro. Ferroptosis induction by RSL3/FIN56 led to increased TFR1 expression and ROS generation. The pro‐ferroptotic effect of these drugs could be reversed by TFR1 knockdown. Hence, TFR1 appears to be crucially implicated in the cell survival and proliferation and ferroptosis sensitivity of malignant cells. Temozolomide in combination with siRNA‐mediated gene silencing showed a significantly higher antitumor effect than the drug or silencing alone. This may be one of the important therapeutic vulnerabilities of GBM. High TFR1 expression was associated with shorter overall survival in all gliomas together but not in GBM separately.

Background Breast cancer has surpassed lung cancer as the most diagnosed cancer globally. This retrospective audit, conducted in Eastern India, aimed to evaluate the clinicopathological profile and 5-year survival outcomes of 584 non-metastatic invasive breast cancer patients treated with curative intent between June 2016 and May 2023. Methods Clinical and pathological data were analyzed, and patients underwent various treatments, including neoadjuvant therapy, surgery, and adjuvant therapy. Hormone receptor and HER2/neu status were considered in the analysis. Results The majority of patients were postmenopausal (60.5%), with T2 tumors (52.2%), clinical node-positive disease (61.5%) and most commonly clinical stage at presentation was Stage IIA (52.7%). Hormone receptor positivity was observed in 61.5% of cases, and HER2/neu positivity in 38.4%. Neoadjuvant therapy was administered to 39.4% of patients. The 5-year disease-free survival was 68.1%, and overall survival was 78.8%. Recurrence, particularly distant recurrence (72%), was the primary cause of treatment failure. Factors influencing survival included clinical nodal positivity and presence of lymphovascular invasion. HER2/neu-positive patients had a 5-year DFS of 65.9%, while triple-negative disease patients had the lowest DFS at 63.5%. Conclusion This audit provides important insights into breast cancer management at a tertiary care center in Eastern India. Most patients presented with Stage II or Stage III disease, reflecting the persistent burden of locally advanced presentation in the Indian setting. Survival outcomes were comparable to those reported in other large Indian series. These findings emphasize the need for improved early detection and the role of continuous institutional audits in refining healthcare delivery and improving outcomes.

Thyroglossal duct cysts are the most common midline neck swelling in childhood, occurring in the line of descent of the thyroid, anywhere between the foramen caecum and the isthmus of the thyroid. However, the most common location is the thyrohyoid. We present a case of an adolescent male who presented with a suprasternal mass, which was clinically diagnosed as a branchial cyst. However, on histopathology, it was diagnosed to be a suprasternal thyroglossal cyst. With this article, we aim to highlight the importance of keeping thyroglossal cyst as a differential diagnosis for midline neck swelling, even below the location of the thyroid gland, so that proper excision of the tract can be planned and review the literature on suprasternal thyroglossal cyst.

Monocarboxylate transporters (MCTs) are crucially implicated in cancer cell metabolism by transporting lactate/H+ ions and thus regulating the pH of the microenvironment. We assessed MCT1 and MCT4 expression in 98 cases of adult‐type hemispheric Glioblastomas (GBMs) (IDH wild‐type), along with 51 cases of IDH‐mutant astrocytic and oligodendroglial tumors (grade 2–4) for comparison. U87MG and LN229 cell lines were used for in vitro analysis. Both MCT‐1 and MCT‐4 showed significantly higher expression in GBMs on immunohistochemistry than in IDH‐mutated gliomas, which mostly showed weak or negative immunoreactivity. The mRNA expression was also in a similar line. Interestingly, in all areas of the pathological endothelial proliferation of grade 4 tumors, there was MCT‐1 loss of expression, unlike the nonproliferating endothelium. High MCT1/4 expression was associated with shorter overall survival in all gliomas together but not in GBM separately. Syrosingopine, a dual MCT1/4 inhibitor, showed significant antitumor effects in both the glioma cell lines, including dose‐dependent cytotoxicity, increased apoptosis, and decreased migration/invasion. The results indicated the role of MCT1/4 in the pathobiology of GBM and the diagnostic utility at the immunohistochemical level. Syrosingopine, an antihypertensive agent with good CNS penetration and previously used in different malignancies, may be an essential therapeutic adjunct in GBM.