Single-stranded DNA gaps (ssDNA gaps) have emerged as a potential indicator of therapeutic response in cancer. Accumulation of ssDNA gaps is associated with increased sensitivity of cancer cells to genotoxic therapies like PARP inhibitors (PARPi) and cisplatin chemotherapy. However, efficient repair or suppression of ssDNA gap formation is associated with therapy resistance and treatment failure. Therefore, understanding how ssDNA gaps form and are repaired can help identify biomarkers that can guide new treatment strategies to overcome resistance. In this review, we discuss different sources of ssDNA gap formation and the repair mechanisms that have been characterized to date. We bring together current knowledge on how these gaps are processed and what their ultimate fate may be. Finally, we discuss how established drugs like PARPi, hydroxyurea, and platinum compounds, induce and/or exploit ssDNA gaps. Throughout this review, we highlight ssDNA gaps as a potential therapeutic vulnerability that can be used to advance personalized cancer therapy.

Accurate preoperative staging is essential for rectal cancer treatment. The revolutionary approach to treating rectal cancer is neoadjuvant treatment (NAT). NAT has a significant effect on local recurrence even though it has no effect on overall survival (OS) or disease-free survival (DFS). This is where preoperative Magnetic resonance imaging (MRI) comes in, helping to accurately stage the T and N stage and categorize patients for either upfront surgery or NAT. This study aims to compare the preoperative local MRI staging of rectal cancer with postopera-tive histopathology. This cross-sectional study comprised of patients with rectal cancer, who admitted to Bangladesh Medical University (BMU), within the period of January 2023 to December 2023. After diagnosis of rectal cancer preoperative local staging was done by MRI. Ac-cording to stage treatment was given. MRI T and N stage was compared with post operative his-topathology. Among the 45 patients 64.44% (n=29) patients were male. Mean age was 41.5 years. Patients (n=14) who had NAT had ypT downstaging in 43.0% (n=6) cases and among them two patients had pathological complete response (pCR). In this NAT group of patients 64.0% (n=9) did not re-spond to NAT. Patients who had upfront surgery (n=31) MRI successfully matches the histo-pathology in 87.0% (n=27) cases. To identify the correct nodal involvement in this upfront group MRI had 67.0% (n=21) success rate. MRI had 90.0% accuracy in identification of MRF involvement preoperatively. There was no correlation between tumor grade and CEA level. MRI is highly accurate in preoperative T and reasonably accurate in N staging for rectal cancer. Its accuracy in diagnosis influences treatment choices, providing physicians with a thorough understanding of the distinctive characteristics of the disease and enhancing the standard of care.

Breast discharge represents the third most common reason women seek medical attention for breast-related concerns. A triple assessment is recommended for additional screening in cases of suspected ductal illness if there is nipple discharge. This study aimed to evaluate the different clinical characteristics of ductal breast disease in relation to Triple Assessment (Clinical examination, Imaging, Histopathology). This cross-sectional study was conducted among 100 purposively included female patients presented with nipple discharge (ND) selected from both Outdoor and Indoor Department of Surgery, Rajshahi Medical College Hospital (RMCH), Rajshahi, Bangladesh. Data regarding clinical, biochemical and surgical profiles were recorded. Informed written consent was taken from all the patients before data collection. Data was collected from May 2019 to October 2019. In descriptive statistics, the frequency distribution was done using STATA-18. The findings of the Triple assessment were categorized as malignant and non-malignant using the chi-squared test. All statistical tests were two-tailed. A p-value of 0.05 or less than 0.05 was considered statistically significant. Age 40 years or above (p<0.001), presence of a breast lump (p<0.001), micro-calcification found in mammography (p<0.001) and suspected malignancy in ultrasonography (p<0.001), bloody nipple discharge (p<0.001) were found statistically significant in association with malignancy compared to benign lesions. Triple assessment can help to assess high-risk patients, requiring careful treatment to rule out malignancy. Patients aged 40 years or more with the presence of breast lump and bloody discharge are at high risk of cancer. The risk of underlying cancer can be precisely established by applying the methodical, gold standard approach of Triple Assessment.

Various tumors can involve the orbital space. Although orbital tumors are rare, these sight-threatening and possibly life-threatening disorders consist of a broad disease spectrum. The purpose of the study is to determine the prevalence of orbital tumors presenting in a tertiary eye care centre and evaluate their Demographic pattern and Clinical findings. This cross-sectional descriptive study was conducted in the Department of Oculoplasty, Ispahani Islamia Eye Institute & Hospital from August 2019 to July 2020. 30 patients were selected of all age and sex presented with primary orbital tumors during study period. All patient was examined properly. Their demographic, clinical, radiological and histopathological data was collected. Total 30 patients meet the inclusion criteria. Among them 8 cases were diagnosed by clinical & radiological examinations. Twenty two (22) cases were diagnosed by histopathology. Among 30 diagnosed patients 16 patients were male and 14 patients were female. Age range of 30 patients were 1 months to 60 years. 1-10 years category 13 patients, 11-20 years 4 patients, 21-30 years 1 patients, 31-40 years 3 patients, 41-50 years 0 patients and 50+ years 9 patients. 09 patients were diagnosed as malignant neoplasm and other 21 patients were diagnosed as benign neoplasm. Among 9 malignant neoplasms 8 cases are diagnosed as NHL and rest one was Adenoid cystic carcinoma. Among 21 benign cases 6 were diagnosed as dermoid cyst, 4 cases were diagnosed as orbital lymphangioma, 2 cases were diagnosed as orbital capillary hemangioma, 2 cases Optic nerve glioma and plexiform neurofibroma, optic nerve meningioma, pleomorphic adenoma, schwannoma, glomus tumor, Langerhans cell histiocytoma, cavernous hemangioma one case each. The age distribution of diagnosed 30 patients exhibited two peaks, at 0 to 10 years (13 patients) and 50+ years (9 patients). In the 0- to 9-year-old patients, the most common tumors were dermoid cyst 6 patients and in 50+ years patient age group most common diagnosis was NHL (8 patients). The most common sign and symptom were proptosis (76.66%), palpable mass (73.33%) and restricted ocular movement 46.66%. A wide range of tumors can involve the orbit. The prevalence of malignant tumors increased with age, and in younger age group vascular and cystic tumors are more common. Most common malignancy is NHL occurs in older age group and most common benign orbital tumor is dermoid cyst occurs in younger age group. Among all tumors proptosis, palpable mass and restricted movement was the most common presenting features.

Basal cell carcinoma (BCC) is the most common cutaneous malignancy worldwide. The face is the most frequent site and presents reconstructive and functional challenges after excision. This study describes the clinical profile, surgical strategies and reconstructive outcomes of facial BCC cases managed in a tertiary hospital in Bangladesh. Retrospective analysis of 62 consecutive patients with histologically confirmed facial BCC treated surgically between January 2021 and December 2024 at the Burn and Plastic Surgery Department, Mymensingh Medical College and Hospital. Demographic, clinical, operative and follow-up data were extracted from the institutional records. The primary outcomes were lesion distribution, reconstructive method, complications and need for re-excision. Sixty-two patients (mean age 54.3±13.7 years; male 54.8%) were included. Lesions were most commonly on the right side of the face (51.6%). Mean wound dimension was 17.06±10.43 cm². One-stage surgery was performed in 71.0% of patients; two-stage procedures in 29.0%. Re-excision was required in 3(4.8%) patients. The most used reconstructive options were split-thickness skin graft (STSG) (41.9%), full-thickness skin graft (FTSG) (11.3%) and local advancement flaps (12.9%). Major complications occurred in 4(6.5%) cases; most complications required revision. Mean postoperative stay was 3.9±2.48 days and mean follow-up was 9.7±2.96 weeks. Facial BCC in our series presented mainly in middle-aged adults and was most frequently managed by surgical excision with reconstruction using skin grafts and local flaps. Overall complication and re-excision rates were low. Surgical excision with appropriate reconstructive planning remains the cornerstone of facial BCC management.

The heat shock response is a highly conserved cellular defense mechanism against proteotoxic stress, characterized by the induction of heat shock proteins (HSPs) that function as molecular chaperones to maintain protein homeostasis. Central to this response are the heat shock transcription factors (HSFs), which regulate the expression of HSPs. This Review explores the structural and functional relationships of the mammalian HSF family, including HSF1, HSF2, HSF4 and HSF5. We highlight HSF gene expression and function during organismal development and details of HSFs involvement in neurodegenerative diseases, in which they mitigate/counteract protein aggregation and promote neuronal survival, and in cancer, in which they support tumor growth and metastasis. We also examine the interplay between different HSFs and their context-dependent functions, emphasizing their relevance as potential targets for therapeutic intervention. Understanding the diverse roles of these factors is essential for advancing our knowledge of physiological regulation, and for developing targeted therapies for a broad range of diseases.

Autoimmune pancreatitis (AIP) is a relatively rare chronic fibroinflammatory disorder of the pancreas caused by autoimmune mechanisms. Patients with this condition generally show a clear response to glucocorticoid therapy. Notably, its clinical and imaging features often resemble those of pancreatic cancer (PC), particularly when AIP presents as a focal mass. In such cases, clinicians may confuse the two diseases. Given that AIP and PC differ considerably with respect to their biological behavior and treatment, diagnostic errors can lead to unnecessary surgery or delayed treatment. Consequently, it is essential to accurately distinguish between these conditions. Recent diagnostic advances, including the application of liquid biopsy and artificial intelligence, are now being evaluated as alternative approaches to conventional diagnostic methods, and may contribute to improving the distinction between AIP and PC. In this review, we summarize the current evidence, outline the clinical profile of AIP, and compare AIP with PC with respect to epidemiological, clinical, serological, imaging, and histopathological dimensions. In addition, we discuss the advantages and limitations of these new diagnostic tools. Furthermore, we propose a practical three-stage diagnostic algorithm based on the present guidelines. This stepwise approach may provide a practical method for integrating routine and emerging tests for evaluating patients with suspected AIP or PC.

The recommended first-line therapy for BRAF V600E mutant non-small cell lung cancer (NSCLC) is a combination of dabrafenib and trametinib. Most patients respond to the initial therapy, but some show resistance in the early stages. Additionally, immune checkpoint inhibitors (ICIs) are often used after resistance develops; however, the benefits of ICIs in patients with BRAF V600E mutant NSCLC remain unclear.

As a key experimental method to study the pathogenesis of brain tumors, the establishment of standardized operation process for intracranial orthotopic tumor modeling is of great significance. At present, although this technology has become the main method for brain tumor research, it has been reported in the literature that there is significant heterogeneity in the injection sites, and there is a lack of systematic verification, which leads to the repeatability of the experiment being questioned. In view of this technical bottleneck, this study used female C57BL mice as a model to establish a standardized intracranial tumor formation operation system. By systematically analyzing the two anatomical markers of bregma and lambda in mice, we not only clarified the quantitative relationship between body weight and bregma-lambda distance in C57BL mice, but also defined the normal range of bregma-lambda distance. More importantly, we found and verified a new standardized injection site. Based on this finding, this study finally constructed a complete set of intracranial tumor formation technology scheme including positioning method, operation specification and quality control.

To overcome limitations in melanoma therapy by developing a targeted nanoplatform based on reduced graphene oxide quantum dot (rGOQD) that integrates photothermal therapy (PTT), chemodynamic therapy (CDT), and immune modulation.

Objective. The BAG cochaperone 1 (BAG1) binds to oncogene BCL2 and markedly enhances its anti-apoptotic effects. This cochaperone represents a link between growth factor receptors and anti-apoptotic mechanisms mediated by endoplasmic reticulum stress. BAG1 interacts with the glucocorticoid receptor and modulates its transcription activity. As a cochaperone for several HSP70 proteins, it participates in control of protein folding. The present study aims to investigate the regulation of the BAG1 mRNA expression in U87MG glioblastoma cells by hypoxia and glucose or glutamine deprivation, depending on the inhibition of ERN1 (endoplasmic reticulum to nucleus signaling 1) with the intent to reveal the role of ERN1 signaling in the regulation of this gene expression and function in oncogenesis. Methods. The U87MG glioblastoma cells (transfected by an empty vector; control) and cells with inhibited ERN1 endoribonuclease and protein kinase (dnERN1) or only ERN1 endoribonuclease (dnrERN1) were used. Silencing of ERN1 and XBP1 mRNAs for suppression of ERN1 function was also used. A hypoxic condition was created by dimethyloxalylglycine (4 h). DMEM medium without glucose or glutamine was used for glucose and glutamine deprivation (16 h). The expression level of the BAG1 mRNA was studied by real-time qPCR and normalized to the beta-actin mRNA. Results. Inhibition of the endoribonuclease activity of ERN1 significantly decreased BAG1 mRNA expression. However, a lesser suppression of this mRNA expression was observed in dnERN1 cells (with inhibited ERN1 endoribonuclease and protein kinase) indicating the involvement of protein kinase in controlling BAG1 expression. The silencing of ERN1 and XBP1 mRNAs also reduced the expression of BAG1 mRNA demonstrating the involvement of XBP1s in this regulation. The expression of the BAG1 gene was resistant to glutamine deprivation and upregulated in response to glucose deprivation in control glioblastoma cells. However, the inhibition of ERN1 increased the sensitivity of BAG1 gene expression to both glucose and glutamine deprivation. Furthermore, the expression of the BAG1 gene was increased under hypoxia in control U87MG cells; however, a greater induction was observed in dnERN1 cells. Conclusion. The results of this study demonstrated that ERN1 inhibition reduces BAG1 mRNA expression through the endoribonuclease activity of ERN1 and that protein kinase activity counteracts endoribonuclease in regulating the expression of BAG1 mRNA. Moreover, ERN1 inhibition also enhances the sensitivity of BAG1 mRNA expression to nutrient supply and hypoxia resulting in reduced resistance of glioblastoma cells.

Objective. Phosphoenolpyruvate carboxykinase (PCK) catalyzes the conversion of oxaloacetate to phosphoenolpyruvate and regulates pyruvate metabolism and gluconeogenesis in response to glucocorticoid and insulin stimuli. Mitochondrial isoform of this enzyme (PCK2) is overexpressed in glioblastoma cells and participates in metabolic reprogramming and cell proliferation. This study aims to examine the impact of ERN1 (endoplasmic reticulum to nucleus signaling 1) inhibition on PCK2 expression and sensitivity to glucose and glutamine deprivation to determine the role of ERN1 signaling in the regulating its expression in glioblastoma cells. Methods. The glioblastoma cell line U87MG and two genetically modified variants of these cells were used. These were glioblastoma cell sublines with suppressed endoribonuclease and protein kinase activities of ERN1 (dnERN1) or only ERN1 endoribonuclease (dnrERN1), and control cells transfected with an empty vector. The suppression of ERN1 function by silencing of ERN1 and XBP1 mRNAs was also used. Hypoxia was generated using the HIF1A prolyl hydroxylase inhibitor dimethyloxalylglycine. For glucose and glutamine deprivation, DMEM medium without glucose or glutamine was used. The expression level of the PCK2 mRNA was analyzed by real-time qPCR and normalized to the beta-actin mRNA. Results. It has been demonstrated that PCK2 mRNA expression is significantly decreased in dnERN1 glioblastoma cells. Similar suppression of this mRNA expression was also observed in cells with only the endoribonuclease activity of ERN1 inhibited, indicating that this enzymatic activity is involved in the regulation of PCK2 expression. The silencing of ERN1 and XBP1 mRNAs also induced similar changes in PCK2 mRNA expression, possibly mediated by XBP1s. The expression of PCK2 was enhanced under glutamine deprivation in control glioblastoma cells, but inhibition of ERN1 activity strongly increased this effect. Upregulated PCK2 expression was also observed in control glioblastoma cells under glucose deprivation. However, the inhibition of ERN1 activity strongly increased the sensitivity of this gene expression to glucose deprivation. Furthermore, PCK2 mRNA expression was resistant to hypoxic conditions in cells with native ERN1. At the same time, in glioblastoma cells with inhibited ERN1 activity, a strong induction of PCK2 expression was observed. Conclusion. The results of this study demonstrated that ERN1 inhibition reduces PCK2 mRNA expression through the ERN1 endoribonuclease activity. This mRNA expression is upregulated under glutamine and glucose deprivation. Moreover, ERN1 inhibition strongly enhanced the sensitivity of PCK2 mRNA expression to glucose and glutamine deprivation as well as to hypoxia.

Although neoadjuvant systemic treatment (NST) is well established in the management of early breast cancer, there are limited clinical data available beyond the highly selected population evaluated in clinical trials. In this study, we assessed real-world outcomes of NST in early breast cancer through a retrospective review of 201 patients treated between November 2019 and February 2025. Pathological complete response (pCR) rates were highest in HER2-positive (60.2%) and triple-negative (53.1%) breast cancer subtypes and lowest in those who were identified as oestrogen receptor-positive (ER-positive)/HER2-negative (11.1%). In HER2-positive disease, pCRs were more frequent in ER-negative (75.8%) than ER-positive (50.0%) cases, while pCR rates in triple-negative breast cancer were similar with and without immunotherapy. Baseline positron emission tomography/computed tomography (PET/CT) upstaged 37% (35/94) of patients and showed 87% concordance with pathology, whereas magnetic resonance imaging (MRI) demonstrated a false-negative rate of 17% and a false-positive rate of 1.1%. In these cases, MRI results suggested residual disease despite a complete pathological response, with discrepancies varying by tumour subtype. Forty-two percent of the patients underwent chemotherapy dose reductions; 12% required hospitalisation. NST was effective across aggressive subtypes, with pCR rates comparable to those observed in clinical trials. In summary, our results highlighted the contributions of functional imaging with PET/CT and MRI to staging, treatment response assessments and surgical planning in real-world clinical practice.

To investigate the efficacy and adverse reactions of radiotherapy with omitted clinical target volume (CTV) in unresectable stage III non-small cell lung cancer (NSCLC).

BACKGROUND The purpose of this report is to explore the clinicopathological characteristics, diagnosis, and differential diagnosis of primary solitary fibrous tumor (SFT) of the pancreas. This report provides a retrospective analysis of the clinical features, histopathological findings, and immunohistochemical profiles of 2 patients with pancreatic SFT, supplemented by a review of the relevant literature. CASE REPORT Both patients were postmenopausal women who were incidentally found to have pancreatic masses during routine physical examinations. Similarly, both patients were misdiagnosed with neuroendocrine tumors of the pancreas on imaging (CT or MRI). Neither patient exhibited symptoms in their daily lives. Microscopically, both cases revealed distinct spindle cell tumors with poorly defined margins within pancreatic tissue. The tumors exhibited an expansile growth pattern with cells arranged in bundle-like structures or in a disordered arrangement, showing no cellular atypia or mitotic activity. Antler-like vessels were observed in the tumor stroma, with no evidence of necrosis. However, one of the tumors showed a sparse density of tumor cells with prominent collagen fiber hyperplasia. Immunohistochemical analysis showed that both tumors exhibited nuclear expression of STAT6. CONCLUSIONS Pancreatic SFT is clinically rare, with an overall favorable prognosis. However, owing to the general lack of symptoms in patients and nonspecific imaging manifestations, it is often misdiagnosed clinically. Histologically, given its morphological diversity, it needs to be differentiated from spindle cell tumors such as pancreatic gastrointestinal stromal tumors, fibromatosis, inflammatory myofibroblastic tumors, and pancreatic sclerosing epithelioid fibrosarcoma. Nuclear expression of STAT6 and the presence of NAB2: : STAT6 fusion are important characteristics of SFT.

BACKGROUND For patients with advanced ovarian cancer undergoing cytoreductive surgery, achieving optimal surgical outcomes has significant clinical implications for the design of adjuvant therapy and surveillance strategies. This retrospective, single-center cohort study aimed to develop a radiomics model based on preoperative PET-CT imaging parameters to predict optimal cytoreductive surgery outcomes, thereby providing clinical decision-making support to improve the prognosis of patients with advanced ovarian cancer. MATERIAL AND METHODS Patients with clinically staged IIIC-IVB high-grade serous ovarian carcinoma (HGSOC) who underwent primary cytoreductive surgery between October 2020 and October 2023 were enrolled and divided into training and validation cohorts. A radiomics model based on preoperative PET-CT was developed, and its performance was quantitatively evaluated and compared within the validation cohort. Subsequently, the PET-CT radiomics model was combined with the Suidan score to generate a combined model. RESULTS Optimal cytoreduction rates were 72.86% (training) and 75.0% (validation). The PET-CT radiomics model demonstrated superior discriminative ability (AUC: 0.808, 95%CI: 0.665-0.951) compared to the Suidan score (AUC: 0.773, 95%CI: 0.615-0.931) in validation. The combined model achieved the highest predictive performance (AUC: 0.836, 95%CI: 0.706-0.966), with sensitivity 81.8%, specificity 83.9%, PPV 64.3%, NPV 92.9%, and accuracy 83.3%. CONCLUSIONS The combined model integrating PET-CT radiomics and Suidan score provides accurate preoperative prediction of cytoreductive outcomes, optimizing treatment strategies for advanced ovarian cancer.

Metanephric tumors of kidney comprise a triad of benign tumors, namely metanephric adenoma (MA), fibroma, and adenofibroma, categorized based on the proportion of epithelial and/or stromal components. A review of published literature revealed only two cases of malignant transformation, both with sarcomatous transformation. We report an unusual case of malignant transformation in MA in a 35-year-old woman. Histopathologic examination of the mass showed areas reminiscent of benign metanephric tumors, which seamlessly merged with regions displaying high-grade carcinomatous/dedifferentiated features. To the best of our knowledge, this is the first reported case of MA with carcinomatous transformation. We propose expanding the spectrum of metanephric tumors of the kidney to include both carcinomatous and sarcomatous counterparts in future classifications.

Mixed-phenotype acute leukemias (MPALs) are a rare and aggressive group of leukemias, accounting for approximately 2%-5% of all leukemia cases. MPAL is characterized by the expression of markers from more than one hematopoietic lineage, either myeloid and lymphoid, which can be identified through flow cytometry immunophenotyping. This study aims to describe the clinicopathological, immunophenotypic, and cytogenetic features of a cohort of 27 patients diagnosed with MPAL at our institution.

Oncocytic subtypes of adrenocortical carcinomas are rare tumor entities, with relatively better prognosis than the conventional subtype. Owing to its rarity, oncocytic adrenocortical carcinomas (OACCs) have not been studied extensively. The study aims to analyze the clinicopathological and therapy-relevant immunohistochemical profile of OACC.

Ewing family of tumors (EFT) encompass a group of small blue round cell tumors, including Ewing sarcoma (ES) and EWSR1-negative undifferentiated small round cell sarcoma. The distinction between the EFTs is essential from a clinical perspective due to prognostic and therapeutic differences and is substantiated by the advent of molecular testing in the modern era. In this study, we tried to characterize EFTs by using fluorescent in situ hybridization (FISH) and reverse transcriptase polymerase chain reaction (RT-PCR).