In non-Hodgkin's lymphoma, diffuse large b-cell lymphoma (DLBCL) is one of the most prevalent and commonly diagnosed subtypes. There is a need to develop more effective drugs since the currently approved drugs still have limitations.

This analysis was aimed to characterize cutaneous manifestations associated with tuberous sclerosis complex (TSC) and management of facial angiofibroma in the United States from a patient/caregiver perspective. Data was collected from an international survey of TSC Alliance conducted during May-June 2017 by distributing a link to patients/caregivers through various channels including social media.

Objective: To establish a niraparib-resistant ovarian cancer cell line and preliminarily explore its biological characteristics and metabolic signatures. Methods: (1) Using ovarian adenocarcinoma cell line A2780 as parental cells, the niraparib-resistant cell line A2780-NiraR was established by the method of concentration gradient increased induction, and its morphological characteristics were observed using inverted phase-contrast microscope. The half-inhibitory concentration (IC50) of niraparib was determined by cytotoxicity assay. (2) Cell proliferation was determined by cell count kit-8 (CCK-8) assay and direct cell counting assay, cell cycle distribution was analyzed by flow cytometry. (3) The differential metabolites between A2780 and A2780-NiraR cells were detected by non-target metabolomics based on ultra-high performance liquid chromatography-high resolution mass spectrometry (UPLC/HRMS). Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis was conducted on the above differential metabolites to explore related metabolic pathways. Results: (1) Compared with the parental A2780 cells, A2780-NiraR cells exhibited predominantly short-spindle or oval morphology with reduced cellular projections and indistinct cell borders. The IC50 values of niraparib were 3.17 and 26.19 μmol/L against A2780 cells and A2780-NiraR cells, respectively (F=98.50, P<0.001). (2) A2780-NiraR cells had a slower proliferation rate compared with A2780 cells (F=146.80, P<0.001). The doubling time of A2780-NiraR cells [(37.5±1.9) hours] was significantly longer than that of A2780 cells [(14.5±1.0) hours; t=10.50, P<0.001]. Compared with the parental A2780 cells, A2780-NiraR cells had a significantly lower S phase fraction [(44.5±0.7)% in A2780 cells, (30.2±2.9)% in A2780-NiraR cells; t=4.78, P<0.001] and higher G0/G1 phase fraction [(35.4±1.2)% in A2780 cells, (52.2±3.1)% in A2780-NiraR cells; t=5.10, P<0.001]. (3) The metabolites of A2780 and A2780-NiraR cells were analyzed by non-target metabolomics. Forty-four differential metabolites between A2780 and A2780-NiraR cells were screened using the orthogonal partial least squares-discriminant analysis (OPLS-DA) model, the majority of which were significantly increased, such as pyrrolidone carboxylic acid, L-lysine and 1-pyrroline-4-hydroxy-2-carboxylate. Pathway enrichment analysis indicated that the arginine metabolism, purine metabolism, and pyrimidine metabolism were the most significantly enriched pathways. Conclusion: A2780-NiraR cells have acquired a stable niraparib resistance phenotype, and metabolic pathways including arginine metabolism may serve as potential therapeutic targets for enhancing niraparib efficacy in ovarian cancer.

Objective: To investigate the effectiveness and safety of secondary cytoreductive surgery (SCS) in patients with platinum-sensitive recurrent epithelial ovarian cancer who progressed after first-line maintenance therapy with poly adenosine diphosphate ribose polymerase inhibitor (PARPi). Methods: Clinical pathological data and prognostic information were retrospectively collected from 30 ovarian cancer patients who underwent SCS between January 2018 and June 2024. The Kaplan-Meier method was used to analyze the second progression-free survival (PFS2) time and 3-year overall survival (OS) rate. Results: (1) Primary treatment: the median age at diagnosis was 51.3 years. A total of 40% (12/30) patients underwent primary debulking surgery with an expectation of achieving no gross residual disease (R0), while 60% (18/30) received neoadjuvant chemotherapy and interval debulking surgery. Optimal cytoreduction was achieved in 93% (28/30) of patients. BRCA1/2 gene testing was performed in 29 patients (testing rate 97%, 29/30), identifying 11 BRCA-mutated (37%, 11/30) and 18 BRCA wild-type (60%, 18/30) patients. The median duration of PARPi maintenance therapy among the 30 patients was 11.9 months; patients with BRCA gene mutations had a median duration of 19.2 months, while those with BRCA wild-type had a median duration of 10.1 months. (2) Secondary surgery: pathologically confirmed recurrence patterns, single lesion in 9 patients (30%, 9/30), oligo-lesion (2 lesions) in 3 patients (10%, 3/30), and multi-lesion (≥3 lesions) in 18 patients (60%, 18/30). Among the 30 patients, optimal cytoreduction was achieved in 97% (29/30) of SCS patients, with suboptimal cytoreduction in 1 patient (3%, 1/30). Adjuvant chemotherapy included platinum+paclitaxel in 24 (80%, 24/30) patients and platinum+liposomal doxorubicin in 6 (20%, 6/30) patients. PARPi re-treatment was administered to 17 patients (57%, 17/30) after chemotherapy. (3) Efficacy and safety: as of the follow-up cutoff in June 2024, the median follow-up time was 28.0 months. A total of 19 (63%, 19/30) patients experienced the next recurrence. The median PFS2 time after SCS was 18.5 months. Recurrence occurred in 7 BRCA-mutated and 12 BRCA gene wild-type patients. Median PFS2 time was significantly longer in BRCA-mutated patients compared to BRCA wild-type patients (25.7 vs 14.1 months; P=0.028). Three deaths occurred during follow-up, resulting in a 3-year OS rate of 90%. Among the 30 patients, postoperative complications occurred in 4 patients (13%, 4/30). One patient developed a ureteral fistula on 7 days post-SCS requiring ureteral stenting, and one patient was transferred to the intensive care unit on 1 day post-SCS due to hypovolemic shock. No deaths occurred within 30 days after SCS. Conclusion: For platinum-sensitive recurrent ovarian cancer patients progressed after first-line PARPi maintenance therapy who are anticipated to achieve R0 resection, SCS represents a safe and effective second-line treatment option.

Objective: To evaluate the safety and effectiveness of fuzuloparib for the treatment of ovarian epithelial cancer patients in the real world setting. Methods: A retrospective analysis was conducted on the baseline data of 4 620 ovarian cancer patients who had received fuzuloparib monotherapy or combination therapy. Another 224 ovarian cancer patients who were willing to receive fuzuloparib monotherapy or combination therapy were prospectively enrolled, and their baseline characteristics, drug effectiveness, and safety data were analyzed. Results: (1) Among the 4 620 patients in the retrospective cohort, the median age of patients was 60 years; tumor types: 89.8% (4 149/4 620) had ovarian cancer. Among patients with clearly documented information, the vast majority had a histological type of serous carcinoma (82.9%, 3 770/4 546) and International Federation of Gynecology and Obstetrics (FIGO) staging of Ⅲ-Ⅳ (90.9%, 1 537/1 691). (2) Among the 224 patients in the prospective cohort, the median age of patients was 57 years; tumor types: 83.9% (188/224) had ovarian cancer. Among patients with clearly documented records, the predominant pathologic type was serous carcinoma (91.9%, 193/210), and FIGO stage was Ⅲ-Ⅳ in 79.9% (139/174). (3) Among the 224 prospective patients: 84 patients received first-line fluzoparib maintenance therapy, 92 patients received fluzoparib maintenance therapy after platinum-sensitive recurrence, 23 patients received direct fluzoparib treatment after platinum-sensitive recurrence, 19 patients received direct fluzoparib treatment after platinum-resistant recurrence. The median follow-up durations were 8.5, 8.7, 7.9, and 6.7 months, respectively. The median durations of fluzoparib treatment were 6.7, 4.8, 3.1, and 1.9 months, respectively. The median progression-free survival (PFS) times were not reached during follow-up, 12.6 months, not reached during follow-up, and 4.8 months, respectively. The 1-year PFS rates were 84.1%, 55.0%, 69.8%, and 45.5%, respectively. The remaining 6 patients received other fluzoparib regimens. (4) Among the 224 patients in the prospective dataset, 205 had safety data recorded. Of these, 127 patients (62.0%, 127/205) experienced treatment-related adverse events, with common events including anemia (24.4%, 50/205), thrombocytopenia (21.0%, 43/205), and leukopenia (19.5%, 40/205). Among the 205 patients, 43 (21.0%, 43/205) experienced grade 3 or higher treatment-related adverse events, with common events including anemia (8.3%, 17/205) and thrombocytopenia (8.3%, 17/205). Conclusions: The effectiveness of fuzuloparib in clinical application is generally consistent with other drugs in the same class, with good safety. This study provids new clinical evidence for the treatment of ovarian cancer with fuzuloparib.

Paraneoplastic acral vascular syndrome (PAVS) is a rare condition characterised by signs of digital ischaemia, including Raynaud's phenomenon, acrocyanosis and digital gangrene, in the context of an underlying neoplastic process. Prompt recognition of this syndrome, as well as accurate identification and classification of the associated neoplastic condition, are crucial.This report describes the case of a woman diagnosed with PAVS secondary to stage IV non-small cell lung adenocarcinoma harbouring a Kirsten Rat Sarcoma viral homolog oncogene (KRAS) G12A mutation (p.Gly12Ala).

Chemoimmunotherapy (CIT) has significantly improved outcomes in patients with extensive-stage small cell lung cancer (ES-SCLC). However, relapses are common. Long-term survival (LTS) is possible for some patients with ES-SCLC treated with CIT regimens; however, the optimal duration for maintenance immunotherapy remains unknown. There is no data on optimal treatment options if LTS patients relapse while off therapy. Here, we are presenting a patient with ES-SCLC, who stopped treatment at 2 years, with disease relapse shortly afterwards. She was treated with a second course of single-agent immunotherapy with another durable remission.

A female patient in her sixth decade of life presented with a 7-day history of progressive diminution of vision and restricted ocular motility associated with fever, headache and vomiting. On general examination, she was febrile (temperature 100.4°F) and had enlarged submandibular lymph nodes, along with multiple nodules on the scalp and upper back. At baseline, ocular examination revealed visual acuity of 20/30 in the right eye and hand movements close to the face in the left eye. A relative afferent pupillary defect was noted in the left eye. The Hirschberg test revealed left esotropia (15°°) with an abduction deficit, suggestive of left sixth cranial nerve paresis. Fundus examination was unremarkable. A provisional diagnosis of left orbital apex syndrome (OAS) was made. A comprehensive work-up in neurology and dermatology was performed. Contrast-enhanced MRI of the brain and orbit suggested an asymmetrically enhancing lesion of the cavernous sinus, soft tissue involvement of the left orbital apex and a nodule involving the white matter of the left parietal lobe. Hormone analysis suggested a decreased level of thyroid-stimulating hormone, follicular-stimulating hormone and luteinising hormone. Fine needle aspiration cytology of a submandibular lymph node and nodules of the scalp and upper back was suggestive of metastatic mucin-secreting adenocarcinoma. Tumour marker analysis revealed raised CEA and CA 125. Further, a positron emission tomography scan revealed active lesions in the lungs with multiorgan spread, supporting the diagnosis of primary lung carcinoma with disseminated metastases manifesting as OAS. In view of the poor prognosis, the patient refused further treatment and succumbed to her condition 1 month following her diagnosis.This case highlights the importance of recognising subtle ocular signs, as they can be indicative of underlying life-threatening conditions. Early detection and thorough investigation of such symptoms are crucial, as they can lead to the identification of serious systemic diseases, such as metastatic cancer, that may otherwise be overlooked.

Solitary small-intestinal metastasis of malignant melanoma is rare. If curative intent resection surgery for small intestinal metastasis can be performed, then a good prognosis can be expected. A 49-year-old woman underwent resection for malignant melanoma of the upper extremity 17 months previously and was admitted to our hospital with vomiting as the main complaint. A tumor causing bowel obstruction of the small intestine was detected, and we diagnosed a solitary small intestinal tumor using positron emission tomography computed tomography (PET-CT). Suspecting a high possibility of solitary malignant melanoma metastasis, we performed a laparoscopic resection for the small intestine and confirmed the absence of abdominal dissemination. The pathological diagnosis was small intestinal metastasis of malignant melanoma. The combination of PET-CT and laparoscopic surgery is useful for the preoperative identification of solitary small intestinal metastasis, and complete resection is possible, with a good prognosis achievable.

CT-guided transthoracic lung biopsy (CT-TTNB) is an essential method for the diagnosis of pulmonary nodules and masses. With a sensitivity of 85-97% and a specificity of 85-100%, it offers high diagnostic accuracy. By using core-needle biopsies, high-quality tissue samples can be obtained that enable molecular analyses for personalised therapy.At the same time, lung ablation has established itself as a valuable minimally invasive therapy. Procedures such as radiofrequency ablation (RFA), microwave ablation (MWA) and cryoablation enable targeted tumour destruction, particularly in inoperable patients with NSCLC or lung metastases. Studies have shown a high level of local tumour control with acceptable complication rates. The combination of imaging and interventional technique significantly improves patient safety and treatment outcomes and offers good results with low complication rates.Overall, CT-guided puncture and ablation are integral components of modern lung cancer diagnostics for primary and secondary lung tumours, while offering a new treatment option and therapy. They offer precise, low-risk alternatives to invasive procedures and can therefore make a significant contribution to effective patient care.

A comparative analysis of the International Academy of Cytology-International Agency for Research on Cancer-World Health Organization Reporting System for Head and Neck Cytopathology (WHO) and the Milan System for Reporting Salivary Gland Cytopathology (MSRSGC) was performed.

Our study aimed to evaluate the survival impact of adjuvant radiotherapy (RT) following breast-conserving surgery (BCS) in elderly male patients with early-stage, low-risk breast cancer (node-negative, HR+), and to identify RT-benefiting subgroups using machine learning and causal inference approaches. We conducted a retrospective cohort study using Surveillance, Epidemiology, and End Results (SEER) database (2000-2021), including 360 patients after propensity score matching (PSM). Patients were grouped by RT and non-RT (NRT) status, and a 1:3 nearest neighbor PSM was applied. Overall survival (OS), relative survival (RS), standardized mortality ratio (SMR), and transformed Cox regression were used to estimate RT benefit. Additionally, machine learning models, including random forest, support vector machines and causal forest model, were applied for survival prediction and validation. In early-stage, low-risk male breast cancer (MBC) patients treated with BCS, adjuvant RT did not demonstrate a significant survival advantage over NRT. After PSM, 15-year OS, RS, and SMR were 31.8%, 15.2%, and 2.14 for RT versus 34.1%, 21.5%, and 2.25 for NRT (p = 0.36, 0.68, and 0.81, respectively). The cumulative incidence of breast cancer-related death (BCRD) and non-BCRD also showed no statistically significant differences between groups (p = 0.06 and 0.75). Machine learning models (Cox, GBM, and XGBoost) confirmed the limited contribution of RT to survival prediction, with the Cox model demonstrating the best discrimination (C-index = 0.713). While RT was associated with a lower risk of death within the first 10 years, its benefit diminished over time. Causal forest analysis revealed notable heterogeneity in treatment effects across subgroups. Patients who were younger, diagnosed earlier, or had stage I disease showed relatively higher estimated benefit from RT, while older patients or those with more recent diagnoses demonstrated attenuated benefit. In elderly, low-risk MBC patients treated with BCS, adjuvant RT was not associated with improved long-term survival. While our findings suggest that RT may be safely omitted in selected individuals, this decision should be made cautiously in the absence of recurrence data. Model-based analyses underscore the importance of tailoring treatment to patient-specific risk profiles. Prospective studies dedicated to MBC are needed to support individualized de-escalation strategies.

Heat shock proteins (HSPs) are evolutionarily conserved molecular chaperones that maintain cellular proteostasis under physiological and stress conditions. HSPH1 (Heat Shock Protein Family H Member 1, also known as HSP105 or HSP110) belongs to the HSP110 family and functions as a nucleotide exchange factor for HSP70, enhancing its folding activity. Beyond its canonical role, HSPH1 is increasingly recognized for its involvement in tumor progression. It has been reported to regulate cell proliferation, invasion, metastasis, and resistance to therapy in several cancers, including breast, lung, and liver cancer. Pan-cancer transcriptomic analyses have identified HSPH1 as frequently overexpressed and correlated with poor prognosis. In hepatocellular carcinoma (HCC), while other HSPs such as HSP70 and HSP90 are well-studied, the biological role of HSPH1 remains unclear. In this study, we systematically analyzed HSPH1 expression in HCC using TCGA and GEO datasets, and validated its clinical relevance in patient samples. HSPH1 was significantly upregulated in HCC tissues and associated with advanced tumor stage and worse overall survival. Functional enrichment and immune infiltration analyses suggested that HSPH1 participates in oncogenic pathways (e.g., p53, cell cycle) and modulates the tumor immune microenvironment. Knockdown of HSPH1 in HCC cell lines inhibited proliferation and colony formation. Together, our findings highlight HSPH1 as a potential prognostic biomarker and therapeutic target in HCC.

This study investigates the mechanisms of Osimertinib resistance in lung adenocarcinoma (LUAD) by identifying prognostic genes associated with SUMOylation. We performed differential expression analysis to identify differentially expressed genes (DEGs) in LUAD samples, Osimertinib-tolerant cell samples and SUMOylation-related genes (SRGs). Utilizing Cox regression and LASSO regression, we developed a prognostic model that highlighted five key prognostic genes-BIRC5, AURKA, BLM, NR3C2, and NDC1. These genes were significantly associated with LUAD progression, revealing their predominant expression in epithelial cells, which play a vital role in tumor development. Furthermore, we explored the biological functions and signaling pathways linked to these prognostic genes, discovering that their expression levels and corresponding risk scores could serve as indicators of CD4 T cell and memory B cell activation. The enriched signaling pathways in LUAD were regulated by ubiquitin-related small modifiers, highlighting the complex interplay between SUMOylation and tumor biology. Our findings suggest the important role of SUMOylation-regulated genes in LUAD progression and Osimertinib resistance, suggesting their potential as valuable biomarkers for prognosis and therapeutic targets to enhance treatment strategies for patients with EGFR-mutant lung adenocarcinoma.

Anti-programmed cell death-1 (PD-1) immunotherapy and platinum-based chemotherapy are key components of first-line treatment for advanced Gastric or Gastroesophageal Junction (G/GEJ) cancer. However, the role of immune cells infiltrating the tumor microenvironment (TME) in predicting both therapy responses is still unclear.

The Kocher maneuver is the most common surgical approach for duodenal tumors. However, the extensive dissection required for the second and third portions of the duodenum complicates laparoscopic procedures. This study introduces the anterior and transmesocolic approaches in laparoscopic and endoscopic cooperative surgery for duodenal neoplasms (D-LECS). Thirty patients who underwent D-LECS at our institute between November 2016 and August 2024 were included. The median age was 62.5 years, and the median pathological tumor size was 15 mm. Tumors were located in the first, second, and third portions of the duodenum in 5, 20, and 5 patients, respectively. The anterior approach was performed in the first to upper second portion of the duodenum in seven patients; the transmesocolic approach was performed in the second to third portions of the duodenum in 23 patients. All patients underwent full-thickness suture reinforcement after endoscopic submucosal dissection. The median operation time and bleeding volume were 281 min and 10 mL, respectively, for the anterior approach and 297 min and 0 mL, respectively, for the transmesocolic approach. Postoperative complications, such as delayed perforation, were not observed. All patients underwent curative resection. Pathological analyses revealed 21, 7, 1, and 1 case of adenoma, adenocarcinoma, gastrointestinal tumor, and neuroendocrine tumor, respectively. Disease recurrence was not observed during the follow-up (median, 35 months). D-LECS using the anterior and transmesocolic approaches based on tumor location may allow for individualized surgical management in patients with early duodenal neoplasms.

Lymph node (LN) metastasis is a key prognostic factor in laryngeal squamous cell carcinoma (LSCC). Emerging evidence implicates the role of the microbiome in cancer progression. This study aimed to investigate the microbial features associated with lymph node metastasis in LSCC and their potential for patient stratification. Using 16 S rRNA gene sequencing, we characterized the microbiome of tumor tissues, adjacent normal tissues, lymph nodes, and oral rinses from 108 LSCC patients, including 36 with (LN+) and 72 without (LN-) cervical LN metastasis. Microbial functional potential was predicted using PICRUSt2. Based on repeated stratified 3 cross-validation, random forest models were used to identify metastasis-associated genera. Significant microbial differences were observed between LN + and LN- tumor tissues, with Ralstonia enriched in LN + tumors and Fusobacterium more abundant in LN- cases. All genera detected in lymph nodes were also found in tumor tissues. Functional predictions revealed enrichment of lipid biosynthesis, energy metabolism, and cell wall synthesis pathways in LN + patients, particularly in tumor and oral rinse samples, with low intra-group variability. Classifiers based on tumor, lymph node, and oral microbiota demonstrated the ability to distinguish LN + from LN- patients. The lymph node-derived classifier achieved an accuracy of 84.31% (95% confidence interval [CI]: 81.76% - 86.85%), followed by the tumor-based model (AUC = 84.11%, 95% CI: 81.75% - 86.46%) and oral rinse classifier (AUC = 79.88%, 95% CI: 77.09% - 83.11%). A tumor-specific 17 genera panel showed a discriminative efficacy of 84.11% (95% CI: 81.75% - 86.46%) in tumor tissues. These findings suggest that microbiome alterations may be associated with lymph node metastasis in LSCC. In addition, the oral microbiome showed potential as a non-invasive tool for occult lymph node metastasis detection. However, these results are preliminary and require validation in larger, independent cohorts.

Gastric cancer (GC) is a prevalent malignancy and one of the leading causes of cancer-related mortality worldwide. The role of transmembrane channel-like 5 (TMC5) in GC remains unknown. In this study, we analyzed the expression of TMC5 in GC using a multi-faceted approach, including analysis of public databases, immunohistochemical assays, and Western blot analyses. Our results demonstrated that TMC5 was overexpressed in GC tissues and cell lines, which was associated with poor prognosis and various clinical characteristics. We observed that the mutation rates of TMC5 in GC were low, and its methylation status was inversely related to its expression levels. Furthermore, functional assays demonstrated that TMC5 promoted GC cell proliferation, migration, and invasion in vitro, as well as tumor growth and metastasis in vivo. Furthermore, the TMC5 expression level was positively correlated with stemness and chemotherapy resistance in GC. Additionally, TMC5 was associated with multiple immune cell infiltration levels, immunotherapy response and immune checkpoint genes. Subsequently, the co-expression genes of TMC5 in GC were screened and verified by qRT-PCR. Gene set enrichment analysis showed that these genes were mainly involved in biosynthesis, metabolic pathways, and multiple classic cancer-related signaling pathways. In conclusion, our study reveals the important role of TMC5 in GC and provides potential new targets and strategies for the diagnosis and treatment of GC.

Molecular mechanisms underlying glyphosate-induced nephrotoxicity and carcinogenicity were investigated through integrated network toxicology, molecular docking, and dynamics simulations. Screening identified 47 potential glyphosate targets; intersection analysis yielded 20 kidney injury and 31 kidney cancer shared targets. Protein-protein interaction networks highlighted matrix metalloproteinases (MMP9, MMP2, MMP8, MMP3) and PLG as topological hubs. Pathway enrichment revealed significant alterations in extracellular matrix reorganization and nitrogen metabolism. Molecular modeling demonstrated stable glyphosate binding within catalytic domains of MMPs (affinities: -5.03 to - 6.29 kcal/mol), with dynamics simulations confirming persistent complex formation over 100 ns. Results indicate MMP-mediated dysregulation of structural homeostasis, alongside metabolic pathway perturbation, as contributory factors in glyphosate-associated renal pathology. The prominence of MMPs across target networks and functional analyses suggests their role as molecular conduits for glyphosate toxicity.