This study aimed to explore the biological functions and clinical value of mothers against decapentaplegic homolog (SMAD) 7 in head and neck squamous cell carcinoma (HNSCC) through bioinformatics analysis and basic experiments.

The v-Raf murine sarcoma viral oncogene homolog B (BRAF) gene is one of the most critical proto-oncogenes and functions as a key regulator in the mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) signaling pathway. The incidence of BRAF mutations in non-small cell lung cancer (NSCLC) patients ranges from 1.5% to 5.5%, with BRAF V600 mutations accounting for approximately 30%-50% of all BRAF mutations, among which BRAF V600E represents the most prevalent mutation type. Currently, the combination of Dabrafenib and Trametinib has been recommended as first-line therapy for BRAF V600-mutant NSCLC by multiple domestic and international guidelines including National Comprehensive Cancer Network (NCCN), European Society of Medical Oncology (ESMO), and Chinese Society of Clinical Oncology (CSCO). However, there are no clear targeted treatment recommendations for BRAF non-V600 mutations. Although case reports suggest that Dabrafenib combined with Trametinib may be effective for patients with BRAF non-V600 mutations, the efficacy and safety require further validation due to limited sample size and lack of large-scale clinical trial data. This article reports a case of NSCLC with a rare BRAF insertion and deletion mutation that responded well to the treatment of Dabrafenib in combination with Trametinib, aiming to enhance clinicians' understanding of such NSCLC cases with extremely rare mutation and provide a reference for future treatment strategies.
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Advances in targeted therapy and immunotherapy have significantly improved clinical outcomes for patients with advanced non-small cell lung cancer (NSCLC), reshaping treatment paradigms. However, most patients ultimately face drug resistance, with limited options for subsequent therapies and suboptimal treatment efficacy, presenting a prominent challenge in current clinical practice. Antibody-drug conjugates (ADCs), characterized by high efficacy and favorable safety profiles, have emerged as a promising therapeutic frontier in recent years. This systematic review provides a comprehensive overview of the latest advancements in ADCs-based therapies for lung cancer, alongside discussions of the prevailing challenges in this rapidly evolving domain.
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Human epidermal growth factor receptor 2 (HER2) mutations play a role as a driver gene in non-small cell lung cancer (NSCLC). Patients with advanced NSCLC harboring HER2 mutations exhibit poor responses to conventional chemotherapy and immunotherapy, hence targeted therapies against HER2 are under extensive investigation. This review analyzes the biological characteristics of HER2, an overview of clinical trials for targeted therapy drugs, including monoclonal antibodies, tyrosine kinase inhibitors (TKIs), and antibody-drug conjugate, and research directions for drug resistance in NSCLC. Currently, Pyrotinib and Trastuzumab deruxtecan have been approved for the treatment of advanced NSCLC with HER2 mutations, suitable for patients who have failed standard therapy, which is far from meeting the clinical demands. Novel selective HER2 TKIs are gradually emerging. Future exploration trends are gradually shifting from single drugs to combination strategies, and are exploring more precise selection strategies as well as research on resistance mechanisms. These studies will provide a theoretical basis for clinical treatment strategies for advanced NSCLC with HER2 mutations, promoting the development of personalized therapy.
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Lung adenocarcinoma is an important pathohistologic subtype of non-small cell lung cancer (NSCLC). Invasive non-mucinous pulmonary adenocarcinomas (INMA) tend to have a poor prognosis due to their significant heterogeneity and diverse histologic components. Establishing a histologic grading system for INMA is crucial for evaluating its malignancy. In 2021, the International Association for the Study of Lung Cancer (IASLC) proposed that a new histological grading system could better stratify the prognosis of INMA patients. The aim of this study was to establish a visualized nomogram model to predict INMA IASLC grading preoperatively by means of dual-energy computed tomography (DECT), fractal dimension (FD), clinical features and conventional CT parameters.

Neoadjuvant therapeutic strategies play a pivotal role in the comprehensive treatment of non-small cell lung cancer (NSCLC). However, lung squamous cell carcinoma (SCC) generally exhibits a more favorable response to neoadjuvant therapy compared with lung adenocarcinoma (ADC). The aim of this study is to elucidate how baseline cancer-associated fibroblasts (CAFs) and tumor-associated endothelial cells (TAECs) influence the differential therapeutic outcomes of neoadjuvant treatment in SCC versus ADC.

The incidence of leptomeningeal metastasis (LM) in patients with advanced non-small cell lung cancer (NSCLC) is increasing gradually. However, it poses therapeutic challenges due to limited effective interventions. Intrathecal Pemetrexed (IP) holds broad application prospects in the therapeutic domain of LM. This study aims to evaluate the efficacy, safety, and optimal combination strategies of IP in NSCLC-LM patients with epidermal growth factor receptor (EGFR) mutation-positive status, with the aim of providing real-world data support for exploring more precise personalized treatment strategies for these patients.

With the rising incidence of breast cancer among women, neoadjuvant chemotherapy (NAC) is becoming increasingly crucial as a preoperative treatment modality, enabling tumor downstaging and volume reduction. However, its efficacy varies significantly among patients, underscoring the importance of predicting pathological complete response (pCR) following NAC. Early research relied on statistical methods to integrate clinical data for predicting treatment outcomes. With the advent of artificial intelligence (AI), traditional machine learning approaches were subsequently employed for efficacy prediction. Deep learning emerged to dominate this field, and demonstrated the capability to automatically extract imaging features and integrate multimodal data for pCR prediction. This review comprehensively examined the applications and limitations of these three methodologies in predicting breast cancer pCR. Future efforts must prioritize the development of superior predictive models to achieve precise predictions, integrate them into clinical workflows, enhance patient care, and ultimately improve therapeutic outcomes and quality of life.

Tumor treating fields (TTF) therapy is an innovative tumor treatment modality. Currently, the TTF devices predominantly employ insulated ceramic electrodes as the electric field transmission medium, resulting in low energy transfer efficiency of the electric field and poor portability of the devices. This study proposed an innovative TTF transmission mode and independently designed a conducted-electrode TTF cell culture dish utilizing inert titanium materials. The electric field conduction characteristics were verified through finite element simulations and experimental tests. Finally, based on the self-manufactured conducted-electrode TTF cell culture dish, experiments on the proliferation inhibition of U87 tumor cells by TTF were conducted. The results demonstrated that under an applied TTF voltage of 10 V and frequency of 200 kHz, the electric field intensities within the medium for conducted and insulated electrodes are approximately 2.5 V/cm and 0.7 V/cm, respectively. Compared to conventional insulated TTF systems, the conducted-electrode TTF configuration exhibited a lower electrode voltage drop and a higher electric field intensity in the culture medium, indicating superior electric field transmission efficiency. Following 36 hours of treatment with conducted-electrode TTF on U87 cells, the proliferation inhibition rate reached approximately 50%, demonstrating effective suppression of tumor cell growth. This approach presents a potential direction for optimizing TTF treatment modality and device design.

Objective:To analyze the relationship between the optimal surgical margin value and clinical prognosis of transoral robotic surgery（TORS） in treating human papillomavirus（HPV） -positive oropharyngeal squamous cell carcinoma. Methods:A single-center, prospective, observational cohort study was conducted, enrolling patients with early and moderated stage（≤T3 stage） oropharyngeal carcinoma undergoing TORS between July 2020 and April 2024. The proposed optimal surgical margin cutoff value for TORS was set as 2 mm. The primary objectives were to evaluate the optimal clear margin for TORS and its association with overall survival（OS） and progression-free survival（PFS）. Logistic regression was used to analyze correlations between surgical margins and clinical variables, while Cox regression models assessed the impact of surgical margins on OS and PFS. Results:A total of 90 patients（60 males, 66.7%） were included, all had squamous cell carcinoma, with a mean age of 58.0±9.0 years（range: 39-84 years） old. The 1, 2 and 3-year OS rates were 92.3%, 89.9% and 85.0%, respectively, while the 1, 2 and 3-year PFS rates were all 90.1%. For surgical margins ≤2 mm, the 1, 2 and 3-year OS rates were 80.8%, 69.3% and 69.3%, respectively, and PFS rates were 77.9% across three time points. For surgical margins>2 mm, the 1, 2 and 3-year OS rates were 96.5%, 96.5% and 90.6%, respectively, with PFS rates of 94.6%. Logistic regression showed no correlation between surgical margins and tumor type, T/N stage, smoking, alcohol use, or gender（P>0.05）. Cox analysis identified surgical margins>2 mm as a significant factor improving PFS（HR=0.14, 95%CI 0.02-0.90, P=0.038）. Conclusion:This systematic analysis suggests setting a 2 mm and longer as clear surgical margin for TORS. Margins>2 mm are associated with superior postoperative PFS rate and prolonged PFS time in HPV-positive oropharyngeal carcinoma patients.

Plasmablastic lymphoma (PBL) is a rare, highly aggressive non-Hodgkin lymphoma subtype for which no standardized therapeutic regimen has been established in clinical practice. This study retrospectively analyzed 18 PBL cases at Shanghai Ruijin Hospital from July 2012 to June 2024. Participants comprised 12 males and 6 females, with a median age of 59 (39-77) years. Twelve (66.7% ) cases presented at stage Ⅲ/Ⅳ, nine (50% ) have cytopenia, 12 (66.7% ) have increased lactate dehydrogenase level, and four (22.2% ) had a Ki-67 index of ≥90%. The tumor cells highly expressed CD38 (15/17, 88.2% ) /CD138 (12/17, 70.6% ), whereas the B-cell marker CD20 was rarely detected (1/17, 5.9% ). Of the 11 cases that underwent genetic sequencing, common mutations included TP53 (27.3% ), KMT2D (18.2% ), and TET2 (18.2% ). After excluding one patient with positive HIV who died without treatment, 17 patients received first-line therapy, achieving a complete response in 10 (58.8% ) and a partial response in 5 (29.4% ) cases. With the median follow-up time of 4.33 (0.17-12.17) years, Kaplan-Meier analysis indicated that the 2-year progression-free survival rate and overall survival rate were (68.5±11.2) % and (75.5±10.1) %, respectively.

Objective: To analyze the clinical features and prognosis of patients with lymphoplasmacytic lymphoma/Waldenström macroglobulinemia (LPL/WM) transformed into diffuse large B-cell lymphoma (DLBCL) . Methods: This study retrospectively analyzed the clinical data of five patients with LPL/WM transformed to DLBCL diagnosed and treated at a multicenter hospital in Hunan Province from December 2020 to April 2023. Clinical manifestations, treatment regimens, and therapeutic efficacy before and after the transformation were compared. Results: Of the five patients, four were male and one was female, with a median age of 64.0 (57.0-80.0) years, all of whom had abnormally increased β(2)-microglobulin levels at diagnosis, and two were combined with increased lactate dehydrogenase levels. The MYD88(L265P) mutation was detected in 4 patients, whereas 1 carried the FAT1 and NOTCH1 mutations, and none demonstrated CXCR4 mutations. Three patients were negative for the TP53 mutation, and two were not tested. Before transformation, three patients were treated with Bruton tyrosine kinase inhibitor therapy, and one patient was treated with the bendamustine plus rituximab regimen. All patients eventually transformed into non-growth center-derived DLBCL, with a median time to conversion of 11.8 (4.0-19.0) months, and most of them presented with weight loss, lymph node enlargement, splenomegaly, and extranodal involvement. Posttransformation, the patients were mainly treated with the rituximab, cyclophosphamide, hydroxydaunorubicin, oncovin, and prednisone (R-CHOP) regimen, with an optimal outcome of partial remission. Disease progression occurred in 4 of the patients, with a median overall survival of 16.8 (10.0-26.0) months. Conclusion: Transformation from LPL/WM to DLBCL is rare. Patients should remain highly vigilant for transformation if they develop rapidly enlarging lymph nodes and/or newly involved lymph nodes, worsening systemic symptoms, and declining body mass. R-CHOP regimen may induce a partial response in some cases; however, the overall prognosis remains poor.

Objective: This study analyzes the clinicopathological features and prognostic factors of early-stage gastric mixed adenoneuroendocrine carcinoma (G-MANEC), which is an exceedingly rare malignancy, in an effort to provide evidence-based insights for clinical decision-making. Methods: A retrospective observational study was conducted using the clinical data of 36 patients with early-stage G-MANEC who underwent surgical resection at Zhongshan Hospital, Fudan University, from July 2014 to May 2022. The observed indicators included clinicopathological data and follow-up information on recurrence, metastasis, and overall survival (OS). Results: Among the 36 patients there were 21 males and 15 females, aged 32-84 (65±11) years. The most common initial symptoms were abdominal pain and distension (19/36, 52.8%), followed by incidental findings during physical examinations (7/36, 19.4%). Tumors were located in the proximal stomach in 13 cases (36.1%), the middle stomach in 4 cases (11.1%), and the distal stomach in 19 cases (52.8%). Average tumor diameter was (2.48±1.18) cm. Gross morphology included elevated type in 12 cases (33.3%), flat type in 20 cases (55.6%), and depressed type in 4 cases (11.1%). Ulceration was present in 12 cases (33.3%). There were 11 cases (30.6%) at T1a stage and 25 cases (69.4%) at T1b stage. Lymph node metastasis was positive in 10 cases (27.8%), and the differentiation grades of the adenocarcinoma component were Grade I, II, and III in 3 (8.3%), 10 (27.8%), and 23 (63.9%) cases, respectively. Furthermore, the proportion of neuroendocrine carcinoma component was ≥50% in 18 cases (50.0%) and <50% in 18 cases (50.0%). Lymphovascular or perineural invasion was present in 18 cases (50.0%). Lauren classification included mixed type in 10 cases (27.8%), intestinal type in 19 cases (52.8%), and diffuse type in 7 cases (19.4%), and chromogranin A (CgA) positivity was found in 20 cases (55.6%). Additionally, the Ki-67 index positivity was found in 26 cases (72.2%). Total gastrectomy was performed in 12 cases (33.3%) and partial gastrectomy in 24 cases (66.7%), with a median follow-up duration of 77.5 months. The 3-year and 5-year OS rates were 88.89% and 79.67%, respectively. Univariate analysis revealed that age, gross morphology, ulceration, proportion of neuroendocrine carcinoma component, lymphovascular or perineural invasion, and chromogranin A (CgA) positivity showed statistical significance in their association with OS (P<0.10). Multivariate Cox regression analysis further identified ulceration (HR=7.74, 95%CI: 1.24-48.30, P=0.028) and CgA positivity (HR=21.76, 95%CI: 1.86-53.97, P=0.014) as independent risk factors of OS. Conclusions: Patients with early-stage G-MANEC are typically asymptomatic, and those with ulceration or positive CgA immunohistochemical staining tend to have a poor prognosis.

Objective: To investigate the impact of the number of examined lymph nodes (ELN) on survival outcomes in gastric cancer patients with postoperative pathological stage pN3b. Methods: This retrospective cohort study included 279 pN3b gastric cancer patients who underwent D2 gastrectomy at Nanfang Hospital, Southern Medical University (September 2008 to April 2023), with 35 patients receiving combination chemotherapy and anti-PD-1 therapy (immunotherapy group) and 244 receiving adjuvant chemotherapy alone (nonimmunotherapy group). Additionally, 422 patients with pN3b from the SEER database (2005 to 2020) were collected as an external validation cohort to determine the optimal cutoff value for the number of lymph nodes examined in the nonimmunotherapy group. The primary endpoints were overall survival (OS) and recurrence-free survival (RFS) in the nonimmunotherapy group of the Nanfang Hospital cohort, stratified by whether the number of examined lymph nodes was above or below the ELN optimal cutoff value. These findings were subsequently validated in the SEER cohort. Results: The optimal ELN cutoff value (34 nodes) was determined using X-tile software and by constructing an ELN-HR fitting model with inflection point identification. In the nonimmunotherapy group, patients with ELN >34 exhibited significantly prolonged survival compared to ELN ≤34 (median OS: 25.0 (95%CI:20.5-29.5) to 17.0 (95%CI:12.7-21.3) months, P=0.004; median RFS: 19.0 (95%CI:15.6-22.4) to 13.0 (95%CI:9.5-16.5) months, P=0.048). Multivariate Cox analysis also showed ELN >34 to be an independent protective factor for both OS (HR=0.576, 95%CI: 0.397-0.836) and RFS (HR=0.701, 95%CI: 0.492-0.998). In the SEER cohort, ELN >34 was associated with a 5-month OS extension (19 to 14 months, P=0.065), with multivariate analysis supporting its independent prognostic significance (HR=0.729, 95%CI: 0.580-0.915, P=0.006). Notably, in the immunotherapy group, patients with ELN >34 (n=30) achieved a median OS of 41 months, but the median OS had not been reached in the ELN ≤34 group (n=5) (1 death at 48 months). Conclusion: Higher ELN (>34) correlates with improved survival in nonimmunotherapy-treated pN3b gastric cancer patients. However, in pN3b gastric cancer patients treated with immunotherapy, the optimal ELN threshold requires further exploration to determine.

To investigate the effect of BRD4 inhibition on migration of esophageal squamous cell carcinoma (ESCC) cells with low acetyl-CoA carboxylase 1 (ACC1) expression.

To investigate the role of SF3B3 in gastric cancer (GC) progression and prognosis and its possible mechanisms.

To investigate the prognostic significance of PDZ-binding kinase (PBK) in pan-cancer and its potential as a therapeutic target for pancreatic cancer.

To evaluate the inhibitory effect of oridonin against proliferation of pancreatic cancer cells and the mechanism underlying the synergistic effect of low-intensity pulsed ultrasound (LIPUS).

To investigate the expression of parathyroid hormone-like hormone (PTHLH) in hepatocellular carcinoma (HCC) and analyze its correlation with clinical prognosis, its regulatory effects on HCC cell behaviors, and the signaling pathways mediating its effects.

To evaluate the regulatory effects of lncRNA LINC00261 on proliferation, invasion, and metastasis of esophageal squamous cell carcinoma (ESCC) cells.