Amlodipine inhibits Synaptotagmin-4's oncogenic activity on gastric cancer proliferation by targeting calcium signaling.

BACKGROUND: Gastric cancer (GC) remains a leading cause of cancer mortality globally. Synaptotagmin-4 (SYT4), a calcium-sensing synaptic vesicle protein, has been implicated in the oncogenesis of diverse malignancies. PURPOSE: This study delineates the role of SYT4 in modulating clinical outcomes and biological behaviors in GC. METHODS: We evaluated SYT4 expression in GC specimens using bioinformatics analyses and immunohistochemistry. Functional assays included CCK8 proliferation tests, apoptosis assays via flow cytometry, confocal calcium imaging, and xenograft models. Western blotting elucidated MAPK pathway involvement. Additionally, we investigated the impact of the calcium channel blocker amlodipine on cellular dynamics and MAPK pathway activity. RESULTS: SYT4 was higher in GC tissues, and the elevated SYT4 was significantly correlated with adverse prognosis. Both univariate and multivariate analyses confirmed SYT4 as an independent prognostic indicator for GC. Functionally, SYT4 promoted tumorigenesis by fostering cellular proliferation, inhibiting apoptosis, and enhancing intracellular Ca2+ influx, predominantly via MAPK pathway activation. Amlodipine pre-treatment attenuated SYT4-driven cell growth and potentiated apoptosis, corroborated by in vivo xenograft assessments. These effects were attributed to MAPK pathway suppression by amlodipine. CONCLUSION: SYT4 emerges as a potential prognostic biomarker and a pro-oncogenic mediator in GC through a Ca2+-dependent MAPK mechanism. Amlodipine demonstrates significant antitumor effects against SYT4-driven GC, positing its therapeutic promise. This study underscores the imperative of targeting calcium signaling in GC treatment strategies.

A case report of abdominal metastatic dermatofibrosarcoma protuberans misdiagnosed as gastrointestinal stromal tumor.

Dermatofibrosarcoma protuberans (DFSP) is a low-grade malignant soft-tissue tumor that originates from the skin. It has a slow onset in the early stages, non-specific clinical symptoms, low specificity, and can easily be overlooked, missed, or misdiagnosed by clinicians and pathologists. In addition, DFSP is prone to recurrence after local surgical treatment; however, distant metastasis, especially abdominal metastasis, is rare, which is also a challenge for the accurate diagnosis of DFSP when it progresses distantly. Now a case of abdominal metastasis of DFSP is reported. The patient has been treated with imatinib for ten years, and the lesion has shrunk, but because the patient has been receiving imatinib treatment, his abdominal lesion was once misdiagnosed as gastrointestinal stromal tumor. Therefore, we report on this case to enhance the understanding of the diagnosis and treatment of DFSP, and to provide reference for the pathological diagnosis and precise treatment of such patients.

Reactive lymphoid hyperplasia of the liver: A rare case report.

BACKGROUND: Hepatic reactive lymphoid hyperplasia (RLH) is a rare benign lymphoproliferative lesion and a poorly understood disease. It is usually asymptomatic and incidental, but it is difficult to distinguish from hepatocellular carcinoma and metastatic liver tumor on imaging, and percutaneous biopsy is not sufficient to distinguish from low-grade malignant lymphoma and extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma), making diagnosis difficult. CASE SUMMARY: A 69-year-old woman came to our hospital for reexamination of pulmonary nodules followed by liver occupation. The lesions showed "wash-in and wash-out" on contrast-enhanced ultrasonography and magnetic resonance imaging. Enhanced magnetic resonance also showed annular envelope enhancement and limited diffusion on the ADC map during the delay period. Imaging revealed metastatic liver cancer, and the patient underwent a partial hepatectomy. However, the final histopathological diagnosis was RLH. CONCLUSION: If small isolated nodules are found in the liver of middle-aged and elderly female patients with no risk factors for liver malignancy, when the enhanced imaging suggests "wash-in and wash-out", further focus should be placed on whether the enhanced imaging shows perinodular enhancement and whether the DWI shows limited diffusion in MRI, in order to emphasize the possibility of liver RLH diagnosis.

Distribution of residual tumors in esophageal squamous cell carcinoma after neoadjuvant PD-1 blockade combined with chemotherapy.

Aims: The distribution of residual esophageal squamous cell carcinoma (ESCC) in the esophageal wall and resected lymph nodes was evaluated after neoadjuvant chemoimmunotherapy (nICT). Methods and results: Clinical data were collected from 137 ESCC patients who underwent anti-programmed death 1 therapy and esophagectomy. Ninety (65.7%) achieved an major pathological response (MPR) in the esophageal wall, and 27 (19.7%) achieved an MPR in the lymph nodes. Pathologically complete response (pCR, ypT0N0) was observed in 26 patients (19%). Residual tumors located in the mucosa and/or submucosa were found in 94.6% of nonpCR patients. In the minor responders, 97.8% had residual tumor >10% in the mucosa or submucosa. A preferential regression direction toward the lumen was found in 76.4% of prepT2 nonpCR patients, or 60.7% of prepT3-4a nonpCR patients. The correlation between pCR in the esophageal wall and in lymph nodes was not significant (P=0.143). Among 19 patients with pCR in resected recurrent laryngeal nerve (RLN) lymph nodes, 31.6% had residual tumor cells in other resected lymph nodes. A significant correlation was found between ypT/ypN downstaging and tumor regression grade (P<0.05). Conclusions: After nICT for ESCC, residual tumors were frequently found in the mucosa or submucosa, with relatively high responsiveness of the invasive front and a significant correlation with downstaging, which may help clinicians make appropriate decisions about postoperative treatment and surveillance. The differences in pCR status in primary tumors, resected lymph nodes, and RLN lymph nodes indicated the importance of assessing regression changes in all resected lymph nodes during clinical practice.

A comparative analysis of clinicopathological factors and survival between esophageal basaloid squamous cell carcinoma and conventional esophageal squamous cell carcinoma.

INTRODUCTION: Recently, the number of diagnosed esophageal basaloid squamous cell carcinoma (EBSCC) has gradually increased. However, available data on EBSCC are limited to date. METHODS: A total of 165 EBSCC (Cohort 1) and 515 conventional esophageal squamous cell carcinoma (ESCC) (Cohort 2) were retrospectively analyzed. RESULTS: In Cohort 1, 70 cases only had invasive EBSCC component (42.4%, defined as Group 1), 73 cases had concomitant invasive ESCC component (44.2%, Group 2), and 22 had concomitant invasive poor-differentiated component (13.3%, Group 3). Lymph node metastasis rates of Group 3, Group 2 and Group 1 were ranked from high to low (P = 0.044). There were higher patient age (P = 0.047), smaller tumor size (P = 0.009), more nerve invasion (P < 0.001), and lower pTNM stage (P < 0.001) in EBSCC (Cohort 1), compared with ESCC (Cohort 2). In Cohort 1 and Cohort 2, pTNM stage was an independent prognostic factor for both DFS and OS. No significant survival difference was found between EBSCC (Cohort 1) and ESCC (Cohort 2) in pIA-B stage, pIIA-B stage, pIIIA-B stage and pIVA-B stage (P > 0.05). CONCLUSION: Our analysis of the largest EBSCC series from a single institution to date with conventional ESCC demonstrated that EBSCC carried a similar prognosis with ESCC in pIA-B stage, pIIA-B stage, pIIIA-B stage and pIVA-B stage. And pure EBSCC, didn't have poorer survival than mixed EBSCC with concomitant ESCC or other components. Our findings may be valuable in the better understanding of EBSCC's biological behaviors, and the related molecular mechanism is needed to be explored in the future.

Clinical and pathological observation of conversion therapy for malignant peritoneal mesothelioma: a case report and literature review.

Background: Malignant mesothelioma (MM) is a tumor originating from the pleura, peritoneum, or pericardial cavity. It is divided into diffuse and localized malignant mesothelioma, with four subtypes in diffuse MM: epithelioid, sarcomatoid, desmoplastic, and biphasic, with biphasic being less common. The onset of this tumor is insidious, and the prognosis is extremely poor in some cases, with a median survival of 6-18 months and no standard treatment options in the past. Aims: We report a case of peritoneal malignant mesothelioma that was successfully treated with transformative therapy. We also review the literature in the hope of providing reference for the treatment and pathological diagnosis of such patients. Methods: The case of the peritoneal malignant mesothelioma was processed and reported in the routine manner for biopsy specimens at different stages. Results and conclusion: We report a case of a malignant tumor originating in the hepatorenal recess, which was diagnosed as biphasic malignant mesothelioma through a biopsy. Immunohistochemical testing showed PD-L1 expression. After multidisciplinary discussion, the patient received transformative treatment, including a trial of combined immunotherapy. The tumor significantly shrank, and the patient obtained a chance for curative surgical resection. Microscopic examination showed significant collagenization in the lesion area, with almost no residual tumor. After 19 months of comprehensive treatment, the patient developed multiple fluffy opacities under the pleura of both lungs. Transthoracic core needle biopsy under CT guidance, the pathology showed organizing pneumonia, considering it as delayed interstitial pneumonitis due to immunotherapy based on previous treatment history. Successful comprehensive treatment was achieved for this case of peritoneal malignant mesothelioma, and the patient has been alive without evidence of disease for 33 months, with long-term follow-up. In this process, the pathologist had three opportunities for pathological diagnosis, which required understanding the patient's medical history, being attentive to the clinical purpose of the specimen, and providing accurate responses to morphological changes at different stages, along with corresponding descriptions and diagnoses to provide effective information for clinical treatment.

Proteomic analysis reveals key differences between squamous cell carcinomas and adenocarcinomas across multiple tissues.

Squamous cell carcinoma (SCC) and adenocarcinoma (AC) are two main histological subtypes of solid cancer; however, SCCs are derived from different organs with similar morphologies, and it is challenging to distinguish the origin of metastatic SCCs. Here we report a deep proteomic analysis of 333 SCCs of 17 organs and 69 ACs of 7 organs. Proteomic comparison between SCCs and ACs identifies distinguishable pivotal pathways and molecules in those pathways play consistent adverse or opposite prognostic roles in ACs and SCCs. A comparison between common and rare SCCs highlights lipid metabolism may reinforce the malignancy of rare SCCs. Proteomic clusters reveal anatomical features, and kinase-transcription factor networks indicate differential SCC characteristics, while immune subtyping reveals diverse tumor microenvironments across and within diagnoses and identified potential druggable targets. Furthermore, tumor-specific proteins provide candidates with differentially diagnostic values. This proteomics architecture represents a public resource for researchers seeking a better understanding of SCCs and ACs.

Clinicopathologic features of gastric glomus tumor: A report of 15 cases and literature review.

Objective: Glomus tumor is a relatively uncommon soft tissue neoplasm predominantly occurring in upper extremity (fingers), less reported in stomach. This study aimed to discuss the clinicopathologic features of gastric glomus tumor (GGT) and then provide reference for clinical practice. Methods: A retrospective analysis of all cases pathologically diagnosed of GGT was performed, pathological findings were correlated with clinical information, immunohistochemical studies, next-generation sequencing, and patient follow-ups. A review of literature by searching similar cases was conducted to summarize previous knowledge of GGTs. Results: Our study identified 15 GGTs included 5 males and 10 females, aged between 35-75 years old (median, 49 years old). The tumor was located to the gastric corpus in 6 cases (40%) and to the antrum in 9 cases (60%). The maximum tumor diameter ranged between 1-4 cm (median, 1.5 cm). There were 11 cases (73%) of solid glomus tumor, 3 cases (20%) of mixture of solid glomus tumor and glomangioma, and 1 case (7%) of glomangiomyoma. Partial spindle cell area was observed in 3 cases (20%), moderate cellular atypia in 1 case (7%), atypical mitosis in 1 case (7%), vascular invasion in 5 cases (33%), neural invasion in 6 cases (40%) and tumor necrosis in 1 case (7%). Tumor cells expressed Collagen type IV, α-smooth muscle actin (α-SMA), and synaptophysin in most cases. The Ki67 index varied from 1% to 30%. Next-generation sequencing reported EGFR, PIK3CA, KEAP1 and TP53 mutation. The outcome information was obtained in 12 (80%) cases, followed for 6-63 months, 11 patients (92%) had tumor-free survival and 1 patient (8%) developed liver metastasis 26 months after surgery. Literature review obtained 16 previously reported malignant GGT cases. In terms of the total 31 cases, univariate analysis revealed that the atypical mitosis (OS: p = 0.009; DFS: p = 0.010) and severe cellular atypia (OS: p = 0.007; DFS: p = 0.004) were significantly associated with poor prognosis (patient death). Conclusion: GGT is indolent, while long-term close follow-up should be required in the presence of increasing number of risk factors. Malignant GGT is relatively uncommon and predisposes to liver metastasis, calling for accumulation of large-sample data and experience.