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Pancreatic neuroendocrine tumor (pNET) is the second most common malignant tumors of the pancreas. Multiple endocrine neoplasia 1 ( MEN1) is the most frequently mutated gene in pNETs and MEN1-encoded protein, menin, is a scaffold protein that interacts with transcription factors and chromatin-modifying proteins to regulate various signaling pathways. However, the role of MEN1 in lipid metabolism has not been studied in pNETs. In this study, we perform targeted metabolomics analysis and find that MEN1 promotes the generation and oxidation of polyunsaturated fat acids (PUFAs). Meanwhile lipid peroxidation is a hallmark of ferroptosis, and we confirm that MEN1 promotes ferroptosis by inhibiting the activation of mTOR signaling which is the central hub of metabolism. We show that stearoyl-coA desaturase (SCD1) is the downstream of MEN1-mTOR signaling and oleic acid (OA), a metabolite of SCD1, recues the lipid peroxidation caused by MEN1 overexpression. The negative correlation between MEN1 and SCD1 is further verified in clinical specimens. Furthermore, we find that BON-1 and QGP-1 cells with MEN1 overexpression are more sensitive to everolimus, a widely used drug in pNETs that targets mTOR signaling. In addition, combined use everolimus with ferroptosis inducer, RSL3, possesses a more powerful ability to kill cells, which may provide a new strategy for the comprehensive therapy of pNETs.

Background and purpose: Pancreatic neuroendocrine tumor (pNET) is a rare tumor. At present, there is still a lack of large-scale clinical research data to summarize the clinical effect of minimally invasive technology in the treatment of pNET. This study analyzed the clinical data of pNET patients undergoing surgical treatment, in order to provide reference for the surgical treatment of pNET. Methods: The clinical data of 118 patients with well-differentiated pNET undergoing minimally invasive surgery admitted by the Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center from September 2018 to July 2022 were retrospectively analyzed. The patients were divided into robot group (n=17) and laparoscopic group (n=101) according to the minimally invasive operation mode. According to the surgical resection mode, they were divided into regular resection group (n=86) and local resection group (n=32). The clinical data of operation and postoperation were collected and analyzed. Results: Of the 118 patients who underwent minimally invasive surgery on pNET included in this study, 17 were in the robot group, and 101 were in the laparoscopic group. There were 32 cases in local resection group and 86 cases in regular resection group. There was no significant difference between robot group and laparoscopic group in operation time and intraoperative bleeding (P>0.05). The operation time of local resection group [(145.3±55.5) min] was significantly shorter compared with regular resection group [(247.4±94.7) min](P 0.05). The incidence of postoperative b-pancreatic fistula was higher in the local resection group than in the regular resection group (P

Neuroendocrine neoplasm (NEN) is a group of heterogeneous malignancies arising from neuroendocrine cells and peptidergic neurons. According to its cell differentiation, NEN can be divided into two distinct groups as well-differentiated neuroendocrine tumor (NET) and poorly-differentiated neuroendocrine carcinoma (NEC). For advanced NEN, medication is the preferred treatment. In this article, we reviewed current clinical trials in medical treatment for NEN and aimed to provide treatment reference in clinical practice.

For decades, great strides have been made in the field of immunometabolism. A plethora of evidence ranging from basic mechanisms to clinical transformation has gradually embarked on immunometabolism to the center stage of innate and adaptive immunomodulation. Given this, we focus on changes in immunometabolism, a converging series of biochemical events that alters immune cell function, propose the immune roles played by diversified metabolic derivatives and enzymes, emphasize the key metabolism-related checkpoints in distinct immune cell types, and discuss the ongoing and upcoming realities of clinical treatment. It is expected that future research will reduce the current limitations of immunotherapy and provide a positive hand in immune responses to exert a broader therapeutic role. Highlights: 1. Attempting to delineate the complex and multidimensional interplays between metabolites (or metabolic enzymes) and predominant immune cell populations. 2. Metabolic checkpoints of immune cells are described and the contribution of these metabolic targets to determine the metabolic adaptations of distinct immune cells in specific tissue environments is emphasized. 3. Proposed cancer-immunometabolism subcycle, enriching the theoretical foundation of the cancer-immunology field. 4. Metabolism-induced disturbances in the acid-base balance of the tumor microenvironment have non-redundant effects on immunotherapy. 5. Pending challenges and clinical concerns in metabolic insights were addressed. [ABSTRACT FROM AUTHOR]

Background: The incidence of postoperative pancreatic fistula (POPF) following enucleation is high, and prophylactic pancreaticojejunostomy (PPJ) is frequently performed. Minimally invasive enucleation (MEN) has been demonstrated to be safe and feasible, leaving most enucleation wounds exposed. Methods: The clinical data of 40 patients who underwent open enucleation with PPJ at our center between 2012 and 2021 were compared with those of 80 patients who underwent MEN. Results: The MEN group had better outcomes than the PPJ group in terms of intraoperative bleeding (50.0 versus 100.0 mL), postoperative semi‐liquid diet recovery (2.0 versus 5.0 days), and postoperative length of stay (7.7 versus 12.5 days). While the MEN group had higher rates of complex enucleation (60.0% versus 40.0%), main pancreatic duct repair (32.5% versus 10.0%), discharge with drains (48.8% versus 25.0%), and grade B POPFs (47.5% versus 17.5%). Both surgical methods effectively preserved pancreatic function; however, two patients in the PPJ group experienced severe haemorrhaging and died. Additionally, during the follow‐up period, gastrointestinal bleeding was found and discomfort in the surgical area was reported. Conclusion: Pancreatic enucleation combined with PPJ should be avoided, and although a biochemical or grade B POPF may develop after MEN, it can be compensated for by preserving pancreatic function and ensuring a good long‐term quality of life in the patients. [ABSTRACT FROM AUTHOR]

Abstract Background Methyl-CpG binding domain protein 1 (MBD1), which couples DNA methylation to transcriptional repression, has been implicated in transcriptional regulation, heterochromatin formation, genomic stability, cell cycle progression and development. It has also been proven that MBD1 is involved in tumor development and progression. However, whether MBD1 is involved in tumorigenesis, especially in gallbladder cancer, is totally unknown. Methods Human GBC-SD and SGC996 cells were used to perform experiments. Invasion, wound healing and colony formation assays were performed to evaluate cell viability. A CCK-8 assay was performed to assess gallbladder cancer cell viability after gemcitabine treatment. Western blot analysis was used to evaluate changes in protein expression. Human gallbladder cancer tissues and adjacent nontumor tissues were subjected to immunohistochemical staining to detect protein expression. Results We found that MBD1 expression was significantly upregulated in gallbladder cancer tissues compared with that in surrounding normal tissues according to immunohistochemical analysis of 84 surgically resected gallbladder cancer specimens. These data also indicated that higher MBD1 expression was correlated with lymph node metastasis and poor survival in gallbladder cancer patients. Overexpression and deletion in vitro validated MBD1 as a potent oncogene promoting malignant behaviors in gallbladder cancer cells, including invasion, proliferation and migration, as well as epithelial–mesenchymal transition. Studies have demonstrated that epithelial–mesenchymal transition is common in gallbladder cancer, and it is well known that drug resistance and epithelial–mesenchymal transition are very closely correlated. Herein, our data show that targeting MBD1 restored gallbladder cancer cell sensitivity to gemcitabine chemotherapy. Conclusions Taken together, the results of our study revealed a novel function of MBD1 in gallbladder cancer tumor development and progression through participation in the gallbladder cancer epithelial–mesenchymal transition program, which is involved in resistance to gemcitabine chemotherapy. Thus, MBD1 may be a potential therapeutic target for gallbladder cancer.