Adult craniopharyngioma concomitant with unruptured intracranial aneurysms: incidence, risk factors, and treatment strategies.

OBJECTIVE: Concomitant unruptured intracranial aneurysms (UIAs) in patients with craniopharyngioma (CP) pose a challenge for surgical management. This study presents the largest known single-institution case series to investigate the incidence of UIA in CP patients, with the aim of exploring the potential risk factors for the occurrence of UIA in CP patients and proposing treatment strategies. METHODS: The authors retrospectively reviewed the records of 289 adult CP patients treated in their department between January 2020 and August 2022. Routine CT angiography (CTA) was performed preoperatively in all cases. Logistic regression analysis was used to identify the risk factors for the occurrence of aneurysms. Aneurysms with the following characteristics were considered to have a high risk of intraoperative rupture and required treatment before tumor resection: 1) preliminary assessment of a high inherent risk of rupture (risk of rupture in their natural progression); and 2) location close to the tumor, irregular shape, and/or growth toward the tumor, even if the preliminary assessment indicated a low inherent risk of rupture. RESULTS: Twenty-three of 289 CP patients (7.96%, 95% CI 5.36-11.6) were diagnosed with both CP and UIA (CP-UIA). Hypertension (OR 4.148, 95% CI 1.654-10.398; p = 0.002), estrogen deficiency (OR 3.097, 95% CI 1.241-7.731; p = 0.015), and suprasellar tumor (OR 4.316, 95% CI 1.596-11.67; p = 0.004) were independent risk factors for intracranial aneurysms (IAs) in CP patients. Among the 23 CP-UIA patients, 6 (26.1%) with a high risk of aneurysm rupture underwent endovascular treatment (EVT) before tumor resection. Seventeen (73.9%) patients with a low risk of rupture underwent tumor resection only. CONCLUSIONS: The incidence rate of IA in patients with CP was higher than that in the general population. Routine preoperative CTA is advised for adult CP patients. Patients with papillary CP exhibited a higher proportion of CP-UIAs. Older age, hypertension, estrogen deficiency, and suprasellar tumor were independent risk factors for the occurrence of IAs in CP patients. IAs in CP patients are predominantly located in the C6 and C7 segments of the internal carotid artery and are often suitable for EVT. When treating CP-UIAs, tumor-related symptoms, risk of aneurysm rupture, the spatial relationship between the tumor and IA, and the approach for tumor resection should be considered.

Clinical effects of neuroendoscopic infratentorial supracerebellar approach surgical technique for resecting pineal tumors: a retrospective study.

OBJECTIVE: Pineal tumors are relatively rare central nervous system lesions with a predilection for the pediatric population. This article aims to explore the clinical effects of neuroendoscopic infratentorial supracerebellar approach for resecting tumors in the pineal area. METHODS: This is a retrospective study that included patients who underwent neuroendoscopic infratentorial supracerebellar approach to resect nine tumors in the pineal area at the Department of Neurosurgery of the Second Hospital of Lanzhou University from December 2017 to October 2023. RESULTS: The results of postoperative MRI revealed that all tumors were resected. Five patients received postoperative radiotherapy, three patients received radiotherapy along with chemotherapy, and one patient received neither radiotherapy nor chemotherapy. The pathological results showed that four patients were diagnosed with germinoma, two patients with teratoma, two patients with mixed germ cell tumors, and one patient with central neurocytoma. After surgery, one patient developed psychiatric symptoms, two patients developed binocular upward vision and diplopia, and one patient developed unstable walking and diplopia. With a follow-up of 1.7-4.8 years, all nine patients lived normally. Furthermore, none of them had tumor recurrence or death. CONCLUSION: The simple neuroendoscopic infratentorial supracerebellar approach has some safety and efficacy. It is suitable for tumors in the pineal region where the disease is mainly located below the Galen vein complex.

α5-nAChR/ADAM10 signaling mediates nicotine-related cutaneous melanoma progression via STAT3 activation.

Skin cutaneous melanoma (SKCM) is the skin malignancy with the highest mortality rate, and its morbidity rate is on the rise worldwide. Smoking is an independent marker of poor prognosis in melanoma. The α5-nicotinic acetylcholine receptor (α5-nAChR), one of the receptors for nicotine, is involved in the proliferation, migration and invasion of SKCM cells. Nicotine has been reported to promote the expression of a disintegrin and metalloproteinase 10 (ADAM10), which is the key gene involved in melanoma progression. Here, we explored the link between α5-nAChR and ADAM10 in nicotine-associated cutaneous melanoma. α5-nAChR expression was correlated with ADAM10 expression and lower survival in SKCM. α5-nAChR mediated nicotine-induced ADAM10 expression via STAT3. The α5-nAChR/ADAM10 signaling axis was involved in the stemness and migration of SKCM cells. Furthermore, α5-nAChR expression was associated with ADAM10 expression, EMT marker expression and stemness marker expression in nicotine-related mice homograft tissues. These results suggest the role of the α5-nAChR/ADAM10 signaling pathway in nicotine-induced melanoma progression.

PKP2 induced by YAP/TEAD4 promotes malignant progression of gastric cancer.

Gastric cancer (GC) exhibits significant heterogeneity and its prognosis remains dismal. Therefore, it is essential to investigate new approaches for diagnosing and treating GC. Desmosome proteins are crucial for the advancement and growth of cancer. Plakophilin-2 (PKP2), a member of the desmosome protein family, frequently exhibits aberrant expression and is strongly associated with many tumor types' progression. In this study, we found upregulation of PKP2 in GC. Further correlation analysis showed a notable association between increased PKP2 expression and both tumor stage and poor prognosis in individuals diagnosed with gastric adenocarcinoma. In addition, our research revealed that the Yes-associated protein1 (YAP1)/TEAD4 complex could stimulate the transcriptional expression of PKP2 in GC. Elevated PKP2 levels facilitate activation of the AKT/mammalian target of rapamycin signaling pathway, thereby promoting the malignant progression of GC. By constructing a mouse model, we ultimately validated the molecular mechanism and function of PKP2 in GC. Taken together, these discoveries suggest that PKP2, as a direct gene target of YAP/TEAD4 regulation, has the potential to be used as an indication of GC progression and prognosis. PKP2 is expected to be a promising therapeutic target for GC.

Gut microbiota composition and metabolic characteristics in patients with Craniopharyngioma.

BACKGROUND: Emerging evidence suggests that the gut microbiota is associated with various intracranial neoplastic diseases. It has been observed that alterations in the gut microbiota are present in gliomas, meningiomas, and pituitary neuroendocrine tumors (Pit-NETs). However, the correlation between gut microbiota and craniopharyngioma (CP), a rare embryonic malformation tumor in the sellar region, has not been previously mentioned. Consequently, this study aimed to investigate the gut microbiota composition and metabolic patterns in CP patients, with the goal of identifying potential therapeutic approaches. METHODS: We enrolled 15 medication-free and non-operated patients with CP and 15 healthy controls (HCs), conducting sequential metagenomic and metabolomic analyses on fecal samples to investigate changes in the gut microbiota of CP patients. RESULTS: The composition of gut microbiota in patients with CP compared to HCs show significant discrepancies at both the genus and species levels. The CP group exhibits greater species diversity. And the metabolic patterns between the two groups vary markedly. CONCLUSIONS: The gut microbiota composition and metabolic patterns in patients with CP differ significantly from the healthy population, presenting potential new therapeutic opportunities.

Positive GLI1/INHBA feedback loop drives tumor progression in gastric cancer.

GLI1, a key transcription factor of the Hedgehog (Hh) signaling pathway, plays an important role in the development of cancer. However, the function and mechanisms by which GLI1 regulates gene transcription are not fully understood in gastric cancer (GC). Here, we found that GLI1 induced the proliferation and metastasis of GC cells, accompanied by transcriptional upregulation of INHBA. This increased INHBA expression exerted a promoting activity on Smads signaling and then transcriptionally activated GLI1 expression. Notably, our results demonstrate that disrupting the interaction between GLI1 and INHBA could inhibit GC tumorigenesis in vivo. More intriguingly, we confirmed the N6-methyladenosine (m6A) activation mechanism of the Helicobacter pylori/FTO/YTHDF2/GLI1 pathway in GC cells. In conclusion, our study confirmed that the GLI1/INHBA positive feedback loop influences GC progression and revealed the mechanism by which H. pylori upregulates GLI1 expression through m6A modification. This positive GLI1/INHBA feedback loop suggests a novel noncanonical mechanism of GLI1 activity in GC and provides potential therapeutic targets for GC treatment.

Targeted ferritinophagy in gastrointestinal cancer: from molecular mechanisms to implications.

Gastrointestinal cancer is a significant global health burden, necessitating the development of novel therapeutic strategies. Emerging evidence has highlighted the potential of targeting ferritinophagy as a promising approach for the treatment of gastrointestinal cancer. Ferritinophagy is a form of selective autophagy that is mediated by the nuclear receptor coactivator 4 (NCOA4). This process plays a crucial role in regulating cellular iron homeostasis and has been implicated in various pathological conditions, including cancer. This review discusses the molecular mechanisms underlying ferritinophagy and its relevance to gastrointestinal cancer. Furthermore, we highlight the potential therapeutic implications of targeting ferritinophagy in gastrointestinal cancer. Several approaches have been proposed to modulate ferritinophagy, including small molecule inhibitors and immunotherapeutic strategies. We discuss the advantages and challenges associated with these therapeutic interventions and provide insights into their potential clinical applications.

miR-200b-3p accelerates progression of pituitary adenomas by negatively regulating expression of RECK.

MicroRNA (miR)-200b-3p has been associated with many tumors, but its involvement in pituitary adenoma is unclear. This study investigated the molecular mechanism underlying miR-200b-3p regulation in pituitary adenomas to provide a theoretical basis for treatment. Bioinformatics was used to analyze pituitary adenoma-related genes and screen new targets related to RECK and miRNA. As well, the relationship between miR-200b-3p and RECK protein was verified using a double-luciferase reporter gene assay. The expression of miR-200b-3p in clinical samples was analyzed by in situ hybridization. Transfection of the miR-200b-3p inhibitor and small interfering-RECK (si-RECK) was verified by qPCR. GH3 cell viability and proliferation were detected using CCK8 and EdU assays. Apoptosis was detected by flow cytometry and western blotting. Wound healing and Transwell assays were used to detect cell migration and invasion. The effects of miR-200b-3p and RECK on GH3 cells were verified using salvage experiments. miR-200b-3p was highly expressed in pituitary tumor tissue. Inhibitors of miR-200b-3p inhibited cell proliferation promoted cell apoptosis, inhibited invasion and migration, and inhibited the expression of matrix metalloproteinases. Interestingly, miR-200b-3p negatively regulated RECK. The expression of RECK in pituitary adenoma tissues was lower than that in neighboring tissues. Si-RECK rescued the function of miR-200b-3p inhibitors in the above cellular behaviors, and miR-200b-3p accelerated the development of pituitary adenoma by negatively regulating RECK expression. In summary, this study investigated the molecular mechanism by which miR-200b-3p regulates the progression of pituitary adenoma through the negative regulation of RECK. The findings provide a new target for the treatment of pituitary adenoma.

Mechanism of metal ion-induced cell death in gastrointestinal cancer.

Gastrointestinal (GI) cancer is one of the most severe types of cancer, with a significant impact on human health worldwide. Due to the urgent demand for more effective therapeutic strategies against GI cancers, novel research on metal ions for treating GI cancers has attracted increasing attention. Currently, with accumulating research on the relationship between metal ions and cancer therapy, several metal ions have been discovered to induce cell death. In particular, the three novel modes of cell death, including ferroptosis, cuproptosis, and calcicoptosis, have become focal points of research in the field of cancer. Meanwhile, other metal ions have also been found to trigger cell death through various mechanisms. Accordingly, this review focuses on the mechanisms of metal ion-induced cell death in GI cancers, hoping to provide theoretical support for further GI cancer therapies.

Myricetin Induces Ferroptosis and Inhibits Gastric Cancer Progression by Targeting NOX4.

Ferroptosis holds great potential as a therapeutic approach for gastric cancer (GC), a prevalent and deadly malignant tumor associated with high rates of incidence and mortality. Myricetin, well-known for its multifaceted biomedical attributes, particularly its anticancer properties, has yet to be thoroughly investigated regarding its involvement in ferroptosis. The aim of this research was to elucidate the impact of myricetin on ferroptosis in GC progression. The present study observed that myricetin could trigger ferroptosis in GC cells by enhancing malondialdehyde production and Fe2+ accumulation while suppressing glutathione levels. Mechanistically, myricetin directly interacted with NADPH oxidase 4 (NOX4), influencing its stability by inhibiting its ubiquitin degradation. Moreover, myricetin regulated the inhibition of ferroptosis induced by Helicobacter pylori cytotoxin-associated gene A (CagA) through the NOX4/NRF2/GPX4 pathway. In vivo experiments demonstrated that myricetin treatment significantly inhibited the growth of subcutaneous tumors in BALB/c nude mice. It was accompanied by increased NOX4 expression in tumor tissue and suppression of the NRF2/GPX4 antioxidant pathway. Therefore, this research underscores myricetin as a novel inducer of ferroptosis in GC cells through its interaction with NOX4. It is a promising candidate for GC treatment.

A Novel Signature Based on m6A Regulator-Mediated Genes Along Glycolytic Pathway Predicts Prognosis and Immunotherapy Responses of Gastric Cancer Patients.

N6-methyladenosine (m6A) modification is involved in many aspects of gastric cancer (GC). Moreover, m6A and glycolysis-related genes (GRGs) play important roles in immunotherapeutic and prognostic implication of GC. However, GRGs involved in m6A regulation have never been analyzed comprehensively in GC. Herein, the study aims to identify and validate a novel signature based on m6A-related GRGs in GC patients. Therefore, a m6A-related GRGs signature is established, which can predict the survival of patients with GC and remain an independent prognostic factor in multivariate analyses. Clinical significance of the model is well validated in internal cohort and independent validation cohort. In addition, the expression levels of risk model-related GRGs in clinical samples are validated. Consistent with the database results, all model genes are up-regulated in expression except DCN. After regrouping the patients based on this risk model, the study can effectively distinguish between them in respect to immune-cell infiltration microenvironment and immunotherapeutic response. Additionally, candidate drugs targeting risk model-related GRGs are confirmed. Finally, a nomogram combining risk scores and clinical parameters is created, and calibration plots show that the nomogram can accurately predict survival. This risk model can serve as a reliable assessment tool for predicting prognosis and immunotherapeutic responses in GC patients.

Risk factors for cerebrospinal fluid leak after extended endoscopic endonasal surgery for adult patients with craniopharyngiomas: a multivariate analysis of 364 cases.

OBJECTIVE: Over the last decade, the extended endoscopic endonasal approach (EEEA) has evolved as a credible surgical alternative for removing craniopharyngiomas. However, postoperative cerebrospinal fluid (CSF) leak remains one of the most pressing concerns. Craniopharyngiomas often invade the third ventricle, resulting in a higher rate of third ventricle opening after surgery and potentially increasing the risk of postoperative CSF leak. Identifying the risk factors associated with CSF leak after EEEA for craniopharyngiomas may have more clinical value. Nevertheless, there is a lack of systematic studies on the topic. Previous studies yielded inconsistent results, probably due to heterogeneous pathologies or small sample sizes. Hence, the authors present the largest known single-institution case series of the use of purely EEEA for craniopharyngiomas to systematically study the risk factors for postoperative CSF leak. METHODS: The authors retrospectively reviewed 364 cases of adult patients with craniopharyngiomas who were treated at their institution from January 2019 to August 2022, and they analyzed the risk factors for postoperative CSF leak. RESULTS: The overall rate of postoperative CSF leak was 4.7%. In the univariate analysis, larger dural defect size (OR 8.293, 95% CI 3.711-18.534, p < 0.001) and lower preoperative serum albumin level (OR 0.812, 95% CI 0.710-0.928, p = 0.002) were associated with higher rates of postoperative CSF leak. Predominantly cystic tumors (OR 0.325, 95% CI 0.122-0.869, p = 0.025) were linked to decreased risk of postoperative CSF leak. However, postoperative lumbar drainage (OR 2.587, 95% CI 0.580-11.537, p = 0.213) and third ventricle opening (OR 1.718, 95% CI 0.548-5.384, p = 0.353) were not related to postoperative CSF leak. In the multivariate analysis, larger dural defect size (OR 8.545, 95% CI 3.684-19.821, p < 0.001) and lower preoperative serum albumin level (OR 0.787, 95% CI 0.673-0.919, p = 0.002) were identified as independent risk factors for postoperative CSF leak. CONCLUSIONS: The authors' repair technique yielded a reliable reconstructive outcome for high-flow CSF leak in EEEA for craniopharyngioma. Lower preoperative serum albumin level and larger dural defect size were identified as independent risk factors for postoperative CSF leak, potentially providing new insights into minimizing the risk of postoperative CSF leak. Third ventricle opening was not associated with postoperative CSF leak. Lumbar drainage may not be necessary for high-flow intraoperative leak, but this finding may require validation with a prospective randomized controlled trial in the future.

PLEK2 mediates metastasis and invasion via α5-nAChR activation in nicotine-induced lung adenocarcinoma.

Evidence has shown a strong relationship between smoking and epithelial mesenchymal transition (EMT). α5-nicotinic acetylcholine receptor (α5-nAChR) contributes to nicotine-induced lung cancer cell EMT. The cytoskeleton-associated protein PLEK2 is mainly involved in cytoskeletal protein recombination and cell stretch migration regulation, which is closely related to EMT. However, little is known about the link between nicotine/α5-nAChR and PLEK2 in lung adenocarcinoma (LUAD). Here, we identified a link between α5-nAChR and PLEK2 in LUAD. α5-nAChR expression was correlated with PLEK2 expression, smoking status and lower survival in vivo. α5-nAChR mediated nicotine-induced PLEK2 expression via STAT3. α5-nAChR/PLEK2 signaling is involved in LUAD cell migration, invasion and stemness. Moreover, PLEK2 was found to interact with CFL1 in nicotine-induced EMT in LUAD cells. Furthermore, the functional link among α5-nAChR, PLEK2 and CFL1 was confirmed in mouse xenograft tissues and human LUAD tissues. These findings reveal a novel α5-nAChR/PLEK2/CFL1 pathway involved in nicotine-induced LUAD progression.

Mitochondrial subtype MB-G3 contains potential novel biomarkers and therapeutic targets associated with prognosis of medulloblastoma.

BACKGROUND: Medulloblastoma is the most common malignant brain tumor in children. There are four groups, each with different causal mutations, affected pathways and prognosis. Here, we investigated the role of mitochondria in medulloblastoma and whether there are differences between the different groups. METHODS: We compared the gene expression levels in the four different medulloblastoma groups (MB-WNT, MB-SHH, MB-G3 and MB-G4), with the focus on genes associated with mitochondria. We used several tools including Salmon, Tximeta, DESeq2, BiomaRt, STRING, Ggplot2, EnhancedVolcano, Venny 2.1 and Metscape. RESULTS: A total of 668 genes were differentially expressed and the most abundant genes were associated with cell division pathway followed by modulation of chemical synaptic transmission. We also identified several genes (ABAT, SOX9, ALDH5A, FOXM1, ABL1, NHLH1, NEUROD1 and NEUROD2) known to play vital role in medulloblastoma. Comparative expression analysis revealed OXPHOS complex-associated proteins of mitochondria. The most significantly expressed genes in the MB-SHH and MB-G4 groups were AHCYL1 and SFXN5 while PAICS was significantly upregulated in MB-WNT group. Notably, MB-G3 contained the most downregulated genes from the OXPHOS complexes, except COX6B2 which was strongly upregulated. CONCLUSIONS: We show the importance of mitochondria and compare their role in the four different medulloblastoma groups.

A Full View of Papillary Craniopharyngioma Based on Expanded Endonasal Approach: A Comprehensive Clinical Characterization of 101 Cases.

OBJECTIVE: The enlarged endonasal approach (EEA) has emerged as the preferred surgical procedure for removing craniopharyngiomas, due to its advantages of direct visualization and reduction of blind corners. However, owing to a low incidence of papillary CPs (PCPs) compared to adamantinomatous CPs (ACPs), a full view of PCP based on the EEA approach is limited. In this paper, the authors present the largest series to date analyzing the clinical characteristics based on the EEA approach for PCPs. METHODS: A retrospective review was conducted on 101 PCPs patients who underwent endoscopic endonasal surgery (EEA) and whose condition was confirmed via postoperative pathology. The PCPs were classified into three types based on MRI data and intraoperative findings from EEA: suprasellar/intra-suprasellar (3V floor intact) type (Type I), suprasellar/intra-suprasellar (3V floor invasive) type (Type II), and intra-third ventricle type (Type III). The general characteristics of the three types of tumors were summarized, and postoperative follow-up was conducted to record detailed information on changes in vision, endocrine replacement, tumor recurrence, and quality of life. RESULTS: Out of the 101 cases, 36 (36.64%) were classified as type I, 52 (51.49%) as type II, and 13 (12.87%) as type III. The mean age of type III patients was 40.46 ± 14.15 years old, younger than the other two types (p = 0.021). Headache (84.62%) and memory decline (61.54%) were prominent features in patients with type III (p = 0.029). Visual impairment was more common in type II (80.77%, p = 0.01). Gross total resection (GTR) was achieved in 91 patients (90.10%). There were no significant differences in GTR rates among the three types of tumors. There were significant differences in quality of life among the three types of PCP (p = 0.004), and type III presented with the highest rate of good postoperative quality of life (92.31%) based on the KPS score. Thirteen (12.87%) tumors recurred within a mean follow-up time of 38 (range, 8-63) months. Type II PCPs (OR 5.826, 95%CI 1.185-28.652, p = 0.030) and relapsed patients (OR 4.485, 95%CI 1.229-16.374, p = 0.023) were confirmed as independent risk factors for tumor recurrence. CONCLUSIONS: Most of the PCPs including intra-third ventricle PCPs can be safely and effectively removed through neuroendoscopy with EEA. Suprasellar/intra-suprasellar (third cerebral ventricle floor-invasive) type PCPs may have a worse postoperative quality of life compared to the other two types, and it may be a strong predictor of tumor recurrence.

α5-nAChR/STAT3/CD47 axis contributed to nicotine-related lung adenocarcinoma progression and immune escape.

OBJECTIVES: The CHRNΑ5 gene, which encodes the α5-nicotinic acetylcholine receptor (α5-nAChR), is related to lung cancer and nicotine addiction. Smoking is closely related to the immunosuppressive effect of macrophages. CD47, a phagocytosis checkpoint in macrophages, is a therapeutic target in various cancer types. Nevertheless, the relationship between α5-nAChR and CD47 in lung cancer is still unclear. METHODS AND RESULTS: The present study showed that α5-nAChR-mediated CD47 expression via STAT3 signaling, consequently leading to tumor progression and immune suppression in lung adenocarcinoma (LUAD). α5-nAChR expression was correlated with STAT3 expression, CD47 expression, smoking status and poor prognosis of LUAD in vivo. In vitro, α5-nAChR expression mediated the phosphorylation of STAT3, and phosphorylated STAT3 bound to the CD47 promoter and mediated CD47 expression. Downregulation of α5-nAChR and/or CD47 significantly reduced cell proliferation, migration, invasion, stemness and IL-10 expression, but increased TNF-α expression and phagocytosis of macrophages in LUAD. Furthermore, α5-nAChR/CD47 signaling contributed to the growth of subcutaneous xenograft tumors and liver metastasis of tumors in mice. CONCLUSION: The α5-nAChR/STAT3/CD47 axis contributed to the progression and immune escape of lung cancer and may be a potential target for LUAD immunotherapy.

Clinical Significance of Plasma Leptin and Its Receptors mRNA Expression in Craniopharyngiomas: A Prospective Study.

Craniopharyngioma (CP) is a benign tumor with a high rate of obesity and frequent recurrence. Moreover, the role of leptin/leptin receptors axis in obesity and the prognosis of CP is still unknown. Plasma leptin concentration and mRNA expression of leptin receptors were assessed in patients with CP. Moreover, the association between leptin/leptin receptors axis, weight-related outcomes, and progression-free survival (PFS) were explored in CP patients. Leptin receptors overexpressed in CP tumor tissue were compared to normal brain tissue (p < 0.05); compared to healthy controls, the concentration of leptin was elevated in CP with or without matched age, sex, and body mass index (BMI) (p < 0.05). The high plasma leptin level was an independent risk predictor for significant weight gain (adjusted odds ratio (aOR) = 2.29, and p = 0.030) and new-onset obesity (aOR = 6.64, and p = 0.016). High plasma leptin level (adjusted hazard ratio (aHR) = 3.74, and p = 0.011) and leptin receptor (LEPR) mRNA expression (aHR = 3.12, and p = 0.045) were independent risk factors for poor PFS in CP. Inappropriately elevated leptin relative to BMI and its failure to inhibit further weight gain indicate the existence of leptin resistance in patients with CP. Leptin and LEPR were independent predictors for PFS of patients with CP. The leptin/leptin receptors axis may be a potential therapeutic target for obesity in patients with CP.

Single-cell analysis of gastric signet ring cell carcinoma reveals cytological and immune microenvironment features.

Gastric signet ring cell carcinoma (GSRC) is a special subtype of gastric cancer (GC) associated with poor prognosis, but an in-depth and systematic study of GSRC is lacking. Here, we perform single-cell RNA sequencing to assess GC samples. We identify signet ring cell carcinoma (SRCC) cells. Microseminoprotein-beta (MSMB) can be used as a marker gene to guide the identification of moderately/poorly differentiated adenocarcinoma and signet ring cell carcinoma (SRCC). The upregulated differentially expressed genes in SRCC cells are mainly enriched in abnormally activated cancer-related signalling pathways and immune response signalling pathways. SRCC cells are also significantly enriched in mitogen-activated protein kinase and oestrogen signalling pathways, which can interact and promote each other in a positive feedback loop. SRCC cells are shown to have lower cell adhesion and higher immune evasion capabilities as well as an immunosuppressive microenvironment, which may be closely associated with the relatively poor prognosis of GSRC. In summary, GSRC exhibits unique cytological characteristics and a unique immune microenvironment, which may be advantageous for accurate diagnosis and treatment.

STAT5A modulates gastric cancer progression via upregulation of CD44.

OBJECTIVE: Signal transduction and transcriptional activator 5A (STAT5A), which has been reported to be frequently phosphorylated in tumors, plays pivotal roles in tumor progression. However, the role of STAT5A in gastric cancer (GC) progression and the downstream targets of STAT5A remain largely unknown. METHODS: The expression of STAT5A and CD44 were assessed. GC cells were treated with altered STAT5A and CD44 to evaluate their biological functions. Nude mice were given injections of genetically manipulated GC cells and growth of xenograft tumors and metastases was measured. RESULTS: The increased level of p-STAT5A is associated with tumor invasion and poor prognosis in GC. STAT5A promoted GC cell proliferation by upregulating CD44 expression. STAT5A directly binds to the CD44 promoter and promotes its transcription. CONCLUSIONS: The STAT5A/CD44 pathway plays a critical role in GC progression, promising potential clinical applications for improving treatment of GC.

Acetylcholine promotes chronic stress-induced lung adenocarcinoma progression via α5-nAChR/FHIT pathway.

Chronic stress significantly elevates the expression levels of various neurotransmitters in the tumour microenvironment, thereby promoting the cell growth and metastasis of lung adenocarcinoma (LUAD). However, the role of chronic stress in the progression of LUAD remains unclear. In this study, we found that chronic restraint stress increases the levels of the neurotransmitter acetylcholine (ACh), and the α5-nicotinic acetylcholine receptor (α5-nAChR) and decreased fragile histidine triad (FHIT) expression in vivo. Crucially, the increased ACh levels promoted LUAD cell migration and invasion via modulation of the α5-nAChR/DNA methyltransferase 1 (DNMT1)/FHIT axis. In a chronic unpredictable stress (CUMS) mouse model, chronic stress promotes tumour development, accompanied by changes in α5-nAChR, DNMT1, FHIT, and vimentin. Together, these findings reveal a novel chronic stress-mediated LUAD signalling pathway: chronic stress enforces lung adenocarcinoma cell invasion and migration via the ACh/α5-nAChR/FHIT axis, which could be a potential therapeutic target for chronic stress-related LUAD.