{"title":"Modulation of the tumor microenvironment by incretins and glucagon: Metabolic and immune mechanisms (Review).","authors":"Min Hu, Chang-Jun Jiang, Cheng Yi","doi":"10.3892/etm.2026.13178","DOIUrl":"10.3892/etm.2026.13178","url":null,"abstract":"<p><p>Glucagon-like peptide-1 receptor agonists (GLP-1RAs) and therapies targeting glucose-dependent insulinotropic polypeptide (GIP) have demonstrated efficacy in the treatment of type 2 diabetes (T2D) and obesity. GLP-1 and GIP are collectively referred to as incretins. The strong epidemiological link between T2D/obesity and cancer risk suggests that GLP-1 and GIP may serve a substantial role in tumor metabolism. The effects of incretin hormones and the counter-regulatory hormone glucagon (GCG) on tumor biology may have important implications for understanding tumor microenvironmental regulation and for informing cancer therapy. The present review summarizes the mechanisms by which these hormones influence the tumor microenvironment. Beyond the fundamental biology of incretins and GCG, the present review details how GLP-1RAs regulate immune cell functions, including the functions of T cells, neutrophils, natural killer cells and macrophages, to foster an antitumor immune microenvironment. Furthermore, the present review explores their roles in tumor metabolic reprogramming, affecting tumor cell cycle progression, extracellular matrix remodeling and mitochondrial function. Although preclinical and clinical data suggest that GLP-1RAs can reduce the incidence and progression of certain obesity-related cancer types, such as pancreatic and liver cancer, their impact on other malignancies, such as breast and endometrial cancer, remains controversial, with GLP-1RAs potentially exhibiting context-dependent pro-tumor effects. However, based on current evidence, the benefits of incretin hormones and GCG in cancer therapy appear to outweigh the risks. The present review suggests that targeting incretin and GCG signaling holds considerable promise in oncology, but necessitates a deeper mechanistic understanding and more careful patient stratification to fully harness its clinical utility while minimizing potential risks.</p>","PeriodicalId":94002,"journal":{"name":"Experimental and therapeutic medicine","volume":"32 1","pages":"183"},"PeriodicalIF":2.3,"publicationDate":"2026-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13200260/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148038680","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Zuoyan Wang, Yang Zhang, Kai Zhang, Xin Huang, Jianjun Peng
{"title":"Changes in iron metabolism after primary PCI in patients with STEMI and ischemia-reperfusion injury.","authors":"Zuoyan Wang, Yang Zhang, Kai Zhang, Xin Huang, Jianjun Peng","doi":"10.3892/etm.2026.13173","DOIUrl":"10.3892/etm.2026.13173","url":null,"abstract":"<p><p>Within the present study, the aim was to investigate the dynamic changes in iron metabolism parameters in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI) and to evaluate their association with the occurrence of ischemia-reperfusion injury (IRI). The present single-center, prospective observational study enrolled 68 patients with STEMI undergoing primary PCI from January to December 2024. Clinical characteristics, laboratory data and echocardiographic findings were collected. Patients were classified into IRI (n=30) and non-IRI (n=38) groups based on predefined IRI criteria. Venous blood samples were obtained pre- and post-PCI to measure ferritin, hepcidin, heme and heme oxygenase-1 (HO-1) levels. Statistical analyses were conducted to compare the changes in these iron metabolism indices between the two groups. Among the 68 enrolled patients, the incidence of IRI was 44.1%. Ferritin showed a significant increase post-PCI. The rise in ferritin and hepcidin was more pronounced in the IRI group compared with the non-IRI group. Although both IRI and non-IRI groups exhibited an upward trend in heme and HO-1 after PCI, the elevation in heme was higher in the IRI group in comparison with the HO-1. Differences in heme and HO-1 between IRI and non-IRI groups were not statistically significant. In conclusion, post-PCI rises in ferritin and hepcidin were more pronounced in patients with STEMI and IRI, while heme and HO-1 showed non-significant upward trends. These results indicated an association between altered iron/heme metabolism and IRI and therefore support further evaluation of ferritin/hepcidin as candidate biomarkers, pending validation in larger multicenter studies with multivariable adjustment.</p>","PeriodicalId":94002,"journal":{"name":"Experimental and therapeutic medicine","volume":"31 6","pages":"178"},"PeriodicalIF":2.3,"publicationDate":"2026-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13158925/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147936403","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Song Tang, Fan Zhuo, Zhenyu Chen, Huiqiang Cai, Weibin Zhang, Dan Chen
{"title":"Risk factors for anastomotic leakage after anterior resection of rectal cancer with preservation of the left colic artery.","authors":"Song Tang, Fan Zhuo, Zhenyu Chen, Huiqiang Cai, Weibin Zhang, Dan Chen","doi":"10.3892/etm.2026.13172","DOIUrl":"10.3892/etm.2026.13172","url":null,"abstract":"<p><p>Anastomotic leakage (AL) is a frequent and severe complication after anterior resection for rectal cancer. Most previous studies compared AL incidence between high and low ligation; however, the present study evaluated risk factors for AL in patients undergoing low ligation with preservation of the left colic artery, which has been associated with improved overall outcomes. Clinical data of patients with rectal cancer treated in the Second Department of General Surgery (Gastrointestinal Surgery) of The First Affiliated Hospital of Guangdong Pharmaceutical University (Guangzhou, China) between 2015 and 2024 were retrospectively reviewed, and patients meeting the inclusion and exclusion criteria were enrolled. Demographic characteristics and perioperative variables were collected. Differences between the AL group and the non-AL group were assessed using univariate analysis, and independent associations were identified using multivariate analysis to produce odds ratios (ORs). A total of 137 patients were included. Intergroup comparative tests showed significant differences in alcohol consumption, distance from the tumor to the anal verge and distance from the anastomosis to the anal verge between the AL group and the non-AL group (P<0.05). Multivariate analysis identified alcohol consumption (OR=9.845; P=0.0068) and distance from the tumor to the anal verge (OR=0.485; P=0.0368) as independent factors associated with AL. In conclusion, alcohol consumption and distance from the tumor to the anal verge are independent risk factors for AL after anterior resection with preservation of the left colic artery. The risk of AL is 9.845-fold higher in patients with alcohol consumption. For each 1 cm decrease in distance from the tumor to the anal verge, the risk of AL increases by 2.060-fold.</p>","PeriodicalId":94002,"journal":{"name":"Experimental and therapeutic medicine","volume":"31 6","pages":"177"},"PeriodicalIF":2.3,"publicationDate":"2026-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13158904/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147936454","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Xianchao Ding, Daoming Shi, Jieru Wang, Honghua Cai, Zhixin Yan
{"title":"Dexmedetomidine alleviates acute lung injury in humans by modulating the JAK1-STAT3 axis.","authors":"Xianchao Ding, Daoming Shi, Jieru Wang, Honghua Cai, Zhixin Yan","doi":"10.3892/etm.2026.13174","DOIUrl":"10.3892/etm.2026.13174","url":null,"abstract":"<p><p>The clinical efficacy of dexmedetomidine (Dex) in acute lung injury (ALI) and its related molecular mechanisms in human systems are poorly defined. In the present study the modulatory functions of Dex in human ALI were investigated, together with identification of the key molecular pathways involved. Human respiratory epithelial cell lines (A549 and BEAS2b) were cultured <i>in vitro</i> and categorized into four experimental groups: Untreated control (Con), Dex-treated, lipopolysaccharide (LPS)-treated, and both LPS + Dex-treated (LPS + Dex) groups. In BEAS-2B cells, inflammatory cytokine levels in the culture supernatant and cell viability were measured in all groups. In A549 cells, proliferative capacity and apoptosis rates were evaluated. The mRNA levels of caspase-3 and BCL-2, BAX within the BEAS-2B cells after LPS exposure were examined using reverse transcription-quantitative PCR. The levels of Janus kinase 1 (JAK1) and signal transduction and transcription activation 3 (STAT3) proteins, along with their phosphorylated forms in A549 cells, were analyzed via western blotting. Dex substantially suppressed LPS-mediated elevation of IL-1β, IL-6 and TNF-α. LPS-associated reductions in cell viability and proliferative activity were markedly attenuated following Dex treatment. It also lowered the LPS-induced increase in apoptotic cell populations. The upregulation of <i>caspase-3</i> and <i>BAX</i> gene expression after LPS stimulation in BEAS-2B cells was decreased by Dex treatment. The downregulation of BCL-2 gene expression after LPS stimulation in BEAS-2B cells was alleviated by Dex treatment. Moreover, Dex suppressed LPS-induced stimulation of the JAK1/STAT3 signaling cascade, as evidenced by downregulation of phosphorylated (p-)STAT3 and p-JAK1 in the A549 cells. Dex showed a protective effect against human ALI <i>in vitro</i> by reducing inflammatory responses, maintaining epithelial cell viability and decreasing apoptosis rate of epithelial cell. Modulation of the JAK1/STAT3 signaling cascade plays a crucial role in mediating these effects.</p>","PeriodicalId":94002,"journal":{"name":"Experimental and therapeutic medicine","volume":"31 6","pages":"179"},"PeriodicalIF":2.3,"publicationDate":"2026-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13158906/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147936392","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Bacterial meningoencephalitis following allogeneic hematopoietic stem cell transplantation: A case report and literature review.","authors":"Yajun Shi, Ying Han, Jinjin Chen, Heng Liu, Xiaofei Zhang, Rui Song, Xuejie Ma, Qiangsheng Feng, Tao Wu","doi":"10.3892/etm.2026.13169","DOIUrl":"10.3892/etm.2026.13169","url":null,"abstract":"<p><p>Bacterial meningoencephalitis (BME) following allogeneic hematopoietic stem cell transplantation (allo-HSCT) seriously affects the survival of recipients, though it is rarely reported. The present study reported on a 21-year-old man with Ph<sup>+</sup> acute B-lymphocytic leukemia who suddenly had a severe headache, fever and neuropsychiatric disturbances, and quickly became barely conscious at 483 days post-allo-HSCT. <i>Streptococcus pneumoniae</i> (<i>S. pneumoniae</i>) was found in cerebrospinal fluid (CSF) and blood, and the patient was eventually diagnosed with BME. The patient had received empirical antibacterial treatment with meropenem and vancomycin, as well as anti-inflammatory treatment with dexamethasone, before <i>S. pneumoniae</i> was detected in CSF. Headache and fever were quickly relieved. However, due to the delay of antibacterial treatment outside the hospital, the patient presented with severe neurological sequelae in an unconscious state. In conclusion, impaired immune reconstitution post-transplantation increases the risk of BME, a rapidly progressive disease with high disability and mortality rates. This case highlights that recipients presenting with central nervous system symptoms, early identification and diagnosis of BME, as well as empirical antibacterial treatment within 6 h before lumbar puncture, significantly improve the survival of patients.</p>","PeriodicalId":94002,"journal":{"name":"Experimental and therapeutic medicine","volume":"31 6","pages":"174"},"PeriodicalIF":2.3,"publicationDate":"2026-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13158722/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147936384","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Hypertensive crisis during embolization unveils occult catecholamine-secreting glomus jugulare tumor: A case report and management protocol.","authors":"Shucai Jiang, Ting Pan, Yanming Qu, Ke Gu, Guanjie Shang, Xiaoning Lan, Weihai Ning, Hongwei Zhang","doi":"10.3892/etm.2026.13170","DOIUrl":"10.3892/etm.2026.13170","url":null,"abstract":"<p><p>Glomus jugulare tumor (GJT) is a rare paraganglioma arising from neural crest cells. Although the majority of cases are non-functional, a minority of GJTs can secrete catecholamines. Such functional variants are frequently overlooked due to their rarity and may trigger perioperative crises. The present report documents a 53-year-old female patient with a giant occult secretory GJT (65 mm) presenting with prolonged cranial nerve deficits. Preoperative blood pressure was normal, but the patient developed hypertensive crisis (220/130 mmHg) during embolization. Biochemical tests confirmed catecholamine excess. Hemodynamic stability was maintained using calcium channel blockers without α-blockade after embolization. Tumor resection was performed within 72 h, achieving total resection without intraoperative crisis. Catecholamine levels normalized postoperatively with marked neurological improvement. The present case highlights the importance of recognizing occult secretory GJTs and discusses key management considerations regarding preoperative preparation, timing of surgery and anesthetic management. Increased awareness may improve diagnosis and optimize outcomes in these challenging cases.</p>","PeriodicalId":94002,"journal":{"name":"Experimental and therapeutic medicine","volume":"31 6","pages":"175"},"PeriodicalIF":2.3,"publicationDate":"2026-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13158724/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147936418","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Renal function-improving action of Pentadecyl®, a multifunctional triglyceride from <i>Aurantiochytrium limacinum</i>, in a mouse model of chronic kidney disease.","authors":"Keiko Yoneda-Yasui, Hiroshi Nango, Shinpei Fukuhara, Komugi Tsuruta, Koume Nagayama, Tsugumi Tanaka, Yasuko Sakata, Hideaki Ishikawa, Makoto Tsuboi, Hiroko Miyagishi, Yasuhiro Kosuge","doi":"10.3892/etm.2026.13168","DOIUrl":"10.3892/etm.2026.13168","url":null,"abstract":"<p><p>Pentadecyl<sup>®</sup>, derived from <i>Aurantiochytrium limacinum</i>, is a triglyceride primarily composed of odd-numbered fatty acids such as pentadecanoic acid (C15). Pentadecyl<sup>®</sup> improves glucose tolerance in a mouse model of type II diabetes and promotes collagen production in human skin cells. However, its effects on kidney failure and chronic kidney disease (CKD) remain unexplored. The present study examined the effects of continuous Pentadecyl<sup>®</sup> administration on renal dysfunction in 5/6-nephrectomized mice (5/6Nx mice), a well-established model of CKD. Pentadecyl<sup>®</sup> (0.2 g/l) was administered orally <i>via</i> a suspension in drinking water for 8 weeks. Although survival analysis using the log-rank test revealed no significant differences, a significant improvement in body weight gain was observed in 5/6Nx mice treated with Pentadecyl<sup>®</sup> compared with that in untreated controls, despite similar food and water intake. Renal function was assessed by measuring blood urea nitrogen (BUN) and serum creatinine (CRE) levels, both of which were significantly elevated in 5/6Nx mice. Notably, Pentadecyl<sup>®</sup> administration attenuated the increase in BUN and CRE levels. Histopathological analysis through hematoxylin and eosin staining revealed characteristic changes in the kidneys of 5/6Nx mice, including glomerular hypertrophy and tubular dilation. There was no significant difference in the mean glomerular and tubular areas between Pentadecyl<sup>®</sup>-treated mice and 5/6Nx mice. Nonetheless, distribution analyses descriptively showed fewer enlarged tubular profiles. These findings suggest that Pentadecyl<sup>®</sup> exerts protective effects against renal dysfunction in CKD, potentially contributing to the prevention of uremic complications.</p>","PeriodicalId":94002,"journal":{"name":"Experimental and therapeutic medicine","volume":"31 6","pages":"173"},"PeriodicalIF":2.3,"publicationDate":"2026-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13162748/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147936468","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Decitabine monotherapy for pediatric myelodysplastic syndrome: A case report.","authors":"Zhimin Fan, Nengwen Xu, Alicia Senin, Junyu Zhang","doi":"10.3892/etm.2026.13167","DOIUrl":"10.3892/etm.2026.13167","url":null,"abstract":"<p><p>The occurrence of myelodysplastic syndrome (MDS) in children is infrequently documented and most commonly manifests in the form of refractory cytopenia of childhood (RCC). The management of pediatric MDS remains controversial and involves primarily chemotherapy, immunosuppressive therapy (IST) and allogeneic hematopoietic stem cell transplantation (HSCT). However, therapeutic data for patients with RCC who are ineligible for either HSCT or IST are scarce. In the present case, the 8-year-old patient achieved disease stabilization following decitabine monotherapy, thereby suggesting a potential novel therapeutic avenue for children with low-risk chronic MDS or RCC.</p>","PeriodicalId":94002,"journal":{"name":"Experimental and therapeutic medicine","volume":"31 6","pages":"172"},"PeriodicalIF":2.3,"publicationDate":"2026-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13159052/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147936437","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Postmenopausal complete hydatidiform mole: A case report.","authors":"Emre Uysal","doi":"10.3892/etm.2026.13165","DOIUrl":"10.3892/etm.2026.13165","url":null,"abstract":"<p><p>Complete hydatidiform mole (CHM) cases occurring in the postmenopausal period are quite rare and may be delayed in diagnosis. In the present study, the case reported is of a 55-year-old postmenopausal woman (menopausal for 5 years) who presented with painless postmenopausal bleeding in March 2025, ongoing for ~1 month and was diagnosed with CHM. Transvaginal ultrasonography showed endometrial thickness of 28-mm and serum β-human chorionic gonadotropin (β-hCG) level of 187,240 mIU/ml. After ultrasound-guided curettage, the diagnosis of CHM was confirmed in histopathological examination. Since the patient was postmenopausal, laparoscopic hysterectomy and bilateral salpingo-oophorectomy were performed. Postoperative follow-up was performed in accordance with International Federation of Gynecology and Obstetrics (FIGO) guidelines; the protocol used (weekly β-hCG until negative, then monthly for 6 months) is fully consistent with the 2025 FIGO update. By December 2025, the patient had successfully finished the suggested follow-up regimen and was still in total remission with no signs of recurrence. In patients with abnormal uterine bleeding and high β-hCG levels in the postmenopausal period, gestational trophoblastic diseases should be considered in the differential diagnosis. Malignant complications can be prevented with early diagnosis and treatment.</p>","PeriodicalId":94002,"journal":{"name":"Experimental and therapeutic medicine","volume":"31 6","pages":"170"},"PeriodicalIF":2.3,"publicationDate":"2026-04-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13159050/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147936381","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}