Abstract Adenosquamous carcinoma of the duodenum is a malignant tumor consisting of adenocarcinoma and components of squamous cell carcinoma, which is extremely rare. There are very few available case reports, and its clinicopathological features and treatment strategies remain difficult to elucidate. We describe a patient diagnosed with adenosquamous carcinoma of the duodenum and perform a literature review of reported cases. A 55-year-old male patient presented with a history of jaundice and fever with pruritus and clay-colored stools. Preoperative investigations suggested an elevation of transaminase, bilirubin, and tumor markers. Enhanced MRI of the abdomen suggested a mass in the descending portion of duodenum and a mass was visible in the pancreatic region, with no distant metastases. Endoscopy of the upper gastrointestinal tract revealed an infiltrative growth mass invading the duodenal papilla in the descending part of the duodenum. The patient underwent Whipple procedure. Histopathological and immunohistochemical examination confirmed adenosquamous carcinoma of the duodenum. Although R0 resection was performed, the cancer developed hepatic metastases 2 months after surgery and the patient died 4 months after surgery.
The individual variation of carcinogenesis and drug response is influenced by the absorption, distribution, metabolism, and excretion (ADME) of drugs. The utilization of signatures derived from ADME-related genes holds potential for predicting prognosis and treatment response across diverse cancer types. Further investigation is required to completely understand the role of ADME-associated genes in breast cancer. A signature was constructed through the application of a least absolute shrinkage and selection operator regression model, employing prognostic differentially expressed genes found in both cancer tissue and normal tissue. To assess the robustness of the signature, verification analyses were carried out. RT-qPCR was utilized for the validation of gene expression related to risk. Subsequently, a nomogram was developed to enhance the clinical utility of our prognostic tool. The ADME signature, comprising four genes, was established and exhibited a robust association with the prognoses of individuals diagnosed with breast cancer. The nomogram was created by fusing the clinicopathological characteristics with the ADME signature. The ADME signature demonstrated remarkable superiority when compared to the performance of the other individual predictors. Additionally, the analysis of the immune microenvironment revealed that the ImmuneScores of the low-risk group were elevated. The variation in both the infiltration of immune cells and the expression of immune-related genes in the tissues differed among the two groups. For patients with breast cancer, the utilization of ADME signatures as biomarkers presents a significant reference point for prognosis and individualized treatment strategies.
Maslinic acid (MA) is a triterpenoid compound of natural abundance in olive plants possessing numerous biological activities. The effect and molecular mechanism of MA on pancreatic cancer cells remain elusive. Here, we explored the anti-tumor activity of MA on human pancreatic cancer cells and the potential underlying molecular mechanism. The anti-cancer effects of MA on whole-cell processes, including proliferation, migration, and invasion in pancreatic cancer cells, were systematically assessed by colony formation, transwell, and migration assays. The search for potential therapeutic targets was achieved via transcriptomics and proteomics analyses. MA was demonstrated to inhibit the proliferation, migration, and invasion of PANC-1 and Patu-8988 cells, but induced apoptosis of these cells. Several key candidate genes and proteins of functional relevance for the anti-tumor activity of MA were identified through the association analysis of transcriptomics and proteomics. To our knowledge, this is the first transcription and proteomics-based comprehensive analysis of the mechanism of MA against pancreatic cancer. The findings demonstrate that MA holds promise as a therapeutic drug for managing pancreatic cancer.
Objective To observe the association between homocysteine (Hcy)level and low limb vascular disease(LLVD) in newly-diagnosed type 2 diabetic patients. Methods The study subjects were divided into three groups : control group (NO , newly-diagnosed type 2 diabetes group without peripheral artery disease (T2DM) and peripheral artery disease with newly-diagnosed type 2 diabetes group (T2DM+LLVD). Both Hcy and the ankle- brachial index(ABI) were measured in three groups. Results Compared with NC group, clinical parameters of body mass index,waist-to-hip ratio, systolic blood pressure, total cholesterol(TC) , triglycerides(TG) ,low density lipoprotein-cholesterol(LDL-C) ,and glycated hemoglobin A1C (HbA_1c) increased markedly,and the content of high density lipoprotein-cholesterol (HDL-C) was markedly lower in both T2DM and T2DM+LLVD groups. In T2DM + LLVD group the contents of Hcy,LDL-C and HbA_1 c were markedly higher than in T2DM group,but the content of HDL-C decreased significantly. Hcy was independently associated with the development of peripheral artery disease in newly-diagnosed type 2 diabetic patients by logisitic regression analysis. Conclusions Increased Hcy is an independent risk factor for peripheral artery disease in newly-diagnosed type 2 diabetes.
The mTOR signaling pathway is abnormally activated in pancreatic cancer and is related to tumor glucose metabolism. However, its specific regulation mechanism is still unclear. Therefore, this study aims to investigate whether Sestrin2 affects the glucose metabolism of pancreatic cancer by modulating mTOR signal and then affects its biological behavior. We have observed that l -leucine can promote the proliferation of pancreatic cancer cells and increase the expression of Sestrin2 and p-mTOR proteins. In order to further study the role of Sestrin2 and mTOR signaling in pancreatic cancer, we conducted Sestrin2 overexpression and mTOR pharmacological inhibition experiments. We found that Sestrin2 overexpression can increase glycolysis of pancreatic cancer cells and promote their proliferation. This effect can be eliminated by mTOR inhibitors. Finally, we found that Sestrin2 knockdown could inhibit the growth of pancreatic cancer in vivo . In conclusion, these findings suggest that Sestrin2 may promote the occurrence and development of pancreatic cancer through mTOR signaling.
Variants on chromosome 1p13 have been associated with coronary artery disease and acute myocardial infarction risk in different ethnic groups. The present study aimed to investigate the association between 1p13 polymorphisms and the development of peripheral artery disease (PAD) in a Chinese population with type 2 diabetes mellitus.1p13 polymorphisms, rs599839, rs646776 and rs12740374, were assessed in a cohort of 882 type 2 diabetes mellitus patients including 440 type 2 diabetes mellitus patients with PAD (DM + PAD group) and 442 patients without PAD (DM group). Genotyping was carried out using TaqMan assay.Compared with the DM group, the frequencies of the minor G allele of both rs599839 and rs646776 and the minor T allele of rs12740374 decreased (P = 0.013, P = 0.019 and P = 0.005, respectively), and the frequencies of rs599839 AG + GG, rs646776 AG + GG and rs12740374 CT+TT genotypes were statistically significantly decreased as well (P = 0.017, P = 0.011 and P = 0.007, respectively) in the dominant model in the DM + PAD group than in the DM group. Multivariate unconditional logistic regression analyses adjusted for age, glycated hemoglobin, triglyceride, low-density lipoprotein cholesterol, smoking, hypertension, diabetes duration, coronary heart disease and cerebral infarction showed that the genotypic distribution of rs599839 AG + GG, rs646776 AG + GG and rs12740374 CT + TT remained statistically different between the DM and DM + PAD group (P = 0.014, P = 0.003 and P = 0.004, respectively). The frequencies of haplotype GGT were statistically significantly different between groups (P = 0.08).The present study strongly supports that genotypes of rs599839, rs646776 and rs12740374 on 1p13 are protective factors for diabetic PAD in a Chinese population. Haplotype GGT generated by rs599839, rs646776 and rs12740374 might also decrease the risk of the disease.
ACT001 is widely used for the treatment of glioblastomas, breast cancers, and leukemic and the mechanism underlying the effect is anti-inflammatory. However, whether ACT001 has any effects on acute respiratory distress syndrome (ARDS) is not clear. To investigate whether ACT001 helps to reduce mortality and pneumonedema after ARDS, and explore whether the mechanism is related to balance autophagy and inflammatory response. In this study, a rat model based on CLP was used to explore the potency of ACT001 in ARDS. The expression of the autophagy-related protein, lung injuries, cytokines, and inflammatory-related protein was assessed. Compared with CLP group, ACT001 improved the survival rate, and lung wet-to-dry weight ratio. ACT001 activates autophagy, which is involved in the pathophysiologic process of sepsis, balancing the cytokine excessive release and lung injury in ARDS. ACT001 reduces mortality through improved autophagy and attenuates inflammation after ARDS.
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