Pilegaardcohen0922

Left-sided pancreatic adenocarcinoma (LPAC) has a poorer prognosis and has some distinct features compared to cancer of pancreatic head. A reliable model to predict the prognosis of LPAC following surgery is needed in clinical practice. Our study included 231 patients with resected LPAC from 3 Chinese pancreatic disease centers. Cox-regression analysis was conducted to identify independent risk factors of LAPC. Then we established a nomogram and performed C-index, receiver operating characteristic curve, calibration plot and decision curve analysis to assess its discrimination and calibration. As a result, CA19-9, surgical margin, tumor differentiation, lymph node metastasis, and postoperative adjuvant chemotherapy were identified as significant prognostic factors. selleck chemical Based on these predictors, a novel nomogram was constructed. The nomogram achieved high C-indexes in the training cohort (0.805) and validation cohort (0.719), which were superior than the AJCC-8 staging system and other nomograms. The area under curve of the nomogram for predicting patients survival at 1-, 2-, and 3-year in training cohort were more than 0.8. Kaplan-Meier survival curve for the subgroups stratified based on the nomogram showed a better separation than the AJCC-8 stage I, II, III, indicating a superior ability of risk stratification for our model. In summary, we constructed a nomogram which showed a better predictive ability for patients' survival with LPAC after surgical resection than the AJCC staging system and other predictive models. Our model would be helpful to discriminate high-risk LPAC and facilitate clinical decision making.Standard risk stratification (sRisk) guides clinical management in monoclonal gammopathy of undetermined significance (MGUS), smoldering multiple myeloma (SMM) and multiple myeloma (MM). Nonetheless, clinical results are considerably heterogeneous among patients with similar risk status. Blood and bone marrow samples from 276 MGUS, 56 SMM and 242 MM in regular clinical practice were analyzed at diagnosis by flow cytometry. Higher levels of aberrant circulating plasma cells (cPC) (> 0.0035% of leukocytes), combined with albumin, beta2-microglobuline and lactate-dehydrogenase levels, offered minimally-invasive risk stratification (RcPC) with results comparable to sRisk. RcPC and sRisk 10-year progression-free-survival (10y-PFS) rates were 93.8% vs. 95.1% for low-risk, 78.4% vs. 81.7% for intermediate-risk and 50.0% vs. 47.8% for high-risk MGUS; 58.3% vs. 57.8% low-risk, 44.4% vs. 45.8% intermediate-risk and 8.9% vs. 15.0% high-risk SMM; and 44.4% vs. 44.4% low-risk, 36.1% vs. 36.8% intermediate-risk, and 13.3% vs. 16.2% high-risk MM. Circulating-PC > 0.0035% vs. cPC 0.0035% identified MGUS, SMM and MM patients at higher risk of progression or death and predicted a cohort of patients that after relapse from stringent complete response showed shorter OS. These patients could benefit from early consolidation therapy, tandem ASCT or intensive maintenance.Gastric cancer (GC) is one of the most common malignant tumors worldwide and has high rates of morbidity and mortality. This study investigated the role of Krüppel-like factor 16 (KLF16) in GC. Real-time polymerase chain reaction, Western blotting, and immunohistochemistry were used to examine the expression of KLF16 in gastric cells and tissues. Gene overexpression and silencing were applied to study the involvement of KLF16 in GC cell growth and metastasis along with its underlying mechanism. The results indicate that KLF16 overexpression is significantly associated with nodal status, distant metastasis, staging, degree of differentiation, vascular invasion, and patient survival. Multivariate Cox proportional hazards regression model analysis revealed that the overexpression of KLF16 is an independent prognostic biomarker of GC. The in vitro study revealed that up-regulated KLF16 accelerates cell growth and metastasis, whereas the inhibition of KLF16 suppresses these cellular activities. The results of an animal study also indicated that the overexpression and silencing of KLF16 accelerate and repress xenograft proliferation and metastasis. Further studies of affected cell growth and metastasis revealed that KLF16 modulates the cell cycle and epithelial-mesenchymal transition through transcriptional regulation of microfibrillar-associated protein 5. Collectively, these results reveal that KLF16 overexpression is a potential prognostic biomarker and therapeutic target for the treatment of GC.Previous research indicated that mortalin overexpressed in breast cancer and contributed to carcinogenesis. Mortalin was also demonstrated to promote Epithelial-mesenchymal transition (EMT) and was considered as a factor for maintaining the stemness of the cancer stem cells. However, the underlying mechanisms about mortalin maintaining the stemness of breast cancer stem cells (BCSCs) remain unclear. Here, we identified that increased expression of mortalin in breast cancer was associated with poorer overall survival rate. Mortalin was elevated in breast cancer cell lines and BCSC-enriched populations. Additionally, knockdown of mortalin significantly inhibited the cell proliferation, migration and EMT, as well as sphere forming capacity and stemness genes expression. Further study revealed that mortalin promoted EMT and maintained BCSCs stemness via activating the Wnt/GSK3β/β-catenin signaling pathway in vivo and in vitro. Taken together, these findings unveiled the mechanism of mortalin in maintaining and regulating the stemness of BCSCs, and may offer novel therapeutic strategies for breast cancer treatment.Laryngeal squamous cell carcinoma (LSCC) is a common aggressive head and neck squamous cell carcinoma (HNSCC) and racial disparities have been reported to exist in it. However, its molecular mechanism and associated ethnic specificity are still unclear. Here, we leveraged mRNA expression data from 2 gene expression omnibus datasets (GSE142083 & GSE117005) of Chinese samples and the cancer genome atlas (TCGA) datasets of Caucasian samples to demonstrate the expression signature of LSCC. The GSE142083 dataset was used as the discovery set since it had 53 pairs of LSCC tissues and matched adjacent normal tissues, and the GSE117005 dataset was treated as the validation set with 5 pairs of tissues. Differential gene expression analysis and enrichment pathway analysis were performed. Besides, we employed weighted gene co-expression network analysis to identify hub genes in validated pathways. The TCGA datasets were used to evaluate ethnic specificity. Immunohistochemistry (IHC) was employed to further validate the hub gene. Overall, the IL-17 signaling pathway was significantly enriched for upregulated genes in two Chinese datasets while not in TCGA datasets; and IL17RC, MAPK3, S100A8, MMP3, CXCL8, and TNFA1P3 were hub genes regulating such pathway. Therein, IL17RC might be the most important one and the IHC results displayed that the IL17RC gene upregulated in the LSCC tissue. IL-17 signaling pathway has an ethnicity-specific effect in LSCC where it is upregulated in the Chinese while not in the Caucasians and IL17RC might play a key role. Targeting genes located in the IL-17 signaling pathway may be beneficial for Chinese LSCC patients.Malignant melanoma has a high mutational rate. As a result, resistance to current therapies is common. Consequently, there is an unmet medical need to develop novel therapies. Recent data suggest that branched-chain amino acid transaminase 1 (BCAT1) is overexpressed in multiple cancers, and such overexpressed BCAT1 is necessary for individual cancer progression. Therefore, BCAT1 appears to be a good target in cancer treatment. Additionally, because its expression in healthy tissues is highly restricted in adults and is limited to the brain, ovary, and placenta, BCAT1 is especially an ideal target in cancer therapies. Currently, the function of BCAT1 in malignant melanoma has not been demonstrated. Therefore, we investigated the role of BCAT1 in the proliferation and migration of malignant melanomas using human samples and mouse malignant B16 melanoma cell line. Our data showed that BCAT1 was overexpressed in malignant melanoma tissues both in humans and mice. Besides, BCAT1 knockdown suppressed melanoma cell proliferation and migration, which was associated with reduced oxidative phosphorylation. Collectively, our data indicate that BCAT1 is a promising therapeutic target for the treatment of malignant melanomas.Colorectal cancer patients with synchronous liver metastases (CRSLM) can be treated by simultaneous surgery, that is the primary tumor and liver metastasis are removed at the same time. However, criteria for simultaneous surgery are underwent continuously modified and expanded. An appropriate selection of adequate candidates for simultaneous surgery is vital to get best benefits. A retrospective study including CRSLM patients underwent simultaneous surgical treatment was conducted. CRSLM patients from SEER database were screened as development set, while CRSLM patients in Harbin (China) were enrolled as validation set. Overall survival (OS) and cancer-specific survival (CSS) were applied as end-point. Variables were screen by LASSO-Cox regression, then Cox regression was applied to construct 1-, 3- and 5-year OS, and CSS nomograms. Nomograms were compared to TMN stage for survival prediction and evaluated by concordance indexes (C-indexes), Time-dependent receiver operating characteristic (ROC) curves, Decision Curve Analysis (DCA). 1347 and 112 CRSLM patients were included in the development set and validation set respectively. Nine factors were found associated with OS and CSS, i.e., Age, Primary Site, Differentiation grade, Histology type, T stage, N stage, Tumor size, Chemotherapy, CEA. Compared to the TNM stage, OS nomogram in development set and validation set got C-indexes values of 0.701 vs 0.641, 0.670 vs 0.557 respectively. Meanwhile, compared to the TNM stage, CSS nomogram in development set and validation set got C-indexes values of 0.704 vs 0.649, 0.677 vs 0.569 respectively. AUC values of the OS and CSS nomograms were higher than the TNM stage, DCA showed the OS and CSS nomograms got more clinical net benefit than the TNM stage, in both the development set and validation set. Our nomograms for predicting survival might be helpful to identify the right CRSLM patients who can get most benefit from simultaneous surgery.ALL1 fused gene from chromosome 1q (AF1Q) functions as an oncogene in several types of cancers, but it has not been observed in osteosarcoma. In this study, we revealed that AF1Q was overexpressed in multiple osteosarcoma cell lines, and its expression level increased with the severity of tumor malignancy in osteosarcoma biopsies. AF1Q was coupled with the transcription factor T cell factor 4 (TCF4) to assemble a complex to bind to the promoter of cyclooxygenase 2 (COX2) and activate its expression. The individual knockdown of AF1Q, TCF4, or COX2 in osteosarcoma cell lines significantly decreased cell proliferation and invasion in vitro. The tumor xenograft model also indicated that the individual knockdown of AF1Q, TCF4, or COX2 could inhibit tumor growth and metastasis. On the basis of these promising results, we established an in vitro AlphaScreen method to identify the compounds that disrupted the AF1Q-TCF4 interaction in a naturally derived small molecule pool. We discovered a compound called PSM0537, which showed a strong ability to inhibit the AF1Q-TCF4 interaction at a low dose of half-maximal inhibitory concentration (IC50) (210.