Elevated CK-MB levels are associated with adverse clinical outcomes in acute pancreatitis: a propensity score-matched study.

Aim: Cardiac injury, reflected by the measured concentrations of chemicals released from injured cardiac muscle, is common in acute pancreatitis (AP). However, there is no adequate evidence assessing the impact of cardiac injury on AP-related outcomes. Creatine kinase-myocardial band (CK-MB) mainly exists in the myocardium. Therefore, we sought to evaluate the relationship between the increase in CK-MB and the adverse clinical outcomes of AP. Methods: This propensity score-matched study analyzed AP patients admitted to the Department of Gastroenterology in the First Affiliated Hospital of Nanchang University from June 2017 to July 2022. Propensity score matching and multivariate logistic regression analysis were used to explore the relationship between CK-MB elevation and AP outcome variables. Results: A total of 5,944 patients were screened for eligibility, of whom 4,802 were ultimately enrolled. Overall, 896 (18.66%) of AP patients had elevated (>24 U/ml) CK-MB levels, and 895 (99.89%) were paired with controls using propensity score matching. The propensity score-matched cohort analysis demonstrated that mortality (OR, 5.87; 95% CI, 3.89-8.84; P < 0.001), severe acute pancreatitis (SAP) (OR, 2.74; 95% CI, 2.23-3.35; P < 0.001), and infected necrotizing pancreatitis (INP) (OR, 3.40; 95% CI, 2.34-4.94; P < 0.001) were more frequent in the elevated CK-MB (>24 U/ml) group than in the normal CK-MB (≤ 24 U/ml) group. Using the multivariate logistic regression analysis, elevated CK-MB levels were independently associated with increased mortality (OR, 2.753, 95% CI, 2.095-3.617, P < 0.001), SAP incidence (OR, 2.223, CI, 1.870-2.643, P < 0.001), and INP incidence (OR, 1.913, 95% CI, 1.467-2.494, P < 0.001). CK-MB elevation was an independent risk factor for adverse clinical outcomes in AP patients. Conclusion: CK-MB elevation was significantly related to adverse outcomes in AP patients, which makes it a potentially useful laboratory parameter for predicting adverse clinical outcomes of AP.

mRNA vaccination in breast cancer: current progress and future direction.

Messenger RNA (mRNA) vaccination has proven to be highly successful in combating Coronavirus disease 2019 (COVID-19) and has recently sparked tremendous interest. This technology has been a popular topic of research over the past decade and is viewed as a promising treatment strategy for cancer immunotherapy. However, despite being the most prevalent malignant disease for women worldwide, breast cancer patients have limited access to immunotherapy benefits. mRNA vaccination has the potential to convert cold breast cancer into hot and expand the responders. Effective mRNA vaccine design for in vivo function requires consideration of vaccine targets, mRNA structures, transport vectors, and injection routes. This review provides an overview of pre-clinical and clinical data on various mRNA vaccination platforms used for breast cancer treatment and discusses potential approaches to combine appropriate vaccination platforms or other immunotherapies to improve mRNA vaccine therapy efficacy for breast cancer.

Development and validation of a dual-energy CT-based model to estimate the malignant probability of distal gastric wall thickening.

Background: This study developed and validated a viable model for the preoperative diagnosis of malignant distal gastric wall thickening based on dual-energy spectral computed tomography (DEsCT). Methods: The imaging data of 208 patients who were diagnosed with distal gastric wall thickening using DEsCT were retrospectively collected and divided into a training cohort (n=151) and a testing cohort (n=57). The patient's clinical data and pathological information were collated. The multivariable logistic regression model was built using 5 selected features, and subsequently, a 10-fold cross-validation was performed to identify the optimal model. A nomogram was established based on the training cohort. Finally, the diagnostic performance of the best model was compared to the existing conventional CT scheme through evaluating the discrimination ability in the testing cohort in terms of the receiver operating characteristic curve (ROC), calibration, and clinical usefulness. Results: Stepwise regression analysis identified 5 candidate variables with the smallest Akaike information criteria (AIC), namely, the venous phase spectral curve [VP_ SC; odds ratio (OR) 8.419], focal enhancement (OR 3.741), arterial phase mixed (OR 1.030), tumor site (OR 0.573), and diphasic shape change (DP_shape change; OR 2.746). The best regression model with 10-fold cross-validation consisting of VP_SC and focal enhancement was built using the 5 candidate variables. The average area under the ROC curve (AUC) of the model from the 10-fold cross-validation was 0.803 (sensitivity of 69.2%, specificity of 94.1%, and accuracy of 74.8%). In the testing cohort, the DEsCT model identified using the regression model performed better (AUC 0.905, sensitivity 81.3%, specificity 85.4%, and accuracy 84.2%) than did the conventional CT scheme (AUC 0.852, sensitivity 80.0%, specificity 76.6%, and accuracy 77.2%). The nomogram based on the DEsCT model showed good calibration and provided a better net benefit for predicting malignancy of distal gastric wall thickening. Conclusions: Comprehensive assessment with the DEsCT-based model can be used to facilitate the individualized diagnosis of malignancy risk in patients presenting with distal gastric wall thickening.

(±)-Gancochlearols J - N, renoprotective meroterpenoids from Ganoderma cochlear.

Five pairs of meroterpenoid enantiomers, (±)-gancochlearols J - N (1-5), were isolated from the fruiting bodies of Ganoderma cochlear. Their structures were elucidated on the basis of 1D and 2D NMR and HRESIMS data. The absolute configurations of gancochlearols J - M (1-4) were assigned by electronic circular dichroism (ECD) calculations. Biological evaluation showed that (-)-1 and (-)-2 could inhibit renal fibrosis in TGF-ß1-induced rat kidney proximal tubular cells (NRK-52e).

Gancochlearols E - I, meroterpenoids from Ganoderma cochlear against COX-2 and triple negative breast cancer cells and the absolute configuration assignment of ganomycin K.

Five new meroterpenoids, gancochlearols E - I (1, 3-6), and one compound ganomycin K (2) were isolated from the fruiting bodies of G. cochlear. Their structures were assigned by 1D and 2D NMR, MS, and CD analysis. Rh2(OCOCF3)4-induced ECD method was used to clarify the absolute configuration of secondary alcohol in 1 and 2. Biochemical evaluation showed that all the isolates significantly inhibit COX-2 enzyme in vitro with the IC50 values range from 1.03 µM to 2.71 µM. Further cellular assay revealed that (+)-3 and (-)-6 could suppress metastatic phenotype of triple-negative breast cancer (TNBC) cells via impeding the epithelial-mesenchymal transition (EMT).

PHD3 affects gastric cancer progression by negatively regulating HIF1A.

Prolyl hydroxylase 3 (PHD3) is widely accepted as a tumor suppressor; however, the expression of PHD3 in various cancer types remains controversial. The present study aimed to investigate the association between PHD3 expression and the clinicopathological features of gastric cancer using reverse transcription­quantitative polymerase chain reaction and immunohistochemistry. The effects of PHD3 in gastric cancer cell lines were assessed using western blot analysis and transwell migration assays. The present results revealed that PHD3 expression was increased in adjacent non­cancerous tissue compared with in gastric cancer tissue, and PHD3 overexpression was correlated with the presence of well­differentiated cancer cells, early cancer stage classification and the absence of lymph node metastasis. In vitro experiments demonstrated that PHD3 may act as a negative regulator of hypoxia­inducible factor­1α and vascular endothelial growth factor, both of which participate in tumor angiogenesis. In conclusion, the present results suggested that PHD3 may act as a tumor suppressor in gastric cancer. Therefore, the targeted regulation of PHD3 may have potential as a novel therapeutic approach for the treatment of patients with gastric cancer.

Laparoscopic repair of diaphragm perforation with heart patch after microwave ablation.

Microwave ablation (MWA) is a new technology developed in recent years, which is widely used in various disciplines. Microwave ablation is an alternative to surgery in the management of various tumors, and it has been demonstrated to be effective in the management of primary tumors and metastatic tumors. Microwave ablation is widely used in the treatment of hepatocellular carcinoma with an obvious effect and less side effects, and only 2.7% had serious complications. Many studies have confirmed the complications are thermal damage, hemorrhage, pleural effusion, bile leak, tumor seeding, hepatic abscess, cholangitis, and so forth. But diaphragm perforation is rare, and it is probably the first case reported. This article describes diaphragmatic perforation secondary to MWA of the liver with subsequent pleural effusion and diaphragmatic hernia. We also describe its management via the laparoscopic approach.

Recurrent TERT promoter mutations identified in a large-scale study of multiple tumour types are associated with increased TERT expression and telomerase activation.

BACKGROUND: Several somatic mutation hotspots were recently identified in the telomerase reverse transcriptase (TERT) promoter region in human cancers. Large scale studies of these mutations in multiple tumour types are limited, in particular in Asian populations. This study aimed to: analyse TERT promoter mutations in multiple tumour types in a large Chinese patient cohort, investigate novel tumour types and assess the functional significance of the mutations. METHODS: TERT promoter mutation status was assessed by Sanger sequencing for 13 different tumour types and 799 tumour tissues from Chinese cancer patients. Thymic epithelial tumours, gastrointestinal leiomyoma, and gastric schwannoma were included, for which the TERT promoter has not been previously sequenced. Functional studies included TERT expression by reverse-transcriptase quantitative polymerase chain reaction (RT-qPCR), telomerase activity by the telomeric repeat amplification protocol (TRAP) assay and promoter activity by the luciferase reporter assay. RESULTS: TERT promoter mutations were highly frequent in glioblastoma (83.9%), urothelial carcinoma (64.5%), oligodendroglioma (70.0%), medulloblastoma (33.3%) and hepatocellular carcinoma (31.4%). C228T and C250T were the most common mutations. In urothelial carcinoma, several novel rare mutations were identified. TERT promoter mutations were absent in gastrointestinal stromal tumour (GIST), thymic epithelial tumours, gastrointestinal leiomyoma, gastric schwannoma, cholangiocarcinoma, gastric and pancreatic cancer. TERT promoter mutations highly correlated with upregulated TERT mRNA expression and telomerase activity in adult gliomas. These mutations differentially enhanced the transcriptional activity of the TERT core promoter. CONCLUSIONS: TERT promoter mutations are frequent in multiple tumour types and have similar distributions in Chinese cancer patients. The functional significance of these mutations reflect the importance to telomere maintenance and hence tumourigenesis, making them potential therapeutic targets.

Assessing the diagnostic value of serum Dickkopf-related protein 1 levels in cancer detection: a case-control study and meta-analysis.

BACKGROUND: This study aimed to summarize the potential diagnostic value of serum DKK1 levels in cancer detection. MATERIALS AND METHODS: Serum DKK1 was measured using enzyme-linked immunosorbent assay in a case-control study. Then we performed a meta-analysis and the pooled sensitivity, specificity, diagnostic odds ratio, and summary receiver operating characteristic (sROC) curves were used to evaluate the overall test performance. RESULTS: Serum DKK1 levels were found to be significantly upregulated in gastric cancer as compared to controls. ROC curve analysis revealed an AUC of 0.636, indicating the test has the potential to diagnose cancer with poor accuracy. The summary estimates of the pooled sensitivity, specificity and diagnostic odds ratio in meta-analysis were 0.55 with a 95% confidence interval (CI) (0.53-0.57), 0.86 (95%CI, 0.84-0.88) and 12.25 (95%CI, 5.31-28.28), respectively. The area under the sROC was 0.85. Subgroup analysis revealed that the diagnostic accuracy of serum DKK1 in lung cancer (sensitivity: 0.69 with 95%CI, 0.66-0.74; specificity: 0.95 with 95%CI, 0.92-0.97; diagnostic odds ratio: 44.93 with 95%CI, 26.19-77.08) was significantly higher than for any other cancer. CONCLUSIONS: Serum DKK1 might be useful as a noninvasive method for confirmation of cancer diagnosis, particularly in the case of lung cancer.

Up-regulated miR-199a-5p in gastric cancer functions as an oncogene and targets klotho.

BACKGROUND: Recent studies have shown that miR-199a-5p plays opposite roles in cancer initiation and progression of different cancer types, acting as oncogene for some cancer types but as tumor suppressor gene for others. However, the role and molecular mechanism of miR-199a-5p in gastric cancer are largely unknown. METHODS: In this study, miR-199a-5p expression level in gastric cancer was first analyzed by qPCRand then validated in 103 gastric cancer patients by in situ hybridization (ISH). Gastric cancer cell lines were transfected with miR-199a-5p inhibitor and mimic, and underwent in vitro transwell assays. Target genes (klotho) were identified using Luciferase reporter assay. Immunohistochemical staining was also used to investigate on how miR-199a-5p regulates the tumour-suppressive effects of klotho in gastric cancer. RESULTS: In our present study, we found that miR-199a-5p level was significantly increased in gastric cancer tissues compared to paired normal tissues. We observed that miR-199a-5p could promote migration and invasion of gastric cancer cells. In situ hybridization of miR-199a-5p also confirmed that higher miR-199a-5p expression level was associated with increased likelihood of lymph node metastasis and later TNM stage. Luciferase reporter assay and immunohistochemistry revealed that klotho might be the downstream target of miR-199a-5p. CONCLUSIONS: Our present study suggests that miR-199a-5p acts as an oncogene in gastric cancer and functions by targeting klotho.

The MDM2 309T>G polymorphism and ovarian cancer risk: a meta-analysis of 1534 cases and 2211 controls.

BACKGROUND: Recently, there have been a number of studies on the association between MDM2 (Murine Double Minute 2) 309 polymorphism and ovarian cancer risk. However, the results of previous reports remain controversial and ambiguous. Thus, we performed a meta-analysis to explore more precisely the association between MDM2 309 polymorphism and the risk of ovarian cancer. METHODS: A meta-analysis was performed to examine the association between MDM2 309T>G polymorphism and ovarian cancer risk. Odds ratio (OR) and its 95% confidence interval (CI) were used for statistical analysis. RESULTS: Our publication search identified a total of 6 studies with 1534 cases and 2211 controls. No significant association was found between MDM2 309T>G polymorphism and ovarian cancer risk in total population analysis. In the subgroup meta-analysis by ethnicity, a negative association was shown in Asian subgroup (G vs. T OR = 0.774, 95% CI = 0.628-0.955, P = 0.017, P(het) = 0.327; GG vs. TT: OR = 0.601, 95% CI = 0.395-0.914, P = 0.017, P(het) = 0.417; dominant model TG+GG vs. TT: OR = 0.661, 95% CI = 0.468-0.934, P = 0.019, P(het) = 0.880), and no significant association in any genetic models among Caucasians was observed. CONCLUSIONS: This meta-analysis provides evidence for the association between MDM2 309 polymorphism and ovarian cancer risk, supporting the hypothesis that MDM2 SNP309 G allele acts as an important ovarian cancer protective factor in Asians but not in Caucasians.

REG4 contributes to the invasiveness of pancreatic cancer by upregulating MMP-7 and MMP-9.

Recent studies have shown that overexpression of regenerating gene family member 4 (REG4) is associated with the initiation and progression of pancreatic cancer. In our study, we explored the role of REG4 in the invasion of pancreatic cancer. Real-time PCR and Western blot analysis were used to determine REG4 expression in pancreatic cancer cell lines. An MTT assay was carried out to test the effect of REG4 on the growth of pancreatic cancer cells. The involvement of REG4 in cancer cell invasion was examined by Transwell invasion assay. Two MMPs, MMP-7 and MMP-9, were identified from a pool of candidate genes as being related to REG4-induced cell invasion by PCR and Western blotting. Immunohistochemistry was used to confirm the correlation between REG4 and the two MMPs. High expression of REG4 was found in BXPC-3 cells and its culture media. But in PANC-1 and ASPC-1 cell lines, REG4 expression levels were very low, and no detectable protein was found in the culture medium. The MTT and Transwell invasion assays showed that recombinant REG4 protein and BXPC-3 conditioned media significantly promoted the proliferation and invasiveness of pancreatic cancer cells. It was also shown that MMP-7 and MMP-9 are upregulated by REG4 induction using real-time PCR and Western blotting analysis. Immunohistochemical study further verified this result. In conclusion, REG4 promotes not only growth but also in vitro invasiveness of pancreatic cancer cells by upregulating MMP-7 and MMP-9.

Expressions of neutrophil gelatinase-associated lipocalin in gastric cancer: a potential biomarker for prognosis and an ancillary diagnostic test.

The aim of this study was to explore the clinical significance of neutrophil gelatinase-associated lipocalin (NGAL) in the development and prognosis of gastric cancer. NGAL tumor levels were determined in 333 GC patients by immunohistochemistry. NGAL in blood samples from 63 healthy donors and 60 gastric cancer patients were also determined by enzyme-linked immunosorbent assay. Rate of NGAL expression was correlated with the size of tumor (69.3% in >4 cm tumors vs. 46.1% in ≤4 cm tumors), Lauren's classification (84.3% in diffuse type vs. 28.2% in intestinal type), lymph node metastasis (75.6% vs. 16.4% with no metastasis), vascular invasion (74.9% vs. 26.8% with no invasion), distant metastasis (94.3% vs. 50.3% with no distant metastasis), and TNM stage (81.8% in TNM III+IV vs. 20.5% in TNM I+II). NGAL expression can be used as an independent prognostic factor in gastric cancer as indicated by multivariate analysis. Positivity for serum NGAL was higher than that for carbohydrate antigen determinant, CA19-9 (38.1% vs. 12.5%) in TNM I, and higher than that for carcinoembryonic antigen, CEA (58.3% vs. 8.3%) and CA19-9 (58.3% vs. 8.3%) in TNM II. In conclusion, serum NGAL has great potential to be used as an ancillary test for diagnosis of gastric cancer. Increased expression of NGAL in tumors suggests gastric cancer is likely to be at an advanced stage with invasion and metastasis, and also poor prognosis.

MicroRNA-101 is down-regulated in gastric cancer and involved in cell migration and invasion.

MicroRNAs (miRNAs) are short non-coding RNA molecules playing regulatory roles by repressing translation or cleaving RNA transcripts. Dysregulated expression of miRNAs is associated with several diseases, including cancer. In this study, we report that the expression of microRNA-101 (miR-101) is down-regulated in gastric cancer tissues and cells, and ectopic expression of miR-101 significantly inhibits cellular proliferation, migration and invasion of gastric cancer cells by targeting EZH2, Cox-2, Mcl-1 and Fos. Our animal study also indicates that miR-101 could potentially suppress tumour growth in vivo. Collectively, these results suggest that miR-101 may function as a tumour suppressor in gastric cancer, as it has an inhibitory role not only in cellular proliferation, migration and invasion in vitro, but also in tumour growth in vivo.

[Effect of angiogenesis inhibitor SU6668 on the growth and metastasis of gastric cancer in SCID mice].

OBJECTIVE: To study the effect of angiogenesis inhibitor SU6668 on the growth and metastasis of gastric cancer in SCID mice. METHODS: Metastatic model was established by orthotopic implantation of histologically intact human tumor tissue into the gastric wall of SCID mice. Forty-eight mice were randomly divided into four groups, and saline, 5-FU, SU6668, and 5-FU plus SU6668 were administered by i.p. every day for 6 weeks after tumor implantation. The mice were killed and tumor weight, tumor inhibition rate, intratumoral microvessel density(MVD), apoptotic index(AI) and metastasis inhibition were evaluated. RESULTS: Compared with the control, tumor growth was significantly inhibited in mice treated respectively with 5-FU, SU6668 and 5-FU plus SU6668 with inhibition rates of 47.5%, 64.1% and 69.2% respectively. Decreased MVD and increased AI were noted in the mice treated with SU6668 and 5-FU plus SU6668. The incidences of liver and peritoneal metastases was significantly inhibited and decreased to 62.5%, 69.9% in SU6668 group, and 74.9%, 90% in 5-FU plus SU6668 group. The growth and metastasis of human gastric cancer implanted in SCID mice were significantly inhibited in SU6668 group and combined group, especially in combined group. CONCLUSION: Angiogenesis inhibitor SU6668 has a strong inhibitory effect on tumor growth and metastasis of human gastric cancer transplanted in SCID mice, and has synergistic effect combined with cytotoxic agents.

Detection of serum tumor markers in the diagnosis and treatment of patients with pancreatic cancer.

BACKGROUND: Although a variety of tumor markers are available for diagnosis of pancreatic cancer, their sensitivity and specificity have not yet been ideal. The aims of this study was to detect a panel of serum tumor markers and to evaluate their significance in the diagnosis and prognosis of pancreatic cancer patients. METHODS: Eight serum tumor markers including AFP, CEA, CA-50, CA72-4, CA-125, CA153, CA19-9 and CA242 were detected in 129 patients with pancreatic cancer by using chemiluminescence immunoassay, immunofluorescence assay and immunoradiometric assay, respectively. The levels of these markers were compared in 99 patients with non-pancreatic malignant tumor, 63 patients with other benign diseases, and 27 patients with pancreatic cancer after pancreatectomy. RESULTS: Among the 8 tumor markers, CA19-9, CA242, CA-50, and CA72-4 were more sensitive in the diagnosis of pancreatic cancer. Parallel combined testing could increase the diagnostic sensitivity to 89.2%, and serial combined examination could increase the diagnostic specificity to 92.3%. The serum tumor markers levels were decreased significantly after radical tumor resection. CONCLUSIONS: Serum CA19-9, CA242, CA-50, and CA72-4 are the preferred tumor markers to be used in the diagnosis and follow-up of operated cases of pancreatic cancer. Testing of a panel of multiple serum tumor markers may increase the sensitivity and specificity in the diagnosis of pancreatic cancer.