Artichoke as a melanoma growth inhibitor.

Melanoma is the most lethal malignancy in skin cancers. About 97,610 new cases of melanoma are projected to occur in the United States (US) in 2023. Artichoke is a very popular plant widely consumed in the US due to its nutrition. In recent years, it has been shown that artichoke shows powerful anti-cancer effects on cancers such as breast cancer, colon cancer, liver cancer, and leukemia. However, there is little known about its effect on melanoma. This study was designed to investigate if artichoke extract (AE) has any direct effect on the growth of melanoma. Clonogenic survival assay, cell proliferation, and caspase-3 activity kits were used to evaluate the effects AE has on cell survival, proliferation, and apoptosis of the widely studied melanoma cell line HTB-72. We further investigated the possible molecular mechanisms using RT-PCR and immunohistochemical staining. The percentage of colonies of HTB-72 melanoma cells decreased significantly after treated with AE. This was paralleled with the decrease in the optic density (OD) value of cancer cells after treatment with AE. This was further supported by the decreased expression of PCNA mRNA after treated with AE. Furthermore, the cellular caspase-3 activity increased after treated with AE. The anti-proliferative effect of AE on melanoma cells correlated with increased p21, p27, and decreased CDK4. The pro-apoptotic effect of AE on melanoma cells correlated with decreased survivin. Artichoke inhibits growth of melanoma by inhibition of proliferation and promotion of apoptosis. Such a study might be helpful to develop a new promising treatment for melanoma.

Olive: A Potential Suppressor for Cervical Cancer by Upregulation of P21.

Background Cervical cancer is the second deadliest for women between the ages of 20 and 39 years. Even with prevention tactics for screening, incident rates and mortality of cervical cancer remain high. Olive has been shown to have many beneficial effects in humans concerning cardiovascular disease and inflammation. Despite these promising benefits, little is known about its effect on cervical cancer. This study examined the effects and mechanism of effects of olive extract (OE) on the HeLa cervical cancer cell line. Methodology We utilized clonogenic survival assay, quick cell proliferation assay, and caspase-3 activity to investigate the effect of OE on the proliferation and apoptosis of the cervical cancer cell line HeLa. To investigate the mechanisms behind these findings, Reverse transcription polymerase chain reaction and immunohistochemistry were performed. Results OE inhibited the growth and proliferation of HeLa cells. In comparison to the control, the percentage of colonies, as well as the optical density of the cervical cancer cells, was found to be decreased. In addition, the relative activity of caspase-3, a marker for apoptosis, was increased after treatment with OE. The anti-proliferative effect of OE on HeLa cells correlated with the increase of an anti-proliferative molecule p21. However, the pro-apoptotic effect of OE was not correlated with the change in major pro-apoptotic or anti-apoptotic molecules examined in this study. Conclusions Our study suggests that OE inhibits the growth of HeLa cervical cancer cells by upregulation of p21. Further investigation of the effects of OE on cervical cancer and other cancers is warranted by these results.

CTHRC1 Is Associated With Immune Escape and Poor Prognosis in Gastric Cancer.

BACKGROUND/AIM: Collagen triple helix repeat containing-1 (CTHRC1) promotes tumor progression by regulating the immunosuppression of the tumor microenvironment. However, the function of CTHRC1 in gastric cancer (GC) and its relationship with tumor-infiltrating immune cells remains unclear. PATIENTS AND METHODS: Data were downloaded from The Cancer Genome Atlas (TCGA) database. The difference in expression of CTHRC1 in GC and adjacent non-tumor tissues was analyzed by R software and verified by the online database Oncomine. A Kaplan-Meier survival analysis was selected for evaluating the impact of CTHRC1 expression on the survival of GC and verified by the Kaplan-Meier plotter. The relationship between CTHRC1 expression and clinicopathological parameters was assessed by univariate and multivariate Cox regression. The correlation with tumor-infiltrating immune cells was analyzed by Tumor Immune Estimation Resource (TIMER). A gene set enrichment analysis (GSEA) was used to screen the signaling pathways between low and high CTHRC1 expression datasets. RESULTS: The expression of CTHRC1 in GC tissue was higher than that in adjacent non-tumor tissues. The Kaplan-Meier curve showed that patients with higher CTHRC1 expression had a worse prognosis. The univariate and multivariate Cox analyses showed that high expression of CTHRC1 was an important independent predictor of poor overall survival in GC. The TIMER database analysis revealed that CTHRC1 was associated with five tumor immunosuppressive cells in GC. The GSEA indicated that 10 signaling pathways were enriched in samples with a high CTHRC1 expression phenotype. CONCLUSION: CTHRC1 might be a new prognostic biomarker for CG and might be a potential target for treatment of GC.

The Effect of Asparagus Extract on Pancreatic Cancer: An Intriguing Surprise.

BACKGROUND: Pancreatic cancer is the most lethal digestive cancer and the fourth overall cause of cancer death in the US. Asparagus, a widely consumed savory vegetable, is a rich source of antioxidants, saponins, vitamins, and minerals. In recent years, it has been shown that components of asparagus have anticancer effects on endometrial adenocarcinoma, and in prostate, breast, and colon cancer. In pancreatic cancer, it has been shown to have an anticancer effect on the KLM1-R cell line. This study was designed to investigate if asparagus extract (AE) had any effect on the growth of a widely used pancreatic cancer cell line MDAPanc-28 and to elucidate possible molecular mechanisms behind it. MATERIALS AND METHODS: Clonogenic survival assay, proliferation, and caspase-3 activity kits were used to evaluate the effects of AE on cell survival, proliferation, and apoptosis pathway of MDAPanc-28 cells. We further investigated the possible molecular mechanisms by using reverse transcription-polymerase chain reaction. RESULTS: The colony numbers and proliferation of MDAPanc-28 cells were surprisingly increased when treated with AE. The relative caspase-3 activity in cancer cells decreased when they were treated with AE. The pro-proliferative effect of AE on MDAPanc-28 cells correlated with down-regulation of anti-proliferative molecules P21 and P53. The potential anti-apoptotic effect of AE correlated with down-regulation of the pro-apoptotic molecule Fas cell surface death receptor (FAS) and down-regulation of caspase-3 activity. CONCLUSION: AE exhibits a pro-tumor effect on MDAPanc-28 pancreatic cancer cells by down-regulation of P21, P53, and FAS.

Development and Validation of an Inflammatory Response-Related Gene Signature for Predicting the Prognosis of Pancreatic Adenocarcinoma.

Pancreatic adenocarcinoma (PAAD) is a highly dangerous malignant tumor of the digestive tract, and difficult to diagnose, treat, and predict the prognosis. As we all know, tumor and inflammation can affect each other, and thus the inflammatory response in the microenvironment can be used to affect the prognosis. So far, the prognostic value of inflammatory response-related genes in PAAD is still unclear. Therefore, this study aimed to explore the inflammatory response-related genes for predicting the prognosis of PAAD. In this study, the mRNA expression profiles of PAAD patients and the corresponding clinical characteristics data of PAAD patients were downloaded from the public database. The least absolute shrinkage and selection operator (LASSO) Cox analysis model was used to identify and construct the prognostic gene signature in The Cancer Genome Atlas (TCGA) cohort. The PAAD patients used for verification are from the International Cancer Genome Consortium (ICGC) cohort. The Kaplan-Meier method was used to compare the overall survival (OS) between the high- and low-risk groups. Univariate and multivariate Cox analyses were performed to identify the independent predictors of OS. Gene set enrichment analysis (GSEA) was performed to obtain gene ontology (GO) terms and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, and the correlation between gene expression and immune infiltrates was investigated via single sample gene set enrichment analysis (ssGSEA). The GEPIA database was performed to examine prognostic genes in PAAD. LASSO Cox regression analysis was used to construct a model of inflammatory response-related gene signature. Compared with the low-risk group, patients in the high-risk group had significantly lower OS. The receiver operating characteristic curve (ROC) analysis confirmed the signature's predictive capacity. Multivariate Cox analysis showed that risk score is an independent predictor of OS. Functional analysis shows that the immune status between the two risk groups is significantly different, and the cancer-related pathways were abundant in the high-risk group. Moreover, the risk score is significantly related to tumor grade, stage, and immune infiltration types. It was also obtained that the expression level of prognostic genes was significantly correlated with the sensitivity of cancer cells to anti-tumor drugs. In addition, there are significant differences in the expression of PAAD tissues and adjacent non-tumor tissues. The novel signature constructed from five inflammatory response-related genes can be used to predict prognosis and affect the immune status of PAAD. In addition, suppressing these genes may be a treatment option.

IL-39 Reduces Proliferation and Promotes Apoptosis of Bladder Cancer by Altering the Activity of Cyclin E and Fas.

BACKGROUND/AIM: This study was designed to investigate the effect of IL-39 on T24 bladder cancer (BC) cell line survival and growth. MATERIALS AND METHODS: In order to assess the direct effect of IL-39 on survival, proliferation, and apoptosis of T24 BC cells, we utilized a clonogenic survival assay, a cell proliferation assay, and caspase-3 activity kits. Potential proliferative and apoptotic molecular mechanisms were evaluated by RT-PCR. RESULTS: Treatment of T24 BC cells with IL-39 resulted in a significant reduction in the percentage of colonies. The anti-tumor effect of IL-39 on T24 bladder cancer cells correlated strongly with a decrease in cyclin E, in combination with an increase in the mRNA levels of Fas. CONCLUSION: IL-39 impedes the growth and survival of T24 BC cells by inhibiting growth and promoting apoptosis. This ability to modulate gene transcription in neoplastic cells shows promise and warrants further research in immunotherapy.

Single nucleotide polymorphism of rs2596542 and the risk of hepatocellular carcinoma development: A meta-analysis.

BACKGROUND: Major histocompatibility complex class I-related chain A (MICA) is considered as a tumor antigen, and its expression is affected by its genetic polymorphisms. However, the relationship between rs2596542 polymorphisms in MICA promoter region and hepatocellular carcinoma (HCC) is not fully elucidated so far. This study aims to explore the relationship between single nucleotide polymorphism of rs2596542 and the risk of HCC development through meta-analysis. METHODS: MEDLINE, Web of Science, and EMBASE databases were systematically searched to identify relevant studies. A meta-analysis was performed to examine the association between MICA rs2596542 polymorphism and susceptibility to HCC. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated. RESULTS: Fourteen case-control studies involving 4,900 HCC cases and 19,519 controls were included. The MICA rs2596542C allele was significantly associated with decreased risk of HCC based on allelic contrast (OR = 0.76, 95% CI = 0.69-0.83, P < .001), homozygote comparison (OR = 0.57, 95% CI = 0.48-0.69, P < .001), and a recessive genetic model (OR = 0.77, 95% CI = 0.65-0.91, P < .001), whereas patients carrying the MICA rs2596542TT genotype had significantly higher risk of HCC than those with the CT or CC genotype (TT vs CT + CC, OR = 1.57, 95% CI = 1.36-1.81, P < .001). Subgroups analyses based on the ethnic or the source of control groups found very similar findings. CONCLUSION: The C allele in MICA rs2596542 is a protective factor for hepatocarcinogenesis, whereas the T allele is a risk factor. Further large and well-designed studies are needed to confirm this conclusion.