Epigenetic regulation of temozolomide resistance in human cancers with an emphasis on brain tumors: Function of non-coding RNAs.

Brain tumors, which are highly malignant, pose a significant threat to health and often result in substantial rates of mortality and morbidity worldwide. The brain cancer therapy has been challenging due to obstacles such as the BBB, which hinders effective delivery of therapeutic agents. Additionally, the emergence of drug resistance further complicates the management of brain tumors. TMZ is utilized in brain cancer removal, but resistance is a drawback. ncRNAs are implicated in various diseases, and their involvement in the cancer is particularly noteworthy. The focus of the current manuscript is to explore the involvement of ncRNAs in controlling drug resistance, specifically in the context of resistance to the chemotherapy drug TMZ. The review emphasizes the function of ncRNAs, particularly miRNAs, in modulating the growth and invasion of brain tumors, which significantly influences their response to TMZ treatment. Through their interactions with various molecular pathways, miRNAs are modulators of TMZ response. Similarly, lncRNAs also associate with molecular pathways and miRNAs, affecting the efficacy of TMZ chemotherapy. Given their functional properties, lncRNAs can either induce or suppress TMZ resistance in brain tumors. Furthermore, circRNAs, which are cancer controllers, regulate miRNAs by acting as sponges, thereby impacting the response to TMZ chemotherapy. The review explores the correlation between ncRNAs and TMZ chemotherapy, shedding light on the underlying molecular pathways involved in this process.

Progress in targeting PTEN/PI3K/Akt axis in glioblastoma therapy: Revisiting molecular interactions.

Glioblastoma (GBM) is one of the most malignant cancers of central nervous system and due to its sensitive location, surgical resection has high risk and therefore, chemotherapy and radiotherapy are utilized for its treatment. However, chemoresistance and radio-resistance are other problems in GBM treatment. Hence, new therapies based on genes are recommended for treatment of GBM. PTEN is a tumor-suppressor operator in cancer that inhibits PI3K/Akt/mTOR axis in diminishing growth, metastasis and drug resistance. In the current review, the function of PTEN/PI3K/Akt axis in GBM progression is evaluated. Mutation or depletion of PTEN leads to increase in GBM progression. Low expression level of PTEN mediates poor prognosis in GBM and by increasing proliferation and invasion, promotes malignancy of tumor cells. Moreover, loss of PTEN signaling can result in therapy resistance in GBM. Activation of PTEN signaling impairs GBM metabolism via glycolysis inhibition. In contrast to PTEN, PI3K/Akt signaling has oncogenic function and during tumor progression, expression level of PI3K/Akt enhances. PI3K/Akt signaling shows positive association with oncogenic pathways and its expression similar to PTEN signaling, is regulated by non-coding RNAs. PTEN upregulation and PI3K/Akt signaling inhibition by anti-cancer agents can be beneficial in interfering GBM progression. This review emphasizes on the signaling networks related to PTEN/PI3K/Akt and provides new insights for targeting this axis in effective GBM treatment.

Persistent reduction in the age adjusted mortality rate from aortic valve surgery in the United State with elimination of gender gap in recent years.

BACKGROUND: Advancement in the surgical techniques should translate into better outcome. The goal of this study was to evaluate mortality trends from aortic valve surgery in the United State using large inpatient database. METHOD: The Nationwide Inpatient Sample (NIS) database was used to calculate the age-adjusted mortality rate from aortic valve surgery from 1988 to 2011 in the United State using ICD-9 coding for aortic valve surgery. RESULTS: We found that age adjusted mortality rate from aortic valve surgery gradually decreased from 1988 until end of study in 2011 to the lowest level with elimination of gender gap that was seen in the early years. For men, age adjusted mortality rate from aortic valve surgery in 1988 was 438 per 100,000 with steady reduction to the lowest level of 214 per 100,000 in 2011 which remained unchanged from 2007. For women, age adjusted mortality from aortic valve surgery was 620 per 100,000 in 1988 with steady reduction to the lowest level of 235 per 100,000 in 2011 which also remained unchanged since 2007. CONCLUSION: Age adjusted mortality from aortic valve surgery has been gradually decreasing in the last decade and remained stable at the lowest rates in recent years suggesting improvement in surgical technics and post-surgical care.

Multipotent stromal stem cells from human placenta demonstrate high therapeutic potential.

We describe human chorionic mesenchymal stem cell (hCMSC) lines obtained from the chorion of human term placenta with high therapeutic potential in human organ pathology. hCMSCs propagated for more than 100 doublings without a decrease in telomere length and with no telomerase activity. Cells were highly positive for the embryonic stem cell markers OCT-4, NANOG, SSEA-3, and TRA-1-60. In vitro, cells could be differentiated into neuron-like cells (ectoderm), adipocytes, osteoblasts, endothelial-like cells (mesoderm), and hepatocytes (endoderm)-derivatives of all three germ layers. hCMSCs effectively facilitated repair of injured epithelium as demonstrated in an ex vivo-perfused human lung preparation injured by Escherichia coli endotoxin and in in vitro human lung epithelial cultures. We conclude that the chorion of human term placenta is an abundant source of multipotent stem cells that are promising candidates for cell-based therapies.