Targeting critical pathways in ferroptosis and enhancing antitumor therapy of Platinum drugs for colorectal cancer.

Colorectal cancer (CRC) can be resistant to platinum drugs, possibly through ferroptosis suppression, albeit the need for further work to completely understand this mechanism. This work aimed to sum up current findings pertaining to oxaliplatin resistance (OR) or resistance to ascertain the potential of ferroptosis to regulate oxaliplatin effects. In this review, tumor development relating to iron homeostasis, which includes levels of iron that ascertain cells' sensitivity to ferroptosis, oxidative stress, or lipid peroxidation in colorectal tumor cells that are connected with ferroptosis initiation, especially the role of c-Myc/NRF2 signaling in regulating iron homeostasis, coupled with NRF2/GPX4-mediated ferroptosis are discussed.

Targeting cellular energy metabolism- mediated ferroptosis by small molecule compounds for colorectal cancer therapy.

Alterations in cellular energy metabolism, including glycolysis, glutamine and lipid metabolism that affects ferroptosis in the tumour microenvironment (TME), play a critical role in the development and progression of colorectal cancer (CRC) and offer evolutionary advantages to tumour cells and even enhance their aggressive phenotype. This review summarises the findings on the dysregulated energy metabolism pathways, including lipid and fatty acid metabolism especially for regulating the ferroptosis in TME. Moreover, the cellular energy metabolism and tumour ferroptosis to be regulated by small molecule compounds, which targeting the different aspects of metabolic pathways of energy production as well as metabolic enzymes that connect with the tumour cell growth and ferroptosis in CRC are also discussed.

Red Cell Distribution Width as a Prognostic Factor in Patients with Hepatocellular Carcinoma.

Background: The red blood cell distribution width (RDW) was reported to be related to the severity of liver diseases, but its clinical significance in patients with hepatocellular carcinoma (HCC) remains unclear. The aim of this study was to explore the clinical significance of RDW in HCC patients.

Methods: For the retrospective study, 422 HCC patients were enrolled in this study.

The critical role of calcineurin/NFAT (C/N) pathways and effective antitumor prospect for colorectal cancers.

Transcription factors (TFs) like a nuclear factor of activated T-cells (NFAT) and its controller calcineurin are highly expressed in primary intestinal epithelial cells (IECs) due to delamination, damage by tumor-associated flora and selective activation in the intestinal tract tumor are crucial in the progression and growth of colorectal cancer (CRC). This study sought to summarize the current findings concerning the dysregulated calcineurin/NFAT (C/N) signaling involved in CRC initiation and progression. These signalings include proliferation, T-cell functions, and glycolysis with high lactate production that remodels the acidosis, which genes in tumor cells provide an evolutionary advantage, or even increased their attack phenotype.

Role of SCFAs in gut microbiome and glycolysis for colorectal cancer therapy.

Increased risk of colorectal cancer (CRC) is associated with altered intestinal microbiota as well as short-chain fatty acids (SCFAs) reduction of output The energy source of colon cells relies mainly on three SCFAs, namely butyrate (BT), propionate, and acetate, while CRC transformed cells rely mainly on aerobic glycolysis to provide energy. This review summarizes recent research results for dysregulated glucose metabolism of SCFAs, which could be initiated by gut microbiome of CRC. Moreover, the relationship between SCFA transporters and glycolysis, which may correlate with the initiation and progression of CRC, are also discussed.

Myricetin nanoliposomes induced SIRT3-mediated glycolytic metabolism leading to glioblastoma cell death.

As the most aggressive and malignant glioma, glioblastoma multiforme (GBM) abnormally expresses genes that mediate glycolytic metabolism and tumour cell growth. In this study, we investigated myricetin incorporated nanoliposomes and ascertained their prospect in effectively treating cancer via the employment of the GBM cell line DBTRG-05MG. Notably, the myricetin nanoliposomes (MYR-NLs) displayed potent inhibition of proliferation and significantly regulated the levels of proteins related to both glycolytic metabolism and cell survival.

Strategies for targeting energy metabolism in Kirsten rat sarcoma viral oncogene homolog -mutant colorectal cancer.

Alterations in cellular energy metabolism play critical roles in colorectal cancer (CRC). These alterations, which correlate to KRAS mutations, have been identified as energy metabolism signatures. This review summarizes the relationship between colorectal tumors associated with mutated KRAS and energy metabolism, especially for the deregulated energy metabolism that affects tumor cell proliferation, invasion, and migration.

Targeting Strategies for Glucose Metabolic Pathways and T Cells in Colorectal Cancer.

Colorectal cancer is a heterogeneous group of diseases that result from the accumulation of different sets of genomic alterations, together with epigenomic alterations, and it is influenced by tumor-host interactions, leading to tumor cell growth and glycolytic imbalances. This review summarizes recent findings that involve multiple signaling molecules and downstream genes in the dysregulated glycolytic pathway. This paper further discusses the role of the dysregulated glycolytic pathway in the tumor initiation, progression and the concomitant systemic immunosuppression commonly observed in colorectal cancer patients.

Strategies to target energy metabolism in consensus molecular subtype 3 along with Kirsten rat sarcoma viral oncogene homolog mutations for colorectal cancer therapy.

Alterations in cellular energy metabolism play a critical role in colorectal cancer (CRC), which has been identified as the definition of consensus molecular subtypes (CMSs), and CMS3 tumors exhibit energy metabolism signatures along with Kirsten rat sarcoma viral oncogene homolog (KRAS)-activating mutations. This review summarizes the relationship between CMS3 tumors associated with mutated KRAS and energy metabolism in CRC, especially for the dysregulated energy metabolism that affects tumor cell proliferation, invasion, and migration. Furthermore, this review concentrates on the role of metabolic genes and factors and signaling pathways, which coupled with a primary energy source connected with the CMS3 associated with mutated KRAS, induce metabolic alterations.

New strategies for targeting glucose metabolism-mediated acidosis for colorectal cancer therapy.

Colorectal cancer (CRC) is a heterogeneous group of diseases that are the result of abnormal glucose metabolism alterations with high lactate production by pyruvate to lactate conversion, which remodels acidosis and offers an evolutional advantage for tumor cells, even enhancing their aggressive phenotype. This review summarizes recent findings that involve multiple genes, molecules, and downstream signaling in the dysregulated glycolytic pathway, which can allow a tumor to initiate acid byproducts and to progress, thereby resulting in acidosis commonly found in the tumor microenvironment of CRC. Moreover, the relationship between CRC cells and the tumor acidic microenvironment, especially for regulating lactate production and lactate dehydrogenase A levels, is also discussed, as well as comprehensively defining different aspects of glycolytic pathways that affect cancer cell proliferation, invasion, and migration.

Strategy to targeting the immune resistance and novel therapy in colorectal cancer.

Assessing the CRC subtypes that can predict the outcome of colorectal cancer (CRC) in patients with immunogenicity seems to be a promising strategy to develop new drugs that target the antitumoral immune response. In particular, the disinhibition of the antitumoral T-cell response by immune checkpoint blockade has shown remarkable therapeutic promise for patients with mismatch repair (MMR) deficient CRC. In this review, the authors provide the update of the molecular features and immunogenicity of CRC, discuss the role of possible predictive biomarkers, illustrate the modern immunotherapeutic approaches, and introduce the most relevant ongoing preclinical study and clinical trials such as the use of the combination therapy with immunotherapy.

Inhibition of glycolytic metabolism in glioblastoma cells by Pt3glc combinated with PI3K inhibitor via SIRT3-mediated mitochondrial and PI3K/Akt-MAPK pathway.

Glioblastoma multiforme (GBM) is the most malignant and aggressive glioma with abnormal expression of genes that mediate glycolytic metabolism and tumor cell growth. Petunidin-3-O-glucoside (Pt3glc) is a kind of anthocyanin in the red grape and derived beverages, representing the most common naturally occurring anthocyanins with a reduced incidence of cancer and heart diseases. In this study, whether Pt3glc could effectively regulate glycolysis to inhibit GBM cell was investigated by using the DBTRG-05MG cell lines.

Upregulation and biological function of transmembrane protein 119 in osteosarcoma.

Osteosarcoma is suggested to be caused by genetic and molecular alterations that disrupt osteoblast differentiation. Recent studies have reported that transmembrane protein 119 (TMEM119) contributes to osteoblast differentiation and bone development. However, the level of TMEM119 expression and its roles in osteosarcoma have not yet been elucidated.

Meta-analysis of oxaliplatin-based versus fluorouracil-based neoadjuvant chemoradiotherapy and adjuvant chemotherapy for locally advanced rectal cancer.

A meta-analysis was conducted to compare oxaliplatin-based with fluorouracil-based neoadjuvant chemoradiotherapy and adjuvant chemotherapy for locally advanced rectal cancer. MEDLINE, EMBASE and CENTRAL were systematically searched for relevant randomized controlled trials (RCTs) until January 31 2017. Review Manager (version 5.

Strategies to Target Glucose Metabolism in Tumor Microenvironment on Cancer by Flavonoids.

The imbalance between glucose metabolism and cancer cell growth in tumor microenvironment (TME), which are closely related with the occurrence and progression of cancer. Accumulating evidence has demonstrated that flavonoids exert many biological properties, including antioxidant and anticarcinogenic activities. Recently, the roles and applications of flavonoids, particularly in relation to glucose metabolism in cancers, have been highlighted.

Advances in the targeting of HIF-1α and future therapeutic strategies for glioblastoma multiforme (Review).

Cell metabolism can be reprogrammed by tissue hypoxia leading to cell transformation and glioblastoma multiforme (GBM) progression. In response to hypoxia, GBM cells are able to express a transcription factor called hypoxia inducible factor-1 (HIF-1). HIF-1 belongs to a family of heterodimeric proteins that includes HIF-1α and HIF-1β subunits.

Effect of notch1,2,3 genes silicing on NF-κB signaling pathway of macrophages in patients with atherosclerosis.

Background: Notch and NF-κB signaling pathways both play important roles in the regulation of atherosclerosis (AS). However, the mechanisms of notch and NF-κB signaling pathways on AS are still unclear. In this study, we aimed to investigate the effects of notch1,2,3 genes silicing by siRNA on notch and NF-κB signaling pathways of macrophages in patients with atherosclerosis (AS), so as to seek the treatment of AS from genetic perspective.

Meta-analysis of bariatric surgery versus non-surgical treatment for type 2 diabetes mellitus.

Background: To compare short-term and long-term results of bariatric surgery vs non-surgical treatment for type 2 diabetes mellitus (T2DM).

Methods: A systematic search was conducted in the PubMed, Embase, and Cochrane Library databases for randomized controlled trials (RCTs). All statistical analysis was performed using Review Manager version 5.

Novel Strategies to Discover Effective Drug Targets in Metabolic and Immune Therapy for Glioblastoma.

Glioblastoma multiforme is a common primary brain tumor, which exhibits an imbalance between glioma cell growth and glucose metabolism. Recent discoveries have found that the multiple pathways and downstream genes involved in the dysregulated metabolic pathway allow tumor to manifest and progress, which is critical to patients with glioblastoma associated with significant systemic and immunosuppression. Moreover, immune microenvironment is considered a major obstacle to generating an effective antitumor immune response.

Mesenchymal stem cells promote pancreatic adenocarcinoma cells invasion by transforming growth factor-β1 induced epithelial-mesenchymal transition.

Mesenchymal stem cells (MSCs) could be ideal delivery vehicles for antitumor biological agents in pancreatic adenocarcinoma (PA). While the role of MSCs in tumor growth is elusive. Inflammation is an important feature of PA.

MRI measurement on intercondylar notch after anterior cruciate ligament rupture and its correlation.

The knee joint is extremely susceptible to injury, which is usually identified by magnetic resonance imaging (MRI). In the present study, MRI was applied to quantitatively detect the association between anterior cruciate ligament (ACL) rupture and anatomic morphologic changes of the intercondylar notch. Forty patients with unilateral ACL rupture who were treated between July, 2013 and October, 2014 were enrolled in the present study.

Low expression of protocadherin7 (PCDH7) is a potential prognostic biomarker for primary non-muscle invasive bladder cancer.

Bladder cancer is a heterogeneous disease with outcome difficult to predict, and novel predictive biomarkers are needed. PCDH7, a member of protocadherins family, functions as tumor suppressor in several human cancers. The human PCDH7 gene is localized in chromosome 4p15, which is often inactivated in human cancers, including bladder cancer.

Aberrant Protocadherin17 (PCDH17) Methylation in Serum is a Potential Predictor for Recurrence of Early-Stage Prostate Cancer Patients After Radical Prostatectomy.

BACKGROUND Prostate cancer is a one of the most common malignant diseases in men worldwide. Now it is a challenge to identify patients at higher risk for relapse and progression after surgery, and more novel prognostic biomarkers are needed. The aim of this study was to investigate the clinical significance of protocadherin17 (PCDH17) methylation in serum and its predictive value for biochemical recurrence (BCR) after radical prostatectomy.

MicroRNA-101 down-regulates sphingosine kinase 1 in colorectal cancer cells.

MicroRNAs (miRs) dysregulation is a general feature of colorectal cancer (CRC) and other solid tumors, and is associated cancer progression. In the current study, we demonstrate that microRNA-101 (miR-101) inhibits CRC cells probably through down-regulating sphingosine kinase 1 (SphK1). Our results showed that exogenously expressing miR-101 inhibited CRC cell (HT-29 and HCT-116 lines) growth in vitro.

Promoter methylation of protocadherin8 is an independent prognostic factor for biochemical recurrence of early-stage prostate cancer.

Background: Protocadherin8 has been demonstrated to play critical roles in initiation and progression of several human cancers. It is frequently inactivated by promoter methylation in cancers and may be used as a potential biomarker. However, the methylation status of protocadherin8 and its clinical significance in prostate cancer remains largely unknown.