[Effects of BMAL2 on Aerobic Glycolysis and Cell Proliferation in Acute Myeloid Leukemia Cells].

OBJECTIVE: To explore the expression of basic helix-loop-helix ARNT like 2 (BMAL2) in acute myeloid leukemia (AML) patients and its correlation with prognosis, and analyze its effects on the aerobic glycolysis and proliferation of AML cells. METHODS: The expressions of BMAL2 in bone marrow mononuclear cells (BMMCs) of AML patients and normal control group were detected by RT-qPCR. The correlation of BMAL2 expression with prognosis of AML patients was analyzed using public database of National Center for Biotechnology Information (NCBI). The interfering in BMAL2 expression of HL-60 and Kasumi-1 cells was performed using lentiviral vector-mediated shRNA. Cell glucose metabolism and proliferation were detected by using glucose uptake experiment, lactate content test, CCK-8 assay and cell colony formation test. RESULTS: The expression level of BMAL2 mRNA in BMMCs of AML patients was significantly higher than normal control group (P < 0.01). The overall survival time of AML patients with high expression of BMAL2 was significantly shorter than those with low expression of BMAL2 (P < 0.05). Knockdown of BMAL2 significantly reduced glucose uptake and lactate production in AML cell line HL-60 and Kasumi-1 cells. The results of RT-PCR and Western blot showed that BMAL2 promoted aerobic glycolysis by enhancing the expression of HIF1A in AML cells, thereby promoting cell proliferation. CONCLUSION: BMAL2 is highly expressed in AML patients, and promotes aerobic glycolysis by enhancing the expression of HIF1A, thereby promoting cell proliferation.

Accuracy of Fasting Blood Glucose and Body Mass Index in Predicting Gestational Diabetes Mellitus in China.

BACKGROUND: Research suggests that lowering maternal morbidities associated with gestational diabetes mellitus (GDM) can be achieved with earlier risk group identification. AIMS: Therefore, the purpose of this study was to examine potential markers for identifying first-trimester pregnant women who are at high risk for developing GDM. METHODS: This was a retrospective cohort study. The pertinent maternal clinical data were retrieved prior to 13+6 weeks of gestation, and a binary logistic regression analysis was used to identify potential GDM predictors. The predictive accuracy was evaluated using the area below the receiver operating characteristics curves. RESULTS: In comparison to the control group, the GDM group had significantly higher mean values for age, body mass index (BMI), mean fasting blood glucose (FBG), and hemoglobin (p < 0.05). The Pearson's correlation coefficients indicated that the first-trimester FBG was significantly positively correlated with the second-trimester FBG. Higher FBG and BMI values were associated with an increased risk of developing GDM (odds ratio [OR] = 3.04, 95% confidence interval [CI] = 2.03-4.55 and OR = 1.18, 95% CI = 1.12-1.25). In terms of predicting GDM, the FBG parameter demonstrated the greatest area under the curve values (0.66), followed by the BMI parameter (0.69). For GDM prediction, the cut-off value for FBG was 4.32 mM, whereas that for BMI was 23.7 kg/m2. CONCLUSIONS: The first-trimester FBG and BMI could be utilized to predict gestational diabetes.

NPAS2 promotes aerobic glycolysis and tumor growth in prostate cancer through HIF-1A signaling.

BACKGROUND: Prostate cancer (PCa), one of the common malignant tumors, is the second leading cause of cancer-related deaths in men. The circadian rhythm plays a critical role in disease. Circadian disturbances are often found in patients with tumors and enable to promote tumor development and accelerate its progression. Accumulating evidence suggests that the core clock gene NPAS2 (neuronal PAS domain-containing protein 2) has been implicated in tumors initiation and progression. However, there are few studies on the association between NPAS2 and prostate cancer. The purpose of this paper is to investigate the impact of NPAS2 on cell growth and glucose metabolism in prostate cancer. METHODS: Quantitative real-time PCR (qRT-PCR), immunohistochemical (IHC) staining, western blot, GEO (Gene Expression Omnibus) and CCLE (Cancer Cell Line Encyclopedia) databases were used to analyze the expression of NPAS2 in human PCa tissues and various PCa cell lines. Cell proliferation was assessed using MTS, clonogenic assays, apoptotic analyses, and subcutaneous tumor formation experiments in nude mice. Glucose uptake, lactate production, cellular oxygen consumption rate and medium pH were measured to examine the effect of NPAS2 on glucose metabolism. The relation of NPAS2 and glycolytic genes was analyzed based on TCGA (The Cancer Genome Atlas) database. RESULTS: Our data showed that NPAS2 expression in prostate cancer patient tissue was elevated compared with that in normal prostate tissue. NPAS2 knockdown inhibited cell proliferation and promoted cell apoptosis in vitro and suppressed tumor growth in a nude mouse model in vivo. NPAS2 knockdown led to glucose uptake and lactate production diminished, oxygen consumption rate and pH elevated. NPAS2 increased HIF-1A (hypoxia-inducible factor-1A) expression, leading to enhanced glycolytic metabolism. There was a positive correlation with the expression of NPAS2 and glycolytic genes, these genes were upregulated with overexpression of NPAS2 while knockdown of NPAS2 led to a lower level. CONCLUSION: NPAS2 is upregulated in prostate cancer and promotes cell survival by promoting glycolysis and inhibiting oxidative phosphorylation in PCa cells.

Chromosome 1q21 gain is an adverse prognostic factor for newly diagnosed multiple myeloma patients treated with bortezomib-based regimens.

Chromosome 1q21 aberration is one of the most common cytogenetic abnormalities in multiple myeloma, and is considered an important prognostic factor. The present study analyzed the clinical relevance and prognostic impact of 1q21 gain in 194 patients with newly diagnosed multiple myeloma treated with bortezomib-based regimens. 1q21 gain was detected in 45.9% (89/194) of patients, and those with 1q21 gain had a worse prognosis. Strikingly, our results showed that excluding the effects of other coinciding genetic anomalies, patients carrying at least four copies of 1q21 had worse survival outcome. Moreover, del(13q) strongly correlates with 1q21 gain, and the coexistence of del(13q) and 1q21 gain plays an important role in reducing PFS and OS times. Therefore, 1q21 gain should be considered a high-risk feature in multiple myeloma patients treated with a bortezomib-based regimen.

Case reports of robot-assisted laparoscopic radical nephrectomy and inferior vena cava tumor thrombectomy: A retrospective analysis.

ABSTRACT: Renal cell carcinoma is one common type of urologic cancers. It has tendencies to invade into the inferior vena cava (IVC) and usually requires an open surgery procedure. High rates of operative complications and mortality are usually associated with an open surgery procedure. The recently emerged robot-assisted laparoscopic radical nephrectomy (RAL-RN) and IVC tumor thrombectomy have shown to reduce operative related complications in patients with renal cell carcinoma.This case series study aimed to summarize technical utilization, perioperative outcomes, and efficacies of RAL-RN and IVC tumor thrombectomy in our hospital. A retrospective analysis was performed on clinical data from 20 patients who underwent RAL-RN and IVC tumor thrombectomy from January 2017 to December 2019 in our department.Patients had a median age of 59 years (interquartile range [IQR], 46-68). Four patients had renal neoplasm on left side and 16 on right side. Nineteen patients underwent RAL-RN (level 0: n = 2) or RAL-RN with IVC thrombectomy (n = 17) (level I: n = 3; level II: n = 12; and level III: n = 3) and 1 patient was converted into an open surgery. The median operative time was 328 minutes (IQR, 221-453). The estimated median blood loss was 500 mL (IQR, 200-1200). The median size of removed renal carcinoma was 67 cm2 (IQR, 40-91); the length of IVC tumor thrombus was 5 cm (IQR, 3-7). The postsurgery hospital length of stay was 6 days (IQR, 5-7). The complications included intestinal obstruction (n = 1), lymphatic fistula (n = 1), heart failure (n = 1), and low hemoglobin level (n = 1). The outcomes for patients after 16 months (IQR, 11-21) follow-up were tumor-free (n = 10), tumor progression (n = 4), loss of contact (n = 1), and death (n = 5).We concluded that RAL-RN and IVC thrombectomy renders good safety profiles including minimal invasiveness, low estimated median blood loss, short hospitalization, low morbidity, and quick renal function recovery. The long-term efficacy needs a further investigation.

PHLDA3 exerts an antitumor function in prostate cancer by down-regulating Wnt/ß-catenin pathway via inhibition of Akt.

Pleckstrin homology-like domain family A, member 3 (PHLDA3) is a novel tumor-related protein that mediates carcinogenesis of multiple cancers. However, the relevance of PHLDA3 in prostate cancer has not been explored. The purpose of this work was to illustrate the possible roles and mechanisms of PHLDA3 in prostate cancer. Our data showed strikingly lower abundance of PHLDA3 in prostate cancer, and that low levels of PHLDA3 in prostate cancer patients was associated with reduced survival. PHLDA3 was also weakly expressed in prostate cancer cells, and demethylation treatment dramatically up-regulated the expression level of PHLDA3. Up-regulation of PHLDA3 restrained proliferation, induced G1 cell cycle arrest, suppressed epithelial-mesenchymal transition of prostate cancer cells. In addition, up-regulation of PHLDA3 increased the sensitivity of prostate cancer cells to docetaxel In-depth research into the mechanism elucidated that PHLDA3 overexpression decreased the phosphorylation of Akt and suppressed the activation of Wnt/ß-catenin signaling. Overexpression of constitutively active Akt strikingly abolished PHLDA3-mediated inactivation of Wnt/ß-catenin pathway. A xenograft assay revealed that prostate cancer cells with PHLDA3 overexpression displayed reduced tumorigenicity in vivo. Collectively, these data document that PHLDA3 exerts an outstanding cancer-inhibiting role in prostate cancer by down-regulating Wnt/ß-catenin pathway via the inhibition of Akt. This work highlights PHLDA3 as a novel anticancer target for prostate cancer.

Treatment options for older unfit patients with acute myeloid leukemia.

Older acute myeloid leukemia patients usually experience a bleak outcome, especially those in the unfit group. For this unfit category, intensive chemotherapy and allogeneic stem cell transplantation are usually accompanied by higher early mortality, which results from higher risk genetic profiles and worse psychological and physiological conditions. The significant improvement in genetic technology recently has driven the appearance of several mutation-targeted therapies, such as FLT3, Bcl-2, IDH and Hedgehog pathway inhibitors and an anti-CD33 antibody-drug conjugate, which have changed enormously the therapeutic landscape of acute myeloid leukemia. This review describes the treatment dilemma of the unfit group and discusses the objective clinical data of each targeted drug and mechanisms of resistance, with a focus on combination strategies with fewer toxicities and abrogation of drug resistance.

Investigating the Mechanism of Hyperglycemia-Induced Fetal Cardiac Hypertrophy.

Hyperglycemia in diabetic mothers enhances the risk of fetal cardiac hypertrophy during gestation. However, the mechanism of high-glucose-induced cardiac hypertrophy is not largely understood. In this study, we first demonstrated that the incidence rate of cardiac hypertrophy dramatically increased in fetuses of diabetic mothers using color ultrasound examination. In addition, human fetal cardiac hypertrophy was successfully mimicked in a streptozotocin (STZ)-induced diabetes mouse model, in which mouse cardiac hypertrophy was diagnosed using type-M ultrasound and a histological assay. PH3 immunofluorescent staining of mouse fetal hearts and in vitro-cultured H9c2 cells indicated that cell proliferation decreased in E18.5, E15.5 and E13.5 mice, and cell apoptosis in H9c2 cells increased in the presence of high glucose in a dose-dependent manner. Next, we found that the individual cardiomyocyte size increased in pre-gestational diabetes mellitus mice and in response to high glucose exposure. Meanwhile, the expression of ß-MHC and BMP-10 was up-regulated. Nkx2.5 immunofluorescent staining showed that the expression of Nkx2.5, a crucial cardiac transcription factor, was suppressed in the ventricular septum, left ventricular wall and right ventricular wall of E18.5, E15.5 and E13.5 mouse hearts. However, cardiac hypertrophy did not morphologically occur in E13.5 mouse hearts. In cultured H9c2 cells exposed to high glucose, Nkx2.5 expression decreased, as detected by both immunostaining and western blotting, and the expression of KCNE1 and Cx43 was also restricted. Taken together, alterations in cell size rather than cell proliferation or apoptosis are responsible for hyperglycemia-induced fetal cardiac hypertrophy. The aberrant expression of Nkx2.5 and its regulatory target genes in the presence of high glucose could be a principal component of pathogenesis in the development of fetal cardiac hypertrophy.