Transcriptome analysis of a dog model of congestive heart failure shows that collagen-related 2-oxoglutarate-dependent dioxygenases contribute to heart failure.

Fibrosis is an important pathological mechanism in heart failure (HF) and is associated with poor prognosis. We analyzed fibrosis in HF patients using transcriptomic data. Genes differentially expressed between normal control and congestive HF (CHF) dogs included P3H1, P3H2, P3H4, P4HA2, PLOD1 and PLOD3, which belong to the 2-oxoglutarate-dependent dioxygenases (2OGD) superfamily that stabilizes collagen during fibrosis.

A risk stratification model based on four novel biomarkers predicts prognosis for patients with renal cell carcinoma.

Background: Accurate prediction of the prognosis of RCC using a single biomarker is challenging due to the genetic heterogeneity of the disease. However, it is essential to develop an accurate system to allow better patient selection for optimal treatment strategies. ARL4C, ECT2, SOD2, and STEAP3 are novel molecular biomarkers identified in earlier studies as survival-related genes by comprehensive analyses of 43 primary RCC tissues and RCC cell lines.

Analysis of the characteristics of chemotherapy-resistant renal cell carcinomas based on global transcriptional analysis of their tissues and cell lines.

Starvation-resistant renal cell carcinoma (RCC) cell lines are considered dormant-state cells that survive even under glucose starvation. The cellular biological and global transcriptional analysis using these cells identified potential markers of chemotherapy-resistant RCC and therapeutic agent candidates. Recently, we showed that ARL4C was a predictive biomarker for poor prognosis in patients with chemotherapy-resistant RCC by the global transcriptional analysis of patient primary tissues.

ADP-ribosylation factor-like 4C is a predictive biomarker of poor prognosis in patients with renal cell carcinoma.

Renal cell carcinoma (RCC) has the high mortality rate among urological malignancies. The development of RCC cannot be effectively reduced by molecular targeted therapies based on nutrient deprivation, such as inhibition of tumor angiogenesis. The objective of this study was to identify predictive biomarkers of poor prognosis and therapeutic molecular targets in patients with RCC.

Abundance of mitochondrial superoxide dismutase is a negative predictive biomarker for endometriosis-associated ovarian cancers.

Background: Endometrioid ovarian carcinoma and clear cell ovarian carcinoma are both classified as endometriosis-associated ovarian cancers (EAOCs). Despite the high rates of recurrence and mortality of EAOC, only a few prognostic biomarkers have been reported. Mitochondrial superoxide dismutase (SOD2) plays an important role in maintaining mitochondrial function through oxidative stress tolerance and contributes to chemotherapeutic resistance.

ADP-ribosylation factor-like 4C predicts worse prognosis in endometriosis-associated ovarian cancers.

Background: Endometrioid ovarian carcinoma and clear cell ovarian carcinoma are both classified as endometriosis-associated ovarian cancer (EAOC). Despite the high rates of recurrence and mortality of EAOC, no prognostic biomarkers have been determined. ADP-ribosylation factor-like protein 4C (ARL4C) has been reported to be involved in various tumor progression processes, but its clinical significance for predicting prognosis in EAOC cases has never been studied.

Mechanisms of Tumor Growth Inhibition by Depletion of γ-Glutamylcyclotransferase (GGCT): A Novel Molecular Target for Anticancer Therapy.

γ-Glutamylcyclotransferase (GGCT), which is one of the major enzymes involved in glutathione metabolism, is upregulated in a wide range of cancers-glioma, breast, lung, esophageal, gastric, colorectal, urinary bladder, prostate, cervical, ovarian cancers and osteosarcoma-and promotes cancer progression; its depletion leads to the suppression of proliferation, invasion, and migration of cancer cells. It has been demonstrated that the suppression or inhibition of GGCT has an antitumor effect in cancer-bearing xenograft mice. Based on these observations, GGCT is now recognized as a promising therapeutic target in various cancers.

Superoxide dismutase 2 expression can predict prognosis of renal cell carcinoma patients.

Background And Objective: Renal cell carcinoma (RCC) is the urological malignancy with the highest mortality rate and is increasing in incidence. The prognostic and predictive biomarkers are highly desired. This study aims to investigate the significance of superoxide dismutase 2 (SOD2) as a clinical biomarker in patients with renal cell carcinomas.

Abundance of TRAIL attenuated by HIF2α and c-FLIP affects malignancy in renal cell carcinomas.

Dormant cancer cells are starvation-resistant leading to problems in the management of cancer. In renal cell carcinomas (RCCs), starvation-resistant cells are resistant to various currently available therapies. However, targeting hypoxia inducible factor 2-alpha (HIF2-alpha) induces cell death in dormant-like/starvation-resistant RCCs.

Hydroxyl-HIF2-alpha is potential therapeutic target for renal cell carcinomas.

Dormant cancer cells are deprivation-resistant, and cause a number of problems for therapeutic approaches for cancers. Renal cell carcinomas (RCCs) include deprivation-resistant cells that are resistant to various treatments. In this study, the specific characteristics of deprivation-resistant cells were transcriptionally identified by next generation sequencing.

Therapeutic inhibition of mitochondrial function induces cell death in starvation-resistant renal cell carcinomas.

Renal cell carcinomas (RCC) have two types of cells for carbon metabolism and for cell signaling under nutrient-deprivation conditions, namely starvation-resistant and starvation-sensitive cells. Here, we evaluated the mitochondrial characteristics of these cell types and found that the resistant type possessed higher activities for both mitochondrial oxidative phosphorylation and glycolysis than the sensitive types. These higher activities were supported by the stored carbon, lipid and carbohydrate sources, and by a low level of mitochondrial reactive oxygen species (ROS) due to sustained SOD2 expression in the resistant RCC cells.

Metastatic Prostatic Ductal Adenocarcinoma Successfully Treated with Docetaxel Chemotherapy: A Case Report.

A 68-year-old man presented with gross hematuria. A papillary urethral tumor adjacent to the verumontanum was found by cystourethroscopy. Serum prostate-specific antigen (PSA) was 3.

Glucose deprivation induces G2/M transition-arrest and cell death in N-GlcNAc2-modified protein-producing renal carcinoma cells.

Some cancer cells can survive under glucose deprivation within the microenvironment of a tumor. Recently, we reported that N-linked (β-N-acetylglucosamine)2 [N-GlcNAc2]-modified proteins induce G2/M arrest and cell death under glucose deprivation. Here, we investigated whether such a response to glucose deprivation contributes to the survival of renal cell carcinomas, which are sensitive to nutritional stress.

Suppression of cerebral aneurysm formation in rats by a tumor necrosis factor-α inhibitor.

Object: Although cerebral aneurysmal subarachnoid hemorrhage is a devastating disease for humans, effective medical treatments have not yet been established. Recent reports have shown that regression of some inflammatory-related mediators has protective effects in experimental cerebral aneurysm models. This study corroborated the effectiveness of tumor necrosis factor-α (TNF-α) inhibitor for experimentally induced cerebral aneurysms in rats.

Analysis of new biomarkers for cholangiocarcinoma.

Cholangiocarcinoma is one of the most serious diseases in northeast Thailand, where its incidence is reported to be the highest in the world. We tried to develop a new method to detect cholangiocarcinoma in the early stages using serum proteins. We found that after fluorescent labeling of the sugar moiety of serum proteins, a new peak was identified, which might be a promising marker for cholangiocarcinoma.

Female-specific rectal carcinogenesis in cyclin D1b transgenic mice.

Human cyclin D1 generates two major isoforms via alternative splicing: cyclin D1a and cyclin D1b. Cyclin D1b is hardly expressed in normal tissues but is frequently expressed in certain types of cancer tissues. To clarify the oncogenic potential of cyclin D1b variant, we developed cyclin D1b transgenic (Tg) mice and analyzed their phenotypes.

Study of global transcriptional changes of N-GlcNAc2 proteins-producing T24 bladder carcinoma cells under glucose deprivation.

Increased levels of N-linked (β-N- acetylglucosamine)2 [N-GlcNAc2]-modified proteins have been recognized to be an effective response to glucose deprivation. In the first step of this study, using a next generation sequencer, we investigated the global transcriptional changes induced by glucose deprivation in a T24 bladder carcinoma cell line, producing N-GlcNAc2-modified proteins under glucose deprivation. Our transcriptome analysis revealed significant up-regulation of the UDP-GlcNAc biosynthesis pathway and unfolded protein response genes, and down-regulation of G2/M transition-related genes containing mitotic kinases.

A global transcriptome analysis of a dog model of congestive heart failure with the human genome as a reference.

Background: The global molecular changes in cardiac tissue during congestive heart failure (CHF) have not been fully examined. Transcriptome analysis with the use of next-generation sequencers is a useful tool for elucidating the pathogenesis of CHF. Although there are some advantages in a dog CHF model, transcriptome analyses in dogs are limited by the relative lack of genomic information.

PKC-Mediated ZYG1 Phosphorylation Induces Fusion of Myoblasts as well as of Dictyostelium Cells.

We have previously demonstrated that a novel protein ZYG1 induces sexual cell fusion (zygote formation) of Dictyostelium cells. In the process of cell fusion, involvements of signal transduction pathways via Ca(2+) and PKC (protein kinase C) have been suggested because zygote formation is greatly enhanced by PKC activators. In fact, there are several deduced sites phosphorylated by PKC in ZYG1 protein.

RB1CC1 activates the p16 promoter through the interaction with hSNF5.

RB1-inducible coiled-coil 1 (RB1CC1, also known as FIP200) is involved in dephosphorylation and increase of retinoblastoma tumor suppressor protein (RB1), but the RB1CC1 molecular mechanism in the dephosphorylation of RB1 is not fully understood. We determined that RB1CC1 activates the expression of p16 (also called INK4a/CDKN2a) through the activation of its promoter, using chromatin immunoprecipitation (ChIP) and p16 promoter-luciferase reporter assays. In addition, RB1CC1 essentially requires binding with hSNF5 (also known as BAF47/INI1, a chromatin-remodeling factor) to activate the p16 promoter, in order to enhance the RB1 pathway and acts as a tumor suppressor.

O-GlcNAc-specific antibody CTD110.6 cross-reacts with N-GlcNAc2-modified proteins induced under glucose deprivation.

Modification of serine and threonine residues in proteins by O-linked β-N-acetylglucosamine (O-GlcNAc) glycosylation is a feature of many cellular responses to the nutritional state and to stress. O-GlcNAc modification is reversibly regulated by O-linked β-N-acetylglucosamine transferase (OGT) and β-D-N-acetylglucosaminase (O-GlcNAcase). O-GlcNAc modification of proteins is dependent on the concentration of uridine 5'-diphospho-N-acetylglucosamine (UDP-GlcNAc), which is a substrate of OGT and is synthesized via the hexosamine biosynthetic pathway.

RB1CC1 together with RB1 and p53 predicts long-term survival in Japanese breast cancer patients.

RB1-inducible coiled-coil 1 (RB1CC1) plays a significant role in the enhancement of the retinoblastoma tumor suppressor (RB1) pathway and is involved in breast cancer development. However, RB1CC1's role in clinical progression of breast cancer has not yet been evaluated, so, as a first step, it is necessary to establish its usefulness as a tool to evaluate breast cancer patients. In this report, we have analyzed the correlation between abnormalities in the RB1CC1 pathway and long-term prognosis, because disease-specific death in later periods (>5 years) of the disease is a serious problem in breast cancer.

RB1CC1 activates RB1 pathway and inhibits proliferation and cologenic survival in human cancer.

RB1-inducible coiled-coil 1 (RB1CC1, also known as FIP200) plays a role in the enhancement of the RB1 pathway through the direct binding to a GC-rich region 201bp upstream (from the initiation ATG) of the RB1 promoter. Here, we identified hSNF5 and p53 as the binding partners of RB1CC1 by immunoprecipitation and immunofluorescence assays. Interaction between these molecules and the RB1 pathway was analyzed by the assays of chromatin immunoprecipitation, luciferase-reporter, reverse transcription-polymerase chain reaction and immunoblot.

Characterization of the rapidly activating delayed rectifier potassium current, I (Kr), in HL-1 mouse atrial myocytes.

HL-1 is the adult murine cardiac cell line that can be passaged repeatedly in vitro without losing differentiated phenotype. The present study was designed to characterize the rapidly activating delayed rectifier potassium current, I (Kr), endogenously expressed in HL-1 cells using the whole-cell patch-clamp technique. In the presence of nisoldipine, depolarizing voltage steps applied from a holding potential of -50 mV evoked the time-dependent outward current, followed by slowly decaying outward tail current upon return to the holding potential.