Fc-competent multispecific PDL-1/TIGIT/LAG-3 antibodies potentiate superior anti-tumor T cell response.

The landscape of current cancer immunotherapy is dominated by antibodies targeting PD-1/PD-L1 and CTLA-4 that have transformed cancer therapy, yet their efficacy is limited by primary and acquired resistance. The blockade of additional immune checkpoints, especially TIGIT and LAG-3, has been extensively explored, but so far only a LAG-3 antibody has been approved for combination with nivolumab to treat unresectable or metastatic melanoma. Here we report the development of a PDL1 × TIGIT bi-specific antibody (bsAb) GB265, a PDL1 × LAG3 bsAb GB266, and a PDL1 × TIGIT × LAG3 tri-specific antibody (tsAb) GB266T, all with intact Fc function.

Current status and implications of microRNAs in ovarian cancer diagnosis and therapy.

Ovarian cancer is the fifth most common cancer among women and causes more deaths than any other type of female reproductive cancer. Currently, treatment of ovarian cancer is based on the combination of surgery and chemotherapy. While recurrent ovarian cancer responds to additional chemotherapy treatments, the progression-free interval becomes shorter after each cycle, as chemo-resistance increases until the disease becomes incurable.

Inhibition of PTEN gene expression by oncogenic miR-23b-3p in renal cancer.

Background: miR-23b is located on chromosome number 9 and plays different roles in different organs especially with regards to cancer development. However, the functional significance of miR-23b-3p in renal cell carcinoma (RCC) has not been reported.

Methods And Results: We measured miR-23b-3p levels in 29 pairs of renal cell carcinoma and their normal matched tissues using real-time PCR.

miRNA-34b inhibits prostate cancer through demethylation, active chromatin modifications, and AKT pathways.

Purpose: miRNAs can act as oncomirs or tumor-suppressor miRs in cancer. This study was undertaken to investigate the status and role of miR-34b in prostate cancer.

Experimental Design: Profiling of miR-34b was carried out in human prostate cancer cell lines and clinical samples by quantitative real-time PCR and in situ hybridization.

miR-23b represses proto-oncogene Src kinase and functions as methylation-silenced tumor suppressor with diagnostic and prognostic significance in prostate cancer.

The miRNAs have great potential as biomarkers and therapeutic agents owing to their ability to control multiple genes and potential to influence cellular behavior. Here, we identified that miR-23b is a methylation-silenced tumor suppressor in prostate cancer. We showed that miR-23b expression is controlled by promoter methylation and has great promise as a diagnostic and prognostic biomarker in prostate cancer.

MicroRNA-1280 inhibits invasion and metastasis by targeting ROCK1 in bladder cancer.

MicroRNAs (miRNAs) are non-protein-coding sequences that can function as oncogenes or tumor suppressor genes. This study documents the tumor suppressor role of miR-1280 in bladder cancer. Quantitative real-time PCR and in situ hybridization analyses showed that miR-1280 is significantly down-regulated in bladder cancer cell lines and tumors compared to a non-malignant cell line or normal tissue samples.

Genistein suppresses prostate cancer growth through inhibition of oncogenic microRNA-151.

Genistein has been shown to suppress the growth of several cancers through modulation of various pathways. However, the effects of genistein on the regulation of oncogenic microRNA-151 (miR-151) have not been reported. In this study, we investigated whether genistein could alter the expression of oncogenic miR-151 and its target genes that are involved in the progression and metastasis of prostate cancer (PCa).

miRNA-708 control of CD44(+) prostate cancer-initiating cells.

Tumor recurrence in prostate cancer has been attributed to the presence of CD44-expressing tumor-initiating cells. In this study, we report that miR-708 is a key negative regulator of this CD44(+) subpopulation of prostate cancer cells, with important implications for diagnosis and prognosis of this disease. miR-708 was underexpressed in CD44(+) cells from prostate cancer xenografts.

Up-regulation of microRNA-21 correlates with lower kidney cancer survival.

Background: MicroRNA-21 is up-regulated in a variety of cancers like, breast, colorectal, lung, head and neck etc. However, the regulation of miR-21 in renal cell carcinoma (RCC) has not yet been studied systematically.

Methods And Results: We measured miR-21 levels in 54 pairs of kidney cancers and their normal matched tissues by real-time PCR.

MicroRNA-145 is regulated by DNA methylation and p53 gene mutation in prostate cancer.

MiR-145 is downregulated in various cancers including prostate cancer. However, the underlying mechanisms of miR-145 downregulation are not fully understood. Here, we reported that miR-145 was silenced through DNA hypermethylation and p53 mutation status in laser capture microdissected (LCM) prostate cancer and matched adjacent normal tissues.

MicroRNA-205 inhibits Src-mediated oncogenic pathways in renal cancer.

The Src family of protein kinases (SFK) plays key roles in regulating fundamental cellular processes, including cell growth, differentiation, cell shape, migration, and survival, and specialized cell signals in various malignancies. The pleiotropic functions of SFKs in cancer make them promising targets for intervention. Here, we sought to investigate the role of microRNA-205 (miR-205) in inhibition of Src-mediated oncogenic pathways in renal cancer.

MicroRNAs 221/222 and genistein-mediated regulation of ARHI tumor suppressor gene in prostate cancer.

ARHI is an imprinted tumor suppressor gene and is downregulated in various malignancies. However, ARHI expression, function, and mechanisms of action in prostate cancer have not been reported. Here, we report that ARHI mRNA and protein levels were downregulated in prostate cancer tissues compared with adjacent normal tissues.

Cytochrome P450 17 (CYP17) is involved in endometrial cancinogenesis through apoptosis and invasion pathways.

Cytochrome P450 17 (CYP17) encodes cytochrome P450c17α, an enzyme with 17α-hydroxylase and 17, 20-lyase activities involved in estradiol biosynthesis. Here we examine the role of CYP17 gene in endometrial carcinogenesis. Immunohistochemistry staining of endometrial carcinoma and corresponding uninvolved tissues showed that CYP17 is upregulated in endometrial cancers (15 of 24, 62.

Regulation of minichromosome maintenance gene family by microRNA-1296 and genistein in prostate cancer.

The minichromosome maintenance (MCM) gene family is essential for DNA replication and is frequently upregulated in various cancers. Here, we examined the role of MCM2 in prostate cancer and the effect of microRNA-1296 (miR-1296), genistein, and trichostatin A (TSA) on the MCM complex. Profiling results showed that expression of MCM genes was higher in tumor samples.

Crystal structure of the Bacillus anthracis nucleoside diphosphate kinase and its characterization reveals an enzyme adapted to perform under stress conditions.

Nucleoside diphosphate kinases (Ndks) play an important role in a plethora of regulatory and metabolic functions. Inhibition of the B. anthracis Ndk mRNA results in the formation of nonviable aberrant spores.

Spo0B of Bacillus anthracis - a protein with pleiotropic functions.

Spo0B is an important component of the phosphorelay signal transduction pathway, the pathway involved in the initiation of sporulation in Bacillus subtilis. Bioinformatic, phylogenetic and biochemical studies showed that Spo0B of Bacillus anthracis has evolved from citrate/malate kinases. During the course of evolution, Spo0B has retained the characteristic histidine kinase boxes H, N, F, G(1) and G(2), and has acquired nucleotide-binding domains, Walker A and Walker B, of ATPases.

Imaging and analysis of Bacillus anthracis spore germination.

External and internal changes occurring during the process of germination of Bacillus anthracis spores were observed through atomic force microscopy (AFM) and transmission electron microscopy (TEM), respectively. AFM studies showed that in response to L-alanine (4 mM), as a germinant, the spore germinates into a vegetative cell in 3 hours. The temporal size changes occurring during the germination were gradual but the major change in size was observed between the second and third hour.