An anti-glypican 3/CD3 bispecific T cell-redirecting antibody for treatment of solid tumors.

Cancer care is being revolutionized by immunotherapies such as immune checkpoint inhibitors, engineered T cell transfer, and cell vaccines. The bispecific T cell-redirecting antibody (TRAB) is one such promising immunotherapy, which can redirect T cells to tumor cells by engaging CD3 on a T cell and an antigen on a tumor cell. Because T cells can be redirected to tumor cells regardless of the specificity of T cell receptors, TRAB is considered efficacious for less immunogenic tumors lacking enough neoantigens.

LGR5-positive colon cancer stem cells interconvert with drug-resistant LGR5-negative cells and are capable of tumor reconstitution.

The cancer stem cell (CSC) concept has been proposed as an attractive theory to explain cancer development, and CSCs themselves have been considered as targets for the development of diagnostics and therapeutics. However, many unanswered questions concerning the existence of slow cycling/quiescent, drug-resistant CSCs remain. Here we report the establishment of colon cancer CSC lines, interconversion of the CSCs between a proliferating and a drug-resistant state, and reconstitution of tumor hierarchy from the CSCs.

Integration of proteomic analyses to monitor the activity status of phosphorylation signaling.

We performed here MS-based phosphoproteomics using both metal oxide affinity chromatography (pSTY proteomics) and anti-phosphotyrosine antibody (pY proteomics). The former method identified mainly phospho-serine and -threonine of nuclear or cytoplasmic proteins, whereas the latter did phosphotyrosine including more plasma membrane proteins and kinases. The overlap between these two methods was limited (24 tyrosine phosphorylation sites out of 325) and, by combining the two, coverage of the signaling molecules was enhanced as exemplified by Erk signaling.

Phosphoproteomic analysis of distinct tumor cell lines in response to nocodazole treatment.

Here, we report for the first time a comparative phosphoproteomic analysis of distinct tumor cell lines in the presence or absence of the microtubule-interfering agent nocodazole. In total, 1525 phosphorylation sites assigned to 726 phosphoproteins were identified using LC-MS-based technology following phosphopeptide enrichment. Analysis of the amino acid composition surrounding the identified in vivo phosphorylation sites revealed that they could be classified into two motif groups: pSer-Pro and pSer-Asp/Glu.

Cancer DNA microarray analysis considering multi-subclass with graph-based clustering method.

It is well known that various genes related to cell cycle, cell-cell adhesion, and transcriptional regulation cause the onset of cancer. Moreover, environmental factors including age, sex, and lifestyle can also contribute to the onset of cancer. Therefore, it is difficult to ascertain which factors influence the onset.

Association study between Apolipoprotein L and schizophrenia by exhaustive and rule-based combination analysis for identification of multilocus interactions.

Several single marker association and haplotypic analyses have been performed to identify susceptible genes for various common diseases, but these approaches using candidate genes did not provide accurate and consistent evidence in each analysis. This inconsistency is partly due to the fact that the common diseases are caused by complex interactions among various genetic factors. Therefore, in this study, to evaluate exhaustive genotype or allele combinations, we applied the binomial and random permutation test (BRP) proposed by Tomita et al.

Minimal sizes of cases with a susceptible genotype and minimal odds ratios among susceptible individuals in case-control studies.

Objective: Disease risk elevation due to an environmental factor only for individuals with a susceptible genotype is a typical example of gene-environment interaction. In order to identify risk factors interacting with susceptible genotypes in case-control studies, presumptions on minimal size of cases with the susceptible genotype (S (min)) and odds ratio (OR) among the susceptible individuals (OR(susceptible)) are useful.

Model: Proportion of exposed cases (P(1)) and OR for whole cases (OR(whole)) statistically detectable in a case-control study can be calculated in a conventional method.