The world's first CD138/CD3 BiTE-hIgFc targeting T cells, natural killer cells and multiple myeloma cells simultaneously has nanomolar-level affinity to recombinant hCD138 protein and has shown potent antitumor activity against RPMI-8226 tumor cells in vitro and in vivo.

In this study, we found the frequency of HLA-E*0103 allele was increased in patients with serous ovarian cancer, and HLA-E*0103/peptides complex was stable. Thus, the elevated expression of total and cell surface HLA-E molecule with HLA-E*0103 allele increased the inhibitory effect on NK cell lysis, rendering tumor cells escape from NK immune surveillance. This study is the first one to evaluate the correlation between HLA-E alleles and serous ovarian cancer.

To support development of a combined assay for general toxicity and genotoxicty by using transgenic rodents, we provide evidences that indicate equivalence of gpt delta rats, which carry reporter genes to detect in vivo genotoxicity, to their parental wild type in terms of toxicological responses. DEN- or DEHP- treated F344 and SD strains of gpt delta rats display comparable general toxicity and genotoxicity to wild type. Our results indicate that the combined assay using gpt delta rats was applicable for simultaneous detection of both general toxicity and genotoxicity for short durations of administration.

Hepatic SIRT1 activity was repressed in non-B non-C patients, and low activity of SIRT1 may lead to hepatic inflammation and carcinogenesis in non-B non-C patients.

The specific disruption of BIG3-PHB2 complex, which is a critical modulator in estrogen signaling, leads to a novel therapeutic approach for endocrine-resistance in breast cancer cells activated by signaling crosstalk between estrogen and growth factors or HER2 amplification, especially in premenopausal women.

Although the function of SIRT6 could be tumor-promoting or tumor-suppressing, TGF-β1/H₂O₂/HOCl-mediated up-regulation of SIRT6 in HCC cells was tumor-promotional, but not tumor-suppressing. Suppressing the up-regulation of SIRT6 enabled TGF-β1/H₂O₂/HOCl to induce cellular senescence, thereby abrogating the enhancement of HCC cell tumorigenicity by TGF-β1/H₂O₂/HOCl.

To improve the outcome of cancer chemotherapy, the strategies to enhance the efficacy of anticancer drugs are required. Suppression of glycolysis by retinoic acid sensitized hepatocellular carcinoma cells to apoptosis induced by sorafenib via AMPK activation. Our findings suggest that ATRA is useful for enhancing the cytotoxicity of sorafenib against HCC cells by regulating energy metabolism of HCC cells.

Catechol-O-methyltransferase (COMT) serves as a tumor-suppressor for pancreatic cancer. Higher COMT levels in the surgical specimens predict longer survival. COMT also inhibits pancreatic cell growth, increases gemcitabine-induced apoptosis and inhibits invasion.

We demonstrated that up-regulation of the BRCA/Fanconi anemia pathway was one mechanism of chemo-resistance to gemcitabine. GEM exposure would lead to enrichment of the CD24⁺/44⁺ cells highly-expressing BRCA/FA in BTC, which would cause co-resistance to GEM and CDDP. Inhibiting the BRCA/FA pathway decreased the CD24⁺/44⁺ population and restored chemo-resistance in GEM resistant BTC cells.

High IL-11 expression in ccRCC tissues is associated with a greater risk of recurrence and reduced survival in patients with ccRCC, especially in early-stage patients. And high IL-11 expression is an independent predictor of poor clinical outcome in patients with ccRCC. It may help identify patients who could benefit from additional treatments and closer follow-up.

The CADM1 vs. CD7 plot (flow cytometry) for CD4⁺ cells from peripheral blood revealed the diversity of disease stages in asymptomatic HTLV-1 carriers (AC) as well as ATL, and will help us to identify advanced AC with a similar disease status to indolent ATL patients at an early stage. Some cases of smoldering ATL and AC could not be distinguished; therefore, a new clinical category that includes these cases is warranted.

We evaluated the associtation between serum levels of ligands and grade of skin toxicity by anti-EGFR antibody treatment in metastatic clorectal cancer patients. Serum levels of HGF, EREG and AREG were inversely proportional to grades of skin toxicity as determined by the Cochran–Armitage test (P = 0.019, P = 0.047, P = 0.021, respectively). Our study indicated that serum levels such as HGF, EREG and AREG may be significant markers to predict the grade of skin toxicity and the prognosis of anti-EGFR antibody treatment.

The present study showed for the first time the prognosis of Japanese patients with metastatic renal cell carcinoma in the era of molecular-targeted therapy. The JMRC prognostic classification may be clinically useful as a prognostic model.

Considering its possible clinical use, our anti-TF-NC-6300 may continue to exert a high antitumor activity despite the existence of the tumor stromal barrier, since anti-TF-NC-6300 was capable of suppressing tumor growth associated with damage to the tumor vessels and the death of cancer cells in humans.

We found that thiacalixarene-cadmium complex has an anti-proliferative effect against T-cell leukemia cells, with no cytotoxicity in epithelia-derived cancer cells in vitro and minimum accumulations of cadmium in mice. In xenograft tumor model, cadmium-complex treatment significantly suppressed tumor growth of Jurkat cells in mice. These results suggest that thiacalixarene-cadmium complex may have therapeutic potential for treatment of T-cell leukemia.

Alterations of EGFR and AKT1 gene copy numbers in breast cancer cells detected by M-FISH.

This study was conducted to define the potential predictive and/or prognostic value of a miRNA expression profile of desmoid tumors. The results bring the first demonstration of the prognostic value of miRNA profile in DT. The results were obtained in a cohort of patients included in a clinical phase II trial and validated in an independent cohort. The implication of such a discovery will be important in the management of patients with tumors particularly over-treated.

We found that the down-regulation of NELL1 and NELL2 in renal cell carcinoma (RCC) is in part due to the hypermethylation of CpG islands in their putative promoter regions. Furthermore, we found that NELL1 suppresses and NELL2 partially suppresses RCC cell migration, and NELL1 further inhibits RCC cell adhesion.