Japanese Foundation for Cancer Research

About: Japanese Foundation for Cancer Research is a nonprofit organization based out in Tokyo, Japan. It is known for research contribution in the topics: Cancer & Breast cancer. The organization has 2676 authors who have published 5482 publications receiving 221859 citations.

Inhibition of the mitogen-activated protein kinase pathway results in the down-regulation of P-glycoprotein

Abstract: The multidrug resistance gene 1 (MDR1) product, P-glycoprotein (P-gp), pumps out a variety of anticancer agents from the cell, including anthracyclines, Vinca alkaloids, and taxanes. The expression of P-gp therefore confers resistance to these anticancer agents. In our present study, we found that FTI-277 (a farnesyltransferase inhibitor), U0126 [an inhibitor of mitogen-activated protein kinase/extracellular signal-regulated kinase (ERK) kinase (MEK)], and 17-allylamino-17-demethoxygeldanamycin (an inhibitor of heat shock protein 90) reduced the endogenous expression levels of P-gp in the human colorectal cancer cells, HCT-15 and SW620-14. In contrast, inhibitors of phosphatidylinositol 3-OH kinase, mammalian target of rapamycin, p38 mitogen-activated protein kinase, and c-Jun NH(2)-terminal kinase did not affect P-gp expression in these cells. We further found that U0126 down-regulated exogenous P-gp expression in the MDR1-transduced human breast cancer cells, MCF-7/MDR and MDA-MB-231/MDR. However, the MDR1 mRNA levels in these cells were unaffected by this treatment. PD98059 (a MEK inhibitor), ERK small interfering RNA, and p90 ribosomal S6 kinase (RSK) small interfering RNA also suppressed P-gp expression. Conversely, epidermal growth factor and basic fibroblast growth factor enhanced P-gp expression, but the MDR1 mRNA levels were unchanged in epidermal growth factor-stimulated cells. Pulse-chase analysis revealed that U0126 promoted P-gp degradation but did not affect the biosynthesis of this gene product. The pretreatment of cells with U0126 enhanced the paclitaxel-induced cleavage of poly(ADP-ribose) polymerase and paclitaxel sensitivity. Furthermore, U0126-treated cells showed high levels of rhodamine123 uptake. Hence, our present data show that inhibition of the MEK-ERK-RSK pathway down-regulates P-gp expression levels and diminishes the cellular multidrug resistance.

Indications for Lateral Pelvic Lymph Node Dissection Based on Magnetic Resonance Imaging Before and After Preoperative Chemoradiotherapy in Patients with Advanced Low-Rectal Cancer.

Abstract: Background We assessed the magnetic resonance imaging (MRI) findings of lateral pelvic lymph node (LPLN) metastasis in patients with advanced low-rectal cancer treated with preoperative chemoradiotherapy (CRT) and LPLN dissection (LPLD) for clinically suspected LPLN metastasis. Our aim was to identify the optimal indications for LPLD.

Site-specific cancer risk due to diabetes mellitus history: evidence from the Japan Collaborative Cohort (JACC) Study.

Abstract: The study examined the association of diabetes mellitus (DM) history with total and common site-specific cancers using a large cohort of 23,378 men and 33,503 women, extracted from 127,477 healthy participants of the JACC Study who were aged 40-79 years and living in 24 municipalities in Japan. At enrolment during 1988-90, each subject completed a self-administered questionnaire including items for age, sex, body mass index (BMI), smoking, drinking, past history of DM and cancer. Adjusting for age, BMI, smoking, and drinking in the Cox’s proportional hazard model, incidence rate ratios (IRR) with 95% confidence intervals (95%CIs) were estimated for both sexes. During the follow-up period, total cancers and site-specific cancers were identified. A history of DM was reported by 7.5% of men and 4.6% of women. DM significantly increased the risk of liver cancer for both men (IRR=2.30; 95%CI=1.47-3.59) and women (IRR=2.70; 95%CI=1.20-6.05). Significant increased and reduced risk due to DM for men were also found for non-Hodgkin lymphoma (IRR=2.77; 95%CI=1.04-7.38) and stomach cancer (IRR=0.67; 95%CI=0.46-0.99) respectively. For females, a reduced risk of stomach cancer due to DM (IRR=0.49; 95%CI=0.231.04) was also revealed. Since a history of DM here demonstrated significant associations with some site-specific cancers, their relationships should be studied further in Japan for validation.

Interleukin 2 (IL2) is assigned to human chromosome 4.

Abstract: The human gene for interleukin 2 (IL2)was assigned to chromosome 4 using human-mouse somatic cell hybrids and Southern filter hybridization of cell hybrid DNA. To identify IL2,a recombinant DNA probe (pIL2-50A) was used which contained a human interleukin 2 cDNA insert which hybridized to a 3.5-kb fragment in human DNA when cleaved with the restriction enzyme EcoRL.