Guidelines for clinical evaluation of anti-cancer drugs.

Clinical studies intended for regulatory approval must demonstrate the clinical benefits of the drug in a target population. Clinical development of a drug proceeds by stepwise clinical studies; after safety and pharmacokinetics are evaluated and the recommended dosage and administration are determined, efficacy and safety are evaluated in an exploratory manner, and finally clinical benefits are compared with conventional standard therapies. Guidelines for the clinical evaluation of anti-cancer drugs in Japan were established in 1991 and amended in 2006 after molecular-targeted drugs were introduced.

The Cs activity concentration of suspended and dissolved fractions in irrigation waters collected from the 80 km zone around TEPCO's Fukushima Daiichi Nuclear Power Station.

Fifty-four samples of irrigation water were collected in 2014 from agricultural ponds, rivers, and dams within the 80 km zone around TEPCO's Fukushima Daiichi Nuclear Power Station (FDNPS). The samples were filtered with a 0.45 μm pore-size membrane filter to produce suspended and dissolved fractions.

Anti-angiogenic therapy against gastrointestinal tract cancers.

Gastrointestinal tract cancers constitute a group of highest morbidity both in and outside Japan, and the prognosis still remains unfavorable when the disease has progressed to the unresectable stage. Since the late 1990s, a novel category of anti-cancer drugs, 'molecular-targeted drugs', has become available, and angiogenesis has been considered as one of the most important molecular targets for antitumor therapy since it is essential for tumor growth. Anti-angiogenic therapy inhibits tumor angiogenesis and promotes apoptosis of existing tumor blood vessels, thereby intercepting the supply of oxygen and nutrition essential for tumor growth and metastasis.

[Development of HER2-specific humanized antibody Herceptin (trastuzumab)].

HER2 is a member of the human epidermal growth factor receptor family, possessing protein kinase activity in its cytoplasmic domain. There were evidences indicating that (1) amplification of HER2/neu gene and HER2 protein over-expression in tumor cells was observed in 25-30% of human breast cancer and (2) amplification of HER2/neu correlated with poor prognosis, including shorter disease-free and overall survival. These evidences suggested HER2 was a promising candidate for novel molecular targets of breast cancer therapy.

Phase I trial of oral 2'-deoxy-2'-methylidenecytidine: on a daily x 14-day schedule.

2'-deoxy-2'-methylidenecytidine (DMDC) is a potent deoxycytidine analogue. Preclinical studies of DMDC demonstrated activity against a variety of murine and human tumors in cell cultures and murine models and indicate enhanced antitumor activity of DMDC when it was administered in a manner that provided prolonged systemic exposure. In view of this observation, this study was designed to determine the toxicities, maximum-tolerated dose, and pharmacokinetic profile of DMDC.