[A case of castration-refractory prostate cancer showing marked decrease of serum PSA level after zoledronic acid treatment with estramustine phosphate and prednisolone].

A 66-year-old man was referred to our outpatient clinic for an elevated serum prostatic-specific antigen (PSA 4,319 ng/ mL). Magnetic resonance imaging (MRI) showed multiple metastatic lesions in the bones. The patient had received androgen deprivation therapy, but six months after treatment, he was diagnosed as having prostate cancer refractory to hormones. Combined treatment with docetaxel (DOC 30 mg/m²/week )and estramustine phosphate (EMP 560 mg/day) was initiated as first-line chemotherapy, but the treatment was discontinued because of side effects. Then, treatment with zoledronic acid was started(4 mg/4 weeks)and the PSA level decreased dramatically from 457.2 ng/mL to 5.5 ng/mL. Seven months after the diagnosis of CRPC, MRI showed a decrease ofbone metastases, and the PSA levels continued to decrease, eventually reaching 0.3 ng/mL. Zoledronic acid appears to not only show efficacy in preventing skeletal-related events, but has a potential antitumor effect in patients with metastatic CRPC.

Significance of target cell infection and natural killer cells in the anti-tumor effects of bacillus Calmette-Guerin in murine bladder cancer.

Although intravesical instillation of bacillus Calmette-Guerin (BCG) is a clinically well-recognized therapy for bladder carcinoma in situ and recurrence prophylaxis, these mechanisms have not been fully understood. We studied the effects of BCG infection (Connaught strain) on target cancer cells and host immune systems in murine bladder cancer. The bladder cancer cell line, MB49, was used in C57/BL6 mice in vivo and in vitro. In vitro cytotoxicities against the cancer cell line were measured by 24-h 51Cr release assay. For effector cells, spleen mononuclear cells were obtained from mice injected intraperitoneally with BCG or BCG-infected irradiated MB49 cells. Although BCG infection of cancer cells did not affect the proliferation speed in vitro, the mice injected subcutaneously with BCG-infected MB49 cells survived significantly longer than those given untreated cancer cells. The mice surviving without tumor growth after injection of BCG-infected cancer cells could not reject a second injection of intact MB49 cells. In vitro cytotoxicity was enhanced by BCG infection of target cancer cells, but not by immunizing the mice with BCG from which effector cells were obtained. Moreover, cytotoxicity disappeared by depleting natural killer (NK) cells from effector cells. Although in vitro cytotoxicity was increased by immunizing the mice with BCG-infected irradiated MB49 cells, survival did not improve in these mice. These results suggest that a major part of BCG's anti-tumor effects can be attributed to the elimination of BCG-infected cancer cells by NK cells.

The extinct river shark Glyphis pagoda from the Miocene of Myanmar and a review of the fossil record of the genus Glyphis (Carcharhiniformes: Carcharhinidae).

We redescribe an extinct river shark, Glyphis pagoda (Noetling), on the basis of 20 teeth newly collected from three different Miocene localities in Myanmar. One locality is a nearshore marine deposit (Obogon Formation) whereas the other two localities represent terrestrial freshwater deposits (Irrawaddy sediments), suggesting that G. pagoda from the Irrawaddy sediments was capable of tolerating low salinity like the extant Glyphis. Glyphis pagoda likely reached up to at least 185 cm in total body length and was probably piscivorous. The fossil species occurs in rocks of Myanmar and eastern and western India and stratigraphically ranges at least from the Lower Miocene (Aquitanian) to the lower Upper Miocene (mid-Tortonian). It has been classified under at least eight other genera to date, along with numerous taxonomic synonyms largely stemming from the lack of understanding of the heterodonty in extant Glyphis in the original description. Our literature review suggests that known Miocene shark faunas, particularly those in India, are manifested with unreliable taxonomic identifications and outdated classifications that warrant the need for a comprehensive taxonomic review in order to evaluate the evolutionary history and diversity pattern of Miocene shark faunas. The genus Glyphis has a roughly 23-million-year-long history, and its success may be related to the evolution of its low salinity tolerance. While extant Glyphis spp. are considered to be particularly vulnerable to habitat degradation and overfishing, the fossil record of G. pagoda provides renewed perspective on the natural history of the genus that can be taken into further consideration for conservation biology of the extant forms.