A series of quinazoline derivatives with various 4-heterocyclylpiperidino groups at the 4-position was synthesized and tested for cardiotonic activity in anesthetized dogs. Among them, several 6,7-dimethoxyquinazoline derivatives showed potent cardiotonic activity.
There is no standard second-line or salvage treatment for advanced urothelial carcinoma (UC). Here we investigated the efficacy and safety of gemcitabine, cisplatin, and paclitaxel (GCP) combination chemotherapy as salvage chemotherapy for advanced UC. We retrospectively analyzed the cases of 23 patients with advanced UC who showed progression or recurrence after cisplatin-based chemotherapy. Gemcitabine (1000 mg/m2), and paclitaxel (80 mg/m2) were administered on days 1 and 8. Cisplatin (70 mg/m2) was administered on day 1. The 3-week cycle regimen was repeated until disease progression if it had no intolerable toxicity. The overall response rate was 61% (95%CI, 41-78%). The median overall survival and progression-free survival times were 14 months and 5.5 months, respectively. Of the already known risk factors of chemotherapy for advanced UC, only the performance status was a prognostic factor for OS. Overall, 16 of the 23 patients (70%) experienced grade 3/4 toxicities, and no fatal adverse events were observed. GCP therapy was a promising option as second-line or salvage therapy for advanced UC.
Bone metastasis occurs in up to 90% of men with advanced prostate cancer and leads to fractures, severe pain and therapy-resistance. Bone metastases induce a spectrum of types of bone lesions which can respond differently to therapy even within individual prostate cancer patients. Thus, the special environment of the bone makes the disease more complicated and incurable. A model in which bone lesions are reproducibly induced that mirrors the complexity seen in patients would be invaluable for pre-clinical testing of novel treatments. The microstructural changes in the femurs of mice implanted with PCSD1, a new patient-derived xenograft from a surgical prostate cancer bone metastasis specimen, were determined.Quantitative micro-computed tomography (micro-CT) and histological analyses were performed to evaluate the effects of direct injection of PCSD1 cells or media alone (Control) into the right femurs of Rag2-/-γc-/- male mice.Bone lesions formed only in femurs of mice injected with PCSD1 cells. Bone volume (BV) was significantly decreased at the proximal and distal ends of the femurs (p < 0.01) whereas BV (p < 0.05) and bone shaft diameter (p < 0.01) were significantly increased along the femur shaft.PCSD1 cells reproducibly induced bone loss leading to osteolytic lesions at the ends of the femur, and, in contrast, induced aberrant bone formation leading to osteoblastic lesions along the femur shaft. Therefore, the interaction of PCSD1 cells with different bone region-specific microenvironments specified the type of bone lesion. Our approach can be used to determine if different bone regions support more therapy resistant tumor growth, thus, requiring novel treatments.
Photodynamic therapy (PDT), one of the treatment modalities for cancer, uses a photosensitizer and laser irradiation to induce the production of reactive oxygen species in cancers cells. In Japan, the United States, and many other countries, PDT is widely used as a treatment option for solid cancers. In the therapeutic guidelines for lung cancer established in 2002 by the Japanese Ministry of Health, Labor and Welfare based on the principle of evidence-based medicine, PDT is the recommended treatment modality for centrally located early stage lung cancer. It has been reported that PDT rapidly induce apoptosis, inflammatory reaction, tumor specific and/or nonspecific immune reaction and damages the microvasculature of the tumor bed. The mechanism of action of PDT is unique and is not well known. In this paper, we discuss the mechanism of the induction of apoptosis or necrosis following PDT.
