Combination chemotherapy of TS-1, docetaxel and CDDP produces a remarkable response in a patient with advanced esophageal cancer

We report a patient with advanced esophageal cancer who achieved a complete response to combination chemotherapy of TS-1, docetaxel and CDDP. A 74-year-old man was admitted to our hospital for advanced esophageal cancer with a complaint of dysphagia. He received chemotherapy, consisting of TS-1 100 mg/body, docetaxel 35 mg/m(2), and CDDP 10 mg/m(2), every 3 weeks. TS-1 was administered for 14 days followed by 7 days rest; docetaxel and CDDP were administered by intravenous infusion at day one and day 8 after beginning TS-1. After three cycles of chemotherapy, his dysphagia disappeared, and endoscopic examination of the primary esophageal tumor showed a complete response. Endoscopic examination with biopsy confirmed the disappearance of the esophageal cancer. No severe side effects were observed during this chemotherapy. Combination chemotherapy of TS-1, docetaxel, and CDDP can thus be effective for advanced esophageal cancer.     

A successful case of hepatocellular carcinoma with portal venous tumor thrombus (Vp2) treated by transcatheter arterial chemoembolization

We reported a case of hepatocellular carcinoma (HCC) with portal venous tumor thrombus (PVTT) (Vp2) successfully treated by transcatheter arterial chemoembolization (TACE), and the tumor showed complete response and the patient survived for 28 months. A 67-year-old male was diagnosed with HCC in the area of subsegment 5 with PVTT from the P5 to the posterior branch. He was treated by segmental TACE. The tumor markers decreased within normal limits, and localized hepatic infraction in the subsegment 5 and atrophy of the PVTT were recognized. He survived for 28 months with no tumor recurrence after the first TACE. This case suggested that embolization might play a part of treatment to HCC with PVTT, if the liver function was preserved and the lesion of liver infraction was limited.     

A case of scirrhous gastric cancer responding to TS-1/CDDP neoadjuvant chemotherapy

A 72-year-old female with scirrhous-type advanced gastric cancer was treated with TS-1/CDDP as neoadjuvant chemotherapy. TS-1 (80 mg/m(2)/day) was orally administered for 3 weeks and CDDP (60 mg/m(2)) was administered by intravenous drip on day 8. Partial response (PR) was obtained after the first course, and total gastrectomy was performed. The histological diagnosis revealed complete disappearance of cancer cells in the stomach and a few regional lymph node metastases (3/67). The patient has now been in good health without a recurrence for 1 year and 9 months after surgery.     

Lysocellin, a metabolite of the novel drug 'alopestatin', induces G1 arrest and prevents cytotoxicity induced by etoposide

We report here that lysocellin, a polyether antibiotic from a streptomycete, induces G1 phase arrest in human osteosarcoma MG63 cells. Lysocellin up-regulates p21WAF1/Cip1 and down-regulates cyclin D1 at the mRNA level. In addition, cyclin D1 is down-regulated by the proteasome-dependent signal pathway in MG63 cells. In drug combination studies, we found that lysocellin treatment weakened the cytotoxic activity of etoposide in MG63 cells using a colony-formation assay. To study the in vivo efficacy of lysocellin, we isolated a novel compound related to lysocellin from the same streptomycete, and found that the novel drug is converted to lysocellin in vivo and decreases etoposide-induced alopecia in a neonatal rat model. We raise the possibility that this novel drug, named 'alopestatin', may be a promising agent against alopecia.     

Role of bare metal stent in drug eluting stent era

Although drug eluting stent (DES) reduced the target vessel revascularization, there are still some unsolved concerns such as late stent thrombosis, late catch up, adequate duration of dual antiplatelet agents and surgical complication after DES implantation. Individually bare metal stent should be used considering several factors such as patient characteristic, lesion characteristic, the tolerance of dual antiplatelet therapy for long-term, informed consent and also surgery after PCI.     

A toxicoproteomic study on cardioprotective effects of pre-administration of docetaxel in a mouse model of adriamycin-induced cardiotoxicity

Studies suggest that pre-administration of docetaxel (DOC) in adriamycin (ADR)-DOC combination anticancer therapy results in stronger antitumor effects and fewer ADR-induced cardiotoxic deaths in mouse model, yet no mechanism explaining this effect has been established. The aim of this study was to identify cellular processes in mouse heart tissue affected by different ADR/DOC dosing protocols using a toxicoproteomic approach. We applied fluorogenic derivatization-liquid chromatography-tandem mass spectrometry (FD-LC-MS/MS) - which consists of fluorogenic derivatization, separation and fluorescence detection by LC, and identification by LC-tandem mass spectrometry - to the proteomic analysis of heart tissue from control, intermittent-dosing (DOC-ADR), and simultaneous-dosing (ADR&DOC) groups. In DOC-ADR group, ADR was administered 12 h after DOC injection; in ADR&DOC group, both drugs were administered simultaneously; in control group, saline was administered at the same timing as ADR injection of other groups. Heart samples were isolated from all mice 1 week after the treatment. The highly reproducible and sensitive method (FD-LC-MS/MS) identified nine proteins that were differentially expressed in heart tissue of control and the two treatment groups; seven of these nine proteins participate in cellular energy production pathways, including glycolysis, the tricarboxylic acid cycle, and the mitochondrial electron transport chain. Significantly higher expression of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) was observed in the DOC-ADR group, the group with the fewer cardiotoxic deaths, than in the ADR&DOC group. Therefore, GAPDH may have potential as a drug target for protective intervention and a biomarker for evaluation of the cardioprotective effects in pre-clinical studies.