Frameshift mutations and a length polymorphism in the hMSH3 gene and the spectrum of microsatellite instability in sporadic colon cancer.

Mutations in the hMVSH3 gene in sporadic colon cancer with microsatellite instability (MSI) were investigated, since several mismatch repair genes were known to be mutated in cancers with MSI, but only deletions in the (A)8 region in the hMSH3 gene have been reported. We also analyzed the relationships between hMSH3 mutations and the spectrum of MSI. We screened MSI in 79 sporadic colon cancer samples using mono- and dinucleotide repeat markers and the samples with MSI were further analyzed for tri- and tetranucleotide repeat instability and mutations in the hMSH3 gene by polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) analysis. Five (6%) out of 79 tumors were MSI-H and 15 (19%) were MSI-L. Two MSI-H tumors showed insertion in the (C)8 region in the hMSH6 gene and one tumor showed insertion and deletion in the (A)8 region in the hMSH3 gene, and two of the three above tumors showed MSI in tri-and tetranucleotide repeats. One MSI-L tumor showed somatic alteration in a 9-bp repeat sequence in hMSH3. No frameshift mutations were found in the (A)7 and (A)6 regions in hMSH3. Thus, we confirmed that the (A)8 region in hMSH3 is a hot spot and mutations in the (A)7 and (A)6 regions in hMSH3 are not common. The hMSH3 mutation may enhance genomic instability in some colorectal cancers.     

Effects of saiboku-to on dual-phase bronchoconstriction in asthmatic guinea pigs.

In recent years, bronchial asthma has come to be regarded pathologically as a chronic inflammatory disease of the respiratory tract. Inhalational steroids and antiinflammatory drugs are recognized as being effective against bronchial asthma. In this study, the effects of Saiboku-to, a Chinese herbal (Kampo) formulation, were investigated on asthmatic guinea pigs sensitized to ovalbumin (OA). Following 7-day administration of Saiboku-to (500 micrograms/kg), the late asthmatic response (LAR) to an antigen challenge was found to be inhibited. The number of eosinophils in fluid obtained by bronchoalveolar lavage (BAL) 4 h after antigen challenge was decreased while the infiltration of eosinophils and T-lymphocytes into the lung parenchyma was inhibited. These findings suggest that Saiboku-to has the potential to become a useful drug in the treatment of bronchial asthma.     

A new boronated porphyrin (STA-BX909) for neutron capture therapy: an in vitro survival assay and in vivo tissue uptake study.

A new boronated porphyrin compound (STA-BX909) was developed as a possible agent for boron neutron capture therapy. The boron concentration was measured by an in vivo rat experimental brain tumor model and an in vitro cell culture study. This agent was compared to sodium borocaptate (BSH) which has been used in clinical trials of boron neutron capture therapy. In the 9L rat brain tumor model, STA-BX909 achieved a higher boron tumor/blood ratio 24 h after injection in comparison to BSH. A boron concentration study in cultured glioma cell lines (U-251, U-87, 9L) demonstrated an increased boron concentration as a function of exposure time to STA-BX909, while the boron concentration remained stable with increasing exposure time to BSH. Use of a colony forming assay with thermal neutron irradiation revealed more cytotoxicity with STA-BX909 than BSH when the same concentration of 10B was administered. We concluded that STA-BX909 may be an effective drug for use in boron neutron capture therapy and that it merits further investigation.     

Intraperitoneal administration of a combined CDDP, 5-FU and MMC therapy for pseudomyxoma peritonei

Pseudomyxoma peritonei, which is the seeding of the peritoneum by mucin-secreting metastatic deposits and the filling of the peritoneal cavity by these secretions, is a malignancy that even after excision of the metastatic areas has a poor prognosis, since no effective therapy has yet been established. Herein, we report five cases of pseudomyxoma peritonei that responded to a combined postsurgical therapy consisting of CDDP, 5-FU and MMC. A 59-year-old women had a complete response who underwent an appendectomy, a right ovariectomy, and an omentectomy due to pseudomyxoma peritonei, and was postoperatively given a 50 mg intraperitoneal administration of CDDP. Further, a subcutaneous implant-type reservoir was positioned intraperitoneally for postoperative chemotherapy. At 14 days after surgery, therapy was begun which consisted of CDDP (70 mg/m2/day 1), 5-FU (350 mg/m2/day 1) and MMC (6 mg/m2/day 1) administered intraperitoneally, and 5-FU (350 mg/m2/day 1-3) that was continuously infused by an intravenous drip. She received 4 courses of postoperative chemotherapy. As a result of this therapy, the serum CEA values, which had elevated postoperatively, fell to within their respective normal ranges, and at 44 months postoperatively, this patient remains alive. Given the results above, intraperitoneal administrations of this combined CDDP, 5-FU, MMC therapy may be effective for patients with pseudomyxoma peritonei.     

Prophylaxis of recurrence in superficial bladder carcinoma by intravesical chemotherapy--comparative study between instillation of combined double anticancer agents and single anticancer agent

We performed a study to compare the usefulness of double or single anticancer agents in the prophylactic treatment after the transurethral resection (TUR) of superficial bladder cancer. We experienced 127 superficial bladder cancer cases. Of these cases, 42 were treated with intravesical adriamycin (ADR) and peplomycin (PEP), 56 with ADR, PEP, epirubicin (epi-ADR) or pirarubicin (THP) only, and the remaining 29 with TUR only. Nonrecurrence rates were significantly higher in the intravesical treated cases than in the cases with TUR only, and also significantly higher in the cases treated with ADR and PEP than the other treated cases. We concluded that intravesical chemotherapy with combined agents was more effective than with a single agent.     

Why not standard practice guidelines in Japan?

The issue of medical practice guidelines has attracted the attention of doctors and health care professionals in Western countries since the middle 1980s. Such guidelines aim to assist in clinical decision-making in order to reduce variations in care and unnecessary costs for delivered health care service, and to improve the outcomes of medical care. Strangely, however, there is no interest or attention given to this topic in the medical and health care fields in Japan. As the president of the 71st Japanese Gastric Cancer Association, the author hopes to generate interest in this topic by opening a symposium at the annual meeting of the JGCA this year. As an introduction to this session, the present paper provides a short review of medical practice guidelines, their development cycle, and their advantages and disadvantages.     

The cyclin-dependent kinase inhibitor p27 as a prognostic factor in advanced non-small cell lung cancer: its immunohistochemical evaluation using biopsy specimens

The expression of p27, which is known as a cyclin-dependent kinase inhibitor, on surgically resected specimens has considerable value for the prognosis of non-small cell lung cancer (NSCLC) patients. We immunohistochemically investigated the expression of the p27 protein in the biopsy specimens taken from 69 advanced NSCLC patients and assessed its clinical value. There was no significant correlation between p27 positivity and clinical parameters, including sex, age, histological type, clinical stage, smoking index and performance status. Furthermore, p27 positivity was not associated with response to chemotherapy. However, the Kaplan-Meier curve demonstrated that low p27 expression was significantly related to poor prognosis (P = 0.0019, by the log-rank test). Using multivariate analysis, p27, age and serum total protein level were found to be the independent prognostic parameters. The p27 positivity in the biopsy specimens of advanced NSCLC appears to be a useful prognostic marker.     

Prognostic significance of the PC10 index for patients with stage II and III oesophageal cancer treated with radiotherapy

The monoclonal antibody PC10 is used for immunohistochemical staining of the proliferating cell nuclear antigen (PCNA). The percentage of PC10-positive cancer cells is defined as the PC10 index. We evaluated the relationship between the PC10 index in pretreatment endoscopic biopsies and the prognoses of 47 patients with Stage II-III oesophageal squamous cell carcinoma treated with radiotherapy. The patients with a PC10 index > 40% had significantly poorer prognoses than the other patients (p = 0.0007). Proportional hazards model analysis indicated that only the PC10 index was a prognostic factor (p = 0.0009). The patient group of complete responders showed significantly lower PC10 indices compared to patients with a partial response or no change (p = 0.049). The PC10 index can be a good predictive indicator of the prognosis in patients with Stage II-III oesophageal cancer treated with radiotherapy.