Phase II trial of combination chemotherapy with cisplatin, carboplatin and etoposide in stage IIIB and IV small-cell lung cancer

Purpose: A phase II trial combining cisplatin, carboplatin and etoposide was conducted in previously untreated patients with stage IIIB and IV small-cell lung cancer, in an attempt to increase response rates and prolong survival. Methods: Previously untreated patients with small-cell lung cancer, with measurable disease, aged ≤ 72 years, performance status ≤ 2, and adequate hematologic, hepatic and renal function were enrolled in the study. They were treated with 80 mg/m² cisplatin on day 1, 100 mg/m² carboplatin on days 2, 3 and 8, and 50 mg/m² etoposide on days 1, 2, 3 and 8. Results: A total of 46 patients (20 with stage IIIB and 26 with stage IV disease) were enrolled in the study. A total of 186 courses of chemotherapy were given, and the dose was reduced in 27 courses (15%). The chemotherapy was repeated for four or more courses in 30 patients. There were 10 complete responses and 32 partial responses, for a total response rate of 91% (95% confidence interval, 79% to 98%). The median survival time and 2-year survival rates were 18 months and 22% for stage IIIB disease, and 14 months and 15% for stage IV disease. Major side effects were hematologic: leukopenia, anemia, and thrombocytopenia of grade 3 or more occurred in 48%, 46%, and 43% of patients, respectively. Conclusions: The three-drug regimen of cisplatin, carboplatin and etoposide is feasible and active against small-cell lung cancer. Received: 21 May 1997 / Accepted: 11 September 1997     

Structure and Function of G Protein Coupled Receptors

The G protein coupled receptors (GPC-Rs) comprise a large superfamily of genes encoding numerous receptors which all show common structural features, e.g., seven putative membrane spanning domains. Their biological functions are extremely diverse, ranging from vision and olfaction to neuronal and endocrine signaling. The GPC-Rs couple via multiple G proteins to a growing number of recognized second messenger pathway, e.g., cAMP and phosphatidyl inositol turnover. This review summarizes our current knowledge of the molecular mechanisms by which the GPC-Rs activate second messenger systems, and it addresses their regulation and structure.     

Clinicopathologic significance of cyclin A expression in colorectal carcinoma

The clinical significance of cyclin A expression, which has been known to act in the mitotic phase of the cell cycle, as an indicator of malignant potential in human tumors, has been suggested. The aim of this study was to elucidate the significance of immunohistochemical expression of cyclin A in colorectal carcinomas based on a larger study population. Immunohistochemical staining for cyclin A was performed for 167 colorectal carcinomas and the correlation between cyclin A expression and the clinicopathological characteristics was analyzed. One hundred and two carcinomas (61.1%) had cyclin A expression and the other 65 (38.9%) did not. The mean size of the tumors with cyclin A expression was significantly larger than that of tumors without cyclin A expression (p = 0.012). Survival in patients with cyclin A-expressing carcinomas was significantly worse than that in patients with carcinomas without cyclin A expression (p = 0.004). Cyclin A expression (p = 0.030), as well as lymph node metastasis (p = 0.007) and Dukes' stage of the tumors (p < 0.0001) were found to be factors independently associated with unfavorable prognosis in patients with colorectal carcinoma. Our results demonstrated that immunohistochemical expression of cyclin A is an independent prognostic indicator in patients with colorectal carcinoma.     

Role of autologous blood transfusion in sacral tumor resection: patient selection and recovery after surgery and blood donation

We carried out sacral en-bloc resection in six patients (three with chordoma; one with pheochromocytoma; one with malignant schwannoma; and one with giant cell tumor) using preoperatively collected autologous blood, to avoid homologous blood transfusion. An average of 3200 ml was collected preoperatively, with patients receiving recombinant human erythropoietin (r-HuEPO), at a total dose of 130 000 units on average. In four patients, we were able to accomplish the surgery without homologous blood transfusion. Postoperatively, the hemoglobin level in these four patients recovered to the pre-collective level in 4.5 weeks, on average. These clinical results indicate that en-bloc sacrectomy, which requires a large volume of blood transfusion, can be accomplished with preoperatively collected autologous blood alone. Received: July 2, 1999 / Accepted: December 14, 1999     

Current topics in pharmacological research on bone metabolism: inhibitory effects of bisphosphonates on the differentiation and activity of osteoclasts

Despite the extensive use of bisphosphonates (BPs) in the treatment of metabolic bone diseases associated with increased osteoclastic bone resorption, the precise mechanism of their action on bone metabolism is still unclear. To clarify at which stages of osteoclast differentiation and activation that BPs influence, we examined the osteoclasts generated from mononuclear precursors and osteoclasts in the calvaria by laser scanning confocal microscopy. The studies showed that BPs inhibit lipopolysaccharide- or parathyroid hormone-induced osteoclast differentiation, fusion, attachment, actin ring formation, and activation and that both beta3 integrin and osteopontin have an important role in cytoskeletal rearrangements associated with cell attachment and resorption in osteoclasts.     

Proliferating activity of gastric-carcinoma invading the muscularis propria and metastasis to lymph-nodes

From 1965 to 1987, 126 patients who had gastric cancer invading the muscularis propria (pm) were treated with curative resection in the Department of Surgery II, Kyushu University. We examined the correlation between the proliferating activity of the tumor by staining the tissue for proliferating cell nuclear antigen (PCNA) and the occurrence of lymph node metastasis present in 46.8% (59/126) of the patients. Undifferentiated carcinoma was more frequent in these patients and lymphatic and vascular involvement was prominent. Patients with a lymph node metastasis had a higher level of PCNA staining in the tumors than did those without lymph node metastasis (labeling index: 36.5 +/- 9.6% vs. 25.3 +/- 8.3%) (P < 0.01). The survival rate for patients with lymph node metastasis was lower than that for those without this metastasis (P < 0.01). The 10-year survival rate was 63.6% for the patients with lymph node metastasis and 86.8% for those without lymph node metastasis. Thus, the presence of lymph node metastasis is associated with a high growth potential of tumor cells in pm gastric cancer. Close follow-up and adjuvant chemotherapy in the postoperative period is recommended for these patients.