Effect of tamoxifen on serum cholesterol in Japanese women with breast cancer

Background To investigate whether tamoxifen therapy has a favorable effect on plasma lipids, serum cholesterol levels were measured in 228 Japanese women with breast cancer (116 premenopausal women and 112 postmenopausal women). Methods These women were treated with tamoxifen or tamoxifen+chemotherapy (tamoxifen-treated group) or were given no therapy or chemotherapy alone (control group). Results There was no difference between cholesterol levels before treatment and after a 2-year follow-up period in these groups, except for the postmenopausal tamoxifen-treated group. In this particular group, the mean levels of serum cholesterol after 1 and 2 years of follow-up (197 and 188 mg/dL, respectively) were 8% and 12% lower than those before treatment (215 mg/dL,P<0.0001). In addition, the mean level of serum cholesterol after a 2-year follow-up period was significantly higher in the postmenopausal tamoxifen-treated group than in the postmenopausal control group (218 and 188 mg/dL, respectively,P=0.0066). Conclusions In multiple regression models that included age, body mass index, and chemohormonal therapy, only tamoxifen treatment appeared to predict the change between cholesterol levels before treatment and after 2-year follow-up in postmenopausal women. These results suggest that tamoxifen has the potential benefit of reducing the serum cholesterol level, which may be closely related to cardiovascular risk, in Japanese postmenopausal women.     

Pharmacokinetic study of low- versus high-dose medroxyprogesterone acetate (MPA) in women

The present study was conducted to compare the pharmacokinetics (PK) of low-dose versus high-dose medroxyprogesterone (MPA) as a once-daily oral administration. Of 32 patients, all women, enrolled in this PK study, 18 received 600 mg MPA daily and 14 received 1200 mg daily. Detailed PK data were obtained on day 1 and after more than 4 weeks of MPA treatment. In addition, multiple data for the minimum steady-state concentration (Css min) were analyzed. The MPA serum concentrations were measured by high-performance liquid chromatography. Wide interpatient variability was found in the PK parameters obtained both on day 1 and after more than 4 weeks. There were no clear relationships between the oral dose and the MPA peak concentration (Cmax), area under the time versus concentration curve (AUC), or mean Css min. Weight gains of 10% or more were demonstrated more frequently in the high-dose group (P<0.01). Liver dysfunction (n=5) did not influence the PK of MPA. Five patients demonstrated extremely low AUC and Cmax (<10 ng/ml) values on day 1. Phenobarbital, dexamethasone and betamethasone were being taken concomitantly with the MPA each by one patient. The serum MPA concentrations were markedly increased after the discontinuation of phenobarbital in that patient, suggesting a drug interaction. At present we cannot recommend the high dose of MPA, except in clinical studies, from a PK or a pharmacodynamic points of view. Received: 2 May 1997 / Accepted: 13 October 1997     

Evolution of peripheral lung adenocarcinomas: CT findings correlated with histology and tumor doubling time

OBJECTIVE: This study was performed to evaluate the evolution of peripheral lung adenocarcinomas using CT findings and histologic classification related to tumor doubling time. MATERIALS AND METHODS: The subjects were 34 patients, each with an adenocarcinoma smaller than 3 cm. All patients underwent chest radiography and 10 of them had previously undergone CT more than 6 months before surgery. Tumor doubling time was estimated by examining sequential radiographs using the method originally described by Schwartz. Tumor growth was also observed by studying the changes on CT in the 10 patients who had previously undergone CT. The histologic classification (types A-F) was evaluated according to the criteria of Noguchi et al. RESULTS: Five (83%) of the six adenocarcinomas with tumor types A or B showed localized ground-glass opacity on high-resolution CT. All six tumors had a tumor doubling time of more than 1 year. Fifteen (71%) of the 21 tumors with type C showed partial ground-glass opacity mixed with localized solid attenuation on high-resolution CT. Ten (48%) of these 21 type C tumors had a tumor doubling time of more than 1 year. In types B and C, the solid component or the development of pleural indentation and vascular convergence increased during observation before surgery. All seven tumors with types D, E, and F showed mostly solid attenuation, and the tumor doubling time was less than 1 year in six (87%) of the seven tumors. CONCLUSION: Two main types of peripheral lung adenocarcinoma exist. The first type appears on CT as a localized ground-glass opacity with slow growth, and the other appears as a solid attenuation with rapid growth.     

铜绿假单胞菌感应分子对照质粒及整合突变株的构建

目的 研究细胞间信息传递机制之一假单胞菌喹诺酮信号(PQS)在铜绿假单胞菌发病机制中的作用.方法 基于基因融合分析在转录研究中的实用性,构建了两种PQS相关对照质粒和整合突变株.一种是酶切质粒pYHP441获得pqsA'-lacZ片段后,亚克隆入质粒miniCTX-1中,构建成pqsA'的阳性表达质粒,随后将构建的质粒,通过双亲交配过程整合入野生型铜绿假单胞菌株PAO-1染色体组中;另一种是通过点特异插入诱变策略,将四环素基因盒插入启动子pqsD和pqsE之间,构建的阴性质粒转化入大肠杆菌S17-1株后,和上述pqsA'阳性表达突变株进行双亲交配过程.结果 针对今后PQS的相关研究,构建得到稳定表达PQS的质粒和阳性突变株作为阳性对照.构建获得pqsA-E启动子敲除质粒和相应PQS表达受阻的整合突变株作为阴性对照.结论 两种质粒和整合突变株的构建成功,使得PQS的相关研究结论具有客观性、精确性和有效性.     

Metabolism of the alpha,beta-unsaturated ketones, chalcone and trans-4-phenyl-3-buten-2-one, by rat liver microsomes and estrogenic activity of the metabolites.

When chalcone and trans-4-phenyl-3-buten-2-one (PBO) were incubated with liver microsomes of untreated rats in the presence of NADPH, 4-hydroxychalcone and trans-4-(4-hydroxyphenyl)-3-buten-2-one (4-OH-PBO), respectively, were formed as major metabolites. Two minor metabolites of chalcone, 4'-hydroxychalcone and 2-hydroxychalcone, were also observed. The oxidase activity affording 4-hydroxychalcone was inhibited by SKF 525-A, disulfiram, ketoconazole, and alpha-naphthoflavone. The oxidase activities leading to 4-hydroxychalcone and 4'-hydroxychalcone were enhanced in liver microsomes of 3-methylcholanthrene- and phenobarbital-treated rats, respectively. The activity generating 2-hydroxychalcone was enhanced in liver microsomes of 3-methylcholanthrene- and dexamethasone-treated rats. The oxidation of PBO to 4-OH-PBO was inhibited by SKF 525-A, ketoconazole, disulfiram, and sulfaphenazole. This activity was enhanced in liver microsomes of 3-methylcholanthrene-, acetone- and phenobarbital-treated rats. 4-Hydroxylation, 4'-hydroxylation, and 2-hydroxylation of chalcone were catalyzed by rat recombinant cytochrome P450 1A1, 1A2, and 2C6; by 1A1 and 2C6; and by 1A1 and 3A1, respectively. PBO was oxidized by cytochrome P450 1A1, 1A2, 2C6, and 2E1. Chalcone and PBO were negative in an estrogen reporter assay using estrogen-responsive human breast cancer cell line MCF-7. However, 4-hydroxychalcone, 2-hydroxychalcone, 4'-hydroxychalcone, and 4-OH-PBO exhibited estrogenic activity.     

Hand-assisted laparoscopic surgery for a large gastrointestinal stromal tumor of the stomach

We report two cases of large gastrointestinal stromal tumor (GIST) of the stomach that were successfully treated by hand-assisted laparoscopic surgery (HALS). Two patients, a 56-year-old woman and a 60-year-old man, were admitted to our department for the treatment of a large submucosal tumor of the stomach. After gastrointestinal endoscopy, ultrasonography, computed tomography, and magnetic resonance imaging, we suspected that the masses, measuring 7.0 cm and 8.0 cm in diameter, respectively, were GISTs in the stomach. However, preoperatively, we could not rule out the possibility of malignant neoplasms, because they had been bleeding or gradually growing. Hand-assisted laparoscopic wedge resection was safely performed for the diagnosis and treatment of the submucosal tumor of the stomach. The immunohistochemical diagnosis in both patients was GIST of the stomach with intermediate-grade malignancy. HALS may be a good indication for large GISTs of the stomach that are difficult to diagnose preoperatively, whether they are malignant or benign, because it is safe and minimally invasive, promoting rapid recovery.     

Pleural retraction and intra-tumoral air-bronchogram as prognostic factors for stage I pulmonary adenocarcinoma following complete resection

BACKGROUND AND OBJECTIVES: We have retrospectively analyzed the postoperative prognostic factors for 116 patients with stage I adenocarcinoma, with special reference to pleural retraction and intra-tumoral air-bronchogram imaged by computed tomography, which may represent the biological features of pulmonary adenocarcinoma for the retraction of surrounding tissues due to central necrosis and air space-lining growth, respectively. METHODS: The subgroups divided according to the presence of pleural retraction and/or intra-tumoral air-bronchogram on pre-operative CT were compared with respect to the postoperative disease-free survival (DFS) and other clinico-pathological factors. RESULTS: The rates of DFS at 5 years associated with 61 patients with pleural retraction and with 55 patients without pleural retraction were 64.4% and 91.3%, respectively (P = 0.0052), and those associated with 83 patients with air-bronchogram-positive tumors and with 33 patients with air-bronchogram-negative tumors were 81.8% and 64.8%, respectively (P = 0.0040). The DFS at 5 years associated with T1 (73 patients) and T2 (43 patients) were 83.6% and 64.3%, respectively (P = 0.0153). The Cox proportional hazards model analysis revealed that the presence of pleural retraction and the absence of air-bronchogram were independent factors for poor prognosis with relative risks of 7.8 and 5.1, respectively. Pathological T factor was also a significant prognostic factor with a relative risk of 3.2. Seventeen patients with pleural retraction-positive and air-bronchogram-negative tumors showed the high recurrence rate of 47.5% and a poor prognosis with DFS at 5 years of 35.1%. CONCLUSION: These results suggested that, in stage I adenocarcinoma, the degree of malignant potential may be well figured by radiological imaging, with a significant affect on susceptibility of recurrence following complete resection.