[Ecological survey on Rickettsia tsutsugamushi in wild rodents in a rural area, Tama, in Tokyo].
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Animals↗
Biomedical subjects
T Shinkai
Publications and source records attributed to T Shinkai.
Treatment for small cell lung cancer--present status and future prospects.
Strategies for the treatment of small cell lung cancer (SCLC) were reviewed depending on the recent results of treatment. The development of new anti-cancer drugs are essential for the further improvement results of SCLC. However, the candidate of patient for phase II study of new anticancer drug is controversial. Intensified chemotherapy is essential in order to obtain long term survivors, however, the toxic death rate should be less than 5% of whole patients. The theory of non-cross resistant alternative chemotherapy has also been applied to the treatment of SCLC. The protocol study supported by grant-in-aid from the Ministry of Health and Welfare is now on-going by cooperative study. There are many discussions about the efficacy of combined modality in SCLC. However, present randomized trials gave clear answers about the priority of combined modality in SCLC. There are numerous biological studies about SCLC. These studies will contribute to improve the treatment results of SCLC.
Carcinoma, Small Cell↗
The incidence of secondary tumors of the heart and pericardium: a 10-year study.
Secondary tumors of the heart and pericardium are much more common than primary tumors. During a 10-year period (1976-1985), only one instance of a primary tumor (malignant mesothelioma) was identified among 2,649 autopsies of malignant tumors at the National Cancer Center Hospital. In contrast, there were 407 cases in which heart and/or pericardium were secondarily involved with a malignant tumor from other organs. In 78 cases, the secondary tumors were present only in the pericardium, while in 329 cases, the tumors involved the heart itself with or without pericardial involvement. Among the primary tumors, three-quarters were carcinomas of various organs. In addition there were 53 hematologic malignancies, 19 melanomas and 17 sarcomas. In 31 cases, cardiac failure was the direct cause of death. The secondary tumors of the heart were often overlooked clinically because the cardiac dysfunction appeared to be part of the deteriorating general condition. Electrocardiography and echocardiography were often helpful in suggesting the presence of cardiac metastases. Appropriate diagnostic procedures and therapeutic intervention should be considered for the care of patients with advanced malignancy and sudden onset of cardiac failure.
Electrocardiography↗
Prognostic factors in non-small cell lung cancer: multiregression analysis in the National Cancer Center Hospital (Japan).
A total of 190 patients with unresectable non-small cell lung cancer (NSCLC) were analyzed retrospectively using eight pretreatment and three treatment-related prognostic factors in terms of influence on survival. All the patients received chemotherapy with or without chest irradiation, according to the protocol of phase II or phase III trials of the National Cancer Center Hospital Tokyo between April 1980 and December 1985. The eight pretreatment factors selected were performance status, sex, stage, age, histology, and metastasis to brain, bone or, liver. Three treatment-related factors were radiation therapy to the primary site, response to chemotherapy, and treatment period, before or after clinical administration of cis-diamminedichloroplatinum (II) (CDDP). Of the 190 patients, 71 (37.4%) were alive for more than 1 year, but only 17 patients (8.9%) survived 2 years after the initiation of chemotherapy. By univariate analysis, performance status 0-1, female, no metastasis to bone or liver, response to chemotherapy, and treatment period after CDDP were considered to be favorable prognostic factors. By multiregression analysis, performance status, sex, and treatment period after CDDP proved to be important factors for long-term survival. Consideration of these prognostic factors could enable the results of chemotherapy to be more accurately evaluated, and stratification of patients with advanced NSCLC based on performance status and sex before entry into a randomized controlled trial is recommended.
Adenocarcinoma↗
Human tumor clonogenic assay for carcinoma of the lung. II. Factors that influence colony formation in soft agar.
The human tumor clonogenic assay (HTCA) has potential value for studies of both the chemosensitivity and biology of human tumors. However, many technical problems including low plating efficiencies and the preparation of sufficient numbers of viable cells remain. In this study, an improved method for disaggregation of solid tumors increased the yield of single cells. Consequently, more than 10 anticancer drugs could be tested in 94 of 168 specimens (56%). Removal of peripheral blood lymphocytes from cell suspensions derived from effusions also improved colony formation. Adequate growth for sensitivity testing (greater than 30 colonies/plate) was obtained in 122 cases (73%), inadequate growth for drug evaluation (5-29 colonies/plate) in 29 cases (17%), and no colony formation (less than 5 colonies/plate) in 17 cases (10%) of the 168 viable samples. The cloning efficiencies of cells derived from primary tumors (median 0.015%) were higher than those of cells derived from metastatic tumors (0.012%), and they varied with the location of the metastatic site. Cloning efficiencies varied markedly from specimen to specimen, and were unaffected by tumor histology, grade of differentiation, patient age, stage of disease, or prior chemotherapy. The HTCA is promising as a potential tool for studying the biology of tumors.
Agar↗
[The changes in serum neuron-specific enolase in patients with small cell lung cancer].
Serum neuron-specific enolase (NSE) was measured in 48 newly diagnosed untreated patients with small cell lung cancer (SCLC) by radioimmunoassay. Serum NSE level elevated (greater than or equal to 15 ng/ml) in 50% of all patients. The positive ratio of NSE in patients with extensive disease (64%) was significantly higher than those in the patients with limited disease (30%) (p less than 0.05). The positive ratio of NSE in the patients with one metastatic site was 50%, that with two or more metastatic sites was 100% (p less than 0.05). No significant correlation was found between serum NSE levels and metastatic site as well as between serum NSE levels and response to the chemotherapy. In the patients with extensive disease, survival time was shorter in the patients with positive NSE levels than the patients with normal NSE levels. These findings indicate that serum NSE may be a useful marker for staging, monitoring and prognosis in patients with SCLC.
Carcinoma, Small Cell↗
[Recent status of the diagnosis and treatment of bone metastasis in patients with advanced lung cancer].
The incidence and prognosis of patients with bone metastasis in primary advanced lung cancer were studied retrospectively. Between Jan. 1980 and Dec. 1985, 289 cases entered various kinds of chemotherapy protocol studies. Patients with bone metastasis of non-small cell lung cancer (NSC) comprised 44% (86/192), and those with small cell lung cancer (SC) comprised 43% (42/97). Histologically, 48% of adenocarcinoma, 50% of large cell carcinoma and 31% of squamous cell carcinoma showed bone metastasis. 8 percent of NSC bone meta (+) cases had an initial symptom of bone metastasis. Bone scan and bone X-ray were complementary and useful for diagnosis of bone metastasis, and sequential examinations tended to reduce the incidence of false-positive cases. Vertebral column, rib, pelvis and femur were the most common sites. Over 70% of the bone metastasis were in multiple skeletal systems, and 90% showed multiple-site involvement for both NSC and SC. Radiation therapy effectively reduced severe pain but paralysis was hard to control. In very few cases surgical treatment was indicated because of multiple bone metastasis, and systemic dissemination. Bone scan in 12% of SC patients showed apparent improvement with systemic chemotherapy. Among the M1 group of adenocarcinoma, median survival was 9 months in bone (+) cases, 11 months in bone (-) cases, 2 year survival was 8%, and 24%, and 3-year survival 2% and 22%, respectively. Among the bone(+) group and bone(-) group in ED cases of SC, median survival was 10 months vs. 11 months, and 2-year survival rates were both 13%. 22 percent (8/36) of squamous cell carcinomas without bone metastasis showed hypercalcemia (5.5 mEq/l). In patients with advanced lung cancer the major goal of treatment is recovery of the performance status of the patient and the relief of pain. In the case of SC, intensive systemic chemotherapy should be conducted as an adjuvant to local therapy.
Adenocarcinoma↗
Prediction of hematologic toxicity of carboplatin by creatinine clearance rate.
Twenty-six patients with histologically proven lung cancer, treated with carboplatin at the National Cancer Center Hospital between October 1985 and October 1986, were retrospectively analyzed to determine the hematologic toxicity of carboplatin (CBDCA) and to develop guidelines for dose modification. A total of 34 courses of CBDCA were administered, of which 21 were adequate for assessment of the myelosuppression in relation to the renal function. One of three doses of CBDCA was administered by iv drip infusion over one hour (450 mg/m2, 19 courses; 400 12; 300, 3). Myelosuppression was dose-limiting, with thrombocytopenia being more sensitive than leukopenia, neutropenia or anemia. No significant correlation of the absolute count of platelets, white blood cells, polymorphoneutrophils, or hemoglobin with patient's creatinine clearance (Ccr) and dose of CBDCA administered was found. However, the percent reduction in platelets, white blood cells, polymorphoneutrophils, or hemoglobin correlated well with the relative dose of CBDCA [RD = total dose of carboplatin administered (mg/m2)/pretreatment Ccr/m2]. As thrombocytopenia was dose-limiting, we have developed an equation for modification of the dose of CBDCA from the relationship between the relative dose and percent reduction at platelet count nadir: Dosage (mg/m2) = (Ccr/m2/5.34) x [(1-desired platelet count nadir/pretreatment platelet count) x 100-12.9]. After consideration of the range of thrombocytopenia, we have further developed a simple equation to use CBDCA easily and safely: Dosage (mg/m2) = (1/10) x Ccr/m2 x desired % reduction in platelet count nadir = 10 x Ccr/m2 x (1-desired platelet count nadir/pretreatment platelet count. The clinical validity of these two equations is now being evaluated in prospective studies.
Adult↗
In vitro growth inhibition of cisplatin-resistant human lung cancer cell lines by recombinant human tumor necrosis factor and/or recombinant human interferon-gamma by virtue of collateral sensitivity.
The colony-inhibitory effects of recombinant human tumor necrosis factor (rH-TNF) and recombinant human interferon-gamma (rH-IFN-gamma) were evaluated in four human lung cancer cell lines and their cisplatin-resistant sublines. The cell lines tested were PC-7 and PC-9 (adenocarcinoma), H69 and N231 (small cell lung cancer) and four cisplatin-resistant sublines, PC-7/1.0, PC-9/0.5, H69/0.2 and N231/0.2, which were 20.0, 7.1, 4.8 and 8.4 fold resistant to cisplatin, respectively, compared to the respective parental cell line in terms of IC50 in a soft agar colony assay. All parental cell lines were resistant to rH-TNF and rH-IFN-gamma, alone or in combination. However, two resistant sublines showed sensitivity to rH-TNF and rH-IFN-gamma. Colony formation by PC-9/0.5 was significantly inhibited, in the absence or presence of cisplatin, by 10(2) U/ml of rH-TNF (less than 50% of control) and the inhibition was synergistic with that produced by 10(3) or 10(4) U/ml of rH-IFN-gamma. RH-IFN-gamma inhibited the colony formation of H69/0.2 only at the highest concentration tested (10(4) U/ml) (less than 50% of control) and the combined effect with rH-TNF was additive. These results suggest that rH-TNF and rH-IFN-gamma may have some potential in overcoming cisplatin resistance by virtue of collateral sensitivity.
Cisplatin↗
A case report of adenocarcinoma of the lung in which a partial response was achieved by carboplatin.
A 56-year-old housewife was incidentally discovered to have an abnormal shadow in the right B6 area upon a chest X-ray film being taken. A transcutaneous lung biopsy of the mass revealed adenocarcinoma of the lung (WHO classification). A brain computed tomography (CT) scan demonstrated multiple brain metastasis. Following whole brain irradiation, carboplatin (CBDCA) (450 mg/m2) was administered by intravenous drip infusion on March 7, 1986. After three weeks of initial treatment with CBDCA, the size of the tumor in the primary site was found to have decreased on the chest X-ray film by more than 50%, following which, similar doses of CBDCA were administered twice, and reduced (330 mg/m2) doses three times every three to four weeks. She showed a partial response and, for seven months after the beginning of the CBDCA treatment, no progression was seen on the chest X-ray film. It is suggested that there is a need for further phase II studies of CBDCA against non-small cell lung cancer.
Adenocarcinoma↗
[A randomized controlled trial of acute and delayed cisplatin-induced emesis with metoclopramide, dexamethasone and prochlorperazine].
Forty patients with advanced lung cancer who had received chemotherapy containing cisplatin (80 mg/m2) were accrued for a randomized controlled trial to evaluate the additional effect of prochlorperazine on the combination of high-dose metoclopramide and dexamethasone for the treatment of acute cisplatin-induced emesis. The effect of intravenous metoclopramide and dexamethasone in emesis occurring more than 24 hours after cisplatin administration was also evaluated. Excellent emetic control (no emesis during 24 hours after cisplatin administration) was achieved in 70% (14/20) and 76% (16/21) of the patients who received the combination of prochlorperazine, metoclopramide and dexamethasone and the combination of metoclopramide and dexamethasone, respectively. The overall toxicities associated with both regimens were not serious and were similar. Patients treated with metoclopramide and dexamethasone on days 2-7 experienced less delayed emesis, nausea and anorexia compared with those treated with a placebo (delayed emesis, 25% versus 50%, respectively, p = 0.105; more than 4 days of nausea, 10% versus 35%, respectively, p = 0.059; less than 3 days of anorexia, 80% versus 50%, respectively, p = 0.048). It was concluded that metoclopramide and dexamethasone showed an excellent antiemetic effect on acute drug-induced emesis, as well as on delayed emesis, induced by cisplatin.
Adult↗
A case report of pulmonary adenocarcinoma responding to (glycolato-0,0') diammineplatinum (II), a new platinum complex.
The first patient to respond to [(glycolato-0,0') diammineplatinum (II)] (254-S) in a clinical phase I study is reported. The patient was a 52-year-old man complaining of nausea and weight loss. A chest X-ray demonstrated a diffuse infiltrating shadow in the right lung. A transbronchoscopic brushing of the right upper lobe and a biopsy specimen from the right supraclavicular lymph node revealed adenocarcinoma of the lung. He was diagnosed as having primary lung cancer with distant lymph node metastasis. 254-S was administered by intravenous drip infusion to a dose of 100 mg/m2. Two weeks after the second 254-S treatment, a chest X-ray demonstrated a more than 50% reduction in the pulmonary shadow and met the WHO criteria for a partial response. Thrombocytopenia, leukocytopenia and moderate nausea were observed as adverse effects of 254-S but renal toxicity was not found. Pharmacokinetics of free platinum in this patient demonstrated biphasic decay with a peak plasma concentration of 8.09 micrograms/ml. A disease-oriented phase II study of 254-S against non-small cell lung cancer should be performed to establish the efficacy of this new platinum complex.
Adenocarcinoma↗
[Phase I-II study of recombinant interleukin-2].
A phase I-II study of recombinant interleukin 2 (rIL-2) (Shionogi Pharmaceutical Co.) was conducted against carcinoma of the lung (20 cases) and stomach (1 case) as well as metastatic pulmonary tumor (17 cases). The cytotoxicity of lymphocytes against K562, PC-9, PC-14 and Daudi cells was examined before and 1, 2, 3, 5, 7, 14, 21 and 28 days after rIL-2 administration. The subsets of lymphocytes and pharmacokinetics of rIL-2 were also analyzed. Four administration methods were used. 2-h drip infusion of 6.7 X 10(5) U/m2/day (A1: 6 cases) or 2.2 X 10(6) U/m2/day (A2: 8 cases) for 5 consecutive days, subcutaneous injection of 6.7 X 10(5) U/m2/day (B: 3 cases) for 28 consecutive days, 4-h continuous drip infusion of 3.3 X 10(5) U/m2/day (C1: B cases), 6.7 X 10(5) U/m2/day (C2: 7 cases) or 1.1 X 10(6) U/m2/day (C3: 5 cases) for 28 consecutive days, and (D) 24-h continuous drip infusion of 6.7 X 10(5) U/m2/day (D: 6 cases) for 5 consecutive days every week, repeating four cycles of the course. We discussed whether or not the problems of the phase I study with BRMs could be solved.
Drug Administration Schedule↗
A case of adenocarcinoma of the lung which was successfully treated by chemotherapy with patient survival without recurrence for more than three years.
A 63-year-old man was admitted to the National Cancer Center Hospital on December 20, 1983 for a close examination of the abnormal shadows found in chest roentgenograms. Chest radiographs showed a massive right pleural effusion, a large tumor in the right hilar region and swelling of the left hilar nodes. Transcutaneous needle biopsy revealed the tumor's cytological type to be adenocarcinoma. The clinical stage was considered to be T3N2M1 (American joint committee (AJC) stage III M1), and his performance status was 4, so he was given etoposide (VP-16) alone as the initial chemotherapy treatment. He showed a partial response upon two courses of VP-16 therapy. Subsequently, one course of cisplatin (80 mg/m2) + vindesine (3.3 mg/m2), two courses of VP-16 (80 mg/m2 D1-4), five courses of cyclophosphamide (80 mg/m2) + adriamycin (50 mg/m2) + vincristine (1.4 mg/m2) and two courses of VP-16 (100 mg/m2 D1, 3, 5) were administered sequentially until May 31, 1985. No radiation therapy was given and, up to March 31, 1987, no sign of recurrence had been observed.
Adenocarcinoma↗
[Evaluation of a radioimmunoassay kit for neuron specific enolase "gamma-enolase Eiken"].
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Adolescent↗
[Ephedrine administration for cesarean section under spinal anesthesia].
Prophylactic ephedrine was administered to healthy parturients undergoing elective cesarean section under spinal anesthesia. The methods of ephedrine administration were as follows: intramuscular injection of 0.3 mg/kg, 15 minutes before the block (20 cases: group M), infusion of 0.02% solution immediately after the block (20 cases: group D), premedication with atropine 0.5 mg and infusion immediately after the block (20 cases: group AD). The mean ephedrine dosage was 18.8 +/- 2.2 gm (SD) in group M, 12.6 +/- 6.2 mg in group D and 5.2 +/- 0.7 mg in group AD, and there were significant differences among the three groups. The base line (a), the minimal postanesthetic (b) and the maximal postpartum systolic blood pressures (c) revealed no significant difference among the three groups, and 'b' was significantly higher than 'a' and lower than 'c' in all groups. Only one case (group M) was transiently hypotensive, while hypertension was not found in any of the subjects. One- and 5-minute Apgar scores were 8 or more in all, and umbilical acid-base values were within normal limits in all of them, though the base deficit in group AD was significantly lower than that in group M. Atropine premedication makes it possible to retrench the ephedrine dosage without any harmful effect on either mother or fetus, and ephedrine infusion makes it easy to cope with changes in maternal blood pressure. Consequently, for healthy parturients receiving elective cesarean section under spinal block, we recommend atropine premedication and minimal infusion of ephedrine immediately following the block.
Adult↗
The value of two-dimensional echocardiography in detecting malignant tumors in the heart.
Six unusual cases of tumor involvement of the heart and pericardium, diagnosed antemortem by two-dimensional echocardiography (2DE), are described. The tumors consisted one each of sacral chordoma, mediastinal seminoma, leiomyosarcoma of the uterus, osteosarcoma, invasive thymoma, and lung cancer. The current study again recognizes the concept that any type of malignant tumor has a possibility of involving the heart. If cardiac involvement is suspected, 2DE examination should be performed in patients with any kind of malignant tumor. The information obtained not only provides guidance for therapeutic maneuvers, but also is beneficial for follow-up observation of the patients and assessment of the therapy.
Adenocarcinoma↗
Serial plasma carcinoembryonic antigen measurement for monitoring patients with advanced lung cancer during chemotherapy.
The plasma carcinoembryonic antigen (CEA) levels in 243 patients with untreated advanced lung cancer were studied to assess their value for prognosis and for indicating the effectiveness of chemotherapy. Of patients with adenocarcinoma, small cell carcinoma, squamous cell carcinoma, and large cell carcinoma, 43%, 24%, 7%, and 13%, respectively, had elevated CEA levels of 20 ng/ml or greater before treatment. Pretreatment CEA levels were elevated to above 20 ng/ml for 38% of 163 patients with extensive disease and for 22% of 80 patients with limited disease (P less than 0.02). In patients with adenocarcinoma of the lung, the pretreatment CEA levels were not correlated with response to chemotherapy and patients' survival. Serial measurement of plasma CEA was a useful noninvasive technique for monitoring the response to chemotherapy in patients whose pretreatment levels were 20 ng/ml or higher. All of 18 patients with complete or partial responses and 5 of 6 patients with minor responses showed greater than 36% decrease in the CEA level compared with the pretreatment level. In all of nine patients with progressive disease, the CEA levels increased after chemotherapy. Therefore, an increase of greater than 36% beyond the baseline level was a useful guideline criterion for a significant change for determination of tumor response to chemotherapy, although 41% of 22 patients with stable disease exceeded the pretreatment level by 36% or more in either direction (mean percent change +/- standard deviation, -4.1% +/- 52.2%), and 4 of 9 patients with progressive disease did not have levels greater than 36% above the baseline levels.
Adenocarcinoma↗