Biomedical subjects

H Ueoka

Publications and source records attributed to H Ueoka.

At least 73 records · Page 4Linked to original sources

PubMed1993

Long-term results of combination chemotherapy with or without irradiation in small cell lung cancer: a 5- to 11-year follow-up.

Between April 1981 and December 1987, 148 patients with newly diagnosed small cell lung cancer (SCLC) were treated using combination chemotherapy with or without thoracic irradiation and prophylactic cranial irradiation (PCI) in a series of cooperative therapeutic trials. With a minimum follow-up of 4.7 years, 13 (9%) patients survived and were free of SCLC. These included 11 (15%) of 76 patients with limited disease and two (3%) of 72 patients with extensive disease. Three died without any evidence of SCLC (one each from second leukemia, non-small cell lung cancer, and unrelated disease). The remaining 10 (7%) patients are currently alive and free of SCLC beyond 4.7 years. Since late relapse beyond 5 years is a very rare event, these patients may have been cured. However, late toxicity of PCI must be kept in mind. Three among the 10 patients have suffered from neuropsychologic symptoms of varying degrees in severity. Although the long-term survival rate is a benchmark in the treatment of SCLC, modifications of therapy that may potentially avoid such toxicities should be considered hereafter.

Aged↗

PubMed1993

[CAV-PVP chemotherapy and sequential thoracic irradiation (TI) for patients with limited (LD) small cell lung cancer (SCLC)].

In order to assess the effectiveness of sequential TI for the treatment of LD SCLC, we analyzed 69 patients who had received CAV-PVP chemotherapy consisting of cyclophosphamide, adriamycin, vincristine, cisplatin and etoposide, plus sequential TI between 1986 and 1992. TI was delivered at a total dose of 50 Gy, 5 fractions/week for 5 weeks, once patients achieved a maximal response to chemotherapy. Responding patients also received PCI at a total dose of 30 Gy, 5 fractions/week for 3 weeks. Thirty patients achieved CR by chemotherapy and an additional 10 achieved CR after TI, resulting in a CR rate of 58.0%. Of 40 patients achieving CR, 24 have relapsed so far; the primary (in 15) and the brain (in 4) were the major sites of relapse despite TI and PCI. The median survival time was 18.4 months, with a 2-year survival rate of 39% and 3-year survival rate of 20%. Almost all the patients encountered grade 3 or grade 4 leukopenia while receiving chemotherapy, but the toxicity of TI was generally mild. This treatment is useful for patients with LD SCLC.

Adult↗

PubMed1993

[In vitro comparison of podophyllotoxin analogues; etoposide, teniposide and NK 611 using human lung cancer cell lines].

In an attempt to predict the antitumor activity of a new podophyllotoxin analogue, NK 611, in the treatment of lung cancer, we compared the drug with etoposide and teniposide using four human small cell lung cancer (SCLC) cell lines, SBC-2, -3, -4, -7, and two non-small cell lung cancer cell lines, ABC-1, EBC-1. In terms of the fifty percent tumor growth inhibitory concentration (IC 50) determined by MTT assay, teniposide was most potent among the drugs. The degree of cross-resistance of each drug was investigated using an etoposide-resistant SCLC subline (SBC-3/ETP), an adriamycin-resistant subline (SBC-3/ADM 100), and a cisplatin-resistant subline (SBC-3/CDDP). As for relative resistant (the ratio of IC 50 for resistant subline to that for the parent subline), NK 611 was least cross-resistant to etoposide, adriamycin, and cisplatin among drugs tested. These results indicate that NK 611 may play a role in a salvage chemotherapy for patients with resistant SCLC.

Adenocarcinoma↗

PubMed1993

[Cytotoxic effect of topoisomerase II inhibitors against adriamycin- and etoposide-resistant small cell lung cancer sublines].

Using reverse transcription polymerase chain reaction, we determined mRNA expression of topoisomerase (topo) II alpha and beta in adriamycin- and etoposide-resistant small cell lung cancer sublines, SBC-3/ADM 100 and SBC-3/ETP. The expression of topo II alpha mRNA decreased substantially in SBC-3/ADM 100 and SBC-3/ETP as compared with the parent cell line, SBC-3; 0.71-fold in the former and 0.38-fold in the latter. Similarly, that of topo II beta mRNA decreased to an extent of 0.68-fold in SBC-3/ADM 100 and 0.28-fold in SBC-3/ETP as compared with the parent cell line. SBC-3/ADM 100 and SBC-3/ETP were highly resistant to topo II inhibitors such as daunorubicin, epirubicin, pirarubicin, mitoxantrone, and teniposide. However, SBC-3/ADM 100 showed a less resistance to aclarubicin, and SBC-3/ETP was as sensitive to the drug as was in the parent cell line. The resistance to topo II inhibitors excluding for aclarubicin might be partially explained by the decreased expression of topo II alpha and beta mRNA.

Carcinoma, Small Cell↗

PubMed1993

[A case of small cell lung cancer associated with diabetes insipidus and Cushing's syndrome].

A 62-year-old male with small cell lung cancer (SCLC) associated with Cushing's syndrome and diabetes insipidus (DI) is reported. The patient was referred to our hospital for treatment of SCLC. A diagnosis of paraneoplastic Cushing's syndrome was made on the basis of an elevated serum ACTH (623.5 pg/ml) level, elevated excretion of urinary 17-OHCS (18.01 mg/day), obesity, hypertension, hyperglycemia, persistent hypokalemia, alkalosis, and no history of diabetes mellitus. He was also diagnosed as having DI based on polyuria and polydipsia, low specific gravity of the urine (1.007-1.010), low serum ADH (1.4 pg/ml) level, normal plasma osmolarity (29 mOsm/kg H2O), and the results of water deprivation test. DI and a left visual field defect was suggestive of metastasis to the pituitary region, but no lesion was detected by either CT scan or MRI scan. The patient failed to show a good response to intensive chemotherapy, and died of the tumor five months after commencing chemotherapy. Post-mortem examination revealed metastases to the hypothalamic-neurohypophyseal region, lungs, liver, adrenal glands, bone, bone marrow, and hilar and mediastinal lymph nodes.

Carcinoma, Small Cell↗

PubMed1993

[Meningeal carcinomatosis in patients with small cell lung cancer].

Six patients (2.7%) developed meningeal carcinomatosis among 207 patients with small cell lung cancer (SCLC) receiving intensive combination chemotherapy. The cumulative probability of developing meningeal carcinomatosis was 2.7% at 3 years and 7.8% at 5 years after diagnosis of SCLC. Pain in legs, gait disturbance, headache, nausea and vomiting were the characteristic symptoms at the onset of meningeal carcinomatosis. Although cytological examination of cerebro-spinal fluid (CSF) was essential for the diagnosis of meningeal carcinomatosis, elevated protein, LDH, CEA and/or NSE concentration and decreased glucose concentration in CSF were also helpful for the diagnosis. For treatment of meningeal carcinomatosis, all patients received intrathecal administration of methotrexate, cytosine arabinoside and/or prednisolone. Additionally, 3 patients received spinal irradiation, and one received cerebro-spinal irradiation. However, only 2 patients responded, and survival was brief ranging from 2 to 38 weeks. Development of meningeal carcinomatosis seems to be a rare event; however, it may be an obstacle to the prolongation of patient survival in the treatment of SCLC.

Adolescent↗

PubMed1993

[A case of small cell bronchogenic carcinoma accompanied by polyneuropathy and SIADH].

A 77-year-old man with small cell lung cancer (SCLC) accompanied by polyneuropathy and SIADH is reported. The patient first developed peripheral hyperesthesia and muscle weakness 6 months before admission. He was diagnosed as having SCLC by sputum cytology and supraclavicular lymph node biopsy. On admission, chest radiography and CT scan revealed a mediastinal mass, and the conduction velocity in peripheral nerves was delayed. He was also found to have SIADH, on the basis of an extremely low level of serum Na (114 mEq/l) and osmotic pressure (251 mOsm/kg) but with normal urinary Na and osmotic pressure. In association with complete disappearance of the mediastinal mass after intensive chemotherapy, SIADH and polyneuropathy also improved remarkably. When SCLC relapsed in the abdominal lymph nodes 11 months after complete disappearance of the mediastinal mass, polyneuropathy and SIADH also reappeared. These results indicate that both SIADH and polyneuropathy comprised a paraneoplastic syndrome.

Aged↗

PubMed1993

[Assessment of antitumor activity rhizoxin for human lung cancer cell lines: a potent new drug for drug-resistant lung cancer].

Rhizoxin is a new macrocyclic lactone isolated from the fungus Rhizopus chinensis. In an attempt to predict the effectiveness of rhizoxin in the treatment of lung cancer, we compared the antitumor activity of rhizoxin with those of cisplatin and etoposide using four small cell lung cancer (SCLC) cell lines, SBC-2, -3, -4, and -7, and two non-small cell lung cancer (NSCLC) cell lines, ABC-1 and EBC-1. The concentrations producing 50% inhibition of the growth of these cell lines (IC50) for each drug were obtained by MTT assay. The IC50 of rhizoxin for these cell lines ranged 0.408 nM to 1.56 nM, which were significant lower than those of cisplatin (660 nM to 16,300 nM) and etoposide (275 nM to 31,300 nM). The ratio of IC50 for the most sensitive cell line, SBC-3, to that for the most resistant cell line was less than 4-fold in rhizoxin, in contrast to more than 20-fold in cisplatin and 100-fold in etoposide. Cross-resistance of rhizoxin to cisplatin and etoposide was investigated using a cisplatin-resistant SCLC subline, SBC-3/CDDP, and an etoposide-resistant SCLC subline, SBC-3/ETP. Of interest, the parent cell line, and the resistant sublines were equally sensitive to rhizoxin, indicating rhizoxin being non-cross-resistant to cisplatin and etoposide. In conclusion, rhizoxin may be beneficial in the salvage chemotherapy of drug-resistant SCLC and non-SCLC.

Antibiotics, Antineoplastic↗

PubMed1992

Comparison of antitumor activity of new anthracycline analogues, ME2303, KRN8602, and SM5887 using human lung cancer cell lines.

In an attempt to predict the clinical activity of newly developed anthracycline analogues, ME2303, KRN8602, and SM5887 in the treatment of lung cancer, we compared antitumor activity of these drugs with that of adriamycin, using six human lung cancer cell lines and two drug-resistant human lung cancer sublines. Taking the pharmacokinetic data into consideration, we evaluated the relative antitumor activity: the ratio of area under the concentration-time curve of each drug to the 50% inhibitory concentration of the drug. Regarding this ratio, ME2303 was more potent than adriamycin, SM5887, and KRN8602. Cross-resistance of the new analogues to adriamycin was investigated using an adriamycin-resistant small cell lung cancer subline, SBC-3/ADM100 and an etoposide-resistant subline, SBC-3/ETP. SBC-3/ADM100 being 106-fold more resistant to adriamycin than the parent SBC-3 showed less resistance to the analogues: 1.80-fold to KRN8602, 3.80-fold to SM5887, and 8.60-fold to ME2303. SBC-3/ETP which was 52.1-fold more resistant to etoposide and 39.5-fold more resistant to adriamycin were also less resistant to the new analogues: 3.27-fold to KRN8602, 9.07-fold to SM5887, and 17.3-fold to ME2303. In conclusion, ME2303 was found to be the most potent agent among drugs tested for the treatment of lung cancer, and KRN8602 can be expected to be beneficial for the treatment of drug-resistant small cell lung cancer.

Anthracyclines↗

PubMed1992

Establishment and characterization of an etoposide-resistant human small cell lung cancer cell line.

An etoposide-resistant subline, SBC-3/ETP, from a human small cell lung cancer cell line, SBC-3, was developed by continuous exposure to increasing concentrations of etoposide in culture. The SBC-3/ETP was 52.1-fold more resistant to etoposide than the parent cell line. The SBC-3/ETP was highly cross-resistant to teniposide, adriamycin, vinca alkaloids, 4-hydroperoxycyclophosphamide, CPT-11 and mitomycin C, and marginally cross-resistant to cisplatin, while the subline showed a collateral sensitivity to bleomycin. Topoisomerase I activity in the SBC-3/ETP was reduced to an extent of one half and topoisomerase II activity to an extent of one eighth in comparison with those of the SBC-3. Intracellular accumulation of [3H]-etoposide in the SBC-3/ETP was significantly lower in comparison to the SBC-3. An overexpression of MDR1 mRNA, and the presence of its product, P-glycoprotein, were detected in the SBC-3/ETP by Northern blotting and flowcytometry using a monoclonal antibody of the protein, MRK16. These results indicate that a decreased activity of topoisomerase II is the major factor for the development of etoposide resistance, and that an overexpression of the MDR1 gene is responsible, in part, for the development of resistance to the drug and some structurally unrelated compounds such as adriamycin and vinca alkaloids.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed1992

Clinical features of 125 patients with sarcoidosis: Okayama University Hospital review of a recent 10-year period.

Clinical features were studied in 125 patients with sarcoidosis (72 females and 53 males) diagnosed at Okayama University Hospital during a recent 10-year period. The age distribution had two peaks in patients in their 20s and the 50s. Over half of the patients were detected at health screening check and were asymptomatic, while the remaining were symptomatic. Twelve patients were in stage 0, 41 were in stage I, 54 were in stage II, 16 were in stage III, and 2 were in stage IV according to the chest x-ray findings. Serum angiotensin converting enzyme levels and serum lysozyme levels were elevated in 60% and 76% of the patients, respectively. The bronchoalveolar lavage fluid showed lymphocytosis, especially of helper T-cells. The clinical features of sarcoidosis appear to depend on the duration of the disease.

Adolescent↗

PubMed1992

[Treatment of small cell lung cancer in the elderly: the progress and limitation of chemotherapy].

In order to assess the progress and limitation of chemotherapy in the treatment of small cell lung cancer in the elderly, we analyzed 218 patients who had entered into protocol studies between 1982 and 1990. Among those, there were 101 elderly patients (age of greater than or equal to 66 years) and 117 non-elderly patients (age of less than or equal to 65 years). Response to chemotherapy with or without chest irradiation was almost comparable for the elderly and the non-elderly; complete response rate was 52% for limited disease (LD) and 33% for extensive disease (ED) in the elderly, and it was 68% for LD and 23% for ED in the non-elderly. Survival figures of the two groups were quite similar: The median survival time was 12.6 months for the elderly and 14.5 months for the non-elderly, and the 3-year survival rate was 14% for both groups. An improvement of patient survival was observed along with the chronology of the protocols, i.e., with a escalation of dose intensity. Of interest, the improvement was rather evident in the elderly than in the non-elderly. Hematologic toxicity was considerable more frequent and severe in the elderly than in the non-elderly with non-significant statistics. The incidense of fever episodes while neutropenic was significantly more frequent in the elderly. Non-hematologic toxicity was almost comparable for the two groups, with a exception that the elderly showed a trend being predisposed to renal toxicity. In conclusion, such elderly patients as eligible for entry into a protocol study can benefit from intensive treatment as equally as non-elderly patients can.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1992

[Serum neuron specific enolase (NSE) levels in patients with non small cell lung cancer].

Serum NSE levels were measured in 126 patients with previously untreated NSCLC. The NSE level was greater than 10 ng/ml in 29 patients (23.0%) and this was considered to be positive. Elevation of serum NSE levels correlated closely with clinical stage except stage I and II. The effect of chemotherapy was evaluated in 74 cases included 22 NSE-positive cases. The response rate was 50% in positive cases and 34.6% in negative cases. However, the median duration of response in positive cases (2.2 months) was significantly shorter than that in negative cases (6.6 months). The median survival time of 6.0 months in positive cases was brief compared with 9.6 months in negative cases. These results indicate that elevation of serum NSE level in patients with NSCLC may be a marker of poor prognosis.

Adenocarcinoma↗

PubMed1992

[New anthracycline analogues in the treatment of lung cancer].

Doxorubicin is one of the most potent drugs for the treatment of small cell lung cancer (SCLC), but less potent for non-small eell lung cancer (NSCLC). The prevalent use of doxorubicin is limited by the development of cardiomyopathy. Therefore, TUT-7 SM-5887, and ME2303 have been under the clinical studies to find new anthracyclines with less cardiotoxicity and higher therapeutic indices not only for SCLC but also for NSCLC. The dose-limiting factor of these drugs determined in phase I studies was leukocytopenia. Phase II studies which are currently under way have indicated that SM-5887 is possibly most potent for the treatment of NSCLC, and that these drugs have less cardiotoxicity compared to the mother compound, doxorubicin.

Anthracyclines↗

PubMed1992

An adriamycin-resistant subline is more sensitive than the parent human small cell lung cancer cell line to lonidamine.

Lonidamine, a unique new type of anticancer agent, has been shown to exert marginal activity in patients with resistant small cell lung cancer. We have assessed cytotoxic activity using seven human small cell lung cancer cell lines and the drug resistant small cell lung cancer sublines, Adriamycin-resistant SBC-3/ADM100, etoposide-resistant SBC-3/ETP and cisplatin-resistant SBC-3/CDDP. Although lonidamine had only a minimal activity in seven human small cell lung cancer cell lines, SBC-3/ADM100 cells were more sensitive to lonidamine than the parent SBC-3 cells to a 1.6-fold extent in terms of IC50. SBC-3/CDDP and SBC-3/ETP had no cross-resistance to lonidamine at all. These observations may be of potential clinical significance in treating small cell lung cancer.

Antineoplastic Agents↗

PubMed1992

[Immunohistochemical detection of carcinoembryonic antigen and P-glycoprotein in small cell lung cancer at diagnosis and relapse, with special reference to the tissue expression of CEA and response to chemotherapy].

Small cell lung cancer (SCLC) is one of the most sensitive tumors to drug therapy; however, the majority of patients eventually relapse within a few years. Emergence of drug resistance is thought to play a major role in the dismal course of this disease. However, the mechanism of drug resistance in SCLC still remains obscure. Based on the clinical observation that a significant proportion of patients with relapsing tumor show an elevated serum carcinoembryonic antigen (CEA) concentration while serum neuron-specific enolase (NSE) concentration remains normal, we attempted to determine whether the tissue of CEA is indicative of a clonal change in SCLC, in contrast with the tissue expression of NSE and P-glycoprotein (P-gp). We examined 22 SCLC patients with tumor specimens available both at diagnosis and at relapse. Of the 22 patients, two had CEA expression at diagnosis, and a further three patients showed CEA expression at relapse. It is of note that there were two patients whose tumors expressed NSE alone at diagnosis but expressed CEA alone at relapse. Serum CEA concentration was concordant with the tissue expression of CEA; however, serum NSE concentration was not concordant with the tissue expression of NSE. Tumors with CEA expression at relapse were generally resistant to salvage chemotherapy, while there was no close relationship between the tissue expression of P-gp and refractoriness to drugs at relapse. These findings indicate that the tissue expression of CEA in SCLC is a marker of a clonal change during chemotherapy, and such a clonal change would play a role in the emergence of drug resistance in SCLC.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed1992

[A case of locally advanced esophageal cancer effectively treated with concurrent chemotherapy and radiotherapy].

A case of a 69-year-old man with locally advanced esophageal cancer was reported. The patient received five courses of chemotherapy consisting of cisplatin (30 mg i.v. days 1-5), 5-fluorouracil (500 mg i.v. days 1-5) and bleomycin (5 mg i.m. days 1-5) every four weeks with a split course irradiation at a dose of 50 Gy, which was concurrently given at the second, third and fourth course of the chemotherapy. Treatment was effectively carried out without severe toxicities. The patient achieved a histologically-confirmed complete remission after completion of the treatment. The patient is disease-free and fully active 28 months after the beginning of chemotherapy. The treatment modality appears to be useful for advanced esophageal cancer.

Aged↗

PubMed1992

[Six cases of primary pulmonary cryptococcosis].

Six patients with asymptomatic primary pulmonary Cryptococcosis are reported. In all of the patients, the disease was detected by annual chest X-ray during mass screening for lung cancer or during follow-up for pulmonary tuberculosis or gastric cancer. The chest X-ray findings consisted of a solitary pulmonary nodule in 4 patients and multiple pulmonary nodules in 2. Only one patient who could not be histologically diagnosed by bronchofiberscopy underwent surgical resection. However, the other 5 patients were histologically diagnosed by transbronchial biopsy with bronchofiberscopy. They were treated with oral antifungal agents, namely flucytosine (5-FC) and/or fluconazole, with marked improvement of chest X-ray findings. These results indicate that transbronchial biopsy with bronchofiberscopy and oral administration of antifungal agents instead of initial surgical resection are useful in the diagnosis and treatment of primary pulmonary cryptococcosis.

Adult↗