Biomedical subjects

T Ohnoshi

Publications and source records attributed to T Ohnoshi.

At least 37 records · Page 2Linked to original sources

PubMed1993

Immunohistochemical detection of P-glycoprotein and carcinoembryonic antigen in small cell lung cancer: with reference to predictability of response to chemotherapy.

In an attempt to elucidate the tumor properties relating to responsiveness to chemotherapy, we examined immunohistochemically the expression of P-glycoprotein (P-gp) and carcinoembryonic antigen (CEA) in small cell lung cancer (SCLC) tumors. Tumor specimens from 33 patients were obtained at the time of diagnosis and relapse. Four patients expressed P-gp in their initial tumors, and 7 others did in recurrent tumors. The overall response rate to chemotherapy of the initial tumors was 75% for P-gp-positive initial tumors and 86% for P-gp-negative tumors, whereas the disease-free and overall survival times were significantly shorter in the former than the latter. Three patients showed CEA in their initial tumors, and 5 others did in recurrent tumors. The patients with CEA-positive initial tumors tended to relapse earlier than those with CEA-negative tumors. In addition, recurrent tumors expressing CEA were resistant to salvage chemotherapy. A clear correlation between CEA expression by tumors and the CEA level in the serum was observed at diagnosis as well as at relapse. These findings indicate that P-gp and/or CEA expression by a tumor and elevated CEA level in the serum may predict refractoriness of the tumor to chemotherapy.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed1993

Mortality and morbidity in two-year disease-free survivors of small cell lung cancer after treatment with combination chemotherapy with or without irradiation.

We evaluated the long-term outcome of 148 patients with small cell lung cancer (SCLC) who had been entered into clinical trials of chemotherapy with or without thoracic and prophylactic cranial irradiation (PCI) between 1981 and 1987. Eighteen patients (12%) survived for 2 or more years. With a minimum follow-up of 4.5 years, 10 of the 18 patients who remained disease-free at 2 years are currently alive and free of SCLC. Seven of these 10 patients currently function as they did before diagnosis. However, three suffer from central nervous system changes of varying degrees in severity which appeared 2-3 years after PCI. Eight of the 18 patients who were disease-free at 2 years have died. Two died of isolated relapse in the brain at 3.6 and 4.2 years after initiation of chemotherapy. Five died of other malignancies while continuing their complete response to SCLC; two of non-small cell lung cancer, two of acute myelogenous leukemia, and one of hepatocellular carcinoma. Another patient died of an unrelated disease without any evidence of SCLC. A small but substantial proportion of patients who underwent intensive treatment will achieve long-term survival; however, these patients remain at higher risk for second cancers and late toxicities. Therefore, attention must be directed to defining the safest way to employ such treatment in the management of SCLC.

Adult↗

PubMed1993

Establishment of an adriamycin-resistant subline of human small cell lung cancer showing multifactorial mechanisms of resistance.

A subline highly resistant to Adriamycin (SBC-3/ADM100) was isolated in vitro from the human small cell lung cancer cell line, SBC-3, by culturing in progressively higher concentrations of Adriamycin. The SBC-3/ADM100 cells were 106-fold more resistant to the drug than the parent cells in an inhibitory concentration of 50% determined by the MTT assay. The population-doubling time was much longer in SBC-3/ADM100 than in the parent cells. Northern blot hybridization revealed marked overexpression of the MDR1 mRNA in the resistant cells. P-glycoprotein overexpression and a decrease in intracellular accumulation of Adriamycin were demonstrated in SBC-3/ADM100, indicating that outward drug transport was the major mechanism of resistance in this subline. Additionally, a significant elevation of the intracellular glutathione content coupled with the glutathione S-transferase (GST) pi level and a decrease in DNA topoisomerase II (Topo II) activity were noted in this resistant subline. These results indicate that the mechanism of resistance to Adriamycin is multifactorial; involving altered growth characteristics, an enhanced outward transport, enhanced drug detoxification process, and decreased target enzyme activity. The resistant subline will serve as a useful tool in the search for ways to overcome drug resistance.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed1993

Successful treatment of non-Hodgkin's lymphoma in a patient with common variable immunodeficiency.

A case of common variable immunodeficiency (CVID) who developed non-Hodgkin's lymphoma (NHL) of the rectum is reported. A 22-year-old male student in whom CVID was diagnosed at 7 years of age was referred to our department for the treatment of rectal NHL. The patient had stage IE disease confined to the rectum after clinical diagnostic procedures. He was initially treated with radiation therapy alone, but a relapse soon occurred in the paraaortic lymph nodes. He was successfully treated with CHOP-Bleo chemotherapy and supplementation with immunoglobulin preparations. He has since remained free of NHL and infectious complications for over 30 months despite his persistent immunodeficiency.

Adult↗

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

[Non-Hodgkin's lymphoma of the bone, with reference to MRI findings following treatment].

A 38-year-old man was admitted to our department on April, 1991 for a progressive mass in his right thigh. He had pain in the same area since April, 1990, but did not notice lymph node swelling until March, 1991. The biopsy specimen of the mass showed diffuse large cell non-Hodgkin's lymphoma (NHL) with an immunohistochemical feature of B cell. He achieved a complete remission (CR) by a doxorubicin-containing combination regimen and received involved field irradiation with a total dose of 35 Gy thereafter. He has been in CR since September, 1991. Primary NHL of the bone is rare and there have been few reports on MRI findings during the treatment. These findings and management of primary NHL of the bone were discussed.

Adult↗

PubMed1993

Brief induction chemotherapy followed by involved-field irradiation for the treatment of localized intermediate- and high-grade non-Hodgkin's lymphoma.

In an attempt to assess the effects and toxicity of brief induction chemotherapy plus involved-field irradiation for localized intermediate- and high-grade non-Hodgkin's lymphoma, we conducted a single-arm prospective trial between May 1987 and July 1991. Patients received four cycles of a five-drug chemotherapy regimen consisting of cyclophosphamide, doxorubicin, vincristine, prednisolone, and bleomycin (CHOP-Bleo) followed by involved-field irradiation of 30 Gy. Of 32 patients consecutively enrolled, 30 patients had measurable and/or evaluable disease, while two had no evaluable disease, as their major tumors had been surgically removed. All the patients were in complete remission at the conclusion of all treatment. Four patients have relapsed so far and one died of the disease at 17 months. With a median follow-up time of 33 months (range, 8 to 58), the actuarial disease-free survival rate was 82% and the overall survival rate was 96%. The toxicity was generally mild and all the patients received the planned treatment course. This treatment modality appeared to be safe and effective for localized intermediate- and high-grade non-Hodgkin's lymphoma.

Adult↗

PubMed1993

Alternating chemotherapy of CHOP-Bleo and POEM-Bleo for diffuse large-cell lymphoma: a single-institutional study with a long-term follow-up.

Diffuse large-cell lymphoma (DLCL) is a neoplasm that is curable with chemotherapy in an appreciable percentage of patients. However, not all patients are cured and the best drug combination and optimal dose intensity have not yet been established. In an attempt to improve complete response rate and survival with minimal toxicity, we devised an alternating combination chemotherapy consisting of CHOP-Bleo (cyclophosphamide, doxorubicin, vincristine, prednisolone, and bleomycin) and POEM-Bleo (prednisolone, vincristine, etoposide, mitoxantrone, and bleomycin). Between March 1986 and October 1990, 30 newly-diagnosed patients with advanced DLCL were treated with the regimen. Of these 30 patients, 14 (47%) were 61 years of age or more, 15 (50%) had stage IV disease, 14 (47%) presented with constitutional symptoms, and 7 (23%) had T-cell lymphoma. After the completion of therapy, 23 (77%) achieved a complete response and 6 (20%) had a partial response. The actuarial relapse-free survival at 5 years is 52% and the overall survival projected to 5 years is 47%. Toxicity was generally mild and well tolerated. Although this alternating regimen had substantial activity as front-line chemotherapy for advanced DLCL, we conclude that the observed response rate and survival do not essentially differ from those achieved with conventional regimens and further clinical trials are thus not warranted.

Adult↗

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

Inhibitory effects of cholera toxin on in vitro growth of human lung cancer cell lines.

Cholera toxin (CT) inhibited the growth of three out of 10 small cell lung cancer (SCLC) cell lines and two out of seven non-small cell lung cancer (NSCLC) cell lines when tested by 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) assay. These CT-sensitive as well as CT-resistant cell lines bound well to the non-toxic CT-B subunit-fluorescein isothiocyanate conjugate (FITC-CTB) when assayed by flow cytometry. Using the reaction of horseradish peroxidase-conjugated CT-B (HRP-CTB) on thin-layer chromatography (TLC), we analyzed gangliosides extracted from SCLC cell lines, CT-resistant SBC-1, minimally CT-sensitive SBC-3 and CT-sensitive SBC-5. HRP-CTB was found to react not only with GM1, but also with Fuc-GM1, GD1b and other gangliosides on TLC. Although CT-resistant SBC-1 cells bound well to FITC-CTB, the binding of gangliosides extracted from SBC-1 cells to HRP-CTB was markedly decreased when compared to those from CT-sensitive SBC-5 cells. The CT resistance of the minimally CT-sensitive SBC-3 cell lines, which binds weakly FITC-CTB and HRP-CTB, was partially reversed by exogenous GM1 pretreatment. These observations suggest that the amount of gangliosides, such as GM1, Fuc-GM1 and GD1b, on the cells, rather than the CT-binding ability to the cells, plays a major role in cytotoxicity by CT.

Carcinoma, Non-Small-Cell Lung↗

PubMed1993

Primary pulmonary non-Hodgkin's lymphoma in a Japanese renal transplant recipient.

Pulmonary non-Hodgkin's lymphoma (NHL) developed in a 31-year-old renal transplant recipient 3 years after transplantation. Chest roentgenogram showed rapidly progressive multiple nodules in both lungs. The pleural fluid obtained by needle aspiration contained many atypical cells with surface B cell antigen and abnormal karyotype. The patient died of pulmonary edema shortly after combination chemotherapy was begun without regression of the tumors. Autopsy revealed diffuse large cell NHL confined to both lungs. Immunological examination and DNA analysis of the tumor showed monoclonal B cell NHL.

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↗