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Biomedical subjects

Y Ariyoshi

Publications and source records attributed to Y Ariyoshi.

At least 181 records · Page 10Linked to original sources

[The role of tumor markers in lung cancer management].

A variety of substances, including enzymes, hormones, antigens and proteins are called tumor markers. In this report, tumor marker of lung cancer refers to substances in serum of patients with lung cancer. In order to evaluate usefulness of tumor markers in lung cancer management, contributory tumor markers to diagnosis of lung cancer were selected by the incidence of elevation. Consequently CEA, SCC, SSEA-1, CA15-3 and NSE were considered to be possibly useful for diagnosis and also classification of histological types of lung cancer. Then the following areas were examined for these markers: (1) usefulness for making a decision of therapeutic strategy, (2) predictability for drug and radiosensitivity, (3) judgment of therapeutic effect; and (4) value in monitoring clinical course. From these analyses some positive data for tumor markers to be useful in lung cancer management were obtained as follows. Since serum values exceeding 10 ng/ml for NSE were observed mostly in advanced stage of small cell lung cancer, intensive chemotherapy should be carried out in such cases. But inoperability of non-small cell lung cancer could hardly be predicted by elevation of tumor markers. No correlation was proved between expression of any tumor markers to be available in today's clinical practice and therapeutic sensitivity. Response to treatments could be evaluated by serial measurements of serum level although definite criteria for judgment have not been determined. Periodic surveys of tumor markers expressed in lung cancer were predictable for relapse prior to imaging detection. Tumor markers of lung cancer take an important role in lung cancer management.

Antigens, Neoplasm↗

[Initial basic and clinical evaluation of a solid-phase immunoradiometric assay for sialyl SSEA-1 antigen: 1. Evaluation of assay conditions and normal values].

We describe a solid-phase immunoradiometric sandwich assay method for a new tumor marker, sialyl SSEA-1 (sialyl LeX-i), using RIA kits (prepared by Otsuka Assay Laboratories). The assay required only duplicate 20-microliter samples, and the concentration of sialyl SSEA-1 antigen in serum was determined with reference to a standard curve ranging from 0 to 224 arbitrary unit/ml. The intra- and inter-assay reproducibilities and analytical recovery of antigen were excellent. The cut-off value (38 unit/ml) was obtained as mean + 2SD, which was calculated from the antigen concentration in sera from 1,105 healthy individuals. Also described are the alterations of normal values by age, sex, and Lewis blood group status.

Antigens, Neoplasm↗

[Initial basic and clinical evaluation of a solid-phase immunoradiometric assay for sialyl SSEA-1 antigen: 2. Evaluation of clinical significance].

The clinical significance of serum sialyl SSEA-1 antigen was evaluated using the sera of 1261 patients with malignant tumors and 717 patients with non-malignant diseases measured with Otsuka Assay Laboratories' RIA Kits. The results indicate that the antigen was frequently elevated in the sera from the patients with various adenocarcinomas, including lung (45%), pancreas (64%) and ovary (57%). The false positive incidence of antigens in the sera from the patients with non-malignant disorders was as low as 4.9%. No correlation was observed with other tumor markers examined in this study, and the diagnostic efficiency increased significantly by the combined determination of sialyl SSEA-1 antigen level with other markers. The serial determination of the serum sialyl SSEA-1 antigen level has a clinical utility also in monitoring the patients with adenocarcinoma receiving surgical operation and/or chemotherapy as indicated by the results of the longitudinal observation of the patients.

Adenocarcinoma↗

[Second-generation cisplatin analogs].

Since the introduction into clinical practice in 1972, cisplatin (CDDP) has assumed an important role in the treatment of various tumors such as testicular, ovarian or pulmonary cancer. Its toxicities include emesis, renal impairment, neuropathy, hearing loss and anemia. In clinical trials renal toxicity has been proved to be dose limiting factor. Thus the total number of courses which may be given is limited. For this reason second-generation CDDP analogues with reduced toxicity have been tried to develop and are reaching clinical testing. A number of studies have now been published relating the results of these trials. The best studied of these analogues is carboplatin (CBDCA, JM-8) which was noted to be less nephrotoxic, but more myelosuppressive than CDDP in preclinical study. Phase I trials have shown that CBDCA is relatively free of renal toxicity and that its dose limiting factor is myelosuppression, especially thrombocytopenia. In phase II trials CBDCA has been shown to be an active agent in advanced carcinomas of the ovary, head and neck, lung and urogenital organs. Similar results have been obtained in clinical trials of iproplatin (CHIP, JM-9) which is synthesized as an analogue of CDDP. Two other analogues developed in Japan have been evaluated to be active for various mouse tumors in preclinical studies. Phase I trials of these agents is now ongoing.

Bone Marrow↗

[Paraneoplastic endocrine syndromes].

In some instances, tumors can produce signs and symptoms at a distance from the tumor or its metastases. These are defined as paraneoplastic syndrome or humoral syndrome associated with neoplasms. Paraneoplastic syndromes can arise from circulating substances secreted by tumors. The most well-recognized and frequent concomitant of neoplasms is the production of hormones by nonendocrine tumors. These are usually called ectopic hormone-producing tumors and bring about clinically endocrinologic manifestations secondary to hormone excess in patients with nonendocrine tumors. Paraneoplastic endocrine syndromes frequently observed are Cushing's syndrome due to ectopic production of ACTH, SIADH due to ectopic production of ADH, hyper-calcemia, hypoglycemia and so on. In order to establish a paraneoplastic etiology for alteration in hormone production, evidence that the hormone is produced by the tumor must be proved. Paraneoplastic endocrine syndromes should be distinguished from hormone production by benign cells, hormone production by a malignancy of an endocrine organ or alterations in hormone production being due to infiltration into the endocrine organ by a primary tumor. The treatment of ectopic endocrine syndromes should be directed primarily at the tumor. Because the course of this type of syndrome usually runs parallel to the course of the underlying tumor, the ectopically produced hormone can be a useful monitoring marker of the disease.

ACTH Syndrome, Ectopic↗

Two novel cell surface antigens on small cell lung carcinoma defined by mouse monoclonal antibodies NE-25 and PE-35.

Two mouse monoclonal antibodies, NE-25 and PE-35, defining novel cell surface antigens of small cell lung carcinoma (SCLC) were produced. The molecular weight of NE-25 and PE-35 antigens estimated by radioimmunoprecipitation was 25,000 and 35,000, respectively. NE-25 antigen was expressed on the majority of cell lines and tumor specimens of SCLC among lung carcinoma. These NE-25-positive cell lines showed typical growth morphology as SCLC classic lines and expressed high levels of neuroendocrine biomarkers, such as aromatic L-amino acid decarboxylase, while NE-25 antigen-negative lines lacked apparent neuroendocrine properties. This antigen was expressed also on a subset of neoplastic cells with (neuro)endocrine properties, including pulmonary carcinoid, and on various tumors of nervous tissues, such as neuroblastoma. Among the normal cells, Kulchitski cells of lung, thyroid gland, adrenal gland, Langerhans islet, and nervous tissues were positive. Thus, the expression of NE-25 antigen is closely associated with the neural and/or (neuro)endocrine differentiation state. On the contrary, PE-35 antigen was present on four major types of lung carcinomas as well as on squamous cell carcinoma and adenocarcinomas of various tissues, but it was absent from nervous tissue tumors. Thus, PE-35 antibody showed a "pan-epithelial" reactivity. Analysis by NE-25 and PE-35 antibodies provided evidence for the heterogeneities of SCLC by demonstrating four surface phenotypes, with the NE-25+/PE-35+ phenotype being most common. In addition, the results supported the current understanding that various histological types of lung carcinoma, including SCLC, are derived from a stem cell of the bronchial epithelium.

Antibodies, Monoclonal↗

[A case of hepatoma with a remarkable response to gamma-interferon administration].

A 59-year-old male was admitted to our hospital with complaints of general fatigue, abdominal distension and edema in the legs in February, 1985. Laboratory findings were as follows: GOT 152 IU/l, GPT 129 IU/l, LDH 555 IU/l, ALP 1147 IU/l, gamma-GTP 413 IU/l, T.-Bil 2.1 mg/dl and AFP 422.6 ng/ml. Multiple SOLs were recognized in both lobes of the liver by abdominal CT scan and echography. Interferon-gamma (gamma-IFN: KW-2202; Kyowa Hakko Co.) therapy was started in March from an initial dose of 1 X 10(6) units and was increased up to 4 X 10(6) units, 2 X 10(6) units being administered as a maintenance therapy for 12 weeks. The tumors became remarkably smaller in size, AFP was decreased to 38.8 ng/ml, and PR was obtained. The only side effect was temporary fever. The patient was subsequently followed without gamma-IFN at an outpatient clinic for about 100 days, but finally died due to rupture of esophageal varices and hepatic failure.

Carcinoma, Hepatocellular↗

Biological and clinical implication of neuron-specific enolase and creatine kinase BB in small cell lung cancer.

The specificity of neuron-specific enolase (NSE) and creatine kinase BB (CK-BB) for small cell lung cancer (SCLC) was determined by biological and immunohistochemical procedures in lung cancer tissues and cultured cell lines. Average values of extractable NSE and CK-BB of SCLC tissues were significantly higher than those of non-SCLC and normal lung tissues. A large amount of NSE and CK-BB was demonstrated in SCLC cell lines. Immunohistochemical examination showed positive staining for NSE and CK-BB in most cases of SCLC and in a few cases of non-SCLC. From these data NSE and CK-BB should be considered to be highly specific for SCLC. In a clinical study serum values exceeding 10 ng/ml for NSE and 1.5 ng/ml for CK-BB were set as positive for the enzymes. Positive rates in SCLC were 71.4% for NSE and 65.3% for CK-BB, which were significantly higher than those in non-SCLC. All positive cases were in an advanced stage. Consecutive daily NSE determinations during induction chemotherapy showed transient elevation immediately after the initiation of drug administration (tumor lysis syndrome), followed by a decline to normal range in responders. This phenomenon seems to indicate tumor sensitivity to cytotoxic drugs. NSE positive non-SCLC was as sensitive to cytotoxic drugs as SCLC. These findings indicate that lung cancer with elevated serum NSE and CK-BB levels at diagnosis should be strongly suspected of being SCLC in the advanced stage.

Antineoplastic Combined Chemotherapy Protocols↗

[Cardiotoxicity of mitoxantrone].

Cardiotoxicity induced by mitoxantrone was studied in 50 closely followed patients receiving chemotherapy with mitoxantrone. Serial electrocardiograms were recorded. The electrocardiographic parameters (heart rate, P-Q interval, QRS interval, QRS voltage, and QTc interval) were analyzed. The patients who received mitoxantrone showed no significant changes in these parameters. Furthermore, in order to investigate the details of acute cardiotoxicity of mitoxantrone and adriamycin, Holter ECGs were recorded and some of the electrocardiographic parameters were analyzed. The basic rhythm was sinus rhythm in all cases except for only one case which developed intermittent atrial fibrillation after adriamycin therapy. No effect on the specialized conduction system was observed on either group. Supraventricular premature beat showed no significant changes, but ventricular premature beat showed a tendency to increase and the mode of appearance of the ventricular extrasystole was very dangerous in the adriamycin-administered group. Developed ST-T changes were also seen in the adriamycin group. In conclusion, mitoxantrone seemed to have less cardiotoxicity in comparison with that of adriamycin.

Adolescent↗

Highly sensitive enzyme immunoassay for human creatine kinase BB isozyme.

A sensitive sandwich-type enzyme immunoassay method for measurement of brain-type isozyme of human creatine kinase (CK-BB) was developed using purified antibodies specific to the B subunit. The assay system consisted of polystyrene balls with immobilized antibody F(ab')2 fragments and the same antibody Fab' fragments labelled with beta-D-galactosidase from Escherichia coli. The assay was highly sensitive and 1 pg of CK-BB was measurable. The assay was specific to the B subunit of creatine kinase (CK-B), and it cross-reacted about 25% with CK-MB, the heart-type isozyme. However, the assay showed no cross-reactivity with CK-MM, the muscle type-isozyme or with neuron-specific gamma gamma enolase. Coefficients of variation in within-run and between-run precision studies for serum CK-B were less than 8%. Serum CK-B levels in healthy adults of various ages (16-59 yr old) ranged from 0.25-1.44 ng/ml, whereas the CK-B concentrations in children (less than 10 yr old) were relatively high, ranging from 1.3-7.4 ng/ml. The CK-B levels in the cerebrospinal fluids (CSF) could be determined by the present method, and they ranged from 0.10-0.76 ng/ml in the samples from patients with non-neuronal disorders. Determination of immunoreactive CK-B in the extracts of various human tissues confirmed previous reports that CK-B was distributed at high concentrations in the central nervous tissue, prostate, uterus, bladder, gastrointestinal tract and heart muscle.

Adult↗

Creatine kinase B subunit as a biomarker for small cell carcinoma of the lung: comparison with gamma-enolase.

Concentrations of creatine kinase (CK) B subunit (CK-B) in tumor tissues and in sera of patients with various lung carcinomas were determined, together with the concentrations of neuron-specific gamma-enolase (gamma subunit of a gamma and gamma gamma enolases), by the use of a sensitive enzyme immunoassay method. The CK-B and gamma-enolase levels were enhanced in tissues of small cell carcinoma of the lung. The average tissue contents of CK-B in small cell carcinoma (SCCL), adenocarcinoma (ADCL) and squamous cell carcinoma (ECCL) of the lung, and normal lung were 2320, 308, 163, and 372 ng/mg protein, respectively. The contents of gamma-enolase in those tissues were 1460, 276, 225, and 42.7 ng/mg protein, respectively. Serum CK-B concentrations in healthy adults (n = 100) were 0.53 +/- 0.22 ng/ml and ranged from 0.25 to 1.44 ng/ml, but they were significantly increased (greater than 1.5 ng/ml) in some patients with SCCL (26/42 cases, 62%), ADCL (7/36, 19%), ECCL (7/37, 19%), and large cell carcinoma of the lung (LCCL, 4/13, 31%). Serum CK-B was also enhanced in some patients with breast carcinoma and in a few cases in carcinomas of the stomach, colon and pancreas. Serum concentrations of CK-B were well correlated with those of gamma-enolase in patients with SCCL (r = 0.667, n = 83, P less than 0.01) and LCCL (r = 0.689, n = 20, P less than 0.01), but poorly in patients with ADCL and ECCL. Since serum CK-B concentrations in patients with SCCL changed in parallel with the clinical course during treatment, serum CK-B may also be a useful biomarker, as well as neuron-specific gamma-enolase, for monitoring the clinical course of patients with SCCL.

Adenocarcinoma↗

High levels of S-100a0 (alpha alpha) protein in tumor tissues and in sera of patients with renal cell carcinoma.

The alpha alpha form of S-100 protein (S-100a0), which is distributed mainly in the heart and striated muscles, and also in the brain and kidney, was determined in tumor tissues and sera of patients with renal cell carcinoma by employing an enzyme immunoassay system for bovine S-100a0 protein. The average content of S-100a0 in the renal cell carcinoma tissue (n = 10) was about 650 ng/mg protein, 4-fold higher than that in the kidney (n = 6, 160 ng/mg protein). Immunohistochemically, S-100a0 antigen was localized in such epithelial cells as proximal tubules, Bowman's capsules and collecting tubules of normal kidney, and in the cytoplasm, nucleus and occasionally plasma membrane of the tumor cells. The contents of S-100a0 protein in various lung carcinoma tissues were low (less than 10 ng/mg protein). Serum S-100a0 concentrations were less than 0.3 ng/ml in healthy subjects, but they were significantly increased in patients with renal cell carcinoma at diagnosis, showing greater than 0.5 ng/ml in 17/32 cases (53%). Serum S-100a0 levels were also enhanced in some patients with lung cancer (10/33, 30%), breast cancer (4/20, 20%) and other non-neoplastic diseases, indicating that S-100a0 protein in the serum is not a specific biomarker for renal cell carcinoma. However, serum S-100a0 concentrations in patients with renal cell carcinoma changed in parallel with the clinical course during treatment. These results suggest that serum S-100a0 may be a useful biomarker at least for monitoring the clinical course of renal cell carcinoma.

Carcinoma, Renal Cell↗

[Evaluation of neuron-specific enolase as a new tumor marker for carcinoma of the lung].

Neuron-specific enolase (NSE) as a tumor marker for carcinoma of the lung was evaluated by immunostaining or enzyme immunoassay. NSE productions were immunocytochemically detected in most of small cell carcinoma and a few cases of other histological type of carcinoma. The data obtained in this study suggested that NSE is a marker for lung carcinoma which exhibit the properties of neuroendocrine tumors and is not a marker for histogenesis of small cell carcinoma of the lung. Serum NSE analysis is suggested to be useful for the evaluation of disease extent, monitoring the clinical course and prediction of sensitivity to cytotoxic treatments.

Adenocarcinoma↗