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Biomedical subjects

Y Segawa

Publications and source records attributed to Y Segawa.

At least 19 recordsLinked to original sources
PubMed1998

A randomized trial of hybrid administration of cyclophosphamide, doxorubicin, and vincristine (CAV)/cisplatin and etoposide (PVP) versus sequential administration of CAV-PVP for the treatment of patients with small cell lung carcinoma: results of long term follow-up.

BACKGROUND: In an attempt to determine the efficacy of cyclophosphamide, doxorubicin, and vincristine (CAV)/cisplatin and etoposide (PVP) hybrid chemotherapy (HYB), a rapidly alternating chemotherapy, in patients with small cell lung carcinoma (SCLC), the authors conducted a randomized study to compare HYB with CAV-PVP sequential chemotherapy (SEQ). METHODS: Patients in the HYB group received the 3-drug CAV combination on Day 1 and the 2-drug PVP combination on Day 8, repeated every 4 weeks for up to 6 cycles. Patients in the SEQ group received 3 cycles each of CAV and PVP sequentially every 4 weeks, delivered on Days 1 and 8. All responding patients with limited disease (LD) received thoracic irradiation (50 gray) after chemotherapy. RESULTS: Between April 1988 and October 1992, 129 patients were evaluated fully. There were no significant differences in the treatment outcome between patients in the HYB and SEQ groups in terms of the complete response rate (59% for LD patients and 21% for extensive disease [ED] patients in the HYB group vs. 45% for LD patients and 16% for ED patients in the SEQ group), or median survival time (17.9 months for LD patients and 9.7 months for ED patients in the HYB group vs. 20.6 months for LD patients and 12.2 months for ED patients in the SEQ group). CONCLUSIONS: Hybrid CAV-PVP therapy is effective for the treatment of SCLC, but appears to be no better than sequential therapy with the same regimen.

Adult↗
PubMed1998

Measurement and evaluation of serum anti-p53 antibody levels in patients with lung cancer at its initial presentation: a prospective study.

Anti-p53 antibodies in sera are known to be products of the host immune response to mutated p53 protein, and are present in some patients with various types of cancer. In this study, we measured serum anti-p53 antibody levels in 52 patients with lung cancer and 63 normal volunteers to determine the relationship between anti-p53 antibody level and clinical features of lung cancer patients. Anti-p53 antibody level was measured by an enzyme-linked immunosorbent assay and expressed as an anti-p53 antibody index, defined as the ratio of absorption of serum sample to that of p53-positive serum. The median anti-p53 antibody index was 6.6 for lung cancer patients, and higher than that in normal volunteers (1.7) (P = 0.0000). For lung cancer patients, significant differences in index levels were found by histology (4.3, n = 25, adenocarcinoma vs 8.7, n = 18, squamous cell carcinoma vs 64.8, n = 2, large-cell carcinoma vs 9.8, n = 7, small-cell carcinoma; P = 0.0109). High anti-p53 antibody index levels were observed for both large-cell carcinoma and small-cell carcinoma. When the cut-off level was set at 7.2, determined using the twice 95% specificity level for normal volunteers, the sensitivities of anti-p53 antibodies were 46.1% for all lung cancers, 28.0% for adenocarcinoma, 55.6% for squamous cell carcinoma, 100% for large-cell carcinoma and 71.4% for small-cell carcinoma. However, there were no significant differences in index level by gender, age, smoking index, presence of previous or concomitant cancer or disease stage. Multivariate analysis using a logistic regression model demonstrated that histological type of tumour was a dominant factor associated with elevation of anti-p53 antibody index level (P = 0.0184). These findings suggest that serum anti-p53 antibody index level might be independent of tumour burden and the presence of previous or concomitant cancer in our series of lung cancer patients, but is clearly strongly correlated with tumour histological type.

Adenocarcinoma↗
PubMed1998

Upregulation of retinal vascular endothelial growth factor mRNAs in spontaneously diabetic rats without ophthalmoscopic retinopathy. A possible participation of advanced glycation end products in the development of the early phase of diabetic retinopathy.

Vascular endothelial growth factor (VEGF) has recently been shown to be involved in the pathogenesis of proliferative diabetic retinopathy. However, its involvement in the development of the early phase of diabetic retinopathy is not fully understood. In this study we investigated the retinal VEGF mRNA level in spontaneously diabetic Otsuka Long-Evans Tokushima fatty (OLETF) rats, a model of non-insulin-dependent diabetes, without overt retinopathy, using quantitative reverse-transcription polymerase chain reaction. The retinal VEGF mRNA level was 2.2 times higher (p < 0.0005) in OLETF rats than in control rats at the age of 60 weeks. Moreover, their retinal mRNA level was positively correlated with serum concentration of advanced glycation end products (AGEs) but not to serum glucose concentration. Furthermore, the peak latency of the oscillatory potentials in the electroretinogram, one of the most sensitive markers for the early phase of diabetic retinopathy, was significantly prolonged in OLETF rats (p < 0.05), being also correlated with the serum AGE concentration. The results thus suggest that AGEs, which are formed acceleratedly in diabetic conditions, are involved in the development of the early phase of diabetic retinopathy probably through the induction of retinal VEGF mRNAs.

Animals↗
PubMed1997

Risk factors for development of radiation pneumonitis following radiation therapy with or without chemotherapy for lung cancer.

PURPOSE: To determine the risk factors contributing to development of radiation pneumonitis (RP) in patients with lung cancer who undergo radiation therapy to the thorax. METHODS AND MATERIALS: Development and severity of RP were retrospectively analyzed for 89 patients with lung cancer who underwent radiation therapy with or without chemotherapy at the National Shikoku Cancer Center Hospital between 1991 and 1995. The severity of RP was determined using a modified grading scale based on that of the Radiation Therapy Oncology Group and the European Organization for the Research and Treatment of Cancer. RESULTS: Fifty-two (58%) patients developed RP: 34 patients with Grade 1, 5 with Grade 2, 8 with Grade 3, and 5 with Grade 5 RP. Severe RP tended to develop earlier than less severe RP, but not to a significant extent (p = 0.151). On logistic regression analysis including both patient condition and treatment factors, development of Grade 1 or more severe RP was most frequently observed for Stage I-II disease (p = 0.011). The use of chemotherapy, large daily radiation dose, and once-daily fractionation (vs. twice-daily fractionation) were possibly related to the development of RP (p = 0.057, p = 0.069, and p = 0.092, respectively). For the group of 48 patients who underwent chemoradiation therapy, the use of large daily radiation dose was a significant risk factor for RP (p = 0.014). In addition, the use of once-daily fractionation was a marginally significant risk factor (p = 0.052). Among chemotherapy drugs administered, cisplatin was a favorable factor (p = 0.011), while adriamycin was a risk factor (p = 0.061). CONCLUSIONS: In radiation therapy for lung cancer, administration of a large daily dose should be avoided in order to prevent RP, particularly when radiation therapy is combined with chemotherapy.

Adult↗
PubMed1997

Methotrexate suppresses nitric oxide production ex vivo in macrophages from rats with adjuvant-induced arthritis.

We examined the effects of methotrexate (MTX) on the level of nitric oxide (NO) produced by peritoneal macrophages from rats with adjuvant-induced arthritis (AA) ex vivo. During the development of AA, paw swelling increased and LPS enhanced the capacity of peritoneal macrophages to produce NO and prostaglandin E2 (PGE2). MTX (0.1 mg/kg, p.o.) treatment for 21 days reduced the paw swelling, and inhibited the increased NO and PGE2 production. However, when MTX (0.1 mg/kg, p.o.) was administered to rats with established AA, these parameters were not significantly influenced. In normal rats, MTX (0.1 mg/kg, p.o.) treatment for 21 days did not change NO and PGE2 production of LPS-stimulated macrophages. On the other hand, macrophages from normal and AA rats cultured in the presence of MTX (1, 10 and 100 microM), were activated by LPS in vitro. MTX did not influence NO or PGE2 production by LPS-stimulated macrophages in normal and AA rats. By contrast, indomethacin (IM) (1.0 mg/kg, p.o.) treatment for 21 days reduced the paw swelling, and inhibited NO and PGE2 production in AA rats. IM inhibited significantly PGE2 production, but did not influence NO production by LPS-stimulated macrophages in vitro. These results suggest that MTX treatment reduces NO production in peritoneal macrophages in AA rats, and these actions of MTX may have an inhibitory effect without the modulation of PGE2.

Administration, Oral↗
PubMed1997

Serum CD44 levels in patients with non-small cell lung cancer and their relationship with clinicopathological features.

Serum CD44 standard and CD44 variant 6 levels were measured in 45 non-small cell lung cancer (NSCLC) patients and 33 patients with benign lung disease by enzyme-linked immunosorbent assay (ELISA). Expression of CD44 variant 6 in trans-bronchial biopsy specimens from the NSCLC patients was studied by an immunoperoxidase method. CD44 standard and CD44 variant 6 levels in NSCLC patients were not significantly different from those in benign lung disease patients. However, serum CD44 variant 6 level in squamous cell carcinoma patients (226.8 +/- 152.7 ng/ml) was significantly higher than in patients with benign lung disease (154.8 +/- 46.4 ng/ml) (P = 0.011). Neither the serum level of CD44 standard nor that of CD44 variant 6 was correlated with disease Stage and metastasis. CD44 variant 6 expression was most frequently observed in squamous cell carcinoma (P = 0.00058); 15 (79%) of 19 squamous cell carcinoma cases were positive, as were five (22%) of 23 adenocarcinoma cases and two (67%) of three large cell carcinoma cases. Serum CD44 variant 6 levels were 217.1 +/- 143.1 and 156.1 +/- 48.8 ng/ml in patients with and without positive expression of CD44 variant 6, respectively (P = 0.020). Serum CD44 standard and CD44 variant 6 levels are not useful indicators of tumor burden and metastasis in patients with NSCLC. CD44 variant 6 expression might be associated with histological features of NSCLC.

Adenocarcinoma↗
PubMed1997

Serum hepatocyte growth factor/scatter factor levels in small cell lung cancer patients.

Serum hepatocyte growth factor/scatter factor (HGF/SF) levels were measured in 25 patients with small cell lung cancer (SCLC), 16 patients with benign lung diseases and 15 healthy subjects with an enzyme-linked immunosorbent assay. The patients with SCLC did not have bacterial or interstitial pneumonia. Patients with benign lung diseases included eight with bacterial pneumonia, three with interstitial pneumonia, and five with benign lung tumor. Serum HGF/SF levels were significantly higher in patients with SCLC (mean +/- S.D.: 0.40 +/- 0.17 ng/ml) than in healthy subjects (0.26 +/- 0.093 ng/ml) (P = 0.0083). Patients with bacterial pneumonia had significantly higher serum HGF/SF (0.52 +/- 0.19 ng/ml) than did those with benign lung tumors (0.27 +/- 0.058 ng/ml) and healthy subjects (P = 0.013 and P = 0.0019, respectively). By clinical stage of SCLC, HGF/SF levels were 0.34 +/- 0.12 and 0.47 +/- 0.20 ng/ml in patients with limited disease and extensive disease, respectively; this difference was not significant (P = 0.080). Although serum HGF/SF levels were increased in patients with SCLC, this increase might not have been related to tumor burden.

Adult↗
PubMed1997

Measurement of serum p53 protein in patients with small cell lung cancer and results of its clinicopathological evaluation.

Serum p53 protein levels were measured in 36 patients with small cell lung cancer (SCLC) and 35 patients with benign lung diseases in order to evaluate the relationship of these levels to clinicopathological features of SCLC. Serum levels of p53 protein were measured by an enzyme-linked immunosorbent assay, p53 protein level was 23.92 +/- 6.78 pg/ml in patients with SCLC, and similar to that (17.47 +/- 2.86 pg/ml) in patients with benign lung diseases. By the clinical stage of SCLC, the mean level of p53 protein was 16.68 +/- 4.62 pg/ml in 21 patients with limited disease, and lower than that in 15 patients with extensive disease (34.05 +/- 14.84 pg/ml) (P = 0.23). The levels of p53 protein were not correlated with age, smoking index, or presence of cancer history for patients with SCLC. However, immunohistochemical examination disclosed a mild correlation between the expression of p53 protein by SCLC tumor and p53 protein serum level (r = 0.45, P = 0.02). Two patients with SCLC had an elevated serum level of p53 protein (> 2 S.D. above the mean for benign lung diseases). However, measurement of p53 protein serum level was not found to be clinically useful for detection of SCLC.

Age Factors↗
PubMed1997

Methotrexate maintains bone mass by preventing both a decrease in bone formation and an increase in bone resorption in adjuvant-induced arthritic rats.

We examined the effects of low doses methotrexate (MTX) and indomethacin (IND) on bone mass and turnover in normal male Sprague-Dawley rats and those with adjuvant-induced arthritis. Normal and the adjuvant (heat-killed mycobacterium)-injected rats, 6 weeks of age, were given MTX at daily doses of 0.05, 0.1, or 0.2 mg/kg body weight (BW) or IND at a daily dose of 1.0 mg/kg BW. Rats were killed at the start, or at 14 and 28 days. In normal rats, the administration of these agents did not change the lumbar and femoral BMD values, nor did the serum osteocalcin or urinary deoxypyridinoline (D-Pyr) levels. Lumbar trabecular osteoclast number (Oc.N/BS) and osteoclast surface (Oc.S/BS) were decreased in the rats given IND. In the arthritic rats, the administration of MTX did not prevent an early increase of paw edema in the adjuvant-injected limb, but late inflammatory edema was alleviated in the non-injected limb. However, MTX administration at a dose of 0.1-0.2 mg/kg BW maintained an age-dependent increase in the lumbar and femoral BMD values. While serum osteocalcin levels were decreased and urinary D-Pyr values were increased in the arthritic control rats, these bone markers remained at the levels of the normal rats. Decreases in mineral apposition rate (MAR) and bone formation rate (BFR/BS) and increases in the trabecular Oc.N/BS and Oc.S/BS values were prevented by MTX. While IND almost completely prevented inflammatory paw edema, it did not improve the parameters of bone formation. An increase in osteoclasts was prevented and the osteopenia in the lumbar and the femoral bone was only partially prevented by IND. These data suggest that MTX improves bone mass and turnover in the arthritic rat, in which several cytokines that affect bone cells are involved. An increase in bone resorption may be due to prostaglandins, but bone formation defect was suggested to be due to other cytokines such as IL-1, IL-6, and TNF-alpha in this model.

Animals↗
PubMed1997

Z-100, extracted from Mycobacterium tuberculosis strain Aoyama B, inhibits the development of collagen-induced arthritis in mice.

We evaluated the effects of Z-100, extracted from human type Mycobacterium tuberculosis strain Aoyama B, on collagen-induced arthritis (CIA) in mice. One hundred thirty-five DBA/1J mice, 8 weeks of age, were assigned to 9 groups and immunized with bovine type II collagen (CII) or CFA. From the next day, Z-100 at doses of 0.004, 0.04, or 0.4 mg/kg B.W./d for 48 d was intradermally injected into the tail base. Methotrexate (MTX) at daily doses of 0.1, 0.3, or 1.0 mg/kg B.W. and cyclophosphamide (CY) at a daily dose of 5 mg/kg B.W. were used as reference drugs. The effects of these drugs on CIA mice were evaluated in terms of the incidence of CIA, the arthritis index (AI), and hind paw edema, after which the animals were sacrificed at 49 d, and both anti-CII antibody titer and delayed-type hypersensitivity (DTH) reaction were measured. In the arthritic control groups, the AI and hind paw edema were significantly increased after the second immunization on day 28. The anti-CII antibody titer and DTH reaction were significantly increased compared to normal mice on day 49. Z-100 significantly inhibited the AI at a dose of 0.4 mg/kg/d on day 49, and suppressed the incidence of both CIA and hind paw edema. Increases in both anti-CII antibody titer and DTH reaction in CIA mice were prevented by treatment with Z-100 at 0.4 mg/kg/d. MTX, in a dose-dependent manner, and CY, at a dose of 5 mg/kg/d, inhibited the incidence of CIA, AI, hind paw edema, anti-CII antibody titer and DTH reaction in CIA mice. Z-100 at a dose of 0.4 mg/kg was as effective as MTX was at a dose of 0.3 mg/kg against the DTH reaction, and it had no side effects. These results suggest the usefulness of Z-100 in patients with chronic rheumatoid arthritis.

Adjuvants, Immunologic↗
PubMed1996

Effects of indomethacin administration on bone turnover and bone mass in adjuvant-induced arthritis in rats.

We examined the bone turnover and bone mass in adjuvant-induced arthritis in rats and assessed the effects of indomethacin in this model. One hundred ten SD rats, 6 weeks of age, were assigned to 11 groups and injected with adjuvant or solvent in the right foot. Adjuvant-injected rats were orally administered indomethacin at doses of 0 (vehicle), 0.1 (low), 0.5 (medium), and 1.5 (high) mg/kg body weight from the start (day 0). Animals were sacrificed on days 0, 14 (acute phase), and 28 (chronic phase). In the arthritic-control group, serum osteocalcin level and bone mineral content of the fourth lumbar body (L4) and the femur were significantly reduced on day 14. Serum alkaline-phosphatase was increased on day 28. Trabecular bone volume of L4 was decreased on day 14, and the value was further decreased on day 28. Bone formation rate (BFR/BS) was significantly reduced on day 14, and then osteoclast number (Oc.N/BS) increased on day 28. Indomethacin treatment dose-dependently prevented increases in paw volume and osteoclast number. In the high dose group, these indices were maintained at the same level with those in the normal group. However, indomethacin treatments were not able to maintain the parameters of bone formation such as serum osteocalcin and BFR/BS values, and the trabecular bone mass decrease was only partially prevented. These data clearly indicated both reduced bone formation and increased bone resorption as the causes of bone loss in adjuvant-induced arthritis in rats. Increased bone resorption seemed to be due to the increased activity of prostaglandins, but bone formation defect would be related to other factors in this animal model.

Administration, Oral↗
PubMed1996

Prognostic factors for patients with advanced non-small cell lung cancer: univariate and multivariate analyses including recursive partitioning and amalgamation.

In an attempt to determine the prognostic significance of pretreatment factors for patients with advanced non-small cell lung cancer (NSCLC), 24 pretreatment clinical variables were analyzed for 185 patients with NSCLC who underwent chemotherapy and/or radiotherapy between 1985 and 1994. Following univariate analysis, we applied two multivariate statistical techniques. In a Cox regression mode, independently significant factors influencing patient survival included performance status (PS), disease stage, hemoglobin level, and serum calcium level. Recursive partitioning and amalgamation (RPA) resulted in three distinct prognostic subgroups based on PS, stage, weight loss, and hemoglobin level. The best survival was observed for patients with a good PS and Stage III disease who had a hemoglobin level > 11 g/dl. The worst survival was observed for patients with a poor PS and presence of weight loss irrespective of stage. All other patients had an intermediate prognosis. Median survival times were 95.1 weeks, 17.1 weeks and 39.3 weeks, respectively (P < 0.00005). The results of our analyses show that three important prognostic subgroups could readily be discerned using RPA.

Adult↗
PubMed1996

Primary adenoid cystic carcinoma of the trachea effectively treated with the endoscopic Nd-YAG laser followed by radiation.

We present a case of adenoid cystic carcinoma of the trachea. The tumor could not be resected due to extensive progression but it was effectively treated endoscopically with a Nd-YAG Laser followed by 70 Gy of conventional radiotherapy. Histologically-confirmed complete remission was achieved, and the patient has lived for nearly 9 years without recurrence of disease.

Carcinoma, Adenoid Cystic↗
PubMed1996

A fibrous histiocytoma with a polypoid pattern of growth in a major bronchus.

A 47-year-old man was admitted to our hospital for abrupt onset of hemoptysis and dyspnea. Chest roentgenography revealed a left lower mass shadow with obstruction of the left main bronchus. However, on the third hospital day, he expectorated a coagulum-like substance which resembled bronchial tree, and his symptoms then dramatically subsided. Except for small amounts of bleeding from left B10a, the endobronchus was intact on bronchoscopic examination, and the pathologic diagnosis of the tumor using resected material was fibrous histiocytoma of low-grade malignancy. In addition, given the similarity in histologic findings between the expectorated substance and resected tumor, the expectorated substance was considered to be a part of the tumor which had grown along the endobronchial tree.

Bronchi↗
PubMed1996

Primary lung cancer associated with diffuse granulomatous lesions in the pulmonary parenchyma.

A 60-year-old man was admitted to our hospital for productive cough. Chest roentgenography and CT scan disclosed a left hilar tumor invading the mediastinum, with mediastinal lymphadenopathy and diffuse micronodular shadows in both lung fields. A biopsied sample of the tumor revealed squamous cell carcinoma, while noncaseating epithelioid cell granulomas were observed in the samples obtained by transbronchial lung biopsy. The granulomas in the pulmonary parenchyma were determined to be sarcoid reactions secondary to lung cancer, since there was no evidence of sarcoidosis. Combination chemotherapy was effective for the tumor, and the granulomas disappeared after completion of the chemotherapy. These findings suggest the presence of a relationship between sarcoid reactions and lung cancer in this case.

Carcinoma, Squamous Cell↗
PubMed1996

Clinical usefulness of serum cytokeratin 19 fragment as a tumor marker for lung cancer.

Serum soluble cytokeratin 19 fragment (CYFRA) levels were measured in 251 patients with lung cancer and 139 patients with benign lung diseases to determine the clinical usefulness of CYFRA level determination in the diagnosis and monitoring of lung cancer. Serum levels of CYFRA were measured by a 2-step sandwich ELISA method. When the cut-off value was defined as 3.5 ng/ml, which was associated with a specificity of 95% for benign lung diseases, CYFRA had a high sensitivity (53%) in all patients with lung cancer. Both the serum level of CYFRA and its sensitivity increased significantly with the increase in clinical stage. A comparison of areas under receiver operating characteristic curves showed that CYFRA had the most power of discrimination in the diagnosis of lung cancer among markers including carcinoembryonic antigen, squamous cell carcinoma antigen, carbohydrate antigen 19-9, and neuron-specific enolase. A good correlation was found between serial changes in serum CYFRA levels during therapy and clinical responses for 18 patients who underwent chemotherapy and/or radiotherapy. Our findings suggest that CYFRA may be a marker of choice for screening and monitoring of lung cancer, particularly squamous cell carcinoma.

Adenocarcinoma↗
PubMed1996

[Middle ear cholesteatoma caused by cannonball foreign bodies impacted in the bony eustachian tube: a case report].

We present a 76-year-old male patient with adhesive-type cholesteatoma and with metal foreign bodies which were shown to be located in the bony eustachian tube by computed tomography. He sustained a burn injury of the left tympanic membrane when he was struck by a bomb 52 years ago, during World War II. The cannonball fragments that entered the tympanic cavity were apparently transported to and stuck in the eustachian tube isthmus by mucociliary action after spontaneous closure of the tympanic membrane perforation. Persistent tubal obstruction due to the impacted foreign bodies and surrounding granulation tissue seems to have caused chronic adhesive otitis, leading to cholesteatoma which developed in the attic and mastoid antrum. No foreign bodies became visible after cholesteatoma removal by an intact canal wall technique in conjunction with anterior tympanotomy for wide exposure of the supratubal recess and the tympanic osteum of the eustachian tube. Therefore, anterior tympanotomy was further extended anteriorly to open the enlarged bony eustachian tube, allowing visualization and safe removal of two cannonball-fragments firmly impacted within it. We call this surgical approach to the bony eustachian tube "extended anterior tympanotomy". The transmastoidal accessibility of the bony eustachian tube produced by this technique should be assessed by preoperative computed tomography.

Aged↗