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Biomedical subjects

E Shiba

Publications and source records attributed to E Shiba.

At least 37 records · Page 2Linked to original sources
PubMed1998

Prognostic Factors for Node-negative Breast Cancers: Results of a Study Program by the Japanese Breast Cancer Society.

BACKGROUND: Prognostic factors for predicting the recurrence of node-negativebreast cancers have been controversial. The present study was performed to elucidate practically useful prognostic factors using formalin-fixed paraffin sections. METHODS: This was a case-controlled multi-institutional study that composed 40 patients with recurrent node-negative breast cancer and 80 patients with node-negative breast cancer but without recurrence after radical surgery. Tumors weresmaller than 3 cm in diameter and were treated surgically between January 1, 1985 and December 31, 1990. The recurrent and non-recurrent cases were matched with regard to their age, adjuvant chemotherapy and the year in which surgery was performed. Fourteen immunohistochemical factors and 8 histological factors of theprimary tumor were studied on formalin-fixed, paraffin-embedded sections by immunohistochemical and histochemical analyses. RESULTS: According to univariate analysis, factors such as progesterone receptor (PgR), MIB-1, CD44v6, CD44v9 and platelet-derived endothelial cell growth factor (PDECGF) were significantly different between the recurrent and non-recurrent groups (p &ly; 0.1; Wilcoxon-Mann-Whitney analysis). Chi-squared test showed significant differences in MIB-1, cdc2 and stromal plasminogen activator receptor (suPAR). Histologically, mitotic count was also significantly different between the two groups (p < 0.005). Multivariate analysis revealed that positivity for cdc2 (p=0.01), high mitotic count (p=0.04) and negativity for CD44v9 (p=0.02)were independent prognostic factors among variables selected by univariate analysis, and that positivity for MIB-1 (p=0.03) and cdc2 (p =0.01), and negativity for CD44v9 (p =0.03) were independent prognostic factors among the immunohistochemical markers examined. CONCLUSION: Our results indicated that positivity for MIB-1 and cdc2, high mitotic count and negativity for CD44v9 could serve as independent factors for predicting the recurrence of node-negative breast cancer.

Journal Article↗
PubMed1998

Antitumor effect of medium-chain triglyceride and its influence on the self-defense system of the body.

Medium-chain triglyceride (MCT), long-chain triglyceride (LCT), and their mixture were compared in reference to both cytotoxic effect against human tumor cells and influence on the immune system. MCT showed more potent cytotoxicity than LCT. Continuous contact with MCT also inhibited the cytotoxic effect of lymphokine-activated killer (LAK) cells much more strongly than LCT. However, there is a discrepancy between the concentration of MCT, or the mixture, that could suppress the growth of tumor cells and the concentration that inhibited the cytotoxicity of LAK cells. Moreover, no damage was observed in PBL or LAK cells or in their cytotoxicity when the cells were incubated with TG for 2 h a day. Thus, short-term contact with TG could inhibit tumor growth while immune system was maintained within normal range. Clinically fine control of the concentration of injected triglycerides, especially MCT, can be expected to provide potent antitumor effect and maintenance of normal immune system.

Antineoplastic Agents↗
PubMed1998

Familial isolated hyperparathyroidism caused by single adenoma: a distinct entity different from multiple endocrine neoplasia.

Familial hyperparathyroidism (FHPT) is a hereditary disease where hyperparathyroidism (HPT) is transmitted in an autosomal dominant fashion. FHPT consists of a variety of diseases such as multiple endocrine neoplasia type1 (MEN 1) and type2 (MEN 2), familial isolated hyperparathyroidism (FIHPT) with single adenoma and with multiple adenomas (or hyperplasia), and FHPT with jaw-tumor (FHPT-JT). Isolation of the genes responsible for MEN1, and 2, i.e. MEN1 and RET, respectively, makes it possible to examine the relations among disorders constituting FHPT. We studied germ-line mutations in these 2 genes in a family of FHPT with single parathyroid adenoma. The disorder in this family was proved to be an entity different from MEN1 because no germ-line mutations in MEN1 gene were found in the affected members. The loss of heterozygosity (LOH) at MEN1 gene and PYGM were not found in the abnormal parathyroid in this family, supporting the above conclusion. No mutations in exons 10, and 11 of RET proto-oncogene was found in germ-line DNA of the affected member of the family, suggesting no relation to MEN2A. Linkage study excluded the possibility of FHPT-JT syndrome. PRAD1 was not overexpressed in the parathyroid tumors in this family. The relation of this disorder to FIHPT with multiple enlarged parathyroid glands remains to be clarified. A search for the gene(s) predisposing to FIHPT is needed.

Adenoma↗
PubMed1998

Prognostic impact of urokinase-type plasminogen activator (PA), PA inhibitor type-1, and tissue-type PA antigen levels in node-negative breast cancer: a prospective study on multicenter basis.

Urokinase-type plasminogen activator (u-PA) is a key protease in cancer invasion and metastasis. Recent studies demonstrated that u-PA, plasminogen activator inhibitor type-1 (PAI-1), and tissue-type plasminogen activator (t-PA) are prognostic factors in breast cancer. However, there have been no prospective studies of node-negative breast cancer on a multicenter basis. On the other hand, some patients, even those with node-negative breast cancer, developed recurrence, and only tumor size is available as a predicting factor in this group. Therefore, it is necessary to find other prognostic factors in node-negative breast cancer to determine suitable adjuvant therapies. Tissue samples in this prospective study were obtained from 130 patients with node-negative invasive breast cancer who underwent radical operation at four hospitals. The median follow-up was 52.6 months. u-PA, PAI-1, and t-PA antigen levels were assayed by ELISA kits using the cytosolic fractions of tumors. Patients with high u-PA, high PAI-1, or low t-PA had significantly higher relapse rates than did those with low u-PA, low PAI-1, or high t-PA, respectively, by the Kaplan-Meier method (P = 0.006, 0.032, and 0.028, respectively). Analyses of the combinations of both u-PA and PAI-1 or both u-PA and t-PA showed that the differences in relapse rate between the high- and low-risk groups were statistically very significant. In the univariate analysis, u-PA, PAI-1, t-PA, progesterone receptor, and tumor size (T3 versus T1) were significantly correlated with relapse. However, the multivariate analysis revealed that only u-PA (P = 0.023) was an independent prognostic factor. This study showed that u-PA was a new significant independent prognostic factor in node-negative breast cancer.

Adult↗
PubMed1998

[Characteristics of screening-detected breast cancer and trends in its therapy].

Recently breast cancer has become one of the most common malignancies and one of the major causes of cancer death in Japan. In order to detect earlier stage breast cancer and to stop the increasing mortality, there is a greater need for mass screening. Mass screening performed by physical examination has a history of about thirty years in Japan, but it has had no effect in reducing breast cancer mortality. A new modality, mammography, is effective to detect non-palpable lesions, so it is expected to improve the accuracy of screening and reduce the mortality of breast cancer. Randomized trials in western countries have demonstrated that screening with mammography is effective for breast cancers in women aged 50 -69. In Japan, limited studies reported that effectiveness of screening was improved when mammography was combined with physical examination for detecting early breast cancer, but it is still unknown whether screening reduces breast cancer mortality. Since indications of breast conservation therapy have been rapidly extended it follows that breast conservation surgery for screening-detected cancer has increased. In Japan, because of its medical system, it seems impossible to conduct randomized trials for evaluating the efficacy of screening. Thus, it is important to interpret the screening data in western countries and to compare data with those from screening trials of Japan in the future.

Adult↗
PubMed1998

[Results of clinical study with epirubicin hydrochloride injectable solution and cyclophosphamide in breast cancer].

A 10-center cooperative clinical study with a new formulation of epirubicin hydrochloride injectable solution (Epirubicin-RTU) was conducted in patients with breast cancer. One course of treatment consisted of one intravenous administration of Epirubicin-RTU at the dose of 60 mg/m2 followed by a 3-week drug-free interval and concomitant daily administration of oral cyclophosphamide at 100 mg/day during the period between Days 1 through 14. At least, two courses of treatment were given. Among 20 registered cases, all 20 cases were eligible and 16 cases completed the whole course of the study. In 16 completers, PR was observed in 5 cases, indicating the efficacy rate of 31.3% (5/16).. No local irritation was observed at the injection sites. Adverse reactions frequently observed were leukopenia, neutropenia, anorexia, alopecia, and nausea/vomiting, which were all reversible and tolerable. From the above results, Adverse reactions both locally and systemically were tolerable. Intravenous administration of Epirubicin-RTU was considered to be useful for the treatment of breast cancer.

Administration, Oral↗
PubMed1997

Immunohistochemical Detection of P-glycoprotein in Breast Cancer and Its Significance as a Prognostic Factor.

Overexpression of P-glycoprotein (Pgp) in tumors is one of the major mechanisms which mediates the multidrug resistance (MDR) phenotype. To evaluate the prognostic significance of Pgp in breast cancer, Pgp expression was examined in paraffin-embedded tissue sections of 94 breast cancer specimens by immunohistochemistry. Tissue specimens were obtained by mastectomy without preoperative chemotherapy. UIC2 monoclonal antibody which recognizes an extracellular epitope of human Pgp was employed. Of the 94 breast cancer specimens, 35(37.2%)were positive for Pgp expression. Pgp expression had no correlation with menopausal or hormone receptor status, axillary Iymph node involvement or tumor size. However, a significant correlation was observed between Pgp expression and disease relapse (p=0.0322). Pgp-positive patients showed a significantly shorter disease-free survival period than Pgp-negative patients by the Kaplan-Meier method (p=0.0433). These results suggest that immunohistochemical detection of Pgp in breast cancer tissue may have prognostic value after radical operation.

Journal Article↗
PubMed1997

A prospective study on the prognostic significance of urokinase-type plasminogen activator levels in breast cancer tissue.

Urokinase-type plasminogen activator (u-PA), which cleaves plasminogen to yield plasmin, is a serine protease of fibrinolysis and is presumed to play a key role in extracellular proteolysis and facilitate the migration of cancer cells. This study was conducted prospectively to evaluate the prognostic significance of u-PA antigen level in breast cancer tissues. u-PA concentrations in the cytosol of 226 breast cancer tissues were determined prospectively by enzyme-linked immunosorbent assay using cytosol fractions prepared for steroid hormone assay. The median follow-up period of the patients was 60 months. Various prognostic factors were evaluated by univariate analysis or multivariate analysis using the Cox proportional-hazards method. Patients with primary breast cancer containing high levels of u-PA had a significantly shorter disease-free survival than patients with low levels of u-PA antigens. In multivariate analysis, a high level of u-PA was an independent risk factor for disease-free survival, being independent of age, axillary node status, and estrogen receptor status. Among the major prognostic factors, a high u-PA antigen level, lymph node involvement, and a positive estrogen receptor status were the most important for predicting relapse-free survival (P = 0.044, P < 0.0001, P = 0.0039). This first prospective study confirmed the prognostic significance of the u-PA antigen level in association with other major prognostic factors. The results of our present study suggest that u-PA in breast cancer tissue might be involved in breast cancer invasion and metastasis.

Age Factors↗
PubMed1996

Ca&sup2+;-Dependent Neutral Protease (Calpain) Activity in Breast Cancer Tissue and Estrogen Receptor Status.

Cancer invasion and metastasis require action of tumor-associated proteases, which degrade the extracellular matrix. It has been reported that calpain, a calcium-activated neutral protease and a thiol protease regulated by Ca&sup2+;, proteolyzes estrogen recepor (ER) and that calpain may play an important role in the regulation of ER function. In the present study, the activities of calpain were measured in human normal breast tissues and breast cancer tissues stratified by estrogen receptor levels. There were no correlations between calpain activity and tumor size or lymph node involvement. Activities of calpain were significantly higher in breast cancer tissues compared with those of normal breast tissues, and were higher in the ER-positive tumors than in ER-negative ones. These results indicate that calpain is related to mammary malignant transformation and is involved in the regulation of the ER function in breast cancer tissues.

Journal Article↗
PubMed1996

Pseudointimal hyperplasia of ridged outer wall polytetrafluoroethylene vascular prostheses.

In addition to the polytetrafluoroethylene (PTFE) vascular graft (G) with its conventionally smooth surface, a unique PTFE graft with a ridged outer wall (T) is now also currently available for clinical use. Although an excellent antikinking property is provided by this unique outer structure, the possible influence of the structure on the formation of pseudointima has not yet been investigated in detail. Four kinds of T grafts (3 mm inner diameter, 3 cm long) with various fibril lengths (FL, T-15, T-30, T-60, T-90) and a G graft with 30 microns FL (G-30) were implanted into the inferior vena cava of rabbits. The patency of the grafts at 4 weeks were as follows: 6/8(T-15), 6/8(T-30), 5/8(T-60), 0/8(T-90) and 4/6 (G-30). Pseudointimal hyperplasia (PH) of the T grafts advanced as the FL increased, judging by the thickness of the pseudointima, cellular density, and maturity of fibroblasts. In addition, the maturity of endothelial-like cells on the luminal surface increased as the FL increased. The degree of pseudointimal hyperplasia in G-30 was comparable to that of T-15, although the maturity of the endothelial-like cells was similar to that of T-60. Microscopically, there was a micro-heterogeneity of cellular density in T grafts probably due to the uneven outer structure. In conclusion, not only FL but also the outer structure of PTFE may thus influence the formation of the pseudointima.

Animals↗
PubMed1996

Phyllodes tumor in epileptics: a report of two cases.

Phyllodes tumor is an uncommon breast neoplasm characterized by a proliferation of both stromal and epithelial elements. In 1989, two young patients with phyllodes tumors were referred to our surgical department because of the detection of breast lumps. Interestingly, both patients also had epilepsy and had been taking anticonvulsants. An analytical case control study revealed that no significant difference between the control group and phyllodes group was found for various categories. In addition, no anticonvulsant medication had been prescribed in either the control group or the phyllodes group except for these two cases. We herein report two cases of phyllodes tumors occurring in two young epileptic patients.

Adolescent↗
PubMed1996

The long-term effect of eicosapentaenoic acid on serum levels of lipoprotein (a) and lipids in patients with vascular disease.

The effects of eicosapentaenoic acid (EPA) on serum lipoprotein (a) (Lp(a)) and other lipid levels in patients with vascular disease were examined. The serum levels of Lp(a), total cholesterol (TC), triglyceride (TG), low-density lipoprotein (LDL) and very-low-density lipoprotein (VLDL) were measured in 24 patients with vascular disease. An elevated serum Lp(a) level (39 +/- 22 mg/dl) was noted in 9 patients, elevated total cholesterol level (263 +/- 31 mg/dl) in 12 patients, elevated triglyceride level (240 +/- 98 mg/dl) in 10 patients and elevated LDL level (651 +/- 88 mg/dl) in 6 patients before administration of EPA. EPA (1,800 mg/day) was given to these patients for long periods ranging from 6 to 24 months. The serum levels of Lp(a), TC, TG and LDL were lowered significantly (p < 0.05) after EPA administration for 12 and 18 months, for 6, 12, 18 and 24 months, for 18 months and for 12 and 18 months, respectively. These findings indicated that long-term administration of EPA may lower Lp(a) and serum lipids, which is beneficial for patients with various arterial diseases in terms of preventing progression of the disease.

Administration, Oral↗
PubMed1996

[Somatostatin analogue treatment for malignant hypercalcemia associated with advanced breast cancer].

We describe the successful treatment with octreotide, a somatostatin analogue, of a patient with malignant hypercalcemia associated with advanced breast cancer. A 70-year-old female with advanced breast cancer was admitted to our department for treatment of hypercalcemia. The administration of pamidronate disodium was effective to decrease serum calcium from 6.2 mEq/l to 4.0 mEq/l for the first time, but her hypercalcemia later responded less to pamidronate, and her serum calcium remained raised in spite of the administration of pamidronate and elcatonin. Then, her condition deteriorated with hypercalcemic symptoms, such as nausea vomiting and drowsiness. After octreotide treatment (100 microg/body/day, s.c.) with a combination of prednisolone, her serum calcium level improved from 6.7 mEq/l to 5.0-5.5 mEq/l, Leading to a dramatic improvement in her symptoms. During these treatments, anti-cancer therapy, hydration and the administration of diuretics have been continued. We think octreotide is very useful for the treatment of malignant hypercalcemia associated with advanced breast cancer.

Aged↗
PubMed1995

Clinical evaluation on combined administration of oral prostacyclin analogue beraprost and phosphodiesterase inhibitor cilostazol.

Among various oral antiplatelets, a combination of a novel prostacyclin analogue beraprost (BPT) and a potent phosphodiesterase inhibitor cilostazol (CLZ) may result in untoward clinical effects due to possible synergistic elevation of intracellular cAMP (cyclic adenosine 3',5'-monophosphate). Thereby, a clinical study of the combined administration of the two agents was attempted. Twelve healthy volunteers were assigned to take BPT/CLZ in the following schedule; BPT: 40 micrograms at day 1 and 120 micrograms t.i.d. from day 7 to 14, CLZ: 200 mg t.i.d. from day 3 to 14. At various time intervals, physical examination and blood collection for ex vivo platelet aggregation and determination of intraplatelet cAMP were performed. Throughout the observation period, no significant alteration in vital signs was observed. Seven out of 12 subjects experienced headache of a short duration accompanying facial flush in one and nausea in one, especially after ingestion of CLZ. All of these symptoms, probably caused by the vasodilating effect of the two agents, were of mild degree and no special treatment was required. Intraplatelet cAMP content was gradually but significantly increased to 9.84 +/- 4.59 pmol per 10(9) platelets at day 14 in comparison with the initial value (6.87 +/- 2.25 pmol). The platelet aggregability was significantly suppressed at various time intervals but no additive or synergistic inhibitory effect by the combined administration was noted. In conclusion, the combined administration of BPT/CLZ is safe at doses used in the study, though the beneficial clinical effect of the combined administration has yet to be elucidated.

Adult↗
PubMed1995

Involvement of dysplasminogenemia in occurrence of deep vein thrombosis.

Although various hematological disorders have been considered to be etiologic factors in deep vein thrombosis (DVT), the involvement of dysplasminogenemia (DPG) in DVT has not been studied in detail. In 72 consecutive DVT patients, the presence of DVT was suspected based on a history of lower limb swelling and tenderness with acute onset, and was confirmed by duplex scanning, radioisotope venography, or contrast venography. DPG was identified by the observation of dissociation between the activity and antigenicity of plasminogen. Of the 72 patients, 9 (12.5%) were diagnosed as having DPG, and several antithrombin-III deficiency and protein C and S deficiency were identified. The mean age of the genetically normal and DPG patients was 52 +/- 15 and 40 +/- 15 years, respectively (p < 0.05). Thus, these findings suggest that DPG is deeply related to the development of DVT, and that abnormality of the fibrinolytic system is one of the major etiologic factors in DVT.

Adult↗
PubMed1995

Effect of recombinant human erythropoietin on anaemia after gastrectomy: a pilot study.

OBJECTIVE: To evaluate the role of recombinant human erythropoietin in reducing the need for homologous blood transfusion during operations by studying its effect on the recovery of postoperative anaemia. DESIGN: Randomised controlled trial. SETTING: University hospital, Japan. SUBJECTS: 10 patients with gastric cancer undergoing distal gastrectomy. INTERVENTIONS: 5 Patients were given erythropoietin 200 IU/kg/day together with ferric pyrophosphate 40 mg/day intravenously for seven days before operation and 14 days afterwards, and 5 were given ferric pyrophosphate 40 mg/day alone (control group). MAIN OUTCOME MEASURES: Packed cell volume, haemoglobin concentration, and white and red cell counts. RESULTS: There was no significant change in packed cell volume after the operation in the erythropoietin group, but in the control group it dropped from a mean (SD) of 0.378 (0.074) before operation to 0.329 (0.068) on day 1 (p < 0.05). Haemoglobin concentrations were significantly higher in the erythropoietin group than the control group on day 7 (mean (SD) 137 (14) compared with 110 (19) p < 0.05), and on day 10 (140 (9) compared with 108 (15) p < 0.01) after operation. CONCLUSION: Erythropoietin prevented postoperative anaemia after gastrectomy as judged by packed cell volume, haemoglobin concentration, and red cell count. Erythropoietin given before and after operation therefore has the potential to reduce the need for homologous blood transfusion during and after major operations.

Adult↗
PubMed1994

Suppression by antithrombotic agents of pseudointimal hyperplasia of polytetrafluoroethylene graft implanted into venous system.

The lumen of the polytetrafluoroethylene graft (PTFE) implanted into a rabbit inferior vena cava (IVC) was markedly narrowed by 4 weeks after grafting. This was due to initial thrombosis on the luminal surface of the graft, which was followed by pseudointimal hyperplasia (PIH). To elucidate the role of the initial thrombosis in subsequent PIH, the effect of ticlopidine (T) and/or warfarin (W) on PIH was studied in an animal model. A PTFE tube graft was implanted into a rabbit IVC. Twenty eight rabbits were randomly assigned to the following experimental groups. Eight rabbits without antithrombotic agents were observed for 2 weeks (A, n = 4) and 4 weeks (B, n = 4) after grafting. T (100 mg/kg/day) and W (0.33 mg/kg/day) were orally administered for 4 weeks to group C (n = 4) and group D (n = 4), respectively. A combination of a half dose of T and W ((T + W)/2) was given for 2 weeks (E, n = 4) and 4 weeks (F, n = 4) after grafting. Four rabbits in group G received the combination of T and W for the first 2 weeks and were observed for an additional 2 weeks without medication. All the grafts were patent at time of harvest. The dry weight of the intraluminal deposit (DW) was determined as an indicator of PIH (A:35 +/- 1 mg/graft, B:40 +/- 8, C:22 +/- 3, D:22 +/- 3, E:14 +/- 2, F:15 +/- 3, G:23 +/- 2). Administration of T or W was equally effective in reducing DW and (T+W)/2 was more effective than a single agent.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗