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Biomedical subjects

Y Iino

Publications and source records attributed to Y Iino.

At least 19 recordsLinked to original sources

Serum concentration of hepatocyte growth factor in patients with metastatic breast cancer.

The serum concentration of hepatocyte growth factor (HGF) was examined in 34 patients with metastatic breast cancer. Although no significant difference was observed between HGF concentration and the site of metastasis, serum HGF levels were slightly higher in patients with liver metastasis and in patients with multiple metastatic sites than in patients with other lesions. Significantly higher levels of serum HGF were observed in patients with progressive metastasis of breast cancer compared with those with stable metastasis. The patients with high HGF levels exhibited a significantly shorter survival rate than those with low HGF levels. Circulating HGF levels may be a useful indicator for the progression of metastatic lesions and the prognosis of patients with metastatic breast cancer.

Adult

Expression pattern of the C. elegans P21-activated protein kinase, CePAK.

The C. elegans p21-activated protein kinase (CePAK) has a high amino-acid sequence similarity to mammalian PAKs. Tissue specificity of the expression of CePAK was examined using lacZ and GFP reporters. This analysis indicated that CePAK is expressed mainly in pharyngeal muscles, the CAN neurons, and motor neurons in the ventral nerve cord, as well as several cells in the tail region and the distal tip cells. The CePAK::GFP fusion protein was preferentially localized to the cell surface in pharyngeal muscles.

Animals

A combination chemoendocrine therapy of mitoxantrone, doxifluridine, and medroxyprogesterone acetate for anthracycline-resistant advanced breast cancer.

Between January 1993 and October 1995, 34 patients with anthracycline-resistant advanced breast cancer were treated with a combination chemoendocrine therapy of mitoxantrone (MIT), doxifluridine (5'-DFUR) and medroxyprogesterone acetate (MPA). Of 34 patients, 28 were evaluable for efficacy of this combination therapy, and 30 including 2 for whom data were incomplete were assessed for adverse drug reactions. Adriamycin (ADM) was used for pretreatment in 12 patients, 4'-epi-ADM in 6, and THP-ADM in 12. In the eligible patients, 8.0 mg/m2 MIT was administered intravenously every 4 weeks, and 600 mg MPA and 600 mg 5'-DFUR were given orally every day. The median follow-up period was 25 weeks (range 2-90 weeks). The median cumulative dose of mitoxantrone was 66 mg (range 12-121 mg). Of the 28 patients, 11 (39.3%) responded to this combination therapy. As for response in relation to predominant site of lesion, 1 of 5 soft tissue lesions (20%) and 8 of 12 bone metastases (66.7%) showed a partial response, and one complete response and one partial response (25.0%) were seen in eight lung lesions. None of three pleural lesions responded to this therapy. The median duration of response was 31 +/- weeks (range 12-82 weeks). Adverse drug reactions were controllable or tolerable. Combined chemoendocrine therapy with a low dose of MIT is a well-tolerated and moderately effective regimen for the treatment of anthracycline-resistant advanced breast cancer.

Adult

High proportion of missense mutations of the BRCA1 and BRCA2 genes in Japanese breast cancer families.

Mutations in either of two recently identified genes, BRCA1 and BRCA2, are thought to be responsible for approximately two-thirds of all cases of autosomal-dominantly inherited breast cancer. To examine the nature and frequency of BRCA1 and BRCA2 mutations in Japanese families exhibiting a high incidence of breast cancer, we screened 78 unrelated families in this category for mutations of these two genes. Examining the entire coding sequences as well as exon-intron boundaries of both genes by polymerase chain reaction (PCR) single-strand conformation polymorphism (SSCP) and multiplex-SSCP analysis, we identified possible disease-causing alterations in BRCA1 among affected members of 15 families and in BRCA2 in another 14 families. In 15 of those 29 families, the affected individuals carried missense mutations, although most germline mutations reported worldwide have been deletions or nonsense mutations. Our results, indicating that missense mutations of BRCA1 and BRCA2 tend to predominate over frameshifts or nonsense mutations in Japanese breast cancer families, will contribute significantly to an understanding of mammary tumorigenesis in Japan, and will be of vital importance for future genetic testing.

BRCA2 Protein

Characterization of the C. elegans gap-2 gene encoding a novel Ras-GTPase activating protein and its possible role in larval development.

BACKGROUND: The Ras signalling pathway plays several important roles in the development of the nematode Caenorhabditis elegans. So far, two types of Ras-GTPase activating proteins (Ras-GAPs) have been identified in this organism. To aid the study of the regulation and function of the Ras pathway, we set out to isolate a new GAP gene from C. elegans by transcomplementation of the fission yeast gap1 mutant. RESULTS: We isolated a C. elegans cDNA that encoded a protein which was similar to, but not exactly homologous with mammalian p120 Ras-GAP. This gene, named gap-2, generated at least nine distinct mRNA species through transcription from different promoters and subsequent alternative splicing involving 25 exons. These isoforms were differentially expressed among tissues. A deletion of gap-2 caused no obvious phenotype by itself, but a loss of gap-2 function could suppress larval lethality in both let-23 and let-60 reduction-of-function mutants, in which the Ras activity was lowered. CONCLUSIONS: C. elegans gap-2 encodes a novel Ras-GAP, which is similar to vertebrate p120 but which may constitute a new GAP subfamily. gap-2 mRNA isoforms arise by an unusually extensive variation in initiation sites and associated alternative splicing, and each isoform may play a distinct role in specific tissues. GAP-2 appears to function as a negative regulator of LET-60 Ras during larval development.

Alternative Splicing

[Association analysis of angiotensin-converting enzyme gene polymorphism with end-stage renal disease].

BACKGROUND: Intron 16 insertion/deletion (I/D) polymorphism in the angiotensin-converting enzyme (ACE) gene may be associated with the progression of renal insufficiency in patients with renal diseases. The objective of this study was to determine whether D allele is a risk factor for the progression of the disease in end-stage renal disease (ESRD) patients. METHODS: Using PCR techniques, genetic analysis of the ACE I/D polymorphism was performed on 326 dialysis patients. We compared the distribution of genotypes and allele frequency of this polymorphism in dialysis patients and the normal Japanese population. The clinical courses of 47 patients were studied retrospectively, and the progression of chronic renal failure using time plots of the reciprocal of serum creatinine (1/Cr) was estimated. RESULTS AND CONCLUSION: The frequencies for II, ID, and DD genotypes were 134, 148 and 44, respectively. The frequency for I allele was 0.64, and for D allele 0.36. These results were similar to the frequencies found in the normal Japanese population. However, patients with polycystic kidney disease (PKD) showed a high frequency for D allele (0.54: p = 0.023 by chi 2 method). In longitudinal courses, we did not find any association between ACE gene polymorphism and the declining rate of renal function. However, in patients with PKD, the DD genotype may influence the clinical course of renal disease.

Adult

[Improvement of insulin sensitivity after renal transplantation measured by a glucose clamp technique].

There is much evidence indicating that indicates end-stage renal failure induces insulin resistance. We examined the effects of renal transplantation on insulin resistance with an insulin clamp technique. Insulin sensitivity and insulin secretion rates were measured in 13 renal transplant patients, 7 hemodialysis patients, and 6 healthy controls. Insulin sensitivity was assessed with the euglycemic insulin clamp technique. The clamp was applied for 120 minutes and the average of the glucose disposal rates measured from 90 to 120 minutes was regarded as insulin sensitivity. There was a significant increase in the glucose disposal rate in the renal transplantation patients (6.67 +/- 1.44 mg/kg/min) compared to the hemodialysis patients (4.54 +/- 1.44 mg/kg/min) (p < 0.05). Also, there was a significant decrease in the glucose disposal rates in the hemodialysis patients (4.45 +/- 1.44 mg/kg/min) compared to the healthy controls (7.25 +/- 2.07 mg/kg/min) (p < 0.05). There was no significant difference in the glucose disposal rates between the renal transplant patients and the healthy controls. However, patients treated with beta-blockers had lower glucose disposal rates compared to patients without beta-blockers (4.67 +/- 1.58 vs 6.67 +/- 1.44 mg/kg/min, p < 0.05). In this study, we found that insulin resistance, shown by the euglycemic insulin clamp technique, was recovered after successful renal transplantation that but, beta-blockers affected insulin resistance. In conclusion shows that, the hyperglycemic clamp technique, although many factors such as medication may affect insulin sensitivity, renal transplantation restores insulin resistance found in renal failure patients, but not insulin secretion.

Adult

c-erbB-2 status is an independent predictor of survival after first recurrence.

We studied retrospectively the interaction between c-erbB-2 overexpression and the prognosis in 239 invasive breast cancer patients who underwent radical operations between January 1984 and April 1991. The c-erbB-2 protein was overexpressed in 42 (17.6%) of 239 patients. There was no correlation between c-erbB-2 overexpression and age at operation, tumor size, lymph node involvement, or clinical stage. Only an inverse correlation was found between c-erbB-2 overexpression and hormone receptor levels. Patients with c-erbB-2 overexpression had a significantly worse overall survival than those without c-erbB-2 overexpression. In relation to lymph node involvement or estrogen receptor status, a significant difference in overall survival between the c-erbB-2-positive and -negative groups was found in patients with lymph node metastasis or in those with estrogen receptor-negative tumors. Out of 237 patients (two were lost to follow-up), 42 recurred and 25 died of breast cancer. The c-erbB-2-negative patients survived significantly longer after the time of first recurrence than the c-erbB-2-positive patients. In a multivariate analysis using Cox proportional-hazard regression model, c-erbB-2 status and disease-free interval were independent predictors of survival after first recurrence. In conclusion, c-erbB-2 status is an independent prognostic indicator of survival after first recurrence.

Biomarkers, Tumor

Angiogenesis and stromal fibronectin expression in invasive breast carcinoma.

Angiogenesis and stromal fibronectin (SFN) expression were immunohistochemically analyzed in 83 breast cancer specimens. Microvessel count (MVC), which correlated with lymph node metastasis, TNM stage, recurrence, and mortality, was relatively low in SFN-positive tumors. SFN expression did not correlate with lymph node metastases or tumor size. However, SFN positivity was less likely in patients with recurrent disease than in those without recurrence, and relapse-free survival was significantly better in patients with SFN-positive tumors than in those with SFN-negative tumors. MVC and SFN positivity were significant independent predictors of relapse-free survival as well as tumor size and axillary nodal status (Cox's proportional hazards regression analysis). Angiogenesis and SFN expression, both of which are inversely related, can be used prognostically in patients with breast cancer.

Antineoplastic Combined Chemotherapy Protocols

[Facial nerve anomalies of children with congenital anomalies].

It is well known that congenital anomalies are often associated with malformation of the inner, middle and external ear. In temporal bone studies, it has been found that abnormality of the facial nerve often occurs in patients with congenital aberrations. The temporal bone collections of the Teikyo University School of Medicine include 32 human temporal bones obtained from 19 infants ranging in age from one day to 7 months, who had chromosomal aberration and severe visceral anomalies. We histologically studied routinely processed sections of these temporal bones under a light microscope. Facial anomaly was observed in 20 of the 32 ears (63%). An abnormal course was observed in 18 ears (56%); 5 ears showed hypoplastic development, 4 showed displacement of geniculate ganglion cells into the internal auditory meatus, and 3 ears showed bifurcation. Abnormal course of the facial nerve was found in a significant number of ears with aural and mandibulal abnormalities (76%). However patients with multiple inner ear anomalies showed an abnormal course and hypoplasia of the facial nerve. There was no correlation between the incidence of facial abnormalities and inner ear anomalies.

Abnormalities, Multiple

[Genetic testing for ret mutation for early diagnosis and treatment in familial medullary thyroid carcinoma: a case report].

A 13-year-old girl and her older sister were referred to our hospital because her father and another older sister and been suffering from medullary thyroid carcinoma (MTC). Physical examinations revealed no thyroid mass. Ultrasonography (US) detected a small hypoechoic lesion in the right thyroid lobe, 3 mm in size. The serum calcitonin level was slightly elevated for their age. One and half year later, US finding showed a slightly larger mass, 7 mm in size, which was not palpable. Genetic testing for ret protooncogene mutation revealed a point mutation at codon 634 (Cys-->Arg) in exon 11. Surgical treatment was recommended, however, the patient wanted to receive it only after the admission to senior high school. Her sister had no mutation in ret protooncogene. The patient underwent total thyroidectomy with modified neck dissection at 16 years of age. At that time, a new mass emerged in the left thyroid lobe and the serum calcitonin level increased to 171 pg/ml. MTC was found in each lobe with positive staining of CEA and carcitonin. No lymph node metasis was found. Her postoperative course was uneventful. Genetic testing for ret mutation is effective for early diagnosis and treatment of patient with FMTC, and is recommended as standard management for hereditary MTC in affected families.

Adolescent

The Schizosaccharomyces pombe cdc6 gene encodes the catalytic subunit of DNA polymerase delta.

The cdc6 mutants of Schizosaccharomyces pombe have been classified as being defective in progression through the G2 phase of the cell cycle. We cloned an S. pombe gene that could complement the temperature-sensitive growth of the cdc6-23 mutant. Unexpectedly, the cloned gene was allelic to pol3, which encodes the catalytic subunit of DNA polymerase delta. Integration mapping confirmed that ccd6 and pol3 are identical. The cdc6-23 mutant carries one amino acid substitution in the conserved N3 region of Pol3.

Amino Acid Sequence

Spindle cell carcinoma of the breast.

Spindle cell carcinoma is a rare breast tumor. We present herein three cases of spindle cell carcinoma of the breast and review its characteristics from the literature. Spindle cell carcinoma frequently forms a large and well-circumscribed tumor with gross cyst formation. Histologically, its dominant component is of sheets of spindle shaped cells, and it includes such contiguous carcinoma components as squamous differentiation or invasive ductal carcinoma. Estrogen receptor expression and lymph node metastasis tend to be low. Despite the sarcomatous features, spindle cells are likely to be derived from epithelial cells of mammary glands. Immunohistochemical and ultrastructural examination demonstrated the expression of keratin and the desmosome-like junctional structure in the spindle cell components. Relatively favorable prognosis is expected in spindle cell carcinoma of the breast compared to common breast carcinoma.

Aged