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Biomedical subjects

F Kasumi

Publications and source records attributed to F Kasumi.

At least 73 records · Page 4Linked to original sources
PubMed1996

Two distinct commonly deleted regions on chromosome 13q suggest involvement of BRCA2 and retinoblastoma genes in sporadic breast carcinomas.

BACKGROUND: Frequent allelic losses on the long arm of chromosome 13 in sporadic breast carcinomas suggest that a tumor suppressor gene(s) on 13q is involved in this type of carcinoma. The presence of a familial breast carcinoma susceptibility gene, BRCA2, and the retinoblastoma susceptibility gene (RB) on the same chromosomal arm implies that one or the other, or both, of these genes may be critically affected by those allelic losses. METHODS: To investigate the possible involvement of BRCA2 and RB in sporadic breast carcinomas, the authors examined allelic losses in 246 breast carcinomas with 14 polymorphic microsatellite markers on 13q12.q14. RESULTS: Allelic loss was observed in 95 of the 246 sporadic breast carcinomas (39%). Detailed deletion mapping identified two commonly deleted regions. The more proximal of these two segments was located in a 6-cM interval flanked by marker loci D13S289 and D13S267 and containing the BRCA2 gene; the more distal region was located in a 9-cM interval flanked by marker loci D13S328 and D13S172 and containing the RB gene. Allelic loss on 13q was found more frequently in tumors of the solid tubular histologic type (36 of 66; 55%) than in other types (52 of 146; 36%) (P = 0.0096). Furthermore, a significant association was observed between allelic loss on 13q and the absence of progesterone receptor (P = 0.0001). CONCLUSIONS: The results indicate that BRCA2 and RB are independent targets of allelic loss and that inactivation of either of these genes may play a role in the development of some sporadic breast carcinomas, particularly those of the solid tubular type.

Chromosome Mapping↗
PubMed1996

Mutations in the BRCA1 gene in Japanese breast cancer patients.

Predisposing germline mutations in the BRCA1 gene were identified recently in families with 17 q-linked breast and ovarian cancers. Using single-strand conformation polymorphism (SSCP) analysis, we examined primary breast cancers for mutations in coding exons of BRCA1 in a panel of 103 patients, of whom all either represented early-onset cases (< 35 of age), were members of multiply-affected families, and/or had developed bilateral breast cancers. Mutations were detected in tumors from four patients, all of whom had developed breast cancers bilaterally: a frame-shift due to a 2-bp deletion at codon 797; a nonsense mutation at codon 1214; and two missense mutations, one at codon 271 leading to Val-->Met substitution, and the other at codon 1150 leading to Pro-->Ser substitution. In each case the same mutation was present in constitutional DNA. The mean age of onset was 49 years among the Japanese carriers of BRCA1 mutations identified in this study, in contrast to the mean age of 35 observed among carriers of BRCA1 mutations in a similar U.S. study (Futreal et al., 1994). The evidence reported here supports a rather limited role of BRCA1 in breast carcinogenesis.

Adult↗
PubMed1996

Mutation analysis in the BRCA2 gene in primary breast cancers.

Breast cancer, one of the most common and deleterious of all diseases affecting women, occurs in hereditary and sporadic forms. Hereditary breast cancers are genetically heterogeneous; susceptibility is variously attributable to germline mutations in the BRCA1 (ref. 1), BRCA2 (ref. 2), TP53 (ref. 3) or ataxia telangiectasia (ATM) genes, each of which is considered to be a tumour suppressor. Recently a number of germline mutations in the BRCA2 gene have been identified in families prone to breast cancer. We screened 100 primary breast cancers from Japanese patients for BRCA2 mutations, using PCR-SSCP. We found two germline mutations and one somatic mutation in our patient group. One of the germline mutations was an insertion of an Alu element into exon 22, which resulted in alternative splicing that skipped exon 22. The presence of a 64-bp polyadenylate tract and evidence for an 8-bp target-site duplication of the inserted DNA implied that the retrotransposal insertion of a transcriptionally active Alu element caused this event. Our results indicate that somatic BRCA2 mutations, like somatic mutations in the BRCA1 gene, are very rare in primary breast cancers.

BRCA2 Protein↗
PubMed1996

[Assessment of response to chemotherapy by tumor marker in solid neoplasms].

The points at issue in the assessment of response to chemotherapy by tumor marker are discussed, and our guideline is proposed. In cancer clinics, many paradoxical movements of tumor marker are usually recognized in the situations such as heterogeneity changes of neoplasms, acute tumor cytolysis, non-peculiar rise of tumor marker, low level rise of markers near the basal level, which show paradoxical movements apart from clinical response to treatment. Then the guidelines must be settled based under the consideration of these phenomena and tumor marker kinetics. Partial response > = 65% decrease over 4 weeks; No change within < 65% decrease or < 40% increase over 8 weeks; Progressive disease > = 40% increase over 8 weeks. CR must not be defined.

Biomarkers, Tumor↗
PubMed1996

[Recent progress in the diagnosis of nonpalpable breast lesions].

Recent advances in the diagnosis of nonpalpable breast lesions are reviewed. Recently, the technique of stereotaxic fine-needle breast biopsy for nonpalpable, mammographically detected breast lesions is available, and the technique has been proposed as an alternative to surgical biopsy. New equipment of stereo-guided breast biopsy system (LORAD co, system), which is produced for the use of stereotaxic core biopsy, is introduced. We examined 103 nonpalpable, mammographic lesions by this system and 14 carcinomas, including 11 noninfiltrating ones, were discovered. This system has been evident as a cost-effective and reliable method of evaluating mammographic lesions.

Biopsy, Needle↗
PubMed1996

[Genetic alterations and DNA-based diagnosis in breast cancer].

Human carcinomas are generally considered to develop through the accumulation of various genetic abnormalities. The major types of genetic alterations that are frequently observed in breast cancer are amplification of protooncogenes (MYC, ERBB2); mutation of TP53; and loss of heterozygosity on chromosomes 1, 3p, 8p, 11p, 13q, 17q, 17, and 22q. The latter may correspond to losses or inactivations of tumor suppressor genes. Recently, two major distinct breast susptibility genes were isolated, namely BRCA1 and BRCA2. We performed PCR-SSCP analysis to determine the role of the BRCA1 gene in Japanese breast cancer and investigated how multiple genetic alterations contribute to tumor development and/or progression in primary breast cancer, using a large number of tumor materials.

BRCA1 Protein↗
PubMed1996

[The early breast cancer].

In general usage, the term early breast cancer conjures up the image of a small-sized cancer with good prognosis. In medical circles, it is expected to refer to T1, n0 cases (n0 according to pathological evaluation). However, early breast cancer should be defined by clinical conditions. Thus, although in the strict sense, early breast cancer is limited to T1, n0 cases, in practice, T1N0 and T1N1a cases also suit this diagnosis, since it was found that in over 80% of such cases could be expected a favorable prognosis. For early breast cancers, multi-modality diagnosis, not only of the breast cancer itself, but also of its spread inside the breast will be necessary if breast conservation is to be expected.

Breast Neoplasms↗
PubMed1995

Experience of quadrantectomy with axillary dissection without radiotherapy sustained by serial pathological examination for stage I breast cancer.

Breast conserving treatment usually consists of lumpectomy and axillary dissection followed by a limited dose of irradiation so that no significant side-effects occur. However, the precision of lumpectomy depends on the surgical maneuver and pathological evaluation performed at each institution. For this reason, post-operative irradiation to the preserved breast and for the occult carcinoma in the same breast is absolutely mandatory, and effectively becomes a routine step. In 1986, we started to adopt the new breast-conservation method of quadranectomy with axillary dissection for restricted stage I breast cancer without using radiotherapy, at the Cancer Institute Hospital, Tokyo, Japan. As an alternative to irradiation to ensure safety, we chose to administer an elaborate pathological examination on serial sections. The pathological proof has saved troublesome post-operative irradiation, and the results have shown this method to be safe and clear-cut compared to the traditional breast-conserving treatment cited in the literature. From July 1986 to December 1994, we performed 321 cases of quadranectomy and axillary dissection (Q+Ax). If the detailed pathological examination of 5-mm serial sections revealed the stump to be negative, we did not treat the preserved breast with radiotherapy. Out of 321 cases, 247 were analyzed as being stump-negative and of these 235 did not receive radiotherapy at all. During a 5 year 4 month observation period, we have not yet encountered any local recurrence. However, we have experienced 4 cases (1.70%) in which a second cancer developed in the conserved breast. The annual incidence rate was 0.32%. These results are the best so far compared to other published world reports.

Aged↗
PubMed1995

Incidence of latent breast cancer in Japanese women.

Detection of small or early neoplastic lesions is essential for the secondary prevention of cancer, and for this purpose information concerning their incidence and characteristics is required. Although data for latent or early cancers are available for various organs, details are limited in the case of the breast. The present investigation was carried out to cast light on the incidence of latent cancers, considered as lesions, in women with no symptoms and no palpable mass of the breast. Out of 2126 women visiting our hospital for initial breast examination during July to December in 1987, 542 (25.5%) had no complaint and neither a detectable mass on careful palpation nor a tumor shadow on mammography. However, 21 (3.9%) demonstrated microcalcification, 7 giving the impression of a possible malignancy. Subsequent biopsy of the 7 cases revealed 3 carcinomas. The detection rate of breast cancer in this population was thus 0.6% (3/542). Adopting the frequency (36%) of microcalcification detectable on mammography in 185 breast cancers diagnosed in this period as a base, the incidence of latent breast cancer among women visiting our hospital was calculated to be 1.5%.

Adult↗
PubMed1995

Association of genetic alterations on chromosome 17 and loss of hormone receptors in breast cancer.

To investigate possible relationships between genetic alterations and hormonal deregulation during breast cancer development and/or progression, we examined 616 primary breast cancers for loss of heterozygosity (LOH) at chromosomal regions 16q24, 17p13.3 and 17q21, and for amplifications of the ERBB2 and c-MYC loci. A comparison of oestrogen receptor (ER) and progesterone receptor (PgR) status in tumour cells with data concerning these genetic alterations revealed that LOH at 17q21 was significantly correlated with absence of oestrogen receptors (ER) (P < 0.0003) or progesterone receptors (PgR) (P < 0.0001), and with the absence of both (P < 0.0001). Similarly, a significant association was observed between amplification of ERBB2 and the absence of either ER or PgR. LOH at 17p13.3 was associated with the absence of PgR (P < 0.01). These data suggest a possible relationship between specific genetic changes on chromosome 17 and hormonal deregulation in the progression of breast cancer.

Breast Neoplasms↗
PubMed1995

[Pharmacological and biochemical investigation of intracavital fluorinated pyrimidine chemotherapy].

We investigated the biochemical and molecular pharmacological parameters of fluorinated pyrimidines using malignant cells in pleural effusion or ascites from patients with malignant disease both before and after fluorinated pyrimidine chemotherapy, either systemically or intravesically. In four out of fifteen cancer patients, we could analyze the alteration of thymidylate synthase (TS) catalytic activity both before and after the treatment, showing that there was a decrease ranging 28% through 96.9%. We also analyzed a level of TS messenger RNA and TS protein using molecular biotechniques. None of these mutual correlations has so far been demonstrated, indicating that the data were analyzed through samples from patients not responding to the fluorinated pyrimidines. In a responding patient with advanced breast cancer, pre-treatment total TS protein was 130 fmol/mg and the TS activity was 3.27 pmol/mg/min. After intrapleural instillation of a combination of 5-FU 250 mg and leucovorin 3 mg, the total amount and the catalytic activity of TS could be measured. On the 11th day of treatment, the TS protein level decreased to 26 fmol/mg and the TS catalytic activity also decreased to 0.1 pmol/mg/min resulting in a TS inhibition rate of 92.3 percent. On the 17th day, the patient's malignant pleural effusion disappeared almost completely, suggesting that substantial TS inhibition may reflect the clinical evidence. This particular data showed that it would be predictable for clinical outcome to evaluate these parameters before and after fluorinated pyrimidine chemotherapy. Further study is warranted to evaluate the exact role of analyzing these parameters in clinical practice.

Aged↗
PubMed1995

[Therapeutic efficacy of hepatectomy in the treatment of hepatic metastases from breast cancer].

This study was performed to evaluate whether or not surgical excision of hepatic metastases from breast cancer has any effect on the prognosis. Between September 1985 and April 1993, eight patients with hepatic metastases (solitary in four cases, multiple in four cases) underwent hepatectomy. Two patients among them had other remote recurrence besides that arising in the liver. Right hepatectomy in two cases, left hepatectomy in one, extended left hepatectomy in one and partial hepatectomy in four were done. No postoperative complications developed. Four patients incurred liver recurrence within an average period of 11.5 months after hepatectomy, with three of average period of 11.5 months after hepatectomy, with three of them dying from the disease within 16 to 36 months after hepatectomy. The other four were free of liver recurrence and remained alive for 3 to 65 months post-operatively. The 50% survival time was 36 months after hepatectomy and 40 months after the discovery of hepatic metastases. Although hepatectomy could only be applied to a restricted number of patients and these results are obviously insufficient, we believe that surgical procedure for liver metastases from breast cancer, if possible, is undoubtedly beneficial in prolonging the survival in such patients.

Breast Neoplasms↗
PubMed1994

Genetic studies of 457 breast cancers. Clinicopathologic parameters compared with genetic alterations.

BACKGROUND: Human breast cancers frequently show loss of heterozygosity (LOH) and/or amplification at specific chromosomal regions. METHODS: To investigate the roles of these genetic alterations during tumor development and/or progression, 457 cases of primary breast cancer were examined for LOH at chromosomal regions 16q24, 17p13.3, and 17q21, and for amplification of the erb-B2 locus at 17q11.2 and the c-myc locus at 8q24. The genetic changes then were compared with lymph node metastasis, histologic type, and tumor stage. RESULTS: The LOH at 17q21 was observed more frequently in tumors of the solid, tubular type (41 of 75 [55%]) than in other types (48 of 187 [26%]) (P < 0.0001). The LOH at 17p13.3 was more frequent in scirrhous and solid, tubular tumors (77 of 141 [55%] and 48 of 88 [55%]) than in other types (29 of 89 [33%]) (P = 0.0004). Generally, mutations were seen more often in tumors with axillary lymph node metastases, undifferentiated tumors, and large or invasive tumors than in tumors considered less aggressive histopathologically. However, 22 tumors bearing three or more genetic alterations were found among 187 tumors histologically diagnosed as free of axillary lymph node metastasis; similarly, 12 of 122 t1 classification tumors and 4 of 89 histologically well differentiated tumors each contained three or more genetic alterations. Although these tumors would be regarded as having a relatively good prognosis on the basis of conventional clinicopathologic diagnosis, the authors suspect that, in fact, they do not. CONCLUSIONS: Patients whose tumors contain multiple genetic alterations should be treated as a new high risk group with respect to operative and/or postoperative management.

Blotting, Southern↗
PubMed1994

[Clinical study of serum ErbB-2 protein using sandwich radioimmunometric assay (ErbB-2 IRMA 'Eiken')].

Sandwich radioimmunometric assay (ErbB-2 IRMA 'Eiken') was developed to determine the levels of c-erbB-2 oncogene product (ErbB-2 protein) in human sera, and a clinical investigation was carried out to evaluate this novel oncogene product. The mean serum concentration of the ErbB-2 protein determined from 364 donors was 4.0 +/- 0.69 ng/ml (mean +/- SD) for females and 4.5 +/- 0.96 ng/ml for males. Cut-off values were set at 5.4 ng/ml for females and 6.5 ng/ml for males. The positivities of serum ErbB-2 protein in patients with breast carcinoma were 13.0% for primary cases and 47.9% for recurrent cases. Patients with hepatic disorders also had positive serum ErbB-2 protein levels, ie, 43.8% (7/16) for hepatocellular carcinoma and 28.9% (11/38) for hepatitis and liver cirrhosis, although the increase was slight and barely exceeded 10 ng/ml. In comparison with the levels of other tumor markers, such as CEA, CA 15-3 and NCC-ST 439, the serum ErbB-2 level was shown to have poor correlations, and was thus assumed to be useful for combination with those tumor markers. In serial determinations of serum ErbB-2 protein in two patients with recurrent breast carcinoma, the antigen increased preceding the increases in the other tumor markers, thereby also showing usefulness as a monitoring marker for breast carcinoma. In conclusion, these results indicated that ErbB-2 measurement improves the assessment of breast cancer in combination with other tumor markers and is useful as a tool for monitoring the clinical condition and the response for treatment in breast cancer.

Aged↗
PubMed1994

[Clinical evaluation of serum ErbB-2 protein using enzyme immuno assay (ErbB-2 EIA [Nichirei])].

The levels of ErbB-2 protein in serum samples from patients with breast cancer, other various malignant tumors, and benign diseases were determined using the sandwich EIA for clinical evaluation. In 364 healthy blood donors, cut-off values were set at 5.4 ng/ml for females and 6.5 ng/ml for males. The positive rate of primary breast cancer was 13.0% (24/185) and that of recurrent breast cancer was 51.2% (62/121). No significant correlation was found between serum levels of ErbB-2 protein and other tumor markers, such as CEA, CA 15-3, and ST 439. Measurement of ErbB-2 protein in combination with these tumor markers showed increased sensitivities. The positive rates and levels of ErbB-2 protein in sera of patients with metastasis to multiple organs were significantly higher than those in patients with metastasis to only a single organ. In postoperative follow-up of two patients with recurrent breast cancer, the levels of ErbB-2 exceeded its cut-off value a few months earlier than did the other tumor markers. These results indicate that the measurement of the ErbB-2 protein in serum is useful for the diagnosis and a monitoring the relapse of breast carcinoma.

Biomarkers, Tumor↗
PubMed1994

[Clinical evaluation of ErbB-2 protein in tissue extract using an enzyme immuno assay (ErbB-2 EIA "Nichirei")].

ErB-2 protein levels in breast cancer tissue extracts were determined by an enzyme immuno assay (ErbB-2 EIA "Nichirei") using anti-c-erbB-2 monoclonal antibodies, and compared with the c-erbB-2 gene amplification detected by dot blot hybridization or differential PCR, and with the overexpression detected by immunostaining. The positivities of c-erbB-2 gene amplification and overexpression in breast cancer tissues were 25.0% (14/56) and 39.3% (46/117), respectively. The cut-off values of the Erb B-2 protein in tissue extract by EIA were set at 18.0 ng/mg-protein for gene amplification and 10.4 ng/mg-protein for overexpression, respectively, from the data of breast cancer tissues which were negative for c-erbB-2 gene. The accuracy of the ErbB-2 protein levels in tissue extract with c-erbB-2 gene amplification and overexpression were 90.6% and 79.2% using these cut-off values respectively. The result of c-erbB-2 gene amplification, overexpression, and ErbB-2 protein levels were significantly correlated with negative estrogen receptor (ER) and progesterone receptor (PgR) status in tissue cytosol fraction. These results indicate that measurement of ErbB-2 protein in tissue extract is useful to estimate the c-erbB-2 gene amplification and/or overexpression in breast cancer tissues.

Antibodies, Monoclonal↗