Biomedical subjects

Yuuki Takamura

Publications and source records attributed to Yuuki Takamura.

54 records · Page 3Linked to original sources

PubMed2003

14-3-3 sigma possibly plays a constitutive role in papillary carcinoma, but not in follicular tumor of the thyroid.

Jun activation domain-binding protein 1 (jab1) is known as a coactivator of the AP1 transcription factor. Recent studies have demonstrated that jab1 contributes to carcinoma progression by degrading p27/Kip1 protein. In this study, we immunohistochemically investigated jab1 expression in thyroid neoplasms. jab1 overexpression tended to be frequently observed in follicular carcinoma compared to adenoma. Larger-sized papillary carcinoma overexpressed jab1 in higher incidence than microcarcinomas (1.0 cm or less in maximum diameter). In anaplastic carcinoma, jab1 was more frequently overexpressed than in papillary and follicular carcinomas. An inverse relationship was detected between jab1 overexpression and p27 expression in papillary and anaplastic carcinomas, but not in follicular tumor. These results suggest that jab1 plays a role in the progression of thyroid carcinomas, especially those of aggressive phenotypes, and it may be responsible for p27 degradation in anaplastic and papillary carcinomas.

14-3-3 Proteins↗

PubMed2003

p130 expression in thyroid neoplasms: its linkage with tumor size and dedifferentiation.

p130 belongs to the retinoblastoma-related gene family, and its gene product works to negatively regulate cell cycle progression in the G1 phase. In this study, we investigated p130 expression in thyroid neoplasms. p130 overexpression was observed in 33.3% of follicular adenoma and 50% of follicular carcinoma and the incidences were not significantly different. In papillary carcinoma, it was overexpressed in 36.5% of cases, but in microcarcinoma, the incidence was significantly lower (14.3%). Furthermore, in anapalstic carcinoma, p130 overexpression was less frequently seen than in papillary carcinoma except for microcarcinoma and follicular carcinoma, and only 14.3% of cases overexpressed this protein. These findings suggest that: (1) reduced p130 expression may contribute to the aggressive character of anplastic carcinoma; and (2) p130 may specify the growth characteristics of microcarcinoma.

Carcinoma↗

PubMed2003

Increased expression of BRCA1 mRNA predicts favorable response to anthracycline-containing chemotherapy in breast cancers.

Clinical significance of BRCA1 and BRCA2 mRNA levels in tumor tissues as predictors of response to anthracycline-containing chemotherapy was studied in breast cancer patients. Fifty-one patients with locally advanced breast tumors (n = 43) or locally recurrent tumors (n = 8) underwent tumor biopsy and were treated with CE (cyclophosphamide (600 mg/m2) plus epirubicin (60 mg/m2), q3w). BRCA1 and BRCA2 mRNA levels in the tumors were determined by a real-time PCR assay, and the expression of p53 and erbB2 in tumors was determined by immunohistochemistry. BRCA1 mRNA levels (1.317 +/- 0.277, mean +/- S.E.) of responders were significantly (p < 0.05) higher than those (0.609 +/- 0.097) of non-responders but there was no significant difference in BRCA2 mRNA levels between responders (1.590 +/- 0.326) and non-responders (1.586 +/- 0.410). Tumors were dichotomized into the BRCA1 mRNA levels high and low group according to the cut-off value of 0.55. Response rate (65%) of tumors with high BRCA1 mRNA levels was significantly (p < 0.05) higher than that (32%) of tumors with low BRCA1 mRNA levels. There was no significant association between response to CE and the expression of p53 or erbB2. Positive predictive value, negative predictive value, and diagnostic accuracy of BRCA1 mRNA determination in the prediction of response to CE were 65, 68, and 67%, respectively. These results suggest a possibility that BRCA1 mRNA levels in tumor tissues might be useful in the prediction of response to CE treatment in breast cancer patients.

Antibiotics, Antineoplastic↗

PubMed2003

Y-box binding protein expression in thyroid neoplasms: its linkage with anaplastic transformation.

Recent studies have demonstrated that Y-box binding protein (YB-1) regulates the transcription of genes linked to carcinoma progression. In this study, we investigated the expression of this protein in thyroid neoplasms to elucidate its significance. The expression of YB-1 was immunohistochemically investigated using the monoclonal antibody for various thyroid neoplasms. Normal follicles did not overexpress YB-1, and only moderate overexpression of YB-1 was observed in some follicular tumors and papillary carcinoma, especially those of a larger size. In contrast, 92.9% of anaplastic carcinoma strongly overexpressed YB-1. YB-1 immunoreactivity was seen in both cytoplasms and cell nuclei, but the former was more predominant. These findings suggest that YB-1 plays a role in regulating the transcription as well as translation of genes contributing to the anaplastic transformation of thyroid carcinoma.

Adenocarcinoma, Follicular↗

PubMed2003

KAI1 expression in thyroid neoplasms: its linkage with clinicopathologic features in papillary carcinoma.

KAI1 is a metastasis suppressor gene located on human chromosome 11p11.2. Previous studies have shown that the down-regulation of KAI1 mRNA and decreased expression of its gene product are significantly linked to carcinoma progression, including metastatic ability. In this study, we investigated KAI1 protein expression in thyroid neoplasms. KAI1 overexpression was observed in 64.0% of papillary carcinoma cases, and the incidence was significantly higher than in cases of follicular carcinoma (20.0%) (p = 0.0001). In papillary carcinomas, decreased KAI1 expression was frequently observed in cases invading beyond the thyroid capsule (p = 0.001), as well as in lymph node metastases (p = 0.0047) and poorly differentiated lesions (p = 0.0299). Furthermore, in anaplastic carcinoma, the incidence of KAI1 overexpression was lower than in papillary carcinoma (p < 0.0001), and only 4.2% of the cases overexpressed this gene. These results suggest that KAI1 down-regulation is significantly related to the progression of papillary carcinoma, including lymph node metastasis, and its anaplastic transformation.

Adenocarcinoma, Follicular↗

PubMed2003

An observation trial without surgical treatment in patients with papillary microcarcinoma of the thyroid.

The recent prevalence of ultrasound-guided fine-needle aspiration biopsy has resulted in a marked increase in the number of patients with papillary microcarcinoma (maximum diameter, </= 10 mm) of the thyroid detected by this sophisticated tool. On the other hand, it is debatable whether patients with papillary microcarcinoma should always undergo surgery after diagnosis, because a high incidence of occult papillary carcinoma has been observed in autopsy studies. Thus, we proposed observation without surgical therapy as a treatment option in 732 patients diagnosed with papillary microcarcinoma by the above technique from 1993 to 2001. One hundred sixty-two patients chose observation and were classified as the observation group. During the follow-up period for patients in the observation group, more than 70% of tumors either did not change or decreased in size compared to their initial size at diagnosis. They enlarged by more than 10 mm in 10.2%, and lymph node metastasis in the lateral compartments appeared in only 1.2% of patients during follow-up. On the other hand, 570 patients chose surgical treatment at diagnosis and 56 patients in the observation group who underwent surgery after a period of follow-up were classified as the surgical treatment group. Of these 626 patients, lymph node dissection was performed in 594 patients, and metastasis was confirmed histologically in 50.5%. Multiple tumor formation was seen in 42.8% of patients. In this group, the rate of recurrence was 2.7% at 5 years and 5.0% at 8 years after surgery. Our preliminary data suggest that papillary microcarcinomas do not frequently become clinically apparent, and that patients can choose observation while their tumors are not progressing, although they are pathologically multifocal and involve lymph nodes in high incidence.

Adolescent↗

PubMed2003

Changes in serum TSH receptor antibody (TRAb) values in patients with Graves' disease after total or subtotal thyroidectomy.

TSH receptor antibodies (TRAb) are generally regarded as mediators of thyroid stimulation in Graves' disease. In addition, a high serum TRAb value during pregnancy is one of the risk factors for intrauterine death, prematurity, and fetal or neonatal hyperthyroidism. Recently, correlations between a high serum TRAb value and endocrine opthalmopathy were also suggested. Surgical resection of the thyroid is usually followed by a reduction of serum TRAb levels in variable degrees. The relation between the extent of the thyroidectomy and the degree of reduction is still controversial. In addition, the changes in the TRAb value after total thyroidectomy (TT) over a long period of time have never been studied. We studied the changes in serum TRAb values after TT and subtotal thyroidectomy (ST) for more than 7 years. Forty-one patients with Graves' disease underwent TT, and 99 patients underwent ST. The serum TRAb values and the ratio of the patients who achieved normal values among each group (normalization rates of TRAb) at 3 and 6 months, 1, 3, 5 and 7 years after surgery were compared between the TT group and ST group. The mean preoperative TRAb values were not significantly different between the TT and ST groups, and the mean TRAb values measured 3, 6 and 12 months after surgery were not significantly different between the groups. However, the TRAb values measured 3, 5 and 7 years after surgery were significantly (p<0.05) lower in the TT group than in the ST group (16.7 +/- 3.3% vs 28.0 +/- 2.6%, 12.6 +/- 3.4% vs 29.3 +/- 3.8%, 5.6 +/- 0.9% vs 25.4 +/- 4.1%, respectively). The normalization rates of TRAb were not significantly different between the groups until 1 year after surgery. However, the normalization rates 3, 5 and 7 years after surgery were significantly (p<0.05) higher in the TT group than in the ST group (65.7% vs 42.4%, 77.3% vs 46.7%, 100% vs 59.1%, respectively). The surgical complication rates of TT were similar to ST except for permanent hypoparathyroidism. TT is a treatment option for Graves' disease, especially in patients with a high TRAb value who wish to have children or who have Graves' opthalmopathy.

Adolescent↗

PubMed2002

Prediction of chemotherapeutic response by collagen gel droplet embedded culture-drug sensitivity test in human breast cancers.

Collagen gel droplet embedded culture-drug sensitivity test (CD-DST) is the newly developed in vitro chemosensitivity test that has several advantages over the conventional ones. The aim of the present study is to examine the clinical usefulness of this test in the prediction of response to chemotherapy in breast cancer patients. Seventy patients with primary (n = 45) or locally recurrent (n = 25) breast cancers were recruited, and each patient underwent tumor biopsy before chemotherapy. The biopsy specimens were used for CD-DST and immunohistological examination of 6 biological markers (P-gp, erbB2, p53, BCL2, MIB1 and ER-alpha). As chemotherapy, cyclophosphamide 600 mg/m(2) plus epirubicin 60 mg/m(2) q3w (CE, n = 28) or docetaxel 60 mg/m(2) q3w (DOC, n = 42) was given. Interpretable results using the CD-DST assay were obtained from 84.3% (59/70) of tumor specimens studied. Of the 18 tumors diagnosed as CE sensitive by CD-DST, 15 (83.3%) exhibited a response to CE therapy and none of the 5 tumors diagnosed as CE resistant by CD-DST exhibited a response to CE therapy. Of the 14 tumors diagnosed as DOC sensitive by CD-DST, 13 (92.9%) exhibited a response to DOC therapy and only one of the 22 tumors diagnosed as DOC resistant by CD-DST exhibited a response to DOC therapy. P-gp expression was found to exhibit a significant (p < 0.05) association with the resistance to CE therapy but not to DOC therapy. Diagnostic accuracy (72.7%) achieved by P-gp was lower than that (87.0%) achieved by CD-DST in CE therapy. Expressions of other biological markers (erbB2, p53, BCL2, MIB1 and ER-alpha) were not significantly associated with response to CE or DOC therapy. These results demonstrate that CD-DST can predict the response to CE and DOC therapy with a high accuracy in breast cancer patients and seems to be superior to the conventional predictors.

Adult↗

PubMed2002

Prediction of response to docetaxel by CYP3A4 mRNA expression in breast cancer tissues.

We studied the relationship between response of breast cancer to docetaxel (DOC) or cylophosphamide + epirubucin (CE) treatment and CYP3A4 mRNA expression in breast tumors. CYP3A4 inactivates DOC but not E, which is a predominant effector in CE treatment. Twenty patients with locally advanced breast tumors and 18 patients with locally recurrent tumors underwent tumor biopsy before chemotherapy, and CYP3A4 mRNA expression levels in tumor tissues were assayed by real-time quantitative polymerase chain reaction. Twenty-three patients were treated with DOC (60 mg/m(2) q3w) and 15 patients were treated with CE (C 600 mg/m(2) and E 60 mg/m(2) q3w). Patients with low CYP3A4 mRNA levels (n = 14) exhibited a significantly (p < 0.01) higher response rate (71%) to DOC treatment than those (n = 9) with high CYP3A4 mRNA levels (response rate, 11%). Positive predictive value, negative predictive value and diagnostic accuracy of CYP3A4 mRNA levels in the prediction of response to DOC were 71, 89, and 78%, respectively. However, no significant association was observed between CYP3A4 mRNA expression and response to CE treatment. These results suggest that intratumoral CYP3A4 mRNA levels might be useful as a predictor of response to DOC treatment, but not to CE treatment, in breast cancer patients. The increased inactivation of DOC by CYP3A4 in tumor tissues may play some role in the acquisition of resistance to DOC.

Adult↗

PubMed2002

Comparison between periareolar and peritumoral injection of radiotracer for sentinel lymph node biopsy in patients with breast cancer.

BACKGROUND: The technique of sentinel lymph node (SLN) biopsy in patients with breast cancer varies among reports, and the optimal method remains to be established, particularly with regard to the site of radiotracer injection. The aim of this study was to compare periareolar and peritumoral injection of radiotracer in detecting SLN in patients with breast cancer. METHODS: Patients with T1-2 breast cancer (n = 155) were enrolled in this study. In phase 1 (n = 62), SLN biopsy was performed by using peritumoral injection of blue dye alone followed by backup axillary lymph node dissection. In phase 2, SLN biopsy was performed by using peritumoral injection of blue dye and peritumoral (group A, n = 41) or periareolar (group B, n = 52) injection of technetium 99m tin colloid. RESULTS: In phase 1, the detection rate of SLN was 81% and the false-negative rate was 5.6%, indicating our skill in SLN biopsy. In phase 2, the success rate of lymphoscintigraphy was significantly (P <.001) higher in group B (90%) than in group A (51%). The mean ex vivo radioactivity of SLN in group B (117 counts per second; range, 5 to 900) was also significantly (P <.05) higher than in group A (51 counts per second; range, 8 to 260). In addition, the detection rate of SLN was significantly (P <.05) higher in group B (100%) than in group A (90%). CONCLUSIONS: Periareolar injection of radiotracer for SLN biopsy is superior to peritumoral injection because of its simplicity, achieving a high success rate in lymphoscintigraphy and SLN detection.

Adult↗

PubMed2002

Expression of G2-M modulators in thyroid neoplasms: correlation of cyclin A, B1 and cdc2 with differentiation.

Previous studies have demonstrated that cell proliferating activity accurately reflects the biological aggressiveness of thyroid neoplasms. In this study, we focused on the G2-M boundary regulators of the cell cycle and investigated the expression of three proteins, cyclin A, cyclin B1 and cdc2. The incidence of cyclin A overexpression was significantly linked to carcinoma differentiation (p < 0.0001) and, in particular, all 21 cases of undifferentiated carcinoma overexpressed this protein. On the other hand, cyclin B1 was overexpressed in four undifferentiated carcinomas (19.0%), but not in carcinomas of other types. Cdc2 overexpression was also related to carcinoma differentiation (p < 0.0001), and was directly linked to cyclin A overexpression (p < 0.0001), but not to cyclin B1 overexpression. No significant relationship could be established between the overexpression of these proteins and the histological type of follicular tumor. These results suggest that cyclin A, rather than cyclin B1, contributes significantly to the aggressive character of thyroid carcinoma, together with cdc2.

Adenoma↗

PubMedDate not supplied

Bag-1 expression in thyroid neoplasm: its correlation with Bcl-2 expression and carcinoma dedifferentiation.

BACKGROUND: Apoptosis, programmed cell death, is one of the promnent factors in the evaluation of carcinoma characteristics. It is well-known that bcl-2 and its related proteins significantly modulate apoptosis. Bag-1 is a recently identified bcl-2-related protein and is known to be linked to the biological aggressiveness of some carcinomas. MATERIALS AND METHODS: We immunohistochemically investigated bag-1 and bcl-2 expression in various thyroid neoplasms using monoclonal antibodies. RESULTS: High bag-1 expression was observed in 66.7% of follicular adenoma and 75.0% of follicular carcinoma, and no statistical difference was established between them. In papillary carcinoma, 60.7% were classified with high bag-1 expression, whereas only 4.5% of anaplastic (undifferentiated) carcinoma highly expressed bag-1, and the incidence was significantly lower (p < 0.0001) than in papillary and follicular carcinomas. Furthermore, in thyroid neoplasm, bag-1 expression was directly linked (p < 0.0001) to bcl-2 expression. CONCLUSION: These findings suggest that bag-1 may interact with bcl-2 to play an important role in thyroid neoplasm before anaplastic transformation, and the disruption of events mediated by bag-1 and bcl-2 may be a typical characteristic of undifferentiated carcinoma.

Adenocarcinoma, Follicular↗

PubMedDate not supplied

Decreased expression of cyclin G2 is significantly linked to the malignant transformation of papillary carcinoma of the thyroid.

BACKGROUND: Cyclin G2 is a novel cyclin negatively regulating the cell cycle progression, contrary to the characteristics of conventional cyclins. However, little is known about the cyclin G2 expression in human carcinomas. We thus investigated cyclin G2 expression in human thyroid neoplasms. MATERIALS AND METHODS: We immunohistochemically examined cyclin G2 expression in 40 normal thyroids and 80 thyroid neoplasms. RESULTS: Normal thyroids expressed cyclin G2 in more than 5% of follicular cells. Of 30 papillary carcinomas including 6 microcarcinoma, cyclin G2 expression was not, or only occasionally, observed in carcinoma cells, indicating its expression decreased in all these cases. On the other hand, in 16 of the 24 follicular adenomas (66.7%) and 5 of the 23 follicular carcinomas (21.7%), cyclin G2 expression was retained (more than 5% of neoplastic cells were positive), and adenomas more frequently (p = 0.0032) retained cyclin G2 expression than carcinomas. CONCLUSION: Our results suggest that lack of cyclin G2 plays an important role in the malignant transformation of papillary carcinoma. Also, it may play an adjuvant role in the transformation of follicular adenoma to carcinoma. This is the first study of the expression of cyclin G2, a novel cyclin having a role opposite to that of conventional cyclins, in human carcinoma.

Carcinoma↗

PubMedDate not supplied

Decreased expression of p107 is correlated with anaplastic transformation in papillary carcinoma of the thyroid.

BACKGROUND: Previous studies have demonstrated that two members of the Rb family, pRb and p130, are expressed in thyroid neoplasms. However, our knowledge about the expression and physiological role of the third member of this family, p107, remains poor. We therefore investigated p107 expression in various thyroid neoplasms. MATERIALS AND METHODS: We immunohistochemically investigated p107 expression in 16 anaplastic carcinomas, 50 papillary carcinomas, 15 follicular carcinomas and 17 follicular adenomas using a rabbit polyclonal antibody against p107. RESULTS: Normal follicular cells only occasionally expressed p107. In papillary carcinoma, p107 was positive in 84.0% of the cases, regardless of various biological characteristics. Follicular carcinoma less frequently expressed p107 than follicular adenoma (p = 0.0278). Furthermore, only 12.5% of anaplastic carcinomas were p107-positive and the incidence was significantly less than that in papillary carcinoma (p < 0.0001). CONCLUSION: Our findings suggest that p107 plays a constitutive role in the progression of papillary carcinoma and that decreased p107 expression may contribute to the transformation from follicular adenoma to follicular carcinoma and anaplastic transformation.

Carcinoma↗

PubMedDate not supplied

Telomerase activity in thyroid neoplasms evaluated by the expression of human telomerase reverse transcriptase (hTERT).

BACKGROUND: The recent availability of a monoclonal antibody against human telomerase reverse transcriptase (hTERT) has enabled us to investigate the telomerase activity of tissue specimens more easily than by classical TRAP assay. In this study, we studied teromerase activity in thyroid tumors using this antibody. MATERIALS AND METHODS: We immunohistochemically investigated hTERT expression in 166 thyroid neoplasms. RESULTS: Normal follicular cells did not express hTERT. In papillary carcinoma, high hTERT expression was observed in 34.5% of cases and it was directly linked to stage and the presence of lymph node metastasis. In follicular carcinoma, 39.2% were classified as the high hTERT expression group, showing a significantly higher incidence than that in follicular adenoma, 9.8%. In anaplastic carcinoma, 73.7% were regarded as the high hTERT expression group, which was larger than the percentages in papillary and follicular carcinomas. We investigated the diagnostic usefulness of hTERT measurement for discriminating follicular carcinoma from adenoma. Its specificity and positive predictive value were high at 90.2% and 83.3%, respectively, while the sensitivity and negative predictive value were low. CONCLUSION: These results suggest that: i) telomerase activity contributes to anaplastic transformation of differentiated carcinoma and ii) hTERT measurement may contribute to diagnosing follicular carcinoma, but whether it can be applied to preoperative diagnosis by fine-needle aspiration biopsy specimens remains unclear.

Adenocarcinoma, Follicular↗

PubMedDate not supplied

Expression of p8 protein in breast carcinoma; an inverse relationship with apoptosis.

BACKGROUND: P8 is a transcription factor and its expression is elevated in response to apoptotic stimuli. However, p8 in human carcinoma tissue has not been investigated in depth. In this study, we investigated p8 expression in breast carcinoma. MATERIALS AND METHODS: We immunohistochemically investigated p8 expression in 50 cases of breast carcinoma, including 7 non-invasive ductal carcinomas. RESULTS: High expression of p8 was observed in 60% of cases, which was inversely related to tumor size and UICC stage. All non-invasive ductal carcinomas diffusely expressed p8. Furthermore, in tumors of 2 cm or larger, the p8 expression was inversely linked to the apoptotic index. CONCLUSION: These results suggest that p8 plays a role in the early phase of breast carcinoma progression and especially in tumors of larger size, acting as an inhibitor of apoptosis of breast carcinoma cells.

Apoptosis↗

PubMedDate not supplied

Expression of p8 protein in medullary thyroid carcinoma.

BACKGROUND: The p8 protein is involved in various cells under cellular stress, such as apoptotic stimuli. In this study, p8 protein expression was investigated in human medullary thyroid carcinoma. in order to elucidate its physiological significance. MATERIALS AND METHODS: We immunohistochemically investigated p8 expression in 69 cases of medullary thyroid carcinoma. RESULTS: Thirty cases (43.4%) were regarded as a high group of p8 expression with a labelling index of 50% or higher. The p8 expression level was directly linked to lymph node metastasis, extrathyroid extension and UICC stage. Furthermore, there were no cases showing low p8 expression, but 24.8% of those with high p8 expression showed recurrence. However, p8 expression was not linked to the apoptotic index. CONCLUSION: These findings suggest that p8 expression plays an important role in the progression of medullary carcinoma, but does not have an anti-apoptotic function.

Adolescent↗

PubMedDate not supplied

Decreased expression of tumor protein p53-induced nuclear protein 1 (TP53INP1) in breast carcinoma.

BACKGROUND: Tumor protein p53-induced nuclear protein 1 (TP53INP1) is a stress-induced protein and plays a role in cell cycle arrest and p53-mediated apoptosis. In this study, TP53INP1 expression in human breast carcinoma was investigated. MATERIALS AND METHODS: TP53INP1 and aberrant p53 expression were investigated immunohistochemically in 81 cases of breast carcinoma. RESULTS: Diffuse and intense TP53INP1 expression was observed in the normal mammary gland. Decreased TP53INP1 expression was found in 45 cases (55.6%) of breast carcinoma. The TP53INP1 expression level was inversely linked to tumor size, positive lymph node metastasis, high histological grade and aberrant p53 expression. CONCLUSION: Decreased expression of TP53INP1 is involved in breast carcinoma progression.

Breast Neoplasms↗