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K Kakudo

Publications and source records attributed to K Kakudo.

At least 19 recordsLinked to original sources
PubMed2006

A review of 227 cases of small papillary thyroid carcinoma.

AIMS: To review differences in biological aggressiveness, clinical behaviors or selected surgical treatments between the PMC and the slightly larger PTC of 1.0<T<or=2.0 cm. METHODS: Two hundred and twenty-seven cases of papillary thyroid carcinoma not larger than 2.0 cm, diagnosed and treated at the Kuma Hospital, Kobe, Japan, with a 10-year follow-up from 1992 to 2003, were reviewed. RESULTS: The small PTCs demonstrated excellent outcomes, and persistent/recurrent disease was identified in only nine patients (4%). None of the patients died of the disease. A multivariate analysis revealed that massive extrathyroidal extension at presentation was the only independent prognostic factor for locoregional recurrence. Subdivision into PMCs and slightly larger tumors (1<T<or=2 cm) did not affect the excellent outcomes, but the patients in the latter subgroup received more lymph node surgery and displayed more aggressive clinico-histological features such as higher rates of extrathyroidal extension, lymph node metastasis, loss of polarity, invasive growth pattern and loss of cohesiveness. CONCLUSIONS: Small PTC not larger than 2.0 cm could be considered as favorable a prognosis as PMC.

Adenocarcinoma, Papillary↗
PubMed2006

Mastopathic fibroadenoma of the breast: a pitfall of aspiration cytology.

OBJECTIVE: To assess the correlation between cytological diagnoses and histological subtypes of fibroadenoma (FA) and to clarify the cytological features of a specific group of FA displaying variable features similar to fibrocystic disease (mastopathic type, MFA), and to evaluate the significance of this subtype in cytological diagnosis. METHODS: A review of 141 cases of histologically proven FA was performed. We re-classified them into four subtypes according to Kinoshita's criteria [Jpn J Breast Cancer6 (1991) 377] and further selected 92 cases for which both fine needle aspiration (FNA) smears and histological specimens were available. Among them, 18 cases of MFA and their cytological smears were selected for the present study. RESULTS: There was significant correlation between MFA and cytological diagnosis of 'indeterminate' or 'suspicious for malignancy' (P < 0.01). Although no false-positive diagnosis was experienced in our series, 56% of the MFAs (10/18) had cytological diagnoses of indeterminate or were included in the category 'suspicious for malignancy'. Smears from MFA revealed high cellularity (9/18 smears had more than 10 epithelial clusters each composed of more than 50 cells), presence of cellular discohesiveness (13/18, 72.2%), but only mild nuclear atypia (5/18, 27.8%). Anisonucleosis was present in fewer than half the cases and no apparent condensed chromatin was identified. CONCLUSION: We highlight the significance of subclassification of MFA in aspiration cytology of breast. MFA had a significantly higher chance of falling into the 'suspicious for malignancy' or 'indeterminate' diagnostic category in aspiration cytology. It might be a diagnostic challenge for cytopathologist to identify this subtype of FA in FNA smears.

Adolescent↗
PubMed2006

Importance of lymph vessels in gastric cancer: a prognostic indicator in general and a predictor for lymph node metastasis in early stage cancer.

BACKGROUND: Metastasis to regional lymph nodes (LNs) through lymphatic vessels is common in cancer progression and is an important prognostic factor in many cancers. Recent evidence suggests that tumour lymphangiogenesis promotes lymphatic metastasis. AIMS: To study the role of lymph vessel density (LVD) in gastric cancer and investigate whether LVD is associated with LN metastasis/prognosis. METHODS: Lymphatics of 117 primary human gastric cancer cases were investigated by quantitative immunohistochemical staining for podoplanin. The relation between LVD and LN metastasis and other established clinicopathological parameters was analysed. The relation between LVD and prognosis was also studied. RESULTS: Mean LVD of "hot spots" was 11.6/case. LVD significantly correlated with LN and podoplanin positive lymphatic invasion. High LVD was associated with worse overall survival. In multivariate analysis, positive LVD was a significant independent predictor of overall survival, depth of invasion, and TNM stage. LVD significantly correlated with LN metastasis at surgery and podoplanin positive lymphatic invasion. In multivariate analysis, positive LVD was an independent significant predictor of LN metastasis. CONCLUSIONS: Increased podoplanin expression is significantly associated with LN metastasis, and may play an important role in detecting LN metastasis in gastric cancer. Furthermore, LVD may be a significant prognostic factor in gastric cancer at any stage. In addition, LVD and lymph vessel invasion detected by podoplanin immunohistochemistry are associated with LN metastasis in T1 early gastric cancer. LVD assessment by podoplanin immunohistochemistry may become a useful predictor of LN metastasis in T1 early gastric cancer and may influence the decision making process for additional surgery.

Biomarkers, Tumor↗
PubMed2005

Expression of S100A2 and S100A6 in thyroid carcinomas.

AIMS: S100 calcium-binding proteins are known to play multiple roles in carcinoma development. In this study, we focused on two kinds of these proteins, S100A2 and S100A6, and investigated their expression in thyroid neoplasms. METHODS AND RESULTS: We investigated S100A2 and S100A6 expression in 141 thyroid neoplasms by immunohistochemistry. S100A2 was not expressed in normal follicles or follicular tumours, with one exception. Although 89.5% of papillary carcinoma were positive for S100A2, the expression was heterogeneous except in two cases. In anaplastic carcinoma, 78.5% of cases expressed S100A2 diffusely, while the remaining cases were negative. In normal follicles, S100A6 expression was always low, while 8.3% of follicular adenomas and 39.5% of follicular carcinomas showed increased expression. In papillary carcinomas, S100A6 expression was increased in 75% of cases, but in anaplastic carcinomas it was decreased, with only 14.3% showing high expression. CONCLUSIONS: The expression patterns of S100A2 and S100A6 in thyroid neoplasms are unique compared with those of other carcinomas, suggesting that: (i) S100A2 and S100A6 contribute to certain events in papillary carcinoma progression, and (ii) S100A2 expression is one of the biological characteristics of anaplastic carcinoma.

Adenocarcinoma, Follicular↗
PubMed2005

Osteoclast-like cells express receptor activity modifying protein 2: application of laser capture microdissection.

Receptor activity modifying proteins (RAMPs) act as receptor modulators that determine the ligand specificity of receptors for the calcitonin (CT) family. The purpose of this study was to analyze the expression of RAMPs in osteoclast-like cells using the laser capture microdissection (LCM) technique. Mouse bone marrow and spleen cells were co-cultured on a film designed for LCM. After 10 days, 250 osteoclast-like cells were captured using the LCM system. Total RNA from these cells was used to synthesize cDNA and RT-PCR analysis was performed. Osteoclast-like cells expressed CT receptor (CTR), CT receptor-like receptor (CRLR) and RAMP2, but did not express RAMP1 or RAMP3. These results indicated (1) that a pure population of osteoclast-like cells can be prepared by LCM and gene expression of this population can be analyzed by RT-PCR and (2) that RT-PCR shows that osteoclast-like cells express RAMP2, CTR and CRLR, suggesting the potential for adrenomedullin binding to osteoclast-like cells. This is the first report that osteoclast-like cells express RAMP2.

Animals↗
PubMed2004

Polo-like kinase 1 overexpression is an early event in the progression of papillary carcinoma.

Polo-like kinase 1 (PLK1) is one of the serine threonine kinases that contributes to cell mitosis and is regarded as a marker of cellular proliferation. However, its protein expression in human carcinoma has not been studied in depth. We investigated PLK1 expression in various thyroid neoplasms in order to elucidate its physiological significance in thyroid carcinoma. Normal follicular cells only occasionally expressed PLK1. In follicular tumours and anaplastic carcinoma, PLK1 overexpression was not a common event and only 5.9% of follicular adenoma, 7.1% of follicular carcinoma, and 11.8% of anaplastic carcinoma overexpressed this protein. However, 43.7% of papillary carcinoma overexpressed PLK1. Polo-like kinase 1 overexpression was more frequently observed in smaller papillary carcinoma lesions, and 62.5% of microcarcinoma (ranging from 4 mm to 1.0 cm) and even 66.7% of incidental carcinoma (less than 4 mm) overexpressed it, whereas this phenomenon could only be seen in 20.0% of lesions larger than 4.0 cm. Furthermore, PLK1 overexpression was not related to cell-proliferating activity evaluated by Ki-67 labelling index, but it was inversely linked to UICC stage, extrathyroidal invasion, and the presence of poorly differentiated lesion as proposed by Sakamoto et al. These findings strongly suggest that, unlike other carcinomas previously studied, PLK1 does not act as a cell cycle regulator but plays a constitutive role in papillary carcinoma especially in the early phase, and may contribute to the malignant transformation of this carcinoma.

Blotting, Western↗
PubMed2004

Parathyroid invasion, nodal recurrence, and lung metastasis by papillary carcinoma of the thyroid.

AIMS: Parathyroid invasion by papillary thyroid carcinoma (PTC) is found in a small proportion of surgical specimens, but the clinicopathological relevance of this phenomenon is not well understood. This study investigated the possible prognostic relevance of parathyroid invasion in PTC. METHOD: Parathyroid involvement was seen in 14 patients with PTC, and the clinicopathological characteristics and follow up data of these patients were analysed and compared with 164 patients without parathyroid involvement, in whom histological parathyroid examination had been undertaken, and 177 other patients without parathyroid examination (341 patients without parathyroid involvement in total). RESULTS: Parathyroid invasion was found in older patients and there were more male patients in this group than in those without parathyroid invasion. These patients had more extrathyroid extension and were frequently in an advanced stage of disease. Lung metastasis was seen in two of the 14 patients, which was significantly more than that seen in control cases. Moreover, male patients with parathyroid invasion and those who were older than 55 years had reduced disease free survival compared with those without parathyroid invasion. CONCLUSION: Parathyroid invasion seen in thyroid carcinoma may be an important histological feature indicating a greater chance of nodal recurrence and lung metastasis.

Age Factors↗
PubMed2004

Papillary carcinoma of the thyroid in Japan: subclassification of common type and identification of low risk group.

AIMS: Papillary thyroid carcinoma (PTC) is classified into two subgroups-common type and other histological variants. Correlations between further subgrouping of the common type and patient prognosis are not well documented. AIMS: To introduce two novel histological parameters to characterise PTC-loss of cellular polarity and loss of cellular cohesiveness. To investigate a new subgroup of common type PTC with possible prognostic value. METHODS: In total, 213 patients with PTCs larger than 1 cm were studied. Histological characteristics of these PTCs, including tumour growth pattern, encapsulation, extrathyroidal invasion, loss of cellular polarity, and loss of cellular cohesiveness were examined and correlated with disease free survival (DFS). RESULTS: Multivariate analysis revealed that invasive growth of unencapsulated PTC, in addition to sex (male) and tumour size (>4 cm) were significant and independent parameters for poor DFS, whereas loss of cellular polarity and cohesiveness, old age (>60 years), extrathyroid invasion, and completeness of surgery were significant only in univariate analysis. PTCs that showed expansive growth and retained cellular polarity had a favourable course, with no recurrence and no cancer related deaths. In contrast, PTCs exhibiting loss of cellular polarity and/or invasive growth with no tumour capsule had a higher risk of recurrence. CONCLUSION: Cytological features alone cannot predict patient outcome in PTC. This study indicates for the first time that loss of cellular polarity and the tumour growth pattern are useful parameters for identifying the so called low risk group in common type PTC and in predicting patient outcome in terms of tumour recurrence and cancer related death.

Age Factors↗
PubMed2002

Expression of cdc25A and cdc25B proteins in thyroid neoplasms.

Cdc25B and cdc25A phosphates are prominent stimulators of cell cycle progression and recent studies have also suggested their oncogenic roles. To elucidate the role of these proteins in thyroid neoplasms, we immunohistochemically investigated their expression, and neither protein was expressed in normal follicular cells. Cdc25B was frequently overexpressed in follicular adenoma and minimally invasive follicular carcinoma, but the incidence was significantly lower in widely invasive follicular carcinoma. Furthermore, the cdc25B expression level significantly decreased with the dedifferentiation of thyroid carcinoma. Cdc25A overexpression was observed in high incidences in all types of thyroid neoplasms. These results suggest that cdc25B and cdc25A play oncogenic roles in thyroid follicules and that cdc25B works predominantly in the early phase of the progression of thyroid carcinoma, whereas cdc25A plays a fundamental role in the development of thyroid neoplasms.

Adenoma↗
PubMed2002

Caveolin-1 overexpression is an early event in the progression of papillary carcinoma of the thyroid.

Caveolin-1 is a major structural component of caveolae, which are plasma membrane microdomains implicated in the regulation of intracellular signalling pathways. Previous in vitro and in vivo studies on the function of caveolin-1 in carcinoma showed controversial results, indicating that the physiological role of caveolin-1 varies according to the origin of carcinoma. In this study, we investigated caveolin-1 expression in thyroid neoplasms by means of immunohistochemistry using a rabbit polyclonal antibody against caveolin-1. Normal follicular cells did not express caveolin-1. In papillary carcinoma, caveolin-1 expression was observed in high incidence, and especially in microcancer (less than 1.0 cm in diameter), caveolin-1 was positive in all cases except one. In undifferentiated (anaplastic) carcinoma, its incidence was significantly reduced. On the other hand, all cases of follicular carcinoma and adenoma were classified as negative for caveolin-1. These results suggest that caveolin-1 may play a role predominantly in the early phase of papillary carcinoma, whereas it has little influence on follicular tumours.

Adenoma↗
PubMed2001

Phosphorylation of mitogen-activated protein kinase is inhibited by calcitonin in DU145 prostate cancer cells.

One of the causes of insensitivity to androgen ablation therapy in prostate cancer is thought to be attributable to elevated neuropeptides secreted by neuroendocrine cells in the tumor mass. Calcitonin (CT), one of these neuropeptides, is reported to be associated with the growth of prostate cancer. There is an increase in mitogen-activated protein (MAP) kinase activation as prostate cancer progresses to a more advanced and androgen-independent disease. We examined the effect of CT on signal transduction and the relation between CT and early-response genes in the human androgen-insensitive prostate cancer cell line, DU145. The basal phosphorylation level of extracellular signal-regulated kinase 1/2, which is a key kinase in the mediation of growth factor-induced mitogenesis in prostate cancer cells, was constitutively up-regulated. N-[2-(4-bromocinnamyl) aminoethyl]-5-isoquinoline-sulfonamide (H89), a specific inhibitor of protein kinase A, potentiated the effects of more increased phosphorylation of extracellular signal-regulated kinase 1/2. CT induced the inhibition of this MAP kinase phosphorylation, and this effect was completely abolished by pretreatment with H89. Our findings demonstrate that CT caused the inhibition of constitutive MAP kinase phosphorylation in a protein kinase A-dependent manner in DU145. The transient increase of c-fos expression was detected after CT treatment, whereas expression of c-jun RNA was down-regulated after CT treatment. These results suggest that CT may regulate early-response genes, c-fos and c-jun, via a MAP kinase cascade. In conclusion, these findings suggest that DU145 might be a useful model as a therapeutic approach of neuropeptides in androgen-independent prostatic carcinoma.

Calcitonin↗
PubMed2001

Prognostic significance of BRCA1 expression in Japanese sporadic breast carcinomas.

BACKGROUND: BRCA1 is a tumor suppressor gene that is responsible for hereditary breast and ovarian carcinoma syndrome. The primary objective of the current study was to investigate the influence of BRCA1 expression on the prognoses of sporadic breast carcinomas. METHODS: A cohort of 175 Japanese women with invasive breast carcinoma who had no family history in first-degree relatives was studied. Expression of BRCA1 was determined by an immunohistochemical procedure in which the MS110 monoclonal antibody was used. Kaplan--Meier and Cox proportional regression survival analyses were used to compare negative and positive BRCA1 patients. RESULTS: One hundred fifteen (65.7%) of the 175 specimens showed positive BRCA1 staining (> 10% cells were immunoreactive). During a median follow-up of 4.4 years, negative BRCA1 patients had worse disease free survival than positive BRCA1 patients (35 % vs. 7%, respectively; P < 0.0001). BRCA1 expression was significantly inversely correlated with histologic grade (P < 0.0001) but not with lymph node status or other conventional prognostic markers. In multivariate analysis using the Cox regression model, positive BRCA1 emerged as an independent prognostic indicator for disease free survival. CONCLUSIONS: The results of this study suggest that BRCA1 may be a valuable marker for identifying women with sporadic breast carcinoma at high risk of developing recurrence, and who may be candidates for trials investigating new therapies in combination with standard adjuvant therapy.

Adult↗
PubMed2001

Loss of calcitonin binding in rat is not related to calcitonin receptor gene abnormality.

C-cell tumors occur frequently (50%) in old WAG/Rij rats. Interestingly, genetically transmitted loss of CT binding sites in the kidney has also been demonstrated in WAG/Rij rats. To determine if these issues are resulted from mutation of calcitonin receptor (CTR), we analyzed the CTR genomic abnormality in WAG/Rij rat. We demonstrated that both Wistar and WAG/Rij rats expressed type-C1a CTR by RT-PCR analysis and their mRNA expressions were approximately equal by Northern blotting analysis. Direct sequence of RT-PCR products for CTR showed no different nucleotide sequences between the two strains. There were three polymorphisms at the first transmembrane domain and the fourth intracellular membranes, which are different from Sprague-Dawley rat. We concluded that the loss of CT binding in WAG/Rij rat is not related to CTR gene abnormality. Abnormal system of CTR amino acid modification may be occurred in WAG/Rij rat.

Animals↗
PubMed2001

Calcitonin receptor gene polymorphism in japanese women: correlation with body mass and bone mineral density.

We have identified a polymorphism at position 1377 of the calcitonin receptor (CTR) gene which generates CC, CT, or TT genotype. In this study, the genotypes of the CTR and their relationship with the body height, the body weight, the bone mineral density (BMD), and osteocalcin levels were examined in 152 healthy Japanese women aged 16-43 years. The CTR genotypic frequencies in the Japanese population were 77.0% for CC, 20.4% for CT, and 2.6% for TT. The height, BMD, and osteocalcin levels were not significantly different among these three genotypes. The body weight adjusted for height in these three groups was significantly different in the order of TT, CT, and CC (P = 0.0454 by analysis of covariance). In combined analysis of the VDR genotype (B,b) and the CTR genotype (C,T), the body height was found to be significantly different between CCB and others (P = 0.0236). In addition, analysis of the CTR genotypic frequency using 64 blood samples from Japanese and 47 blood samples from Caucasians indicated that there was a significant difference between the two races (P < 0.0001). We found that C allele was predominant in the Japanese population, however, Caucasians have an almost equal ratio of the C and T. In conclusion, the CTR allele is one of the genetic factors regulating body weight in Japanese women.

Absorptiometry, Photon↗
PubMed2001

Correlation between nuclear grade and biological prognostic variables in invasive breast cancer.

BACKGROUND: Grading of carcinomas is an estimation of differentiation. Nuclear grading is the cytological evaluation of tumor nuclei in comparison with the nuclei of normal mammary epithelial cells. Because nuclear grading does not involve an assessment of the growth pattern of the tumor, it applies not only to invasive ductal carcinoma but also to other subtypes of breast carcinoma. METHODS: A total of 215 primary breast carcinomas obtained from the Affiliated Kihoku Hospital of Wakayama Medical College were enrolled in our present study. Nuclear grade was evaluated according to the criteria of the National Surgical Adjuvant Study of Breast Cancer (NSAS-B) protocol. Immunohistochemistry was also performed to determine Bcl-2, p53, c-erbB-2, estrogen receptor (ER) and MIB-1 expression in paraffin-embedded tissues for all cases. RESULTS: Thirty-two (14.9%) of the patients were graded as 1,124 (57.7%) as 2, and 59 (27.4%) as 3. Nuclear grade displayed a negative correlation with Bcl-2 expression (r=-0.308, p<0.0001), and a positive correlation with c-erbB-2 overexpression (r= 0.172, p=0.0117) and tumor proliferative index labeling by MIB-1 (r=0.485, p<0.0001). CONCLUSIONS: These results imply that nuclear grade is related to the characteristics of tumor biology, indicating that the morphology and biology of breast cancer are tightly linked. Our present results also suggest that adding the nuclear grade to the pathological diagnosis of invasive breast carcinoma may be clinically useful for predicting tumor behavior, for example aggressiveness, and for prognostication.

Biomarkers, Tumor↗
PubMed2001

Biallelic inactivation of retinoic acid receptor beta2 gene by epigenetic change in breast cancer.

A growing body of evidence supports the hypotheses that retinoic acid receptor beta2 (RAR beta2) is a tumor suppressor gene. Although the loss of RAR beta2 expression has been reported in many malignant tumors, including breast cancer, the molecular mechanism is still poorly understood. We hypothesized that loss of RAR beta2 activity could result from multiple factors, including epigenetic modification and loss of heterozygosity (LOH). Using methylation-specific polymerase chain reaction and LOH analysis, we found that biallelic inactivation via epigenetic changes of both maternal and paternal alleles, or epigenetic modification of one allele combined with genetic loss of the remaining allele, could completely suppress RAR beta2 expression in breast cancer. Thus, it is possible that substantial numbers of human cancers arise through suppressor gene silencing via epigenetic mechanisms that inactivate both alleles. Because of this, chromatin-remodeling drugs may provide a novel strategy for cancer prevention and treatment.

Alleles↗
PubMed2001

Allelic loss of chromosome 3p24 correlates with tumor progression rather than with retinoic acid receptor beta2 expression in breast carcinoma.

A tumor suppressor gene. retinoic acid receptor (RAR) beta2, has been mapped to chromosome 3p24, a region where loss of heterozygosity (LOH) has been observed commonly in carcinomas of various tumor tissues. RAR beta2 expression is reduced or lost in many malignant tumors including breast cancer, however, whether LOH accounts for the loss of expression of RAR beta2 in breast cancer is unknown. We, therefore, assessed LOH on chromosome band 3p24 to correlate it with RAR beta2 expression and other established prognostic parameters in 52 breast carcinomas. Based on three microsatellites, D3S 1283, D3S 1293 and D3S 1286. all of the tumors were informative, of these, 12 (23%) exhibited LOH. RAR beta2 expression was lost in 42% (19/45) of these samples. We found that LOH on chromosome band 3p24 was not correlated with loss of RAR beta2, but correlated with higher histological grade, p53-positivity, and loss of estrogen and progesterone receptors. Our findings suggest that LOH of the RAR beta2 gene does not account for the frequent loss of RAR beta2 expression in breast cancer but the genomic structural alteration at or close to the RAR beta2 gene locus are likely to be associated with tumor progression and/or loss of hormonal dependency.

Breast Neoplasms↗