Biomedical subjects

T Hasebe

Publications and source records attributed to T Hasebe.

At least 19 recordsLinked to original sources

PubMed2006

Impact of isolated tumor cells in sentinel lymph nodes detected by immunohistochemical staining.

AIM: Isolated tumor cells (ITCs) in lymph nodes are defined histologically as node-negative. The clinical impact of ITCs in sentinel lymph nodes (SLNs) remains unclear. We report the prognosis of breast cancer patients with ITC-positive SLNs detected by immunohistochemical staining. PATIENTS AND METHODS: One hundred and sixty-five breast cancer patients with histologically negative SLNs were seen between January 1998 and December 2000. In 69 patients, sentinel node biopsy (SNB) was immediately followed by axillary lymph node dissection, and 96 had undergone SNB alone. Permanent sections of 301 SLNs were re-examined after hematoxylin-eosin staining and cytokeratin 19 immunohistochemical staining. RESULTS: ITCs were found in 18 SLNs of 17 patients and a micrometastasis was found in one SLN of one patient. As of November 2005, only one patient with ITCs in one SLN had supraclavicular lymph node recurrence. In contrast, 18 of the 147 patients with negative SLNs had tumor recurrence. Surgical management of the axilla had no influence on recurrence-free survival in all of the patients. CONCLUSION: This study shows that breast cancer patients with ITC-positive SLNs should be clinically managed as node-negative patients.

Adult↗

PubMed2005

Predictors of tumour involvement in remaining axillary lymph nodes of breast cancer patients with positive sentinel lymph node.

AIMS: To characterize the various clinicopathologic features in cases of breast cancer with positive sentinel lymph nodes (SLNs), in order to determine factors that might help in predicting the involvement of the non-SLNs. METHODS: A retrospective database review was performed of 726 breast cancer patients with stage 0-II, in whom SLNs were successfully identified. One hundred eighty-five of these patients showed positive SLNs, and subsequently underwent axillary lymph node dissection (ALND). These cases were divided into two groups based on the presence or absence of metastases in the non-SLNs, i.e. positive non-SLNs (NSLN+; 81 cases) and negative non-SLNs (NSLN-; 104 cases). RESULTS: Multivariate analysis revealed that a larger size of the primary tumour (>2.0cm), presence of lymphatic invasion, larger size of the largest SLN metastasis (>2mm), and a 100% metastatic rate in the SLNs (number of positive SLNs/number of harvested SLNs) were significantly associated with NSLN+. Among the cases in which all the four factors were present, 73% (30/41) were found to have NSLN+. CONCLUSION: We found four independent predictors in relation to non-SLN metastasis. Although these factors might be useful for determining the need of additional ALND, it would seem that even the presence of all of these four factors in combination may be insufficient to safely omit ALND. Thus, until further evidence is accumulated from the results of large clinical trials, ALND would still be recommended for patients with SLN metastasis.

Axilla↗

PubMed2005

Primary tumour-vessel tumour-nodal tumour classification for patients with invasive ductal carcinoma of the breast.

There are many studies that show biological differences between invasive ductal carcinoma (IDC) with and without nodal metastasis, but no prognostic classification taking into consideration any biological differences between them is currently available. We previously investigated the histological characteristics that play an important role in tumour progression of IDCs according to their nodal status, and a new prognostic histological classification, the primary tumour-vessel tumour-nodal tumour (PVN) classification, was devised based on the histological characteristics of IDCs with and without nodal metastasis. Multivariate analyses using the Cox proportional hazard regression models were used to compare the ability of the PVN classification to predict tumour recurrence and death in 393 IDC patients based on the following histological classifications: (1) the pTNM classification, (2) the Nottingham Prognostic Index, (3) the modified Nottingham Prognostic Index, and (4) the histologic grade. In IDCs without nodal metastasis, only the PVN classification significantly increased the hazard rates (HRs) of tumour recurrence and death (P<0.05), independent of the hormone receptor status. Similarly, in IDCs with nodal metastases, only the PVN classification significantly increased the HRs of tumour recurrence and death (P<0.05), independent of the hormone receptor status. We conclude that the PVN prognostic histological classification is the best classification available for IDC of the breast.

Breast Neoplasms↗

PubMed2004

Overexpression of TGF-beta by infiltrated granulocytes correlates with the expression of collagen mRNA in pancreatic cancer.

Pancreatic cancer is often associated with an intense production of interstitial collagens, known as the desmoplastic reaction. To understand more about desmoplasia in pancreatic cancer, the expression of mRNA for type I and III collagens and potent desmoplastic inducing growth factors transforming growth factor-beta (TGF-beta), connective tissue growth factor (CTGF), acidic and basic fibroblast growth factor (FGF), platelet-derived growth factor (PDGF) A and C and epidermal growth factor (EGF) was analysed by quantitative RT-PCR. Expression of both collagens in 23 frozen primary pancreatic cancer nodules was significantly higher than that in 15 non-neoplastic pancreatic tissues. The expressions of mRNAs for TGF-beta, acidic FGF, basic FGF and PDGF C were likewise higher in surgical cancer nodules, while that of CTGF, PDGF A and EGF were not. Among these growth factors, the expression of TGF-beta mRNA showed the most significant correlation with that of collagens (P<0.0001). By immunohistochemistry, TGF-beta showed faint cytoplasmic staining in cancer cells. In contrast, isolated cells, mainly located on the invasive front surrounding cancerous nests, were prominently and strongly stained. These TGF-beta-positive cells contained a segmented nucleus, were negative for anti-macrophage (CD68) and positive for anti-granulocyte antibodies, indicating their granulocytic nature. In conclusion, TGF-beta seemed to play a major role among the various growth factors in characteristic overproduction of collagens in pancreatic cancer. Moreover, the predominant cells that express TGF-beta were likely to be infiltrated granulocytes (mostly are neutrophils) and not pancreatic cancer cells.

Adenocarcinoma↗

PubMed2002

Sentinel node biopsy for breast cancer patients in Japan.

Sentinel node biopsy may become a standard procedure to detect lymph node metastases in early breast cancer. Numerous studies have confirmed and demonstrated the reliability of the hypothesis of sentinel node biopsy, with a high identification rate and overall accuracy connected with dye-guided and radio-guided sentinel node biopsy. To assess the benefit of sentinel node biopsy, randomized clinical trials are underway in Western countries comparing sentinel node biopsy with conventional axillary lymph node dissection. In Japan, feasibility studies on sentinel node biopsy started in the mid-1990s. The dye and radiopharmaceuticals associated with sentinel node biopsy commonly used in Western countries are not available in Japan. Japanese investigators have attempted to perform sentinel node biopsy using other dyes and radiopharmaceuticals. The results from feasibility studies have been similar to those reported previously. In conclusion, sentinel node biopsy for breast cancer patients is successful in Japan. The current status and the problems are discussed.

Breast Neoplasms↗

PubMed2001

Prostate-specific antigen induces osteoplastic changes by an autonomous mechanism.

The high prevalence of osteoplastic bone metastasis in prostate cancer (PC) is believed to be attributable to the production of osteoblast-stimulating factors by PC cells. Prostate-specific antigen (PSA) is a serine protease and an important serological marker for PC. Exposure of osteoblasts to PSA in vitro was found to result in cell proliferation and marked upregulation of transforming growth factor-beta (TGF-beta) mRNA expression. This PSA-induced increase in osteoblast proliferation was inhibited by anti-TGF-beta antibodies and serine protease inhibitors. In vivo, PSA markedly enhanced osteoplastic changes in human adult bone implanted into NOD/SCID mice without PC cells, and alpha(1)-antichymotrypsin prevented the PSA-induced increase in bone volume. PSA promotes osteoplastic change by activating an osteoblast autonomous mechanism that is independent of the production of bone growth factors by PC cells.

Aged↗

PubMed2001

Establishment of a novel species- and tissue-specific metastasis model of human prostate cancer in humanized non-obese diabetic/severe combined immunodeficient mice engrafted with human adult lung and bone.

Bone is the most common site of metastasis in prostate cancer (PC), and to generate an animal model to investigate the basis of the unique organ tropism of PC cells for bone, we engrafted humanized non-obese diabetic/severe combined immunodeficient (NOD/SCID-hu) mice with human adult bone (HAB) and lung (HAL). Human PC cell lines LNCaP (1 x 10(7)) and PC-3 (5 x 10(6)) were injected into male NOD/SCID-hu mice via the lateral tail vein at 3-4 weeks after implantation. At 8 weeks after the injection, LNCaP and PC-3 cells had metastasized specifically to HAB in 35 and 65%, respectively, of the mice. The tumors formed by LNCaP appeared to be the osteoblastic type, whereas the PC-3 tumors consisted of osteolytic lesions without any surrounding osteogenic response. A feature of experimental metastasis of PC in NOD/SCID-hu mice was its specificity for HAB tissue. Human PC cells had no or very low metastatic potential in regard to implanted HAL, mouse bone, or native mouse bone. These findings indicate that metastasis of PC cells to HAB is both species and tissue specific. The availability of this small animal model could provide a useful tool for identifying and analyzing important features of the human PC metastatic process that cannot be addressed in conventional metastasis models.

Aged↗

PubMed2001

Evaluation of the expression of NADPH oxidase components during maturation of HL-60 clone 15 cells to eosinophilic lineage.

OBJECTIVE: Superoxide-generating NADPH oxidase consists of the membrane-bound cytochrome b558 (gp91phox and p22Phox) and the cytosolic components (p67phox, p47phox, p40phox and rac). In this study, we evaluated the superoxide-generating activity and the expression of NADPH oxidase components during eosinophilic maturation using HL-60 clone 15 cell line. MATERIALS AND METHODS: HL-60 clone 15 cells were matured to eosinophils by incubation with 0.5 mM butyrate for 7 days, and NADPH oxidase components were detected by Northern blot, Western blot analyses and immunocytochemical staining. Moreover, superoxide-generating activity was examined by nitro blue tetrazolium (NBT) assay. RESULTS: Northern blot and Western blot analyses revealed that mRNAs and proteins for gp91phox, p67phox and p47phox were expressed after eosinophilic myelocyte stages, whereas mRNAs and proteins for p40phox and rac-2 were expressed from the promyelocyte stage. Interestingly, p22phox mRNA was expressed from the promyelocyte stage, but its protein was expressed after eosinophilic myelocyte stages. Consistent with the results of Western blotting, immunocytochemical staining of butyrate-induced HL-60 clone 15 cells indicated that gp91phox, p22phox, p67phox and p47phox were detected after eosinophilic myelocyte stages (eosinophilic myelocytes, eosinophilic metamyelocytes, eosinophilic band cells and eosinophilic-segmented cells), whereas p40phox and rac-2 were expressed from the promyelocyte stage. Moreover, almost the same results as those with butyrate-treated HL-60 clone 15 cells were obtained using human bone marrow cells by immunocytochemical staining. Furthermore, nitro blue tetrazolium (NBT) assay indicated that superoxide could be produced after eosinophilic myelocyte stages but not produced before the promyelocyte stage. CONCLUSIONS: Together these observations indicate that all the components for NADPH oxidase are expressed, and the superoxide-producing activity is obtained after myelocyte stages during eosinophilic maturation.

Amino Acid Sequence↗

PubMed2001

Invasive carcinoma derived from intraductal papillary-mucinous carcinoma of the pancreas: clinicopathologic and immunohistochemical study of eight cases.

Most intraductal papillary-mucinous carcinomas (IPMCs) of the pancreas are resectable and curable, but some develop into frankly invasive carcinomas. We studied the clinicopathologic features of eight cases of invasive carcinoma derived from IPMC (IC-IPMC) of the pancreas. The patients were aged 54-75 years (mean, 66.6 years); six were male and two were female. The mean tumor size was 7.7 cm (range 5.5-10.5 cm). Two patients without lymph node metastasis had no peripancreatic invasion, and survived longer (115 and 20 months). Three out of four patients with extrapancreatic invasion died of their tumors or developed tumor recurrence within a year. One patient with evidence of liver and lymph node metastasis at the time of first surgery again showed metastatic tumor 21 months later. One patient died of another cause. We also performed a comparative study of the immunohistochemical features of IC-IPMCs in 9 IPMCs (including minimally invasive cases) and 15 ductal adenocarcinomas. CEA cytoplasmic positivity was observed in most of the IC-IPMCs (87.5%) and ductal adenocarcinomas (93.3%), but in only 1 IPMC (11.1%). The frequency of p53 nuclear staining in ductal adenocarcinoma (73.3%) was higher than in IPMC (33.3%) or IC-IPMC (37.5%). In conclusion, IC-IPMC with extrapancreatic invasion should be treated as ductal carcinoma because of its aggressive behavior after resection. Some IPMCs might progress to invasive carcinoma via pathways that are different from those followed by ductal adenocarcinomas.

Adenocarcinoma, Mucinous↗

PubMed2001

Macroscopic typing with wall stricture sign may reflect tumor behaviors of advanced colorectal cancers.

No appropriate macroscopic classification of advanced colorectal cancers (A-CRC) is available for assessing their tumor behavior. In the present study, A-CRC were classified macroscopically as either stricture or nonstricture type, and the differences in clinicopathological features, mode of recurrence, and prognosis between the two types were investigated. The subjects were 166 patients with A-CRC invading beyond the muscular layer who had undergone curative surgical resection. Fresh resected specimens from these patients were used for the study. The A-CRC were classified as of stricture or nonstricture type according to whether or not they showed marked fold convergence and/or stricture of the intestinal tract (more than 30% wall shrinkage) that had the appearance of a "bow tie". Of the 166 A-CRC, 47 (28%) were classified as stricture type. This type was significantly more frequent in the colon (37%; 37/101) than in the rectum (15%; 10/65) (P = 0.003). The stricture type was more frequently associated with an abundance of fibrosis than the nonstricture type (76%; 28/37 vs 39%; 25/64 in colon; P < 0.001; 100%, 10/10 vs 42%, 23/55 in rectum; P < 0.001). The recurrence rate was also higher in the stricture type than in the non-stricture type in both the colon (51%, 19/37 vs 17%, 11/64; P = 0.003) and rectum (80%, 8/10 vs 38%, 21/55; P = 0.01). The time to recurrence was significantly shorter for the stricture type in both the colon (P < 0.001) and rectum (P = 0.02). These results indicate that the macroscopic typing of A-CRC according to the presence or absence of wall stricture sign may reflect their tumor behavior, although this behavior appears to be complex and related to tumor progression. This classification could be important clinically to assess tumor behavior in a simple way.

Aged↗

PubMed2001

Combination radiotherapy for hepatocellular carcinoma with intraductal tumor thrombus: a case report.

We report the successful treatment of hepatocellular carcinoma (HCC) associated with an intraductal tumor thrombus in a 67-year-old male. Abdominal ultrasonography (US) and computed tomography (CT) revealed intrahepatic biliary dilatation in the left hepatic lobe and an intraductal tumor thrombus. The main tumor lesion was not clearly visualized on abdominal US, dynamic CT, and hepatic angiography. We biopsied the intraductal tumor thrombus under US guidance. Histologically the biopsy specimen was a poorly differentiated HCC We thus diagnosed HCC with intraductal tumor thrombus. The total serum bilirubin level gradually rose to 3.1 mg/dl. This tumor was inoperable because of severe hepatic dysfunction. We chose to treat the patient with radiotherapy aimed only at the intraductal tumor thrombus because the main tumor was unclear. A percutaneous transhepatic biliary drainage (PTBD) tube was inserted into the common bile duct beyond the tumor thrombus and the tube was dilated. Once total serum bilirubin had reached the normal range, a combination of external beam radiation therapy (EBRT) plus an intraluminal brachytherapy, 192Ir boost was administered. The intraductal tumor thrombus was found to have vanished and the PTBD tube was removed. After this treatment, transcatheter hepatic arterial embolization was performed at the point of tumor appearance. This patient had a relatively long survival, approximately 30 months, with no clinical evidence of recurrent disease and biliary drainage was not necessary.

Aged↗

PubMed2001

Highly proliferative fibroblasts forming fibrotic focus govern metastasis of invasive ductal carcinoma of the breast.

We have already reported that invasive ductal carcinomas (IDCs) with fibrotic focus (FF) have more aggressive characteristics than those without FF. FF is composed of a mixture of fibroblasts and various amounts of collagen fibers, suggesting that highly proliferative fibroblasts forming FF increase the malignant potential of IDCs with FF. The purpose of this study was to examine whether there is a difference of proliferative activity of fibroblasts forming and not forming FF, which plays an important role in the tumor progression of IDCS: Two hundred three consecutive cases of IDC of the breast surgically treated at the National Cancer Center Hospital East formed the basis for this study. The proliferative activity of the fibroblasts forming the FF was immunohistochemically evaluated by using mouse MIB-1 monoclonal antibody against Ki-67 antigen. The MIB-1 labeling index (LI) is the percentage of fibroblasts forming FF that have positively stained nuclei, and 300 fibroblasts were counted in each FF. The significance of the proliferative activity of fibroblasts forming FF with regard to lymph node metastasis (LNM) or distant-organ metastasis (DOM) was compared with well-known prognostic parameters. Multivariate analysis demonstrated that high MIB-1 LI of fibroblasts forming FF significantly increased the relative risk of LNM and the hazard rate of DOM (P < .001 and P = .009). The present study indicated that the metastatic ability of IDCs with FF is highly dependent on the proliferative activity of the fibroblasts forming FF.

Adult↗

PubMed2001

Highly proliferative intratumoral fibroblasts and a high proliferative microvessel index are significant predictors of tumor metastasis in T3 ulcerative-type colorectal cancer.

Fibroblast and endothelial cell mitotic figures are seen in some areas of colorectal cancers, and the purpose of this study was to investigate whether the proliferative activity of fibroblasts and endothelial cells plays an important role in tumor progression of T3 ulcerative-type colorectal cancer. The tumor area of 157 colorectal cancers was divided into marginal elevated area and central depressed area (CDA), and at half the depth of the depression the CDA was in turn divided into CDA upper area (CDAU) and CDA lower area (CDAL). The proliferative activity of the tumor cells, fibroblasts, and endothelial cells was assessed immunohistochemically by double CD31/MIB-1 (anti--Ki-67 antigen) staining. The proliferative microvessel index was estimated as the percentage of microvessels lined by MIB-1-positive endothelial cells relative to the total microvessel count. Proliferative activities of tumor cells showed significant associations with those of fibroblasts and the proliferative microvessel indices in all of the corresponding areas. Proliferative activities of fibroblasts also showed significant associations with proliferative microvessel indices in all of the corresponding areas. Colorectal cancers with nodal metastasis showed significantly higher proliferative activities of fibroblasts in the CDAU than those without nodal metastasis (P <.001). The high proliferative activities of fibroblasts and proliferative microvessel indices in the CDAU showed significant associations with short distant organ metastasis-free periods in colorectal cancers without nodal metastasis (P <.001 and P =.010, respectively) and those with nodal metastasis (P =.024 and P =.036, respectively). Multivariate analysis showed that the highly proliferative fibroblasts in the CDAU significantly increased hazard rates of distant organ metastasis of colorectal cancer patients with nodal metastasis (P =.018). Proliferative activities of fibroblasts and endothelial cells in the CDAU are useful parameters for predicting tumor metastasis in patients with T3 ulcerative-type colorectal cancer. HUM PATHOL 32:401-409.

Cell Division↗

PubMed2001

Overexpression of sialyl Lewis x antigen is associated with formation of extratumoral venous invasion and predicts postoperative development of massive hepatic metastasis in cases with pancreatic ductal adenocarcinoma.

The clinicopathological factors and expression of sialyl Lewis antigens which are the cell adhesion molecules to endothelial cells were compared in relation to the extent of the postoperative hepatic metastasis in 23 consecutive patients with pancreatic ductal adenocarcinoma whose clinical courses were carefully monitored and documented. The overall survival of cases with massive hepatic metastasis (MHM) was significantly poorer than that of those with local or no hepatic metastasis (p = 0.0453). Postoperative MHM was significantly correlated with the presence of duodenal invasion (p = 0.0418), the presence of portal vein invasion (p = 0.0435), the presence of extratumoral venous invasion (p = 0.0052) and high expression of sialyl Lewis x antigen (p = 0.0022). Multivariate analysis confined significant correlation between the high expression of sialyl Lewis x antigen and the development of MHM (p = 0.0402). Kaplan-Meier analysis revealed that the overall survival of patients with a high expression of sialyl Lewis x antigen was significantly poorer than that of patients with a low expression of the antigen (p = 0.0216). These results indicate that the overexpression of sialyl Lewis x antigen plays an important role in the development of MHM, and also predicts a poorer overall survival of these patients. Further studies with more cases are warranted to confirm these results.

Adult↗

PubMed2001

Involvement of cytosolic prolyl endopeptidase in degradation of p40-phox splice variant protein in myeloid cells.

Our previous studies indicated that an alternatively spliced variant mRNA of p40-phox, a cytosolic component of NADPH oxidase, is expressed but its protein is hardly detected in myeloid cells such as promyelocytic HL-60 cells and neutrophils. Here, we have examined the stability of p40-phox variant protein in undifferentiated HL-60 cells. When in vitro-translated proteins were incubated with subcellular fractions of HL-60 cells, p40-phox variant protein but not native p40-phox was degraded by the cytosol and granule fractions. The degradation of variant protein by the granule fraction was observed using sonicated but not intact granules, suggesting that the variant protein is unlikely to be degraded by the granules in intact cells. To identify the enzyme(s) involved, we examined the effects of various enzyme inhibitors on the degradation of variant protein by the cytosol fraction. Degradation was completely inhibited by proline-specific serine protease (prolyl endopeptidase) inhibitors but not by proteasome, calpain, and metalloprotease inhibitors. Furthermore, the variant protein was degraded by a purified prolyl endopeptidase, and the degradation was protected by treating HL-60 cells with a cell-permeable inhibitor (S17092-1) for prolyl endopeptidase. These observations suggest that a cytosolic prolyl endopeptidase is involved in the degradation of p40-phox variant protein in myeloid cells.

Alternative Splicing↗

PubMed2001

Image analysis of microvessel surface area predicts radiosensitivity in early-stage laryngeal carcinoma treated with radiotherapy.

PURPOSE: The tissue oxygenation level, which is theoretically governed by distance from blood vessels, is one of the most important modulators of the radiosensitivity of carcinoma. A computed image analysis system for the detection of tissue oxygenation was developed to establish a method of predicting radiosensitivity in early-stage laryngeal carcinoma treated by curative radiotherapy. EXPERIMENTAL DESIGN: Microvessel structures labeled with CD31 antigen were investigated in 55 patients undergoing curative radiotherapy for T1 and T2 laryngeal carcinoma. We calculated (a) microvessel density [(MVD) vessels/field] under a microscope; (b) the ratio of the total microvessel number (TN):tumor area (TA) [TN:TA; vessels/mm2]; (c) the ratio of the total microvessel perimeter (TP):TA (TP:TA; mm/mm2); and (d) the ratio of tumor tissue area >150 microm from microvessels (hypoxic ratio; %) as parameters of tissue oxygenation in each whole biopsy specimen by using an image analyzer. We compared each of these factors with radiosensitivity. RESULTS: Mann-Whitney's U test revealed that tumors with a high MVD (median, 42 vessels/field), high TN:TA ratio (median=40.9 vessels/mm2), high TP:TA ratio (median, 2.92 mm/mm2), and low hypoxic ratio (median, 30.3%) had significantly greater radiosensitivity than tumors with a low MVD, low TN:TA ratio, low TP:TA ratio or high hypoxic ratio (P = 0.002, P = 0.0004, P < 0.0001, and P = 0.004, respectively). CONCLUSIONS: Prediction of radiosensitivity on the basis of the TP:TA ratio can be used as an efficient means of avoiding ineffective radiation, complications after salvage surgery, and prolonged hospital stays.

Adult↗

PubMed2000

Tumor thickness is a histopathologic predictive parameter of tumor metastasis and prognosis in patients with Dukes stage C ulcerative-type colorectal carcinoma. A two-hospital-based study.

BACKGROUND: Metastasis to the liver or lymph nodes is an important prognostic factor in patients with colorectal carcinoma. The purpose of the current study was to estimate the power of tumor thickness in predicting metachronous liver metastasis (MLM), lymph node metastasis (LNM), or overall survival (OS) in patients at two hospitals (the National Cancer Center Hospital [NCCH] and the National Cancer Center Hospital East [NCCHE]) to confirm the reproducibility of the study. METHODS: The subjects of this study were 74 and 186 consecutive patients with ulcerative-type colorectal carcinoma treated at the NCCH and NCCHE, respectively. Tumor thickness was measured in three areas: 1) the marginal elevated area (MEA), 2) the central depressed area (CDA), and 3) the most thickened area (MTA). Studies were performed with well known histologic parameters to compare the predictive power of tumor thickness on MLM, LNM, and OS using the Cox proportional hazards regression model or analysis of variance. RESULTS: A significant correlation between tumor thickness and MLM was observed only in the CDA in the NCCH patients (P = 0.005). The authors applied a tumor thickness cutoff value in the CDA of 10 mm (</= 10 mm and > 10 mm) for further study. Multivariate analyses demonstrated that a tumor CDA thickness > 10 mm was associated significantly with MLM, multiple LNMs, and OS in NCCH patients with Dukes Stage C disease (P = 0.002, P = 0.023, and P = 0.002, respectively). A significant predictive power for tumor CDA thickness for MLM, multiple LNMs, and OS was confirmed by multivariate analysis in NCCHE patients with Dukes Stage C disease (P = 0.008, P = 0.021, and P = 0.010, respectively). CONCLUSIONS: The CDA thickness of the tumor was found to be a useful predictive parameter for MLM, multiple LNMs, and OS in patients with Dukes Stage C ulcerative-type colorectal carcinoma who were being treated in two independent hospitals.

Aged↗

PubMed2000

Role of CCAAT/enhancer-binding protein site in transcription of human neutrophil peptide-1 and -3 defensin genes.

The human neutrophil defensins (human neutrophil peptides (HNPs)), major components of azurophilic granules, contribute to innate and acquired host immunities through their potent antimicrobial activities and ability to activate T cells. Despite being encoded by nearly identical genes, HNP-1 is more abundant in the granules than HNP-3. We investigated the regulation of HNP-1 and HNP-3 expression at the transcriptional level using a promyelocytic HL-60 cell line. Luciferase analysis showed that transcriptional levels of HNP-1 and HNP-3 promoters were equivalent and that an approximately 200-bp region identical between promoters was sufficient for transcriptional activity. Furthermore, overlapping CCAAT/enhancer-binding protein (C/EBP) and c-Myb sites in the region were found to be required for efficient transcription. Gel mobility shift assay demonstrated that C/EBPalpha predominantly bound to the C/EBP/c-Myb sites using HL-60 nuclear extracts. No specific binding to C/EBP/c-Myb sites was observed in nuclear extracts from mature neutrophils, which expressed neither C/EBPalpha protein nor HNP mRNAs. Taken together, these findings suggest that the difference in the amounts of HNP-1 and HNP-3 peptides in neutrophils is caused by posttranscriptional regulation and that C/EBPalpha plays an important role in the transcription of HNP genes in immature myeloid cells.

5' Untranslated Regions↗