Yohei Hamaguchi

Yokohama City University, Yokohama, Kanagawa, Japan

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Publications (18)49.82 Total impact

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    ABSTRACT: The feasibility and efficacy of adriamycin or epirubicin in combination with cyclophosphamide followed by weekly paclitaxel (AC/EC-weekly PAC) as adjuvant chemotherapy for breast cancer was investigated. Node-positive breast cancer was treated with AC/ EC-weekly PAC, namely AC at 60/600 mg/m(2) or EC at 90/600 mg/m(2) x4 at three-week intervals, followed by weekly PAC (80 mg/m(2)) x 12, namely four cycles of single weekly administration for three weeks followed by a one-week rest (3 x 4 PAC) or single weekly administration for 12 consecutive weeks (12 PAC). One hundred and three of 109 consecutive patients enrolled were analyzed, of whom 96 (93.2%) completed the regimen. Grade 3/4 neutropenia occurred in 52.4% receiving AC/EC, and 10.9% of 55 receiving 12 PAC but only 2.1% of 48 receiving 3 x 4 PAC. Neuropathy disorders occurred in more than half receiving PAC, which did not improve after one-week rest in 3 x 4 PAC. AC/EC-weekly PAC is feasible and without serious complications.
    Anticancer research 06/2009; 29(5):1515-20. · 1.71 Impact Factor
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    ABSTRACT: Fine-needle aspiration cytology (FNA) is less traumatic and technically easy to apply to small breast tumors. A total of 382 cases of palpable breast lesions that had undergone fine needle aspiration and histopathologic diagnosis were reviewed with an emphasis on the rate of false positive diagnoses in benign breast lesions. A diagnosis of " malignant " was made in 98 of the 382 specimens (25.6%). The predictive value for malignancy was 97.9%. The sensitivity, specificity, and accuracy of FNA were 86.3%, 98.2%, and 93.2%, respectively, when the " suspicious " group was considered positive for malignancy. The histologic subtypes of the 4 false-positive cases were epithelial proliferative lesions, ductal or lobular hyperplasia. None of these 4 cases were definitely diagnosed as " malignant " by radiological studies. Four false-negative cases by FNA were suspicious for malignancy radiologically. There was no specific pathological subtype associated with false-negative status on FNA in this study. Palpable breast tumors can be definitively diagnosed based on a combination of physical examination, radiological studies and FNA, when the radiological studies concur with the diagnosis by FNA.
    Breast Cancer 02/2007; 14(4):388-92. · 1.33 Impact Factor
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    ABSTRACT: Matrilysin, MMP-7, is an important target for anti-metastasis therapy of colorectal cancer because it is a strong proteolytic factor secreted from the cancer cell itself and it induces tumor angiogenesis. In a previous report, we showed that matrilysin accelerated human umbilical vein endothelial cell (HUVEC) proliferation in low serum conditioned medium. In the present study, we show that matrilysin stimulation decreased VE-cadherin expression, induced accumulation of beta-catenin in the nucleus of the HUVEC, and up-regulated matrilysin mRNA expression. These results compel a hypothesis that matrilysin cleaves VE-cadherin and releases beta-catenin from the VE-cadherin/catenin complex; the free beta-catenin can activate T-cell factor (Tcf) DNA binding protein, which accelerates cell proliferation and matrilysin expression.
    Oncology Reports 03/2006; 15(2):311-5. · 2.30 Impact Factor
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    ABSTRACT: To examine four-node axillary sampling assisted by a blue dye (4NAS/dye) technique as a sentinel node biopsy (SNB) for breast cancer. Lymphatic mapping was performed by injection of patent blue for 33 consecutive cases with breast cancer. Axillary sampling was performed until four nodes were obtained. This was followed by back-up axillary lymph node dissection to examine the feasibility of 4NAS/dye. The same study with 30 cases was conducted at an independent hospital to confirm the feasibility of this method. This method was then applied to 101 consecutive clinically node-negative patients to avoid axillary-node dissection, with intraoperative diagnosis made by frozen section examination. The median numbers of blue-stained nodes and nodes excised by 4NAS/dye were 1.7 and 3.4, respectively. The identification rate of sentinel lymph nodes (SNs) was 81.8% using the dye alone and 97.0% when the combination was used. Pathological examination revealed that the nodal status was correctly predicted by the dye alone in 62.5% of cases with metastasis, whereas in 100% by 4NAS/dye. The dye alone was not sufficient to identify SNs, especially in cases with prior excisional biopsy. The identification rate of SNs and the accuracy rate in another feasibility study were 100% and 92.5% in 30 consecutive cases, respectively. 4NAS/dye successfully detected SNs in 100 of 101 cases of the subsequent observational study with an acceptable post-operative axillary morbidity and thus succeeded as an SNB. The 4NAS/dye method is reliable for the detection of SNs. This method could be applied to observational studies without radio-isotope.
    European Journal of Surgical Oncology 01/2006; 31(10):1119-24. · 2.61 Impact Factor
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    ABSTRACT: We assessed changes in gene expression of hypertrophied liver after portal vein ligation (PL) in a test group of rats compared to a control group, which had the same size liver but no PL. The portal veins of the left and median lobes in the test group were ligated in an initial operation. Four days after the PL, the liver volume of the posterior caudate lobe (5%) increased two-fold and comprised 10% of the liver. A 90% hepatectomy was then performed, leaving only the hypertrophied posterior caudate lobe, and leaving the normal anterior and posterior caudate lobes (10%) in the control (sham) group. A comparison of the expression profiles between two groups was performed using cDNA microarrays and the hepatic ATP level was measured. The survival rate for the PL group was significantly higher than for the sham group at 4 days after the hepatectomy (56.3% and 26.7%, P < 0.05). Gene expression of cyclin D1, proliferating cell nuclear antigen, cyclin A and B was upregulated, and the cyclin-dependent kinase inhibitor was downregulated. Increases were observed in: (i) pyruvate dehydrogenase, the tricarboxylic acid cycle cycle regulator, (ii) acyl-CoA dehydrogenase, the oxidation regulator, and (iii) cytochrome oxidases, the oxidative phosphorylation regulator. Hepatic ATP concentration after hepatectomy was better maintained in the PL group than in the sham group (0.48 +/- 0.01 micromol/ml vs. 0.33 +/- 0.01 micromol/ml, P < 0.05). The regenerating liver increased tolerance for extended hepatectomy compared to normal liver. It is believed that this is because the induced rapid regeneration of the remaining liver after hepatectomy increases ATP metabolism.
    Liver international: official journal of the International Association for the Study of the Liver 06/2004; 24(3):253-8. · 3.87 Impact Factor
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    ABSTRACT: We assessed the utility of dynamic magnetic resonance imaging (MRI) in differentiating benign from malignant lesions of the breast and then applied MRI to diagnose intraductal breast tumors with nipple discharge. Gadolinium (Gd)-enhanced MR mammography was performed on 74 patients with breast tumors and 8 patients with nipple discharge. The steepest slopes of the contrast medium uptake (S slope) s from time-intensity curves were significantly different between malignant and benign lesions. At S slope threshold of 0.95% /second, malignancy was predicted with a sensitivity and specificity of 75% . Six of 8 cases with nipple discharge were successfully identified by MR ductography by injecting Gd-DTPA into discharging ducts. Among them, 2 non-invasive ductal carcinomas were differentiated from benign lesions by the S slope value. Dynamic MR mammography is an useful modality for differentiating breast lesions and has potential for evaluating intraductal lesions with nipple discharge.
    Breast Cancer 02/2004; 11(3):288-94. · 1.33 Impact Factor
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    ABSTRACT: Docetaxel is an active agent as first-line chemotherapy in patients with advanced breast cancer at a dosage of 100 mg/m2. However, the efficacy of this agent as a first-line drug when used at a lower dosage is unclear. This study was performed to evaluate the clinical efficacy and safety of 60 mg/m2 docetaxel for the treatment of breast cancer. This study enrolled 23 patients with advanced and/or metastatic breast cancer, who had not been treated with an anthracycline or taxane previously. Treatment with docetaxel was continued in patients showing a response until there was evidence of disease progression or unacceptable toxicity. Among 20 fully evaluated patients, the overall response rate was 50.0% and the median time to progression was 31 weeks. The most commonly observed adverse events were neutropenia (78.2%) and fatigue (60.9%). Fluid retention occurred in only 8.7% of the patients. Adverse events did not cause discontinuation of the treatment. Docetaxel achieved good disease control with mild adverse events in first-line treatment at a dosage of 60 mg/m2.
    Breast Cancer 02/2004; 11(4):374-9. · 1.33 Impact Factor
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    ABSTRACT: Matrix metalloproteinases (MMP) are considered to play important roles in angiogenesis. In angiogenic processes, endothelial cells secrete MMP-2 or MMP-1 to dissolve the basement membrane or connective tissue around the vessels. MMP-7 (matrilysin) is secreted from the neovasculars induced by cancer and is a metastatic factor of colorectal cancer. The effect of matrilysin on angiogenesis is still unclear, however. We therefore examined the effect of MMP-7 on the proliferation of human umbilical vein endothelial cells (HUVECs) in vitro. Our results showed that recombinant MMP-7 (rMMP-7) accelerated the proliferation of endothelial cells dose-dependently, and did so for endothelial cells cultured not only on type IV collagen, but also on type I collagen. MMP-7 also upregulated MMP-1, -2 secretion, but did not stimulate vascular endothelial growth factor (VEGF) secretion. From this study, we conclude that MMP-7 directly induces angiogenesis, and that therefore MMP-7 would be a good target of cancer therapy.
    Cancer Letters 04/2002; 177(1):95-100. · 4.26 Impact Factor
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    ABSTRACT: We report a 35-year-old woman with locally advanced mucinous carcinoma of the breast with sudden growth acceleration. A pea-sized mass developed into an ulcerated large tumor within 1 month. After the combination of chemotherapy, radiation and hyperthermia, a radical mastectomy was performed, followed by repair of the skin defect by latissimus dorsi and rectus abdominis musculocutaneous flaps. Histological examination revealed a pure mucinous carcinoma with axillary lymph node involvement. Estrogen and progesterone receptors were not detected in the tumor. Twenty-five months after treatment, there is no sign of recurrent disease. Pure mucinous carcinoma generally has a less aggressive growth pattern as defined by tumor size, adherence to the overlying skin/bottom fasciae, estrogen and progesterone receptor positive and primary lymph axillary lymph node metastases. This case showed completely opposite features to all of these typical biological features of pure mucinous carcinomas.
    Japanese Journal of Clinical Oncology 03/2002; 32(2):64-7. · 1.90 Impact Factor
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    ABSTRACT: The efficacy of a phosphorothioate antisense oligonucleotide (ASO) for KDR/Flk-1 (KDR/Flk-1-ASO), an endothelial cell-specific vascular endothelial growth factor (VEGF) receptor, was investigated on the peritoneal dissemination and angiogenesis of a human gastric cancer cell line in nude mice. Green fluorescent protein (GFP)-transduced NUGC-4 (NUGC-4-GFP) human gastric cancer cells were implanted into the peritoneal cavity of nude mice. KDR/Flk-1-ASO, -SO, or phosphate-buffered saline was administrated from days 7 to 14, 200 microg/mouse, once a day. The mice were sacrificed on day 28. Disseminated peritoneal tumor nodules expressing GFP were visualized by fluorescence microscopy. KDR/Flk-1-ASO significantly decreased the extent of peritoneal dissemination of the tumors. The number of cells undergoing apoptosis was significantly increased in the KDR/Flk-1-ASO-treated tumors. Microvessel density was significantly reduced in the KDR/Flk-1-ASO-treated tumor nodules. The KDR/Flk-1 antisense strategy, therefore, decreases tumor dissemination apparently by inhibiting angiogenesis.
    Cancer Gene Therapy 03/2002; 9(2):197-201. · 2.95 Impact Factor
  • The European Journal of Surgery 02/2002; 168(7):428-30.
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    ABSTRACT: Brain metastases occur in 15% to 30% of breast cancer patients, usually as a late event. The patterns of metastases to different organs are determined by the tumor cell phenotype and interactions between the tumor cells and the organ environment. We investigated the gene expression profile occurring in brain metastases from a breast cancer cell line. We used cDNA microarrays to compare patterns of gene expression between the mouse breast cancer cell line Jyg MC (A) and a subline that often metastasis to brain, (B). By Microarray analysis about 350 of 21,000 genes were significantly up-regulated in Jyg MC (B). Many candidate genes that may be associated with the establishment of brain metastasis from breast cancer were included. Interestingly, we found that the expression of astrocyte derived cytokine receptors (IL-6 receptor, TGF-beta receptor and IGF receptor) were significantly increased in Jyg MC (B) cells. These results were confirmed by RT-PCR. These results suggest that cytokines produced by glial cells in vivo may contribute, in a paracrine manner, to the development of brain metastases from breast cancer cells.
    Breast Cancer 02/2002; 9(1):26-32. · 1.33 Impact Factor
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    ABSTRACT: We confirmed the expression of cathepsin K, the most abundant and specific cysteine protease found in osteoclasts, at the mRNA level in most of our cases of breast cancer, and even at the protein level in bone metastatic lesions. Therefore, we investigated the functions of cathepsin K in osteoclasts with special attention to bone metastasis from breast cancer. Mouse osteoclast-like cells (OCLs) were established by coculture of mouse bone marrow cells and osteoblastic cells. Rodent cathepsin K antisense (AS) or random control (CL) oligonucleotides were added on day 0, 3, or 6 of culture. Tartrate-resistant acid phosphatase staining confirmed the formation of OCLs after 9 d of incubation. AS treatment significantly reduced both the number of TRAP-positive cells and the percentage of multinuclear cells. For the pit-forming assay, after 9 d of incubation, mature OCLs were collected and incubated on ivory slices with AS or CL for 48 h. The antisense oligonucleotides also inhibited the bone-resorbing activity of OCLs. CL treatment did not affect either the number of TRAP-positive cells or pit formation. Cathepsin K may play important roles in bone resorption as well as in differentiation of osteoclasts. These findings indicate that the inhibition of this enzyme may prevent the development of bone metastasis from breast cancer.
    Molecular Carcinogenesis 11/2001; 32(2):84-91. · 4.27 Impact Factor
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    ABSTRACT: We confirmed the expression of cathepsin K, the most abundant and specific cysteine protease found in osteoclasts, at the mRNA level in most of our cases of breast cancer, and even at the protein level in bone metastatic lesions. Therefore, we investigated the functions of cathepsin K in osteoclasts with special attention to bone metastasis from breast cancer. Mouse osteoclast-like cells (OCLs) were established by coculture of mouse bone marrow cells and osteoblastic cells. Rodent cathepsin K antisense (AS) or random control (CL) oligonucleotides were added on day 0, 3, or 6 of culture. Tartrate-resistant acid phosphatase staining confirmed the formation of OCLs after 9 d of incubation. AS treatment significantly reduced both the number of TRAP-positive cells and the percentage of multinuclear cells. For the pit-forming assay, after 9 d of incubation, mature OCLs were collected and incubated on ivory slices with AS or CL for 48 h. The antisense oligonucleotides also inhibited the bone-resorbing activity of OCLs. CL treatment did not affect either the number of TRAP-positive cells or pit formation. Cathepsin K may play important roles in bone resorption as well as in differentiation of osteoclasts. These findings indicate that the inhibition of this enzyme may prevent the development of bone metastasis from breast cancer. © 2001 Wiley-Liss, Inc.
    Molecular Carcinogenesis 09/2001; 32(2):84 - 91. · 4.27 Impact Factor
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    ABSTRACT: We have systematically characterized gene expression patterns in 49 adult and embryonic mouse tissues by using cDNA microarrays with 18,816 mouse cDNAs. Cluster analysis defined sets of genes that were expressed ubiquitously or in similar groups of tissues such as digestive organs and muscle. Clustering of expression profiles was observed in embryonic brain, postnatal cerebellum, and adult olfactory bulb, reflecting similarities in neurogenesis and remodeling. Finally, clustering genes coding for known enzymes into 78 metabolic pathways revealed a surprising coordination of expression within each pathway among different tissues. On the other hand, a more detailed examination of glycolysis revealed tissue-specific differences in profiles of key regulatory enzymes. Thus, by surveying global gene expression by using microarrays with a large number of elements, we provide insights into the commonality and diversity of pathways responsible for the development and maintenance of the mammalian body plan.
    Proceedings of the National Academy of Sciences 02/2001; 98(5):2199-2204. · 9.81 Impact Factor
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    ABSTRACT: Telomerase activity has been reported in cancer cells after treatment with antineoplastic agents. Assessment of telomerase activity could be a valuable tool to measure the reduction of aggression caused by chemotherapy. This study was designed to investigate the significance of telomerase for chemotherapy with respect to Adriamycin (ADM)-resistance. MCF-7 and its ADM-resistant line (AdrR) were treated with ADM, 5-fluorouracil (5FU) or taxotere (TAXO). Telomerase activity and human telomerase RNA component (hTR) were quantitatively measured by the telomeric repeat amplification protocol assay and RT-PCR, respectively. Cell counting and MTT assay were also performed. In MCF-7, enzyme activity was significantly reduced by ADM and 5FU treatments. In AdrR, 5FU and TAXO reduced enzyme activity, while ADM significantly increased the activity. No significant changes in hTR were seen in these two cell lines after treatment with any of these drugs. When Bcl-2 expression was examined after drug treatments, ADM increased Bcl-2 expression in AdrR cells, while not changing it in MCF-7 cells. We conclude that an unusual reaction of telomerase activity in AdrR may explain, at least in part, one of the mechanisms of the malignant biological behavior related with the drug-resistance to ADM.
    Cancer Letters 08/1999; 141(1-2):187-94. · 4.26 Impact Factor
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    ABSTRACT: Telomerase activity has been reported in cancer cells after treatment with antineoplastic agents. Assessment of telomerase activity could be a valuable tool to measure the reduction of aggression caused by chemotherapy. This study was designed to investigate the significance of telomerase for chemotherapy with respect to Adriamycin (ADM)-resistance. MCF-7 and its ADM-resistant line (AdrR) were treated with ADM, 5-fluorouracil (5FU) or taxotere (TAXO). Telomerase activity and human telomerase RNA component (hTR) were quantitatively measured by the telomeric repeat amplification protocol assay and RT-PCR, respectively. Cell counting and MTT assay were also performed. In MCF-7, enzyme activity was significantly reduced by ADM and 5FU treatments. In AdrR, 5FU and TAXO reduced enzyme activity, while ADM significantly increased the activity. No significant changes in hTR were seen in these two cell lines after treatment with any of these drugs. When Bcl-2 expression was examined after drug treatments, ADM increased Bcl-2 expression in AdrR cells, while not changing it in MCF-7 cells. We conclude that an unusual reaction of telomerase activity in AdrR may explain, at least in part, one of the mechanisms of the malignant biological behavior related with the drug-resistance to ADM.
    Cancer Letters - CANCER LETT. 01/1999; 141(1):187-194.
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    ABSTRACT: Bone resorption markers have become available for the diagnosis of bone metastasis. We evaluated cross-linked collagen C-and N-telopeptides (ICTP and NTx) in diagnosing bone metastasis from breast cancer. For a threshold of 4.5 ng/ml of 1CTP and 55.0 pmol BCE/micromol of NTx, bone metastasis could be predicted with an accuracy of 84% and 63%, respectively. All the patients who had metastatic lesions, but showed lower than 4.5 ng/ml of ICTP, had a solitary lesion of bone metastasis. Although ICTP is not sensitive enough to detect an early stage of bone metastasis, it is a better biochemical marker than NTx for detecting bone metastasis from breast cancer.
    Oncology Reports 9(3):595-8. · 2.30 Impact Factor