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Human Breast Carcinoma (human + breast_carcinoma)
Terms modified by Human Breast Carcinoma Selected AbstractsCopper-transporting P-Type Adenosine Triphosphatase (ATP7B) Is Expressed in Human Breast CarcinomaCANCER SCIENCE, Issue 1 2002Atsuko Kanzaki This is the first report to show that a copper-transporting P-type adenosine triphosphatase, ATP7B, is expressed in certain breast carcinomas, and a priori knowledge of its expression is important for the choice of therapy. We investigated the hypothesis that ATP7B, which was shown to be associated with cisplatin resistance in vitro, is expressed in certain breast carcinomas. To test this hypothesis, ATP7B expression and protein level were examined in 41 breast carcinomas using RT-PCR and immunohistochemistry. ATP7B gene/protein could be detected in 22.0% (9/41) of breast carcinomas and ATP7B gene expression was correlated well with the protein expression. In nine ATP7B-positive tumors, adjacent normal breast tissue was similarly analyzed, revealing that ATP7B is upregulated in breast carcinoma. ATP7B gene expression in poorly differentiated carcinoma was significantly higher than that in well-/moderately differentiated carcinoma (P=0.012). Furthermore, we found no association between the ATP7B gene/protein expression and that of MDR1, MRP1, LRP and BCRP. These findings suggested that ATP7B gene expression might be a chemoresistance marker for cisplatin in patients with poorly differentiated breast carcinoma. [source] Expression of Multidrug Resistance-related Transporters in Human Breast CarcinomaCANCER SCIENCE, Issue 4 2001Atsuko Kanzaki The expression levels of mRNA for multidrug resistance 1 (MDR1) gene, multidrug resistance protein 1 (MRP1), lung resistance-related protein (LRP) and breast cancer resistance protein (BCRP), which confer multidrug resistance in vitro, were examined in 43 untreated breast carcinoma patients, of whom 38 subsequently received doxorubicin-based chemotherapy after surgery, in order to elucidate the roles of these genes in drug resistance in vivo. The mRNA levels were determined using a semi-quantitative reverse-transcription polymerase chain reaction method in breast carcinoma tissues including at least 80% carcinoma cells. The expression level of BCRP gene was low and did not vary markedly in comparison with that of MDR1, MRP1 or LRP gene. The expressions of MDR1 and MRP1 genes were correlated with each other, but the expression of BCRP or LRP gene did not correlate with that of other genes. These four gene expressions were independent of age, TNM categories and the status of progesterone or estrogen receptor. The expression levels of these four genes were not related to the relapse or prognosis of the 38 patients treated with doxorubicin-based chemotherapy. P-glycoprotein (P-gp)/MDRl, MRP1 and LRP may play more important roles than BCRP in chemotherapy of human breast carcinoma. [source] In situ estrogen production and its regulation in human breast carcinoma: From endocrinology to intracrinologyPATHOLOGY INTERNATIONAL, Issue 11 2009Hironobu Sasano The great majority of breast carcinomas arising in postmenopausal women are estrogen dependent or positive for estrogen receptor (ER) in carcinoma cells despite markedly low plasma or circulating estrogen concentrations. In these patients, biologically active estrogens are locally produced from circulating inactive steroids including adrenal androgens in an intracrine mechanism in the breast cancer tissues and confer estrogenic activities on carcinoma cells. A series of enzymes are involved in this intra-tumoral or in situ production of estrogens in breast carcinoma tissues but aromatase, a member of the cytochrome P450 family, is a key enzyme of estrogen production through conversion from circulating adrenal androgens in estrogen-dependent postmenopausal breast cancer. It then becomes important to identify the sites of this estrogen production. There has been, however, controversy regarding intra-tumoral localization of aromatase in breast carcinoma, especially whether intra-tumoral production of estrogens through aromatase occurs in carcinoma or stromal cells. The enzyme was demonstrated to be expressed in both carcinoma and stromal cells in breast carcinoma tissues on immunohistochemistry with a well-characterized mAb 677 and combined laser capture microdissection/qualitative reverse transcriptase,polymerase chain reaction. Intra-tumoral aromatase in both of these cell types was subsequently demonstrated to be induced by carcinoma,stromal interactions associated with carcinoma invasion in breast tissue. The signals through various nuclear receptors, especially estrogen-related receptor-, in carcinoma cells and liver receptor homologue-1 in adipocytes adjacent to carcinoma invasion, in conjunction with various cytokines and/or growth factors, play pivotal roles in this induction of intra-tumoral aromatase. This increased aromatase subsequently results in increased in situ estrogen concentrations of breast cancer. Aromatase inhibitors are currently established as the gold standard for the treatment for ER-positive breast carcinoma but resistance to the therapy still remains to be solved by other modes of suppression of intra-tumoral estrogen production. [source] Chromogenic in situ hybridization analysis of HER-2/neu status in breast carcinoma: Application in screening of patients for trastuzumab (Herceptin®) therapyPATHOLOGY INTERNATIONAL, Issue 8 2001Hiroyuki Kumamoto Evaluation of HER-2/neu status is important in the management of patients with breast carcinoma, especially in determining the possible application of trastuzumab, a humanized anti-HER-2/neu monoclonal antibody. Chromogenic in situ hybridization (CISH) detection of the HER-2/neu oncogene is a newly developed in situ hybridization method that utilizes a robust and unique-sequence DNA probe labeled with digoxygenin, and sequential incubations with antidigoxygenin fluorescein, antifluorescein peroxidase, and diaminobenzidine. In this study, we examined 20 archival specimens of human breast carcinoma using CISH, and we correlated findings with immunohistochemical findings for HER-2/neu. HER-2/neu immunohistochemistry was carried out with HercepTestTM, a standardized immunohistochemical examination system for HER-2/neu overexpression in surgical pathology specimens. CISH analysis could be done in 18 out of 20 cases examined. Gene copy signals for HER-2/neu were recognized as intranuclear brown dots in both neoplastic and non-neoplastic cells. Seven carcinomas showed an increased number or size of signals and were interpreted as being positive for HER-2/neu amplification. Eight cases were positive with the HercepTestTM. Seven out of eight carcinoma cases found to overexpress immunoreactive HER-2/neu also demonstrated HER-2/neu gene amplification following CISH analysis. There was a significant correlation between immunohistochemical and CISH analyses (P< 0.001). We found that CISH was a specific, sensitive and easily applicable method for the detection of HER-2/neu gene amplification, which may be used together with immunohistochemical examination for the evaluation of patients with breast carcinoma. [source] Synthesis, Photophysical Studies and Anticancer Activity of a New Halogenated Water-Soluble PorphyrinPHOTOCHEMISTRY & PHOTOBIOLOGY, Issue 4 2007Janusz M. D, browski ABSTRACT A water-soluble halogenated porphyrin, namely 5,10,15,20 -tetrakis(2-chloro-3-sulfophenyl)porphyrin (TCPPSO3H), was prepared and evaluated as sensitizer for photodynamic therapy (PDT). Photophysical properties of TCPPSO3H, such as high photostability, long triplet lifetime and high singlet oxygen quantum yield suggest high effectiveness of this class of halogenated porphyrins in PDT. TCPPSO3H is non-toxic in the dark and causes a significant photodynamic effect examined against MCF7 (human breast carcinoma), SKMEL 188 (human melanoma) and S91(mouse melanoma) cell lines upon red light irradiation (cutoff < 600 nm) at low light doses. Time-dependent cellular uptake of TCPPSO3H reached plateau at 120 min and was the highest for S91, 20% lower for MCF7 and 70% lower for SKMEL 188. Our results show that this halogenated water-soluble porphyrin is an efficient photosensitizer and reveal the potential of this class of compounds as PDT agents. [source] Human liver-specific organic anion transporter-2 is a potent prognostic factor for human breast carcinomaCANCER SCIENCE, Issue 10 2007Mitsuhisa Muto Human liver-specific organic anion transporter-2 (LST-2/OATP8/SLCO1B3) has been demonstrated to be expressed in various gastrointestinal carcinomas and also to play pivotal roles in the uptake of a wide variety of both endogenous and exogenous anionic compounds, including bile acids, conjugated steroids and hormones, into hepatocytes in the human liver. However, the biological significance of LST-2 in human carcinomas remains unknown. In the present study, we examined the expression of LST-2 in 102 cases of breast carcinoma using immunohistochemistry and correlated the findings with various clinicopathological parameters in order to examine the possible biological and clinical significance of LST-2. LST-2 immunoreactivity was detected in 51 cases (50.0%); of these 51 positive cases, LST-2 immunoreactivity was inversely correlated with tumor size (P = 0.0289). In addition, LST-2 immunoreactivity was significantly associated with a decreased risk of recurrence and improved prognosis by both univariate (P = 0.02 and P = 0.01) and multivariate (P = 0.03 and P = 0.01) analyses. In the estrogen receptor-positive groups, the LST-2-positive patients showed good prognoses. Considering that LST-2 transports estrone-3-sulfate, these results suggest that LST-2 overexpression is associated with a hormone-dependent growth mechanism of the breast cancer. The results of our present study demonstrate that LST-2 immunoreactivity is a potent prognostic factor in human breast cancer. (Cancer Sci 2007; 98: 1570,1576) [source] Purification and characterization of 66-kDa glycoprotein from human breast carcinomaCANCER SCIENCE, Issue 9 2007Renqing Feng We extracted a 66-kDa glycoprotein (GP-1D8) from breast invasive ductal carcinoma tissues. The monoclonal antibody (mAb) against GP-1D8 was prepared in our laboratory. Western blotting with the purified protein using the mAb demonstrated a single band of 66 kDa. Immunocytochemical and immunohistochemical analysis revealed strong expression of GP-1D8 protein in the cytoplasm of MCF-7 cells and different types of breast carcinoma tissues, but GP-1D8 is absent in normal breast and benign breast tumor tissues. Glycosylation analysis showed GP-1D8 contained methylated salic acid. GP-1D8 was identified using mass-spectrometric techniques and N -terminal sequencing. These data were used to identify the protein through the SWISSPROT protein sequence database and BLAST homology search. These results showed GP-1D8 had some similarity to human albumin precursor. Co-immunoprecipitation assays of lysate from MCF-7 cells and mass spectrometric analysis revealed the interaction of GP-1D8 with ,-tubulin. This is the first time human breast carcinoma tissues and MCF-7 cells have been shown to express a 66-kDa glycoprotein similar to human albumin precursor. These results might be important in the detection of novel potential biomarkers and may provide insight into the molecular mechanisms of tumorigenesis. (Cancer Sci 2007; 98: 1344,1349) [source] Expression of Multidrug Resistance-related Transporters in Human Breast CarcinomaCANCER SCIENCE, Issue 4 2001Atsuko Kanzaki The expression levels of mRNA for multidrug resistance 1 (MDR1) gene, multidrug resistance protein 1 (MRP1), lung resistance-related protein (LRP) and breast cancer resistance protein (BCRP), which confer multidrug resistance in vitro, were examined in 43 untreated breast carcinoma patients, of whom 38 subsequently received doxorubicin-based chemotherapy after surgery, in order to elucidate the roles of these genes in drug resistance in vivo. The mRNA levels were determined using a semi-quantitative reverse-transcription polymerase chain reaction method in breast carcinoma tissues including at least 80% carcinoma cells. The expression level of BCRP gene was low and did not vary markedly in comparison with that of MDR1, MRP1 or LRP gene. The expressions of MDR1 and MRP1 genes were correlated with each other, but the expression of BCRP or LRP gene did not correlate with that of other genes. These four gene expressions were independent of age, TNM categories and the status of progesterone or estrogen receptor. The expression levels of these four genes were not related to the relapse or prognosis of the 38 patients treated with doxorubicin-based chemotherapy. P-glycoprotein (P-gp)/MDRl, MRP1 and LRP may play more important roles than BCRP in chemotherapy of human breast carcinoma. [source] BUB1 infrequently mutated in human breast carcinomas,,HUMAN MUTATION, Issue 5 2003Anita Langerød Abstract The BUB1 gene is a key player in the mitotic spindle checkpoint machinery that monitors proper segregation of sister chromatides during mitosis. It has been suggested that mutations in BUB1 may disrupt the spindle checkpoint and thereby cause chromosomal instability, which is a hallmark of solid tumors including those from the breast. From a series of breast carcinomas we selected 20 cases with genomic instability, as scored by Comparative Genome Hybridization (CGH), and without somatic TP53 (p53) mutations, and sequenced the entire coding region of the BUB1 gene. Two different constitutional sequence variants were found; a base substitution in exon 5, c.481G>A (CAG>CAA, a synonymous change encoding Gln144) in two samples, and a base substitution 8 bp upstream of exon 10, c.1007-8T>C in two other samples. No somatic mutations were detected. These results indicate that genomic instability scored as copy number alterations by CGH in TP53 wild type breast carcinomas is not caused by somatic mutations in the BUB1 gene. © 2003 Wiley-Liss, Inc. [source] Hyaluronidase reduces human breast cancer xenografts in SCID miceINTERNATIONAL JOURNAL OF CANCER, Issue 2 2002Svetlana Shuster Abstract A hyaluronan-rich environment often correlate with tumor progression. and may be one mechanism for the invasive behavior of malignancies. Eradication of hyaluronan by hyaluronidase administration could reduce tumor aggressiveness and would provide, therefore, a new anti-cancer strategy. Hyaluronan interaction with its CD44 receptor and the resulting signal transduction events may be among the mechanisms for hyaluronan-associated cancer progression. We have shown previously that hyaluronidase treatment of breast cancer cells in vitro not only eradicates hyaluronan but also modifies expression of CD44 variant exons of tumor cells. We now determine if such effects occur in vivo and if it is accompanied by tumor regression. SCID mice bearing xenografts of human breast carcinomas were given intravenous hyaluronidase. Tumor volumes decreased 50% in 4 days. Tumor sections showed decreased hyaluronan. Intensity of staining for CD44s was not affected, whereas staining for specific CD44 variant exon isoforms was greatly reduced in residual tumors. Necrosis was not evident. Hyaluronidase, used previously as an adjunct in cancer treatment, presumably to enhance penetration of chemotherapeutic drugs, may itself have intrinsic anti-cancer activity. Removing peritumor hyaluronan appears to cause an irreversible change in tumor metabolism. Continuous hyaluronan binding to CD44 variant exon isoforms may also be required to stabilize inherently unstable isoforms that participate perhaps in tumor progression. Further investigation is required to confirm a cause and effect relationship between loss of hyaluronan, changes in CD44 variant exon expression and tumor reduction. If confirmed, hyaluronidase may provide a new class of anti-cancer therapeutics and one without toxic side effects. © 2002 Wiley-Liss, Inc. 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