Increased expression of ADAM family members in human breast cancer and breast cancer cell lines

Purpose ADAMs (A Disintegrin and Metalloprotease) are multifunctional, membrane-bound cell surface glycoproteins, which have numerous functions in cell growth, differentiation, and motility. We wished to investigate the expression of ADAM 9, 10, 12, 15, and in human breast cancer.Methods Expression of ADAMs was determined in breast cancer specimens and the corresponding non-neoplastic breast tissue from 24 patients, and in the MCF-7 and MDA-MB 453 breast cancer cell lines via quantitative RT-PCR and immunohistochemistry. The effects of anti-ADAM antibodies on cell proliferation were assessed by measuring DNA-synthesis.Results Breast cancer tissue samples showed increased mRNA expression of ADAM 9, 12, and 17, whereas ADAM 10 and 15 were not differently expressed. Protein expression was studied by immunohistochemistry. All ADAMs were expressed in MCF-7 and MDA-MB453 cell lines, with the highest expression levels being observed for ADAM 9, 12, and 17. Application of anti-ADAM 15 and anti-ADAM 17 antibodies significantly inhibited the proliferation of both MCF-7 and MDA-MB453 breast cancer cell lines. In contrast, the growth of MCF-7 cells appeared to be stimulated by the administration of anti-ADAM 12 antibody.Conclusion The results of this study suggest that ADAMs are differentially expressed in human breast cancer and are capable of modulating tumour cell growth.     

Increased serum concentrations of cholesterol and triglycerides in the progression of breast cancer

Summary The course of serum concentrations of cholesterol and triglycerides was investigated in patients with advanced breast cancer. The patients studied were divided into two groups according to their clinical status: group-I consisted of 51 patients who already had metastases at the start of the investigation, but progressed further during the time of observation; group-II consisted of 14 patients in remission who experienced recurrence of disease while under observation. In group-I, 28 patients (54.9%) were found to have normal serum triglyceride levels at the beginning of the observation period; 22 patients (78.6%) from this group experienced a significant (P<0.0001) increase above the normal range upon further disease progression. Similarly, serum cholesterol levels were normal in 32 patients (62.8%) at the start of the investigation, but increased significantly (P<0.0001) above the normal range upon disease progression. In group-II, 8 patients (57.2%) had normal serum triglyceride levels at the beginning of the observation period, but the levels inreased in 4 patients (50%) significantly (P<0.005) upon the occurrence of metastases. Within the same group, a significant increase (P<0.001) of initially normal serum cholesterol levels was found in 4 (44.9%) out of 9 patients. In summary, a rise in serum levels of triglycerides and/or cholesterol should receive increased attention and could indicate progression or recurrence of breast cancer.     

Mitochondrial DNA content in paired normal and cancerous breast tissue samples from patients with breast cancer

Introduction  We develop a multiplex quantitative real-time PCR for synchronized analysis of mitochondrial DNA (mtDNA) and nuclear DNA (nDNA) to investigate relative mtDNA abundance in paired normal and cancerous breast tissues. Materials and methods  The amounts of nDNA and mtDNA in 102 tissue samples were quantified for both glyceraldehype-3-phosphodehydrogenase (GAPDH) gene and mtDNA encoded ATPase (MTATP) 8 gene. The average threshold cycle (Ct) number values of the nDNA and mtDNA were used to calculate relative mtDNA content in breast tissues. Results  The median delta Ct (ΔCt) and the median mtDNA content for normal and cancerous breast tissues were 6.73 and 2.54, as well as 106.50 and 5.80 (P = 0.000, respectively). The mtDNA content was decreased in 82% of cancerous breast tissues compared with the normal ones. The changes were associated with hormone receptor status. Conclusion  Our finding suggests that decreased mtDNA content in breast cancer may have diagnostic and prognostic value for the disease.     

BCRP基因在乳腺癌组织中的表达及意义

目的　研究乳腺癌耐药蛋白 (BCRP)基因在乳腺癌组织中的表达水平 ,探讨其与肿瘤病理分期、淋巴结转移的关系。方法　采用实时荧光定量 RT- PCR检测 5 1例乳腺癌患者癌组织和癌旁组织中 BCRP基因表达。结果　 BCRP基因在乳腺癌组织中的阳性表达率、表达水平均显著高于癌旁组织 (P<0 .0 1、<0 .0 5 ) ;BCRP基因在 、 、 期乳腺癌组织中的表达水平无显著性差异 (P>0 .0 5 ) ;有淋巴结转移者的 BCRP基因表达水平显著高于无淋巴结转移者 (P<0 .0 5 )。结论　 BCRP基因表达水平与肿瘤病理分期无关 ,与淋巴结转移有关 ,BCRP基因过表达可能在乳腺癌的多药耐药中起较重要的作用。     

WWOX基因在乳腺癌中的表达及临床病理意义

目的研究WWOX基因在正常乳腺组织和乳腺癌中的表达与临床意义。方法采用免疫组化Power Vision两步法检测正常乳腺组织或纤维腺瘤、乳腺原位癌、浸润性乳腺癌中WWOX的表达情况。结果WWOX在正常乳腺组织和纤维腺瘤中的表达明显高于乳腺原位癌和浸润性乳腺癌(P均0.01)。结论WWOX起抑癌基因的作用,在乳腺癌中表达降低或缺失,提示其在乳腺癌的发生发展中起重要作用。     

Transferrin receptors in cultured breast cancer cells

Summary Transferrin receptors were demonstrated on the cell membrane of breast cancer epithelial cells in primary or long-term culture. Diferric transferrin binding was saturable, specific and was not related to DNA content or clinical and histological features of the tumour. However a good correlation (p<0.01) was found between transferrin binding and thymidine incorporation. These results suggest the possibility of transferrin receptor measurement as a reflection of the proliferative activity of cultured breast tumour cells.     

Links between obesity,diabetes and ethnic disparities in breast cancer among Hispanic populations

Breast cancer is the most prevalent malignancy in women worldwide and is a growing concern due to rising incidence and ongoing ethnic disparities in both incidence and mortality. A number of factors likely contribute to these trends including rising rates of obesity and diabetes across the globe and differences in genetic predisposition. Here, we emphasize Hispanic populations and summarize what is currently known about obesity, diabetes and individual genetic predisposition as they relate to ethnic disparities in breast cancer incidence and mortality. In addition, we discuss potential contributions to breast cancer aetiology from molecular mechanisms associated with obesity and diabetes including dyslipidemia, hyperglycaemia, hyperinsulinaemia, endocrine dysfunction and inflammation. We propose that unique differences in diet and lifestyle coupled with individual genetic predisposition and endocrine/immune dysfunction explain most of the ethnic disparities seen in breast cancer incidence and mortality.     

长链非编码RNA HOTAIR在乳腺癌中作用的研究进展

乳腺癌已成为女性常见的恶性肿瘤,有着较高的病死率。长链非编码RNA(Lnc RNAs)HOX转录反义RNA(HOTAIR)与多种人类肿瘤的发生、发展、转移和预后等密切相关。该文就Lnc RNA HOTAIR在乳腺癌中作用的研究进展作一综述。     

Estrogen responsive creatine kinase in human breast cancer cells

Summary The brain type (BB) isoenzyme of creatine kinase (CK) is a very sensitive marker of estrogen action in rat uterus and in experimental mammary tumors. In order to detect useful markers for estrogen dependent human breast cancer cell proliferation we measured CK levels and isoenzyme composition in the CG5 cells, an estrogen supersensitive variant of the MCF-7 human breast cancer cell line.Under basal conditions, CK-BB accounted for 10%–15% of total enzymatic activity, while the MM isoenzyme represented the overwhelming component. In cells cultured in the presence of 5% charcoal-treated fetal calf serum, physiological concentrations (0.1–1 nM) of estradiol increased CK-BB levels in a dose- and time-related fashion. The effect was specific for estrogens and was prevented by antiestrogens.Our results show that CK-BB is estrogen regulated in the CG5 cells and suggest a possible role for this enzyme as an additional marker of the hormonal responsiveness of breast cancer.Recipient of an Associazione Italiana per la Ricerca sul Cancro fellowship     

乳腺癌术后即刻假体植入重建乳房的研究进展

乳腺癌术后即刻假体植入乳房重建是众多术后重建方法中的一种,具有手术操作技术相对简单易学和易推广、术后恢复快、创伤小、适应证广、并发症少且易处理等诸多优点,近年在我国得到了广泛的应用。对有关乳腺癌术后即刻假体植入乳房重建文献报道数量的变化、我国公开发表的文献对乳腺癌术后即刻假体植入乳房重建的评价和手术存在的问题等做一综述。     

Estrogen receptor beta in breast cancer

Estrogen is essential for growth and development of the mammary glands and has been associated with the promotion and growth of breast cancer and in line with this, most human breast cancers are initially estrogen-dependent and undergo regression when deprived of their supporting hormone. Estrogen exerts many of its effects via two nuclear estrogen receptors (ERs), ERα and ERβ. The discovery of a second ER, ERβ, demanded a full re-evaluation of estrogen action in all target tissues and different estrogen associated diseases, including human breast cancer. However, despite over 15 years of research, the exact role, if any, of ERβ in human breast cancer remains elusive. The main challenges now are to develop highly selective anti-ERβ antibodies that are applied to large well characterized human breast cancer samples to validate their diagnostic potential and to explore ERβ-selective agonists in animal models of breast cancer to validate their therapeutic potential.     

Increased phospholipase D activity in human breast cancer

Phospholipase D is believed to play an important role in cell proliferation and tumorigenesis. One of its major functions is to cause a sustained activation of protein kinase C through the primary production of phosphatidic acid from phosphatidylcholine by the enzyme, followed by dephosphorylation forming diacylglycerol. Protein kinase C is known to be activated or translocated in some tumors including breast tumors. In order to examine phospholipase D activity in breast tumors, surgical specimens of human breast tumors were obtained by mastectomy or wide excision, and their phospholipase D activities were assayed by determining the formation of phosphatidylethanol from phosphatidylcholine and ethanol. Phospholipase D activity was predominantly localized in the microsomal fraction of the tumor tissue and markedly stimulated by oleic acid. We observed a significant increase in phospholipase D activity in 17 out of 19 spontaneous human breast tumors as compared to adjacent histologically normal breast tissue. The mean specific activity in the tumors was 52.9±41.8 (SD) pmol min^–1 mg protein^–1 whereas the value for the normal breast tissue was 34.0±36.2 (SD) pmol min^–1 mg protein^–1 (P<0.01; paired Wilcoxon's rank-sum test). The mean tumor/normal activity ratio was 2.37. Among prognostic factors, the nuclear grade, evaluated according to Schnitt et al., was found to be correlated with the activity ratio. Our results suggest a role for phospholipase D in human breast tumors. An elevation in phospholipase D activity is useful as a potential marker for malignant disease in the breast.Abbreviations PtdCho phosphatidylcholine - PLD phospholipase D - GroPCho sn-glycero-3-phosphocholine - TLC thin-layer chromatography - PtdOEt phosphatidylethanol This work was supported in part by Grants-in-Aid for Scientific Research from the Ministry of Education, Science, Sports and Culture, Japan     

Plasma malondialdehyde levels and CXCR4 expression in peripheral blood cells of breast cancer patients

Introduction  Breast cancer is one of the most common neoplasms in women and is a leading cause of cancer related deaths worldwide. Chemokines and their receptors are involved in the control of lymphocyte traffic, a critical component of systemic immunity. CXCR4 mRNA could be involved in the development of variety of diseases. Lipid peroxidation, the result of nonenzymatic autooxidation of polyunsaturated fatty acids, presents numerous harmful effects on biological systems and has been implicated in diseases like cancer. This study examined CXCR4 mRNA expression in peripheral blood cells and malondialdehyde (MDA) in plasma from blood donors and breast cancer patients. Materials and methods  CXCR4 expression in peripheral blood cells from 59 breast cancer patients and 76 healthy blood donors was analyzed by real-time PCR. Plasma MDA was analyzed using high-performance liquid chromatography (HPLC). Conclusion  In all stages, MDA levels in total breast cancer patients (1.41 ± 0.11) were significantly higher (P < 0.01) than those in healthy subjects (0.34 ± 0.03). No statistically significant difference occurred between CXCR4 expression in peripheral blood cells from breast cancer patients (1.69 ± 1.05) and the normal healthy control group (1.8 ± 0.65). However, stage II samples differed statistically (4.3 ± 1.72) from control, total cancer patients and stages I, III and IV samples.     

Calcium regulation of heparan sulfate proteoglycans in breast cancer cells

Breast tumor cells have been shown to be responsive to calcium in that external calcium modifies cell calcium, shape and growth. In order to highlight some of the numerous mechanisms by which calcium is operating, we investigated its influence on the cell microenvironment and particularly its effect on membrane-associated heparan sulfate proteoglycans. The breast cancer cells MCF-7 were grown either at low (0.04 mM) or high (2.5 mM) calcium concentration. After 3 days of culture, cells were labeled with Na ₂ ³⁵ SO₄ for 24 h and cell-associated proteoglycans extracted and purified. We showed that calcium enhances approximately twofold the synthesis of sulfated proteoglycans and, among these sulfated proteoglycans, chemical treatments indicated a specific two-to threefold increase of heparan sulfate proteoglycans. In view of the increasing implication of heparan sulfate proteoglycans in numerous mechanisms such as cell-cell contact, cell-matrix interactions and cell growth control, it appears that calcium may be a target for modulating metastatic and growth processes in breast tumor cells.Abbreviations PG proteoglycans - HSPG heparan sulfate proteoglycans - GAG glycosaminoglycans This work was supported by grants from la Fédération Nationale des Centres de Lutte Contre le Cancer (FNCLCC), les Comités du Nord et du Pas-de-Calais de la FNCLCC, La Caisse Régionale d'Assurance Maladie and by funds from the University of Lille II. The authors are indebted to Dr B. Lassalle, Centre d'Analyse d'Images, University of Lille I, for cell cycle study     

乳腺癌中PBK/TOPK mRNA表达的临床意义及功能预测

目的 通过生物信息学分析PDZ结合激酶/T-淋巴因子激活的杀伤细胞来源的蛋白激酶(PBK/TOPK)在乳腺癌(BRCA)中的表达及临床意义,并预测其潜在的分子通路和生物学功能.方法 挖掘Oncomine数据库分析PBK/TOPK信使核糖核酸(mRNA)在不同癌症中的表达情况.下载癌症基因组图谱(TCGA)数据库BRCA...     

Increased risk of breast cancer in first-degree relatives of Crohn''s disease patients: An IG-IBD study

BACKGROUND: Increased rates of colorectal cancer have been reported in patients with ulcerative colitis as well as with Crohn's colitis. This risk could be the result of shared genetic susceptibility and could be co-inherited rather than being just secondary to a long-standing, extensive mucosal inflammation. AIM: To assess the prevalence of all malignancies in first-degree relatives of Crohn's disease patients in order to establish whether any association exists. PATIENTS AND METHODS: A total of 632 outpatients with a diagnosis of Crohn's disease and 632 control subjects were recruited. Information concerning the presence of malignancies was collected in 3,292 first-degree relatives of Crohn's disease patients and in 3,303 first-degree relatives of controls. RESULTS: Two hundred and fourteen (6.5%) subjects were found to be affected by malignancy in the first-degree relatives of Crohn's disease patients and 180 (5.5%) in the first-degree relatives of controls. Forty-seven (7.4%) of Crohn's disease patients had a first-degree relative with IBD, but none of them had cancer. The frequency of extra-intestinal malignancies was higher in first-degree relatives of Crohn's disease patients than in those of controls (p=0.011). Frequency of breast cancer in female relatives of Crohn's disease patients, mainly in mothers, was two-fold higher than that in controls (0.91% versus 0.42%; odds ratio=2.16; 95% confidence interval=1.14-4.08; p=0.015). The presence of breast cancer showed no association with any specific phenotype of disease in Crohn's patients. CONCLUSIONS: These results did not corroborate the hypothesis about a common genetic susceptibility between Crohn's disease and colorectal cancer. An unexpected finding was the more frequent occurrence of extra-digestive malignancies. The prevalence of breast cancer in first-degree relatives of Crohn's disease patients, in particular the mothers, was more than double than in those of controls. This association, if confirmed, would suggest that there may exist common genetic and/or environmental factors for Crohn's disease and breast cancer.     

hsa＿circ＿0001785在乳腺癌患者血清中的表达及临床意义研究

目的 探讨hsa＿circ＿0001785在乳腺癌患者血清中的表达及临床意义。方法 选择2021年9月至2022年3月广州医科大学附属第五医院甲乳外科收治的乳腺癌患者43例(乳腺癌组),乳腺良性肿瘤患者54例(良性肿瘤组),健康体检者45名(健康对照组)。采用实时荧光定量PCR(qPCR)检测其血清hsa＿circ＿0001785的相对表达量,并进行三组间比较。分析hsa＿circ＿0001785表达水平与乳腺癌患者临床病理特征的关联性。采用受试者工作特征(ROC)曲线分析hsa＿circ＿0001785诊断乳腺癌的效能。结果 乳腺癌组血清hsa＿circ＿0001785表达水平显著高于良性肿瘤组和健康对照组(P<0.05),良性肿瘤组和健康对照组比较差异无统计学意义(P>0.05)。ROC曲线分析结果显示,血清hsa＿circ＿0001785具有诊断乳腺癌的应用价值(AUC=0.780,P<0.05),且诊断效能优于癌胚抗原(CEA)、癌抗原125(CA125)。乳腺癌患者血清hsa＿circ＿0001785的表达水平与其年龄、肿瘤类型、TNM分期、淋巴结受累、远处...     

Phospholipids and fatty acids in breast cancer tissue

Summary The fatty acid composition of fractionated phospholipids and neutral lipids was analyzed in human breast cancer tissues and the surrounding, apparently healthy tissue. In the cancer tissues the relative amounts of unsaturated fatty acids were increased in all the phospholipid subclasses analyzed. The differences were more marked in phosphatidylethanolamine than in the other phospholipid fractions and, furthermore, the relative amount of phosphatidylethanolamine was increased in cancerous tissue. In blood-erythrocyte phospholipids, no differences in fatty acid composition could be found between breast cancer and control patients. The present study suggests that the lipid composition of cancerous breast tissues differs from that of the surrounding tissue and may be involved in carcinogenesis.Supported by grants from the J. Vainio Foundation and the Finnish Ministry of Forestry and Agriculture     

Antioxidant enzyme activities and oxidative stress in human breast cancer

We have analysed products of lipid peroxidation reactions and activities of antioxidant enzymes in cancerous breast tissue and in corresponding reference tissue. In addition, the serum lipid peroxidation and peroxyl-radical-trapping capacity of breast cancer patients were compared to those of healthy subjects. A total of 23 patients with breast cancer participated in this study. In the cancerous tissue, catalase activity was lower than in the reference tissue, while the activities of superoxide dismutase, glutathione peroxidase and the hexose monophosphate shunt were elevated. The content of thiobarbituric-acid-reactive material was slightly lower in the cancerous tissues, but the levels in serum were found to be elevated in patients with breast cancer. The amounts of conjugated diene double bonds were essentially equal both in the cancerous and in the reference tissue. Moreover, in breast cancer patients the serum levels of diene conjugation and the peroxyl-radical-scavenging capacity did not differ from those measured in healthy subjects. This study indicates that the antioxidant defence system is altered in cancerous breast tissues, but does not support the hypothesis suggesting that formation of lipid peroxides in the tumour tissue itself is of primary importance in the carcinogenesis.