The biological characteristics of the tumour are used to estimate prognosis and select appropriate systemic therapy for patients with(breast) cancer. The advent of molecular technology has incorporated new biomarkers ...The biological characteristics of the tumour are used to estimate prognosis and select appropriate systemic therapy for patients with(breast) cancer. The advent of molecular technology has incorporated new biomarkers along with immunohistochemical and serum biomarkers. Immunohistochemical markers are often used to guide treatment decisions, to classify breast cancer into subtypes that are biologically distinct and behave differently, and both as prognostic and predictive factors. Steroid hormone receptors, markers of tumour proliferation, and factors involved in angiogenesis and apoptosis are of scientific interest. In this review we will provide information on the immunohistochemical markers used in the management of breast cancer patients using available data from the literature. We consider the utility of established immunohistochemical markers, and discuss the challenges involved in integrating novel molecular markers into clinical practice.展开更多
Resistance to cancer therapy continues to be a major limitation for the successful treatment of cancer. There are many published studies on therapy resistance in breast and prostate cancers; however, there are current...Resistance to cancer therapy continues to be a major limitation for the successful treatment of cancer. There are many published studies on therapy resistance in breast and prostate cancers; however, there are currently no data on molecular markers associated with resistance. The conflicting data were reported regarding the AKT/m-TOR signaling pathway components as markers predicting resistance. The AKT/m-TOR signaling pathway is involved in the development of many human cancers; its activation is related to cell proliferation, angiogenesis, apoptosis, as well as to therapy resistance. Molecular alterations in the AKT/m-TOR signaling pathway provide a platform to identify universal markers associated with the development of resistance to cancer therapy.展开更多
MicroR NAs(miR NAs) are small non-coding RNAs generated by a two-step complex process and are post transcriptional negative regulators of their target m RNAs. Dysregulation of many of these miR NAs has been associated...MicroR NAs(miR NAs) are small non-coding RNAs generated by a two-step complex process and are post transcriptional negative regulators of their target m RNAs. Dysregulation of many of these miR NAs has been associated with tumorigenesis in various cancers including breast cancer. Aberrantly high expression of specific mi RNAs in breast cancer cells is demonstrated to be linked with inhibition of tumor suppressor genes and promote tumorigenesis. They are classified as oncogenic miR NAs. However, the tumor suppressor miR NAs are downregulated in breast cancer cells, since their major targets are oncogenic m RNAs. Understanding mechanism of action of specific miR NAs in breast cancer cells can be utilized to develop newer anti-cancer therapies. Recently, newer techniques are also developed to detect abundance of specific miR NA in the blood plasma samples and can be used in early diagnosis or prognosis in breast cancer. In this review article, we have discussed several mi RNAs dysregulated in breast cancer and their therapeutic potential.展开更多
Breast cancer is a complex disease driven by multiple factors including both genetic and epigenetic alterations.Recent studies revealed that abnormal gene expression induced by epigenetic changes,including aberrant pr...Breast cancer is a complex disease driven by multiple factors including both genetic and epigenetic alterations.Recent studies revealed that abnormal gene expression induced by epigenetic changes,including aberrant promoter methylation and histone modification,plays a critical role in human breast carcinogenesis.Silencing of tumor suppressor genes(TSGs) by promoter CpG methylation facilitates cells growth and survival advantages and further results in tumor initiation and progression,thus directly contributing to breast tumorigenesis.Usually,aberrant promoter methylation of TSGs,which can be reversed by pharmacological reagents,occurs at the early stage of tumorigenesis and therefore may serve as a potential tumor marker for early diagnosis and therapeutic targeting of breast cancer.In this review,we summarize the epigenetic changes of multiple TSGs involved in breast pathogenesis and their potential clinical applications as tumor markers for early detection and treatment of breast cancer.展开更多
Breast cancer remains a leading cause of morbidity and mortality in women mainly because of the propensity of primary breast tumors to metastasize. It is composed of heterogeneous cell populations with different biolo...Breast cancer remains a leading cause of morbidity and mortality in women mainly because of the propensity of primary breast tumors to metastasize. It is composed of heterogeneous cell populations with different biological properties. Breast cancer-initiating cells have been recently identified in breast carcinoma as CD44+/CD24-/low cells, which display stem cell like properties. In the present study, we have isolated breast cancer stem cells from non-metastasis tumor tissue, which is presently at passage 18 and designated as human Breast Cancer Mesenchymal Stem Cells (hBCMSCs) line. These cells showed spindle shaped morphology and formed mammos-pheres as well as pluripotency clones indicating their stem cell nature. Molecular marker study confirmed mesenchymal nature as well as pluripotency, plasticity and oncogenicity of these cells. The hBCMSCs cell line may likely contain a heterogeneous population of malignant cells. Interestingly, we also found that these cells exhibit BRCA 2 mutation, which was found in Indian population. Overall, this study revealed that hBCMSCs cell line may represent a suitable in vitro model to study the mechanism of breast cancer which further leads to an identification of molecular targets for future breast cancer targeted therapy.展开更多
Introduction: Downstream of tyrosine kinase 7 (DOK-7) is a member of the DOK family, which has been associated with the development and progression of various humancancers. Previously, identification of CpG hypermethy...Introduction: Downstream of tyrosine kinase 7 (DOK-7) is a member of the DOK family, which has been associated with the development and progression of various humancancers. Previously, identification of CpG hypermethylation in DOK-7 promoter was identified in breast cancer. Method: DOK-7 mRNA extraction and reverse transcription were performed on fresh frozen breast cancer tissue samples and normal background breast tissue. Transcript levels of expression were analyzed against TNM stage, tumour grade and clinical outcome over a 10-year follow-up period. Results: Levels of DOK-7 expression decreased significantly with increasing TNM stage. Higher DOK-7 expression was correlated with longer disease free and overall survival times. Conclusion: To our knowledge, this is the first study to investigate DOK-7 expression in human breast cancer. We identify a potential DOK-7 tumour suppressor role. DOK-7 as a prognostic biomarker in human breast cancer should be included in future validation studies.展开更多
Breast cancer is the second leading cause of cancerrelated deaths in women worldwide;a prime cancer biomarker to aid in the diagnosis, directed treatment, clinical management, and reoccurrence of this cancer is a MUC1...Breast cancer is the second leading cause of cancerrelated deaths in women worldwide;a prime cancer biomarker to aid in the diagnosis, directed treatment, clinical management, and reoccurrence of this cancer is a MUC1 peptide fragment: cancer antigen 15-3 (CA 15-3). Herein, an immuno-fluorescence assay for CA 15-3 was developed;this ALYGNSA system consists of a protein biolinker (Protein G’) adsorbed onto Poly (methyl methacrylate) (PMMA). The unique interaction of Protein G’ with PMMA, a thermo-plastic polymer has been demonstrated to improve human IgG capture antibody alignment/ orientation and result in greater assay sensitivity. Indeed a previous report (HEALTH 1 325 - 329, 2009) on the shed extracellular domain of HER-2/neu revealed a 10-fold increase in sensitivity of the ALYGSNA assay over a control ELISA assay. Results from this ALYGNSA assay study revealed that a 16-fold increase in detection (≤0.94 U/mL) of CA 15-3 was found in comparison to a commercial control ELISA kit (≤15 U/mL). In conclusion, this enhanced sensitivity of the ALYGNSA assay for CA 15-3, may provide insights into the role/function of this biomarker in normal, as well as, breast cancer and other epithelial cancers.展开更多
背景腋窝淋巴结负荷对乳腺癌患者预后具有一定的提示作用,腋窝高淋巴结负荷(axillary high nodal burden,AHNB)提示预后较差,通常需行腋窝淋巴结清扫和辅助治疗。免疫炎症指标被证明与多种肿瘤预后相关,但其与三阴性乳腺癌腋窝淋巴结负...背景腋窝淋巴结负荷对乳腺癌患者预后具有一定的提示作用,腋窝高淋巴结负荷(axillary high nodal burden,AHNB)提示预后较差,通常需行腋窝淋巴结清扫和辅助治疗。免疫炎症指标被证明与多种肿瘤预后相关,但其与三阴性乳腺癌腋窝淋巴结负荷有无关联尚不确定。目的分析免疫炎症指标对三阴性乳腺癌发生腋窝淋巴结转移和AHNB的预测价值,探讨腋窝淋巴结转移及高负荷的关联因素。方法收集本中心乳腺外科2010年1月—2023年1月收治的可手术的三阴性乳腺癌患者,分析中性粒细胞/淋巴细胞比值(neutrophil to lymphocyte ratio,NLR)、血小板/淋巴细胞比值(platelet to lymphocyte ratio,PLR)、淋巴细胞/单核细胞比值(lymphocyte to monocyte ratio,LMR)、系统性免疫性炎症指数(systemic immune-inflammation index,SII)和泛免疫炎症指数(pan immune-inflammation value,PIV)等免疫炎症指标与三阴性乳腺癌患者腋窝淋巴结转移和AHNB的关联性。结果纳入408例三阴性乳腺癌患者,其中包括255例(62.5%)腋窝淋巴结阴性的患者,153例淋巴结阳性患者,后者包括78例(19.12%)腋窝低淋巴结负荷(axillary low nodal burden,ALNB)患者和75例(18.38%)AHNB患者。单因素Logistic回归分析提示,组织学分级、病理类型、肿瘤大小、脉管侵犯、NLR与三阴性乳腺癌发生腋窝淋巴结转移相关;年龄、组织学分级、肿瘤大小、脉管侵犯与发生AHNB相关(P>0.05)。多因素Logistic回归分析提示,三阴性乳腺癌发生腋窝淋巴结转移的独立关联因素是组织学分级G3(OR=2.081,95%CI:1.334~3.245)、肿瘤≥2 cm(OR=1.658,95%CI:1.083~2.539)、有脉管侵犯(OR=2.884,95%CI:1.562~5.324)。AHNB的独立关联因素是组织学G3(OR=2.391,95%CI:1.310~4.366)、肿瘤≥2 cm(OR=1.968,95%CI:1.130~3.427)、有脉管侵犯(OR=4.592,95%CI:2.433~8.665)。结论组织学分级、肿瘤大小、脉管侵犯对三阴性乳腺癌患者的腋窝淋巴结转移和负荷水平具有一定的提示作用,而免疫炎症指标对腋窝淋巴结负荷的预测能力有限。展开更多
文摘The biological characteristics of the tumour are used to estimate prognosis and select appropriate systemic therapy for patients with(breast) cancer. The advent of molecular technology has incorporated new biomarkers along with immunohistochemical and serum biomarkers. Immunohistochemical markers are often used to guide treatment decisions, to classify breast cancer into subtypes that are biologically distinct and behave differently, and both as prognostic and predictive factors. Steroid hormone receptors, markers of tumour proliferation, and factors involved in angiogenesis and apoptosis are of scientific interest. In this review we will provide information on the immunohistochemical markers used in the management of breast cancer patients using available data from the literature. We consider the utility of established immunohistochemical markers, and discuss the challenges involved in integrating novel molecular markers into clinical practice.
文摘Resistance to cancer therapy continues to be a major limitation for the successful treatment of cancer. There are many published studies on therapy resistance in breast and prostate cancers; however, there are currently no data on molecular markers associated with resistance. The conflicting data were reported regarding the AKT/m-TOR signaling pathway components as markers predicting resistance. The AKT/m-TOR signaling pathway is involved in the development of many human cancers; its activation is related to cell proliferation, angiogenesis, apoptosis, as well as to therapy resistance. Molecular alterations in the AKT/m-TOR signaling pathway provide a platform to identify universal markers associated with the development of resistance to cancer therapy.
基金Supported by In part supported by the American Cancer Society Research Award,No.RSG-10-067-01-TBENIH grant to Chen H,No.1R01CA178386
文摘MicroR NAs(miR NAs) are small non-coding RNAs generated by a two-step complex process and are post transcriptional negative regulators of their target m RNAs. Dysregulation of many of these miR NAs has been associated with tumorigenesis in various cancers including breast cancer. Aberrantly high expression of specific mi RNAs in breast cancer cells is demonstrated to be linked with inhibition of tumor suppressor genes and promote tumorigenesis. They are classified as oncogenic miR NAs. However, the tumor suppressor miR NAs are downregulated in breast cancer cells, since their major targets are oncogenic m RNAs. Understanding mechanism of action of specific miR NAs in breast cancer cells can be utilized to develop newer anti-cancer therapies. Recently, newer techniques are also developed to detect abundance of specific miR NA in the blood plasma samples and can be used in early diagnosis or prognosis in breast cancer. In this review article, we have discussed several mi RNAs dysregulated in breast cancer and their therapeutic potential.
基金supported by grants from the National Natural Science Foundation of China(NSFC)(No.#81072148,#81071634and#30928012)Natural Science Foundation of Chongqing(No.2010BB5101)Shenzhen Science Fund for Distinguished Young Scholars(No.JC201005270328A)
文摘Breast cancer is a complex disease driven by multiple factors including both genetic and epigenetic alterations.Recent studies revealed that abnormal gene expression induced by epigenetic changes,including aberrant promoter methylation and histone modification,plays a critical role in human breast carcinogenesis.Silencing of tumor suppressor genes(TSGs) by promoter CpG methylation facilitates cells growth and survival advantages and further results in tumor initiation and progression,thus directly contributing to breast tumorigenesis.Usually,aberrant promoter methylation of TSGs,which can be reversed by pharmacological reagents,occurs at the early stage of tumorigenesis and therefore may serve as a potential tumor marker for early diagnosis and therapeutic targeting of breast cancer.In this review,we summarize the epigenetic changes of multiple TSGs involved in breast pathogenesis and their potential clinical applications as tumor markers for early detection and treatment of breast cancer.
文摘Breast cancer remains a leading cause of morbidity and mortality in women mainly because of the propensity of primary breast tumors to metastasize. It is composed of heterogeneous cell populations with different biological properties. Breast cancer-initiating cells have been recently identified in breast carcinoma as CD44+/CD24-/low cells, which display stem cell like properties. In the present study, we have isolated breast cancer stem cells from non-metastasis tumor tissue, which is presently at passage 18 and designated as human Breast Cancer Mesenchymal Stem Cells (hBCMSCs) line. These cells showed spindle shaped morphology and formed mammos-pheres as well as pluripotency clones indicating their stem cell nature. Molecular marker study confirmed mesenchymal nature as well as pluripotency, plasticity and oncogenicity of these cells. The hBCMSCs cell line may likely contain a heterogeneous population of malignant cells. Interestingly, we also found that these cells exhibit BRCA 2 mutation, which was found in Indian population. Overall, this study revealed that hBCMSCs cell line may represent a suitable in vitro model to study the mechanism of breast cancer which further leads to an identification of molecular targets for future breast cancer targeted therapy.
文摘Introduction: Downstream of tyrosine kinase 7 (DOK-7) is a member of the DOK family, which has been associated with the development and progression of various humancancers. Previously, identification of CpG hypermethylation in DOK-7 promoter was identified in breast cancer. Method: DOK-7 mRNA extraction and reverse transcription were performed on fresh frozen breast cancer tissue samples and normal background breast tissue. Transcript levels of expression were analyzed against TNM stage, tumour grade and clinical outcome over a 10-year follow-up period. Results: Levels of DOK-7 expression decreased significantly with increasing TNM stage. Higher DOK-7 expression was correlated with longer disease free and overall survival times. Conclusion: To our knowledge, this is the first study to investigate DOK-7 expression in human breast cancer. We identify a potential DOK-7 tumour suppressor role. DOK-7 as a prognostic biomarker in human breast cancer should be included in future validation studies.
文摘Breast cancer is the second leading cause of cancerrelated deaths in women worldwide;a prime cancer biomarker to aid in the diagnosis, directed treatment, clinical management, and reoccurrence of this cancer is a MUC1 peptide fragment: cancer antigen 15-3 (CA 15-3). Herein, an immuno-fluorescence assay for CA 15-3 was developed;this ALYGNSA system consists of a protein biolinker (Protein G’) adsorbed onto Poly (methyl methacrylate) (PMMA). The unique interaction of Protein G’ with PMMA, a thermo-plastic polymer has been demonstrated to improve human IgG capture antibody alignment/ orientation and result in greater assay sensitivity. Indeed a previous report (HEALTH 1 325 - 329, 2009) on the shed extracellular domain of HER-2/neu revealed a 10-fold increase in sensitivity of the ALYGSNA assay over a control ELISA assay. Results from this ALYGNSA assay study revealed that a 16-fold increase in detection (≤0.94 U/mL) of CA 15-3 was found in comparison to a commercial control ELISA kit (≤15 U/mL). In conclusion, this enhanced sensitivity of the ALYGNSA assay for CA 15-3, may provide insights into the role/function of this biomarker in normal, as well as, breast cancer and other epithelial cancers.
