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유방암 환자에서 Cytokeratin 19와 Mammaglobin을 이용한 골수미세전이의 측정과 예후적 가치
정용식(Yong-Sik Jung),이상림(Sang-Lim Lee),정인호(In-Ho Jeong),윤태일(Tae-Il Yoon),안상익(Sang-Ick Ahn),박희붕(Hee Boong Park),임현이(Hyun-Ee Yim),김혜진(Hye-Jin Kim),소의영(Euy-Young Soh),김명욱(Myung-Wook Kim) 대한외과학회 2005 Annals of Surgical Treatment and Research(ASRT) Vol.68 No.6
유방암 환자의 말초혈액에서 역전사효소연쇄중합반응을 이용한 Human Mammaglobin 측정의 임상적 유용성
김재홍,강석윤,송정엽,최태영,임홍석,김선경,김영진,박준성,김현수,최진혁,임호영,김효철 대한조혈모세포이식학회 2001 대한조혈모세포이식학회지 Vol.6 No.2
Background: The mammaglobin gene encodes a novel protein that is secreted from the mammalian epithelium of normal breast tissue as well as malignant breast cancer tissues. In order to ascertain the prognostic value of mammaglobin gene in breast cancer patients, we measured the expression of human mammaglobin (hMAM) by RT-PCR method in various stages of breast cancer patients. Methods: Peripheral blood samples from forty healthy volunteers and 114 breast cancer patients were obtained. Peripheral blood stem cells (PBSC) collected for the purpose of autologous stem cell transplantation in five patients with metastatic breast cancer and ten patient with high risk for relapse and no evidence of disease were used for hMAM assay. Results: All samples from peripheral blood of forty healthy individuals (twenty males and twenty females) were negative for hMAM, whereas 43 of 114 samples (38%) from breast cancer patients were positive for hMAM mRNA. All the normal breast tissues were positive for hMAM mRNA. hMAM mRNA expression was detected in 11 of 42 (26%) in breast cancer patients who underwent for curative resection and had no evidence of disease, in 8 of 25 (34%) with chemo-sensitive relapsed disease, and in 16 of 32 (53%) with chemo-refractory progressive disease. Eight (53%) samples from peripheral blood of 15 breast cancer patients with metastatic disease at diagnosis were positive for hMAM. Three (20%) samples from peripheral blood stem cells of 15 breast cancer patients for high dose chemotherapy were positive for hMAM. Conclusion : In contrast to healthy volunteers, hMAM transcripts were detected in the peripheral blood of breast cancer patients. The frequency of hMAM expression in peripheral blood was correlated with the clinical stages of disease, but, was not significant. The contamination of hMAM expressing cells in the stem cell pool warrants additional effective purging method before the transplantation. The clinical relevance of hMAM RT-PCR-based tumor cell detection in the peripheral blood of breast cancer patients should be further evaluated in prospective studies.
Yu Wei Deng,Wen Jing Hao,Yi Wen Li,Yi Xin Li,Bo Chen Zhao,Dan Lu 한국유방암학회 2018 Journal of breast cancer Vol.21 No.3
Purpose: Multidrug resistance (MDR) remains a major obstacle in the treatment of triple-negative breast cancer (TNBC) with conventional chemotherapeutic agents. A previous study demonstrated that hsa-miRNA-143-3p plays a vital role in drug resistance of TNBC. Downregulation of hsa-miRNA-143-3p upregulated the expression of its target protein cytokine-induced apoptosis inhibitor 1 (CIAPIN1) in order to activate MDR, while upregulation of hsa-miRNA-143-3p effectively enhances the sensitivity of drug-resistant TNBC cells to chemotherapeutics. The present study aimed to further verify these findings in vivo. Methods: We established a hypodermic tumor nude mice model using paclitaxel- resistant TNBC cells. We expressed ectopic hsa-miRNA- 143-3p under the control of a breast cancer-specific human mammaglobin promoter that guided the efficient expression of exogenous hsa-miRNA-143-3p only in breast cancer cells. Thereafter, we overexpressed hsa-miRNA-143-3p in xenografts using a recombinant virus system and quantified the expression of hsa-miRNA-143-3p, CIAPIN1 protein, and proteins encoded by related functional genes by western blot. Results: We successfully completed the prospective exploration of the intravenous virus injection pattern from extensive expression to targeted expression. The overexpression of hsa-miRNA-143-3p significantly alleviated chemoresistance of TNBC by inhibiting viability. In addition, we observed that the expression of CIAPIN1 as a hsa-miRNA-143-3p target protein was remarkably decreased. Conclusion: We partly illustrated the mechanism underlying the hsa-miRNA-143-3p/CIAPIN1 drug resistance pathway. HsamiRNA- 143-3p as a tumor suppressive microRNA may be a novel target to effectively reverse MDR of TNBC in vivo.
Shargh, Shohreh Alizadeh,Movafagh, Abolfazl,Zarghami, Nosratolah,Sayad, Arezou,Mansouri, Neda,Taheri, Mohammad,Pour, Atefeh Heidary,Iranpour, Mostafa,Ghaedi, Hamid,Montazeri, Vahid,Massoudi, Nilofar,H Asian Pacific Journal of Cancer Prevention 2016 Asian Pacific journal of cancer prevention Vol.17 No.no.sup3
Breast cancer is the most prevalent type of cancer among women around the world, and mortality is primarily caused by micro-metastatic disease. The complex mechanisms of breast cancer invasion and metastasis are intrinsically related to the malignant cell type so that early detection of micro-metastases can help prolongation of survival for patient. The aim of the present research work was evaluation of the expression status of mammoglobin protein as a candidate molecular marker in the negative sentinel lymph node (SLN). Fifty tumor specimens, and 50 normal adjacent breast tissue samples from the same patients were selected on the basis of having more than 10% tumor content for RNA extraction from SLNs. Tumor samples and normal adjacent breast tissue were archived in the form of frozen fresh tissue in liquid nitrogen. Real-time PCR was performed on a Bioner life express gradient thermal cycler system. Mammoglobin gene overexpression in breast cancer metastasis was investigated. Single marker results were mammaglobin 66.7% and CK19 50.0%, with 58.3% for the two in combination. Due to improved outcome with at least 3 genes (83.3%), it seems, triple marker evaluation will be most likely useful for detecting micro-metastases instead of studying separate genes.
Murray, Nigel P,Miranda, Roxana,Ruiz, Amparo,Droguett, Elsa Asian Pacific Journal of Cancer Prevention 2015 Asian Pacific journal of cancer prevention Vol.16 No.5
Purpose: To determine the diagnostic yield of primary circulating tumor cells in women with suspicion of breast cancer, detected as a result of an abnormal mammography. Materials and Methods: Consecutive women presenting for breast biopsy as a result of a mammogram BiRADs of 3 or more, had an 8ml blood sample taken for primary circulating tumor cell (CTC) detection. Mononuclear cells were obtained using differential gel centrifugation and CTCs identified using standard immunocytochemistry using anti-mammoglobin. A test was determined to be positive if 1 CTC was detected. Results: A total of 144 women with a mean age of $54.7{\pm}15.6$ years participated, 78/144 (53.0%) had breast cancer on biopsy, 65/140 (46.3%) benign pathologies and 1(0.7%) non-Hogkins lymphoma. Increasing BiRADs scores were associated with increased cancer detection (p=0.004, RR 1.00, 4.24, 8.50). CTC mammoglobin positive had a sensitivity of 81.1% and specificity of 90.9%, with positive and negative predictive values of 90.9% and 81.1% respectively. Mammoglobin positive CTCs detected 87% of invasive cancers, while poorly differentiated cancers were negative for mammoglobin. Only 50% of in situ cancers and none of the intraductal cancers had CTCs detected. Menopausal status did not affect the diagnostic yield of the CTC test, which was higher in women with BiRADS 4 mammograms. There was a significant trend (p<0.0001 Chi squared for trends) in CTC detection frequency from intraductal, in situ and invasive (OR 1.00, 8.00, 472.00). Conclusions: The use of primary CTC detection in women suspected of breast cancer has potential uses, especially with invasive cancer, but it failed to detect intra-ductal cancer and 50% of in situ cancer. There was no difference in the diagnostic yield between pre and post menopausal women. To confirm its use in reducing biopsies in women with BIRADs 4a mammagrams and in the detection of interval invasive breast cancer, larger studies are needed.