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The Chinese-German Journal of Clinical Oncology 2009年第10期8卷 578-581页

作者： Shaobo Zeng Zhiyuan lian Hen Li Bin Yan Min Zhang Men Zhou Bin Jiang Department of General Surgery Taihe Hospital Yunyang Medical College Shiyan 442000 China

Objective： The aim of this study was to investigate the relationship between p38MAPK activity and apoptosis during the drug resistance of breast carcinoma cell lines. Methods： Using p38MAPK special inhibitor SB203580 to analyze the effect on the cell apoptosis of MCF-7/ADM cell. Cell apoptosis was analysed by PI staining and flow cytometry （FCM）（F test）. 50% inhibition concentration （IC50） of adriamycin on MCF-7/ADM was determined by MTT method （F test） in vitro. MDR-1 mRNA expression was detected by RT-PCR （F test） and Western Blot （F test） respectively. Results： After SB203580 24 h action the MCF-7/ADM＇s apoptosis rate was 26.73±4.90%, higher than the control group and untreated group （F = 143.80, P 〈 0.001）. The sensitity to the ADM was improved significantly （F = 148927.1, P 〈 0.001）, and the reversal effect of treat SB203580 group was 68.45%. The P38MAPK protein （F= 685.419, P 〈 0.001） and MDR-1 mRNAexpression after SB203580 24 h action were lower than the control group and untreated group （F = 9139.24, P 〈 0.001）. Conclusion： P38MAPK signal way plays an important role in drug resistance of breast carcinoma ceil. p38MAPK can protect MCF-7/ADM cells from apoptosis, and blocking the p38MAPK signal way can increase the apoptosis for breast carcinoma drug resistance cell lines.

关键词： breast carcinoma cell apoptosis P38MAPK multidrug resistance

breast and Ovarian carcinoma Overexpress HLA-G, a Neglected Cancer Immunosuppressive Protein

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Advances in breast Cancer Research 2022年第3期11卷 153-172页

作者： Xianpeng Jiang Catherine C. Baucom Toby Jiang Robert L. Elliott Sallie Astor Burdine breast Foundation Baton Rouge LA USA

Purpose: HLA-G binds to the inhibitory receptors of uterine NK cells and plays an important role in protection of fetal cells from maternal NK lysis. HLA-G also mediates tumor escape, but the immunosuppressive role is often neglected. These studies have focused on the examination of HLA-G expression in human breast and ovarian carcinoma and HLA-G immunosuppressive role in NK cytolysis. Methods: We examined HLA-G expression in breast and ovarian carcinoma cell lines by real time PCR, ELISA and immunofluorescent staining, and in frozen breast and ovarian carcinoma tissues by immunohistochemistry (IHC). We treated the breast cancer cell lines with anti-human HLA-G antibody or progesterone. Then, NK cytolysis was measured by using MTT assay. Results: We find breast and ovarian cancer cell lines increase the expression of HLA-G mRNA and protein, compared to normal cells. IHC shows that 100% of frozen breast and ovarian carcinoma tissues overexpress HLA-G protein. HLA-G IHC scores of breast and ovarian carcinoma are significantly higher than normal breast and ovarian tissues, respectively (both p breast cancer cells by the antibody increases NK cytolysis. Progesterone upregulates HLA-G mRNA and protein of human breast cancer cell lines. The increased HLA-G expression by progesterone suppresses the NK cytolysis. Conclusion: Human breast and ovarian carcinoma overexpress HLA-G immunosuppressive molecules. Blocking HLA-G protein by antibody improves the cytolysis of NK cells against human breast cancer cell lines. In contrast, upregulation of HLA-G expression by progesterone impairs NK cytolytic function. Thus, HLA-G is a new immune checkpoint protein and potential cancer immunotherapeutic target.

关键词： HLA-G breast carcinoma Ovarian carcinoma NK Cells Immunosuppressive Protein

Signet-ring cell carcinoma of breast presenting with genital tract metastasis

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The Chinese-German Journal of Clinical Oncology 2008年第7期7卷 410-412页

作者： Ying Li Huijuan Lu Department of Pathology The first Maternity and Infant Health Hospital of Shanghai Shanghai 200040 China

Objective: To analyze the clinicopathologic features of breast signet-ring cell carcinoma (SRCC) presenting with genital tract metastasis. Methods: A 54-year-old woman presented with metrorrhagia was described and the immunostaining was performed. Results: Histologically, signet ring cells (SRCs) scattered in the stroma of endometrium and cervix, bilateral fallopian tubes, ovaries and left breast. Immunohistochemistry of these SRCs showed strong reactive for cytokertin 7, CEA, GCDFP-15, and weak reactive for CA125 and negative for cytokertin 20. All these information confirmed the breast origin of SRCC. Conclusion: Primary breast SRCC is extremely rare with metrorrhagia as its first symptom. Gynecologist and pathologist should be aware of this possibility when metrorrhagia is the only symptom. Immunohistochemistry can help differentiate the origin of SRCC.

关键词： signet ring cell carcinoma breast carcinoma metastasis

The Immuno-fluorescence Quantity Analysis of α-Tubulin and γ-Tubulin Protein in Precancerous Lesion and carcinoma of the breast and Its Significance

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Chinese Journal of Clinical Oncology 2008年第1期5卷 16-21页

作者：牛昀张彤文王颖韦丽魏锡胤牛瑞芳天津医科大学附属肿瘤医院(国家)教育部乳腺癌防治重点实验室 Medical Colege Nankai University

OBJECTIVE To investigate the changes and values of the expression of α-tubulin and γ-tubulin in atypical ductal hyperplasia （ADH）, ductal carcinoma in situ （DCIS） and invasive ductal carcinoma （IDC） of the breast. The relationship between centrosome abnormalities and breast tumor development was further discussed. METHODS There were three groups including ADH, DCIS and IDC with 30 cases in each group. They were analyzed by immuno-fiuorescence quantity analysis. The expression levels of α-tubulin and γ-tubulin protein in these tissues were detected by flow cytometry immuno-fiuorescence analysis and compared with the results from normal tissues. Immunohistochemistry was also performed in this research. RESULTS The results showed significant differences of the average of the positive （FITC labeled） cells （P=0.000） among the four groups. The level of the IDC group was the highest, while normal breast tissue showed the lowest level. The results suggested that the expression levels of α-tubulin and γ-tubulin both increased as the grade of cellular proliferation and differentiation increased. The expressions showed significant differences among all the groups, except between the ADH and DCIS. There were no significant differences between α-tubulin and γ-tubulin expression in each group （P〈0.05）, as there was agreement in the immuno-fluorescence and immunohistochemical analysis for protein expression. CONCLUSION There is abnormal expression of centrosome tubulin as an early event in the development of breast tumor. Furthermore these aberrations may play a key role during oncogenesis and promote cellular transformation to malignancy. The immuno-fiuorescence quantitive analysis and immunohistochemistry can complement each other.

关键词： centrosome α-tubulin protein centrosome γ-tubulin protein precancerous lesion breast carcinoma immuno-fluorescence quantity analysis.

The Prognostic Significance of a Combined Determination of Cathepsin D and Estrogen Receptors in breast carcinomas with Positive Axillary Lymph Nodes

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Chinese Journal of Clinical Oncology 2006年第3期3卷 172-175,180页

作者： Yun Niu Xue Yang Yu Fan Ajuan Lu Tieju Liu Xilin Fu Department of breast Pathology and Research Tianjin Medical University Cancer Institute and Hospital Tianjin 30006China.

OBJECTIVE The aim of this study was to investigate the correlation between cathepsin D （Cath-D） and estrogen receptor （ER）expression in breast cancer tissue and to explore the prognostic significance of their combined determination in breast carcinoma patients with positive axillary lymph nodes. METHODS One hundred and thirty-eight cases of breast carcinoma were examined by immunohistochemistry （IHC） and the results relating to patient follow-up analyzed. RESULTS The overall 5-year disease-free survival rate （DFS） was 60.9% （84/138） in the series. The positive rate of Cath-D expression in the tumor cells was 55.07% and the positive ER staining was 51.4%. A definite significant negative correlation was found between the positive rates for Cath-D and ER （r=-0.294, P=0.001） The Cath-D expression for the cases in clinical Stage Ⅱ, ≥10 positive-node and recurrence or distant metastasis, was higher than that those cases in clinical Stage II with fewer node-metastasis and with 5 year DFS （X^2=13.926, P=0.000; X^2=13.070, P=0.001; X^2=10.545, P=0.001）. However, there was no significant difference of Cath-D expression between 2 groups of patients with different ages or among the different histopathologic types of the nonspecific invasive carcinoma. In the combined examination of Cath-D and ER, the cases that were ER （＋） and Cath-D （-） had the highest 5-year DFS compared to other situations. In contrast, the cases that were reversed in expression, ie, ER（-） and Cath-D（＋）, had a lower 5-year DFS. There was a significant difference between the 2 conditions （X2=18.675, P=0.000）. CONCLUSION A combined determination and analysis of Cath-D and ER expression may be more useful to establish a prognosis than the biological characteristics of carcinomas with positive lymph nodes.

关键词： breast carcinoma cathepsin-D estrogen receptor combined determination prognosis.

Metastatic breast cancer to the gastrointestinal tract:A case series and review of the literature

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World Journal of Gastroenterology 2006年第38期12卷 6219-6224页

作者： Jose Nazareno Donald Taves Harold G Preiksaitis Department of Medicine (Gastroenterology) The University of Western Ontario St. Joseph’s Health Care London Ontario Canada Department of Radiology The University of Western Ontario St. Joseph’s Health Care London Ontario Canada

Metastatic breast cancer involving the hepatobiliary tract or ascites secondary to peritoneal carcinomatosis has been well described. Luminal gastrointestinal tract involvement is less common and recognition of the range of possible presentations is important for early and accurate diagnosis and treatment. We report 6 patients with a variety of presentations of metastatic breast cancer of the luminal gastrointestinal tract. These include oropharyngeal and esophageal involvement presenting as dysphagia with one case of pseudoachalasia, a linitis plastica-like picture with gastric narrowing and thickened folds, small bowel obstruction and multiple strictures mimicking Crohn’s disease, and a colonic neoplasm presenting with obstruction. Lobular carcinoma, representing only 10% of breast cancers is more likely to metastasize to the gastrointestinal tract. These patients presented with gastrointestinal manifestations after an average of 9.5 years and as long as 20 years from initial diagnosis of breast cancer. Given the increased survival of breast cancer patients with current therapeutic regimes, more unusual presentations of metastatic disease, including involvement of the gastrointestinal tract can be anticipated.

关键词： breast carcinoma Metastasis Gastrointestinal tract

Downregulation of miRNA-21 and cancer stem cells after chemotherapy results in better outcome in breast cancer patients

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World Journal of Stem Cells 2022年第4期14卷 310-313页

作者： Shailendra Dwivedi Puneet Pareek Jeewan Ram Vishnoi Praveen Sharma Sanjeev Misra Biochemistry All India Institute of Medical Sciences Gorakhpur IndiaGorakhpur 273008Uttar PradeshIndia Department of Radiation Oncology All India Institute of Medical SciencesJodhpur 342005RajasthanIndia Surgical Oncology All India Institute of Medical SciencesJodhpur 342005RajasthanIndia Department of Biochemistry All India Institute of Medical SciencesJodhpur 342005RajasthanIndia Department of Surgical Oncology All India Institute of Medical SciencesJodhpur 342005RajasthanIndia King George’s Medical University Lucknow 226003Uttar PradeshIndia

Epigenetic modifications have been observed as a decline in miRNA-21 expression and breast cancer stem cell(CSC)population after 3 cycles of standard *** epigenetic response(miRNAs expression)and CSCs are also correlated in patients with breast *** patients who tolerated chemotherapy well,miRNA-21(non-coding RNA)expression decreased significantly after three cycles of *** miRNA-21 expression in breast cancer tissue was quantified by quantitative PCR(real-time PCR)using the standard *** addition,breast CSCs(CD44+/CD24-)were also decreased in these *** miRNA-21 regulates cell division,proliferation,and autophagy of cancerous cells(as it targets phosphatase and tensin homolog/AKT/transcription factor EB/programmed cell death 4/autophagy-related protein 5 and chemotherapy also produces similar effects),thereby contributing to these ***,when all of the targets on genes have been explored by mimic miRNA,chemotherapy combined with anti-miRNA21 therapy may prove useful in the care of cancer patients.

关键词： Epigenetic modification miRNA-21 breast carcinoma Autophagy Chemotherapy breast cancer stem cells

COMPARATIVE　PATHOLOGICAL　AND　FCM　STUDIES　ON　THE　PRIMARY　AND　METASTATIC　CANCERS　IN　STOMACH　AND　breast

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Chinese Journal of Cancer Research 1995年第1期7卷 55-60页

作者：张祥宏张杰英谢同欣王俊灵严霞路灵敏王进左连富王风荣 Department of Pathology Hebei Medical College Shijiazhuang

Pathological morphology,differentiation,cellular DNA content and cell Proliferation index(PI) were comparatively studied in the primary and their corresponding metastatic lesions of 54 cases of gastric and breast cancers- The results showed that differentiation and types of metastatic cancers were in accordance with their corresponding primary cancers in more than half cases(18/13) of stomach cancers,differences could be found in the other cases(16/34),and among them,10 were lower and 6 were higher differentially than their corresponding primary *** results were found in breast cancer *** cytometry(FCM) analysis revealed that dramatic DNA Index(DI) differences between metastatic and their corresponding primary cancers existed in 6/34 of gastric and 4/18 of mammary cancers,among them 7 cases were higher than the primary while 3 were lower than the primary(DI).Similar results could also be found in PI *** these suggested that metastasis of gastric and breast cancer was a very complicated process and metastatic cancer did not necessarily always show lower differentiation,higher DNA contents and DNA aneuploidy as well as higher cell proliferative rate.

关键词： Gastric carcinoma breast carcinoma Metastasis Differentiation FCM DNA index Proliferation index.

SIGNIFICANCE AND CORRELATION OF MAPK/ERK2 AND PI3-K IN HUMAN breast TUMORIGENESIS

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Chinese Journal of Cancer Research 2006年第3期18卷 177-182页

作者：马萍李柏林张英宋敏宋继谒 Institute of Tumors The First Affiliated Hospital China Medical University Shengyang 110001 Department of Chemistry China Medical University Shenyang 110001 Department of Pathology China Medical University Shenyang 110001

Objective： MAPK （（Mitogen-actived Protein Kinase） and PI3-K （Phosphatidylinositol 3-kinase） pathways have been implicated in the mitogenic pathways regulating cell growth, proliferation, differentiation and transformation and thus involved in tumorigenesis. This study was designed to examined the protein expression, activity and mRNA levels of both ERK and PI3-K in a series of breast tumors and adjacent mammary glands, and to figure out the changes of ERK2 and PI3-K during the dynamic process of breast tumorigenesis. Methods： A series of breast tumors and adjacent mammary glands were collected at surgery, including 37 cases of breast cancer, 6 cases of atypical hyperplasia-breast carcinoma in situ and 15 cases of benign conditions. Western blot, kinase activity assay and RT-PCR were used to detect the protein expression, kinase activity and mRNA level, respectively. Results： The revels of protein, activity and mRNA of ERK2 were elevated during the stages of both initiation and progression. The increasing tendency in breast cancer was equal to atypical hyperplasia -in situ carcinoma, but higher than in benign lesion and adjacent normal mammary gland. PI3-K was activated during the stage of progression of breast cancer. An inverse correlation between the activity of PI3-K and ERK2 in breast cancer was found. Conclusion： Our findings indicate that ERK2 may perform its function during both the stages of breast cancer initiation and breast cancer progression, while PI3-K may exert its effect during the stage of breast cancer progression. Both PI3-k and ERK2 are involved in the tumorigenesis of breast cancer.

关键词： PI3-K ERK2 breast carcinoma Signal transduction