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Midline2 is overexpressed and a prognostic indicator in human breast cancer and promotes breast cancer

《医学前沿（英文）》 2021年 第15卷 第6期   页码 942-942 doi: 10.1007/s11684-021-0876-z

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Progress in systemic therapy for triple-negative breast cancer

Hongnan Mo, Binghe Xu

《医学前沿（英文）》 2021年 第15卷 第1期   页码 1-10 doi: 10.1007/s11684-020-0741-5

摘要： Triple-negative breast cancer (TNBC) is the most aggressive subtype of breast cancer with a heterogeneous genetic profile. Chemotherapy exhibits substantial activity in a small subset of these patients. Drug resistance is inevitable. Major progress has been made in the genetic analysis of TNBC to identify novel targets and increase the precision of therapeutic intervention. Such progress has translated into major advances in treatment strategies, including modified chemotherapy approaches, immune checkpoint inhibitors, and targeted therapeutic drugs. All of these strategies have been evaluated in clinical trials. Nevertheless, patient selection remains a considerable challenge in clinical practice.

关键词： triple-negative breast cancer     immunotherapy     targeted therapy    

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Midline2 is overexpressed and a prognostic indicator in human breast cancer and promotes breast cancer

null

《医学前沿（英文）》 2016年 第10卷 第1期   页码 41-51 doi: 10.1007/s11684-016-0429-z

摘要：

Midline2 (MID2) is an ubiquitin-conjugating E2 enzyme linked to tumor progression and a novel interacting partner of breast cancer 1, early-onset (BRCA1). However, the role of MID2 in breast cancer remains unknown. This study investigated the expression, prognostic value, and role of MID2 in breast cancer. The expression of MID2 mRNA and protein was significantly upregulated in breast cancer tissue and established cell lines compared with that in normal breast epithelial cells and paired adjacent non-tumor tissue (P<0.001). Immunohistochemical analysis demonstrated that MID2 was overexpressed in 272 of 284 (95.8%) paraffin-embedded, archived breast cancer tissue. Moreover, MID2 expression increased with advanced clinical stage (P<0.001). High MID2 expression was significantly associated with advanced clinical stages and T, N, and M staging (all P<0.05). Univariate and multivariate analyses indicated that high MID2 expression was an independent prognostic factor for poor overall survival in the entire cohort (93.73 vs. 172.1 months; P<0.001, log-rank test) and in subgroups with stages Tis+ I+ II and III+ IV. Furthermore, 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide colony formation, and anchorage-independent growth ability assays were conducted. Results showed that siRNA silencing of MID2 expression significantly reduced MCF-7 and MDA-MB-231 cell proliferation in vitro and blocked the growth of MDA-MB-231 cell xenograft tumors in vivo (P<0.05). This study indicated that MID2 may be a novel prognostic marker and interventional target in breast cancer.

关键词： breast cancer     MID2     proliferation     overall survival     xenograft    

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How to judge the association of postmenopausal hormone therapy and the risk of breast cancer

Ling XU

《医学前沿（英文）》 2010年 第4卷 第3期   页码 290-293 doi: 10.1007/s11684-010-0093-7

摘要： The relevance of postmenopausal hormone therapy (HT) for breast cancer risk has been long debated, although it is one of the most important barriers for women to accept HT. Various opinions have been reported from recent randomized clinical trials and epidemiological studies. These unanswered questions include: whether HT has a positive impact on breast cancer; whether risks of therapy with unopposed estrogen and combined estrogen-progestin are different; and whether different types and routes of estrogen and progestogens, as well as the duration and cessation of HT use, have different impacts on this disorder. Recently, there has been some good news such as the following: the currently available data do not provide sufficient evidence to prove a causal relationship between postmenopausal HT and breast cancer; breast cancer in postmenopausal women using HT usually has better prognosis than that of nonusers. In conclusion, HT is still the most effective method of relieving climacteric symptoms for many postmenopausal women. However, a possible risk of breast cancer associated with long-term HT usage should not be ignored. With respect to prevention of breast cancer, regular evaluation of individual breast cancer susceptibility and close follow-up through mammography and/or breast sonography are necessary strategies for the safety of HT use.

关键词： breast cancer     postmenopausal hormone therapy     unopposed estrogen therapy     combined estrogen-progestin therapy    

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Metabolism and immunity in breast cancer

Deyu Zhang, Xiaojie Xu, Qinong Ye

《医学前沿（英文）》 2021年 第15卷 第2期   页码 178-207 doi: 10.1007/s11684-020-0793-6

摘要： Breast cancer is one of the most common malignancies that seriously threaten women’s health. In the process of the malignant transformation of breast cancer, metabolic reprogramming and immune evasion represent the two main fascinating characteristics of cancer and facilitate cancer cell proliferation. Breast cancer cells generate energy through increased glucose metabolism. Lipid metabolism contributes to biological signal pathways and forms cell membranes except energy generation. Amino acids act as basic protein units and metabolic regulators in supporting cell growth. For tumor-associated immunity, poor immunogenicity and heightened immunosuppression cause breast cancer cells to evade the host’s immune system. For the past few years, the complex mechanisms of metabolic reprogramming and immune evasion are deeply investigated, and the genes involved in these processes are used as clinical therapeutic targets for breast cancer. Here, we review the recent findings related to abnormal metabolism and immune characteristics, regulatory mechanisms, their links, and relevant therapeutic strategies.

关键词： breast cancer     metabolism     immunity     cancer stem cells    

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Meta-analysis of the risk factors of breast cancer concerning reproductive factors and oral contraceptive

Qiong DAI MD, Bei LIU MD, Yukai DU MM,

《医学前沿（英文）》 2009年 第3卷 第4期   页码 452-458 doi: 10.1007/s11684-009-0080-z

摘要： The authors performed a meta-analysis of case-control studies that addressed whether reproductive factors and oral contraceptive use were associated with breast cancer by searching the MEDLINE, PubMed, Proquest, Embase, ScienceDirect, African Healthline, BMJ Health Intelligence and Chinese Periodical net databases for all English-language and Chinese-language papers published from January 1, 1997 to December 31, 2007. A total of 15 studies calculating pool ORs indicated that menopausal age >50yr [odds ratio (OR), 1.39; 95% confidence interval (CI), 1.22―1.57] and oral contraceptive use (OR, 2.12*, “*”: summary OR was adjusted; 95% CI, 1.24―3.62) were correlated with the increase in breast cancer risk while the summary OR based on number of full-term pregnancies ≥1 (OR, 0.63*; 95% CI, 0.60―0.68) and breast-feeding (OR, 0.76; 95% CI, 0.64―0.90) indicated no association with breast cancer risk. The correlation was statistically significant. Menopausal age >50yr and oral contraceptive use are positively correlated with an increase in breast cancer risk while breast-feeding and number of full-term pregnancies ≥1 are protective factors.

关键词： meta-analysis     breast cancer     risk factors     reproductive factors     oral contraceptive use    

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Expression of PC-cell-derived growth factor in breast cancer

Haiping SONG MD, Lan SHI MD, Chunping LIU MD, Tao HUANG MD,

《医学前沿（英文）》 2009年 第3卷 第4期   页码 426-430 doi: 10.1007/s11684-009-0085-7

摘要： This study is mainly aimed at evaluating the expression of PC-cell-derived growth factor (PCDGF) in breast cancer and breast adenofibroma, and to compare with other commonly used clinical pathological indices, then to investigate the diagnostic and targeted therapeutic purpose of PCDGF in breast cancer tissue. In this study, we detected the expression of PCDGF, p53 and CerbB-2 in breast cancer tissue and the expression of PCDGF in breast adenofibroma tissue by immunohistochemical method, and analyzed the relationship between them. We found that PCDGF was expressed in most breast cancer tissue, but was not in breast adenofibroma tissue, and the expression of PCDGF was related with the tumor’s pathological category and the expression of estrogen receptor (ER) and progesterone receptor (PR) and p53, but there was no statistical dependability between PCDGF and cerbB-2. From this study, we predict that PCDGF may serve as a marker in the secondary diagnosis of breast cancer, and may participate in the generation and differentiation of breast cancer cells, and become an effective target of therapy for breast cancer.

关键词： PC-cell-derived growth factor     breast neoplasms     clinical markers    

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A case of primary neuroendocrine breast carcinoma that responded to neo-adjuvant chemotherapy

null

《医学前沿（英文）》 2015年 第9卷 第1期   页码 112-116 doi: 10.1007/s11684-014-0345-z

摘要：

Primary neuroendocrine breast carcinoma (NEBC) is a very rare type of breast cancer. Two characteristic biomarkers, namely, CgA and Syn, should be immunohistochemically detected to diagnose NEBC. In this study, a 43-year-old woman with a large mass of 8.3 cm × 2.9 cm in her right breast was reported. The patient was pathologically diagnosed with NEBC after specific markers, including CgA and Syn, as well as few differential markers, such as CK7, ER, PR, C-erbB-2, NSE, and E-cadherin, were immunohistochemically detected. The patient showed a remarkable response to four cycles of neo-adjuvant chemotherapy (partial response based on RECIST criteria) and sequentially underwent modified radical mastectomy. Moreover, the diagnosis and treatment of NEBC based on this case and available related literature were discussed.d literature were discussed.

关键词： neuroendocrine carcinoma     neo-adjuvant therapy     breast    

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frequency of alternative splicing variants of the oncogene in neuroendocrine tumors of the pancreas and breast

《医学前沿（英文）》   页码 907-923 doi: 10.1007/s11684-023-1009-7

摘要： The characteristic genetic abnormality of neuroendocrine neoplasms (NENs), a heterogeneous group of tumors found in various organs, remains to be identified. Here, based on the analysis of the splicing variants of an oncogene Focal Adhesion Kinase (FAK) in The Cancer Genome Atlas datasets that contain 9193 patients of 33 cancer subtypes, we found that Box 6/Box 7-containing FAK variants (FAK6/7) were observed in 7 (87.5%) of 8 pancreatic neuroendocrine carcinomas and 20 (11.76%) of 170 pancreatic ductal adenocarcinomas (PDACs). We tested FAK variants in 157 tumor samples collected from Chinese patients with pancreatic tumors, and found that FAK6/7 was positive in 34 (75.6%) of 45 pancreatic NENs, 19 (47.5%) of 40 pancreatic solid pseudopapillary neoplasms, and 2 (2.9%) of 69 PDACs. We further tested FAK splicing variants in breast neuroendocrine carcinoma (BrNECs), and found that FAK6/7 was positive in 14 (93.3%) of 15 BrNECs but 0 in 23 non-NEC breast cancers. We explored the underlying mechanisms and found that a splicing factor serine/arginine repetitive matrix protein 4 (SRRM4) was overexpressed in FAK6/7-positive pancreatic tumors and breast tumors, which promoted the formation of FAK6/7 in cells. These results suggested that FAK6/7 could be a biomarker of NENs and represent a potential therapeutic target for these orphan diseases.

关键词： FAK6/7     SRRM4     neuroendocrine neoplasms     pancreas     breast    

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Production of pectic extracts from sugar beet pulp with antiproliferative activity on a breast cancer

Jacqueline CONCHA, Caroline WEINSTEIN, María Elvira Zú?IGA

《化学科学与工程前沿（英文）》 2013年 第7卷 第4期   页码 482-489 doi: 10.1007/s11705-013-1342-5

摘要： In the last years, sugar beet pectins have been the subject of several investigations involving extraction methodologies, chemical composition and functional properties. The structure of pectins, which depends on the extraction method, is decisive in their capacity to induce apoptosis on several cancer cell lines like colon, prostate and breast. In this work, sugar beet pectin extraction was performed in the following steps: lipid extraction with hexane, removal of soluble complex carbohydrates and proteins, and enzymatic treatment with amyloglucosidase, protease, and pectinase. The enzymatic treatment was carried out with Rohapect DA6L under the following conditions: 50°C, pH 4.0, 2% enzyme/substrate (E/S) ratio, 15 h, and a solid to liquid ratio of 1 ∶ 10. The pectic extract showed a degree of polymerization (DP) profile of 55.8% with DP≥7; 4.9% with DP6; 5.8% between DP2 and DP6 ; 4.7% with DP2; and 28.8% with DP1. The pectic extract was examined for its antiproliferative activity on the MCF-7 breast cancer cell line. At a concentration range of 12.5–25 mg/mL the pectic extract killed 80.6% of the cells, exhibiting a higher antiproliferative activity than 4-hydroxytamoxifen (4-OHT), a classical anticancer drug, which killed 56.5% of the cells.

关键词： pectic extracts     antiproliferative activity     breast cancer     enzymatic treatment    

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A comprehensive information database (CID) of breast cancer patients in China

null

《医学前沿（英文）》 2012年 第6卷 第2期   页码 212-216 doi: 10.1007/s11684-012-0185-7

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Decitabine induces -mediated immune responses in p53-mutated triple-negative breast cancer: a clinical

《医学前沿（英文）》 doi: 10.1007/s11684-023-1016-8

摘要： p53 is mutated in half of cancer cases. However, no p53-targeting drugs have been approved. Here, we reposition decitabine for triple-negative breast cancer (TNBC), a subtype with frequent p53 mutations and extremely poor prognosis. In a retrospective study on tissue microarrays with 132 TNBC cases, DNMT1 overexpression was associated with p53 mutations (P = 0.037) and poor overall survival (OS) (P = 0.010). In a prospective DEciTabinE and Carboplatin in TNBC (DETECT) trial (NCT03295552), decitabine with carboplatin produced an objective response rate (ORR) of 42% in 12 patients with stage IV TNBC. Among the 9 trialed patients with available TP53 sequencing results, the 6 patients with p53 mutations had higher ORR (3/6 vs. 0/3) and better OS (16.0 vs. 4.0 months) than the patients with wild-type p53. In a mechanistic study, isogenic TNBC cell lines harboring DETECT-derived p53 mutations exhibited higher DNMT1 expression and decitabine sensitivity than the cell line with wild-type p53. In the DETECT trial, decitabine induced strong immune responses featuring the striking upregulation of the innate immune player IRF7 in the p53-mutated TNBC cell line (upregulation by 16-fold) and the most responsive patient with TNBC. Our integrative studies reveal the potential of repurposing decitabine for the treatment of p53-mutated TNBC and suggest IRF7 as a potential biomarker for decitabine-based treatments.

关键词： p53 mutation     triple-negative breast cancer     decitabine     DNMT1     IRF7     innate immune response    

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Association of SIPA1 545 C>T polymorphism with survival in Chinese women with metastatic breast cancer

null

《医学前沿（英文）》 2013年 第7卷 第1期   页码 138-142 doi: 10.1007/s11684-013-0247-5

摘要：

It has been demonstrated that single nucleotide polymorphisms (SNPs) of SIPA1 (signal-induced proliferation associated gene 1) are associated with metastatic efficiency in both human and rodents. The purpose of this study was to determine whether SIPA1 545 C>T polymorphism was associated with overall survival in patients with metastatic breast cancer. In this study, SIPA1 545 C>T polymorphism was detected in 185 metastatic breast cancer patients using polymerase chain reaction-restriction fragment length polymorphism assay (PCR-RFLP). Survival curves for patients with SIPA1 545 C>T polymorphism was compared using the Kaplan-Meier method with log-rank tests. We found that SIPA1 545 C>T polymorphism was significantly associated with survival in 185 patients with metastatic breast cancer. Patients with SIPA1545 T/T genotype had a significantly worse overall survival (OS) than did patients with C/T or C/C genotype (50.0% vs. 62.9%, P = 0.042). Moreover, in multivariate analysis, as compared with the C/C or C/T genotype, the T/T genotype remained an independent unfavorable prognostic marker of OS in this cohort (hazard ratio [HR] = 2.16; 95% CI= 1.12–4.15; P = 0.022). Our findings indicate that metastatic breast cancer patients with SIPA1 545 T/T genotype have a poorer survival compared to patients with C/C or C/T genotype.

关键词： SIPA1     polymorphism     metastatic breast cancer     survival    

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Function of Slit/Robo signaling in breast cancer

null

《医学前沿（英文）》 2015年 第9卷 第4期   页码 431-436 doi: 10.1007/s11684-015-0416-9

摘要：

Slit and Robo are considered tumor suppressors because they are frequently inactivated in various tumor tissue. These genes are closely correlated with CpG hypermethylation in their promoters. The Slit/Robo signaling pathway is reportedly involved in breast cancer development and metastasis. Overexpression of Slit/Robo induces its tumor suppressive effects possibly by inactivating the β-catenin/LEF/TCF and PI3K/Akt signaling pathways or by altering β-catenin/E-cadherin-mediated cell-cell adhesion in breast cancer cells. Furthermore, loss of Slit proteins or their Robo receptors upregulates the CXCL12/CXCR4 signaling axis in human breast carcinoma. In addition, this pathway regulates the distant migration of breast cancer cells not only by mediating the phosphorylation of the downstream molecules of CXCL12/CXCR4 and srGAPs, such as PI3K/Src, RAFTK/ Pyk2, and CDC42, but also by regulating the activities of MAP kinases. This review includes recent studies on the functions of Slit/Robo signaling in breast cancer and its molecular mechanisms.

关键词： Slit/Robo     hypermethylation     β-catenin     CXCL12/CXCR4     migration    

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Soy food consumption in relation to breast cancer modified by menopause status

YANG Rong, ZHANG Bin, YANG Shaoping, ZHANG Dan, DU Yukai

《医学前沿（英文）》 2008年 第2卷 第4期   页码 348-351 doi: 10.1007/s11684-008-0066-2

摘要： It has been found that lifestyle and diet are associated with the development of cancers. The mortality of breast cancer in Wuhan city is increasing, according to the statistics of recent years. This case control study was aimed to provide data for alimentary therapeutics for breast carcinomas. It included a case group ( = 196) and an age frequency-matched control group ( = 202). A validated food frequency questionnaire was used to obtain information on usual food consumption. The results indicate that intake of soy foods more than 5 times per week was associated with a decreased risk of breast cancer, especially in premenopausal women. The adjusted was 0.294 [95% CI was (0.158–0.546), = 0.000]. Our results indicate that alimentary therapeutics for breast cancer can be adjusted by status of menopause.

关键词： development     control     lifestyle     consumption     information    

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标题 作者 时间 类型 操作

Midline2 is overexpressed and a prognostic indicator in human breast cancer and promotes breast cancer

期刊论文

Progress in systemic therapy for triple-negative breast cancer

Hongnan Mo, Binghe Xu

期刊论文

Midline2 is overexpressed and a prognostic indicator in human breast cancer and promotes breast cancer

null

期刊论文

How to judge the association of postmenopausal hormone therapy and the risk of breast cancer

Ling XU

期刊论文

Metabolism and immunity in breast cancer

Deyu Zhang, Xiaojie Xu, Qinong Ye

期刊论文

Meta-analysis of the risk factors of breast cancer concerning reproductive factors and oral contraceptive

Qiong DAI MD, Bei LIU MD, Yukai DU MM,

期刊论文

Expression of PC-cell-derived growth factor in breast cancer

Haiping SONG MD, Lan SHI MD, Chunping LIU MD, Tao HUANG MD,

期刊论文

A case of primary neuroendocrine breast carcinoma that responded to neo-adjuvant chemotherapy

null

期刊论文

frequency of alternative splicing variants of the oncogene in neuroendocrine tumors of the pancreas and breast

期刊论文

Production of pectic extracts from sugar beet pulp with antiproliferative activity on a breast cancer

Jacqueline CONCHA, Caroline WEINSTEIN, María Elvira Zú?IGA

期刊论文

A comprehensive information database (CID) of breast cancer patients in China

null

期刊论文

Decitabine induces -mediated immune responses in p53-mutated triple-negative breast cancer: a clinical

期刊论文

Association of SIPA1 545 C>T polymorphism with survival in Chinese women with metastatic breast cancer

null

期刊论文

Function of Slit/Robo signaling in breast cancer

null

期刊论文

Soy food consumption in relation to breast cancer modified by menopause status

YANG Rong, ZHANG Bin, YANG Shaoping, ZHANG Dan, DU Yukai

期刊论文