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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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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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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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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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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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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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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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Breast cancer-associated fibroblasts: their roles in tumor initiation, progression and clinical applications

null

《医学前沿（英文）》 2016年 第10卷 第1期   页码 33-40 doi: 10.1007/s11684-016-0431-5

摘要：

Breast cancer is the most common malignant tumor in women, and the incidence of this disease has increased in recent years because of changes in diet, living environment, gestational age, and other unknown factors. Previous studies focused on cancer cells, but an increasing number of recent studies have analyzed the contribution of cancer microenvironment to the initiation and progression of breast cancer. Cancer-associated fibroblasts (CAFs), the most abundant cells in tumor stroma, secrete various active biomolecules, including extracellular matrix components, growth factors, cytokines, proteases, and hormones. CAFs not only facilitate the initiation, growth, angiogenesis, invasion, and metastasis of cancer but also serve as biomarkers in the clinical diagnosis, therapy, and prognosis of breast cancer. In this article, we reviewed the literature and summarized the research findings on CAFs in breast cancer.

关键词： cancer-associated fibroblast     breast cancer     progression     prognosis    

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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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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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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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Neoadjuvant radiohormonal therapy for oligo-metastatic prostate cancer: safety and efficacy outcomes

《医学前沿（英文）》 2023年 第17卷 第2期   页码 231-239 doi: 10.1007/s11684-022-0939-9

摘要： To evaluate the safety and efficacy of neoadjuvant radiohormonal therapy for oligometastatic prostate cancer (OMPC), we conducted a 3 + 3 dose escalation, prospective, phase I/II, single-arm clinical trial (CHiCTR1900025743), in which long-term neoadjuvant androgen deprivation was adopted 1 month before radiotherapy, comprising intensity modulated radiotherapy to the pelvis, and stereotactic body radiation therapy to all extra-pelvic bone metastases for 4‒7 weeks, at 39.6, 45, 50.4, and 54 Gy. Robotic-assisted radical prostatectomy was performed after 5‒14 weeks. The primary outcome was treatment-related toxicities and adverse events; secondary outcomes were radiological treatment response, positive surgical margin (pSM), postoperative prostate-specific antigen (PSA), pathological down-grading and tumor regression grade, and survival parameters. Twelve patients were recruited from March 2019 to February 2020, aging 66.2 years in average (range, 52‒80). Median baseline PSA was 62.0 ng/mL. All underwent RARP successfully without open conversions. Ten patients recorded pathological tumor down-staging (83.3%), and 5 (41.7%) with cN1 recorded negative regional lymph nodes on final pathology. 66.7% (8/12) recorded tumor regression grading (TRG) –I and 25% (3/12) recorded TRG-II. Median follow-up was 16.5 months. Mean radiological progression-free survival (RPFS) was 21.3 months, with 2-year RPFS of 83.3%. In all, neoadjuvant radiohormonal therapy is well tolerated for oligometastatic prostate cancer.

关键词： neoadjuvant     radiotherapy     oligometastatic     prostate cancer     radical prostatectomy    

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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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Transformer2 proteins protect breast cancer cells from accumulating replication stress by ensuring productive

Andrew Best,Katherine James,Gerald Hysenaj,Alison Tyson-Capper,David J. Elliott

《化学科学与工程前沿（英文）》 2016年 第10卷 第2期   页码 186-195 doi: 10.1007/s11705-015-1540-4

摘要： Increased expression levels of the RNA splicing regulator Transformer2 (abbreviated Tra2 ) have been reported in several types of cancer. Recent work has revealed an intimate cross-regulation between Tra2 and the highly similar Tra2 protein in human breast cancer cells, though these two proteins are encoded by separate genes created by a gene duplication that occurred over 500 million years ago. This cross-regulation involves splicing control of a special class of exons, called poison exons. Down-regulation of Tra2 reduces splicing inclusion of a poison exon in the mRNA encoding Tra2 , thereby up-regulating Tra2 protein expression. This buffers any splicing changes that might be caused by individual depletion of Tra2 alone. Discovery of this cross-regulation pathway, and its by-pass by joint depletion of both human Tra2 proteins, revealed Tra2 proteins are essential for breast cancer cell viability, and led to the identification of important targets for splicing control. These exons include a critical exon within the checkpoint kinase 1 (CHK1) gene that plays a crucial function in the protection of cancer cells from replication stress. Breast cancer cells depleted for Tra2 proteins have reduced CHK1 protein levels and accumulate DNA damage. These data suggest Tra2 proteins and/or their splicing targets as possible cancer drug targets.

关键词： RNA splicing     gene expression     breast cancer     DNA damage     CHK1    

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Chimeric antigen receptor T cell targeting EGFRvIII for metastatic lung cancer therapy

Zhao Zhang, Jun Jiang, Xiaodong Wu, Mengyao Zhang, Dan Luo, Renyu Zhang, Shiyou Li, Youwen He, Huijie Bian, Zhinan Chen

《医学前沿（英文）》 2019年 第13卷 第1期   页码 57-68 doi: 10.1007/s11684-019-0683-y

摘要：

Lung cancer is the most common incident cancer and the leading cause of cancer death. In recent years, the development of tumor immunotherapy especially chimeric antigen receptor T (CAR-T) cell has shown a promising future. Epidermal growth factor receptor variant III (EGFRvIII) is a tumor-specific mutation expressed in various types of tumors and has been detected in non-small cell lung cancer with a mutation rate of 10%. Thus, EGFRvIII is a potential antigen for targeted lung cancer therapy. In this study, CAR vectors were constructed and transfected into virus-packaging cells. Then, activated T cells were infected with retrovirus harvested from stable virus-producing single clone cell lines. CAR expression on the surfaces of the T cells was detected by flow cytometry and Western blot. The function of CAR-T targeting EGFRvIII was then evaluated. The EGFRvIII-CAR vector was successfully constructed and confirmed by DNA sequencing. A stable virus-producing cell line was produced from a single clone by limited dilution. The culture conditions for the cell line, including cell density, temperature, and culture medium were optimized. After infection with retrovirus, CAR was expressed on more than 90% of the T cells. The proliferation of CAR-T cells were induced by cytokine and specific antigen in vitro. More importantly, EGFRvIII-CART specifically and efficiently recognized and killed A549-EGFRvIII cells with an effector/target ratio of 10:1 by expressing and releasing cytokines, including perforin, granzyme B, IFN-g, and TNF-α. The in vivo study indicated that the metastasis of A549-EGFRvIII cells in mice were inhibited by EGFRvIII-CART cells, and the survival of the mice was significantly prolonged with no serious side effects. EGFRvIII-CART showed significantly efficient antitumor activity against lung cancer cells expressing EGFRvIII in vivo and in vitro. Therefore, CAR-T targeting EGFRvIII is a potential therapeutic strategy in preventing recurrence and metastasis of lung cancer after surgery.

关键词： chimeric antigen receptor T cells     epidermal growth factor receptor     lung cancer     immunotherapy     tumor immunology    

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标题 作者 时间 类型 操作

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

null

期刊论文

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

期刊论文

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

null

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

Metabolism and immunity in breast cancer

Deyu Zhang, Xiaojie Xu, Qinong Ye

期刊论文

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

null

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

Breast cancer-associated fibroblasts: their roles in tumor initiation, progression and clinical applications

null

期刊论文

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

期刊论文

Progress in systemic therapy for triple-negative breast cancer

Hongnan Mo, Binghe Xu

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

Neoadjuvant radiohormonal therapy for oligo-metastatic prostate cancer: safety and efficacy outcomes

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

Transformer2 proteins protect breast cancer cells from accumulating replication stress by ensuring productive

Andrew Best,Katherine James,Gerald Hysenaj,Alison Tyson-Capper,David J. Elliott

期刊论文

Chimeric antigen receptor T cell targeting EGFRvIII for metastatic lung cancer therapy

Zhao Zhang, Jun Jiang, Xiaodong Wu, Mengyao Zhang, Dan Luo, Renyu Zhang, Shiyou Li, Youwen He, Huijie Bian, Zhinan Chen

期刊论文