非甾体抗炎药降低胃癌患病风险的系统评价

目的系统评价非甾体抗炎药降低胃癌患病风险的有效性。方法检索Cochranelibrary、MEDLINE、EMBASE、CBM、CNKI和VIP等数据库（截至2008年8月）,全面搜集有关非甾体抗炎药（NSAIDs）降低胃癌患病风险的研究,文献质量评价参照Cochrane系统评价员手册。纳入非甾体类抗炎药降低胃癌患病风险的研究,采用CochraneHandbook4．2．5的方法进行评价,同质的研究用RevMan4．2．7软件合并效应量,进行Meta分析。结果共检索到19篇相关文献,评价后纳入9篇文献（9个研究28721名受试者）。纳入研究均为非甾体抗炎药与胃癌患病风险的研究,其中4个研究为单用阿司匹林与胃癌的患病研究,另外5个研究为阿司匹林和非阿司匹林非甾体抗炎药与胃癌的患病研究的对比研究。9个研究均为病例对照研究。按照不同的统计学分组,经异质性检验,无统计学异质性,合并统计量进行分析：结果显示,阿司匹林等非甾体抗炎药为胃癌的保护因素[OR0．73,95％CI（0．68,0．79）].结论长期、规律地使用阿司匹林等非甾体抗炎药有助于降低胃癌的患病风险;目前尚无足够的证据显示短期使用非甾体抗炎药有助于降低胃癌的患病风险。     

类器官在乳腺癌精准治疗中的应用

目的 总结类器官在乳腺癌精准治疗中的应用,并探讨其发展方向。方法 以“类器官、乳腺癌、精准治疗、个体化治疗”为中文关键词,以“organoids, breast cancer、precision treatment、personalized treatment”为英文关键词,应用PubMed及中国知网数据库检索2009年1月-2022年2月发表的相关文献。共检索到中文文献23条,英文文献337条。纳入标准：(1)类器官培养的进展;(2)类器官在乳腺癌精准治疗中的研究;(3)类器官研究面临的问题。排除标准：重复性、数据陈旧的相关文献。最终纳入57篇文献进行分析。结果 乳腺癌类器官在基因编辑、耐药性验证、药物筛选及新药研发等方面取得有价值的进展,为临床研究提供参考。结论 类器官培养技术具有缺陷性,缺乏多种细胞类型及完整免疫微环境成分,需探索新的培养方式完善此模型。     

非甾体类抗炎药对大肠癌的化学预防及机理探讨

非甾体类抗炎药 (nonsteroidal anti-inflamm atory drug,NSAID) ,是一类具有解热、镇痛、消炎及抗风湿作用的药物 ,包括水杨酸类、吡唑酮类、吡罗昔康、吲哚美辛、舒林酸、萘普生等。近年来的流行病学调查 ,临床病例观察及动物模型研究所提供的证据表明 ,非甾体类抗炎药具有抗肿瘤的作用 ,特别对于胃肠道肿瘤 ,某些非甾体类抗炎药还具有使单个腺瘤消失的作用。现将非甾体类抗炎药的抗结直肠肿瘤作用及其有关机制综述如下。1　流行病学调查流行病学研究表明 ,长期有规律地服用阿司匹林能够减少结肠癌发生的危险性。 Kune等 [1 ] 最初在研…     

乳腺癌治疗后妊娠的可行性及安全性

目的 随着乳腺癌逐渐年轻化及国家二胎政策的放开,乳腺癌患者对生育要求增加.本研究旨在探讨乳腺癌治疗后妊娠对患者预后的影响.方法 应用检索维普、万方、CNKI、Medline期刊全文数据库的检索系统,以“乳腺癌、综合治疗、妊娠、预后”等为关键词,检索1957-01-2016-06的相关文献,共检索到英文文献307条,中文文献106条.纳入标准:(1)有关乳腺癌治疗后妊娠;(2)有关生育方面问题.剔除标准:(1)妊娠期乳腺癌;(2)非乳腺癌治疗后妊娠.根据纳入排除标准,符合分析的文献24篇.结果 目前的研究结果显示,乳腺癌治疗后妊娠对预后无不良影响.乳腺癌综合治疗,尤其是化疗,可能会影响患者生育能力,患者治疗前可以考虑卵巢保护措施,化疗中选择对卵巢损害小的药物,以保障治疗后妊娠相对较高的成功率.乳腺癌患者治疗后妊娠不增加其后代畸形或者智力低下的风险.对于早期的乳腺癌患者,建议结束治疗后两年妊娠;Ⅲ期乳腺癌患者建议五年后妊娠.结论 本研究在现有的循证医学证据下发现,在充分的卵巢保护,合理的选择化疗用药,并在乳腺癌综合治疗结束后间隔足够时间的前提下选择妊娠,对乳腺癌患者的预后无不利影响.     

乳腺癌内分泌治疗耐药机制及临床研究进展

目的 总结乳腺癌内分泌治疗可能的耐药机制及相关靶向药物临床研究进展,为临床治疗提供指导.方法 应用PubMed和CNKI期刊全文数据库检索系统,以"乳腺癌、内分泌耐药、靶向治疗"为关键词,检索2009-11-2020-03相关文献,共检索到英文文献384条,中文文献76条.纳入标准:(1)乳腺癌内分泌耐药机制;(2)乳...     

患者源性膀胱癌类器官模型的应用及研究进展

目的 总结类器官在膀胱癌领域的研究现状及应用进展。方法 在PubMed、Web of Science、CNKI等数据库中,分别以“膀胱癌、类器官、癌症研究、三维培养”为中文关键词,“organoids, bladder cancer, precision treatment, drug screening”为英文关键词检索2000年至2022年肿瘤类器官和患者来源类器官相关文献。纳入标准：(1)类器官培养的进展;(2)类器官在膀胱癌中的研究;(3)类器官研究面临的问题。排除标准：重复性、数据陈旧的相关文献。最终纳入48篇文献进行分析。结果 患者源性的肿瘤类器官在药物研发、药物毒性和药效实验、精准医疗等方面取得有价值的进展,为临床研究提供参考。结论 肿瘤类器官培养作为一种新型的肿瘤体外模型,既能够很好的反应肿瘤异质性、模拟肿瘤微环境,又需要较少时间成本和经济成本,在肿瘤生物学研究、药物研发、精准医疗等方面具有显著优势。     

三阴性乳腺癌基因学分子分型和个体化治疗新进展

目的 三阴性乳腺癌(triple negative breast cancer,TNBC)作为乳腺癌的一种特殊类型,具有高侵袭性,极易出现局部复发和远处转移.近年来关于TNBC进一步亚分类,并且针对各亚型进行相应靶向治疗的基础研究和临床研究均较多.本研究对国内外TNBC的分子分型和个体化治疗新进展进行综述分析.对国内外三阴性乳腺癌(triple negarive breast cancer,TNBC)的分子分型以及个体化治疗新进展进行综述分析.方法 应用PubMed及CNKI期刊全文数据库检索系统,以“三阴性乳腺癌、TNBC、分子分型、治疗”等为关键词,检索2011-01-2016-05相关文献,共检索到英文文献240条,中文文献449条.纳入标准:(1)TNBC的生物学功能;(2)TNBC的分子分型;(3)TNBC的个体化治疗.剔除标准:(1)乳腺癌的分子分型;(2)乳腺癌的个体化治疗.根据剔除标准剔除中文文献130条,英文文献141条,最后纳入分析63篇文献.结果 TNBC从基因学角度分为6个亚型,针对每个亚型均有不同的个体化治疗靶向药物,包括表皮生长因子受体(epidermal growth factor receptor,EGFR)抑制剂、铂类、聚腺苷酸二磷酸核糖转移酶(poly-AD-ribose polymerase,PARP)抑制剂、蒽环/紫衫、免疫治疗、血管内皮生长因子受体(vascular endothelial growth factor receptor,VEGFR)抑制剂、雄激素受体(androgen receptor,AR)拮抗剂以及各靶向治疗手段的联合使用.结论 TNBC是异质性疾病,其分子分型的确定对于理解肿瘤的生物学特征和临床行为,以及发展TNBC个体化治疗都是必需的.由于TNBC肿瘤信号通路之间的交联,发展不同靶向药物的联合应用才有望真正的提高该疾病的总生存.     

阿司匹林、其他非甾体类抗炎药以及对乙酰氨基酚用药与绝经后乳腺癌发病率的关系

目的阿司匹林、其他非甾体类抗炎药（NSAID）以及对乙酰氨基酚用药与绝经后妇女的乳腺癌发病率之间的关系尚不明确。本研究从乳腺癌的整体和分子亚型角度对上述关系进行探讨。患者和方法研究自1980年开始，对84602位起初没有罹患癌症的绝经妇女进行观察，持续至2008年6月，并以两年一次的调查问卷形式前瞻性地采集了镇痛药物用药情况、生育史以及其他相关生活方式信息。     

蛋白质棕榈酰化修饰与消化系统肿瘤关系研究进展

目的 总结蛋白质棕榈酰化的机制及与癌症发生发展的关系,通过分析棕榈酰化在消化系统肿瘤中的研究进展,探索靶向棕榈酰化过程用于消化系统肿瘤治疗方面的潜在策略。方法 以“棕榈酰化、翻译后修饰、消化系统肿瘤、肿瘤治疗”为中文检索词,以“protein palmitoylation、post-translational modification、digestive system cancer、tumor therapy”为英文检索词,检索PubMed和中国知网数据库2007年1月-2023年7月的相关文献。纳入标准：(1)棕榈酰化的生化反应机制和特点;(2)棕榈酰化过程与癌症相关机制;(3)棕榈酰化在消化系统肿瘤中的作用;(4)靶向棕榈酰化途径对于肿瘤治疗的潜在作用。排除标准：(1)研究机制模糊文献;(2)会议性和评论类文献;(3)内容相似或重复文献。最终共纳入符合条件文献70篇。结果 蛋白质棕榈酰化对于癌基因(如N-Ras和表皮生长因子受体)的功能至关重要。在调控蛋白质的转运、细胞定位和稳定性等方面都具有重要的作用,参与诸多生物学过程,并与消化系统肿瘤的发生发展关系密切。靶向棕榈酰化过程或联合...     

阿司匹林预防肺癌作用Meta分析

目的:评价阿司匹林预防肺癌发生的疗效,为临床实践和研究提供参考和依据。方法:通过检索中国生物医学文献数据库、中国学术期刊网络出版总库、PudMed和EMbase等国内外权威的数据库,全面收集相关的临床研究,按纳入排除标准筛选文献并收集相关数据和信息,采用Rev Man 5.0统计软件进行Meta分析,并对性别、阿司匹林剂量和疗程等进行亚组分析。结果:共纳入17个临床研究,Meta分析显示,使用阿司匹林者较未使用者肺癌的发生率较低,OR=0.82,95%CI:0.72~0.94。亚组分析显示,低剂量阿司匹林(≤100mg)可能较高剂量阿司匹林(>100mg)效果好,OR及其95%CI分别为0.94(0.81~1.09)和1.01(0.87~1.16);长期服用阿司匹林能降低肺癌发病,服用≤1年、>1~<5年、≥5年与肺癌发生关系的OR值及其95%CI,分别为1.06(0.94~1.20)、0.73(0.57~0.94)和0.73(0.57~0.93)。结论:低剂量(≤100mg)长期(>1年)使用阿司匹林在降低肺癌发病方面收益更大。由于本Meta分析纳入的为观察性临床研究,所以将来有必要开展多中心大样本的随机对照试验来进一步证实。     

Aspirin and other nonsteroidal anti-inflammatory drugs and breast cancer incidence in a large U.S. cohort.

Use of nonsteroidal anti-inflammatory drugs (NSAIDs), particularly aspirin, has consistently been associated with reduced risk of breast cancer in case-control studies. However, results from prospective studies have been less consistent. We examined the association between NSAID use and breast cancer incidence, adjusting for multiple breast cancer risk factors among 77,413 women in the Cancer Prevention Study II Nutrition Cohort. During follow-up from 1992 to 2001, we observed 3,008 cases of incident breast cancer. Information on NSAID use was obtained from a questionnaire completed at enrollment in 1992 or 1993 and was updated using follow-up questionnaires in 1997 and 1999. NSAID use was modeled using time-dependent variables to update exposure status. Neither current total NSAID use (aspirin and other NSAIDs combined) nor current aspirin use were associated with breast cancer incidence even at relatively high levels of use [rate ratio (RR), 1.07; 95% confidence interval (95% CI), 0.96-1.21 for > or =60 NSAID pills per month compared with no reported use of NSAIDs; RR, 1.01; 95% CI, 0.84-1.20 for > or =60 aspirin per month compared with no reported use of aspirin]. Even long-duration regular use (> or =30 pills per month for > or =5 years) was not associated with breast cancer incidence (RR, 1.05; 95% CI, 0.88-1.26 for total NSAIDs; RR, 0.88; 95% CI, 0.69-1.12 for aspirin). Although we cannot exclude a small reduction in breast cancer risk associated with NSAID use, the results of this study provide evidence against a large reduction in risk.     

Association of aspirin and nonsteroidal anti-inflammatory drug use with breast cancer.

OBJECTIVE: Previous epidemiological studies have suggested that use of aspirin or other nonsteroidal anti-inflammatory drugs (NSAIDs) may be associated with reduced risk of breast cancer, but some studies have been limited in their ability to separate the effects of aspirin from other NSAIDs or to account for breast cancer risk factors. METHODS: We examined the incidence of breast cancer in association with self-reported aspirin, as well as other nonaspirin NSAID use in a large prospective cohort of postmenopausal women (n = 27,616). Over 6 years of follow-up, 938 incident breast cancers were identified. RESULTS: After adjustment for other breast cancer risk factors, any current use of aspirin or other NSAIDs compared with no use was associated with a reduction in risk of breast cancer [relative risk (RR) = 0.80, 95% confidence interval (CI) 0.67-0.95]. There was a trend of decreasing risk of incident breast cancer with increasing frequency of aspirin use (P(trend) = 0.0011). The multivariate-adjusted RR of breast cancer was 0.71 (95% CI 0.58-0.87) for women who reported using aspirin six or more times per week compared with women who reported no use. These results did not depend on whether women had early or late stage breast cancer. No association was found between nonaspirin NSAID use and incident breast cancer. The adjusted RR of using other NSAIDs six or more times per week compared with no use was 1.01 (95% CI 0.83-1.25). CONCLUSION: This prospective study corroborates other reports that use of aspirin might reduce risk of breast cancer.     

Non-steroidal anti-inflammatory drug (NSAID) use and breast cancer risk in the Western New York Exposures and Breast Cancer (WEB) Study

Objective

Chronic inflammation is suspected to have a role in breast carcinogenesis. Results of studies of non-steroidal anti-inflammatory drugs (NSAIDs) and breast cancer have been inconsistent. Timing of exposure and analysis of individual NSAIDs should be considered.

Methods

We conducted a population-based case–control study in western New York State between 1996 and 2001. Cases, 35–79 years, had incident, primary, histologically confirmed breast cancer (n = 1,170). Controls (n = 2,115) were randomly selected from NY Department of Motor Vehicles records (<65 years) or Medicare rolls (≥65 years). Participants were queried on use of aspirin, ibuprofen, and acetaminophen in the year prior and on aspirin during adulthood. Unconditional logistic regression was used to estimate adjusted odds ratios (OR) and 95% confidence intervals (95% CI).

Results

Recent aspirin use was inversely associated with breast cancer risk (adjusted OR 0.80, 95% CI: 0.68–0.94); the strongest reduction in risk was observed among those who took ≥2 pills/day on days that aspirin was taken (OR 0.74, 95% CI: 0.61–0. 90). Adult lifetime use was also associated with breast cancer risk (>10 days/month, adjusted OR 0.68, 95% CI: 0.46–1.00). Use of ibuprofen or acetaminophen was not associated with breast cancer.

Conclusions

This is the first study to investigate the association of adult lifetime aspirin intake with breast cancer risk. Our findings provide evidence that aspirin use throughout a woman’s life may confer some benefit.     

Aspirin use and head and neck cancer survival: an observational study of 11,623 person-years follow-up

Background

Acetylsalicylic acid (aspirin) and non-steroidal anti-inflammatory drugs (NSAIDs) have been associated with reduced risks for certain human cancers. However, the effects of aspirin and NSAIDs on head and neck squamous cell carcinoma (HNSCC) remain controversial, and the prognostic effects of these drugs in patients with HNSCC are largely unknown. This study examined the clinical impact of aspirin and NSAIDs on disease recurrence and survival in patients with HNSCC.

Methods

This study analysed a cohort of 1392 consecutive patients who received definitive treatment for previously untreated HNSCC at our tertiary referral center. Aspirin or NSAID use was considered positive if the patients were receiving aspirin or NSAID medication from HNSCC diagnosis to at least 1 year after treatment initiation. Cox proportional hazard models were utilised to determine the association of aspirin and/or NSAID use with recurrence, survival, and second primary cancer occurrence.

Results

Of 1392 patients, 81 (5.8%) and 89 (6.4%) received post-diagnosis treatment with aspirin and NSAIDs, respectively. After controlling for clinical factors, aspirin and NSAIDs were not significantly associated with recurrence, survival, or second cancer occurrence (P > 0.05). The cumulative dose of aspirin or NSAIDs did not alter survival outcomes (P > 0.05).

Conclusion

Our data illustrated that the use of aspirin or NSAIDs has no effect on survival or recurrence in patients with HNSCC.

     

The effect of anticoagulants on cancer risk and survival: systematic review

OBJECTIVES: Several in vitro and in vivo studies have shown that low molecular weight heparin and warfarin may directly inhibit tumour cell growth and prevent metastatic spread. However, the clinical evidence in support of an anti-cancer effect is less conclusive. We summarize the evidence from clinical studies that examine the effect of these anticoagulants on cancer development and briefly describe the current understanding of the potential mechanisms by which anticoagulants may exert an anti-cancer effect. METHODS: English-language articles reporting on warfarin, coumarin or low molecular weight heparin for the treatment or prevention of cancer were selected from PUBMED. All randomized clinical trials, case-control studies, cohort studies, and meta-analyses were retrieved. Detailed data review and abstraction was performed according to pre-specified criteria. RESULTS: Of ninety-nine articles retrieved, 12 warfarin and 17 low molecular weight heparin articles were included in the review. We found no consistent evidence that warfarin may improve cancer survival, though there is indirect evidence that prolonged warfarin use may decrease the risk of urogenital cancer. Low molecular weight heparin may improve survival of patients with small cell lung cancer and those with advanced malignancy who have more favorable prognoses. CONCLUSION: Clinical evidence exists in support of an anti-neoplastic effect of anticoagulants. However, more research is needed to further define which cancer type and stage would most benefit from low molecular weight heparin, as well as to explore the role of warfarin in urogenital tumour development.     

Chemoprevention for pancreatic cancer

For a number of solid tumors, including pancreatic cancer, efforts aimed at disease prevention may be more successful than currently available anticancer treatments. While specific interventions are emerging to prevent breast, prostate, lung, and colorectal cancer, no trials of chemoprevention are being conducted in pancreatic cancer. Importantly, there are significant obstacles to the conduct of such research. However, preclinical and epidemiologic studies suggest that several drugs may have chemopreventive potential in pancreatic cancer. These include aspirin and other non-steroidal antiinflammatory drugs (NSAIDs), selective cyclooxygenase inhibitors, somatostatin analogs, selective estrogen receptor modulators (SERMs), and anti-androgenic agents. As the oncology community evaluates some of these agents in large chemoprevention trials for breast, colon, and prostate cancer, it may be found that pancreatic cancer prevention occurs as an unintended, but desirable consequence. Moreover, other general societal trends, such as smoking cessation and the widespread use of cholesterol-lowering agents and aspirin, could have a role in reducing the risk of pancreatic cancer, and in the future, may lead to a decrease in its incidence.     

Research on complementary/alternative medicine for patients with breast cancer: a review of the biomedical literature.

PURPOSE: This article reviews English-language articles published in the biomedical literature from 1980 to 1997 that reported results of clinical research on complementary and alternative medical treatments (CAM) of interest to patients with breast cancer. METHODS: We searched 12 electronic databases and the bibliographies of the retrieved papers, review articles, and books on CAM and breast cancer. The retrieved articles were grouped by end point: breast cancer (eg, tumor size, survival), disease-related symptoms, side effects of treatment, and immune function. Within each end point, we organized the articles by modality and assessed study design, findings, and qualitative aspects. RESULTS: Of the more than 1,000 citations retrieved, 51 fit our criteria for review. Of the articles reviewed, 17 were randomized clinical trials; three of these were trials of cancer-directed interventions, two of which involved the same treatment (melatonin). Seven articles described observational studies, and the remainder were reports of phase I or II trials. Relatively few CAM modalities reportedly used by many breast cancer patients were mentioned in articles retrieved by this process. Most articles had shortcomings. CONCLUSION: Although many studies had encouraging results, none showed definitively that a CAM treatment altered disease progression in patients with breast cancer. Several modalities seemed to improve other outcomes (eg, acupuncture for nausea, pressure treatments for lymphedema). If CAM studies are well-founded, well-designed, and meticulously conducted, and their hypotheses, methods, and results are reported clearly and candidly, research in this controversial area should acquire credibility both in the scientific community and among advocates of unconventional medicine.     

The role of aspirin in the prevention of polyp recurrence: What is the right dose?

Large cohort studies have demonstrated efficacy of aspirin for cardiovascular disease prevention. Aspirin and other NSAIDs inhibit cyclooxygenase-2 (COX-2), a mediator of prostaglandin production. Nonselective (sulindac) and selective COX-2 inhibitors (celecoxib, rofecoxib) induced regression of adenomas in familial adenomatous polyposis, with dose-dependent efficacy in one such trial. Randomized, controlled trials of patients with previous adenoma or colorectal cancer have shown significant efficacy at daily aspirin doses of 81 to 325 mg/d, although lowest effective aspirin dose was not clearly established. Cohort studies have underscored the need for very long-term (> 10 years) use of aspirin to reduce rates of colorectal cancer. Confounders included intermittent and variable dosing and the use of other NSAIDs and risk modifying drugs, so no clear aspirin dosing message has come from cohort studies. The randomized, controlled trials and cohort studies have taken place during a time when NSAID drug safety has come under challenge. Adverse cardiovascular events in the selective COX-2 inhibitor trials in nonfamilal adenomas have forced reexamination of the safety of NSAIDs in general. New studies will have to balance efficacy and safety more than ever.     

The fibroblast growth factor receptor 1 (FGFR1), a marker of response to chemoradiotherapy in breast cancer?

There is evidence that aspirin use reduces the risk of breast cancer. Increased mammographic density is known to be associated with increased breast cancer risk. Little is known about the association between mammographic density and aspirin or other non-steroidal anti-inflammatory drug (NSAID) use, but it is possible that the association between aspirin use and breast cancer risk might be due to the effect of aspirin on mammographic density. Multiple linear regression was used to investigate the association between measures of mammographic density and the use, frequency, and duration of aspirin and other NSAIDs such as paracetamol (acetaminophen), arthritis medication, and other over-the-counter or doctor-prescribed pain medications in 3286 women from the Australian Mammographic Density Twins and Sisters Study and the Genes Behind Endometriosis Study. We found no association between either dense area or percent dense area with any of the NSAIDs examined (all P > 0.06). If aspirin is reducing the breast cancer risk in women, it is likely doing so via a different pathway other than mammographic density measures that predict breast cancer risk.     

NSAID use and breast cancer risk in the VITAL cohort

OBJECTIVE: We prospectively evaluated the association between average 10-year use of NSAIDs and invasive breast cancer. METHODS: Between 2000-2002, 35,323 postmenopausal women participating in the Vitamins And Lifestyle (VITAL) study provided detailed information regarding NSAID use, lifestyle and breast cancer risk factors. Using a Cox proportional hazards model, we analyzed associations between NSAID use and incident breast cancer (N = 482) ascertained through linkage to the SEER cancer registry. RESULTS: Use of low-dose aspirin at 4+ days/week over ten years was associated with a decreased risk of breast cancer (HR 0.65, confidence interval [CI] 0.43-0.97) versus no use, as was moderate use of other types of NSAIDs (HR 0.78, CI 0.61-0.98) for 10-yr average use up to 3 days/week. However, more frequent use of NSAIDs other than low-dose aspirin was associated with an increased risk (HR 1.26, CI 0.96-1.65), particularly frequent use of regular or extra strength aspirin (HR 1.43, CI 1.02-2.00). CONCLUSIONS: We did not find evidence of a global protective effect of NSAID use for the development of breast cancer. However, long-term moderate use (frequent use of low doses or moderate frequency of high doses) was associated with reduced risk, while frequent use of higher dose products was associated with increased risk.