唑来膦酸在乳腺癌中抗肿瘤作用的研究现状

唑来膦酸作为第3代双膦酸盐药物已广泛用于乳腺癌骨转移相关事件的防治。唑来膦酸在乳腺癌中具有抗肿瘤治疗作用。唑来膦酸通过抑制乳腺癌细胞的增殖和诱导细胞凋亡,降低肿瘤细胞的迁移、侵袭能力,防止有利于肿瘤生长的骨微环境的形成,抑制肿瘤新生血管形成,调节免疫等多种途径直接或间接发挥其抗肿瘤作用,与放化疗及内分泌等辅助治疗有序贯协同增效作用。唑来膦酸在乳腺癌患者辅助治疗中的协同抗肿瘤作用也在几项相关的前瞻性临床试验中进行。     

肿瘤的靶向治疗

靶向治疗是针对肿瘤细胞恶性表型的分子靶点,作用于促进肿瘤生长、存活的特异性细胞受体、信号传导等通道,实现抑制肿瘤细胞生长或促进凋亡的抗肿瘤作用。新的靶向治疗药物rituximab、伊马替尼、赫赛汀和全反式维甲酸已开始用于临床治疗,本文综述这些药物的作用机制、适应证、疗效及安全性。与传统细胞毒化疗不同,肿瘤靶向治疗具有特异性抗肿瘤作用,并且毒性明显减少。肿瘤靶向治疗令人鼓舞的初步成果为其进一步发展奠定了基础,提供了典范,开创了肿瘤化疗的新领域。     

重组人血管内皮抑制素在乳腺癌治疗中的研究进展

大量研究表明抗血管生成治疗与放疗、化疗、免疫治疗及其他抗肿瘤药物联合使用可发挥协同增效作用。重组人血管内皮抑制素（恩度）是一种泛靶点类抗肿瘤血管生成靶向药物,其可通过抑制或调节肿瘤血管生成的多条信号通路,抑制内皮细胞的增殖、迁移,同时诱导内皮细胞的凋亡,抑制血管通透性的增加,使肿瘤血管“正常化”,重塑肿瘤微环境,从而改善肿瘤的综合治疗疗效,抑制肿瘤的生长和转移。近年来,恩度用于治疗乳腺癌的研究逐渐增多,并取得了可观的治疗效果,且不良反应小。全文就恩度的作用机制及其在乳腺癌治疗中的研究进展作一综述,旨在探讨恩度在乳腺癌治疗中的应用前景及优化手段,以期为乳腺癌患者尤其是三阴性乳腺癌患者带来更长远的生存获益。     

乳腺癌化疗耐药中肿瘤干细胞的作用及其机制

目的:了解肿瘤干细胞在乳腺癌化疗耐药中的作用及其相关机制的研究进展。方法:应用检索Pubmed及CNKI数据库检索系统,以肿瘤、干细胞、乳腺癌、化疗和耐药等为关键词,检索1999-01-2011-05的相关文献,纳入标准:肿瘤干细胞与乳腺癌化疗耐药。根据纳入标准分析42篇文献。结果:肿瘤干细胞是导致乳腺癌化疗耐药和治疗失败的主要细胞,其耐药的机制包括ATP结合盒转运子的过度表达、细胞解毒酶的过度活化、细胞存活和凋亡相关信号转导通路的异常激活、肿瘤壁龛对肿瘤干细胞的保护作用以及大部分肿瘤干细胞处于静止期。通过对这些耐药机制的干预,可以逆转肿瘤干细胞的耐药性。结论:肿瘤干细胞是导致乳腺癌化疗耐药的关键细胞,对其耐药机制的研究有助于展开针对肿瘤干细胞的靶向治疗,改善患者的预后。     

卵巢癌肿瘤干细胞耐药性及其治疗的研究进展

肿瘤干细胞是肿瘤组织内具有自我更新能力及无限增殖潜能的一群细胞,对外源细胞毒性药物耐受。卵巢癌肿瘤干细胞在卵巢癌发生、化疗耐药和复发过程中起重要作用。传统治疗对减小肿瘤体积有效,但是治疗后残留的卵巢癌干细胞成为卵巢癌复发和难治的根源,针对卵巢癌肿瘤干细胞的靶向治疗可能在抗卵巢癌治疗中具有重要作用,为临床彻底治愈卵巢癌带来希望。     

协同刺激分子PD-L1、B7-H3与B7-H4在卵巢癌中的表达及其意义

协同刺激分子PD-L1、B7-H3与B7-H4可与T细胞及其受体结合并抑制T细胞的增殖和过度活化,在细胞免疫应答过程中起重要的调控作用,已被多项研究证明与肿瘤的免疫原性及肿瘤的发生、发展密切相关。这3种分子在正常卵巢组织中均不表达,而在卵巢癌组织中呈不同程度的高表达,它们可能在促进卵巢癌的发生、转变及病情进展过程中起重要作用,研究其作用机制对卵巢癌的早期诊断及靶向治疗有一定的意义。     

唑来膦酸联合靶向及免疫调节药物的抗肿瘤研究进展

唑来膦酸是第三代含氮双磷酸盐,在临床中广泛用于治疗骨疾病。既往研究发现唑来膦酸在体内外对多种肿瘤细胞均有抗肿瘤作用,同时可以协同增加化疗、内分泌治疗、放疗等抗肿瘤疗效。最近研究发现,唑来膦酸亦可以协同增加靶向及免疫调节药物的抗肿瘤疗效,其抗肿瘤作用机制与抑制甲羟戊酸代谢途径、影响肿瘤信号通路、调节免疫反应、抗血管生成等有关。本文综述了唑来膦酸联合靶向及免疫调节药物在抗肿瘤治疗方面的研究进展。     

乳腺癌治疗新方向—乳腺癌微环境

乳腺癌是女性发病率最高的恶性肿瘤,严重威胁女性健康,为探究新的治疗方法,研究人员将肿瘤微环境作为潜在的抗癌靶标。肿瘤微环境由几种关键的细胞类型组成,包括成纤维细胞、血管和淋巴内皮细胞、破骨细胞、脂肪细胞和免疫细胞,这些细胞有利于肿瘤的发生、发展和转移,因此,这些宿主细胞有望成为抗肿瘤和抗转移治疗中的潜在靶标。突变和耐药是抗肿瘤治疗失败的重要原因,靶向肿瘤相关宿主细胞的优势是这些细胞较少发生突变和耐药性。本文讨论了宿主细胞在肿瘤发生、发展和转移过程中的作用,以及靶向这些细胞群治疗肿瘤的新发展。     

肿瘤的节拍化疗

节拍化疗指以肿瘤内增殖的血管内皮细胞为靶点,通过持续应用低毒性剂量的药物而抑制肿瘤血管生成的一种化疗模式。节拍化疗在头颈部肿瘤、乳腺癌、消化道肿瘤、卵巢癌和前列腺癌中的成功应用显示了其潜在价值。节拍化疗的作用机制除抗肿瘤血管生成外,还包括刺激免疫和直接抗肿瘤效应,其与其他治疗模式的联合应用尚待深入探索。     

异硫氰酸酯抗肿瘤作用机制研究新进展

异硫氰酸酯(isothiocyanate,ITC)是由硫代葡萄糖苷经黑芥子酶水解形成的天然小分子,广泛存在于十字花科蔬菜中.大量研究证明异硫氰酸酯可以通过诱导肿瘤细胞周期阻滞、促进肿瘤细胞凋亡、诱导活性氧的产生等多种机制抑制肿瘤细胞在体内、体外的增殖.近期研究发现异硫氰酸酯还可以抑制肿瘤细胞侵袭转移、诱导内质网应激和细胞自噬.本文对异硫氰酸酯的抗肿瘤作用机制进行综述.     

Metastatic breast cancer from gastric and ovarian cancer,mimicking inflammatory breast cancer: report of two cases

Breast metastases from extra-mammary malignancies, especially those mimicking primary inflammatory breast carcinoma, are extremely rare. We report here two cases of inflammatory breast metastases from gastric or ovarian cancer. Both patients, who had prior advanced malignant disease, presented with unilateral breast redness and swelling with peau d’orange sign, resembling primary inflammatory breast cancer or acute mastitis. Breast biopsy revealed poorly differentiated adenocarcinoma with signet-ring cells or clear cell carcinoma in the lymphatic vessels and the parenchyma without an in situ lesion, similar to primary lesions of the stomach or ovary, respectively. Immunohistochemical staining for estrogen receptor, progesterone receptor, and gross cystic disease fluid protein 15 was of value for correct diagnosis. Since breast metastasis is a sign of poor prognosis of the primary malignant disease, the possibility of breast metastasis should be considered in appropriate patients to preclude unnecessary major surgery.     

Second primary cancer among 217702 colorectal cancer survivors: An analysis of national German cancer registry data

With improvements in survival after colorectal cancer (CRC), more survivors are at risk of developing a second cancer, particularly in younger populations where CRC incidence is increasing. We estimated the incidence of second primary cancer (SPC) in CRC survivors and its potential risk factors. We identified CRC cases diagnosed between 1990 and 2011 and SPCs until 2013 from nine German cancer registries. Standardized incidence ratios (SIR) and absolute excess risk (AER) per 10 000 person-years were calculated and were stratified by index site: colon cancer (CC) and rectal cancer (RC), age and sex. Cox regression assessed potential SPC risk factors, including primary tumor-related therapy considering death as a competing risk. We included 217 202 primary CRC cases. SPC occurred in 18 751 CRC survivors (8.6%; median age: 69 years). Risk of cancer was significantly higher in CRC survivors than in the general population (SIR males 1.14, 95% confidence interval [CI] 1.12-1.17, AER = 24.7; SIR females 1.20, 95% CI 1.17-1.23, AER = 22.8). Increased risks of SPCs were observed for the digestive system, urinary system and female and male reproductive organs. CRC incidence increased in younger persons (<50 years) and SPC incidence was 4-fold in this group (SIR males 4.51, 95% CI 4.04-5.01, AER = 64.2; SIR females 4.03, 95% CI 3.62-4.48, AER = 77.0). Primary tumor-related factors associated with SPC risk were right-sided cancer and smaller primary tumor size. Treatment and risk of SPC differed for CC (no effect) and RC (lower risk after chemotherapy). CRC survivors have excess risk of developing SPC, with particular characteristics that could guide targeted surveillance.     

Impact of radiotherapy in the risk of esophageal cancer as subsequent primary cancer after breast cancer

PURPOSE: To assess the risk of esophageal cancer as second cancer among breast-cancer patients treated with radiotherapy. METHODS AND MATERIALS: The records of the Finnish Cancer Registry from 1953 to 2000 were used to assess the risk of esophageal cancer as second cancer among 75,849 breast-cancer patients. Patients were treated with surgery (n = 33,672), radiotherapy (n = 35,057), chemotherapy and radiotherapy (n = 4673), or chemotherapy (n = 2,447). The risk of a new primary cancer was expressed as standardized incidence ratio (SIR), defined as the ratio of observed to expected cases. RESULTS: By the end of 2000, the number of observed cases esophageal cancers was 80 vs. 72 expected cases (standardized incidence ratio (SIR) = 1.1, 95% Confidence Interval (CI) = 0.9 to 1.5). Among patients followed for 15 years and treated with radiotherapy, the SIR for esophageal cancer was 2.3 (95% CI = 1.4 to 5.4). No increase in risk was seen for patients treated without radiotherapy. The risk of esophageal cancer was increased among patients diagnosed during 1953 to 1974, although age at the treatment did not have marked effect on the risk estimate. CONCLUSION: Increased risk of second cancer in the esophagus was observed for breast-cancer patients in Finland, especially among patients with over 15 years of follow-up and treated in the earliest period, which may relate to the type of radiotherapy.     

Conundrums in screening for cancer

Screening for cancer has to be carefully organized for maximum effectiveness, and introduced in full understanding of the natural history of the disease. There are major potential harms as well as benefits from screening. The current state of art for breast, cervix and prostate cancer screening is reviewed, only for breast and cervix are policies of screening in the population justified.     

The thrombophilic state in cancer part II: cancer outcomes, occult malignancy, and cancer suppression

The association between malignancy and thrombosis has long been appreciated but remains incompletely understood. This is the second of a two-part review of the complex, integral relationship between these two entities, and addresses the specifics of cancer outcomes, occult malignancy in the presence of thrombosis, and the possibilities of cancer suppression by modulating thrombogenesis.     

单克隆抗体检测大便样品诊断大肠癌的研究

目的应用抗人大肠癌单克隆抗体对正常人群进行筛选和大肠癌诊断的研究.方法采用ELISA法对正常人群和病理切片确诊为大肠癌的患者以及大肠癌患者手术前后的大便样品进行对比研究.结果应用本抗人大肠癌单克隆抗体(Anti-colorectalcancerantibody,Anti-Cca)可以通过检测大便进行正常人群的筛查;对大肠癌患者手术前后的大便进行对比性研究发现,手术前大便的检测结果呈强阳性,手术后为阴性.对临床病理检查已经确诊为大肠癌的患者,再采用抗人大肠癌单克隆抗体检测大便诊断大肠癌,两者的吻合率为100%.结论本实验所使用的大肠癌单克隆抗体可用于从大便中检测大肠癌的脱落细胞,可用于正常人群的筛查和进行大肠癌的诊断研究.     

Screening for colorectal cancer

This review will comprise a general overview of colorectal cancer (CRC) screening. We will cover the impact of CRC, CRC risk factors, screening modalities, and guideline recommendations for screening in average-risk and high-risk individuals. Based on this data, we will summarize our approach to CRC screening.     

Association between endometrial cancer and tamoxifen treatment of breast cancer

A retrospective cohortstudy in 4109 breast cancer patients was undertaken to determine how tamoxifen affected the risk of endometrial cancer. Data on 1701 tamoxifentreated women were analysed. Two thousand four hundred and eight nontamoxifen users served as control group. The occurrence of new primary uterine cancers was assessed by computerized linkage to the Austrian Cancer Registry. Twentyfive women who subsequently developed endometrial cancer were identified. Eight uterine cancers occurred in the tamoxifen group, whereas 17 uterine cancers were found in the control group. The estimate of the relative risk (RR) showed an increased risk to develop endometrial cancer for the tamoxifen group RR 1.136 (95% CI 0.71; 1.80). Analysis of relevant confounding variables did not show any differences in the two groups.In conclusion, this retrospective study demonstrated a nonsignificant increased risk of endometrial cancer in women receiving tamoxifen as treatment for breast cancer. However, the magnitude of RR and the absolute number of endometrial cancer cases in this long term observation demonstrate clearly that the clinical benefit of tamoxifen therapy greatly outweighs the risk.     

Underuse of colorectal cancer screening among men screened for prostate cancer

BACKGROUND:

Evidence suggests that colorectal cancer (CRC) screening reduces disease‐specific mortality, whereas the utility of prostate cancer screening remains uncertain. However, adherence rates for prostate cancer screening and CRC screening are very similar, with population‐based studies showing that approximately 50% of eligible US men are adherent to both tests. Among men scheduled to participate in a free prostate cancer screening program, the authors assessed the rates and correlates of CRC screening to determine the utility of this setting for addressing CRC screening nonadherence.

METHODS:

Participants (N = 331) were 50 to 70 years old with no history of prostate cancer or CRC. Men registered for free prostate cancer screening and completed a telephone interview 1 to 2 weeks before undergoing prostate cancer screening.

RESULTS:

One half of the participants who underwent free prostate cancer screening were eligible for but nonadherent to CRC screening. Importantly, 76% of the men who were nonadherent to CRC screening had a regular physician and/or health insurance, suggesting that CRC screening adherence was feasible in this group. Furthermore, multivariate analyses indicated that the only significant correlates of CRC screening adherence were having a regular physician, health insurance, and a history of prostate cancer screening.

CONCLUSIONS:

Free prostate cancer screening programs may provide a teachable moment to increase CRC screening among men who may not have the usual systemic barriers to CRC screening, at a time when they may be very receptive to cancer screening messages. In the United States, a large number of men participate in annual free prostate cancer screening programs and represent an easily accessible and untapped group that can benefit from interventions to increase CRC screening rates. Cancer 2010. © 2010 American Cancer Society.