中医药在肿瘤治疗中增效减毒作用的研究进展

肿瘤是严重危害人类生命健康的常见多发病。恶性肿瘤的防治与研究是全世界医学家非常关注的课题。传统的肿瘤治疗方法主要有化疗、放疗及手术治疗,三种治疗手段各有千秋。却也都有其不足之处。手术治疗常不适于某些晚期恶性肿瘤及身体极度虚弱患者;放、化疗则常引起如胃肠反应、骨髓抑制等毒副反应,使患者难以坚持治疗。中医药是祖国流传下来的宝贵财富．其独特的中医辨证理论和卓越的中药疗效。     

CAR-T细胞治疗消化系统肿瘤的研究进展

消化系统肿瘤具有高发病率、高病死率的特点,在我国的肿瘤谱中,消化系统肿瘤占一半以上。对于消化系统肿瘤,目前最有效的手段仍然是手术,但是一旦缺乏手术指征,就几乎没有特别有效的治疗手段。因此,亟需发展新型的治疗手段。嵌合抗原受体修饰的T细胞(CAR-T)无疑是最令人期待的治疗手段之一,目前已经有多个针对消化系统肿瘤的临床试验正在开展。最近,个别方案已经取得了令人兴奋的临床研究结果。将对最新进展作一简要综述。     

基于胰腺癌患者来源异种移植模型的化疗药物筛选

目的 利用胰腺癌PDX模型,评估临床化疗药物治疗效果,筛选个体化治疗方案。方法 将新鲜的胰腺癌手术标本移植裸鼠皮下,建立PDX模型并稳定传代;利用STR基因分型检测PDX模型肿瘤组织的溯源性;选择临床使用的奥沙利铂、吉西他滨和伊立替康三种化疗药物进行治疗,并测量肿瘤体积;利用TGD值数学模型方法,辅以血浆CA19-9检测评估三种化疗药物的治疗效果。结果 PDX模型肿瘤组织样本的溯源性为99.99%,与原发瘤保持一致;与对照组相比,伊立替康组和吉西他滨组均具有显著的治疗效果(P=0.001),且吉西他滨抑瘤效果更为明显;伊立替康的药物毒性作用最小,吉西他滨次之。结论 成功建立胰腺癌PDX模型并稳定传代,通过TGD值数学模型法筛选,发现吉西他滨抑制肿瘤生长效果最为显著,推荐其作为该胰腺癌个体化治疗首选药物。     

新辅助化疗对局部晚期宫颈癌低氧诱导因子-1α mRNA表达的影响

目的：探讨新辅助化疗PF方案的两种给药途径（子宫动脉置管与静脉全身化疗）对宫颈癌低氧诱导因子-1α（HIF-1α）表达的影响及其临床意义。方法：应用RT-PCR方法测定43例局部晚期宫颈癌病人子宫动脉置管与静脉全身化疗后癌组织的研究缺氧诱导因子（HIF-1α）mRNA表达的影响,评价化疗近期效果。结果：局部晚期宫颈癌患者经子宫动脉置管与静脉全身化疗比较,临床缓解率相似,但是前者能显著减少化疗引起的骨髓抑制和肝功能损害作用,子宫动脉置管组HIF-1αmRNA表达较静脉全身化疗组明显降低（P〈0．05）。结论：术前子宫动脉置管PF方案化疗,能降低宫颈癌组织的HIF-1αmRNA表达,能减小肿瘤体积。减少化疗的不良反应,改善患者的预后,是一种可行、有效的辅助治疗手段。     

新辅助化疗对局部晚期宫颈癌低氧诱导因子-1αmRNA表达的影响

目的:探讨新辅助化疗PF方案的两种给药途径(子宫动脉置管与静脉全身化疗)对宫颈癌低氧诱导因子-1α(HIF-1α)表达的影响及其临床意义。方法:应用RT-PCR方法测定43例局部晚期宫颈癌病人子宫动脉置管与静脉全身化疗后癌组织的研究缺氧诱导因子(HIF-1α)mRNA表达的影响,评价化疗近期效果。结果:局部晚期宫颈癌患者经子宫动脉置管与静脉全身化疗比较,临床缓解率相似,但是前者能显著减少化疗引起的骨髓抑制和肝功能损害作用,子宫动脉置管组HIF-1αmRNA表达较静脉全身化疗组明显降低(P<0.05)。结论:术前子宫动脉置管PF方案化疗,能降低宫颈癌组织的HIF-1αmRNA表达,能减小肿瘤体积,减少化疗的不良反应,改善患者的预后,是一种可行、有效的辅助治疗手段。     

局部晚期食管癌新辅助治疗的研究进展

食管癌是世界范围内恶性程度高、预后不良的肿瘤之一。手术治疗是局部晚期食管癌治疗的首选方式,但单纯手术治疗效果不佳,总体5年生存率较低。因此,局部晚期食管癌的治疗更倾向于手术联合多种模式的治疗。在局部晚期食管癌中,新辅助治疗展示出了明显的生存获益、良好的临床疗效以及可接受的毒性反应,成为局部晚期食管癌的标准治疗模式之一。新辅助治疗主要包括新辅助化疗、新辅助放化疗、新辅助免疫治疗。本文就局部晚期食管癌新辅助治疗的研究进展进行综述。     

超声引导下肝动脉栓塞化疗治疗晚期肝癌的临床疗效分析

目的:探讨超声引导下肝动脉栓塞化疗治疗进展期大肝癌的疗效和临床应用价值.方法:对我院2009年收治的60例原发性肝癌晚期患者进行超声引导下肝动脉栓塞化疗治疗.并通过彩色多普勒复查肿瘤的血供情况.结果:60例晚期肝癌患者在经过治疗后肝功能有了明显的改善,肿瘤内部及周边血流明显减少,肿瘤血供≥Ⅱ级者由TACE治疗前的90%(54/60)降为术后的71.67%(43/60).结论:在超声引导下准确定位,经肝动脉化疗是晚期肝癌的有效治疗手段,具有较高的安全性和依从性.     

GEMOX方案联合干扰素治疗晚期原发性肝癌32例的临床分析

目的：观察GEMOX方案联合干扰素治疗晚期原发性肝癌的近期疗效和不良反应。方法：32例晚期原发性肝癌均采用GEMOX方案联合干扰素进行化疗及生物治疗,吉西他滨1000 mg/m2,静脉滴注,第1,8天;奥沙利铂100 mg/m2,静脉滴注,第1,8天。21天为一个周期。干扰素600 MIU ih QOD,连用6周。结果：所有患者均完成〉2个周期的GEMOX方案联合干扰素治疗,疾病控制率为65.63%,部分缓解率15.63%,疾病稳定率50%。主要不良反应是骨髓抑制和神经毒性,经治疗均恢复。结论：GEMOX方案联合干扰素治疗晚期原发性肝癌,近期疗效确切,毒副作用可耐受,远期疗效有待观察。     

培美曲塞治疗复发性卵巢癌疗效观察及对糖类抗原125、人肿瘤坏死因子α的影响研究

目的:观察培美曲塞治疗复发性卵巢癌疗效及对糖类抗原125、人肿瘤坏死因子α的影响。方法:回顾性分析2014年3月至2017年6月我院收住院治疗的92例复发性卵巢癌患者的临床资料。根据化疗方式不同分为观察组(培美曲塞)和对照组(紫杉醇联合伊立替康)。统计分析两组患者近期疗效、不良反应、化疗前后血清肿瘤标志物水平。结果:观察组缓解率为60.9%(28/46),明显高于对照组32.6%(15/46),差异具有统计学意义(P0.05)。观察组骨髓抑制发生率为45.7%(21/46),明显低于对照组67.4%(31/46),差异具有统计学意义(P0.05);两组胃肠道反应、脱发、肾功能损害、肝功能损害等不良反应发生率无明显差异(P0.05)。观察组治疗后CA125、TNF-α水平均明显低于对照组,差异具有统计学意义(P0.05)。结论:培美曲塞治疗复发性卵巢癌疗效可靠,安全性高,且对降低患者CA125、TNF-α水平具有重要作用,值得临床借鉴使用。     

进展期胃癌靶向治疗的研究进展

胃癌是消化系统最常见的恶性肿瘤之一,全球每年胃癌新发病例数接近百万,严重影响着人类健康.近年来医学领域发展迅速,不管是胃癌的手术方式,还是放疗、化疗等治疗手段均获得了较大提高.但是由于缺乏有效早期诊断方法,大多数胃癌患者确诊时已进入疾病晚期,所以尽管医学技术不断发展,胃癌的死亡率依然居高不下.随着对胃癌分子机制的不断深入研究,一种直接作用于胃癌主要信号转导通路上某一特定靶点的新型治疗方式-分子靶向治疗逐渐成为当前肿瘤研究的热点.目前已有多种单克隆抗体及小分子靶向药物进入临床,用于人体多种肿瘤的治疗并呈现较好疗效.分子靶向治疗的出现为进展期肿瘤患者带来了新的希望.本文主要就进展期胃癌分子靶向治疗现状以及最新研究进展作一综述.     

应用siRNA干扰胃癌的研究进展

胃癌是消化系统最常见的恶性肿瘤,而我国是胃癌高发区,其发病率和死亡率均高于世界平均水平。在我国大多数患者明确诊断时已进入进展期,所以大多数患者再行手术切除后还需放化疗治疗。近来随着对胃癌的研究深入,可通过对胃癌肿瘤标本行分子检测给予患者药物靶向治疗,实现个体化治疗。RNA干涉(RNAi)技术被广泛用于基因功能的研究,并且在哺乳动物研究中得到飞速发展.si RNA是在RNAi中起中心作用,其可抑制特定m RNA,以调节不同蛋白在肿瘤发生时的异常表达。对si RNA的研究将为胃癌的基因治疗供更广阔的空间。     

Breast cancer local recurrence under the form of inflammatory carcinoma,treated with concurrent radiation and chemotherapy,a case report

The authors present a case report of a patient with breast cancer diagnosed in 2005, treated with conservative surgery, adjuvant chemotherapy and radiotherapy, followed by hormonal therapy until 2010, who relapsed under the form of inflammatory breast cancer in 2011. After tumor progression detected during primary systemic therapy, a concurrent radiation and radiosensitizing chemotherapy were proposed. There was a significant clinical response to this treatment, enabling curative chance with total mastectomy. The histological examination of the breast and regional lymph nodes revealed a complete response, since there was no evidence of residual tumor.There are few reports concerning concurrent radiotherapy and chemotherapy in locally advanced breast cancer, but it could be a suitable “loco regional rescue therapy” to further reduce tumor progression and allow curative surgery. Study of this treatment strategy in randomized clinical trials is warranted.     

细胞凋亡抑制蛋白cIAP 与卵巢癌耐药性的研究进展

卵巢恶性肿瘤是女性生殖系统三大恶性肿瘤之一,其发病率在女性生殖系统肿瘤中占第三位,而死亡率却高居首位。目前对于晚期卵巢癌(Ⅲ或Ⅳ期)多倾向于用新辅助化疗+肿瘤细胞减灭术+术后周期性化疗的治疗方法。但是,尽管多数患者在最初对化疗药物较敏感,但仍有60%~80%最终死于卵巢癌,这些患者大部分都对化疗药物产生了耐药性,在更换新的化疗方案初期是有效的,但最终仍会耐药。近年来,有关细胞凋亡抑制蛋白(cIAP,cellular inhibitors of apoptosis proteins)在卵巢癌复发耐药中的作用机制的研究越来越受到重视。研究证实,cIAP在耐药肿瘤细胞中呈高表达,并与多种因子共同参与形成了上皮性卵巢癌的耐药机制,抑制了化疗药物引起的肿瘤细胞的凋亡。这些发现为攻克卵巢癌的耐药机制提供了重要线索,也为卵巢癌化疗药物的应用指出了新的方向。     

Prognostic implication of HSPA (HSP70) in breast cancer patients treated with neoadjuvant anthracycline-based chemotherapy

Neoadjuvant chemotherapy is used in patients with locally advanced breast cancer to reduce tumor size before surgery. Unfortunately, resistance to chemotherapy may arise from a variety of mechanisms. Heat shock proteins (HSPs), which are highly expressed in mammary tumor cells, have been implicated in anticancer drug resistance. In spite of the widely described value of HSPs as molecular markers in cancer, their implications in breast tumors treated with anthracycline-based neoadjuvant chemotherapy has been poorly explored. In this study, we have evaluated, by immunohistochemistry, the expression of HSP27 (HSPB1) and HSP70 (HSPA) in serial biopsies from locally advanced breast cancer patients (n = 60) treated with doxorubicin (DOX)- or epirubicin (EPI)-based monochemotherapy. Serial biopsies were taken at days 1, 3, 7, and 21, and compared with prechemotherapy and surgical biopsies. After surgery, the patients received additional chemotherapy with cyclophosphamide, methotrexate, and 5-fluorouracil. High nuclear HSPB1 and HSPA expressions were found in invasive cells after DOX/EPI administration (P < 0.001), but the drug did not affect the cytoplasmic expression of the HSPs. Infiltrating lymphocytes showed high nuclear HSPA (P < 0.01) levels at postchemotherapy. No correlations were found between HSPs expression and the clinical and pathological response to neoadjuvant therapy. However, in postchemotherapy biopsies, high nuclear (>31 % of the cells) and cytoplasmic HSPA expressions (>11 % of the tumor cells) were associated with better DFS (P = 0.0348 and P = 0.0118, respectively). We conclude that HSPA expression may be a useful prognostic marker in breast cancer patients treated with neoadjuvant DOX/EPI chemotherapy indicating the need to change the administered drugs after surgery for overcoming drug resistance.     

PF方案同步放化疗治疗中晚期宫颈癌的疗效及毒性反应研究

目的：探究PF 方案同步放化疗治疗中晚期宫颈癌患者的疗效和毒性反应。方法：回顾性分析我院在2014 年6 月～2015 年6 月期间收治的ⅡB～Ⅲ期宫颈癌患者,共152 例,根据治疗方法将其分为单纯放疗组和同步放化疗组,比较两组患者治疗的疗效 和毒性反应。结果：单纯放疗组和同步放化疗组近期疗效总有效率无显著差异,差异不具有统计学意义(P>0.05),但分别对ⅡB 和 Ⅲ期患者进行分析,Ⅲ期患者同步放疗组总有效率显著高于单纯放疗组,差异具有统计学意义(P<0.05);同步放化疗组患者治疗 后骨髓抑制白细胞下降和消化道反应发生率显著高于单纯放疗组,差异具有统计学意义(P<0.05),两组患者皮肤反应的发生情况 比较无显著差异(P>0.05)。结论：PF方案同步放化疗治疗Ⅲ期宫颈癌的临床疗效显著优于单纯放疗治疗,可有效提高近期总有效 率,毒性反应虽较单纯放疗组有所增加,但经临床支持治疗患者均可耐受。     

Changes in circulating VEGF levels in relation to clinical response during chemotherapy for metastatic cancer

Abnormally high blood levels of vascular endothelial growth factor (VEGF) appear to be associated with a poor prognosis in advanced cancer, probably as a consequence of its angiogenic and immunosuppressive effects. The prognostic significance of changes in VEGF secretion during cancer chemotherapy is still unknown. This study aimed to investigate the relation between VEGF variations and therapeutic results during chemotherapy in advanced malignancies. The study included 90 metastatic cancer patients, 59 with non-small cell lung cancer and 31 with colorectal carcinoma. Chemotherapy consisted of cisplatin plus etoposide for NSCLC and camptothecin for colorectal cancer. Abnormally high (> 2 SD with respect to values in healthy controls) pretreatment VEGF levels were found in 38/90 (42%) patients. The percentage of non-progressive disease in response to chemotherapy was significantly higher in patients with normal levels of VEGF prior to therapy than in those with elevated pretreatment values of VEGF (10/32 vs 4/27; p < 0.05). Moreover, the percentage of VEGF level normalization during chemotherapy was significantly higher in patients with objective tumor response or stable disease than in progressing patients (10/18 vs 0/20; p < 0.001). Finally, among patients with tumor response or disease stabilization, the one-year survival rate was significantly higher in patients with chemotherapy-induced normalization of VEGF than in those with persistently high VEGF blood levels (9/10 vs 3/8; p < 0.05). These results suggest that changes in VEGF levels during chemotherapy may represent a useful biomarker to predict the effect of chemotherapy in terms of tumor response and survival in patients with metastatic solid neoplasms.     

P-糖蛋白对结肠癌多药耐药的影响

结肠癌是常见的消化道恶性肿瘤。对术后患者以及无法采用手术治疗的患者,临床多采用化疗、放疗等综合性治疗方法。随着大量化疗药物在临床的广泛使用,结肠癌多药耐药性成为化疗失败的最主要原因。研究表明,P-糖蛋白(P-glycoprotein, P-gp)作为ATP结合盒(ABC)转运蛋白超家族成员之一,与多种肿瘤的多药耐药相关,其介导的多药耐药已经成为目前研究的热点。本文旨在通过对P-糖蛋白的结构、耐药机制以及逆转P-糖蛋白介导的结肠癌多药耐药新发现进行阐述,引导读者对P-糖蛋白在结肠癌多药耐药中的作用有更深入的了解。     

Targeted therapies in epithelial ovarian cancer: Molecular mechanisms of action

Ovarian cancer is the leading cause of death in women with gynecological cancer. Most patients are diagnosed at an advanced stage and have a poor prognosis. Currently, surgical tumor debulking, followed by platinum- and taxane-based chemotherapy is the standard treatment for advanced ovarian cancer. However, these patients are at great risk of recurrence and emerging drug resistance. Therefore, novel treatment strategies are required to improve outcomes for women with advanced ovarian cancer. A variety of molecular targeted agents, the majority of which are monoclonal antibodies and small-molecule protein-kinase inhibitors, have been explored in the management of ovarian cancer. The targets of these agents include angiogenesis, the human epidermal growth factor receptor family, ubiquitin-proteasome pathway, epigenetic modulators, poly(ADP-ribose) polymerase (PARP), and mammalian target of rapamycin (mTOR) signaling pathway, which are aberrant in tumor tissue. The antiangiogenic agent, bevacizumab, has been reported as the most effective targeted agent and should be included in the standard chemotherapeutic regimen for advanced ovarian cancer. PARP inhibitors, which are mainly used in breast and ovarian cancer susceptibility gene-mutated patients, and mTOR inhibitors are also attractive treatment strategies, either alone or combination with chemotherapy, for ovarian cancer. Understanding the tumor molecular biology and identification of predictive biomarkers are essential steps for selection of the best treatment strategies. This article reviews the molecular mechanisms of the most promising targeted agents that are under early phase clinical evaluation for ovarian cancer.     

ncRNAs associated with drug resistance and the therapy of digestive system neoplasms

Digestive system cancer remains a common cancer and the main cause of cancer-related death worldwide. Drug resistance is a major challenge in the therapy of digestive system cancer, and represents a primary obstacle in the treatment of cancer by restricting the efficiency of both traditional chemotherapy and biological therapies. Existing studies indicate that noncoding RNAs play an important role in the evolution and progression of drug resistance in digestive system cancer, mainly by modulating drug transporter-related proteins, DNA damage repair, cell-cycle-related proteins, cell apoptosis-related proteins, drug target-related proteins, and the tumor microenvironment. In this review, we address the potential mechanisms of ncRNAs underlying drug resistance in digestive system tumors and discuss the possible application of ncRNAs against drug resistance in digestive system tumors.