Systemic chemotherapy combining biological targeted therapies is the standard therapy for patients with metastatic colorectal cancer (mCRC), but effective markers are needed to identify clinical responders. Circulating tumour cells (CTCs) have been associated with prognosis in patients with mCRC. This study aimed to explore the relationship between CTC number and the clinical response of patients with advanced CRC.

帕妥珠单抗于2018年12月18日在我国正式上市,帕妥珠单抗联合曲妥珠单抗和紫杉醇类药物可能作为人表皮生长因子受体-2(human epidermal growth factor receptor-2,HER2)阳性晚期乳腺癌患者的一线治疗选择[1-4],未来会有越来越多的转移性乳腺癌患者使用曲妥珠单抗、帕妥珠单抗联合紫杉醇类药物的治疗方案,其不良反应也可能越来越常见.本文报道1例转移性乳腺癌患者采用曲妥珠单抗、帕妥珠单抗联合白蛋白紫杉醇方案治疗后出现指甲脱落为典型表现的不良反应,旨在为临床预防和治疗此类不良反应提供借鉴.

Because clinical oncology course for undergraduates is related to many clinical specialties , traditional teaching of this course is likely to lead to repetition and contradiction of knowledge. Clinical medical college carried out integrated curriculum in clinical oncology for three years during the implementation of teaching reform to overcome the above-mentioned disadvantages. Teaching and research sections related to clinical oncology were horizontally integrated under the guidance of teaching affairs office; On the premise of meeting the requirements of teaching outlines, the clinical oncology in internal medicine, surgery and gynecology was systematically improved in accordance with cognitive laws. Following the previous year, PBL teaching program in clinical oncology still focused on the integration of theoretical course and probation course. After integration, the sub-specialty teacher team was gradually shaped, the teaching quality was significantly improved and the clinical thinking of medical students was enhanced.

The standardized training program for medical oncology residents is still in its starting phase.To improve the training quality,we should modify the existing teaching mode and methods,strength ethics awareness and humanistic concern,and perfect the evaluation and assessment system.Therefore,it is necessary to explore the overall strategies for quality improvement of standardized training for medical oncology residents in order to make a complete high-quality training and assessment system and produce more excellent medical oncology residents.

Backgrounds and Objective: Proteasome inhibitors are a kind of novel anti-tumor agent which can inhibit cell growth and induce apoptosis by inhibiting the function of proteasome system and impacting the degradation of proteins related to cell growth or apoptosis. The aim of the study is to explore the effect of proteasome inhibitor Z-Leu-Leu-Phe-CHO (ZLLFC) singly or combined with cisplatin on proliferation or apoptosis of humnan gastric cancer cell SGC-7901, as well as its influence on the expression level of excision repair cross complementing 1(ERCC1) mRNA. Methods: MTT assay was used to calculate the growth inhibitory rate of human gastric cancer cell SGC- 7901. The apoptotic cell morphology was observed with electron microscopy, the apoptotic rate was analyzed by flow cytometry and by expression level of ERCC1 mRNA detected by RT-PCR. Results: Proteasome inhibitor ZLLFC could inhibit the growth of gastric cancer cell SGC-7901. Combined application of proteasome inhibitor ZLLFC and cisplatin significantly increase the inhibitory effect on SGC-7901 cells, induced apoptosis and increased the apoptotic rate. While, the expression level of ERCC-1 mRNA in SGC-7901 cells in the combined group was significantly lower than that of the cisplatin group (p<0.01). Conclusion: Proteasome inhibitor ZLLFC can inhibit the growth of gastric cancer cell SGC-7901. Combined application of ZLLFC and cisplatin can significantly increase the growth inhibiory effect and the apoptosis-promoting effect of gastric cancer cell SGC-7901.

Chemotherapies are known often to induce severe gastrointestinal tract toxicity but the underlying mechanism remains unclear. This study considers the widely applied cytotoxic agent irinotecan (CPT-11) as a representative agent and demonstrates that treatment induces massive release of double-strand DNA from the intestine that accounts for the dose-limiting intestinal toxicity of the compound. Specifically, "self-DNA" released through exosome secretion enters the cytosol of innate immune cells and activates the AIM2 (absent in melanoma 2) inflammasome. This leads to mature IL-1β and IL-18 secretion and induces intestinal mucositis and late-onset diarrhoea. Interestingly, abrogation of AIM2 signalling, either in AIM2-deficient mice or by a pharmacological inhibitor such as thalidomide, significantly reduces the incidence of drug-induced diarrhoea without affecting the anticancer efficacy of CPT-11. These findings provide mechanistic insights into how chemotherapy triggers innate immune responses causing intestinal toxicity, and reveal new chemotherapy regimens that maintain anti-tumour effects but circumvent the associated adverse inflammatory response.

Therapies designed to target cancer stem cells (CSCs) in colorectal cancer (CRC) may improve treatment outcomes. Different markers have been used to identify CSCs or CSC-like cells in CRC, but the enrichment of CSCs using these markers has yet to be optimized. We recently reported the importance of Lgr5-positive CRC cells in cancer growth. Here, we studied the possibility of using Lgr5 and CXCR4 as CSC markers for CRC. We detected high Lgr5 and CXCR4 levels in stage IV CRC specimens. Both high Lgr5 and CXCR4 levels were associated with poor prognosis in stage IV CRC patients. In vitro, Lgr5+CXCR4-, CXCR4+Lgr5- and Lgr5+CXCR4+ cells were purified in human CRC cell lines and examined for their CSC properties. We found that compared to the unsorted cells, CXCR4+Lgr5-, Lgr5+CXCR4-, and Lgr5+/CXCR4+ cells showed significantly greater cancer mass after subcutaneous transplantation, greater tumor sphere formation, higher resistance to chemotherapy, and higher incidence of tumor formation after serial adoptive transplantation into NOD/SCID mice. Taken together, our data suggest that the combined use of Lgr5 and CXCR4 may facilitate the enrichment of CSCs in CRC, and that treating Lgr5+/CXCR4+ CRC cells may improve the outcome of CRC therapy.

Background/Aims: The Snail family of transcription factors controls epithelial to mesenchymal transition (EMT), a process associated with tumorigenesis originated from epithelial cells. Snail1 is a member from Snail family and upregulation of Snail1 has been detected in gastric cancer (GC), suggesting a potential role of Snail1 in GC metastasis. We have recently reported that FBXL5 regulates cortactin by inducing its ubiquitylation and subsequent proteasomal degradation, resulting in inhibition of metastasis of GC. However, a role of FBXL4 in regulation of other EMT-associated proteins is not unknown. Methods: The levels of FBXL5 and Snail1 as well as their relationship were determined in GC specimen. Co-immunoprecipitation (IP) was performed to detect the interaction between Snail1 and FBXL5 in GC cells. The effects on Snail1 by FBXL5 were examined by overexpression of depletion of FBXL5 in GC cells. The invasiveness of the FBXL5-modified GC cells was examined in both scratch wound healing assay and transwell matrix penetration assay. Results: FBXL5 also physiologically interacted with Snail1. FBXL5 inhibited Snail1 to suppress GC cell invasiveness. Conclusion: FBXL5 negatively regulates several EMT-enhancing factors. FBXL5 is an attractive novel target for inhibiting invasion and metastasis of GC cells.

The relative efficacy and safety of first-line metastatic colorectal cancer (mCRC) treatment regimens, capecitabine with irinotecan (CAPIRI) and 5-fluorouracil/leucovorin plus irinotecan (FOLFIRI), are not well defined. We identified and subsequently examined seven independent, randomized controlled clinical trials, performing a meta-analysis to compare these two treatment regimens. Using Medline, EMBASE, Cochrane Library (CENTRAL), and the American Society of Clinical Oncology Annual Meeting to search available literature until February 2014, we identified seven studies comparing safety and efficacy of CAPIRI and FOLFIRI in mCRC patients. These studies were pooled and evaluated for rates of progression-free survival (PFS), objective response rate (ORR), overall survival (OS), and diarrhea. CAPIRI and FOLFIRI demonstrated similar efficacy outcomes, though CAPIRI was associated with a higher incidence of diarrhea. CAPIRI and FOLFIRI are equally effective options for first-line treatment of mCRC.

The molecular regulation of the growth of colorectal cancer (CRC) cells is not completely understood. Here, we report expression of Lgr5, a stem cell marker for the intestine and hair follicle, in some of the CRC cells in the patients. To determine the role of Lgr5-positive cells in the tumorigenesis of CRCs, we prepared an adeno-associated virus (AAV) that carries diphtheria toxin fragment A (DTA) under the control of Lgr5 promoter (AAV-pLgr5-DTA). Transduction of several CRC cell lines with this virus selectively killed Lgr5-positive cells, resulting in significant inhibition of the CRC cell growth in vitro and in vivo. Thus, our data highlight a potential role of Lgr5-positive cells in the tumorigenesis of CRCs, and suggest that treating these Lgr5-positive cells in CRCs may substantially improve the outcome of CRC therapy.

Cortactin, an actin-interacting protein, is implicated in cytoskeletal architecture and often amplified in several types of cancer including gastric adenocarcinomas. Downregulation of cortactin decreases cell migration and invasion. However, how to regulate cortactin in gastric cancer remains largely unknown. Here, we report that FBXL5 interacts with and targets cortactin for ubiquitylation and subsequent proteasomal degradation. Furthermore, we showed that FBXL5-induced cortactin degradation is mediated by extracellular regulated signal kinase (ERK). Serine phosphorylation sites mutant, cortactinS405A/S418A, prevent FBXL5-induced cortactin degradation. Moreover, CortactinS405A/S418A exhibited stronger effects in promoting gastric cancer cell migration when compared to wild-type cortactin. Taken together, our data suggested a novel molecular mechanism for the negative regulation of cortactin by FBXL5 in gastric cancer cells migration.

Objective Applying the CBL (Case-based Learning) teaching method to oncology teaching ward round,including case selection criteria establishing,teaching ward round process standardization.Evaluating the implementation effect of CBL teaching method in teaching ward round compared with the traditional LBL (lecture based learning) teaching method.Methods Oncology residents at Shanghai jiao tong university affiliated first people' s hospital were randomly divided into two groups.One group with CBL teaching method,the other group with traditional LBL teaching ward-round and comparing the difference between the two groups.Results Fifty students were admitted to our study with 26 cases in CBL group and 24 cases in LBL group.We examined the basic concept,preliminary diagnosis and treatment level,the ability of analysis question and the overall scores prior to admission,with no difference between the two groups.After oncology clinical training,we evaluated above three aspects again.The mean scores of CBL group were(26.3±2.0)、(35.3±3.3)、(25.5±2.4) and the overall score was (87.0±5.9).The mean scores of LBL group were(25.0±2.8) 、(29.0±3.6) 、(21.8±2.7) 、(75.9± 6.9).The P values were 0.3847,0.0002,0.0001,0.0001 separately.Conclusion The CBL teaching method can significantly improve the students' ability of diagnosis and treatment of diseases,ability of analyzing and resolving problem and overall scores compared with conventional LBL teaching ward round model in the oncology teaching ward round.

The UGT1A1*28 polymorphism, although closely linked with CPT-11-related adverse effects, cannot be used alone to guide individualized treatment decisions. However, CPT-11 dosage can be adjusted according to measured SN-38 pharmacokinetics. Our study is designed to investigate whether there is a relationship between SN-38 peak or valley concentrations and efficacy or adverse effects of CPT-11-based chemotherapy. We retrospectively studied 98 patients treated with advanced colorectal cancer in various UGT1A1*28 genotype groups (mainly (TA)6/(TA)6 and (TA)6/(TA)7 genotypes) treated with CPT-11 as first-line chemotherapy in Shanghai.

目的:回顾性分析2010年6月-2012年1月来自于多家医疗中心的69例进展期结直肠癌接受以伊立替康(irinotecan,CPT-11)为基础的二线联合化疗患者的尿苷二磷酸葡醛酰转移酶1A1 (uridine diphosphateglucuronosyl transferase 1A1,UGT1A1)*28基因多态性的表达情况,探讨UGT1A1*28 (TA)6/(TA)6和(TA)6/(TA)7型患者接受CPT-11治疗后的葡萄糖醛酸化SN-38(SN-38 glucuronide,SN-38G)峰浓度和谷浓度与不良反应和疗效之间的关系.方法:这是一项多中心的回顾性研究.研究对象为2010年6月-2012年1月接受以CPT-11为基础的二线联合化疗的69例进展期结直肠癌患者.化疗之前,检测UGT1A1基因多态性;在CPT-11化疗1.5和49.0 h时,应用高效液相色谱法检测SN-38血药浓度.观察近期疗效和不良反应,采用逐步回归分析法分析不同的UGT1A1*28基因型患者SN-38血药浓度与近期疗效和不良反应的关系.结果:69例患者中,(TA)6/(TA)6型45例(65.22％),(TA)6/(TA)7型24例(34.78％),未发现(TA)7/(TA)7型.CPT-11治疗后,(TA)6/(TA)7型患者的SN-38平均峰浓度和谷浓度均高于(TA)6/(TA)6型患者(P=0.001,P=0.000).逐步回归分析结果显示,(TA)6/(TA)6型患者的SN-38峰浓度与无病生存期相关,SN-38谷浓度与近期疗效相关;而(TA)6/(TA)7型患者的SN-38峰浓度与骨髓抑制相关,SN-38谷浓度与治疗后血浆总胆红素水平和迟发性腹泻相关.(TA)6/(TA)6型患者SN-38峰浓度＞43.20 ng/mL和谷浓度＞9.41 ng/mL的中位无进展生存期优于SN-38峰浓度≤43.20 ng/mL (6.0和4.6个月,x2=25.57,P=0.00)和谷浓度≤9.41 ng/mL的患者(6.0和5.2个月,x2=6.81,P=0.01).(TA)6/(TA)7型患者SN-38峰浓度＞50.60 ng/mL和谷浓度＞16.29 ng/mL的中位无进展生存期并不明显优于SN-38峰浓度≤50.60 ng/mL(7.0和6.0个月,x2=0.18,P=0.67)和谷浓度≤16.29 ng/mL的患者(6.0和7.3个月,x2=0.56,P=0.46),而骨髓抑制发生率(P=0.02,P=0.02)和迟发性腹泻发生率(P=0.04,P=0.03)较高.结论:进展期结直肠癌患者以UGT1A1*28 (TA)6/(TA)6型和(TA)6/(TA)7型占绝大多数.对于(TA)6/(TA)6型患者,如果CPT-11化疗后SN-38峰浓度≤43.20 ng/mL或谷浓度≤9.41 ng/mL,可逐步增加CPT-11剂量以提高治疗效果;对于(TA)6/(TA)7型患者,如果CPT-11化疗后SN-38峰浓度＞50.60 ng/mL或谷浓度＞16.29 ng/mL者,可适当减少CPT-11剂量以减轻不良反应,而不影响化疗效果.

多学科综合治疗已经成为当前肿瘤治疗的最佳实践模式,这对传统的肿瘤学教学查房提出了很大的挑战。要求老师必须具备广博的临床知识和深厚的肿瘤学知识,鼓励医生科学家参与教学查房;教学查房形式多样,以LBL和CBL教学法并举;提倡多学科联合查房。

Case based learning was introduced in the teaching ward round on oncology. Our heuristic, interactive, discussion-style teaching model was focused on real clinical cases, by raising questions to discuss strategies for solving problems. Therefore, we can foster clinicians' ability of solving problems, their innovative spirit and team-work spirit so as to meet the requirements of multidisciplinary treatment in new era oncology.

Background: Proteasome inhibitors block the degradation of protein in ubiquitin-proteasome pathway, causing the accumulation of misfolding and damaged proteins and initiating the heat shock response, thereby leading to cells death. Growth of various malignant tumor cells could be inhibited by proteasome inhibitors. Aims: To investigate the effect of proteasome inhibitor Z-Leu-Leu-Phe-CHO (ZLLFC) alone or in combination with cisplatin on the proliferation and apoptosis of human gastric cancer cell line SGC-7901 in vitro and the mRNA expression of multidrug resistance-related excision repair cross-complement group 1 (ERCC1) gene. Methods: SGC-7901 cells were treated with ZLLFC, cisplatin alone or in combination. Methyl thiazolyl tetrazolium (MTT) assay was used to assess the survival rate of SGC-7901 cells. The morphology of apoptotic cells was observed under transmission electron microscope, and the apoptosis rate was assessed by flow cytometry. Expression of ERCC1 mRNA was determined by reverse transcriptase polymerase chain reaction (RT-PCR). Results: ZLLFC or cisplatin alone could inhibit the proliferation of SGC-7901 cells, the survival rate was significantly lower than that of controls (P<0.01), and mild apoptotic features were observed under electron microscope. Combined use of ZLLFC and cisplatin significantly decreased further the survival rate of SGC-7901 cells and increased the apoptosis rate (P<0.01), the cells presented typical apoptotic morphology. Expression of ERCC1 mRNA in combined group was significantly lower than that of cisplatin alone group (P<0.01). Conclusions: Proteasome inhibitor ZLLFC can modestly inhibit the growth of human gastric cancer cell line SGC-7901 and induce cell apoptosis. A synergistic effect is achieved when ZLLFC is combined with cisplatin. ZLLFC might reverse the cisplatin resistance by down-regulating ERCC1 transcription, thereby enhances the anti-tumor effect of cisplatin.

现代医学证明,细胞基因组保持其完整性对于细胞的增殖、分化等生物学行为具有至关重要的意义,如果基因的损伤不能及时得到修复,将导致细胞凋亡、生长失控以及恶性肿瘤发生等多种生物学变化.