To explore the mechanism of anticancer prescription in treatment of gastric cancer based on network pharmacology and molecular docking

Objective:To explore the mechanism of anticancer prescription in treatment of gastric cancer based on network pharmacology and molecular docking.Methods:By searching TCMSP database,the active components and corresponding targets of anticancer prescriptions were screened out.GeneCards,PharmGkb,OMIM,DrugBank and TTD database were used to collect action targets of gastric cancer.And Venny 2.1 software was used to screen drug-disease co-action targets.Then,String and Cytoscape software were used to analyze and construct PPI network,and Cytonca plug-in was used to cany out topology analysis to select the core targets.ClueGO plugin was used for GO function enrichment analysis and KEGG pathway analysis.Finally,the AutoDock software was used to conduct molecular docking between the core target and the main active ingredients of the anticancer prescription.Results:Sixty-four active compounds,159 common targets and 12 core targets of anti-cancer prescriptions were screened out,which involved 2373 GO functions and 172 KEGG pathways.Finally,the core target proteins MAPKI TP53 and JUN were screened and molecularly docked with 8 major active components.Among them,theflavonoid quercetin and luteolin had the best binding activity with MAPK1,Quercetin baicalin also had high binding activity with FOS.Conclusion:The preliminary study showed that flavonoids were an important active ingredient in the anti-cancer prescription,which mainly treated gastric cancer through multiple targets and multiple pathways,such as the effect of MAPK1 on chemical carcinogenesis in reaction with drugs,bacterial and viral infection and cell apoptosis.

Esophageal diverticulum exposed during endoscopic submucosal dissection of superficial cancer

Endoscopic submucosal dissection(ESD) is now widely accepted as a strategy to treat superficial esophageal neoplasms.The rate of adverse events,such as perforation,has been decreasing with the improvement of devices and techniques.In this paper,we report a case of esophageal cancer that had a diverticulum under cancerous epithelium.The diverticulum was not detected during preoperative examination,and led to perforation during the ESD procedure.Our case shows that,although rare,some diverticula can exist underneath the mucosal surface without obvious depression.If there is any sign of hidden diverticula during ESD,surgeons should proceed with caution or,depending on the case,the procedure should be discontinued to avoid adverse events.

Solitary mediastinal lymph node recurrence after curative resection of colon cancer

We report two cases of solitary mediastinal lymph node recurrence after colon cancer resection. Both cases had para-aortic lymph node metastasis at the time of initial surgery and received adjuvant chemotherapy for 4 years in case 1 and 18 mo in case 2. The time to recurrence was more than 8 years in both cases. After resection of the recurrent tumor, the patient is doing well with no recurrence for 6 years in case 1 and 4 mo in case 2. Patients should be followed up after colon cancer surgery considering the possibility of solitary mediastinal lymph node recurrence if they had para-aortic node metastasis at the time of initial surgery.

Alterations in genes other than EGFR/ALK/ROS1 in non-small cell lung cancer:trials and treatment options

During the last decade, we have seen tremendous progress in the therapy of lung cancer. Discovery of actionable mutations in EGFR and translocations in ALK and ROS1 have identified subsets of patients with excellent tumor response to oral targeted agents with manageable side effects. In this review, we highlight treatment options including corresponding clinical trials for oncogenic alterations affecting the receptor tyrosine kinases MET, FGFR, NTRK, RET, HER2, HER3, and HER4 as well as components of the RAS-RAF-MEK signaling pathway.

A nomogram model for predicting the prognosis of colorectal cancer patients based on preoperative Fbg,PAR and CA199

Objective:To construct a nomogram model for predicting the prognosis of colorectal cancer patients based on preoperative fibrinogen(Fbg),platelet to albumin ratio(PAR)and carbohydrate antigen 199(CA199).Methods:In this retrospective study,we included 323 patients who underwent colorectal cancer(CRC)surgery in our hospital.The preoperative test indexes and relevant clinicopathological data of the patients were collected.According to the cut-off value of Fbg and PAR calculated from the receiver operating characteristic(ROC)curve,they were divided into the high and low expression groups.Univariate and multivariate Cox proportional hazards models were used to screen independent prognostic factors which were used to construct a nomogram.Results:According to ROC curve,the cut-off values of Fbg and PAR were 2.80 and 6.05.Multivariate Cox regression analysis showed that Fbg,PAR,CA199,TNM stage and grade were independent risk factors affecting the prognosis of patients(P<0.05).Fbg,PAR,and CA199 jointly built the risk score that was included into the nomogram.The area under the curve(AUC)in the ROC of the training and verification set was greater than 0.6.The calibration curve and ideal curve fit well.Conclusion:The nomogram based on Fbg,PAR and CA199 has well accuracy and can provide individualized prediction for the overall survival of CRC patients.

Banxiashengjiangdaizheshi decoction combined with warm acupuncture in the treatment of 10 cases of postoperative gastroparesis of gastric cancer

Objective: To study the tr eatment of postope rative gast ropa resis in pa ti ents with gast ric cancer. Methods: 18 patients with gast ropa resis afte r gast ric cance r sur gery were divided into two gr oups, including 10 pa ti ents in the obse rva tion group and 8 pati ents in the cont rol group. The observation group was treated with traditional Chinese medicine combined with warm acupuncture and moxibustion, and the control group was treated with western medicine. Results: After 7 days tr eatment, the re was significant diffe rence in cure r ate and total effective rate between the two groups (P < 0.01), and the treatment group was obviously superior to the control group. Conclusion: Traditional Chinese medicine combined with warm acupuncture is effective in the treatment of postoperative gastroparesis of gastric cancer.

Laparoscopic vs open abdominoperineal resection in the multimodality management of low rectal cancers

AIM: To evaluate the safety and feasibility of laparoscopic abdominoperineal resection compared with the open procedure in multimodality management of rectal cancer.METHODS: A total of 106 rectal cancer patients who underwent open abdominoperineal resection(OAPR) were matched with 106 patients who underwent laparoscopic abdominoperineal resection(LAPR) in a 1 to 1 fashion, between 2009 and 2013 at Fudan University Shanghai Cancer Center. Propensity score matching was carried out based on age, gender, pathological staging of the disease and administration of neoadjuvant chemoradiation. Data regarding preoperative staging, surgical technique, pathologicalresults, postoperative recovery and complications were reviewed and compared between the LAPR and OAPR groups. Perineal closure around the stoma and pelvic floor reconstruction were performed only in OAPR, not in LAPR. Therefore, abdominoperineal resection procedure-specific surgical complications including parastomal hernia and perineal wound complications were compared between the open and laparoscopic procedure. Regular surveillance of the two cohorts was carried out to gather prognostic data. Diseasefree survival was analyzed using Kaplan-Meier estimate and log-rank test. Subgroup analysis was performed in patients with locally advanced disease treated with preoperative chemoradiation followed by surgical resection. RESULTS: No significant difference was found between the LAPR group and the OAPR group in terms of clinicopathological features. The operation time(180.8 ± 47.8 min vs 172.1 ± 49.2 min, P = 0.190), operative blood loss(93.9 ± 60.0 m L vs 88.4 ± 55.2 m L, P = 0.494), total number of retrieved lymph nodes(12.9 ± 6.9 vs 12.9 ± 5.4, P = 0.974), surgical complications(12.3% vs 15.1%, P = 0.549) and pathological characteristics were comparable between the LAPR and OAPR group, respectively. Compared with OAPR patients, LAPR patients showed significantly shorter postoperative analgesia(2.4 ± 0.7 d vs 2.7 ± 0.6 d, P < 0.001), earlier first flatus(57.3 ± 7.9 h vs 63.5 ± 9.2 h, P < 0.001), shorter urinary drainage time(6.5 ± 3.4 d vs 7.8 ± 1.3 d, P < 0.001), and shorter postoperative admission(11.2 ± 4.7 d vs 12.6 ± 4.0 d, P = 0.014). With regard to APR-specific complications(perineal wound complications and parastomal hernia), there were no significant differences between the two groups. Similar results were found in the 26 pairs of patients administered neoadjuvant chemoradiation in subgroup analysis. During the follow-up period, no port site recurrences were observed. CONCLUSION: Laparoscopic abdominoperineal resection for multidisciplinary management of rectal cancer is safe, and is associated with earlier recovery and shorter admission time in combination with neoadjuvant chemoradiation.

Breakthrough therapy for peritoneal carcinomatosis of gastric cancer:Intraperitoneal chemotherapy with taxanes

The effect of chemotherapy on peritoneal carcinomatosis(PC) of gastric cancer remains unclear.Recently,the intraperitoneal(IP) administration of taxanes [e.g.,paclitaxel(PTX) and docetaxel(DOC)] during the perioperative period has shown promising results.Herein,we summarized the rationale and methodology for using IP chemotherapy with taxanes and reviewed the clinical results.IP administered taxanes remain in the IP space at an extremely high concentration for 48-72 h.The drug directly infiltrates peritoneal metastatic nodules from the surface and then produces antitumor effects,making it ideal for IP chemotherapy.There are two types of perioperative IP chemotherapy with taxanes: neoadjuvant intraperitoneal and systemic chemotherapy and sequential perioperative intraperitoneal chemotherapy(SPIC).In SPIC,patients receive neoadjuvant IP chemotherapy and the same regimen of IP chemotherapy after cytoreductive surgery(CRS) until disease progression.Usually,a taxane dissolved in 500-1000 m L of saline at ordinary temperature is administered through an IP access port on an outpatient basis.According to phase Ⅰ?studies,the recommended doses(RD) are as follows: IP DOC,45-60 mg/m2; IP PTX [without intravenous(IV) PTX],80 mg/m2; and IP PTX(with IV PTX),20 mg/m2.Phase Ⅱ studies have reported a median survival time of 14.4-24.6 mo with a 1-year overall survival of 67%-78%.A phase Ⅲ study comparing S-1 in combination with IP and IV PTX to S-1 with IV cisplatin started in 2011.The prognosis of patients who underwent CRS was better than that of those who did not; however,this was partly due to selection bias.Although several phase Ⅱ studies have shown promising results,a randomized controlled study is needed to validate the effectiveness of IP chemotherapy with taxanes for PC of gastric cancer.

Effect size in papers published by the Journal of Forestry Research:A missing treasure?

P values based on standard hypothesis testing are commonly reported in articles published by the Journal of Forestry Research(JFR).However,effect sizes are barely used and reported,even if they are of direct relevance to the primary questions of many of the published studies.The incorporation of effect sizes in studies published by JFR should be encouraged and promoted.Inclusion of effect sizes as a requirement in the journal guidelines will facilitate a major change in the way data are tested and interpreted,with the ultimate goal to exempt researchers from the custom of drawing conclusions merely based upon a dichotomous statistical result(P value).Such a policy can also lead to more informed decisions of whether identified effects are of practical relevance to the forestry.

原发性肺癌的磁共振诊断(附42例分析)

目的探讨肺癌的磁共振影像学表现。方法分析42例经病理证实的肺癌MRI资料。42例患者均进行MRI常规轴位T_1WI、T_2WI,冠状位T_2WI、轴位DWI扫描。结果 42例肺癌:中央型14例,周围型26例,纵膈型2例;13例有胸腔积液,8例有肺内转移,8例有肋骨转移;病灶T_1WI 64%呈等信号,T_2WI 97.6%呈高信号,DWI呈高信号。结论MRI可以显示肺癌外部和内部影像特点,在纵膈、胸壁侵犯方面有很好的优势。

Novel understanding of ABC transporters ABCB1/MDR/P-glycoprotein, ABCC2/MRP2, and ABCG2/BCRP in colorectal pathophysiology

AIM: To evaluate ATP-binding cassette(ABC) transporters in colonic pathophysiology as they had recently been related to colorectal cancer(CRC) development. METHODS: Literature search was conducted on Pub Med using combinations of the following terms: ABC transporters, ATP binding cassette transporter proteins, inflammatory bowel disease, ulcerative, colitis, Crohns disease, colorectal cancer, colitis, intestinal inflammation, intestinal carcinogenesis, ABCB1/P-glycoprotein(P-gp/CD243/MDR1), ABCC2/multidrug resistance protein 2(MRP2) and ABCG2/breast cancer resistance protein(BCRP), Abcb1/Mdr1 a, abcc2/Mrp2, abcg2/Bcrp, knock-out mice, tight junction, membrane lipid function. RESULTS: Recently, human studies reported thatchanges in the levels of ABC transporters were early events in the adenoma-carcinoma sequence leading to CRC. A link between ABCB1, high fat diet and gut microbes in relation to colitis was suggested by the animal studies. The finding that colitis was preceded by altered gut bacterial composition suggests that deletion of Abcb1 leads to fundamental changes of hostmicrobiota interaction. Also, high fat diet increases the frequency and severity of colitis in specific pathogenfree Abcb1 KO mice. The Abcb1 KO mice might thus serve as a model in which diet/environmental factors and microbes may be controlled and investigated in relation to intestinal inflammation. Potential molecular mechanisms include defective transport of inflammatory mediators and/or phospholipid translocation from one side to the other of the cell membrane lipid bilayer by ABC transporters affecting inflammatory response and/or function of tight junctions, phagocytosis and vesicle trafficking. Also, diet and microbes give rise to molecules which are potential substrates for the ABC transporters and which may additionally affect ABC transporter function through nuclear receptors and transcriptional regulation. Another critical role of ABCB1 was suggested by the finding that ABCB1 expression identifies a subpopulation of pro-inflammatory Th17 cells which were resistant to treatment with glucocorticoids. The evidence for the involvement of ABCC2 and ABCG2 in colonic pathophysiology was weak. CONCLUSION: ABCB1, diet, and gut microbes mutually interact in colonic inflammation, a well-known risk factor for CRC. Further insight may be translated into preventive and treatment strategies.

动态增强MRI在肺癌疗效评估中的应用

肺癌严重威胁人们的生命健康,在中国,肺癌预计在未来几十年内都呈增长态势,动态增强磁共振(dynamic contrast-enhanced magnetic resonance imaging,DCE-MRI)的各种动力学参数、曲线能间接反映肿瘤血供和肿瘤血管表面渗透性,在指导肺癌个体化治疗,评价疗效方面有独特优势,本文对动态增强磁共振在非小细胞肺癌疗效评估中的应用和进展进行综述。

Cutting edge of endoscopic full-thickness resection for gastric tumor

Recently,several studies have reported local full-thickness resection techniques using flexible endoscopy for gastric tumors,such as gastrointestinal stromal tumors,gastric carcinoid tumors,and early gastric cancer(EGC). These techniques have the advantage of allowing precise resection lines to be determined using intraluminal endoscopy. Thus,it is possible to minimize the resection area and subsequent deformity. Some of these methods include:(1) classical laparoscopic and endoscopic cooperative surgery(LECS);(2) inverted LECS;(3) combination of laparoscopic and endoscopic approaches to neoplasia with non-exposure technique; and(4) non-exposed endoscopic wall-inversion surgery. Furthermore,a recent prospective multicenter trial of the sentinel node navigation surgery(SNNS) for EGC has shown acceptable results in terms of sentinel node detection rate and the accuracy of nodal metastasis. Endoscopic full-thickness resection with SNNS is expected to become a treatment option that bridges the gap between endoscopic submucosal dissection and standard surgery for EGC. In the future,the indications for these procedures for gastric tumors could be expanded.

丹参酮逆转结肠癌细胞多药耐药性应用于治疗的潜能(英文)

Multidrug resistance(MDR)develops during chemotherapy in nearly all colorectal cancerpatients.It is envisaged that reversal of MDR plays a pivotal role in the success of chemotherapy.This study investigated thepotential pharmacological action in reversing MDR in colon cancer cells by the two most potent tanshinones,namely cryptotanshinone and dihydrotanshinone.They targeted two common MDR mechanisms,including overexpression of P-glycoprotein(P-gp)and suppression of apoptosis.Using a bi-directional transport assay,the two tanshinones decreased P-gp-mediated digoxin effluxin Caco-2 cells.They also potentiated the cytotoxicities of doxorubicin and irinotecan in P-gp overexpressing SW620Ad300 cells via increased intracellular accumulation of both anti-cancer drugs,as a result of down-regulation of P-gp mRNA and protein levels as well as inhibition of P-gp ATPase activity.In addition,the level of apoptosis was also found to be relatively suppressed in SW620Ad300 cells as compared with the parental SW620 cells.Interestingly,although cryptotanshinone and dihydrotanshinone induced less apoptosis in SW620Ad300 cells as compared to their parental cells,they produced more autophagic cell death in these MDR cells.In this regard,the drug resistant SW620Ad300 cells were more prone to cell death in response to the anti-cancer action of thetwo tanshinones.Furthermore,the cytotoxic action of the two tanshinones was shown to be p53-independent,further demonstrated theirunique anti-cancer activities in overcoming drug resistance due to the reduction of p53 expression together with a decrease of apoptosis in colon cancer cells.Taken together,the current findings indicate a great potential for cryptotanshinone and dihydrotanshinone against MDR colon cancer cells,in spite of P-gp overexpression and suppression of apoptosis.They are promising candidates to be developed as therapeutic agents and/or as an adjuvant therapy for colorectal cancer,especially for patients with MDR cancer types.

曲妥珠单抗在乳腺癌辅助治疗中的临床疗效研究

目的通过对人表皮生长因子受体2(HER-2)阳性乳腺癌患者临床资料的分析,探讨曲妥珠单抗在乳腺癌辅助治疗中的疗效、不良反应及影响预后的因素。方法依据是否使用过曲妥珠单抗辅助靶向治疗及雌激素受体(ER)的免疫组织化学检测结果,采用回顾性方法将本院107例HER-2阳性乳腺癌患者分为治疗组和未治疗组,其中各组又分为ER-及ER+亚组。对患者的临床特征采用SPSS17.0统计软件进行分析,并用Kaplan-Meier法和Cox回归分析患者的无瘤生存情况及预后影响因素。结果在107例HER-2乳腺癌患者中,治疗组43例,未治疗组64例,未治疗组的无瘤生存低于治疗组的患者(P=0.04);再进一步分为ER+治疗组(22例,20.56%)、ER-治疗组(21例,19.63%)、ER+未治疗组(46例,42.99%)及ER-未治疗组(18例,16.82%),这4组间的无瘤生存差异明显有统计学意义(P=0.02);ER-治疗组的无瘤生存率高于ER-未治疗组(P=0.04),ER+治疗组与ER+未治疗组的无瘤生存率差异无统计学意义(P=0.25)。经Cox多因素预后分析发现淋巴结及激素受体状况是影响HER-2阳性乳腺癌预后的重要因素;淋巴结转移多、ER阴性患者的预后差较差(P<0.05)。结论 HER-2阳性的乳腺癌患者予曲妥珠单抗辅助治疗能提高其无瘤生存率,其中ER-的患者获益明显;HER-2阳性乳腺癌患者中,淋巴结及激素受体状况是影响预后的重要因素,淋巴结转移多或ER阴性的预后较差。

过表达Mfn2对人乳腺癌裸鼠移植瘤血管表皮生长因子受体的影响

目的探讨过表达线粒体融合素-2(Mitofusin-2,Mfn2)对表皮生长因子受体(Epidermal Growth Factor Receptor,EGFR)表达的影响及对人乳腺癌裸鼠移植瘤生长、血管形成的影响。方法分别构建稳定转染空质粒pEGFP-N1(MCF-7 pEGFP-N1)及转染Mfn2质粒的pEGFP-Mfn2(MCF-7 pEGFP-Mfn2)的MCF-7细胞稳系。分别将人乳腺癌细胞MCF-7、MCF-7 pEGFP-N1、MCF-7 pEGFPMfn2接种于裸鼠右侧乳房垫内,观察裸鼠生长状况,每周两次测量肿瘤大小,绘制肿瘤生长曲线。5周后处死裸鼠,采用免疫组化验证肿瘤Mfn2蛋白的表达并检测CD34来观测肿瘤微血管密度(MVD),检测EGFR蛋白的表达情况。结果 pEGFP-Mfn2组肿瘤明显小于pEGFP-N1组和对照组(P<0.05)。pEGFP-Mfn2组微血管数目明显小于pEGFP-N1组和对照组(P<0.05)。pEGFP-N1组EGFR的表达与对照组相比差异无统计学意义(P>0.05),与对照组、pEGFP-N1组相比pEGFP-Mfn2组EGFR的表达明显降低(P<0.05)。结论 Mfn2明显抑制人乳腺癌裸鼠移植瘤的生长。下调EGFR表达、减少微血管生成可能为其抗肿瘤机制。