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Objective:To investigate the surgical efficacy and prognosis influencing factors of hilar cholangiocarcinoma based on multidisciplinary diagnosis and treatment.Methods:The retrospective cohort study was conducted. The clinicopathological data of 91 patients with hilar cholangiocarcinoma who underwent surgery in Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School from April 2004 to April 2021 were collected. There were 59 males and 32 females, aged (61±10)years. Patients who were admitted from April 2004 to March 2014 underwent traditional surgical diagnosis and treatment, and patients who were admitted from April 2014 to April 2021 underwent multidisciplinary diagnosis and treatment. Observation indica-tors: (1) surgical situations; (2) postoperative situations; (3) postoperative pathological examina-tions; (4) postoperative prognosis analysis; (5) influencing factors of postoperative prognosis. Follow-up was conducted using telephone interview and outpatient examination. Patients were followed up once every 6 months after surgery to detect survival. The follow-up was up to April 2023. Measure-ment data with normal distribution were represented as Mean± SD, and comparison between groups was conducted using the independent sample t test. Measurement data with skewed distribution were represented as M(range), and comparison between groups was conducted using the Mann-Whitney U test. Comparison of ordinal data was conducted using the rank sum test. Count data were described as absolute numbers or percentages, and comparison between groups was conducted using the chi-square test or Fisher exact probability. The Kaplan-Meier method was used to draw survival curve and calculate survival rate. The Log-Rank test was used for survival analysis. Univariate and multivariate analyses were conducted using the COX proportional hazard model. Results:(1) Surgical situations. Of the 91 patients, there were 65 cases receiving hemi- or expanded hemi-hepatectomy, 13 cases receiving tri-hepatectomy, 9 cases receiving partial hepatectomy, 4 cases receiving extrahepatic bile duct resection. There were 24 cases receiving combined vein resection and reconstruction, 8 cases receiving combined pancreaticoduodenectomy, 6 cases receiving com-bined hepatic artery resection and reconstruction, including 24 cases receiving extended radical surgery (tri-hepatectomy, hepatic artery resection and reconstruction, hepatopancreaticoduodenec-tomy). The operation time, volume of intraoperative blood loss and intraoperative blood transfusion rate of 91 patients was (590±124)minutes, 800(range, 500?1 200)mL and 75.8%(69/91), respectively. Of the 91 patients, cases receiving extended radical surgery, the volume of intraoperative blood loss were 4, 650(range, 300?1 000)mL in the 31 patients who were admitted from April 2004 to March 2014, versus 20, 875 (range, 500?1 375)mL in the 60 patients who were admitted from April 2014 to April 2021, showing significant differences between them ( χ2=4.39, Z=0.31, P<0.05). (2) Post-operative situations. The postoperative duration of hospital stay and cases with postoperative infectious complications were (27±17)days and 50 in the 91 patients. Cases with abdominal infection, cases with infection of incision, cases with bacteremia and cases with pulmonary infection were 43, 7, 5, 8 in the 91 patients. One patient might have multiple infectious complications. Cases with bile leakage, cases with delayed gastric emptying, cases with chylous leakage, cases with liver failure, cases with pancreatic fistula, cases with intraperitoneal hemorrhage, cases with reoperation, cases dead during the postoperative 90 days were 30, 9, 9, 6, 5, 3, 6, 3 in the 91 patients. Cases with abdominal infection was 10 in the 31 patients who were admitted from April 2004 to March 2014, versus 33 in the 60 patients who were admitted from April 2014 to April 2021, showing a significant difference between them ( χ2=4.24, P<0.05). Cases dead during the postoperative 90 days was 3 in the 31 patients who were admitted from April 2004 to March 2014, versus 0 in the 60 patients who were admitted from April 2014 to April 2021, showing a significant difference between them ( P<0.05). (3) Post-operative pathological examinations. Of the 91 patients, cases with Bismuth type as type Ⅰ?Ⅱ, type Ⅲ, type Ⅳ, cases with T staging as Tis stage, T1 stage, T2a?2b stage, T3 stage, T4 stage, cases with N staging as N0 stage, N1 stage, N2 stage, cases with M staging as M0 stage, M1 stage, cases with TNM staging as 0 stage, Ⅰ stage, Ⅱ stage, Ⅲ stage, ⅣA stage, ⅣB stage, cases with R 0 radical resection, cases with R 1 or R 2 resection were 15, 46, 30, 1, 9, 25, 30, 26, 49, 36, 6, 85, 6, 1, 7, 13, 58, 6, 6, 63, 28. Cases with R 0 radical resection, cases with R 1 or R 2 resection were 15, 16 in the 31 patients who were admitted from April 2004 to March 2014, versus 48, 12 in the 60 patients who were admitted from April 2014 to April 2021, showing a significant difference between them ( χ2=9.59, P<0.05). (4) Postoperative prognosis analysis. Of the 91 patients, 3 cases who died within 90 days after surgery were excluded, and the 5-year overall survival rate and median overall survival time of the rest of 88 cases were 44.7% and 55 months. The 5-year overall survival rate was 33.5% in the 28 patients who were admitted from April 2004 to March 2014, versus 50.4% in the 60 patients who were admitted from April 2014 to April 2021, showing a significant difference between them ( χ2=5.31, P<0.05). Results of further analysis showed that the corresponding 5-year overall survival rate of cases without lymph node metastasis was 43.8% in the 16 patients who were admitted from April 2004 to March 2014, versus 61.6% in the 31 patients who were admitted from April 2014 to April 2021. There was a significant difference in the 5-year overall survival rate between these patients without lymph node metastasis ( χ2=3.98, P<0.05). The corresponding 5-year overall survival rate of cases with lymph node metastasis was 18.5% in the 12 patients who were admitted from April 2004 to March 2014, versus 37.7% in the 29 patients who were admitted from April 2014 to April 2021. There was no significant difference in the 5-year overall survival rate between these patients with lymph node metastasis ( χ2=2.25, P>0.05). (5) Influencing factors of postoperative prognosis. Results of multivariate analysis showed that poorly differentiated tumor and R 1 or R 2 resection were inde-pendent risk factors influencing prognosis after surgical treatment of hilar cholangiocarcinoma ( hazard ratio=2.62, 2.71, 95% confidence interval as 1.30?5.29, 1.30?5.69, P<0.05). Conclusions:Compared with traditional surgical diagnosis and treatment, treatment of hilar cholangiocarcinoma based on multidisciplinary diagnosis and treatment can expand surgical indications, reduce proportion of dead patients within 90 days after surgery, improve proportation of radical resection and long-term survival rate. Poorly differentiated tumor and R 1 or R 2 resection are independent risk factors influencing prognosis after surgical treatment of hilar cholangiocarcinoma.
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With the rapid development of tumor immunotherapy in recent years, therapeutic cancer vaccines are attracting increased attention. Compared with personalized neoantigen vaccines, in situ vaccines could form an antigen reservoir in the tumor itself. Subsequently, antitumor immunity is initiated and the response to immune-checkpoint inhibitors of some patients improve without necessitating these patients to undergo the complicated procedures of detecting personalized antigen and customizing and synthesizing antigen peptide. At this stage, the potential of realizing the clinical translation of in situ vaccination is tremendous. In this review, we primarily introduce the mechanisms of radiotherapy and intratumoral immune injection as in situ vaccination and discuss the current status of preclinical study and clinical application of their combination to attract more attention from researchers and clinicians toward in situ vaccination.
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Objective:To analyze the survival efficacy, prognostic factors and failure patterns of patients with esophageal squamous cell carcinoma (ESCC) underwent postoperative radiotherapy (PORT) using modified clinical target volume (CTV) based on postoperative high-frequency recurrence regions, so as to provide reference for the further optimization of CTV of PORT.Methods:The patients with ESCC underwent radical operation in Comprehensive Cancer Center of Nanjing Drum Tower Hospital, Affiliated Hospital of Nanjing University Medical School from April 28, 2014 to November 29, 2018 were retrospectively analyzed. Patients with stage pT 3-4aN 0 or N +, who underwent PORT with modified CTV based on postoperative high-frequency recurrence regions, were included in the study. Kaplan-Meier method was used to calculate overall survival (OS) and locoregional recurrence free survival (LRFS) , adverse events of patients were evaluated, Cox proportional hazards model was used for univariate and multivariate survival analysis, and the failure patterns of patients after PORT were analyzed. Results:A total of 85 patients were included in this study, and the median follow-up time was 52.6 months. The median OS of the whole group was 74.1 months. The 1-year, 2-year and 3-year OS rates were 97.6%, 84.7% and 71.7% respectively. The median LRFS was not reached, and the 1-year, 2-year and 3-year LRFS rates were 92.9%, 78.6% and 71.5% respectively. The incidence of grade 3-4 adverse events was 17.6% (15/85) , mainly including lymphopenia, bone marrow suppression, gastrointestinal reaction and skin reaction. Univariate analysis of OS after PORT showed that the degree of differentiation (set G1+G1-2+G2 group as the control group, G2-3+G3 group HR=4.19, 95% CI: 1.91-9.17, P<0.001; NA+basal-like group HR=4.16, 95% CI: 1.29-13.44, P=0.017) and postoperative stage ( HR=2.19, 95% CI: 1.09-4.39, P=0.030) were the influencing factors of OS. Cox multivariate analysis showed that the degree of differentiation was an independent prognostic factor for OS after PORT (set G1+G1-2+G2 group as the control group, G2-3+G3 group HR=5.24, 95% CI: 2.30-11.93, P<0.001; NA+basal-like group HR=4.83, 95% CI: 1.33-17.62, P=0.017) . The first failure patterns analysis showed that 39 cases (45.9%) had recurrence, among which, 22 cases (25.9%) had locoregional recurrence with the median onset time of 15.2 months after operation, 19 cases (22.4%) had distant metastasis with the median onset time was 14.1 months after operation, and 2 cases (2.4%) were mixed failure mode. Among the locoregional recurrence, 16 cases (72.7%) recurred in the radiation field. Among all the local recurrence sites, the lymph node drainage regions in the supraclavicular, upper middle mediastinum and upper abdominal perigastric/celiac artery trunk areas were the most common sites. Among the distant metastatic organs, lung, bone and liver metastases were the most common. Conclusion:Patients of ESCC with high risk of recurrence after radical esophagectomy have long survival time and high safety after PORT with modified CTV according to the high-frequency recurrence regions. It is worthy of further confirmation by multicenter, large sample and prospective clinical trials.
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Chemoradiation has been the standard treatment of stage Ⅲ unresectable non-small cell lung cancer (NSCLC) for a long period of time. However, the clinical efficacy of chemoradiation has not been significantly improved in recent two decades. In the past 2-3 years, the role of immune-checkpoint inhibitors in metastatic NSCLC has been persistently strengthened. Moreover, the synergistic effect between radiotherapy and immune-checkpoint blockade has been conformed in pre-clinical and clinical studies. Recent clinical trials have demonstrated that the combination of radiotherapy and immune-checkpoint blockade has been proven to be more effective in the treatment of stage Ⅲ unresectable NSCLC. In this article, the latest clinical studies since 2017 regarding the application value of this combined treatment of stage Ⅲ unresectable NSCLC were summarized.
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Objective@#To evaluate the safety and efficacy of helical tomotherapy using simultaneously integrated boost and simultaneous integrated protection technique in the treatment of unresectable biliary tract cancers.@*Methods@#The data of 23 patients with unresectable biliary tract cancer who received tomotherapy-based hypofractionated radiotherapy at Comprehensive Cancer Centre of Drum Tower Hospital,the Affiliated Drum Tower Clinical College of Nanjing Medical University between February 2015 and October 2017 were analyzed. There were 10 males and 13 females, aged from 40 to 85 years(median:58 years). Pathological type included intrahepatic cholangiocarcinomas(n=11), gallbladder cancers(n=6),extrahepatic cholangiocarcinomas(n=6). The irradiated sites covered primary tumors and areas of local invasion,including metastatic lymph nodes which were confined to the abdominal or retroperitoneal space. Dose escalation was achieved using simultaneously integrated boost(SIB) technique, and simultaneous integrated protection(SIP)technique was used to protect gastrointestinal tracts and other adjacent organs. Cox regression modal and Kaplan-Meier analysis were used to analyze the associations between patients′ characteristics and overall survival(OS).@*Results@#The median total radiation dose was 54 Gy(range: 28-72 Gy)and median biologically effective dose(BED)was 74.4 Gy(range: 37.8-115.2 Gy).The median planning target volume(PTV)was 445.79 cm3(range:126.02-950.12 cm3). Based on the various PTV,patients received 2.4-6.0 Gy/fraction with 8-28 fractions. The local control rate was 65.2% and the median OS was 11.3 months(range:2.1-31.9 months).The most common cause of death was out-field failure and only 3 patients died of in-field failures. The longest survival was 31.9 months. BED≥70 Gy significantly improved OS,compared to BED<70 Gy(16.8 months vs.5.1 months)(HR=0.146, 95%CI:0.028-0.762, P=0.022). No patients developed grade ≥4 toxicities.@*Conclusions@#Helical tomotherapy-based hypofractionated radiotherapy is effective and well tolerated for patients with unresectable biliary tract cancer. The dose escalation with higher BED could improve the survival for such patients.
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Objective:To evaluate the association of microsatellite status with clinicopathological features of colorectal cancer patients after surgery.Methods:In total,572 colorectal cancer cases with clear pathological diagnosis and clinicopathological features from the Department of Pathology,Nanjing Drum Tower Hospital from June 2014 to June 2017 were included in the study.Microsatellite status and RAS mutations were detected by polymerase chain reaction.Ki67,EGFR,MGMT,and Lgr5 were detected by immunohistochemis-try.Clinicopathological features were analyzed based on the microsatellite states.Results:In this study,we found MSI-H in 7.0% of all patients,whereas 93.0% cases showed MSS/MSI-L.Compared with MSS and MSI-L colorectal cancer cases,MSI-H colorectal cancer cases showed the following characteristics:1)more likely located in the right colon,2)comparable incidences at different ages,3)ear-ly cancer stage(Ⅰ/Ⅱ)(P=0.003),4)a lower proportion of lymph node metastasis(P=0.023),5)a lower proportion of cancerous nod-ules(P=0.005),6)a lower mutation rate of KRAS(P=0.004),and no mutation of NRAS.There was no significant difference in the posi-tive rates of MGMT,EGFR,Lgr5,and Ki67 between the two groups.Conclusions:Compared with MSS/MSI-L patients,MSI-H patients have specific clinicopathological features.A lower mutation rate of KRAS/NRAS and higher methylation rate of MGMT were also found in MSI-H patients.Our results provide a basis for individual diagnosis and treatment in colorectal cancer.
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The accumulation of genomic and epigenetic changes gives rise to the tumorigenesis and progression. Currently, clonal evolution model and cancer stem cell model, two leading theories of caner origin, are becoming complementary to one another to explain the nature of tumor heterogeneity. Precision medicine that is based on the next generation sequencing and big data describes the phenomena of tumor heterogeneity more precisely. The future cancer therapy may need more comprehensive and dynamical understandings of the distinct subclones of tumor and follow the trends of cancer evolution.
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Scientific research of clinical disciplines has its own characteristics and requirements, in which the directions and topic selection are an essential step.This article introduces the author's experience in determining the directions and topics of clinical disciplinary research from the aspects of its practicality, advancement, innovativeness, feasibility and comprehensiveness, and some methods for cultivating medical graduates' ability of topic selection in clinical disciplinary research.
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Objective Based on the previous research that the ethanolic extract from traditional Chinese medicine fructus forsythiae (Lianqiao) can obviously inhibit cancer cells in vitro, the article aimed to investigate the anti-proliferation effects of dammar-24-ene-3β-acetate-20S-ol (DM) extracted from fructus forsythiae on gastric cancer cells and its mechanism.Methods MTT assay was used to assess the anti-proliferation effects of DM on gastric cancer cells including SGC-7901, BGC-823, and MKN-45 in vitro.There were MKN-45 control group and its low dose and high dose groups, BGC-823 control group and its low dose and high dose groups, SGC-7901 control group and its low dose and high dose groups in the experiment.Flow cytometry was used to analyze the cell apoptosis rate.Cellquest software was used to analyze the results and record the ratio of cells at different cycles.DCFH-DA probe was applied to detect the ROS levels of blank control group, docetaxol group and DM group.The reaction system of microtubule assembly test was set with 10?mol/L docetaxol, 50 or 100 μmol/L DM final density and no medicine in blank control group.The readings of UV spectrophotometer were recorded.Microtubule assembly assay and microtubule immunofluorescence staining were applied to investigate the effects of DM on microtubule system.Results The inhibition ratio of 50 μg/L DM on the proliferation three gastric cell lines were all above 80%, with IC50s of MKN-45 11.72±1.35 μg/mL, BGC-823 17.19±0.82 μg/mL, SGC-7901 7.55±0.79 μg/mL.8 days′ low density culturing at 48 hours after 2 μg/mL DM treatment, compared with control group, the number of cell clones significantly reduced without much change in clone size, while 48 hours after 10 μg/mL DM treatment, besides a few clones of BGC-823, there were just several megascopic clones of SGC-7901 and MKN-45.In comparison with apoptotic cell ratio in MKN-45 control group[(21.1±2.5)%], its low dose group and high dose group resulted in significant rise of apoptotic cell ratio[(25.1±1.3)% and (55.2±2.3)%] (P0.05).In comparison with MKN-45 control group, the ratio of cells at S phase decreased in its low dose group[(14.5±2.7)% vs (12.3±3.3)%,P>0.05].In comparison with BGC-823 control group, the ratio of cells at S phase increased in its low dose group[(12.2±5.4)% vs (20.2±2.1)%,P<0.05].In comparison with SGC-7901 control group, the ratio of cells at S phase increased in its low dose group[(21.5±3.8)% vs (31.3±2.6)%,P<0.05].From the detection of intracellular active oxygen after DM treatment, dose-dependent ROS level increased in all three cell lines 48 hours after 10μg/mL and 50μg/mL DM treatment.From the results of microtubule immunofluorescence staining, 48 hours after the treatment of IC50 docetaxol and 10μg/mL DM, the fluorescence signals were in local concentration and disorder.Conclusion Dammar-24-ene-3β-acetate-20S-ol demonstrated anti-proliferation effects due to the apoptosis induced by cell cycle arrest at S phase.
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Objective To monitor the dynamic changes of radiation-induced parotid damage using T2 ? mapping.Methods Thirty-four patients with nasopharyngeal carcinoma (NPC)were enrolled.All patients underwent T1 WI,T2 WI and T2 ? mapping for bilateral parotid glands at pre-RT (2 weeks before radiotherapy),mid-RT (5 weeks after the beginning of radiotherapy)and post-RT (4 weeks after the completion of radiotherapy).Parotid MR parameters,mean radiation dose and xerostomia degrees of the patients at different time points were recorded.Furthermore,nine healthy volunteers were enrolled,who undergone T2 ? mapping twice with an interval of 4 weeks in order to analyze the reproducibility of T2 ? value.Results From pre-RT to mid-RT and post-RT,parotid volume decreased [atrophy rates,(25.34±11.33)％ and (25.74±9.93)％,respectively]and T2 ? values decreased [change rates,(-5.63±8.86)％ and (-4.81±10.67)％, respectively]significantly (all P < 0.01 ).Parotid normalized T1 signal intensity decreased significantly from pre-RT to post-RT [change rate,(-7.43±10.61)％,P =0.007],and the change rate was correlated inversely with mean radiation dose significantly (r =-0.646, P <0.001).Parotid volume and T2 ? value changed correspondingly with xerostomia degrees of the patients during radiotherapy.Parotid MR parameters showed excellent reproducibility (intraclass correlation coefficient,0.843 -0.993).Conclusion The dynamic changes of radiation-induced parotid damage in patients with NPC can be noninvasively evaluated by routine MRI and T2 ? mapping.
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Objective To monitor the dynamic changes of radiation-induced parotid damage using T2 ? mapping.Methods Thirty-four patients with nasopharyngeal carcinoma (NPC)were enrolled.All patients underwent T1 WI,T2 WI and T2 ? mapping for bilateral parotid glands at pre-RT (2 weeks before radiotherapy),mid-RT (5 weeks after the beginning of radiotherapy)and post-RT (4 weeks after the completion of radiotherapy).Parotid MR parameters,mean radiation dose and xerostomia degrees of the patients at different time points were recorded.Furthermore,nine healthy volunteers were enrolled,who undergone T2 ? mapping twice with an interval of 4 weeks in order to analyze the reproducibility of T2 ? value.Results From pre-RT to mid-RT and post-RT,parotid volume decreased [atrophy rates,(25.34±11.33)％ and (25.74±9.93)％,respectively]and T2 ? values decreased [change rates,(-5.63±8.86)％ and (-4.81±10.67)％, respectively]significantly (all P < 0.01 ).Parotid normalized T1 signal intensity decreased significantly from pre-RT to post-RT [change rate,(-7.43±10.61)％,P =0.007],and the change rate was correlated inversely with mean radiation dose significantly (r =-0.646, P <0.001).Parotid volume and T2 ? value changed correspondingly with xerostomia degrees of the patients during radiotherapy.Parotid MR parameters showed excellent reproducibility (intraclass correlation coefficient,0.843 -0.993).Conclusion The dynamic changes of radiation-induced parotid damage in patients with NPC can be noninvasively evaluated by routine MRI and T2 ? mapping.
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Objective CA125 has been proved to be closely related to peritoneal metastasis of gastric cancer.This study aimed to screen and identify a novel ssDNA aptamer targeting the extracellular domain of Mucin16. Methods Using capillary elec-trophoresis, we screened the aptamers targeting the synthetic peptide of the extracellular domain of Mucin16 and quantitatively deter-mined the Kd value of each cycle and the affinity of the aptamers for the synthetic peptide by CE-SELEX.Then we evaluated the ability of the obtained aptamers to target cancer cells using confocal laser imaging. Results After five cycles of screening, sequencing, af-finity determination, we obtained an ssDNA aptamer targeting the extracellular domain of Mucin16, with a Kd value of 122.7 nm and visible green fluorescent signals on the cell membrane of the human ovarian cancer cell line expressing Mucin16, but not on that of the normal hepatocytes not expressing Mucin16.This confirmed the binding ability of the aptamer to the extracellular domain of Mucin16. Conclusion A novel aptamer targeting the synthetic peptide of the extracellular domain of Mucin16 was successfully obtained by capil-lary electrophoresis, which could be used as a new agent in the diagnosis and treatment of peritoneal metastasis of gastric cancer.
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A number of medications have been proved to be able to either improve the antitumor effect of chemotherapeutics and molecular targeted drugs or reverse the resistance of tumors to chemotherapeutics and molecular targeted drugs,which are not traditionally used as anticancer drugs.Especially for late-stage tumors after multiple treatments,these agents are good alternatives when used independently or in combination with chemotherapeutics and molecular targeted drugs.These drugs include proton modulators,hypoglycemic agents and cardiovascular agents,etc.
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Gastric cancer is the fifth most common cancer and the third leading cause of death globally .Apart from the suc-cessful phase Ⅲclinical trial of trastuzumab and Ramucirumab , other targeted therapies in gastric cancer ( GC) have fallen short or still in early clinical development .In this review, we will summarize the most up to date information on many of the potential actionabledriver genesin gastric cancer and the importance of using the optimal diagnostic test to select for these molecularly defined patients . We focus on the following aspects:HER-2, EGFR, FGFR, MET, IGF-1R and VEGF.
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Background and purpose:Mir-21 has been demonstrated high expressed in many kinds of tumor tissues and cell lines. High expressed miR-21 leads to chemoresistance. Circulating miRNA is a novel biomarker for chemosensitivity prediction. The aim of our study was to investigate the role of plasma and tumor miR-21 levels as predictive biomarkers for irinotecan in gastric cancer. Methods: The histoculture drug response assay (HDRA) was used to determine irinotecan and cisplatin sensitivity on 35 freshly removed gastric tumor specimens. miR-21 expressions in tumor and plasma were determined by quantitative reverse transcription polymerase chain reaction. Results:Plasma miR-21 was closely correlated with corresponding miR-21 mRNA level in tumor tissues (rho=0.736, P<0.001) and was not correlated with sex, age, pathology type, differentiation, lymph node metastasis, TNM stage or tumor location. Patients with stage Ⅱ-Ⅲhad higher miR-21 levels. The tumor miR-21 expressions in cisplatin-sensitive group and resistant group were 1.32 (95%CI:0.73-1.90) and 4.06 (95%CI:1.71-6.41)(P=0.004), respectively. The plasma miR-21 expressions in cisplatin-sensitive group and resistant group were 5.25 (95%CI:0.14-10.64) and 5.82 (95%CI: 2.27-9.37)(P=0.19). The tumor miR-21 expressions in irinotecan-sensitive group and resistant group were 1.09 (95%CI:0.65-1.54) and 4.94 (95%CI:2.44-7.44)(P<0.001), respectively. The plasma miR-21 expressions in irinotecan-sensitive group and resistant group were 1.86 (95%CI:1.08-2.64) and 12.42 (95%CI:3.14-21.70)(P=0.001). Conclusion:A signiifcant correlation was observed between plasma and tumor miR-21 level. The low plasma miR-21 level could benefit from treatment with irinotecan. And low tumor miR-21 expression correlated with increased irinotecan and cisplatin response rate.
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Background and purpose: It has been reported that some low dose chemotherapy drugs have antiangiogenetic effects. The purpose of this study was to investigate the effect of inhibiting angiogenesis by low dose hydroxycamptothecin on H22 hepatoma transplantation tumor mouse models. Methods: H22 transplantation tumor mouse models were established, CTX was administrated in abdominal cavities as positive control group. 0.9%NaC1 solution was administrated as negative control group. Intra abdominal cyclophosphamide and hydroxycamptothecin (0.2 and 0.4 mg/kg) were injected for 10 days continuously. The growth of tumor were observed and measured. The tumor inhibitory rates were tested in animal tumor model with experimental treatment. The expression of VEGF and CD34 were measured by means of immunohistochemistry. Results: Hydroxycamptothecin had effect on tumor growth. Tumor weight inhibitory rates of hydroxycamptothecin with 0.2 and 0.4 mg/kg were 23.53% and 43.25% respectively. The difference was significant when compared with the negative control group (P<0.05). The expression of VEGF and MVD can be suppressed significantly than negative control group in vivo (P<0.05). Conclusion:Hydroxycamptothecin have inhibitory effect on tumor growth and the expression of VEGF and MVD with H22 hepatoma transplantation tumor mouse models in low dose. The mechanism possibly involved inhibiting the angiogenesis.
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Objective:The aim of this study was to investigate the association of mRNA expressions of ERCC1 (excision repair cross-complementing group 1) and BRCA1 (breast cancer 1) with chemosensitivity to cisplatin in malignant pleural and peritoneal effusions.Methods:Malignant pleural and peritoneal effusions were collected from 46 patients diagnosed with stage Ⅳ malignant tumor, prospectively. The tumor cells were isolated and the sensitivity of tumor cells to cisplatin was detected by adenosine triphosphate-bioluminescence assay (ATP-TCA). Real-time quantitative PCR was used to determine the mRNA expressions of ERCC1 and BRCA1. Results:The expression level of ERCC1 mRNA was negatively correlated with sensitivity of non-small cell lung cancer (NSCLC) to cisplatin (P= 0.001, r=0.685). BRCA1 mRNA expression level had negative correlation with sensitivity to cisplatin in both NSCLC (P=0.014, r=0.541) and gastric cancer (P=0.002, r=0.625). A significant interaction was found between the effects of ERCC1 and BRCA1 mRNA expressions on sensitivity to cisplatin (P=0.010 for all patients;P=0.027 for gastric cancer patients).Conclusion:ERCC1 and BRCA1 mRNA expression levels correlated with ex vivo chemosensitivity of tumor cells to cisplatin in malignant pleural and peritoneal effusions. Detection of both ERCC1 and BRCA1 may have a higher reliability in predicting the sensitivity of tumor cells to cisplatin than detection of single ERCC1 or BRCA1 expression.
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Objective To evaluate the significance of COLD-PCR in detecting KRAS mutation of pancreatic cancer and colorectal cancer patients. Methods First, set up COLD-PCR and compared the sensitivities of COLD-PCR/Sanger sequencing with PCR/Sanger sequencing using mixed cell lines ( KRAS wild-type cell line SW116 and KRAS mutant cell line SW480).Then, detected KRAS mutation of 20 formalin-fixed paraffin-embedded samples of pancreatic cancer and 39 formalin-fixed paraffin-embedded samples of colorectal cancer using PCR/Sanger sequencing and COLD-PCR/Sanger sequencing, respectively and compared the coincidence rate and consistency. Results The low detection limits of PCR/Sanger respectively. KRAS frequency detected by COLD-PCR/Sanger sequencing [75% (15/20)] in 20 cases of pancreatic cancer was higher than that detected by regular PCR/Sanger sequencing [40% ( 8/20 ) ,x2 =5.013, P < 0.05]. KRAS frequency detected by COLD-PCR/Sanger sequencing [44% (17/39)] in 39 cases of colorectal cancer was higher than that detected by regular PCR/Sanger sequencing [31% (12/39) ,x2 =1. 372, P = 0. 174]. The coincidence rate of these two methods was 0. 730 and the difference had no statistical significance. The coincidence rate of detecting KRAS mutation was 65% in pancreatic cancer and the results showed a good correlation between two methods and the two methods had bad agreement in diagnosis (Kappa = 0. 364, P < 0. 05 ). COLD-PCR/Sanger sequencing could detect more cases of KRAS mutations from pancreatic caner than regular PCR/Sanger sequencing. This was because there were many non-tumor cells in pancreatic tumor tissue and COLD-PCR/Sanger sequencing was more sensitive than regular PCR/Sanger sequencing. The coincidence rate of detecting KRAS mutations was 87% in colorectal cancer and the results were showed a good correlation between two methods and the two methods had substantical agreement in diagonsis ( Kappa = 0. 730, P < 0. 05 ) . Conclusion COLD-PCR/Sanger sequencing is highly sensitive to screen KRAS mutation in pancreatic cancer and colorectal cancer patients.
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Objective To investigate whether the single nucleotide polymorphisms (SNP) in DNA repair gene XRCC1(X-ray repair cross-complementing 1) were associated with the survival of cisplatin based combination concurrent chemoradiotherapy in esophagus cancer. Methods Overall 286 esophagus cancer patients receiving cisplatinum based chemotherapy were investigated. 5' nuclease allelic discrimination assay (TaqMan) and real-time PCR were taken to assess XRCC1 genotypes. Efficacies and adverse-effects were analyzed individually according to their genotype. Results Short-time effects showed the RR rate in patients with Arg/Arg and Arg/GIn genotypes(A group) was 93.56 %, significantly higher than 69.81% (P<0.05) in patients with GIn/GIn genotype (B group). The 1-year and 3-year survival rates were 82.8 %, 41.2 % in A group, significantly (P<0.05) different from 58.5 %, 26.4 % in B group, respectively. No statistically differences were found on adverse effects. Conclusion Significant relationships are found between single nucleotide polymorphisms in XRCC1 and outcome in esophagus cancer receiving cisplatin based concurrent chemoradiotherapy.
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Resistance is one of the most important reasons that restrict the clinical application of most chemotherapeutic medicines. Docetaxel is a very widely applicated antitumor medicine. Most of the researches on the mechanism of resistance against docetaxel focused on the drug transporters, changes in drug metabolism and pathway alteration of cell cycle and apoptnsis. The mechanism of docetaxel resistance and the predictive data based on clinical research to docetaxel therapy in cancer treatment were reviewed.