长春瑞滨、氟尿嘧啶联合顺铂治疗晚期食道癌的临床观察

目的:观察以长春瑞滨为主的联合化疗方案治疗晚期食道癌的疗效和安全性。方法:经病理学确诊的晚期食道癌病人56例,随机分为两组:每组28例。治疗组采用长春瑞滨首日静脉推注10mg,第1~5天每日10mg泵维持24h,第1~5天静脉滴注氟尿嘧啶0.5g/m2;第1~3天静脉滴注顺铂30mg/m2。对照组氟尿嘧啶、顺铂用法、剂量与治疗组完全相同,每4周重复一次,连用3周期评定结果。结果:治疗组和对照组的有效率分别为53.4%和35.7%,在统计学上有显著性差异(P<0.05);中位生存期分别为9.5个月和8.2个月;主要毒副作用为骨髓抑制及消化道反应。结论:以长春瑞滨为主的联合化疗方案治疗晚期食道癌,疗效好、毒性小,值得进一步推广。

Survey of Radiosensitizing Agents (Synthesized Chemicals and Gene Therapeutic Agents) Since 2000

Radiotherapy has played an important role in treatment of tumor patientssince it appeared about 80 years ago, and has been an indispensable part of the management of about50% of tumors (especially 60% - 70% of malignant tumors). Currently, radiotherapy is used in simpleand palliative therapy, adjuvant therapy after or before surgery, simultaneous radio-chemotherapy,combined BRM (biological response modifier) therapy, ets. Radiosensitizing agents enhance theradiation effects on tumor cells so as to have better responses in radiotherapy. Tumor intrinsicradiosensitivity is affected by the hy-poxic level in solid tumor, the ability of the cells torepair the radiation-induced DNA damage, the number of cells which have a clonogenic capability toreestablish uncontrolled cell growth, the amount of dividing cells, and the distribution of cellsthroughout the cell cycle. Consequently , it is necessary and useful to add one or moreradiosensitizing agents in radiotherapy to increase the radio-sensitivity of tumor cells.

Enhanced therapeutic effects of combined chemotherapeutic drugs and midkine antisense oligonucleotides for hepatocellular carcinoma

AIM: To evaluate the effect of combined antisense oligonucleotides targeting midkine (MK-AS) and chemotherapeutic drugs [cisplatin(DDP), 5-fluorouracil (5-FU) and adriamycin (ADM)] on inhibition of HepG2 cell proliferation, and to analyze the efficacy of MK-AS used in combined ADM in in situ human hepatocellular carcinoma (HCC) model. METHODS: HepG2 cells were treated with MK-AS and/or chemotherapeutic drugs mediated by Lipofectin, and cell growth activity was determined by MTS assay. An in situ HCC model was used in this experiment. MK- AS, ADM and MK-AS + ADM were given intravenously for 20 d, respectively. The animal body weight and their tumor weight were measured to assess the effect of the combined therapy in vivo. RESULTS: Combined treatment with MK-AS reduced the IC50 of DDP, 5-FU and ADM in HepG2 cells. MK-AS significantly increased the inhibition rate of DDP, 5-FU and ADM. Additionally, synergism (Q 1.15) occurred at a lower concentration of ADM, 5-FU and DDP with combined MK-AS. Combined treatment with MK-AS and ADM resulted in the more growth inhibition on in situ human HCC model compared with treatment with chemotherapeutic drugs alone. CONCLUSION: MK-AS increases the chemosensitivity in HepG2 cells and in situ human HCC model, and thecombination of MK-AS and ADM has a much better in vitro and in vivo synergism.

Successful treatment of multiple lung metastases of hepatocellular carcinoma by combined chemotherapy with docetaxel, cisplatin and tegafur/uracil

We report the successful treatment of multiple lung metastases after hepatic resection for hepatocellular carcinoma (HCC) with combined docetaxel, cisplatin (CDDP), and enteric-coated tegafur/uracil (UFT-E). A 68-year-old man was diagnosed with multiple lung metastases of HCC 7 mo after partial hepatectomy for HCC. Oral UFT-E was given daily and docetaxel and CDDP were given intra-arterially (administered just before the bronchial arteries) every 2 wk via a subcutaneous injection port. One month after starting chemotherapy, levels of tumor marker, protein induced by vitamin K absence(PIVKA--), decreased rapidly,and after a further month, chest X-ray and computed tomography revealed the complete disappearance of multiple liver metastases. Two years after the combined chemotherapy, HCC recurred in the liver and was treated but no pulmonary recurrence occurred. In the absence of a standardized highly effective therapy, this combined chemotherapy with docetaxel, CDDP and UFT-E may be an attractive option for multiple lung metastases of HCC.

Retrospective study of cetuximab in combination with chemotherapy for patients with colorectal cancer

Objective： To evaluate the efficacy and safety of cetuximab combined with chemotherapy in colorectal cancer （CRC）. Methods： 35 cases of CRC were retrospectively analyzed. Efficacy and adverse events were observed. Results： 29 cases of CRC were evaluated by RECIST criteria, showing 7 PR （partial response, 24.1%） and 15 SD （stable disease, 51.8%）, disease control rate （DC） was 75.9%. Subgroup analysis showed response rate （RR） of 36.4% and DC of 91% in the 1st line therapy, RR of 20% and DC of 70% in the 2rid line therapy, RR of 12.5% and DC of 62.5% in heavily pre-treated cases. Rash appeared in 74.3% of patients （grade 3 was 8.6%）, and the severity was relevant with disease control rate （DC）. Neutropenia of grade 3/4 was 14.3%, and infusion related reaction （IRR） of grade 3 happened in 1 case （2.9%）. Conclusion： Cetuximab combined with chemotherapy is safe and effective for patients with metastatic colorectal cancer. The combination therapy shows high DC, especially in 1st line therapy. Severity of rash may predict efficacy.

Docetaxel and cisplatin combination chemotherapy in anthracyclines-resistant advanced breast cancer

Objective： To observe the effect and toxicity of docetaxel with cisplatin in anthracyclines-resistant advanced breast cancer. Methods： Forty-five female patients received docetaxel 60 mg/m^2 on dl and cisplatin 30 mg/m^2 on d1-d3 of every 28 days. Every patient was treated with at least 2 cycles and a median of 3 cycles （2-6 cycles ）. Results： Five patients achieved complete response （11.1%） and 18 partial response （40.0%）, 10 stable disease （22.2%）. The overall response rate was 51.1%. The clinical disease control rate was 73.3%, median time to tumor progression （TTP） was 7.8 months （1.0-34.5 months）, median survival time was 17.6 months （range 1.9-48.0 months）, and one year survival rate was 65.2%. The main side effect was marrow suppression. The treatment was well tolerated with grades Ⅲ and Ⅳ leukopenia in nine （20%） and ten （22.2%） patients. Conclusion： Combinative chemotherapy of docetaxel and cisplatin has a good anti-tumor activity on refractory advanced breast cancer with manageable toxicity.

The short-time effects of chemotherapy with combinations of hydroxycamptothecine and oxaliplatin in treatment of advanced colorectal cancer

Objective： Although 5-fluarouracil-based chemotherapy has become a standard regimen for treatment of advanced colorectal cancer, the efficacy, as second line therapy, is not high. It is necessary to find a new regimen as a substitute for these patients. The study was to evaluate the short-time effects and toxicity of combination of HCPT plus L-OHP regimen in treatment of advanced colorectal cancer. Methods： Forty-seven patients with pathological evidence of advanced colorectal cancer were enrolled and were treated with HCPT plus L-OHP regimen for 86 cycles. All patients were treated with L-OHP 130 mg/m^2 day 1 and HCPT 6 mg/m^2day 1-4, the chemotherapy was repeated every 3 weeks as a cycle. The Short-time efficats and side effects were evaluated after 2 cycles for each patient. Results： 38 cases can be evaluated to short-time effects and achieved the overall response rate （CR＋PR） was 36.8%. KPS improved in 20 cases （52.6%）. In the total 86 cycles, the leucopenia occurred in 59 cycles （68.6%）,18 cycles （30.5%） in grade Ⅲ and Ⅳ and the diarrhea occurred in 48 cycles （55.8%）, 18 cycles （37.5%） in grade Ⅲ and Ⅳ. Conclusion： A satisfied response rate was obtained in advanced colorectal cancer patients treated by HCPT plus L-OHP regimen, especially who were the failure of first-line chemotherapy with 5-FU. The limited-dose toxicity was leucopenia and diarrhea.

Experimental study on effect of recombinant human growth hormone combined with chemotherapy on stomach neoplasms implanted in nude mice

Objective: To investigate the effect of different doses of recombined growth hormone (rhGH) on stomach neo- plasms implanted in nude mice, and its efficacy in combining with chemotherapy (flurouracil, 5-FU). Methods: Human stom- ach neoplasms model was established in nude mice. The nude mice were divided into control group, moderate-dose of rhGH group, low-dose rhGH group, 5-FU group, moderate-dose rhGH/5-FU group, and low-dose rhGH/5-FU group. The results of each group were observed after ten days. Results: After therapy, the body mass of rhGH groups was significantly increased compared with control group (P<0.05), the body mass of rhGH/5-FU groups was significantly increased compared with 5-FU group (P<0.05), but it was no significant difference between rhGH/5-FU groups and control group (P>0.05). The average tumor mass and volume of rhGH groups were not significantly increased compared with control group (P>0.05), but they were significantly reduced in 5-FU group and rhGH/5-FU groups (P<0.05). They were no significant difference between rhGH/5- FU groups and 5-FU group (P>0.05). After treatment, the percentages of S, G0/G1 and G2/M phases and proliferation index (PI) were not significantly changed in rhGH groups compared with control group (P>0.05), and the same with rhGH/5-FU groups compared with 5-FU group (P>0.05). The difference caused by dose of rhGH was not significant. Conclusion: rhGH enhances body mass, does not stimulate tumor growth, and has no adverse effects on tumor bearing nude mice. Combined with flurouracil, rhGH does not influence the efficacy of chemotherapy, and has no effect on tumor cell cycle kinetics.

Clinical Study of Combining Chemotherapy of Oxaliplatin or 5-Fluorouracil/Leucovorin with Hydroxycamptothecine for Advanced Colorectal Cancer

OBJECTIVE To estimate effects, survival rate after the short-time efficacy, side the treatment of combining chemotherapy of oxaliplatin or 5-fluorouracil/leucovorin with hydroxycamptothecine （HCPT） for the patients with advanced colorectal cancer. METHODS From January 2002 to November 2005, 59 patients with advanced colorectal cancer confirmed by pathology were enrolled into this study in the department of medical oncology, in the Sixth People＇s Hospital of Shanghai Jiaotong University, Shanghai. Patients＇ characteristics in two groups were similarly confirmed by statistic. All 37 patients in OH group received oxalip21atin （130 mg/m^2 d1） plus hydroxycamptothecine （6 mg/m d1-4）, and all 22 patients in the HLF group received hydroxycamptothecine （6 mg/m^2 d1-4） plus leucovorin （300 mg d1-5） and 5-fluorouracil （0.375 g/m^2 d1-5）. The regimens in both groups were 21-day cycle that was repeated three weeks. The side effects were evaluated. The efficacy was estimated after two cycles of chemotherapy for each patient. RESULTS The efficacy of the treatment in the OH group with 37 patients and in the HLF group with 22 patients was estimated. The overall response rate （CR ＋ PR） was 32.4% in the OH group and 22.7% in the HLF group. There was no complete response （CR） and there was no statistical significantly difference （%2= 0.876, P = 0.704） in two groups. The 1-year survival rate was 30.98% in the OH group and 15.02% in the HLF group, and it had no significant difference between the two groups. The median PSF and OS were 5.83 months and 11.17 months in the OH group vs. 7.40 months and 10.48 months in the HLF group, and it had no significant differences between the two groups （P 〉 0.05）. The major side effects of grade III and IV in the two groups were myelosuppression and gastrointestinal reactions. The statistically significant difference in side effects appeared in leukopenia （χ^2= 17.173, P = 0.001）, nausea/vomiting （χ^2= 6.426, P = 0.039）, diarrhea （χ^2= 16.245, P = 0.000） and peripheral neuropathy. CONCLUSION The efficacy was almost equal between the OH and the HLF groups, and the two regimens can be used as the second-line treatments for the patients with colorectal cancer. Leucopenia, nausea, diarrhea and peripheral neuropathy appeared more in OH group, and anemia and thrombocytopenia were almost equal between the OH and the HLF groups.

Diagnosis and therapy of ascites in liver cirrhosis

Ascites is one of the major complications of liver cirrhosis and is associated with a poor prognosis. It is important to distinguish noncirrhotic from cirrhotic causes of ascites to guide therapy in patients with noncirrhotic ascites. Mild to moderate ascites is treated by salt restriction and diuretic therapy. The diuretic of choice is spironolactone. A combination treatment with furosemide might be necessary in patients who do not respond to spironolactone alone. Tense ascites is treated by paracentesis, followed by albumin infusion and diuretic therapy. Treatment options for refractory ascites include repeated paracentesis and transjugular intrahepatic portosystemic shunt placement in patients with a preserved liver function. Potential complications of ascites are spontaneous bacterial peritonitis (SBP) and hepatorenal syndrome (HRS). SBP is diagnosed by an ascitic neutrophil count > 250 cells/mm3 and is treated with antibiotics. Patients who survive a first episode of SBP or with a low protein concentration in the ascitic fluid require an antibiotic prophylaxis. The prognosis of untreated HRS type 1 is grave. Treatment consists of a combination of terlipressin and albumin. Hemodialysis might serve in selected patients as a bridging therapy to liver transplantation. Liver transplantation should be considered in all patients with ascites and liver cirrhosis.

Irritable bowel syndrome subtypes differ in body awareness, psychological symptoms and biochemical stress markers

AIM: To elucidate the differences in somatic, psycho-logical and biochemical pattern between the subtypes of irritable bowel syndrome (IBS). METHODS: Eighty IBS patients, 30 diarrhoea pre-dominant (D-IBS), 16 constipation predominant (C-IBS) and 34 alternating IBS (A-IBS) underwent physi-otherapeutic examinations for dysfunctions in body movements and awareness and were compared to an apparently healthy control group (AHC). All groups an-swered questionnaires for gastrointestinal and psycho-logical symptoms. Biochemical variables were analysed in blood. RESULTS: The D-IBS group showed less body aware-ness, less psychological symptoms, a more normal sense of coherence and psychosocial rating as well as higher C-peptide values. C-IBS had a higher degree of body dysfunction and psychological symptoms, as well as the lowest sense of coherence compared to controls and D-IBS. They also demonstrated the most elevated prolactin levels. A-IBS had the lowest degree of body disturbance, deteriorated quality of life and affected bi-ochemical pattern. All subtypes had higher pain scores compared to controls. In addition they all had signifi -cantly increased triglycerides and elevated morning cortisol levels, however, without statistical signifi cance compared with the controls.CONCLUSION: IBS subtypes showed different pro-files in body awareness, somatic and psychological symptoms and in biochemical variables. D-IBS differed compared to the other groups by lowered body aware-ness, less psychological symptoms and a higher sense of coherence and elevated C-peptide values. C-IBS and A-IBS subtypes suffered more from depression and anxiety, associated with a lower quality of life. These differences may be important and will be taken into account in our treatment of these patients.

Effective siRNA targets screening for human telomerase reverse transcriptase

AIM: To study the inhibitory effects of siRNAs targeting different hTERT sequences and to screen the effective siRNA sequence.METHODS: Five double-stranded siRNAs targeting coding and non-coding regions of hTERT gene were designed and synthesized by T7 transcription system in vitro. siRNA4sequence was screened by full length gene targeting technique and the rest of the siRNA sequences were selected randomly. After being purified by ethanol precipitation, the siRNAs were transfected to the human hepatocellular carcinoma cell (HepG2) by Lipofectamine 2000TM. At 48-72 h after siRNAs transfection, MTT assay,RT-PCR and Western-blot were applied to evaluate the effects of siRNAs on cell growth, mRNA and protein expression level of hTERT gene, respectively.RESULTS: Compared to the control cells, the cells treated with the five double-stranded siRNAs exhibited different degrees of inhibition of cell proliferation in a dose-dependent manner. siRNA2 and siRNA4, exhibited obvious effects of inhibiting hTERT mRNA and protein expression in HepG2cells.CONCLUSION: siRNAs targeting different hTERT sequences have significantly various inhibitory effects on hTERT gene expression. The siRNA sequence screened by full length gene targeting technique has comparable inhibitory effect with the rest siRNA sequences screened by random selection, suggesting that siRNAs and antisense oligonucleic acids may have the same effective target sites. Compared with chemical synthesis method,synthesizing double-stranded siRNA by T7 transcription system in vitro is a rapid, simple, and inexpensive method suitable for screening high-effect siRNA targeting site for specific gene.

Matrix metalloproteinase-2 as a superior biomarker for peritoneal deterioration in peritoneal dialysis

AIM： To investigate the effcacy of effuent biomarkers for peritoneal deterioration with functional decline in peritoneal dialysis （PD）.METHODS： From January 2005 to March 2013, the subjects included 218 PD patients with end-stage renal disease at 18 centers. Matrix metalloproteinase-2 （MMP-2）, interleukin-6 （IL-6）, hyaluronan, and cancer antigen 125 （CA125） in peritoneal effluent were quantified with enzyme-linked immunosorbent assay. Peritoneal solute transport rate was assessed by peritoneal equilibration test （PET） to estimate peritoneal deterioration.RESULTS： The ratio of the effuent level of creatinine （Cr） obtained 4 h after injection （D） to that of plasma was correlated with the effluent levels of MMP-2 （ρ = 0.74, P 〈 0.001）, IL-6 （ρ = 0.46, P 〈 0.001）, and hyaluronan （ρ = 0.27, P 〈 0.001）, but not CA125 （ρ = 0.13, P = 0.051）. The area under receiver operating characteristic curve for the effluent levels of MMP-2, IL-6, and hyaluronan against high PET category were 0.90, 0.78, 0.62, and 0.51, respectively. No patient developed new-onset encapsulating peritoneal sclerosis for at least 1.5 years after peritoneal effuent sampling.CONCLUSION： The effuent MMP-2 level most closely reflected peritoneal solute transport rate. MMP-2 can be a reliable indicator of peritoneal deterioration with functional decline.

Neoadjuvant plus adjuvant chemotherapy benefits overall survival of locally advanced gastric cancer

Neoadjuvant chemotherapy (NAC) has drawn more attention to the treatment of locally advanced gastric cancer (AGC) in the current multidisciplinary treatment model. EORTC trial 40954 has recently reported that NAC plus surgery without postoperative adjuvant chemotherapy could not benefit the locally AGC patients in their overall survival. We performed a meta-analysis of 10 studies including 1518 gastric cancer patients. Stratified subgroups were NAC plus surgery and NAC plus both surgery and adjuvant chemotherapy (AC), while control was surgery alone. The results showed that NAC plus surgery did not benefit the patients with locally AGC in their overall survival [odds ratio (OR) = 1.20, 95% CI 0.80-1.80, P = 0.37] and the number needed to treat (NNT) was 74. However, the NAC plus both surgery and AC had a slight overall survival benefit (OR = 1.33, 95% CI 1.03-1.71, P = 0.03) and NNT was 14, which is superior to the NAC plus surgery. Therefore, we recommend that combined NAC and AC should be used to improve the overall survival of the locally AGC patients.

Comprehensive treatment of advanced primary live cancer with intraperitoneal chemotherapy or in combination with other therapies:therapeutic observation of 72 cases

Objective： To evaluate the effect of intraperitoneal chemotherapy or in combination with other therapies in patients with advanced primary liver cancer. Methods： 72 patients with advanced primary liver cancer with no indication for surgery received intraperitoneal chemotherapy in combination with other therapies including transcatheter arterial chemoembolization （TACE）, radiofrequency catheter ablation （RFA）, percutaneous ethanol injection therapy （PELT） and radiotherapy. Of them, 29 cases were complicated with hilar or retroperitoneal multiple lymph node metastases, 14 with portal vein embolus, 15 with intrapedtoneal and diaphragmatic metastases, 6 with chylous ascites, one with cancerous ascites, and 7 with suspected cancerous ascites （referring to large amounts of ascites without hypoproteinemia while exfoliative cytology of the ascites was positive）. The mean maximum tumor size was 8.2 cm in diameter. Liver function at the initial treatment was Child A in 53 cases, and Child B in 19 cases. I ntrapedtoneal chemotherapy was performed in all these patients. The intraperitoneal chemotherapy protocols included： 5-FU 0.5-0.75 g/d for 10-15 consecutive days, with a total dosage of 5-12.5 g, and at the last day of chemotherapy 10 mg mitomycin （MMC） or 100 mg carboplatin was injected. For 7 cases of cholangiocarcinoma, Gemzar 800-1000 mg was administered additionally. A majority of all these patients received another one or two therapy methods followed by intraperitoneal chemotherapy. TACE was performed in the patients with multiple tumors or nodule more than 5 cm in diameter in the liver, RFA or PElT with nodule fewer than 4 in number and 5 cm or less than 5 cm in diameter and radiotherapy, only for metastases, with metastatic lymph nodes, localized metastasis within the abdominal cavity or portal vein embolus. Interval time between two methods was one month or so. Two months after the sequential therapy, repeated treatment would be given if general medical condition and liver function were perfect at that time. Results： The median survival time of the group was 13.97 ± 6.27 months. The 1- and 2-year survival rates were 59.7% and 30.6% respectively. The mean survival time of the patients with liver function Child A was 15.91 ± 5.49 months, and that of the patients with Child B was 8.55 ± 5.09 months. The difference was statistically significant （P 〈 0.05）. Conclusion： Intraperitoneal chemotherapy or in combination with other therapies in patients with advanced primary liver cancer with metastases to abdominal cavity is an effective method. It can prolong the survival time and improve life quality for a certain percentage of patients with advanced pnmary liver cancer.

Study of hepatic arterial infusion of Endostar combined with TACE on advanced hepatocellular carcinoma

Objective:To study the efficacy and safety of hepatic arterial infusion of Endostatin(YH-16,Endostar),combined with transcatheter arterial chemoembolization(TACE) on advanced hepatocellular carcinoma.Methods:Thirty patients with advanced hepatocellular carcinoma were enrolled in the study.The patients received hepatic arterial infusion of Endostar combined with TACE.The efficacy was evaluated strictly after 1-2 cycles according to RECIST criteria and the value of AFP;quality of life(QOL) was evaluated according to Karnofsky scores.Adverse effects were evaluated too.Results:29 cases' efficacy was evaluated among the total 30 cases.The KPS were significantly increased after the treatment(80.39 ± 8.37 vs 73.93 ± 9.22,P = 0.002).Compared with control group,the objective response rate(CR and PR) and the rate of AFP negative changed were significantly higher(P = 0.021,P = 0.046).The adverse effects were not obvious.Conclusion:The QOL and preliminary efficiency of patients of advanced hepatocellular carcinoma may be improved by hepatic arterial infusion of Endostar combined with TACE,the rate of AFP negative changed were significantly higher too,and there are little of adverse effects.It is worthy to clinical generalization and further clinical observation.

Integrating TYMS, KRAS and BRAF testing in patients with metastatic colorectal cancer

AIM To investigate the impact of thymidylate synthase(TYMS), KRAS and BRAF in the survival of metastatic colorectal cancer(m CRC) patients treated with chemotherapy. METHODS Clinical data were collected retrospectively from records of consecutive patients with m CRC treated with fluoropyrimidine-based chemotherapy from 1/2005 to 1/2007. Formalin-fixed paraffin-embedded tissues were retrieved for analysis. TYMS genotypes were identified with restriction fragment analysis PCR, while KRAS and BRAF mutation status was evaluated using real-time PCR assays. TYMS gene polymorphisms of each of the 3' untranslated region(UTR) and 5'UTR were classified into three groups according to the probability they have for high, medium and low TYMS expression(and similar levels of risk) based on evidence from previous studies. Univariate and multivariate survival analyses were performed.RESULTS The analysis recovered 89 patients with m CRC(46.1% de novo metastatic disease and 53.9% relapsed). Of these, 46 patients(51.7%) had colon cancer and 43(48.3%) rectal cancer as primary. All patients were treated with fluoropyrimidine-based chemotherapy(5FU or capecitabine) as single-agent or in combination with irinotecan or/and oxaliplatin or/and bevacizumab. With a median follow-up time of 14.8 mo(range 0-119.8), 85 patients(95.5%) experienced disease progression, and 63 deaths(70.8%) were recorded. The 3-year and 5-year OS rate was 25.4% and 7.7% while the 3-year progression-free survival rate was 7.1%. Multivariate analysis of TYMS polymorphisms, KRAS and BRAF with clinicopathological parameters indicated that TYMS 3'UTR polymorphisms are associated with risk for disease progression and death(P < 0.05 and P < 0.03 respectively). When compared to tumors without any del allele(genotypes ins/ins and ins/loss of heterozygosity(LOH) linked with high TYMS expression) tumors with del/del genotype(low expression group) and tumors with ins/del or del/LOH(intermediate expression group) have lower risk for disease progression(HR = 0.432, 95%CI: 0.198-0.946, P < 0.04 and HR = 0.513, 95%CI: 0.287-0.919, P < 0.03 respectively) and death(HR = 0.366, 95%CI: 0.162-0.827, P < 0.02 and HR = 0.559, 95%CI: 0.309-1.113, P < 0.06 respectively). Additionally,KRAS mutation was associated independently with the risk of disease progression(HR = 1.600, 95%CI: 1.011-2.531, P < 0.05). The addition of irinotecan in 1st line chemotherapy was associated independently with lower risk for disease progression and death(HR = 0.600, 95%CI: 0.372-0.969, P < 0.04 and HR = 0.352, 95%CI: 0.164-0.757, P < 0.01 respectively).CONCLUSION The TYMS genotypes ins/ins and ins/LOH associate with worst prognosis in m CRC patients under fluoropyrimidine-based chemotherapy. Large prospective studies are needed for validation of our findings.

Primitive neuroectodermal tumor of uterus——A rare entity

Primitive neuroectodermal tumor (PNET) of uterus is the rare of the rarest among the tumors of female genital tract. We herein reported a 32 years old female operated for lower abdominal lump,which was diagnosed,as PNET later confirmed by immunohistochemistry (IHC). She was lost to follow-up and presented 10 months later with recurrence. She was treated with cyclical combination chemotherapy followed by definitive surgery and is in complete remission at present.

Intergranular Corrosion of AISI 304 Heat Treated at 800℃ Varying Range Times

Austenitic stainless steels, when exposed to welding conditions or aging for length of service, it＇s observed the formation of numerous deleterious phases, such as several kinds of carbides type MC, M6C, M7C3, M23C6, and intermetallic secondary phases （sigma, chi, laves）, which cause the process of intergranular corrosion. The aim of this work was verifying the formation of the types of carbides and/or intermetallic phases existing in the stainless AISI 304 at 800 ℃, varying the timing of heat treatment between 30, 360 and 1,440 min. The optical microscopy analysis revealed the predominant formation of the carbide type M23C6. The results of DL-EPR （double loop electrochemical potentiokinetic reactivation） tests showed a gradual increase in the precipitation of this carbide with the increase of treatment time. The potentiodynamic polarization showed that the precipitation of this carbide reduce the formation of the Cr2O3 passive layer, suggesting that the precipitate carbide to be predominantly of the Cr23C6 type.

Combined effects of Cantide and chemotherapeutic drugs on inhibition of tumor cells' growth in vitro and in vivo

AIM: To investigate the combination effect of hTERT antisense oligonucleotide 'Cantide' and three chemotherapeutic drugs (cisplatin, 5-fluorouracil (5-FU) and adriamycin (ADM)) on inhibiting the proliferation of HepG2, BGC and A549 cell lines in vitro, and to investigate the efficacy of Cantide used in combination with cisplatin (DDP) in vivo. METHODS: Cantide was transfected into these tumor cells by Lipofectin, and cell growth activity was calculated by microcytotoxicity assay. In vivo study, cells of HepG2 were implanted in Balb/c nude mice for 4 d. Then Cantide, DDP and Cantide+DDP were given intra peritonea Ily for 24 d respectively. The body weights of the tumor-bearing animals and their tumor mass were measured later to assess the effect of combination therapy in the nude mice. To evaluate the interaction of Cantide and these chemotherapeutic drugs, SAS software and Jin Zhengjun method were used. RESULTS: Combination treatments with 0.1μmol/L Cantide reduced the IC50 of DDP, 5-FU and ADM from 1.07, 4.15 and 0.29 μg/mL to 0.25,1.52 and 0.12 μg/mL respectively. The inhibition ability of DDP, 5-FU and ADM respectively in combination with Cantide in these tumor cells was higher than that of these drugs alone (P<0.0001). And synergism (Q≥1.15)was observed at the lower concentration of DDP (≤1μg/mL) and ADM (≤0.1 μg/mL) with combination of Cantide. In vivo, combination treatment with Cantide and DDP produced the greater growth inhibition of human liver carcinoma cells HepG2 in nude mice (0.65±0.19 g tumor) compared with that when only one of these drugs was used (Cantide group: 1.05±0.16 g tumor, P= 0.0009<0.001; DDP group: 1.13±0.09 g tumor, P= 0.0001<0.001). CONCLUSION: These findings indicate that Cantide may enhance therapeutic effectiveness of chemotherapeutic drugs over a wide range of tumor cells in vitro, and the combination use of Cantide and DDP can produce much higher inhibition rates, as compared with when either of these drugs was used only in vivo.