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Dihydroorotate dehydrogenase (DHODH) is a flavin-dependent metabolic enzyme that oxidizes dihydroorotate acid to orotic acid in the de novo synthesis pathway of pyrimidine metabolism. DHODH is located in mitochondria, closely related to cellular oxidative phosphorylation, and an important suppressor of the ferroptosis pathway. This study investigates the influence of DHODH on the progression of malignant tumors, including its important role in the de novo synthesis of pyrimidine, oxidative phosphorylation, and ferroptosis. The objective is to present evidence that DHODH is a potential target for the clinical treatment of tumors.
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Colorectal cancer is a common gastrointestinal malignant tumor with morbidity and mortality rising year by year. In recent years, the studies in and out of China have reported that metformin could inhibit the growth of colorectal cancer cells and improve the prognosis of patients by indirectly reducing the levels of insulin and glucose in the blood, or directly activating the AMP-activated protein kinase signaling pathways, promoting apoptosis of tumor cells, enhancing sensitivity to chemotherapy, inhibiting inflammatory responses, affecting the intestinal flora, and regulating the immune function, etc. This article reviews the current research status and controversies related to metformin against colorectal cancer, in an effort to provide new evidences for the treatment of colorectal cancer.
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Anastomotic leakage is one of the common and serious complications after colorectal cancer surgery, and it should be detected, prevented and treated as soon as possible. In recent years, the causes, diagnosis and treatment of postoperative anastomotic leakage of colorectal cancer have always been the focus of clinical attention, and relevant reports and prediction indicators continue to emerge. This article reviews the current situation and progress of biomarkers for predicting postoperative anastomotic leakage of colorectal cancer, in order to provide theoretical basis for early clinical detection and treatment of anastomotic leakage.
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Mitochondrial DNA (mt-DNA) is an important carrier of extranuclear genetic information. Recent research results show that mt-DNA is closely related to the occurrence and metastasis of various malignant tumors, and can be used for early diagnosis and targeted therapy of cancer. Therefore, further research on the mechanism of mt-DNA in digestive system malignant tumors has important clinical significance for screening and identifying tumor molecular markers for anti-tumor drug targets, cancer diagnosis and prognosis analysis. This article reviews the research progress on the potential relationship, clinical application and therapeutic targets of mt-DNA and digestive system malignancies.
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The functional loss of the mismatch repair system is related to the occurrence of colorectal cancer. Some colorectal cancers have mismatch repair defects, however, the methylation of the MLH1 promoter cannot be detected, and germline mutations of the mismatch repair genes are not detected. Because this part of the group is very similar to Lynch syndrome, it is named Lynch-like syndrome. Lynch-like syndrome has certain genetic characteristics, but the pathogenesis has not been fully understood; and it cannot be simply classified as sporadic colorectal cancer or Lynch syndrome, and there is a lack of genetic knowledge and monitoring standards of these patients. This article introduces the progress of Lynch-like syndrome.
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With the development of biotechnology and medical technology, screening methods for colorectal cancer have been gradually improved, including invasive and non-invasive methods. Because of the high price of invasive tests and poor patient compliance, it is not yet possible to use them independently for the nationwide colorectal cancer screening. There is an urgent need for simpler, more economical, more specific and sensitive examinations as auxiliary means, so the non-invasive examination method has become a research hotspot in this field. The invasive examination is mainly endoscopy, while the non-invasive examination is mainly imaging examination and detection based on different sample sources. This article reviews the current status and research progress of colorectal cancer screening methods.
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As a member of the β-thymosin family, thymosin β 10 (Tβ10) is mainly involved in the isolation of intracellular actin. Studies have shown that the expression change of Tβ10 is closely correlated with breast cancer, esophageal cancer, liver cancer, cholangiocarcinoma, ovarian cancer and other malignant tumors. Tβ10 is expressed in different states according to the type of cancers, and the mechanism is unclear. The recent research of Tβ10 in chemotherapy and serum findings play a significant role in predicting the efficacy of chemotherapy in cancer patients.
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As a member of the β-thymosin family, thymosin β 10 (Tβ10) is mainly involved in the isolation of intracellular actin. Studies have shown that the expression change of Tβ10 is closely correlated with breast cancer, esophageal cancer, liver cancer, cholangiocarcinoma, ovarian cancer and other malignant tumors. Tβ10 is expressed in different states according to the type of cancers, and the mechanism is unclear. The recent research of Tβ10 in chemotherapy and serum findings play a significant role in predicting the efficacy of chemotherapy in cancer patients.
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Ring finger protein 43 (RNF43) gene is closely associated with the development of various types of human tumors.The mainly mechanisms of RNF43 gene are mutation and aberrant expression.Activated RNF43 protein participates in the proliferation, apoptosis, metastasis through some signal pathways and influences the tumorigenesis and development in colorectal cancer, hepatocellular carcinoma, which plays a role of oncogene.However, it is considered as a tumor suppressor gene in mucinous ovarian tumors and intraductal papillary mucinous neoplasms of the pancreas.
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Objective To precious localize DNase Ⅰ hypersensive sites exactly in the promoter region of CD133 of cell line SW480 by inverse-PCR.Methods The colonel cancer cell SW480 nuclei were suspended in digested buffer,treated with DNase Ⅰ at the concentration of 10 U/ml for 10 min.The inversePCR was performed as follows.DNA treated by DNase Ⅰ was purified,fragmented with restricted enzyme EcoRI and Xmal Ⅰ.Then the ends were blunted,ligated by T4 ligase.PCR was performed,and production was sequenced.The restricted enzymes cut sites were near DNase Ⅰ cleavage sites.Results 9 DNase Ⅰ cut sites were identified in CD133 promoter region.The DNaseI hypersensitive sites all distributed in a region -300 bp--700 bp up to transcription start site.Conclusion The DNase Ⅰ cleavage sites could identified preciously by application of inverse-PCR.These sites locate in a region of-300 bp--700 bp up to transcription start site.
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Objective To investigate the diagnosis and treatment of anorectal malignant melanoma,in order to regulate surgical methods and explore multi-modality treatment.Methods Clinical pathological features,diagnosis and treatment procedures of 38 patients with anorectal melanoma were reviewed,and their correlation with prognosis were analyzed.Results In 38 patients,10 of them were male and 28 were female,with the mean age of 58.7 years old (ranged 28-75 years old).28 patients underwent abdominoperineal resection,10 patients underwent wide local excision.The 1-,3-,and 5-year disease-free survival rates were 64.9 %,18.5 % and 5.7 %,respectively.The 1-,3-,and 5-year overall survival rates were 85.8 %,24.1% and 6.4 %,respectively.Tumor thickness (≥ 1.51 rm) and tumor diameter (≥3 cm) were associated with lymph metastases (x2 =13.093,4.449,P =0.011,0.020),tumor thickness was also associated with distant metastases (x2 =11.965,P =0.018).According to the Kaplan-Meier method,comprehensive treatment after surgery had significant effects on disease-free survival (x2 =7.441,P =0.006).Tumor thickness,lymph metastases,and clinical staging had significant effects on overall survival (x2 =16.741,16.474,16.775,P =0.002,0.000,0.000).Cox proportional hazards model indicated that comprehensive treatment after surgery was the independent prognostic risk factors of disease-free survival (95 % CI 1.420-17.621,P =0.012).Tumor thickness and lymph metastases were the independent prognostic risk factors of overall survival (95 % CI 0.250-0.949,1.033-2.573,P =0.035,0.036).Conclusion Early detection,reasonable surgical procedure,generalized systemic focus on immunotherapy treatment are the key to improve quality of life and prolong the survival time of anorectal malignant melanoma patients.
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Objective To investigate the clinical application of early postoperative enteral nutrition in patients undergoing colon cancer operation.Methods 90 patients suffering from colon cancer were randomly divided into the enteral nutrition group,indwelling stomach tube group and the control group.The control group was given conventional treatment and the indwelling gastric tube group was received postoperative intermittent clamping of stomach tube and enteral nutrition.Moreover,patients in the enteral nutrition group were pulled out the tube on the first postoperative day while giving enteral nutrition.All patients were observed for exhaust defecation time,length of hospital stay postoperative and nutrition indicators.Results Exhaust defecation time,length of hospital stay postoperative had significant difference among three groups.Indwelling stomach tube group set minimum length of stay and first passage of flatus and defecation in the three groups [the enteral nutrition group:(50.07±11.59) h,(76.75±27.37) h,(10.1 1±1.57) d,the control group:(62.03±12.31) h,(90.67±25.64) h,(11.80±1.83) d,indwelling stomach tube group:(43.53±11.94) h,(61.17± 22.67) h,(8.70±1.53) d (P < 0.05)].The levels of hemoglobin and plasma albumin one week after operation were statistically lower than pre-operation,while that the level of these nutrition indicators were higher in indwelling stomach tube group compare to control group (all P < 0.05).The same result was observed between enteral nutrition group and control group.Whereas,the change of nutrition indicators between the enteral nutrition group and the control group was not statistical significant (P > 0.05).Conclusion Indwelling stomach tube combined with enteral nutrition is a reasonable choice for patients after colonic cancer surgery.
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10.3969/j.issn.1000-8179.2013.12.009
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Anorectal malignant melanoma is a rare disease with atypical clinical symptoms and has a high misdiagnosis rate.Combined with rectal touch,endoscopy,ultrasonic inspection,CT,MRI,PET-CT,electron microscopy and the result of immunohistochemistry could help improve the diagnosis rate.This tumor tends to relapse and metastasis with poor prognosis,and there is no effective treatment.We should be on the alert for it,and the main point is early discovery,correct diagnosis,multi-disciplinary comprehensive treatment,in order to improve the survival rate of patients.
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Objective To investigate the diagnosis,the treatment methods and the prognosis of rectal cancer patients after renal transplantation.Methods Four patients with rectal cancer were found in 1035 renal transplantation recipients.Three of four patients were treated with anterior resection (AR) or abdomenoperineal resection (APR) with total mesorectal excision (TME).The two patients accepted regular adjuvant chemotherapy for six months period after surgery,but one patient rejected to accept any chemotherapy after surgery.Otherwise,one patient was only treated with chemotherapy and best support therapy for diagnosed as rectal cancer with multiple liver metastases.Results Two patients were fine to be followed up,8 months and 21 months after rectal resection respectively.Two other patients eventually died of metastasized cancer 5 months and 31 months respectively after therapy had been initiated.Conclusion Transplantation patients should receive standard oncology treatment,including operation and adjuvant treatment,so long as their general condition and organ graft functions allow to do so,although a higher degree of morbidity might be encountered,and periodical colorectal screening should be performed before and after renal transplantation.
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A methodology for preparing and certifying the reference material of 3-amino-2-oxazolidinone(AOZ) in eel muscle lyophilisates was presented. Furazolidone was accessed to eel by dipping fish in pond with furazolidone solution at a dosage of ca 0.16 mg/L. With the metabolism of furazolidone in eel, the muscles contain a certain concentration of AOZ as furazolidone metabolite was obtained. Lyophilization of the muscles was performed in one batch and 400 bags of samples were obtained by the procedure of homogenation, cryodesiccation and irradiation. The homogeneity and stability of the sample was examined. The value of the chemical constituent of the sample was certified through the collaborative analysis program participated by 11 laboratories using isotope dilution liquid chromatography-tandem mass spectrometry, and the uncertainty assessment was performed. The reference materials have been approved as certified reference materials by AQSIQ, China (State General Administration of the People′s Republic of China for Quality Supervision and Inspection and Quarantine) in 2009 after one year of trial period. The serial numbers is GBW(E)100180.
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Objective To investigate the safety and clinical outcome of laparoscopic resection of rectal cancer. Methods The clinical data of 347 patients with rectal cancer who were admitted to the Shanxi Tumor Hospital from May 2004 to July 2008 were prospectively analyzed. Of all the patients, 343 met the inclusion criteria,and they were randomly allocated to laparoscope group (n = 169) and open group (n= 174). The diameter of the tumors, number of lymph node dissected, length of rectum resected, morbidity, the mean operation time, number of patients receiving blood transfusion, time to out-of-bed activity, first flatus, bowel movement and liquid diet were observed. All data were analyzed using the t test and chi-square test. The survival rate was calculated using the Kaplan-Meier method. Results The diameter of the tumors, number of lymph node dissected, length of rectum resected and number of patients receiving blood transfusion in the laparoscope group were (4.3 ± 1.3 ) cm, 7 ± 5,(19.1±2.2)cm and 4, and they were (4.2±1.3)cm, 7 ±5, (19.0±2.3)cm and 8 in the open group,respectively, with no significant difference between the two groups ( t = 0. 629, - 0. 726, 0. 562, x2 = 1. 264,P >0.05). The mean operation time in the laparoscope group was 19 minutes longer than that in the open group (t = 7. 904, P < 0.05 ). The time to out-of-bed activity, first flatus, bowel movement and liquid diet in the laparoscope group were 0.6, 0.3, 0.3 and 0.6 days earlier than those in open group( t = - 6. 392, - 3.581, - 3. 802,- 3. 493, P < 0.05 ). There were no significant differences in postoperative infection, anastomotic leakage, intestinal obstruction and deep vein thrombosis between the two groups ( x2 = 0. 236, 0. 354, 0. 000, 0. 000, P >0.05). A total of 167 patients in the laparoscope group and 172 patients in the open group had been followed upuntil 1 may, 2010. The 1-, 2-year survival rates were 94.0% and 82.6% in the laparoscope group and 95.3% and 91.2% in the open group. There was no significant difference in the 2-year survival between the two groups (x2 =0.541, P >0.05). The survival time of the patients in the laparoscope group and open group were 55.9 and 57.9 months, respectively. Conclusions Laparoscopic surgery is safe and feasible for patients with rectal cancer, with quick recovery after the operation.
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Objective To compare the efficacy and side effects between systemic chemotherapy and hepatic arterial infusion by combination of oxaliplatin and 5-fluorouracil (FOLFOX-6) with 5-fluorouracil in the patients who have developed hepatic metastasis after colorectal cancer operation. The factors that would affect the prognosis without operational treatment were also analyzed. Methods 46patients who had signed the informed consents were allocated into two groups: the group with general chemotherapy (Trial Group includes 26 cases) and the one with hepatic arterial infusion chemotherapy (Control Group includes 20 cases). The total effective rate, the prognosis, the cytoxicitic side effects,quality of life, the total survival rate and the responses were the main parameters determined. Kaplan-Meier was used to analyze Mono-factor to the prognostic responses and the Cox mode was used to analyze poly-factor to the prognostic responses. Results The overall survival rate was significantly higher by using systemic treatment versus HAI(median, 15. 0 v 11.2 months;P<0.05). The difference in overall responsive rate (CR+PR) between the two groups was statistically significant (50% v 10%;P=0. 011). No significant difference was found in PS scale during the treatment. (P=0. 126). Except for myelosuppression and abdominal pain, no significant difference was found in the other side effects. Univariate analysis revealed that the invasive lesions to serosa, the distribution of liver metastases, the size and number of liver metastases, primary carcinoma involving lymph nodes and the treatment were correlated with prognoses. Cox regression analysis showed that the larger diameter of liver metastases, the number of liver lesions, primary carcinomas involved in serosal layer and the treatment modules were independent prognostic factors. Conclusions The oxaliplatin-based FOLFOX-6 chemotherapy regiment has a better responsive rate and survival rate than the traditional infusion with 5-fluorouracil to the main hepatic artery for interventional therapy. The diameter of the hepatic metastasis larger than 5em, multiple hepatic metastasis and the primary lesions penetrating serosal layer suggest the poor prognosis. The oxaliplatin-based systematic chemotherapy has a better prognosis. Therefore,it is worth carrying on further study on modification of traditional hepatic arterial infusion and on evaluation of therapy by combination of the hepatic arterial infusion with the systematic chemotherapy.
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Objective To compare Th1/Th2 drift situation in patients with lymphoma with that in patients with solid tumors, and establish the effective immune function detectable criterion of lymphoma in biological treatment process. Methods The whole blood samples of 10 patients with lymphoma, 202 patients with solid tumors including 36 patients with upper digestive tract cancer, 64 colorectal cancer, 43 lung cancer and 20 the other malignancies, and 30 healthy persons as controls were collected. Stimulation agent was used to stimulate the cells in order to increase cell factor expression and fluorescent labeled specific anti-cytokine monoclonal antibody was used to bind with specific antigen. The expression of specific cytokines was detected by flow cytometry. Results Positive percentages of IFN- γ and IL-4 and ratio of IFN- γ /IL-4 in CD+4 T cells of human peripheral blood had statistically differences between in patients with lymphoma and controls (P < 0.05). The ratio of Thl/Th2 (CD+4 intracellular cytokine INF-α/IL-4) in patients with lymphoma was lower than that in patients with upper digestive tract cancers (esophagus and stomach cancers) (P = 0.023), however, had no statistical differences with that in patients with other solid tumors (colorectal, lung, kidney, breast and other tumors), but had a downward trend. Conclusion Immune functions in patients with lymphoma are lower than those in patients with solid tumors and immune treatment is a necessary to adjuvant chemotherapy. The ratio of Th1/Th2 (INF- α/IL-4) is expected to become effective detection criterion.