Role of p53 in Anticancer Drug Treatment- and Radiation-Induced Injury in Normal Small Intestine 免费阅读 下载全文 <正>In the human gastrointestinal tract,the functional mucosa of the small intestine has the highest capacity for absorption of nutrients and rapid proliferation rates,making it vulnerable to chemoradiotherapy.Recent understanding of the protective role of p53- mediated cell cycle arrest in the small intestinal mucosa has led researchers to explore new avenues to mitigate mucosal injury during cancer treatment.A traditional p53 inhibitor and two other molecules that exhibit strong protective effects on normal small intestinal epithelium during anticancer drug treatment and radiation therapy are introduced in this work.The objective of this review was to update current knowledge regarding potential mechanisms and targets that inhibit the side effects induced by chemoradiotherapy.
Photodynamic Therapy for Gynecological Diseases and Breast Cancer 免费阅读 下载全文 <正>Photodynamic therapy(PDT) is a minimally invasive and promising new method in cancer treatment.Cytotoxic reactive oxygen species(ROS) are generated by the tissue-localized non-toxic sensitizer upon illumination and in the presence of oxygen.Thus, selective destruction of a targeted tumor may be achieved.Compared with traditional cancer treatment,PDI has advantages including higher selectivity and lower rate of toxicity.The high degree of selectivity of the proposed method was applied to cancer diagnosis using fluorescence.This article reviews previous studies done on PDT treatment and photodetection of cervical intraepithelial neoplasia,vulvar intraepithelial neoplasia,ovarian and breast cancer,and PDT application in treating non-cancer lesions.The article also highlights the clinical responses to PDT,and discusses the possibility of enhancing treatment efficacy by combination with immunotherapy and targeted therapy.
Molecular Mechanisms Contributing to Resistance to Tyrosine Kinase-Targeted Therapy for Non-Small Cell Lung Cancer 免费阅读 下载全文 <正>One of the most important pathways in non-small cell lung cancer(NSCLC) is the epidermal growth factor receptor(EGFR) pathway. This pathway affects several crucial processes in tumor development and progression,including tumor cell proliferation,apoptosis regulation,angiogenesis,and metastatic invasion.Targeting EGFR is currently being intensely explored.We are witnessing the development of a number of potential molecular-inhibiting treatments for application in clinical oncology.In the last decade,the tyrosine kinase(TK) domain of the EGFR was identified in NSCLC patients,and it has responded very well with a dramatic clinical improvement to TK inhibitors such are gefitinib and erlotinib.Unfortunately,there were primary and/or secondary resistance to these treatments,as shown by clinical trials.Subsequent molecular biology studies provided some explanations for the drug resistance phenomenon.The molecular mechanisms of resistance need to be clarified.An in-depth understanding of these targeted-therapy resistance may help us explore new strategies for overcoming or reversing the resistance to these inhibitors for the future of NSCLC treatment.
Male Breast Cancer： lO-Year Experience at Mansoura University Hospital in Egypt 免费阅读 下载全文
The Effect of the Surgical Margins on the Outcome of Patients with Head and Neck Squamous Cell Carcinoma： Single Institution Experience 免费阅读 下载全文 <正>Objective To assess the impact of close or positive surgical margins on the outcome,and to determine whether margin status influence the recurrence rate and the overall survival for patients with head and neck cancers. Methods Records from 1996 to 2001 of 413 patients with primary head and neck squamous cell carcinoma(SCC) treated with surgery as the first line treatment were analysed.Of these patients,82 were eligible for the study.Patients were followed up for 5 years. Results Patients with margins between 5-10 mm had 50%recurrence rate(RR),those with surgical margins between 1-5 mm had RR of 59%and those with positive surgical margins had RR of 90%(P=0.004).The 5-year survival rates were 54%,39%and 10%,respectively(P=0.002). Conclusions Unsatisfactory surgical margin is an independent risk factor for recurrence free survival as well as overall survival regardless of the other tumor and patient characteristics.
TET2 Expression in Bone Marrow Mononuclear Cells of Patients with Myelodysplastic Syndromes and Its Clinical Significances 免费阅读 下载全文 <正>Objective To investigate the expression of TET2 mRNA and protein in the bone marrow mononuclear cells(BMMNC) of patients with myelodysplastic syndrome(MDS) and its clinical significance. Methods The expression of TET2 mRNA and protein in bone marrow mononuclear cells(BMMNC) of 32 patients with MDS and 20 healthy donors was examined by qPCR and Western blot. Results The expression of TET2 mRNA in BMMNC was down-regulated in MDS patients compared with the donor group [(0.41±0.28)%vs.(1.07±0.56)%](P<0.001).Compared with lower expression group(TET2<0.4)[(6.53±6.17)%],patients with higher expression of TET2(≥0.4) presented significantly lower proportion of bone marrow blasts[(1.21±1.56)%](P<0.05).The expression of TET2 mRNA in BMMNC of MDS patients was inversely correlated with malignant clone burden(r=-0.398,P<0.05) and IPSS(r=-0.412, P<0.05).The expression of TET2 protein was down-regulated in MDS patients compared with that in the donor group. Conclusions The mRNA and protein expression of TET2 in BMMNC of MDS patients is decreased,which might be useful as an important parameter for the evaluation of MDS clone burden.
Initial Progression-Free Survival after Non-First Line TKIs Therapy Potentially Guides Immediate Treatment after Its Failure in Advanced Non-Small Cell Lung Cancer 免费阅读 下载全文 <正>Objective The standard therapy after failure of the initial non-first line epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) treatment in advanced non-small cell lung cancer(NSCLC) has not yet been established.The aim of the current study was to identify whether the 2 TKI treatment or chemotherapy(paclitaxel-containing or non-paclitaxel regimen) is the appropriate treatment for patients with NSCLC based on the efficacy of the initial TKIs. Methods Seventy-two advanced NSCLC patients who had accepted 2 TKIs or chemotherapy immediately after failure of the initial TKIs in non-first line setting from May 1,2004 to January 31,2010 at the Sun Yat-sen University Cancer Center were enrolled.The primary endpoint[2 progression-free survival(PFS)]and the second endpoint[overall survival(OS)]were compared among the 2 TKI and chemotherapy groups as well as their subgroups. Results(1) Twenty-one patients were treated with 2 TKIs,and 51 patients were administered chemotherapy after failure of the initial non-first line TKI treatment.There was nonsignificant difference in the responses(P=0.900)[2 PFS(P=0.833) and OS(P=0.369)] between the 2 TKI and chemotherapy groups.(2) In the 2 TKI group,9 patients exhibited PFS>7 months.The initial TKI treatment group exhibited a longer 2 PFS than the other 12 patients with an initial PFS<7 months(7 months vs.2 months,P=0.019).However, these groups had nonsignificantly different OS(P=0.369).(3) In the chemotherapy group,patients with PFS<5 months exhibited longer 2 PFS than those with PFS > 5 months in the initial TKI treatment(3 months vs.2 months,P=0.039).(4) In the chemotherapy group, patients treated with paclitaxel-containing regimen showed longer 2 PFS than those treated with non-paclitaxel regimen(5 months vs.2.3 months,P=0.043). Conclusions Patients with PFS>7 months or <5 months under the initial TKI treatment potentially benefit from the 2 TKI treatment or chemotherapy immediately after failure of the non-fir...Microsurgery Resection of Intrinsic Insular Tumors via Transsylvian Surgical Approach in 12 Cases 免费阅读 下载全文 <正>Objective To investigate the clinical characteristics,operative methods,and diffusion tensor imaging(DTI) in the resection of intrinsic insular gliomas via transsylvian approach. Methods From June 2008 to June 2010,12 patients with intrinsic insular gliomas were treated via transsylvian microsurgical approach,with preoperative magnetic resonance imaging diffusion tensor imaging(MR DTI) evaluation.The data of these patients were retrospectively analyzed. Results All patients had astrocytoma,including 8 patients of Grades I to II,2 patients of Grades III to IV,and 2 patients of mixed glial tumors.The insular rumors were completely removed in 9 patients,whereas they were only partially removed from 3 patients. No death was related to the operations.Two patients had transient aphasia,2 experienced worsened hemiplegia on opposite sides of their bodies,and 2 had mild hemiplegia and language function disturbance. Conclusions Most of the insular gliomas are of low grade.By evaluating the damage of the corticospinal tract through DTI and using ultrasonography to locate the tumors during operation,microsurgery treatment removes the lesions as much as possible, protects the surrounding areas,reduces the mobility rate,and improves the postoperative quality of life.
Expression of Bmi-1, P16, and CD44v6 in Uterine Cervical Carcinoma and Its Clinical Significance 免费阅读 下载全文 <正>Objective Bmi-1,a putative proto-oncogene,is a core member of the polycomb gene family,which is expressed in many human tumors.The pl6 protein negatively regulated cell proliferation,whereas CD44v6 is associated with proliferation as an important protein.Additionally,CD44v6 is an important nuclear antigen closely correlated to tumor metastasis.The present study aims to investigate the expression and significance of Bmi-1,pl6,and CD44v6 in uterine cervical carcinoma(UCC). Methods A total of 62 UCC,30 cervical neoplasic,and 20 normal cervical mucosal tissues were used in the current study.The expression of Bmi-1,pl6,and CD44v6 in these tissues was determined using immunohistochemical assay.The relationships among the expression of these indices,the clinicopathologic features of UCC,and the survival rate of UCC patients were also discussed.The correlation between Bmi-1 protein expression and pl6 or CD44v6 protein in UCC was analyzed. Results The expression of Bmi-1,p16,and CD44v6 was significantly high in cervical carcinoma compared with that in the cervical neoplasia and normal colorectal mucosa(P<0.05).The over-expression of Bmi-1 protein in UCC was apparently related to the distant metastasis(P<0.01) and the tumor,nodes and metastasis-classification,i.e.the TNM staging,World Health Organization(P<0.05). Nevertheless,the positive expression of pl6 protein in UCC was not significantly associated with the clinicopathologic features (P>0.05).The Kaplan-Meier survival analysis showed that the over-expression of Bmi-1 significantly decreased the survival rate of UCC patients(P<0.05).A strong correlation indicated that there was statistical significance between the expression of Bmi-1 and CD44V6 proteins in UCC(r=0.419,P<0.001). Conclusions The over-expression of Bmi-1 and CD44v6 protein closely correlate to the tumorigenesis,metastasis,and prognosis of UCC.Bmi-1 and CD44v6 may be used to predict the prognosis of cervical carcinoma.Bmi-1 may indirectly regulate the e...Defining a Subgroup Treatable for Laparoscopic Surgery in Poorly Differentiated Early Gastric Cancer： the Role of Lymph Node Metastasis 免费阅读 下载全文 <正>Objective The present study aims to identify the clinicopathologic factors predictive of lymph node metastasis(LNM) in poorly differentiated early gastric cancer(EGC) and to expand the possibility of using laparoscopic surgery for the treatment of poorly differentiated EGC. Methods Data from 70 cases of poorly differentiated EGC treated with surgery were collected.The association between clinicopathologic factors and the presence of LNM was retrospectively analyzed by univariate and multivariate logistic regression analyses. Results Univariate analysis showed that tumor size,depth of invasion,and lymphatic vessel involvement(LVI) were the significant and independent risk factors for LNM(all P<0.05).The LNM rates were 6.9%,45.5%,and 60.0%,respectively.There was no LNM in 25 patients without the above three risk factors. Conclusions Laparoscopic surgery is a sufficient treatment for intramucosal poorly differentiated EGC if the tumor is less than or equal to 2.0 cm in size and when LVI is absent upon postoperative histological examination.
Serological Diagnosis of Liver Metastasis in Patients with Breast Cancer 免费阅读 下载全文 <正>Objective To diagnose and explore the serological diagnostic factors for liver metastasis in patients with breast cancer before symptoms occur. Methods A total of 430 female in-patients with breast cancer of stages 0 to IIIC who came to Tianjin Medical University Cancer Institute and Hospital from January 2003 to January 2004 were studied and followed up until May 2011.Serum levels of biochemical markers for tumor and liver were measured at the time of diagnosis. Results Liver metastasis was more likely to occur in patients with stage III cancer or c-erbB-2-positive expression.Alanine aminotransferase,aspartate aminotransferase,γ-glutamyltransferase(GGT),alkaline phosphatase,lactate dehydrogenase(LDH),and carbohydrate antigen 153(CA153) levels were significantly higher in patients with liver metastasis than those without liver metastasis. Diagnostic indices of LDH,GGT,and CA153 were 174 U/L,32 U/L,and 26.48μg/L,respectively.The areas under the curves of LDH, GGT,and CEA were 0.795,0.784,and 0.661,respectively,and sensitivities of parallel tests for LDH and CA153 and for GGT and CA153 were 88.6%and 85.7%,respectively.The specificity of serial tests for both pairs of enzymes was 97.7%. Conclusions The sensitivity and specificity of combined tumor and biochemical markers could be used as indicators during screening for breast-liver metastasis.
Meta-Analysis of the Association between Mir-196a-2 Polymorphism and Cancer Susceptibility 免费阅读 下载全文 <正>Objective MicroRNA plays a vital role in gene expression,and microRNA dysregulation is involved in carcinogenesis.The miR- 196a-2 polymorphism rsll614913 is reportedly associated with cancer susceptibility.This meta-analysis was performed to assess the overall association of miR-196a-2 with cancer risk. Methods A total of 27 independent case-control studies involving 10,435 cases and 12,075 controls were analyzed for the rsll614913 polymorphism. Results A significant association was found between rsll614913 polymorphism and cancer risk in four genetic models(CT vs.TT, OR=1.15,95%CI=1.05-1.27;CC vs.TT,OR=1.23,95%CI=1.08-1.39;Dominant model,OR=1.17,95%CI=1.06-1.30;Additive model, OR=1.08,95%CI=1.01-1.14).In the subgroup analysis of different tumor types,the C allele was associated with increased risk of lung, breast,and colorectal cancer,but not with liver,gastric,or esophageal cancer.In the subgroup analysis by ethnicity,a significantly increased risk of cancer was found among Asians in all genetic models,but no associations were found in the Caucasian subgroup. Conclusions The meta-analysis demonstrated that the miR-196a-2 polymorphism is associated with cancer susceptibility,especially lung cancer,colorectal cancer,and breast cancer among Asian populations.
PRAME Gene Expression in Acute Leukemia and Its Clinical Significance 免费阅读 下载全文 <正>Objective To investigate the expression of the preferentially expressed antigen of melanoma（PRAME） gene in acute leukemia and its clinical significance. Methods The level of expressed PRAME mRNA in bone marrow mononuclear cells from 34 patients with acute leukemia（AL） and in 12 bone marrow samples from healthy volunteers was measured via RT-PCR.Correlation analyses between PRAME gene expression and the clinical characteristics（gender,age,white blood count,immunophenotype of leukemia,percentage of blast cells, and karyotype） of the patients were performed. Results The PRAME gene was expressed in 38.2%of all 34 patients,in 40.7%of the patients with acute myelogenous leukemia （AML,n=27）,and in 28.6%of the patients with acute lymphoblastic leukemia（ALL,n=7）,but was not expressed in the healthy volunteers.The difference in the expression levels between AML and ALL patients was statistically significant.The rate of gene expression was 80%in M3,33.3%in M2,and 28.6%in Ms.Gene expression was also found to be correlated with CD15 and CD33 expression and abnormal karyotype,but not with age,gender,white blood count or percentage of blast cells. Conclusions The PRAME gene is highly expressed in acute leukemia and could be a useful marker to monitor minimal residual disease.This gene is also a candidate target for the immunotherapy of acute leukemia.
F1000 Spotlight 免费阅读 下载全文
Instructions for Authors 免费阅读 下载全文