p53 gene is a 16-20 kb of cellular DNA located on the short arm of human chromosome 17 at position 17pl3.1. This gene encodes a 393-amino acid nuclear phosphoprotein which involves in the regulation of cell proliferation. Loss of normal p53 function is associated with the cell transformation in vitro and the development of neoplasms in vivo. More than one-half of human malignancies were shown to contain an altered p53 gene. Most p53 gene alterations are the missense mutations, giving rise to an altered protein. The inactivation of wild-type p53 is currently regarded as an important genetic pathway for haman carcinogenesis generated by endogenous factors and exogenous carcinogens, as well as several tumor viruses. To gain more insight into the functional role of wild-type p53 in human colo-rectal carcinoma, a 2. 1 kilobase human wild-type p53 cDNA with 5' and 3' untranslated sequences was cloned into the BamHI site of pREP9 (episomal mammalian expression vector) in sense orientation. We performed experiments to transfer wild-type p53 into human colon adenocarcinoma cell line (SW1116) harboring mutant p53 genes with electroporation method. We assessed G4I8-resistant clonal growth, cell growth properties and cell cycle pattern by flow cytometry. The results demonstrated that human wild type p53 gene can suppress the phenotype of SW1116 cell line. So gene therapy based on restoration of the defective or mutant p53 function plays an important role in colo-rectal cancer treatment.

Unilateral thyroidectomy (lobeetomy) plus (or) isthmectomy were performed surgically and all patients recovered satisfactorily. No recurrence was found after a mean of 37 months follow-up(9 months-6 years).

Objective To investigate BRAFV600E mutation and sodium iodide symporter (NIS) expression and its clinical significance in papillary thyroid carcinomas (PTC).Methods BRAFV600E mutation was evaluated by direct sequencing and BRAFV600E mutation was determined in 40 cases of PTC.NIS expression was examined by means of immunohistochemistry.The relationship between BRAFV600E mutation and the clinicopathologic features of PTC was analyzed.The relationship between NIS expression and BRAFV600E mutation in PTC was analyzed.Results Positive BRAFV600E mutation was determined in 23 of 40 cases of PTC (57.5％),whereas positive NIS expression was showed in 7 of 40 cases (12.5％).BRAFV600E mutation was associated with extrathyroid invasion and a high risk of disease recurrence in PTC (P ＜ 0.05).Positive NIS expression was found in only one of 23 cases of PTC with BRAFV600E mutation,and positive NIS expression was associated with a statistically significant lower BRAFV600E mutation in PTC (P =0.011).Conclusions BRAFV600E mutation might be associated with higher aggressiveness,higher disease recurrence and a poorer prognosis.Lower NIS expression may be responsible for poor 131I uptake in

The expression of Rap1 GAP protein was detected in 69 cases of papillary thyroid carcinoma and adjacent normal thyroid tissues with immunohistochemistry method.Methylation of Rapl GAP gene was analyzed by methylation-specific-PCR (MSP) in these tissues.The immunohistochemistry results indicated that the Rap1GAP protein was down-regulated in tumor tissues of 54 ( 78％ ) cases compared with normal thyroid tissues.Statistical analysis demonstrated that the decreased level of Rap1 GAP protein expression was significantly correlated with the tumor stage T according to American Joint Committee on Cancer ( AJCC,P =0.043 ).The MSP results demonstrated that 46 cases of Rap1GAP gene methylation were detected in 54 cases with down-regulated expression of Rap1GAP (66.7％),but only 1 case of methylation was found in 15 cases without obvious change of Rap1GAP expression (6.67％),showing significant difference ( P＜0.01 ).There was no methylation in normal thyroid tissues.These results suggest that raised methylation of promoter region may contribute to the low expression of Rap1GAP protein in papillary thyroid carcinoma.

Objective To summarize the experience in diagnosis and management for the space occupying lesion of spleen. Method The clinical data of 29 cases treated by surgery were retrospectively analyzed. Results There were 15 patients with benign masses including 7 hamartomas, 5 hemangiomas, 1 pseudocyst, 2 tuberculoses of the spleen, and 14 with malignant tumors including 9 lymphomas, 3 angiosarcomas, 2 metastatic tumors in the spleen. Splenectomy was performed in all patients. All patients with benign masses survived except 2 patients lost follow up and 1 coexisting with hepataocellular carcinoma died half a year after the operation. Twelve of 14 patients with malignant tumor were followed up.Of them, 5 patients survived more than 5 years and 2 were alive 1 and 3 years after the operation respectively; 5 patients died 6 months to 4 years after the operation. Conclusions Ultrasonography and CT or MRI are the main means of diagnosis for the space occupying lesion of spleen.It is difficalt to make diagnosis of the splenic tuberculosis before operation.Splenectomy is a primary procedure of surgery.

OBJECTIVETo clarify growth inhibition in pancreatic cancer cells by interference with the hTR component of the telomerase reverse transcriptase enzymatic complex.

METHODSA 593 bp full length hTR cDNA was subcloned into a mammalian expression vector pcDNA3.1(-) in the antisense orientation to construct an antisense hTR expression plasmid. These were introduced into panc1 cells, a human pancreatic carcinoma cell line, by lipofectin and G418-resistant stable transformants were expanded. Resulting stable clones were screened for the presence of the hTR insert by PCR with T7 and BGH reverse primers located on the flanks of the multiclonal site of the pcDNA3.1 vector. Cell growth rate, hTR expression, telomerase activity and anchorage-independent growth properties were analyzed.

RESULTSSignificant downregulation of endogenous hTR was evident in the antisense-hTR transformed cells and telomerase activity was markedly decreased compared to control cells in standard TRAP assays. Furthermore, cell proliferation and the anchorage-independent growth ability in antisense-hTR expressing cells were significantly decreased compared with control parental cells. However, no crisis or senescence phenomena were observed.

CONCLUSIONSThese data indicate that hTR may be a critical component of human telomerase activity and suggest that downregulation of the RNA component of human telomerase is a possible target for anticancer strategies.

DNA-Binding Proteins ; Humans ; Pancreatic Neoplasms ; pathology ; therapy ; RNA, Antisense ; therapeutic use ; Reverse Transcriptase Polymerase Chain Reaction ; Telomerase ; antagonists & inhibitors ; genetics ; Tumor Cells, Cultured

Objective To investigate the clinicopathologic features and treatment of thyroid microcarcinoma (TMC). Methods From January 1997 to December 2006,311 patients who underwent surgery and defined as TMC(tumor size≤1 cm)were enrolled. Results TMC was identified incidentally by frozen pathologic examination on thyroidectomy specimens in tentative benign goiters in 181 patients; another 130 patients with clinically detectable primary tumors or suspected nodal metastases were grouped to as clinically overt TMC. The clinically overt TMC had a higher incidence of bilateral multifocal tumors (18.5%vs.9.4%,P=0.03),and cervical lymph node metastases(27.7%vs.10.5%,P=0.000)than that in clinically occult TMC group. Conclusion TMC may vary considerably in clinical and biologic behaviors between these two subtypes: clinically overt and occult. Lobectomy for single lesion, total or near total thyroidectomy for multifocal with central compartment nodal dissection should be performed, lateral nodal dissection was not carried out unless US or physical examination detected nodal metastases. Lobetomy, subtotal or more limited thyroidectomy for occult TMC, diagnosed incidentally following thyroid surgery for initially tentative benign thyroid disease, could all be treatment of choice depending on the preference of surgeons.

Targeted therapy has brought revolutionary breakthroughs for radioiodine-refractory differentiated thyroid cancer. New targeted drugs have prolonged the survival of patients with advanced differentiated thyroid cancer. Multiple tyrosine kinase inhibitors, represented by sorafenib and lenvatinib, have remarkably improved the progression-free survival of patients. Novel tyrosine kinase inhibitors targeting BRAF and RET mutation have also achieved remarkable curative effects, greatly enriching the treatment methods for thyroid cancer. This article reviews the latest research progress on targeted therapy in radioiodine-refractory differentiated thyroid cancer.

Objective To evaluate the change of clinicopathological features and prognosis of papillary thyroid cancer over a 15-year period.Methods The clinicopathological features and outcomes of papillary thyroid cancer patients were analyzed in three groups according to the time of diagnosis:group Ⅰ (1997-2001),group Ⅱ (2002-2006),and group Ⅲ (2007-2011).Results As time advanced,the average age of papillary thyroid cancer patients increased,tumor stage,like size,extrathyroid invasion and lymph node metastasis decreased dramatically (P ＜ 0.01).The percentage of multifocality and bilaterality increased.The long-term follow up data (median follow up time was 6.6 years),indicated that the 15-year over all survival was 97.8％ and the 15-year disease-free survival was 90.2％.Tumor ≥3 cm,bilaterality,extrathyroid invasion,lymph node metastasis and AJCC stage were correlated with tumor recurrence.By multivariate COX-regression analysis only lymph node metastasis and bilaterality were independent risk factors.Conclusion The clinicopathological features of papillary thyroid cancer changed over 15 years,with the percentage of early-staged patients increased.Lymph node metastasis and bilaterality are two risk factors for tumor recurrence.

Objective To analyze clinicopathological characteristics and the potential risk-related factors of female breast hyperplasia in different age groups.Method From Jan 2015 to Dec 2016,patients diagnosed with breast hyperplasia in 12 hospitals were evaluated.All patients completed the self-designed questionnaires on women'health,including basic demographic information,clinic examination information,radiologic information and pathologic results.The patients were divided into a young group (＜ 45 years old) and an elderly group (from 45 to 75 years old).Results There were 3 684 cases of breast hyperplasia,including 2 291 cases in young group and 1 393 cases in elder group,respectively Clinically breast pain type were most commonly observed in both young and older groups (50.3％ vs.42.7％,P ＜ 0.001).While pathological research based on biopsy showed that breast adenopathy were the most common changes in both groups (67.9％ vs.61.7％,P ＜0.001).More breast cancer cases were identified in elder group than that in young group,especially in clinically lump type patients (9.4％ vs.4.2％,P ＜ 0.001).Compared with elder group,patients in young group have different distribution characteristics regarding to fertility factors,lifestyle factors and psychology scale including anxiety and depression.Conclusion Distributions of clinicopathological characteristics and risk factors of female breast hyperplasia differ across different age groups.