Progress on Targeted Therapy of Radioiodine-refractory Differentiated Thyroid Cancer / 肿瘤防治研究

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.

Clinicopathological characteristics and risk factors of female breast hyperplasia in different age groups / 中华普通外科杂志

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.

Clinicopathological characteristics of gastric cancer with enteroblastic differentiation / 中国肿瘤临床

Objective: To investigate the clinicopathological features and molecular phenotypes of gastric cancer with enteroblastic dif-ferentiation (GCED). Methods: A retrospective analysis of 337 patients with gastric adenocarcinoma diagnosed by the pathology de-partment of the First Affiliated Hospital of Zhejiang University in March 2013-2017 was conducted. Of them, 8 patients were diag-nosed with gastric carcinoma with intestinal blastocyte differentiation. All the patients were elderly, including 6 men and 2 women. The onset age was 68-83 years (mean 76.6 years). Two cases had serum AFP≥200 μg/L before treatment. According to the histopatho-logical morphology, the immunophenotype was analyzed by immunohistochemistry, the SALL4 gene was detected using reverse tran-scription-polymerase chain reaction (RT-PCR), and the relevant literature was reviewed. Results: Microscopically, all cases had primi-tive enteroid structures, consisting of cubic or columnar cells with clear cytoplasm, and immunohistochemical staining showed positivi-ty for either AFP and GPC3 or SALL4. The expression of SALL4 mRNA was significantly increased by RT-PCR. Follow-up from 1 to 5 years showed that 5 patients had liver and other organ metastases, 2 patients died, and 1 patient survived without a tumor. Conclusions:GCED is a rare invasive gastric adenocarcinoma with a worse prognosis than that of normal intestinal adenocarcinoma. The treatment of general intestinal adenocarcinoma has little effect. There are some characteristic changes in histology. It would be helpful for diag-nosis and differential diagnosis if clinicians are familiar with the tumor spectrum and genetic characteristics. Target therapy for an origi-nal marker, such as SALL4, has a bright future.

Transition analysis in the clinicopathology and prognosis of 2 682 papillary thyroid carcinoma cases over a 15-year period / 中华普通外科杂志

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.

BRAFV600E mutation and NIS expression in papillary thyroid carcinomas / 中华普通外科杂志

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

Expression of Rap1GAP and its methylation status in papillary thyroid carcinoma / 中华内分泌代谢杂志

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.

Mechanisms of RON-mediated epithelial-mesenchymal transition in MDCK cells through the MAPK pathway

The epithelial-mesenchymal transition (EMT) is involved in neoplastic metastasis, and the RON protein may be involved. In the present study, we determined the role and the mechanisms of action of RON in EMT in Madin-Darby canine kidney (MDCK) cells by Western blot and cell migration analysis. Activation of RON by macrophage stimulating protein (MSP) results in cell migration and initiates changes in the morphology of RON-cDNA-transfected MDCK cells. The absence of E-cadherin, the presence of vimentin and an increase in Snail were observed in RE7 cells, which were derived from MDCK cells transfected with wt-RON, compared with MDCK cells. Stimulation of RE7 cells with MSP resulted in increased migration (about 69 percent of the wounded areas were covered) as well as increased activation of extracellular signal-regulated kinase 1/2 (Erk1/2) and glycogen synthase kinase-3β (GSK-3β; the percent of the activation ratio was 143.6/599.8 percent and 512.4 percent, respectively), which could be inhibited with an individual chemical inhibitor PD98059 (50 μM) specific to MAPK/ERK kinase (the percent inhibition was 98.9 and 81.2 percent, respectively). Thus, the results indicated that RON protein could mediate EMT in MDCK cells via the Erk1/2 pathway. Furthermore, GSK-3β regulates the function of Snail in controlling EMT by this pathway.

Clinical analysis of 26 patients with thyroid Hiirthle cell tumor / 中华内分泌代谢杂志

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).

Thyroid microcarcimoma / 中华普通外科杂志

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.

Stable expression of antisense hTR inhibits in vitro pancreatic cancer cell growth / 中华医学杂志(英文版)

<p><b>OBJECTIVE</b>To clarify growth inhibition in pancreatic cancer cells by interference with the hTR component of the telomerase reverse transcriptase enzymatic complex.</p><p><b>METHODS</b>A 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.</p><p><b>RESULTS</b>Significant 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.</p><p><b>CONCLUSIONS</b>These 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.</p>

Space occupying lesion of the spleen / 中国普通外科杂志

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.

Construction of Wild-type p53 Gene Recombinant Expression Vector and Its Antitumorigenic Effects on Human Colon Adenocarcinoma Cells / 中国肿瘤生物治疗杂志

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.