The epidermal growth factor receptor tyrosine kinase inhibitor(EGFR-TKI)is a kind of high-efficiency and low-toxicity tumor molecular targeted drugs.It becomes a research hotspot in non-small cell lung cancer (NSCLC)treatment because of its unique curative effect and well tolerance.EGFR-TKI is mainly applied to the second and third line treatment of patients with advanced NSCLC or first line treatment of EGFR mutation patients.With the development of research,the indications of EGFR-TKI expand unceasingly.The preoperative neoadjuvant therapy is likely to become a new kind of treatment mode.

ObjectiveTo investigate the expression of psoriasin in actinic keratosis(AK),Bowen's disease and squamous cell carcinoma(SCC) tissues.MethodsImmunohistochemistry was carried out to quantify the expression of psoriasin protein in tissue specimens from the lesions of 20 patients with AK,25 patients with Bowen' s disease,21 patients with well differentiated SCC,and16 patients with poorly differentiated SCC,as well as from the skin of 18 normal human controls.ResultsThe expression rate of psoriasin was 11.1％ in the control specimens,significantly different from that in the AK(95.0％),Bowen's disease (88.0％),well differentiated SCC (95.2％),and poorly differentiated SCC (92.3％) specimens (all P ＜0.01 ).Psoriasin was expressed in the cytoplasm of keratinocytes and dyskeratotic keratinocytes in stratum corneum and upper 1 to 3 layers of stratum spinosums in AK tissue,in the cytoplasm of keratinocytes as well as the membrane and cytoplasm of vacuolated cells in all layers of the epidermis in Bowen's disease tissue.In well differentiated SCC,cornified pearl and dyskeratotic keratinocytes located in the stratum comeum and all layers of the stratum spinosums stained positive for psoriasin,and in poorly differentiated SCC,psoriasin was distributed in the stratum corneum and upper 1 to 5 layers of the stratum spinosums,but absent in poorly differentiated squamous cells.The expression intensity of psoriasin in tissues sequentially increased from AK,Bowen's disease to well differentiated SCC.Though the expression intensity of psoriasin in poorly differentiated SCC decreased,but was still higher than that in normal skin tissue(P ＜ 0.05).ConclusionPsoriasin is abnormally expressed in skin disorders with dysdifferentiation of squamous cells.

Objective The survival and prognosis factors of thoracic esophageal squamous cell carcinoma patients after radical resection was investigated.Methods 1923 patients of thoracic esophageal squamous cell carcinoma after radical resection were included in our study from January 1th 2000 to January 1th 2010 in Zhejiang Cancer Hospital,1 670 male and 253 female.the age in the majority with 40 to 59 years old(1 076/1 923,56.0％).Eighteen prognosis factors were collected.A multivariate analysis of these selected variables was performed using Cox proportional model and prognosis index.We used life table for accumulated survival rate.Results The accumulated survival rate for all patients were 82％,48％ and 35％ in 1 year,3 years and 5 years,respectively.Median survival time was 35.42 months.The significant prognosis factors included body mass index,length of tumor,depth of invasion,differentiation degree,lymph node metastatic degree and region,complication of surgery.Conclusion The prognosis of thoracic esophageal squamous cell carcinoma was affected by multi-factors and prognosis index can predict survival condition.

Objective To study the effect of NS398, an inhibitor of cyclooxygenase 2 (COX2), on the growth and apoptosis of human squamous cell carcinoma cell line Tca8113. Methods Cultured Tca8113 cells were incubated with NS398 (0, 6.25, 12.5, 25, 50, 100 μmol/L) for 24, 48 and 72 hours, respectively. Thereafter, MTT method, flow cytometry and transmission electron microscopy were applied to detect the proliferation, cell cycle and apoptosis of Tca8113 cells, respectively. Results The proliferation of Tca8113 cells was inhibited by NS398 in a dose- and time-dependent manner (both P<0.05). FCM analysis showed the appearance of a typical hypodiploid apoptotic (Sub-G1) peak, an increase in the percentage of cells at G0/G1 phase and a decrease in that at S and G2/M phases in NS398 ( 100 μmol/L) -treated Tca8113 cells. Moreover, the cell proliferation index was significantly downregulated by NS398 of 100 μmol/L from 41.03 to 24.33 (P<0.05). Under an electron microscope, morphological changes characteristic of apoptosis were observed in NS398-treated Tca8113 cells. Conclusion NS398, an inhibitor of COX2, could effectively inhibit the growth of Tca8113 cells in vitro by induction of apoptosis.

Objective To investigate the effect of narrow-band UVB (NB-UVB ) on melanocytes proliferation,melanin production,tyrosinase activities and miRNA-2 5 expression so as to explore the relationship between NB-UVB and miRNA-25 and the possible mechanism of NB-UVB for treatment of vitiligo.Methods Melanocytes cultured in vitro were treated with 40 mJ/cm2 dose of NB-UVB for 72 h,the effects of NB-UVB on cell proliferation,tyrosinase activity and melanin content were investigated.After NB-UVB stimulation for 1 2 h,the effect of NB-UVB on miRNA-2 5 expression in melanocytes was detected. Melanocytes were transfected with miRNA-2 5 mimics,miRNA-2 5 inhibitor and miRNA-2 5 mutant,respectively,the changes of cell proliferation, tyrosinase activitiy and melanin content were observed.Cell viability was detected using MTT method.Tyrosinase activities were measured with levodopa as the substrate.NaOH assay was used for the detection of melanin content. Real-time quantitative polymerase chain reaction (qRT-PCR)was used to detect miRNA-25 expression.Results After NB-UVB of 40 mJ/cm2 dose was used for the cells cultured for 72 h,the viability of melanocytes,tyrosinase activities,and melanin content were significantly increased (P<0.05 ).After NB-UVB stimulation for 12 h, miRNA-2 5 expression was significantly lower than that in the control group (P<0 .0 5 ).After knockdown of miRNA-2 5 ,the cell proliferation of melanocytes,tyrosinase activities and melanin content were increased,whereas overexpression of miRNA-2 5 decreased the cell proliferation, tyrosinase activities and melanin production.Overexpression of miRNA-2 5 partially inhibited the effect of NB-UVB on the treatment of melanocytes. Conclusion NB-UVB may promote cell proliferation,increase tyrosinase activities and melanin formation through partially downregulating the expression of miRNA-2 5 in melanocytes.

Thyroid cancer is one of the most common endocrine malignant tumors, and its molecular pathogenesis is also a process of multiple genes involved in many steps of carcinogenesis. With the development of molecular biology technology, a variety of related gene mutations and epigenetic phenomena have been found in thyroid cancer tissues. It is helpful to understand the latest progress in the research of the gene mutation and epigenetics of thyroid cancer for its early diagnosis, prevention and the development of targeted drugs.

OBJECTIVE To investigate the clinical significance of preoperative recurrent laryngeal nerve palsy (RLNP) for thyroid nodules with regard to the incidence of malignancy,recurrent laryngeal nerve involvement and histopathological character.METHODS Eighty patients with preoperative RLNP treated in Zhejiang Cancer Hospital between Jan 2007 to Dec 2014 were enrolled,their clinicopathological data were recorded and retrospectively analyzed.RESULTS Of 80 patients,16 patients had benign thyroid disease,while the other 64 had malignancies (80.0％).The preoperative RLNP incidence of benign and malignant lesions was 0.3％ and 0.9％ respectively.Poorly differentiated and anaplastic thyroid cancer had the higher incidence of preoperative RLNP comparing with other pathology types (25.93％,P＜0.05).The RLN did not preserved intraoperatively in 2 patients with benign lesions (2/16,12.5％) and in 42 patients with malignancy lesions (42/48,87.50％).All nerves were sacrificed in poorly differentiated and anaplastic thyroid cancer patients.The RLN could be isolated from 14 benign lesions and 6 malignancies,with or without adhesion,and the nerve function was recovered postoperatively.CONCLUSION The probability of preoperative RLNP is significantly higher in malignant lesions than benign lesions.Thyroid tumors with RLNP are strongly suggested of malignancy,with higher rate of intraoperative nerve sacrifice.The RLN should be preserved if it has not been invaded by the tumor,which offers a chance of functional recovery postoperatively.

Peripheral blood circulating tumor DNA(ctDNA) is a kind of DNA that is released into the blood circulation system after the tumor cell somatic cell DNA is exfoliated or when the cell apoptosis is released.ctDNA is a characteristic tumor biomarker, known as " liquid biopsy" . It can reflect the invasion and metastasis of the tumor, and can monitor the effect and prognosis of the tumor.The current research is mainly focused on relatively mature breast cancer, lung cancer and other diseases.In this study, the development of ctDNA inspection technology and its current research status at home and abroad are reviewed.

Objective: To explore the effects of miR-149-3p on the proliferation, apoptosis, invasion and migration of cervical cancer HeLa cells and the possible mechanisms. Methods: HeLa cells were randomly divided into five groups, including untransfected (HeLa) group, mimic-scramble group (the negative control of miR-149 mimic), miR-149 mimic group, FOXP3 over-expression (pc-FOXP3) group, and co-transfection (mimic+pc-FOXP3) group. The targeted relationship of miR-149-3p and FOXP3 was verified by luciferase assay. The expressions of miR-149-3p and FOXP3 mRNA were tested by quantitative real-time reverse transcription PCR (qRT-PCR). The protein levels of FOXP3 were measured by Western blotting. The proliferation was detected by CCK-8; the apoptosis was tested by flow cytometry, the cell invasion was measured by transwell invasion assay and cell migration was detected by scratch assay. Results: The luciferase assay showed that miR-149-3p could target combine with FOXP3. Compared with untransfected group, the expression of miR-149-3p was increased while mRNA level of FOXP3 was decreased in miR-149 mimic group (all P<0.01). Moreover, the protein level of FOXP3 in miR-149 mimic group was lower than that in untransfected group (P<0.01), while the protein level of FOXP3 in pcFOXP3 group was higher than that in untransfected group (P<0.01); Compared with pc-FOXP3 group, the protein levels of FOXP3 in mimic+pc-FOXP3 group were reduced (P<0.01). The proliferation in miR-149 mimic group was lower than that in untransfected group (P<0.01), while the proliferation in pc-FOXP3 was higher than that in untransfected group (P<0.01); compared with pc-FOXP3 group, the proliferation in mimic+pc-FOXP3 group was decreased (P<0.01). The apoptosis rate of HeLa cells in miR-149 mimic group was higher than that in untransfected group (P<0.01), while the apoptosis rate in pc-FOXP3 was lower than that in untransfected group (P< 0.01); compared with pc-FOXP3 group, the apoptosis in mimic+pc-FOXP3 group was elevated (P<0.01). The number of invasive cells per field and wound healing rate in miR-149 mimic group was lower than those in untransfeccted group (P<0.01) while the invasive cells and wound healing rate in pc-FOXP3 group was higher than those in untransfeceted group (P<0.01); compared with pc-FOXP3 group, the number of invasive cells per field and wound healing rate in mimic+pc-FOXP3 group was reduced (P<0.01). Conclusion: miR-149-3p inhibits proliferation, invasion and migration and promotes apoptosis of cervical cancer HeLa cells via targeting FOXP3.

Objective To investigate the predictive factors for central lymph node metastasis (CLNM) in papillary thyroid microcarcinoma(PTMC).Methods A retrospective study including 2511 cases of PTMC admitted from Jan.2013 to Jan.2016 were enrolled in our study.Chi-square test was used in univariate analysis.Logistic regression analysis was applied for multivariate analysis.The relation between age,sex,tumor size,multifocality,thyroidal extension,nodular goiter and central lymph node metastasis is analyzed.Results Univariate analysis showed that age,sex,tumor size,multifocality,thyroidal extension and nodular goiter had statistical significance.Age less than 45(P＜0.001,x2=17.442);Male gender(P＜0.001,x2=17.029);Tumor size less than 5 mm (P＜0.001,x2=70.164.);Extrathyroid extension factor (P＜0.001,x2=63.197);Nodular hyperplasia factor (P=0.017,x2=5.611).Multivariate analysis showed there was a significant relationship between multifocality and the central lymph node positivity.The odds ratio (OR) was 1.587 in patients with tumor foci ≥2(P＜0.001).While OR increased sharply near to 3 in patients withtumor foci ≥3(OR=2.730).Tumor size(OR=1.926);Extrathyroid extension(OR=1.606).Conclusions Multifocalty,tumor size and thyroidal extension are the main predicative factors for central lymph node metastasis in PTMC.Among them,tumor foci ≥ 3 is an important predictor.Besides the conventional factors such as tumor size,thyroidal extension etc,multifocalty should also be taken into consideration.