Objective To investigate the expression of Shh，Gli-1 in human breast cancer resistant cell line and discuss the relationship between Hedgehog signaling pathway and drug resistance of breast cancer. Methods Drug-resistant strains of human breast cancer MCF-7 was established by high concentration intermittent induction. Paclitaxel（PTX）to half maximal inhibitory concentration（IC50）on MCF-7 and MCF-7／PTX cells was determined by MTT. QPCR was used to detect the mRNA expression of Shh，Gli-1 in MCF-7 and MCF-7／PTX cells. Protein expression of Shh，Gli-1 in MCF-7 and MCF-7／PTX cells was detected by Western blotting. Results IC50 of PTX for MCF-7 cells was（0.10+0.02）mg／L，and for MCF-7／PTX cell was（5.30+0.01） mg／L. The drug resistance index was 53.0. The expression of Shh mRNA in MCF-7 and MCF-7／PTX cells was 0.78 ± 0.12 and 1.45 ± 0.56（P＜0.01），and the expression levels of Gli-1 mRNA was 1.86±0.02 and 3.56±0.26（P＜0.01）. The expression level of Shh protein in MCF-7 and MCF-7／PTX cells was 0.58 ±0.06 and 1.03 ± 0.22（P＜0.01）. Gli-1 protein expression in MCF-7 and MCF-7／PTX cells was 1.17±0.12 and 2.78±0.09（P＜0.01）. Conclusion Shh，Gli-1 are highly expressed in MCF-7／PTX cells，indicating that chemotherapy may guide drug resistance of breast cancer by up-regulating the protein and gene of hedgehog signaling pathway. The target to hedgehog signaling pathway may be a new direction to overcome drug resistance.

Objective To investigate the expression of human telomerase reverse transcriptase（hTERT）and hypermethylation of proteintyrosine phosphatase receptor（PTPRO）in human esophageal cancer cell line Eca-109 treated with norcantharidin（NCTD）. Methods Eca-109 cells were treated with different concentrations of NCTD（1，2，4，8，16 μg／ml）and the proliferation was determined by MTT assay at 12 h and 24 h. Cell apoptosis of NCTD+Eca-109 group（experimental group）and Eca-109 group（control group）were detected by TUNEL and laser scanning confocal microscope（LSCM）. Methylationspecific PCR（MSP）was used to detect the PTPRO methylation status in both experimental and control groups. hTERT protein was tested using Western blotting. Results MTT method showed that NCTD could increase the proliferation inhibitory rate of Eca-109 cells in a dose and time depended manner. The proliferation inhibitory rates of Eca-109 cells were statistically different among different concentrations of NCTD, as wall as different exposure time. Distinct morphological changes of apoptosis were found in experimental group tested by TUNEL and LSCM. PTPRO methylation status was found in control group by MSP test.The expression of hTERT protein was reduced in experimental group compared with control group（P＜0.05）. Conclusion NCTD can significantly inhibit the growth of esophageal cancer cell line Eca-109，which is associated with the down-regulation of hTERT and PTPRO methylation status.

Objective To investigate the effect of 20（s）-Ginsenoside Rg3 （Rg3） on regulating autophagymediated sorafenib sensitivity of hepatocellular carcinoma cells. Methods Hep3B cells were used in this study and treated by Rg3，autophagy inhibitor 3-Methyladenine（3-MA），sorafenib，Rg3 plus sorafenib and 3-MA plus sorafenib. The sensitivity of Hep3B cells to Rg3，sorafenib and 3MA was detected by MTT method. Hep3B cells proliferation inhibition of Rg3，3-MA plus sorafenib were detected by CCK-8 method. The interaction of sorafenib with 3-MA and Rg3 was assessed by q value. LC3 conversion and LC3 turnover assay were used to detect the autophagic regulation effect of sorafenib and Rg3. Autophagy related proteins，including Bcelin1，LC3 and p62，were detected by Western blotting. Results MTT showed that Rg3，sorafenib and 3-MA inhibited Hep3B cell proliferation in a dose and time-dependent manner. CCK-8 test showed that the inhibition effects of low（0.5 μg／ml）and medium（1 μg／ml） doses of sorafenib in combination with Rg3 or with 3-MA were significantly higher than sorafenib alone with synergistic effect（P＜0.01）. High dose（2 μg／ml） of sorafenib in combination with Rg3 showed a higher inhibitory rate to Hep3B cells（P＜0.01），but no difference was observed on the inhibitory rate of high dose of sorafenib with or without 3-MA（P＞0.05）. The interaction of high dose of sorafenib in combination with Rg3 or 3-MA appeared addictive effect. LC3 conversion assay showed that with the extension of the duration of drug action，Rg3 and sorafenib increased the LC3-II level gradually. LC3 turnover assay showed that LC3 II level was significantly higher in sorafenib combined with CQ than that of sorafenib alone（P＜0.01），while Rg3 combined with or without CQ had no obvious changes of LC3-II levels（P＞0.05）. Western blotting showed that compared with control group， Rg3 and sorafenib increased Beclin1 protein expression obviously（P＜0.01）. Compared with sorafenib，Beclin1 decreased significantly when sorafenib combined with Rg3 instead of in combination with 3-MA. Rg3，3-MA and sorafenib caused the rising levels of LC3-II（P＜0.05）.LC3-II level in Rg3 combined with sorafenib was higher than that of sorafenib alone（P＜0.01），but there was no significant difference between 3-MA and 3-MA in combination with sorafenib（P＞0.05）. The level of p62 in Hep3B cells treated by 3-MA or sorafenib alone was significantly lower than that of control group（P＜0.05）.Rg3 combined with sorafenib increased p62 level significantly（P＜0.01），while sorafenib combined with 3-MA decreased p62 level significantly（P＜0.01）. Conclusion Sorafenib induced autophagy in hepatocellular carcinoma cells leads to decreased drug sensitivity by increasing the expression of Beclin1. Rg3 can increase the sensitivity of hepatocellular carcinoma to sorafenib possibly through inhibiting degradation of sorafenib-induced autophagy.

Objective To investigate the in vitro effect of DNA methyltransferase inhibitor SGI-1027 on proliferation，apoptosis and cell cycle of colon cancer LoVo cells, as well as the possible mechanism. Methods The LoVo cells in the logarithmic growth phase were used in this study，and the LoVo cells exposured to SGI-1027 with final concentrations of 0.1，1，5 and 10 μmol／L were chosen as experimental group. Inverted phase contrast microscope was used to observe morphology of LoVo cells. The cells in control group were synchronously cultured in RPMI 1640 with 10％ fetal bovine serum. The proliferation inhibition rates of SGI-1027 on LoVo cells were detected by adding MTT solution after 24，48 and 72 h. After SGI-1027 treatment，1×106 cells per concentration were harvested for the detection of cell apoptosis rate and cell cycle phase distribution by flow cytometry with Annexin-V fluorescein isothiocyanate（FITC）／propidium iodide（PI）double staining and PI staining，respectively. The effect of SGI-1027 on PI3K／Akt pathway was evaluated by Western blotting. Results Inverted phase contrast microscope showed that the morphological chages of LoVo cells were more obvious treated by SGI-1027 in dose and time dependent manner. In addition to the treatment with 0.1 μmol／L SGI-1027 for 24 h，the proliferation inhibitory rates were increased in time and dose dependent manner. Compared with control group，the apoptotic rates of LoVo cells treated by SGI-1027（0.1-10 μmol／L）at 24, 48 h were all increased， and the differences between different concentrations were statistically significant（P＜0.05）. Compared with control group，the proportion of G0／G1 phase and the level of PTEN increased after SGI-1027 treatment（1-10 μmol／L）,but the proportions of both S phase and G2／M phase cells as well as the level of Akt decreased（P＜0.05）. Conclusion SGI-1027 could inhibit the proliferation of LoVo cells and induce apoptosis and G0／G1 arrest，and the time and concentration of SGI-1027 treatment have effect on the malignant behavior of LoVo cells.

ObjectiveTo discuss the clinical features and prognostic factors of gastrointestinal stromal tumor（GIST）with hepatic metastasis. Methods From January 2002 to January 2014，138 patients with recurrent or metstatic GIST were enrolled，among whom 74 cases occurred with hepatic metastasis. According to the recurrent sites，patients were divided into 3 groups：hepatic metastasis only group （n=34），abdominal metastasis group（n=64），and abdominal and hepatic metastasis group（n=40）. All patients were given imatinib mesylate orally with initial dose of 400 mg per day. Logistic regression model was used to analyze factors affecting short-term efficacy; Kaplan-Meier method was employed to analyze long-term efficacy; prognostic factors were analyed by Cox proportional hazards regression model. Results A total of 135 cases could be evaluated for curative effect.In 74 cases with hepatic metastasis，11 received CR，41 received PR，18 received SD，and 4 received PD. The response rate（RR）and disease control rate（DCR）were 70.3％ and 94.6％，respectively. There were no statistical differences in RR and DCR among the 3 groups（P＞0.05）. According to the Logistic regression model analysis，simultaneous liver metastasis was the independent factor affecting RR. The median progression-free survival（PFS）and median overall survival（OS）of the whole group were 52 months and 66 months，respectively. The 1-，2-，3-and 5-year survival rates were 97.0％，89.6％，82.3％ and 60.0％，respectively. The median PFS and OS of patients with hepatic metastasis were 45 months and 68 months，respectively. The 1-，2-，3-and 5-year survival rates were 97.2％，92.5％，87.4％ and 59.2％，respectively. The median PFS of hepatic metastasis only group，abdominal metastasis group，and abdominal and hepatic metastasis group were 61, 56 and 30 months，respectively. The median OS of the 3 groups were 75, 65 and 63 months，respectively. According to the Cox proportional hazards regression model analysis，companying with other organ metastasis and short term efficacy were the independent factors affecting PFS，while companying with other organ metastases and age were the independent factors affecting OS. The main adverse reactions of the three groups were edema，leukopenia and diarrhea，mainly in grade 1-2. There were no statistical differences in adverse reactions among the 3 groups. Conclusion Short term efficacy is not affected by hepatic metastasis in GIST patients taking imatinib mesylate. Extrahepatic lesions，age and response rate are important factors affected the survival of the GIST patients who have hepatic metastasis.

Objective To explore the expression of fibroblast growth factorinducible 14（Fn14）and Janus kinase／signal transducerand activator of transcription（JAK／STAT）in non-small cell lung cancer（NSCLC）tissues with EGFR exon 19 deletion. Methods In this study，125 NSCLC cases with EGFR 19-Del were selected by amplification refractory mutation system. And the 30 cases of paired adjacent normal tissues were collected. Expressions of Fn14，p-JAK1 and p-STAT1 were detected in these samples using immunohistochemistry and the correlation of Fn14 expression with JAK／STAT expression was analyzed by statistics. Results The expression of Fn14 was mainly located on cell membrane and cytoplasm, while the expression of p-JAK1 and p-STAT1 were mainly located in cytoplasm and cell nucleus. Compared to normal lung tissues，the higher expression rates of Fn14，p-JAK1 and p-STAT1 protein were 100.0％（125／125），83.2％（104／125）and 100.0％（125／125）in NSCLC tissues with EGFR 19-Del（P＜0.05）. There were significant differences of Fn14，p-JAK1 and p-STAT1 expression in histological grades，pTNM stages and lymph node metastasis（P＜0.05），while there were no significant differences in sex，age，smoking history and pathological types（P＞0.05）. The correlation of Fn14 with p-JAK1 and p-STAT1 were obvious（P＜0.05，r＞0.3）in pathological classification，histological grads and pTNM stage of NSCLC. Conclusion Fn14，p-JAK1 and p-STAT1 proteins are highly expressed in NSCLC with EGFR 19-Del，suggesting that the above three proteins would be likely to associate with the development of NSCLC. The good correlations between Fn14 expression and p-JAK1，p-STAT1 hints that Fn14 may effect on the expression of p-JAK1，p-STAT1. All these provide important basis for the mechanism study of Fn14 affecting on the development of NSCLC with EGFR 19-Del.

Objective To investigate the methylation status of promoter of HOXA10 gene in lung adenocarcinoma and its correlation with clinicopathologic characteristics and prognosis. Methods Methylation-specific polymerase chain reaction（MSP）was used to examine the promoter hypomethylation in 30 lung adenocarcinoma samples and their corresponding lung normal tissues. The relationship between the hypomethylation status and clinicopathologic features， prognosis was analyzed. Results MSP test indicated that 17 cases（56.7％）of 30 lung adenocarcinoma samples showed hypomethylation of HOXA10 promoter，and 4 cases were even complete demethylation. But only 6 cases（20.0％）of 30 corresponding lung normal tissues showed promoter hypomethylation（P＜0.05）. Analysis revealed that the frequency of hypomethylation was correlated with size of tumor，clinical stage and lymph node metastasis（P＜0. 05），but not with age，gender and tumor differentiation（P＞0.05）. Statistical analysis showed that the median diseasefree survival of patients with HOXA10 hypomethylation was 27.0 months，which was significantly lower than 46.0 months of those with HOXA10 methylation（P=0.002）. Conclusion HOXA10 gene promoter hypomethylation is a frequent epigenetic event in lung adenocarcinoma，which indicates poor prognosis of patients. It may be a biological marker to predict the prognosis for lung adenocarcinoma.

Objective To explore the expression of long non-coding RNA of colon cancer associated transcript 1（LncRNA-CCAT1）in hepatocellular carcinoma（HCC）tissues and cell lines, as well as its clinical significance. Methods CCAT1 expression in 42 pairs of HCC tissues and paired adjacent normal tissues as well as 4 types of HCC cell lines（SMMC-7721，Hep3B，Hub7 and HepG2）and normal hepatic cell line LO2 were tested by QPCR. The relationship between the expression of CCAT1 and common clinical pathological parameters（gender，age，alpha-fetoprotein，tumor size，tumor number，lymph node metastasis，differentiation and TNM stage）were analyzed accordingly. Results Compared with normal hepatic cell line LO2，there was a high expression of CCAT1 in SMMC-7721, Hep3B, Hub7 and HepG2 cell lines with significant difference（P＜0.05）, especially in HepG2 cell line. The expression of CCAT1 in HCC tissue was higher than that in the adjacent tissues，and the difference was statistically significant（P＜0.05）. The expression of CCAT1 in HCC was related with tumor size，alpha fetoprotein，differentiation，TNM stage and lymph node metastasis（P＜0.05）, but not with age, gender and tumor number（P＞0.05）. Conclusion LncRNA CCAT1 has a role in the occurence,development and prognosis of HCC，worthy of further research on its mechanism.

Objective To investigate the motion of clinical target volume（CTV）by using cone beam computed tomography（CBCT）on linear accelerator and to determine a internal margin（IM）value for the internal target volume（ITV）during intensity-modulated radiotherapy（IMRT） for non-surgical cervical cancer. Methods One hundred and forty CBCT images from 20 non-surgical cervical cancer patients who underwent radical IMRT from Dec 2013 to Oct 2014 were selected for this study. The deformation and displacement between the simulation CT and CBCTs were measured. Results The volume reductions of CTV1 between the simulation CT and CBCTs were（33.56±22.52）cm3（range from 1.04-110.22 cm3）and the percentages of the volume reductions were（10.19±6.32）％（range from 0.37％-32.01％）. The motion between the simulation CT and CBCTs were（1.19±0.82）cm,（0.80±0.55）cm,（0.16±0.25）cm,（0.23±0.29）cm,（0.27±0.42）cm,（0.18±0.24）cm and（0.78±1.09）cm in the anterio-posterior directions of uterus，anterio-posterior directions of cervix，superior directions of uterus，lateral directions of the same side，the opposite side of the bottom of uterus，respectively. If the IM was set less than 2 cm，the CTV of 85％ CBCTs could be covered completely. 95％ patients showed greater uterus motions than cervical motions in all directions. The motion of CTV1 had great individual difference. Conclusion The strategies of target outline for different IM size at three dimensional direction obtained by CBCT and different IM size of uterus and cervix, in combination with individualized image guided radiotherapy may be a good clinical form for realizing precise radiotherapy in cervical cancer.

Objective To analyze the clinical characteristics of cutaneous metastases from internal cancers, and enhance the understanding of cutaneous metastases. Methods In the retrospective study，the clinical features，primary sites of cancers, morphological features and occurence of 62 cases of cutaneous metastases from internal cancers diagnosed in Beijing Friendship Hospital from January 2002 to December 2015 were analyzed. Results There were 40 males and 22 females among the 62 patients. The median age at the onset of skin lesions was 60.0 years（range 33-82 years）.Cutaneous metastases occurred at various locations of the body，including abdomen，chest，back，scalp，limbs and etc. Abdominal wall was the most common site of cutaneous metastases，accounting for 72.6％ of patients with cutaneous metastases. The most common types of primary cancer were lung cancer，gastric cancer and colorectal cancer. Pathological biopsy showed that 40 cases were in complete agreement with the pathologic types of the primary lesions，and 3 cases were consistent with the morphology of the primary tumors，but the degree of tumor differentiation was different.One case was confirmed with second primary cancer by skin biopsy. Seventeen patients were comfirmed with cutaneous metastases when the primary cancers were diagnosed. Most patients were diagnosed with cutaneous metastases within 4 years after the primary cancers were comfirmed. Conclusion With increasing incidence of cancers，cutaneous metastases from internal cancers increased in recent years. Raising awareness of cutaneous metastases is helpful for early diagnosis，treatment and prolonging patients'life.

Objective To explore the clinicopathological characteristics of male breast cancer and the factors affecting prognosis. Methods Clinical data of 55 patients with histopathologically confirmed male breast cancer who received operation from January 1999 to May 2010 were enrolled. The survival curves were draw by Kaplan-Meier method. Log-rank test and Cox proportional harzard regression model were used for survival and prognostic analysis. Results The 5-year survival rate of the whole group was 61.8％. The 5-year survival rates for stage Ⅰ，Ⅱ，Ⅲ and Ⅳ were 75.0％,69.6％,45.4％ and 20.0％ with statistical difference（P＜0.05）. The 5-year survival rates for histological grade Ⅰ，Ⅱ and Ⅲ were 83.3％,67.5％ and 33.3％ with statistical difference（P＜0.05）. Single factor analysis showed that histological grade，T stage，lymph node's metastasis，TNM stage and radiotherapy significantly influenced the 5-year survival rate（P＜0.05）. Cox regression analysis showed that histological grade（HR=3.690，95％CI：1.476-9.225，P＜0.05）and TNM stage（HR=3.437，95％CI：1.447-8.163，P＜0.05）were dependent prognostic factors influenced the overall survival for male breast cancer. Conclusion Histological grade and TNM stage are dependent prognostic factors for male breast cancer. The diagnosis and treatment of male breast cancer remains to be further studied.

Objective To explore the curative effect of bortezomib-CHOP（B-CHOP）regimen versus CHOP regimen on elderly patients with recurrent mantle cell lymphoma. Methods Thirty-eight elderly patients with recurrent mantle cell lymphoma from Jan 2009 to Jan 2015 were enrolled in this study and randomly assigned to CHOP regimen（control group，n=19）and B-CHOP regimen（experimental group，n=19）. B-CHOP regimen：bortezomib 1.6 mg／m2 iv bolus d1，d8；cyclophosphamide 750 mg／m2 iv d2；doxorubicin 50 mg／m2 iv d2；vincristine 1.4 mg／m2（max dose 2 mg／m2）iv d2；prednisone 100 mg／d po d2-d6. CHOP regimen：cyclophosphamide 750 mg／m2 iv d1；doxorubicin 50 mg／m2 iv d1；vincristine 1.4 mg／m2（max dose 2 mg／m2）iv d1；prednisone 100 mg／d po d1-d5. All the patients underwent 8 cycles of chemotherapy with 28 days as a cycle. The efficacy evaluation was carried out at the 4th and 8th cycle according to the non-Hodgkin's lymphoma international standard. The long-term survival was analyzed using the follow-up data. Results In experimental group，there were 10 cases of complete remission（CR），4 cases of partial remission（PR），3 cases of no response（NR）and 2 cases of progression（PD）after 4 cycles，and 12 cases of CR，4 cases of PR，1 case of NR and 2 cases of PD after 8 cycles. In control group，there were 3 cases of CR，2 cases of PR，10 cases of NR and 4 cases of PD after 4 cycles，and 5 cases of CR，3 cases of PR，7 case of NR and 4 cases of PD after 8 cycles. In experimental group，the response rate（RR）of 4th and 8th cycles were 73.7％and 84.2％，which were higher than 26.3％and 42.1％of control group（P＜0.05）. The median overall survival in experimental group was 56.0 months，longer than 29.0 months in control group（P＜0.05）. The main side effects of the two groups were fever, leukopenia, thrombocytopenia, and peripheral neuritis, and etc. The incidence of side effects between the two groups had no difference（P＞0.05）. Conclusion B-CHOP regimen shows better RR and overall survival than CHOP regimen in elderly patients with recurrent mantle cell lymphoma.

Objective To explore the effect of whole course nutrition support on the response and treatment compliance of nasopharyngeal carcinoma（NPC）patients. Methods A total of 87 patients with NPC from January 2013 to December 2014 were enrolled in this study，with 26 patients as observation group and 61 as control group. Oral nutritional preparations or nasal feeding were defined for full nutritional support during radiotherapy procedure in observation group. Intensity modulated radiotherapy was treated with 6MV X-ray. The prescription dose was 66-74 Gy／30-33 f and 66-70 Gy／30-33 f for nasopharynx and neck lymph node metastasis. During radiotherapy，the quality of life（KPS score），the body weight and the acute response（RTOG）were recorded，and the nutritional status was evaluated by using body mass index（BMI）. Treatment compliance was evaluated at the 30 fraction of radiation. Results All the patients in observation group completed radiotherapy, but treatment disruption was found in 7 cases in control group，among whom 5 cases failed to complete radiotherapy. KPS score and nutritional status of observation group were better than those in control group at the 4th week and the end of radiotherapy（P＜0.05）. The scores of radiodermatitis, mucositis, odynophagia and myelosuppression were obviously lower in observation group compared with control group （P＜0.05）, but the scores of dry mouth in the two groups had no difference（P＞0.05）. The treatment compliance in observation group was 88.5%（23/26）, significantly better than 37.7%（23/61）in control group（P＜0.05）. Conclusion Total nutrition support can significantly reduce the acute radiation response of NPC，improve quality of life and treatment compliance of patients.

Objective To investigate clinical characteristics，diagnosis and surgical treatment for thyroid microcarcinoma. Methods Sixty-three patients with thyroid microcarcinoma from January 2005 to August 2014 were enrolled. The clinical data including diagnosis，surgical treatment，clinicopathological characteristics and follow-up results were reviewed. Results There were 32 cases（50.8％）suspected of micocarcinoma by color Doppler ultrasound before operation. Biopsy by fine-needle aspiration guided by color Doppler ultrasound were performed in 4 cases（6.4％）before operation，and 3（4.8％）of them were confirmed. There were 41 cases（74.6％）confirmed by frozen section pathological diagnosis during operation. Postoperative pathologic diagnosis of 63 cases was papillary carcinoma. Total thyroidectomy was performed in 12 cases. Subtotal thyroidectomy was performed in 17 cases. Lobectomy and isthmectomy for tumor side and subtotal lobectomy for another side were performed in 20 cases. Subtotal lobectomy for tumor side and lobectomy for another side and isthmectomy were performed in 8 cases. Lobectomy and isthmectomy were performed in 4 cases. Lobectomy and isthmectomy for tumor side and partial lobectomy for another side were performed in 2 cases. Functional neck dissection was performed in 2 cases. Central district dissection was performed in 4 cases. Follow-up was ranged from 1 year and 3 months to 10 years and 11 months，and 1 case lost contact in our survey；62 patients were alive，among them 1 case was found recurred after surgery and total thyroidectomy was performed then. Conclusion The prognosis of most of thyroid microcarcinoma is satisfied by surgical treatment，but partially is aggressive. Individualized treatment should be emphasized.

Objective To analyze clinical and pathological characteristics of 10 cases of gastric small cell neuroendocrine carcinoma （SCNEC-G）and to explore the main points of diagnsis and differentiate diagnosis，hoping to improve the accuracy of pathological diagnosis and provide the basis for the comprehensive treatment. Methods From 2010 to 2015, the tissue sections from SCNEC-G specimens of 10 cases underwent radical operation were observed by light microscopy. The tissue sections were labeled by immunohistochemistry and the expression of synaptophysin（Syn），chromogranin（CgA），neural cell adhesion molecule（CD56），thyroid transcription factor-1（TTF-1）and Ki-67 were analyzed. Results Under light microscope，the tumor cells were arranged irregularly with invasive growth potential. The arrangement of cancer cells was diffuse and different sized nest or spindle-shaped structures. Some of the cases showed focal pseudoglandular pattern. The internal surface of the tumors showed nuclear debris and coagulative necrosis. Cancer cells were small，round，oval，spindle-shaped with hyperchromatic nuclei，nucleoli and morenuclear fission. The invasion of 10 cases of gastric cancer was from deep muscle layer to whole layer. There were infiltrations in peripheral adiposetissue in some cases. All samples had nerve invasion and intravascular cancer embolus. The percentages of 10 SCNEC-G samples with positive to strong positive immunoreactivity were 80.0％，70.0％，80.0％，40.0％ and 100.0％ for Syn，CgA，CD56，TTF-1 and Ki-67，respectively. Conclusion SCNEC-G has a higher sensitivity to neural markers，while part of some cases also express TTF-1. In some metastatic TTF-1 positive small cell carcinoma of unknown primary lesion，we should consider the possibility of SCNEC-G.

Objective To explore the clinical features，diagnosis and treatment of 13 patients with primary breast diffuse large B cell lymphoma（PB-DLBCL）. Methods The clinical data of 13 patients with PB-DLBCL from Jan 2010 to Nov 2015 were retrospectively analyzed. Eight cases received breast mass excision，4 cases underwent modified radical mastectomy，and 1 case received unilateral mastectomy. Results All of the cases were female. The involved breasts were left-sided in 6 cases，right-sided in 6 cases，and bilateral breast was found in 1 case. The size ranged from 1.5 cm to 8.0 cm. Two cases were preoperatively diagnosed as breast fibroadenoma，1 case as giant fibroadenoma，and 10 cases as breast carcinoma. Thirteen cases were diagnosed as PB-DLBCL by using immunohistochemistry. According to Ann Arbor staging，10 cases were in stageⅠ，and 3 cases were in stage Ⅱ. Twelve cases received chemotherapy of CHOP or R-CHOP regimen after operation，and 1 case gave up treatment. The follow-up time ranged from 1 month to 5 years. During follow-up，2 cases relapsed，2 cases died，and 9 cases survived without relapse. Conclusion PB-DLBCL is not common in clinic，and mainly occurs in female. PBDLBCL is easily misdiagnosed by preoperative examination and intraoperative frozen section，and the exact diagnosis is confirmed by immunochemistry. Chemotherapy based comprehensive treatment is the main method for PB-DLBCL.

Objective To investigate the accuracy rate of ultrasound-guided core needle biopsy（CNB）in diagnosis of nonpalpable breast lesions less than 1 centimeter. Methods Clinical and pathological data of consecutive 124 female patients underwent CNB and surgical excisions were reviewed from January 2010 to July 2015. Results Among 124 patients，29 cases of breast cancer and 95 cases of non-cancer were diagnosed by CNB. The CNB diagnosis of all 29 breast cancer cases and 84 non-cancer cases were consistent with surgical diagnosis，and the coincidence rate was 91.1％（113/124），with Kappa value of 0.781（P＜0.001）. The remaining 11 cases diagnosed non-cancer by CNB were confirmed breast cancer by surgical excision，of which，10 cases were histological underestimate，and 1 case was false negative. Conclusion Ultrasound-guided CNB diagnosis is a simple and accurate method for breast lesions less than 1 centimeter.

Lung cancer is one of the malignant tumors with the highest mortality in the world. Epidermal growth factor receptor tyrosine kinase inhibitors（EGFR-TKIs）significantly improve the quality of life of advanced non-small cell lung cancer（NSCLC），and prolong the overall survival. However，only a certain subpopulation of lung cancer patients carrying specific activating mutations in EGFR respond clinically to EGFR-TKIs.Even among these patients，the median progression-free survival（PFS）is about 12 months owing to drug resistance. Recently，quite a few patients acquired drug resistance with NSCLC transitioned to small cell lung cancer（SCLC）were reported. In this review，we discuss the recent advances in the understanding of the phenomenon and possible mechanisms for the conversion of NSCLC into SCLC. The treatment strategies of patients with EGFR mutations in SCLC will be recommended according to the therapy scheme after EGFR-TKIs resistance of NSCLC and treatment proposal of the individual reported.

Recently，maintenance therapy of traditional Chinese medicine（TCM）for advanced non-small cell lung cancer（NSCLC）has been carried out in many places of China. This paper trimmed the theoretical foundation，main content and the current situation of maintenance therapy，and summed up the literature of this field related to TCM in recent years. We obtained a result that TCM could relief clinical symptoms，prolong the progression-free survival，and improve the quality of life of advanced NSCLC. Meanwhile，there's some insufficiency in these studies，such as inadequate sample，low quality，and etc. We look forward to more highquality and normalized study.

Colon cancer is one of the most common gastrointestinal malignancy. In the past decade，the adjuvant therapy of colon cancer has made great progress. Although surgery is the mainstay of treatment in colon cancer，adjuvant treatment is also an important aspect of increasing disease-free survival and overall survival in patients with colon cancer. In patients with colon cancer who suffer radical surgery，approximately one-third of patients are with regional lymph node metastasis，and one-quarter of patients are not associated with regional lymph node metastasis，but they have high risk factors for recurrence. The role of adjuvant therapy is to eliminate cancer micrometastasis sediments，which can increase the chance of cancer recurrence. In this article, the duration of chemotherapy，how do patients with different clinical stages start adjuvant therapy，adjuvant therapy of elderly patients and international prevailing disputes about adjuvant therapy are reviewed.