Predictive value of co-expression patterns of immune checkpoint molecules for clinical outcomes of hematological malignancies

Co-expression of immune checkpoint(IC)molecules can exacerbate T cell exhaustion in patients with hematological malignancies(HMs)and contribute to the immune escape of tumor cells,which is related to poor clinical outcome.It is worth establishing and optimizing an ideal prediction model based on the co-expression patterns of IC molecules to evaluate the immune status of HM patients and predict their clinical outcome.In this perspective,we summarize the co-expression patterns of IC molecules and their importance as biomarkers that predict the prognosis of patients with different HMs,providing new insights for designing dual IC blockades(ICBs).

Striatins and STRIPAK complex partners in clinical outcomes of patients with breast cancer and responses to drug treatment

Objective: Striatins(STRNs) family, which contains three multi-domain scaffolding proteins, are cornerstones of the striatins interacting phosphatase and kinase(STRIPAK) complex. Although the role of the STRIPAK complex in cancer has become recognized in recent years, its clinical significance in breast cancer has not been fully established.Methods: Using a freshly frozen breast cancer tissue cohort containing both cancerous and adjacent normal mammary tissues, we quantitatively evaluated the transcript-level expression of all members within the STRIPAK complex along with some key interacting and regulatory proteins of STRNs. The expression profile of each molecule and the integrated pattern of the complex members were assessed against the clinical-pathological factors of the patients. The Cancer Genome Atlas(TCGA) dataset was used to evaluate the breast cancer patients’ response to chemotherapies. Four human breast cancer cell lines, MDA-MB-231, MDA-MB-361, MCF-7, and SKBR-3, were subsequently adopted for in vitro work.Results: Here we found that high-level expressions of STRIP2, calmodulin, CCM3, MINK1 and SLMAP were respectively associated with shorter overall survival(OS) of patients. Although the similar pattern observed for STRN3, STRN4 and a contrary pattern observed for PPP2CA, PPP2CB and PPPR1A were not significant, the integrated expression profile of STRNs group and PPP2 group members constitutes a highly significant prognostic indicator for OS [P<0.001, hazard ratio(HR)=2.04, 95% confidence interval(95% CI), 1.36-3.07] and disease-free survival(DFS)(P=0.003, HR=1.40, 95% CI, 1.12-1.75). Reduced expression of STRN3 has an influence on the biological functions including adhesiveness and migration. In line with our clinical findings, the breast cancer cells responded to STRN3 knockdown with changes in their chemo-sensitivity, of which the response is also breast cancer subtype dependent.Conclusions: Our results suggest a possible role of the STRIPAK complex in breast cancer development and prognosis. Among the members, the expression profile of STRN3 presents a valuable factor for assessing patients’ responses to drug treatment.

Risk-stratification model to select conversion surgery for advanced gastric cancer patients

Objective: Conversion surgery is a surgery with a purpose of R0 resection in primary advanced gastric cancer(GC) that responded well to systemic chemotherapy. This study aimed to explore the efficacy of conversion surgery for advanced GC.Methods: A total of 618 advanced GC patients receiving systemic chemotherapy were stratified into low-,moderate-and high-risk groups based on a nomogram-predicted probability of overall survival. The survival of conversion surgery and chemotherapy alone groups was compared using the log-rank test and Cox regression analysis after propensity score matching(PSM).Results: A nomogram with good discrimination(concordance index: 0.65) and accurate calibration was constructed. After PSM, the median survival time(MST) of conversion surgery was 26.80 months, compared with16.60 months of chemotherapy alone(P<0.001). Conversion surgery was associated with a longer MST for patients in the low-risk group(30.40 months vs. 20.90 months, P=0.013), whereas it was not associated with prolonged survival in the moderate-and high-risk groups(P=0.221 and P=0.131, respectively).Conclusions: Conversion surgery was associated with longer survival, especially for low-risk population.

IGHG1 promotes motility likely through epithelial-mesenchymal transition in ovarian cancer

Objective： Ovarian cancer（OC） is one of the leading causes of death for female cancer patients. COC166-9 is an OC-specific monoclonal antibody and we have identified immunoglobulin γ-1 heavy chain constant region（IGHG1） as its antigen. We explore the function of IGHG1 in proliferation, apoptosis and motility of OC cells further in this research.Methods： IGHG1 expression in OC specimens was detected through immunohistochemistry. Real-time quantitative polymerase chain reaction（RT-q PCR） or western blotting assay was used to test IGHG1 expression in OC cells. Viability of OC cells was tested by 3-（4,5-dimethylthiazol-2-yl）-2,5-diphenyltetrazolium bromide（MTT）assay. Flow cytometry or western blotting assay was used to detect cell cycle and apoptosis. Cellular motility was analyzed by using transwell assay and the markers of epithelial-mesenchymal transition（EMT） were tested through immunoblots.Results： Although it exerts negligible effect on the viability and apoptosis of OC cells, IGHG1 could promote migration and invasion of malignant cells in vitro. Mechanistically, IGHG1 increases the expression of N-cadherin and Vimentin while decreases E-cadherin expression. Additionally, IGHG1 expression in OC specimens is higher relative to the paired normal counterparts. Further analysis demonstrates that the increased IGHG1 expression correlates positively with the lymph node metastasis of OC.Conclusions： IGHG1 promotes the motility of OC cells likely through executing the EMT program. Increased IGHG1 expression in OC specimens is associated with the lymph node metastasis.

Clinical characteristics and response to tyrosine kinase inhibitors of patients with non-small cell lung cancer harboring uncommon epidermal growth factor receptor mutations

Objective： To investigate the clinical features of patients with non-small cell lung cancer（NSCLC） harboring uncommon epidermal growth factor receptor（EGFR） mutations, and the treatment outcomes of EGFR tyrosine kinase inhibitors（TKIs） in these patients.Methods： We retrospectively analyzed the data of 128 NSCLC patients pathologically diagnosed with uncommon EGFR mutation in the Department of Pathology, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences ＆ Peking Union Medical College and Beijing Hospital from January 2010 to December 2015, including 40 advanced patients who received EGFR-TKI.Results： Among the total 128 patients, 11 patients were non-adenocarcinoma, including squamous carcinoma（3.9%）, adenosquamous carcinoma（2.3%）, large cell carcinoma（0.8%）, and composite neuroendocrine carcinoma（1.6%）. Single mutations accounted for 75.0%（96/128）, including G719X（29.7%）, S768I（18.0%）, 20 exon insertion（13.3%）, L861Q（12.5%）, De novo T790M（0.8%）, and T725（0.8%）. Thirty-two patients harbored complex mutations. Forty advanced patients received EGFR-TKI, the objective response rate（ORR） was 20.0%,the disease control rate（DCR） was 85.0%, and the progression-free survival（PFS） was 6.4 [95% confidence interval（95% CI）, 4.8–7.9] months. The exploratory analysis of tumor response and PFS in 33 patients with G719X/S768I/L861 Q subtypes showed that ORR was 21.2%（7/33）, the DCR was 93.9%（31/33）, and PFS was 7.6（95% CI, 5.8–9.4） months. Patients with exon 20 insertion mutation and De novo T790 M experienced rapid disease progression with PFS no more than 2.7 months.Conclusions： Uncommon EGFR-mutant NSCLCs are heterogeneous, EGFR-TKIs can have different efficacy in this specific subtype, and thus further individual assessment is required for each case.

Extent of lymphadenectomy has no impact on postoperative complications after gastric cancer surgery in Sweden

Objective： Curative gastric cancer surgery entails removal of the primary tumor with adequate margins including regional lymph nodes. European randomized controlled trials with recruitment in the 1990＇s reported increased morbidity and mortality for D2 compared to D 1. Here, we examined the extent of lymphadenectomy during gastric cancer surgery and the associated risk for postoperative complications and mortality using the strengths of a population-based study. Methods： A prospective nationwide study conducted within the National Register of Esophageal and Gastric Cancer. All patients in Sweden from 2006 to 2013 who underwent gastric cancer resections with curative intent were included. Patients were categorized into DO, D I, or D I ＋/D2, and analyzed regarding postoperative morbidity and mortality using multivariable logistic regression. Results： In total, 349 （31.7%） patients had a DO, 494 （44.9%） DI, and 258 （23.4%） DI＋/D2 lymphadenectomy. The 30-d postoperative complication rates were 25.5%, 25.1% and 32.2 % （DO, D I and D1 ＋/D2, respectively）, and 90-d mortality rates were 8.3%, 4.3 % and 5.8%. After adjustment for confounders, in mukivariable analysis, there were no significant differences in risk for postoperative complications between the lymphadenectomy groups. For 90-d mortality, there was a lower risk for D1 vs. DO. Conclusions： The majority of gastric cancer resections in Sweden have included only a limited lymphadenectomy （DO and DI）. More extensive lymphadenectomy （DI＋/D2） seemed to have no impact on postoperative morbidity or mortality.

Retrospective analysis of interventional treatment of hepatic metastasis from gastroenteropancreatic neuroendocrine tumors

Objective： To analyze the angiography appearance of liver metastases from gastroenteropancreatic neuroendocrine tumors （GEP-NETs）, and evaluate the clinical efficacy and prognostic factors of interventional treatment for hepatic metastases. Methods： Fifty GEP-NETs patients with hepatic metastases were treated from January 2012 to December 2016, and received transarterial embolization （TAE） in the hepatic tumor or hepatic arterial infusion chemotherapy （HAIC）. All patients received 179 times of the intervention therapy in total. Results： Blood supplies were identified in the 50 eases with angiography, which showed that 35 cases had abundant vessels, while 15 eases had poor blood supply. Twenty-two cases were found either collateral blood supply, or portal vein invasion or arterial-portal vein fistula. The best curative efficacy was complete remission （CR） in 4 cases, partial remission （PR） in 28 cases and stable disease （SD） in 18 eases during the process of treatment. The angiography （P=0.047） and the frequency of intervention （P=0.037） showed significantly statistical difference with Kaplan-Meier analysis. The Cox analysis showed that more than 3 times of interventional therapy was an independent prognostic factor. Conclusions： Interventional treatment is safe and effective for GEP-NETs, and is beneficial to patients with main hepatic metastases after endocrine therapy.

Diffusion-tensor imaging as an adjunct to dynamic contrastenhanced MRI for improved accuracy of differential diagnosis between breast ductal carcinoma in situ and invasive breast carcinoma

Objective： To determine the value of diffusion-tensor imaging （DTI） as an adjunct to dynamic contrastenhanced magnetic resonance imaging （DCE-MRI） for improved accuracy of differential diagnosis between breast ductal carcinoma in situ （DCIS） and invasive breast carcinoma （IBC）. Methods： The MRI data of 63 patients pathologically confirmed as breast cancer were analyzed. The conventional MRI analysis metrics included enhancement style, initial enhancement characteristic, maximum slope of increase, time to peak, time signal intensity curve （TIC） pattern, and signal intensity on FS- T2WI. The values of apparent diffusion coefficient （ADC）, directionally-averaged mean diffusivity （D^vg）, exponential attenuation （EA）, fractional anisotropy （FA）, volume ratio （VR） and relative anisotropy （RA） were calculated and compared between DCIS and IBC. Multivariate logistic regression was used to identify independent factors for distinguishing IBC and DCIS. The diagnostic performance of the diagnosis equation was evaluated using the receiver operating characteristic （ROC） curve. The diagnostic efficacies of DCE- MRI, DWI and DTI were compared independently or combined. Results： EA value, lesion enhancement style and TIC pattern were identified as independent factor for differential diagnosis of IBC and DCIS. The combination diagnosis showed higher diagnostic efficacy than a single use of DCE-MRI （P=0.02）, and the area of the curve was improved from 0.84 （95% CI, 0.67-0.99） to 0.94 （95% CI, 0.85-1.00）. Conclusions： Quantitative DTI measurement as an adjunct to DCE-MRI could improve the diagnostic performance of differential diagnosis between DCIS and IBC compared to a single use of DCE-MRI.

Annual report on status of cancer in China,2010

Objective：Population-based cancer registration data in 2010 were collected,evaluated and analyzed by the National Central Cancer Registry （NCCR） of China.Cancer incident new cases and cancer deaths were estimated.Methods：There wvere 219 cancer registries submitted cancer incidence and death data in 2010.All data were checked and evaluated on basis of the criteria of data quality from NCCR.Total 145 registries＇ data were qualified and accepted for cancer statistics in 2010.Pooled data were stratified by urban/rural,area,sex,age group and cancer site.Cancer incident cases and deaths were estimated using age-specific rates and national population.The top ten common cancers in different groups,proportion and cumulative rate were also calculated.Chinese census in 2000 and Segi＇s population were used for age-standardized incidence/ mortality rates.Results：All 145 cancer registries （63 in urban and 82 in rural） covered a total of 158,403,248 population （92,433,739 in urban and 65,969,509 in rural areas）.The estimates of new cancer incident cases and cancer deaths were 3,093,039 and 1,956,622 in 2010,respectively.The morphology verified cases （MV％） accounted for 67.11％ and 2.99％ of incident cases were identified through death certifications only （DCO％） with mortality to incidence ratio （M/I） of 0.61.The crude incidence rate was 235.23/100,000 （268.65/100,000 in males,200.21/100,000 in females）,age-standardized incidence rates by Chinese standard population （ASIRC,2000） and by world standard population （ASIRW） were 184.58/100,000 and 181.49/100,000 with the cumulative incidence rate （0-74 years old） of 21.l 1％.The cancer incidence and ASIRC were 256.41/100,000 and 187.53/100,000 in urban areas whereas in rural areas,they were 213.71/100,000 and 181.10/100,000,respectively.The crude cancer mortality in China was 148.81/100,000 （186.37/100,000 in males and 109.42/100,000 in females）,age-standardized incidence rates by Chinese standard population （ASMRC,2000） and by world standard population （ASMRW） were 113.92/100,000 and 112.86/100,000,and the cumulative incidence rate （0-74 years old） was 12.78％.The cancer mortality and ASMRC were 156.14/100,000 and 109.21/100,000 in urban areas,whereas in rural areas,they were 141.35/100,000 and 119.00/100,000 respectively.Lung cancer,gastric cancer,colorectal cancer,liver cancer,esophageal cancer,pancreas cancer,encephaloma,lymphoma,female breast cancer and cervical cancer,were the most common cancers,accounting for 75％ of all cancer cases in urban and rural areas.Lung cancer,gastric cancer,liver cancer,esophageal cancer,colorectal cancer,pancreatic cancer,breast cancer,encephaloma,leukemia and lymphoma accounted for 80％ of all cancer deaths.Conclusions：The coverage of cancer registration population had a rapid increase and could reflect cancer burden in each area and population.As the basis of cancer control program,cancer registry plays an irreplaceable role in cancer epidemic surveillance,evaluation of cancer control programs and making anticancer strategy.China is facing serious cancer burden and prevention and control should be enhanced.

Distribution and drug resistance of pathogenic bacteria isolated from cancer hospital in 2013

Objective： To understand distribution and drug resistance of pathogenic bacteria from a specialized cancer hospital in 2013 in order to provide a basis for rational clinical antimicrobial agents. Methods： Pathogenic bacteria identification and drug sensitivity tests were performed with a VITEK 2 compact automatic identification system and data were analyzed using WHONET5.6 software.Results： Of the 1,378 strains tested, 980 were Gram-negative bacilli, accounting for 71.1%, in which Klebsiella pneumonia, Escherichia coli and Pseudomonas aeruginosa were the dominant strains. We found 328 Gram-positive coccus, accounting for 23.8%, in which the amount of Staphylococcus aureus was the highest. We identified 46 fungi, accounting for 4.1%. According to the departmental distribution within the hospital, the surgical departments isolated the major strains, accounting for 49.7%. According to disease types, lung cancer, intestinal cancer and esophagus cancer were the top three, accounting for 20.9%, 17.3% and 14.2%, respectively. No strains were resistant to imipenem, ertapenem or vancomycin.Conclusions： Pathogenic bacteria isolated from the specialized cancer hospital have different resistance rates compared to commonly used antimicrobial agents; therefore antimicrobial agents to reduce the morbidity and mortality of infections should be used.

Magnetic resonance imaging for prostate cancer clinical application

As prostate cancer is a biologically heterogeneous disease for which a variety of treatment options are available, the major objective of prostate cancer imaging is to achieve more precise disease characterization. In clinical practice, magnetic resonance imaging （MRI） is one of the imaging tools for the evaluation of prostate cancer, the fusion of MRI or dynamic contrast-enhanced MRI （DCE-MRI） with magnetic resonance spectroscopic imaging （MRSI） is improving the evaluation of cancer locafon, size, and extent, while providing an indication of tumor aggressiveness. This review summarizes the role of MRI in the application of prostate cancer and describes molecular MRI techniques （including MRSI and DCE-MRI） for aiding prostate cancer management.

Maffucci syndrome with unilateral limb: a case report and review of the literature

Maffucci syndrome is a congenital, non-hereditary mesodermal dysplasia manifested by multiple enchondromas and hemangiomas. It is associated with diverse secondary musculoskeletal deformities, which is exceedingly rare. We report a case of hemangiomas and enchondromas localized in the unilateral limb in a patient with Maffucci syndrome. Treatment consists of orthopedic and surgical intervention to minimize deformities and for cosmetic purpose. Careful surveillance for malignant degeneration of both skeletal and non-skeletal tumors, especially in the brain and abdomen, is essential.

Laparoscopy-assisted D2 radical distal gastrectomy for gastric cancer (Billroth Ⅱ anastomosis)

Laparoscopic radical gastrectomy has been increasingly applied in China. However, how to reduce surgery-related trauma, shorten operative time and achieve the long-term prognosis equal to the conventional open surgery is still hot research topics. Along with the change in learning curve and the optimization of endoscopic techniques, laparoscopic lymph node dissection can achieve or even exceed the extent that can be achieved in open surgery. Therefore, it has gradually replaced the conventional digestive tract reconstruction using an auxiliary incision. By completing the laparoscopic digestive tract reconstruction with EndoGIA, we describe the laparoscopy-assisted D2 radical distal gastrectomy for gastric cancer （Billroth Ⅱ anastomosis）.

Primary small cell carcinoma of kidney after renal transplantation:a case report and literature review

Extrapulmonary small cell carcinoma （EPSCC） is a rare neoplasm comprising 2.5％ to 5％ of small cell carcinomas （SCCs）.Bladder SCC is the most common site of genitourinary tract.Primary renal SCC is extremely rare.We report a case of primary SCC of the kidney which is rarely reported in the urinary tract and presents an aggressive clinical picture.A 59-year-old female visited a urologic clinic with complaint of persistent left flank soreness 10 years after undergoing renal transplantation.Abdominal computed tomography showed a left renal pelvis tumor.After the patient received left nephroureterectomy with bladder cuff resection,her pathology results showed SCC.After surgery,she received adjuvant systemic chemotherapy,and her recovery has been uneventful as of 8 months.Primary renal SCC presents with an advanced tumor stage and a short median survival period,therefore early intervention and close follow-up are recommended.

CPT-11 Chemotherapy Rescued A Patient with Atypical Sclerosing Epithelioid Fibrosarcoma from Emergent Condition

Sclerosing epithelioid fibrosarcoma （SEF） is a rare and poorly defined variant of fibrosarcoma, but generally insensitive to chemotherapy and progresses with poor prognosis. We report the marvelous effect of irinotecan hydrochloride （CPT-11） chemotherapy in rescuing a patient with atypical SEF from emergent condition, who underwent recurrences after several treatment methods. Small dose of CPT-11 was administered to the patient, with which, the size of superficial mass （cervical lymph node） gradually decreased observed by the naked eyes in 5 days. X-ray and CT image proved a marked reduction in the size of the tumor. CPT-11 is valuable for the treatment of this aggressive sarcoma. In condition of emergency caused by sarcoma oppression, administering a tolerable small dose of topoisomerase I-inhibiting drug could be a beneficial choice.

Vascular Invasion as An Independent Prognostic Indicator in Radically Resected Non-small Cell Lung Cancer

Objective： A retrospective study was performed to analyze the impact of vascular invasion on prognosis in a series of radically resected non-small cell lung cancer （NSCLC） and the subgroup of T1-4 nodal negative NSCLC patients. Methods： A total of 259 NSCLC patients who had undergone radical resection were entered into this study. Detailed clinical data including five-year survival were obtained for all the patients. The tumors were reviewed for the presence or absence of vascular invasion. Fisher＇s exact tests were used to assess the relationship between vascular invasion and other clinicopathological variables. Survival time was defined as the interval from the date of operation to either death from lung cancer or the last follow-up. Univariate analysis of survival curve was performed by the Kaplan-Meier method using the Log rank test. Multivariate survival analysis was carried out by Cox regression. P〈0.05 was considered statistically significant. Results： In 259 patients, 33 cases were diagnosed as having vascular invasion. The overall 5-year survival was 37.5%. Patients with vascular invasion had a median survival of 20 months compared with 43 months for those without vascular invasion （P〈0.01）. Multivariate analysis indicated that vascular invasion was a significant independent prognostic predictor for shortened cancer-related survival in the patients. The relative risk for cancer-related survival was 2.2-fold greater in patients with vascular invasion （95% CI： 1.45-3.32）. Subgroup analysis revealed that patients with vascular invasion had a 5-year survival of 11.1% compared with 57.1% for those without vascular invasion in the resected lung cancer patients at T1-4N0M0 （P=0.002）. Conclusion： Vascular invasion can serve as an independent prognostic factor in radically resected NSCLC.

Over-expression of EGFR in Breast Cancer

Objective： To explore the relationship of overexpression of epidermal growth factor receptor （EGFR） in occurrence, development and treatment of breast cancer. Methods： Samples of 46 breast adenoma tissues and 86 breast cancer tissues were regularly dehydrate-fixed, embedded in paraffin, sliced in to 5μm thick, stained with SABC immunohistochemistry and coloured with DAB. Results： The positive staining of EGFR was shown as brown- yellow and distributed in cytoplasm. The positive rates in the tissues of breast adenosis and breast cancer were 17.04% （6/46） and 56.98% （49/86） respectively. The positive rates of EGFR in the tissue of invasive ductal carcinoma was 64.49% （41/59）, which was significantly higher than that in in situ carcinoma （P〈0.05）. The positive rate of lymph metastasis group was higher than that in non-lymph metastasis group （P〈0.05）. Conclusion： The overexpression of EGFR was related with occurrence, lymph metastasis and pathologic types of breast cancer. The examination of EGFR in the breast cancer can serve as a guidance for target chemotherapy.

Effect of Celecoxib on Apoptosis of Endometrial Carcinoma Cell

Objective： To investigate the effect of Celecoxib on proliferation and apoptosis of the endometrial carcinoma cell HEC-1B and the effect on the expression of Fas and Survivin mRNA. Methods： The inhibition on the growth of human endometrial carcinoma cell HEC-1B was investigated by cell culture and MTT experiment when treated with different concentrations of Celecoxib. The cell apoptosis was detected by flow cytometry and DNA Ladder Electrophoresis. The change of the expression of Fas and Survivin mRNA after the treatment of Celecoxib was detected With RT-PCR. Results： Celecoxib could effectively inhibit the growth of HEC-1B cells and induce apoptosis. Survivin mRNA expression was decreased and Fas mRNA expression was increased after treating with Celecoxib. Conclusion： Celecoxib could inhibit HEC-1B cell proliferation and induce its apoptosis.

Relationship between ERCC2 Polymorphism and Risk of Lung Cancer in Chinese Nonsmoker

Objective： Excision repair cross-complimentary group 2 （ERCC2） is one of the important DNA repair genes. ERCC2 codon 751 polymorphism has been shown to modulate cancer risk. We therefore assessed the relationship between the ERCC2 polymorphism and the susceptibility to lung cancer in nonsmoking females via a hospital-based case-control study. Methods： There were 105 lung cancer cases and matched healthy controls in this study. Information concerning demographic and risk factors was obtained, each person donated 2 ml blood for biomarker testing. ERCC2 genotypes were determined by PCR-RFLP method. All of the statistical analyses were performed with SPSS （v 12.0）. Results： All of the subjects in this study were nonsmoking females in Shenyang. There was significant difference between the frequencies of ERCC2 polymorphism in cancer cases and controls （P〈0.05）. The frequencies of ERCC2 751 Gin allele were 6.2% in controls and 13.8% in cancer cases. The individuals with Lys/Gln＋Gln/Gln combined genotype were at an increased risk for lung cancer as compared with those carrying the Lys/Lys genotype （adjusted OR=2.80, 95%=CI 1.21-6.48）. We analyzed the environmental risk factors for lung cancer in nonsmoking females. The cancer patients showed a higher prevalence of exposure to cooking fumes compared with controls （OR=2.44, P〈0.05）. Furthermore, an interaction between exposure to cooking fumes and the variant ERCC2 751 Gin allele on the risk of lung cancer was observed. Individuals with both risk genotype and exposure to cooking fumes had a higher risk of cancer than those with only one of them. Conclusion： The above findings indicate that the genetic polymorphism in the ERCC2 codon 751 is associated with the risk of lung cancer in nonsmoking females.

ADENOVIRUS-MEDIATED EXPRESSION OF PEX, A NONCATALYTIC FRAGMENT OF MATRIX METALLOPROTEINASE-2, AND IT’S INHIBITION ON ANGIOGENESIS AND TUMOR GROWTH

Objective： To develop an adenovirus system to deliver biologically active peptides or proteins such as angiogenesis inhibitors in vivo for the treatment of cancer. Methods： DNA recombination techniques were employed to construct adenovirus shuttle vector, in which angiogenesis inhibitor was put downstream of rat growth hormone signal peptide, and the C-terminal was the myc-epitope 10-amino-acid peptide for the following up of the protein. Adenovirus was made using the bacteria recombination method. We tested this system using an angiogenesis inhibitor chick MMP-2 C-terminal hemopexin-like fragment （PEX） in Sarcoma 180 （S-180） bearing Kunming mice. The anti-angiogenie effect was performed by chick chorioallantoic membrane assay. Results： PEX was readily secreted outside human stomach carcinoma BGC823 cells as demonstrated by immunofluorcscent staining and western blot infected by adenovirus with rat growth hormone signal peptide （E-T-rGH-PEX）. However, without signal pcptide （E-T-PEX）, PEX was expressed and localized in the cytoplasm of the infected cells, and formed large aggregates, which suggested that PEX was insoluble. The adenovirus E-T-rGH-PEX could inhibit angiogenesis, while E-T-rGH-PEX not. The adenoviruses of E-T-rGH-PEX inhibited the growth of S-180 tumor significantly compared with the empty virus control group E-T （P=0.026） and without signal peptide group E-T-PEX （P=0.006） respectively, while E-T-PEX had little effect. Conelusion： These results suggest that this adenoviral system is likely to be used in the gene therapy of cancer to deliver angiogenesis inhibitors.