Objective:To investigate the expressions and their clinical significance of vascular endothelial growth factor (VEGF) and extracellular matrix (ECM) components in non-small cell lung cancer (NSCLC). Methods:Expressions of VEGF and ECM components (fibronectin, FN and collagen Ⅳ, cⅣ) in 50 cases of NSCLC tissues and 20 cases of normal lung tissues were detected by immunohistological analysis. Their relationship with clinical features of NSCLC and the correlation of expression of VEGF and Fn and cⅣ were analyzed.Results:The positive expression rates of VEGF, Fn, and cⅣ were 96%, 78%, and 50% in NSCLC tissues. The expressions of VEGF and Fn were significantly higher than those in normal lung tissues (P<0.05). The expression of Fn and over-expression of VEGF were associated with lymph node metastasis (r=1.00, P<0.001). The survival rate of patients with over-expression of VEGF was greatly lower than that with weak expression of VEGF (P=0.022). The survival rate of Fn-negative patients was markedly higher than that of Fn-positive patients (P=0.046). Conclusion:VEGF and ECM component Fn were highly expressed in NSCLC, which correlated with lymph node metastasis and survival rate. Expression of ECM and VEGF had positive correlations, suggesting that ECM might be one of the anti-angiogenesis targets for tumor therapy.

Objective:To study the alteration of K-ras mutations in different stages of colorectal cancer(CRC) and its influence on the progression of CRC. Methods:The 20 paraffin-embedded tissues, including primary foci, metastatic lymph nodes, remoter metastatic foci, colorectal adenoma, and normal colorectal tissues, were collected from 20 patients with colorectal cancer. The sequence of PCR-amplified products were analyzed. Results:The wild K-ras gene was expressed in normal colorectal tissues. The mutation frequency of K-ras gene was 20.0% (4/20) in colorectal adenoma, 30.0% (6/20) in primary foci, 25.0% (5/20) in metastatic lymph nodes, and 30% (6/20) in remote metastatic lesions. In the samples with K-ras mutations, the consistency of the types of K-ras mutations between primary foci and colorectal carcinoma, lymph node metastatic lesions, remote metastatic lesions was 0.0%(0/4), 40.0%(2/5), and 50.0%(3/6), respectively.Conclusion:The colorectal adenoma, metastatic lymph nodes and remote metastatic lesions were not suited for K-ras analysis as routine samples in clinical practice. If the samples of primary lesions were not available, the detection results of metastatic lymph nodes and remote metastatic remote lesions will provide some reference values. K-ras gene had several different mutations in the progression of CRC.

Objective:The protein of missing in metastasis (MIM), a novel discovered actin-binding scaffold protein, is involved in actin cytoskeleton rearrangements, signal transduction and transcriptional activation, and has close association with tumor growth, invasion, and metastasis. Recently, much focus has been placed on the role of MIM performed in tumor progression. In recent years, more and more attention is focused on its action mechanism in various kinds of tumors, which has a wide foreground of investigation. In this paper, we make a comprehensive review of the association of MIM with cancer development, in order to provide the theoretical basis and new strategies for application of MIM proteins in cancer diagnosis and treatment.

Objective:The efficacy and toxicity of anticancer drugs differ in different tumor patients. It could not meet the requirements of optimization of tumor treatment if only under the guidance of clinical and pathologic characteristics. More and more attention is focused on individualized therapy based on individual gene profiles. It has been identified that gene polymorphisms are responsible for different outcomes of individuals. Gene polymorphisms, including sequence polymorphism and single nucleotide polymorphism, will decrease the clinical efficacy of chemotherapeutic drugs or increase adverse reactions by influencing the expression or activity of the corresponding proteins. In recent years several gene polymorphisms related to drug metabolism, transportation, or inactivation may affect the outcomes of chemotherapy and the frequency of adverse reactions. Identification of the polymorphism genes is important for individual therapy for tumor patients.

Objective:Tumor suppressor gene nitrogen permease regulator like 2 (NPRL2), also called tumor suppressor candidate gene 4 (TUSC4), widely exists in all kinds of human tissues and is highly conserved in different kinds of biological species. The expression of NPRL2 is markedly decreased in many human tumor tissues, such as lung cancer, breast cancer,renal carcinoma, et al. NPRL2 is located in human chromosome 3p2.13, and participates in DNA mismatch modification, regulation of signal transduction du-ring cell cycle progression, and apoptosis induction. NPRL2 gene inactivation is related with the initiation and progression of several malignant tumors. The mechanism underlying the tumor-inhibiting activity of NPRL2 gene is not clear and needs to be further investigated.

Objective:To observe the efficacy, median progression-free survival (PFS) and adverse reaction induced by rh-endostatin injection (Endostar) plus platin-based chemotherapy for advanced non-small cell lung cancer (NSCLC).Methods:Fifty five histologically or cytologically confirmed advanced NSCLC patients received Endostar combined with platin-based chemotherapy for more than 2 cycles. The evaluated parameters included PFS, response rate (RR), clinical benefit rate (CBR) and adverse reaction. Results:Of the 51 patients who can be evaluated for response, 15 (29.4%) achieved partial response (PR), 27 (52.9%) had stable disease (SD), 9 (17.6%) had progressive disease(PD), no patient had complete response(CR). The overall RR was 29.4% (15/51) and CBR was 82.4% (42/51). The median PFS was 6.3 months. There were no significant differences in the short-term efficacy and PFS between the patients who had different pathological features (P=0.037), those had naive or relapsed diseases (P=0.101), or those received different chemotherapeutic regimens (P=0.232). The total white cells and platelets decreased by 72.7% and 54.5%, respectively. The frequency of grade Ⅲ or Ⅳ neutropenia and thrombocytopenia were 36.4% (20 caces) and 21.8% (12 cases), respectively. Four patients stopped the therapy for adverse reaction. One died of gastrointestinal hemorrhage; one had uncontrolled grade Ⅲ hypertension; one had superventricular arrhythmia; one had grade Ⅳ hepatic dysfunction. Conclusion:The combination of Endostar and platin-based chemotherapy increased the CBR and prolonged the PFS of the patients with advanced NSCLC. The toxicities were tolerable.

Objective:To evaluate the clinical value of percutaneous transhepatic cholangial drainage (PTCD) and percutaneous transhepatic cholangial stent(PTCS)implantation therapy for malignant biliary obstruction in the elderly patients.Methods:Fifty three patients over 60 years-old were treated with PTCS implantation (n=35),PTCD for internal-external drainage(n=11),or single external drainage(n=7). The imaging examination was performed for all the patients one week after surgery. The serum levels of total bilirubin (TBIL) and alanine aminotransferase (ALT) were detected before and after surgery.Rusults:Metallic stents were successfully implanted in 32 patients during the surgery, and 3 patients were implanted 5 to 7 days later after PTCS. Both total serum levels of TBIL and ALT were significantly decreased at one week after surgery (P<0.05). The mean survival periods were 11.5 months for stent implantation patients and 5.5 months for PTCD patients. Conclusion:PTCD and PTCS are easy to perform and safe and effective in the treatment of malignant biliary obstruction of elderly patients.

Objective:To make a prospective study on the effectiveness and safety of toremifene (TOR) combined with novelbine/cisplatin (NP) in the treatment of patients with advanced non-small cell lung cancer (NSCLC) whose first line platinum-based chemotherapy was failure. Methods:Forty-four patients with stage ⅡB-Ⅳ NSCLC, who failed in the first line cisplatin-based chemotherapy from January 2004 to February 2006, were enrolled in this study. All the patients received TOR combined with NP second line chemotherapy for two cycles. The response rate and adverse reaction were evaluated. The survival rate was analyzed.Results:The 44 patients received average 1.8 cycles of chemotherapy (1-3 cycles). The response of 37 patients could be evaluated including 21 patients who received NP regimen before and 16 patients who received platinum-based chemotherapy. After second line therapy, 4 of the 37 patients had partial response (PR), 19 had stable disease (SD), 14 had progressive disease (PD), and no patient had complete response (CR). The total response rate (CR+PR) was 10.8% (4/37). The disease-controlling rate (CR+PR+SD) was 62.2% (23/37). The response rate and disease-controlling rate of squamous cell lung cancer (SCC) were 27.3% (3/12) and 72.7% (8/12), which were significantly higher than adenocarcinoma [0% (0/18) and 44.4% (8/18), P<0.05]. The median survival time was 8.2 months, the median time for SD was 4.0 months (1.0-10.2 months), and the 1-year survival rate was 24.4%. The median survival time and 1-year survival rate of SCC patients had no significant difference compared with adenocarcinoma patients (9.2 vs 7.1 months; 33.3% vs 27.7%, P＝0.72). There was no significant difference in survival rate between male and female patients. One patient stopped therapy for liver function injury (hyperbilirubinemia). The adverse reactions induced by chemotherapy mainly included gastrointestinal reaction, bone marrow suppression, and liver function injury. No serious adverse reaction occurred. Conclusion:The clinical efficacy of second line TOR combined with NP regimen is similar with the first line regimen for NSCLC patients, especially for SCC patients. The frequency of adverse reaction is not increased.

Objective:To compare the difference between 20 cases of subcutaneous panniculitis-like T-cell lymphoma (SPTL) and 19 cases of cutaneous extra-nodal nasal-type NK/T-cell lymphoma (cutaneous NK/T-cell lymphoma). Methods:The two types of lymphoma were compared in clinical pathology, immunological marker, Epstein-Barr (EB) virus infection, and T-cell receptor (TCR) gene rearrangement. Results:Differentiated diagnosis of the two types of lymphomas was not easy based on their clinical manifestations,but the cutaneous NK/T-cell lymphoma was always followed by extracutaneous dissemination and had a poor prognosis. Histopathologically, SPTL was usually limited in subcutaneous fatty tissues while the cutaneous NK/T-cell lymphoma showed diffused infiltration around the dermis and it often infiltrated into the subcutaneous fat tissues. Coagulation necrosis, angiocentric infiltration and epidermotropism were often observed in cutaneous NK/T-cell lymphoma. When compared with immunophenotypes, SPTL often expressed βF1, membrane CD3 and CD8 but did not express CD4 and CD56, while most of the cutaneous NK/T-cell lymphomas expressed CD56 and cytoplasm CD3ε and only a few cases expressed CD3 and CD8. The differences in the expression of CD56, CD3, CD8, and βF1 were significant between the two types of lymphomas(P<0.05). The positive rate of EBER1/2 was 25% (5/20) in SPTL while it was 100% in cutaneous NK/T-cell lymphoma. The difference was statistically significant (P<0.05). Monoclonal TCR-γ gene rearrangement was found in 16 out of 20 cases of SPTL (80%) but only in 4 of 18 cases in the cutaneous NK/T-cell lymphoma (22.2%). The difference was significant(P<0.05). Conclusion:The key points to distinguish the two lymphomas are (1) extracutaneous dissemination, coagulation necrosis, angiocentric infiltration and epidermotropism; (2) the expressions of CD56, CD3, CD3ε, CD8, and βF1; (3) the positivity of in situ hybridization of EB virus; (4) detection of the monoclonal TCR-γ gene rearrangement. To make an acute differentiated diagnosis of the two lymphomas, comprehensive analysis is necessary to integrate the results of clinical manifestation, histopathology, immunophenotype, infection of EB virus and gene rearrangement.

Objective:To screen the early biomarkers associated with lung carcinoma by using proteomic method. Methods:The proteins of early lung squamous cell carcinoma tissues and adjacent normal tissues were separated by two-dimensional gel electrophoresis (2-DE) and differentially expressed proteins were screened by mass spectrometry (MS). The differential expressions of part proteins were verified by immunohistochemical method. Results:The proteomic profiles of lung squamous cell carcinoma and the adjacent normal tissues were established and the average matched protein spots in the two group were 626 and 602, respectively. Ten protein spots with higher expression in lung squamous cell carcinoma tissues were identified as Annexin 1(Anx-A1),heat shock proteins (HSP27), etc. The proteins were mainly related with cell cycle and signal transduction. The results of immunohistochemistry showed that the positive expression rates of Anx-A1 and HSP27 in lung squamous cell carcinoma tissues were significantly increased (P<0.05). Conclusion:Proteomic technology was an effective method for preliminary identification of the proteins associated with early lung carcinoma. The identified proteins laid a solid foundation for further screening the molecular markers for early diagnosis and treatment of lung cancer.