Ai zheng = Aizheng = Chinese journal of cancer最新文献

Background and objective: LRP16 is a human novel gene linked to leukemia identified recently. However, its biological function is not fully clarified so far. This study was to investigate the biological function of human LRP16 gene by database-aided bioinformatics analysis.

Methods: The structures and functions of LRP16 gene promoter and its coding protein were analyzed using bioinformatics prediction, and further experimental testing was performed. The recombinants of pGL3-basic and LRP16 promoter subclones were constructed for luciferase activity analysis. The recombinant of LRP16 open reading frame coding sequence and pcDNA3.1 eukaryotic expression vector was established and transfected into HL-60 and K562 cell lines. DNA damage of HL-60 cells after ultraviolet irradiation was evaluated using single cell gel electrophoresis. Cell cycle of K562 cells was analyzed by flow cytometry.

Results: LRP16 promoter was a typical class II eukaryotic promoter and its core regulation sequence was located within upstream -600 bp of transcriptional start site. In addition, seven cis-acting elements, which may be implicated in cell cycle, hematopoiesis regulation, cell proliferation and repair of DNA damage, were identified. Long type LRP16 coding protein contained homologous sequences of hismacro, COG2110, and A1pp with human histone H2A1C between 148 and 315 amino acid residue. The number of comet cells and the length of comet tail in HL-60 cells irradiated were significantly decreased and the number of living cell was significantly increased in LRP16-overexpression group compared with empty plasmid control group. The proliferation rate and ratio or quantity of G2/M and S phases were significantly increased in LRP16-overexpression K562 group compared with empty plasmid control group. LRP16-overexpression in K562 cells promoted the transition of G1 to S phase and plateau phase of cell proliferation was advanced.

Conclusions: Promoter regulation prediction and protein domain analysis based on bioinformatics contribute to the study of gene function. LRP16 may play an important role in leukemia progression by promoting cell proliferation, regulating cell cycle, and antagonizing radiation-induced DNA damage.

As a highly conserved nuclear protein, death domain-associated protein(Daxx) plays an important role in transcriptional control, carcinogenesis, resistance to virus infection, and so on. Daxx can be localized in promyleocytic leukaemia protein oncogenic domains, nucleoplasm, nucleolus, cytoplasm, and heterochromatin. The subcellular localization of Daxx can be changed by modification or interacting with other proteins. Under cellular stress, Daxx can interact with many kinds of molecules, and thus affect its downstream signaling pathway. The purpose of this review was to discuss Daxx's subcellular localization in different conditions and its translocation between subcellular compartments.

Background and objective: Even though most breast cancers occur in postmenopausal women in western countries, age <35 is one of the prognostic factors. This study was to compare the clinicopathologic characteristics and prognosis between premenopausal breast cancer patients aged of <35 and > or =35 in south China, and to explore the prognostic factors.

Methods: A total of 905 consecutive premenopausal patients were evaluated, with first diagnosis of breast cancer referred to surgery at the Sun Yat-sen University Cancer Center from October 2003 to December 2006. The clinicopathologic factors and the survival rates between the very young group(aged of <35 at diagnosis) and the non-young group(aged of > or =35 at diagnosis) were retrospectively compared.

Results: The overall median follow-up time was 27.77 months. The 3-year disease-free survival rate was significantly lower (78.0% vs. 89.1%, P<0.001) and the 3-year survival rate relatively lower(94.3% vs. 96.8%, P=0.10) in the very young group than in the non-young group. In addition, the 3-year survival and disease-free survival rates were significantly lower in the very young group with HR (hormone receptor)-positive than in the non-young group (P<0.05). The univariate and multivariate analysis of clinicopathologic characteristics between two groups showed that age <35 at diagnosis, axillary lymph node involvement, presence of vascular invasion, and high expression of Ki67 were risk factors for recurrence.

Conclusion: Compared with non-young premenopausal patients, very young breast patients with HR-positive cancer have a worse outcome.

Epimutations are errors in the normal process of epigenetic regulation which can result in aberrant transcriptional silencing of a normally active gene or reactivation of a normally silent gene. Epimutations are generally considered to be somatic events and to be confined in affected tissues. However, recent studies of patients with hereditary nonpolyposis colorectal cancer (HNPCC) have showed that allele-specific hypermethylation of CpG islands in the promoter region of the MLH1 gene, one of the causes of the tumor, existed in all the tissues examined. In addition, germ-line epimutations of other tumor suppressor genes (TSGs), such as MSH2 and BRCA1, have also been reported, demonstrating that epimutations might arise in the germ-line (during gametogenesis or early embryonic development). The role of germ-line epimutations might be as important as germ-line mutations in human disease. We reviewed the update on germ-line epimutations of TSGs including the possible mechanisms underlying germ-line epimutations, the possibility of transgenerational inheritance, and their impact on our understanding of human disease.

Background and objective: The gene polymorphism is used to predict the sensitivity of chemotherapy, which is significant for the individualized treatment of tumor. This study was to explore the correlation of codon 194 and codon 399 polymorphisms of DNA repair gene X-ray repair cross complementing (XRCC1) with the sensitivity of non-small cell lung cancer (NSCLC) to NP (vinorebine and cisplatin) chemotherapy.

Methods: XRCC1 polymorphisms at codon 194 and codon 399 were detected in 164 patients with NSCLC using polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP). The haplotype of XRCC1 gene was analyzed using SHEsis analysis software. Patients treated with NP chemotherapy were evaluated after two periods of treatment, then the correlation of the sensitivity of chemotherapy with polymorphisms was analyzed.

Results: The patients with the XRCC1 codon 194 C/T+T/T polymorphisms were 2.038 times as sensitive to the chemotherapy as the patients with C/C genotype (P=0.036, 95% CI:1.044-3.976). The effective rate to chemotherapy was no significant difference between the patients with XRCC1 codon 399 G/G, A/G, and A/A polymorhism. The effective rate of chemotherapy of the patients with T-A haplotype significantly increased compared with those with other haplotype (P=0.031), while that of the patients with C-A haplotype significantly decreased compared with others(P=0.035).

Conclusions: The sensitivity to NP chemotherapy significantly increased in the NSCLC patients with XRCC1 194 CT and TT genotypes compared with those with CC genotype. XRCC1 codon 194 and codon 399 polymorphisms may be used to predict the sensitivity of NSCLC to NP chemotherapy.

Background and objective: Ewing's sarcoma family of tumor (ESFT) is aggressive. The optimal therapy modality for ESFT is still to be found. This study was to explore the clinical characteristics and therapy for ESFT.

Methods: Ninety-two cases of ESFT were collected from January 1995 to April 2008 in Sun Yat-sen University Cancer Center and analyzed retrospectively.

Result: Of 92 cases, 23 were Ewing's sarcoma of bone, 21 extraosseous Ewing's sarcoma, 43 peripheral primitive neuroectodermal tumor, and 5 Askin tumor. Median follow-up time was 31.5 months (range, 10-137 months). Thirty-eight patients received multidisciplinary therapy and 19 single model therapy in non-metastasis group. Three-year overall survival (OS) and event-free survival (EFS) were significantly different between non-metastatic multidisciplinary therapy group and non-metastatic single model group (63% vs. 20%, 46% vs. 18%, respectively, P<0.001). The patients who received surgery plus chemotherapy and plus radiation or not had longer survival than those treated with chemotherapy plus radiation in non-metastatic multidisciplinary therapy group (Chi2=7.591, 9.212; P=0.006, 0.002). CAV/IE alternative regimen was superior to other regimens in event-free survival, but not in overall survival (Chi2=6.950, 3.530; P=0.008, 0.06). Cox regression analysis suggested therapy model and response to treatment were independent prognostic factors for ESFT.

Conclusions: Our studying showed multidisciplinary therapy could significantly improve non-metastatic ESFT patients' survival. Chemotherapy plus surgery and plus radiation or not were superior to chemotherapy plus radiation in local control for the non-metastatic ESFT. Therapy model and response were independent prognostic factors.

Background and objective: For squamous cell carcinoma of the middle thoracic esophagus, surgical resection of left or right transthoracic approach has its advantages and disadvantages, respectively. This study was to compare the outcomes between the two approaches.

Methods: A total of 482 consecutive patients with middle thoracic esophageal squamous cell carcinoma (ESCC) underwent transthoracic esophagectomy between January 1999 and June 2005. These patients were divided into left transthoracic approach group (n=350) and right transthoracic approach group (n=132). Surgical resection rate, postoperative complications, lymphadenectomy, recurrence pattern, disease-free survival, and overall survival of the two groups were compared retrospectively.

Results: The surgical resection rate was 92.0% in left approach group and 92.4% in right approach group (P=0.878). The incidence of postoperative complications was higher in right approach group than in left approach group (57.6% vs. 35.4%, P<0.001). The average number of lymph nodes resected was 11.8+/-6.6 in left approach group and 16.3+/-8.0 in right approach group (P<0.001). Lymphatic recurrence rate was lower in right approach group than in left approach group (51.1% vs. 69.6%,P=0.028), especially occurring to mediastinal lymph nodes (15.6% vs. 38.4%,P=0.005). Three-year disease-free survival was higher in right approach group than in left approach group(22.92+/-0.74 vs. 25.09+/-1.22, P=0.039).

Conclusion: Although left transthoracic resection reduced the incidence of postoperative complications, esophagectomy of right transthoracic approach was more effective in survival improvement.

Background and objective: Telomerase transcriptional elements-interacting factor (TEIF) gene found recently by our research group is a transcription factor of a kind of human telomerase reverse transcriptase (hTERT) gene, and expresses in many kinds of tumor tissues. This study was to evaluate the expression of TEIF protein in human colorectal tumors and to explore its correlation with centrosome abnormality.

Methods: The expression of TEIF in 10 specimens of normal intestinal mucosa tissue, 30 specimens of colorectal cancer, and 54 specimens of colorectal adenoma was detected by immunohistochemistry. The expression of gamma-tubulin was detected by immunofluorescence.

Results: Immunohistochemistry results showed that the differences of TEIF protein expression between the normal group and each tumor groups were statistically significant (P<0.01), and the difference of TEIF protein expression between the malignant tumor group and the benign group was not significant (P>0.05). TEIF strong positive rate (> or =++) was significantly higher in the carcinoma group than in the adenoma group or normal group (all P<0.001); the differences of TEIF strong positive rate between Grade I adenoma and Grade II or III adenoma were statistically significant (P<0.05), and the difference of TEIF strong positive rate between Grade II adenoma and Grade III adenoma was not statistically significant (P>0.05). Immunofluorescence results showed that centrosome amplification-positive rate was significantly higher in the colorectal cancer group than in the normal group or the adenoma group (both P<0.01); the difference of the centrosome amplification positive rate between Grade I adenoma and Grade III adenoma was statistically significant (P<0.05), and the differences of the centrosome amplification positive rate between Grade II adenoma and Grade I or III adenoma were statistically significant (P>0.05).

Conclusions: TEIF protein and centrosome amplification is commonly found in colorectal tumors. The expression level of TEIF is related to tumor histological grade and malignant degree. TEIF protein expression and centrosome amplification showed a high degree of positive correlation.

Background and objective: Metastatic alveolar soft tissue sarcoma (ASTS) of the central nervous system is rare and is easy to be misdiagnosed as other primary tumors of central nervous system. This study was to analyze the clinical and pathological features of four patients with ASTS of the central nervous system and to clarify their differential diagnosis as well as prognosis.

Methods: HE slices and clinical data of the four cases were reviewed and immunohistochemical staining was performed. Antibodies included Vimentin, Myosin, Myoglobin, S-100, Actin, Desmin, CgA, Syn, NSE, and CK.

Results: All four patients had a skin nodule of the extremities removed previously. Clinical symptoms included headache and sight blurring. The metastatic lesions were located in the posterior cranial fossa, closely associated with the meninges. The tumor cells had clear or eosinophilic cytoplasm and prominent nucleoli, arranged in alveolar structures, which were surrounded by delicate blood sinuses. The immunohistochemical staining results showed that the positive stainings of Actin, Desmin and S-100 were in 2 cases; the weakly positive stainings of NSE and Vimentin were in 1 case; the positive staining of PAS was in all four cases. The follow-up data showed that one case died during one year after surgery, two cases died during three years. The fourth case had half year after operation and had been alive without tumour.

Conclusion: ASTS of the central nervous system was mostly metastatic and should be differentiated from other CNS tumors such as meningioma, melonocytic tumor, rhabdomyosarcoma and paraganglioma. Metastatic ASTS of the central nervous system had poor prognosis and the five-year survival rate was low.