[Show abstract][Hide abstract] ABSTRACT: Background:
Hypoxia-inducible factor 1α (HIF-1α) plays an important role in regulating cell survival and angiogenesis, which are critical for tumor growth and metastasis. Genetic variations of HIF1A have been shown to influence the susceptibility to many kinds of human tumors. Increased expression of HIF-1α has also been demonstrated to be involved in tumor progression. However, the prognostic value of single nucleotide polymorphisms (SNPs) in the HIF1A gene remains to be determined in most cancer types, including colorectal cancer (CRC). In this study, we sought to investigate the predictive role of HIF1A SNPs in prognosis of CRC patients and efficacy of chemotherapy.
Materials and methods:
We genotyped two functional SNPs in HIF1A gene using the Sequenom iPLEX genotyping system and then assessed their associations with clinicopathological parameters and clinical outcomes of 697 CRC patients receiving radical surgery using Cox logistic regression model and Kaplan Meier curves.
Generally, no significant association was found between these 2 SNPs and clinical outcomes of CRC. In stratified analysis of subgroup without adjuvant chemotherapy, patients carrying CT/TT genotypes of rs2057482 exhibited a borderline significant association with better overall survival when compared with those carrying CC genotype [Hazard ratio (HR), 0.47; 95% confidence interval (95% CI): 0.29-0.76; P < 0.01]. Moreover, significant protective effects on CRC outcomes conferred by adjuvant chemotherapy were exclusively observed in patients carrying CC genotype of rs2057482 and in those carrying AC/CC genotype of rs2301113.
Genetic variations in HIF1A gene may modulate the efficacy of adjuvant chemotherapy after surgery in CRC patients.
Full-text · Article · Jun 2014 · Asian Pacific journal of cancer prevention: APJCP
[Show abstract][Hide abstract] ABSTRACT: Primary inflammatory myofibroblastic tumor (IMT) of the breast is extremely rare; only 19 cases have been reported in the English literature. In the present study, we present a case of IMT in a 56-year-old female patient who was admitted to our hospital due to a mass found in her right breast. Mammogram and ultrasound revealed a well-circumscribed mass and surgery was performed. Histopathologically, the lesion was composed of spindle and inflammatory cells, including plasma cells and lymphocytes. Mitotic figures were not observed. Immunohistochemically, the tumor cells were positive for SM-actin, anaplastic lymphoma kinase (ALK) and vimentin and focal positive for desmin, but negative for NSE, S-100, CD117, CD34, NF, CD21, CD35 and CD68. Thus, we made a diagnosis of IMT and advised regular follow-up. However, the patient had local recurrence and metastasis to the left groin area 3, 7 and 10 months after the initial surgery. Notably, the histopathological characteristics of the recurrent and metastatic foci were similar to those of the initial specimen, but mitotic figures were clearly observed. Thus, we conclude that IMT shows occasionally malignant biological behavior although it is a neoplasm of intermediate biological potential that frequently recurs and rarely metastasizes. We advise that clinical physicians should regularly follow up patients after focal resection for IMT.
No preview · Article · Jan 2013 · Oncology letters
[Show abstract][Hide abstract] ABSTRACT: In the female population in Asia, systematic investigation concerning alterations in cancer-related genes in breast carcinoma is rare, and the correlation among oncogene or suppressor gene expression with tumor cell apoptosis, cell cycle regulation and tumor cell autophagy remains to be clarified. In this study, a tissue microarray consisting of 360 individual samples from three different breast tissues was generated. By comparing the expression of the tumor-suppressor genes (BRCA1, BECN1, CCND1, PTEN and UVRAG) in ductal breast cancer and normal breast tissues, respectively, we were able to assign changes in the expression of these mRNAs to specific stages and allocate them to define the roles in the multi‑step process of breast carcinogenesis. Tumor-suppressor genes, such as BRCA1 and BECN1, usually had lower signals in the carcinomatous tissues (10.2 and 6.6%) compared to the normal tissues (31 and 32.6%), while stronger positive dots (positive cells >30%) usually existed in the normal tissues. The patients in the oldest age group had the lowest expression rate. Only BECN1 and CCND1 expression showed a significant association with patient age (p=0.030 and p=0.003). A significant association was observed between BRCA1 and BECN1 expression and tumor size (p=0.028 and p=0.021). BECN1 gene expression was positively correlated with UVRAG and PTEN expression (p=0.006 and p=0.000). CCND1 was negatively correlated with PTEN, BECN1 and BRCA1 expression (p=0.011, p=0.000 and p=0.000). Abnormal expression of BRCA1, BECN1, CCND1, PTEN and UVRAG may play a role in human breast carcinogenesis through dysregulated mRNA expression. Overexpressed CCND1 may shorten the G1 phase of the cell cycle, suppress cell apoptosis and contribute to the formation of invasive ductal carcinoma (IDC).
Preview · Article · Feb 2012 · Molecular Medicine Reports
[Show abstract][Hide abstract] ABSTRACT: Erdheim-Chester disease (ECD) is a rare non-Langerhans form of histiocytosis characterized by xanthomatous tissue infiltration with foamy histiocytes. It is still controversial whether these histiocytic proliferations represent monoclonal neoplastic populations or are part of a polyclonal reactive process. This is a case report of ECD in a 76-year-old Chinese woman. We investigated the clinicopathological features and clonality of the histiocytes using laser microdissection and a clonality assay based on X-chromosomal inactivation mosaicism in female somatic tissues, as well as on the polymorphism of phosphoglycerate kinase (PGK) and androgen receptor (AR). According to our results, the lesion was composed of lipid-laden histiocytes and focal fibrous tissues. The lipid-laden histiocytes were positive for CD68 and CD163, but negative for CD1a and S-100. Electron-microscopic examination showed no Birbeck granules, but the presence of lipid vacuoles. Moreover, the result of the clonality assay demonstrated that these cells formed a polyclonal population. In conclusion, ECD is a rare non-Langerhans' cell histiocytosis. Its nature may be a non-neoplastic lesion; however, additional studies with larger sample sizes are necessary to conclusively prove our hypothesis.
No preview · Article · Apr 2009 · Pathology - Research and Practice
[Show abstract][Hide abstract] ABSTRACT: Snail functions as a key regulator in the induction of a phenotypic change called epithelial to mesenchymal transition (EMT). Aberrant expression of Snail prevails in the onset and development of tumor. Here, we have observed increased expression of Snail under the treatment of hydrogen peroxide (H(2)O(2)). Investigation into the underlying mechanisms revealed that stabilization of Snail mRNA contributes partially to this process. H(2)O(2)-induced the luciferase activity of the reporter construct contains the 3'UTR of Snail. Deletion of the AU-rich elements in the UTR eliminated the response of the reporter to H(2)O(2), suggesting the potential role of HuR in the process. Lowering of endogenous HuR levels through knockdown of HuR by siRNA greatly reduced the inducability and half-life of Snail mRNA, which consequently inhibited the downregulation of E-cadherin by H(2)O(2). Our findings indicate that HuR plays a major role in regulating H(2)O(2)-induced Snail expression by enhancing Snail mRNA stability, which in turn enhances cell migrating ability through repressing expression of E-cadherin.
No preview · Article · May 2007 · Biochemical and Biophysical Research Communications
[Show abstract][Hide abstract] ABSTRACT: To investigate whether hyperthermia can enhance the killing effect of 5- fluorocytosine (5- FC) on human colorectal carcinoma cell lines SW480 transfected with carcinoembryonic antigen (CEA) tissue- specific cytosine deaminase (CD) gene in vitro,and study its mechanism.
Human colorectal carcinoma cell lines SW480 transfected with G1CEACDNa were cultured. The proliferated colonies were treated with the combined therapy of 5-FC and hyperthermia at a temperature of 43 degrees C for 30 min. After eight days, MTT was used to calculate the cellular survival rate,to analyze the killing effect of 5-FC combined with hyperthermia on SW480 cells transfected with CD gene. Flow cytometry was performed to analyze the cellular cycle and transmission electron microscope was used to observe the morphologic changes of SW480 cells after thermochemotherapy.
Hyperthermia combined with 5-FC had an enhanced killing effect on SW480-CEACD cells than 5-FC alone (P< 0.05, t =2.403, n=9). Flow cytometry revealed that the proportion of S stage cell increased in the group treated with hyperthermia and 5- FC (P< 0.001, t =7.158, n=6). Transmission electron microscope showed apoptosis after thermo- chemotherapy.
Hyperthermia can improve the anti- tumor effect of 5- FC on human colorectal carcinoma cell lines SW480 transfected with CD gene, and the cells were blocked at S stage of cellular cycle and apoptosis was induced following thermochemotherapy.
No preview · Article · May 2006 · Zhonghua wei chang wai ke za zhi = Chinese journal of gastrointestinal surgery
[Show abstract][Hide abstract] ABSTRACT: With the pComb3X-displaying Fab antibody libraries, to achieve the humanization of murine HAb18 against HCC by guided selection.
With the optimized primers, the human Fd and C(L) repertoire genes were amplified by RT-PCR from PBMC of HCC patients. The Fd repertoire genes were paired with murine HAb18 C(L) gene to construct pComb3X-displaying hybrid Fab library. The recombinant HAb18GE was used as antigens to select the target antibodies and got the Fd fragments. Then the human C(L) genes were paired with the selected human Fds to construct human Fab library. After the panning, the complete human Fab antibodies were got and analyzed.
With the murine HAb18 C(L) gene as template, the heavy chain Fd shuffling was achieved by panning the hybrid Fab library. Then with the selected Fds as template, the human Fabs were obtained through the light chain shuffling. Two of the resulting human Fabs (HuFab2 and HuFab11), with same Fd and different light chains, bound to HAb18G/CD147 specifically. The competitive ELISA, Western blotting, FCM, fluorescent cell staining and so on demonstrated that the human Fabs resembled its parental murine Fab in that they both perhaps recognized the same epitope. K(D) indicated (HuFab2=210 nm and HuFab11=280 nm) the selected Fabs had available affinity.
Through guided-selection, we got the available human Fab antibodies for the subsequent research. These results suggest that guided selection is a promising strategy in murine mAb humanization.
Preview · Article · Jan 2006 · Cancer biology & therapy