bcl-2 and c-myc protein expression were studied in 44 epidermal (8 seborrheic keratoses, 21 squamous cell carcinomas, and 15 basal cell carcinomas), and 26 melanocytic tumors(8 nevi, and malignant melanomas) by immunohistochemistry using the specific anti-bcl-2 and anti-c-myc monoclonal antibodies. 14 out of 15 basal cell carcinomas(BCC) (93.3%) showed expression of bcl-2 protein, 12 of which (85.7%) showed coexpression of c-myc protein. In the melanocytic tumors, 7 out of 8 nevi showed bcl-2 expression (87.5%). Five of these 7 cases (62.5%) also showed c-myc protein expression. Eight of 18 malignant melanomas(MM) (44.4%) showed expression of bcl-2 protein and 7 of these 8 cases (38.9%) also showed c-myc protein expression. All seborrheic keratoses and squamous cell carcinoma(SCC) were negative for bcl-2 proteins. 12 of 15 SCCs(80%) were positive for c-myc protein. In conclusion, bcl-2 and c-myc proteins were coexpressed in BCCs, nevi, and MMs. Coexpression of bcl-2 and c-myc proteins in these tumors was statistically significant(p<0.01), while no considerable differences of bcl-2 and c-myc expression were found between nevi and MMs. These results suggests that bcl-2 may cooperate with c-myc to promote tumorigenesis of BCCs, nevi, and MMs(p<0.01).
Cell Transformation, Neoplastic

BACKGROUND AND OBJECTIVES: Although the role of c-myb in head and neck tumor has not been studied, aberrant expression of c-myb in various cancer has been demonstrated recently, suggesting that c-myb may play a role in tumorigenesis. Consequently, disrupting c-myb function might prove a possible stratergy for controlling cancer cell growth. The purpose of this study is to investigate the possibility of clinical application of adenovirus-mediated dominant negative c-myb (DN-myb) gene therapy in head and neck cancer. MATERIALS AND METHOD: All tissues were obtained from patients undergoing therapeutic operation for head and neck tumors and were assayed the expression of c-myb and bcl-2 in tumor and normal tissue by RT-PCR. We have generated a replication-deficient recombinant adenovirus encoding the dominant negative c-myb (Ad/DN-myb) or control adenovirus encoding no transgene (Ad/GFP) and infected adenovirus to SNU-1076, head and neck tumor cell line. We examined cell proliferation by 3H-thymidine assay, apoptosis by DNA fragmentation, bcl-2 expression and Akt/PKB phosphorylation by Western immunoblot, and IGF-II, VEGF mRNA expression by RT-PCR. RESULTS: c-myb expression of head and neck tumor tissues was significantly higher than that of normal tissue, indicating that these genes may play an important role in carcinogenesis of head and neck tumor. Ad/DN-myb infected SNU-1076 cells decreased cell proliferation, IGF-1I and VEGF expression, and remarkably increased their apoptosis through the down-regulation of bcl-2 expression and the inhibition of Akt/PKB pathway activation. CONCLUSION: Results obtains from these study suggest that DN-myb induced apoptosis of head and neck tumor cells and the adenovirusmediated DN-myb gene therapy may be a potential molecular therapy for the treatment of head and neck tumor.
Cell Transformation, Neoplastic

N-acetyl-seryl-aspartyl-lysyl-proline (Ac-SDKP) is an endogenous short peptide produced through the continuous hydrolysis of Thymosin β4 by meprin-α and prolyl oligopeptidase. It has the functions of immune regulation, promoting angiogenesis, tumorigenesis and anti-fibrosis in organs. In this paper, according to some our research results and related literatures in recent years, a review of Ac-SDKP research progress was written.
Humans ; Oligopeptides ; Cell Transformation, Neoplastic

Immunohistochemical studies of the molecules associated with gastric tumor progression and metastasis were done to evaluate their relationship with known prognostic factors and their usefulness in assessment of the progression of gastric carcinoma in 127 gastric carcinoma tissues. The 4 antibodies used in this study were CD44H, CD44v6, erbB-2, and p53. The CD44H expression was detected in 76 (59.8%), CD44v6 in 63 (49.6%), erbB-2 in 18 (14.2%), and mutant p53 in 98 (77.2%) out of 127 cases of gastric carcinomas. There was no significant correlation between the expression rates of each four proteins. The expression rates of all 4 proteins were not significantly correlated with age and sex of the patients and lymph node metastasis, but the correlation between CD44v6 expression and the depth of tumor invasion and tumor stage was significant (p<0.05). These results suggest that CD44v6 is closely associated with tumor invasion, and high levels of CD44H, erbB-2 and p53 are associated with tumorigenesis of the stomach as they are highly expressed in early as well as in advanced gastric carcinomas. The findings also support the conclusion that the loss of control of alternative CD44 mRNA splicing resulted in production of CD44v6 splicing variant in tumor cell facilitates tissue invasion by increased adherence of the tumor cell to an extracellular matrix or by tumor cell migration. It can be expected that CD44v6 overexpression in tumor cells appears to be an important prognostic indicator for gastric tumor progression.
Neoplasm Metastasis ; Cell Transformation, Neoplastic ; Stomach Neoplasms

Autophagy is an evolutionarily well conserved cellular catabolic process.Cellular proteins and organelles are engulfed to autophagosomes and eventually delivered to lysosomes for degradation. Autophagy is closely associated with a variety of human diseases especially cancer. At present, it has been widely accepted that autophagy is a "double-edged sword" in cancer: it blocks tumorigenesis at the early stage, while it facilitates tumor development at the promotion and progression stage. Moreover, autophagy can be induced by chemotherapy and radiotherapy, which is generally play a pro-survival function. Thus, autophagy is an important target for cancer therapy, and suppression of autophagy to enhance the efficacy of cancer therapeutic agents is a novel strategy in cancer therapy under active clinical trials.
Autophagy ; Cell Transformation, Neoplastic ; Humans ; Neoplasms

The aims of this study were to assess the role of p53 overexpression in colorectal tumorigenesis and the association with clinicopathological features. The immunohistochemical results were semiquantitatively assessed. Expression of aberrant p53, tumor-suppressor gene product, was studied immunohistochemically using a monoclonal antibody in 11 nonneoplastic polyps, 19 tubular adenomas, 9 villous adenomas, and 48 colorectal carcinomas. Five out of 11 nonneoplastic polyps, 14 out of 19 tubular adenomas and one out of 9 villous adenomas expressed p53 protein. Seven out of 24 colorectal carcinomas without lymph node metastasis and 14 out of 24 colorectal carcinomas with lymph node metastsis expressed p53 protein. The case of more than 75% positivity of p53 in colorectal carcinoma with lymph node metastasis was seven out of 24, but that in lymph node negative group was two out of 24. In the colorectal carcinoma with lymph node metastasis group; metastatic intranodal neoplastic cells were expressed positively for p53 in 10 out of 14 cases and zero out of 10 cases in group of positive and negative expression of primary lesions, respectively. p53 protein expression was not significantly correlated with variable clinicopathologic features such as age, sex, tumor location, tumor size, differentiation and Dukes' stage. It is suggested that p53 protein overexpression could be a early event in pathogenesis of colon cancer but is not involved in progression of villous adenoma to adenocarcinoma. p53 overexpression seems to be involved in metastatic ability of colorectal carcinomas.
Adenoma ; Neoplasm Metastasis ; Cell Transformation, Neoplastic

Phospholipase C (PLC) plays a pivotal role in transmembrane signal transduction pathway for cellular proliferation differentiation and growth. Thus far, there have been few reports in which PLC activity was investigated in human malignant neoplastic tissues. In the present study, we evaluated PLC activity in 23 human gastric cancer tissues and normal mucosal tissues to investigate whether alteration of PLC activity is associated with gastric cancer. The amount of [14C] diacylglycerol, one of the earliest products of inositol phospholipid hydrolysis by PLC, was measured by thin layer chromatography. Also, expression of PLC-gamma1, which is one of the most important PLC isozymes,was examined by immunohistochemistry using specific monoclonal antibody directed against PLC-gamma1. The results are summarized as follows. PLC activity in all 23 gastric cancer tissues (1.35+/-1.04 units/mg of protein) was significantly higher than normal mucosal tissues (0.28+/-0.21 units/mg of protein) (P<0.001). PLC activity in gastric cancer tissues was not correlated with histologic grade (P>0.05). PLC-gamma1 immunoreactivity was detected in all of 23 cases studied. The intensity and extent of PLC-gamma1 immunoreactivity was not correlated with PLC enzyme activity, although stronger intensity was demonstrated in malignant cells in comparison to normal gland epithelial cells. The present study provides the first evidence of significant elevation of PLC activity in human stomach cancer tissues. Our results strongly suggest that PLC might be involved in tumorigenesis and/or progression(uncontrolled continuous cycling of cells) of human gastric cancer. Further studies are needed to elucidate the role of elevated PLC activity in cancer tissues.
Humans ; Cell Transformation, Neoplastic ; Stomach Neoplasms

The unique ability of tumour cells to proliferate indefinitely is crucial to neoplastic progression as it allows these cells to express the aggressive properties of cancer without the censure of physiological ageing. This is in contrast to normal somatic cells which are subject to a "mitotic clock," a phenomenon that has been linked to telomeric shortening after each round of cell replication, so that eventually the loss of genetic material reaches a critical stage and the cells undergo senescence and cell death. A study was conducted to investigate the role of telomerase, an RNA-containing enzyme that restores the telomere length, in the neoplastic cell immortalization and progression process. Fresh human tissue samples taken from excision specimens received by the Department of Pathology, University of Malaya Medical Centre, were investigated for telomerase activity using a commercial Telomerase PCR-ELISA kit (Boehringer Mannheim). Specimens comprised 33 breast lesions (10 infiltrating breast adenocarcinoma, 13 fibroadenoma and 10 non-neoplastic breast tissue), 27 colonic lesions (17 colonic adenocarcinoma and 10 non-neoplastic colonic mucosa) and 42 cervical lesions (20 cervical carcinoma and 22 non-neoplastic cervical tissues). Telomerase activity was found in 6 (60%) of 10 breast carcinomas, 6 (46%) of 13 fibroadenomas, none of the 10 nonneoplastic breast samples, 3 (17.6%) of 17 colon carcinomas and none of the 10 non-neoplastic colonic mucosal samples, 12 (60%) of 20 cervical carcinoma and 3 (13.6%) of 22 non-neoplastic cervical samples. 5/10 (50%) Stage I, 4/7 (57%) Stage II, 2/2 (100%) Stage III and 1/1 (100%) Stage IV cervical carcinomas showed telomerase activity. These findings support a contributory role for telomerase in tumourigenesis with activation occurring from neoplastic transformation and increasing with tumour progression.
Telomerase ; seconds ; Breast ; neoplastic cell ; Progression

Long non-coding RNAs(LncRNA)may play a key role in tumorigenesis by regulating gene expression and intervening transcription. Recent studies have demonstrated that a series of patterns including protein modification,chromosomal reconstruction,regulation of target gene expression,transcription intervention,epigenetic modification,and natural antisense transcript are involved in this process. This article reviews recent research advances in this aspect with an attempt to better understand the role of LncRNA in tumorigenesis.
Cell Transformation, Neoplastic ; Epigenesis, Genetic ; Gene Expression Regulation, Neoplastic ; Humans ; RNA, Long Noncoding

Not all cancer cells are born equal. While the great majority of the cells that make up tumours are destined to differentiate, albeit aberrantly, and eventually stop dividing, a handful of cancer cells appear to possess limitless replicative potential. This review presents compelling evidence to suggest that the bulk of malignant cells of most cancers are generated by a rare fraction of stem cell-like cancer cells. These cells, dubbed cancer stem cells, are phenotypically similar to the normal stem cells of the corresponding tissue of origin, but they exhibit dysfunctional patterns of self-renewal and differentiation. Cancer stem cells that are capable of recapitulating brain tumours as xenografts in mice are characterised by defined stem cell markers. These brain tumour stem cells demonstrate enhanced chemoresistance and radioresistance mechanisms compared to non-stem cells in the heterogeneous tumour, which suggest that they may be the likely candidates for tumour progression and recurrence. Indeed, recent work has shown that such aberrant signalling pathways may be targeted in novel anti-cancer therapeutic strategies. The stem cell concept of tumour progression prompts immediate attention to a new paradigm in cancer research with a focus on this minority subset of cells, and the design of novel therapeutic strategies to target these cells that are insignificant within the population of tumour cells, but that are in fact the relevant cells to be destroyed.
Cell Transformation, Neoplastic ; Glioma ; pathology ; radiotherapy ; Humans ; Models, Biological ; Neoplastic Stem Cells ; drug effects ; pathology ; Singapore