Journal of Carcinogenesis最新文献

Background: The golden Syrian hamster is an emerging model organism. To optimize its use, our group has made the first genetically engineered hamsters. One of the first genes that we investigated is KCNQ1 which encodes for the KCNQ1 potassium channel and also has been implicated as a tumor suppressor gene.

Materials and methods: We generated KCNQ1 knockout (KO) hamsters by CRISPR/Cas9-mediated gene targeting and investigated the effects of KCNQ1-deficiency on tumorigenesis.

Results: By 70 days of age seven of the eight homozygous KCNQ1 KOs used in this study began showing signs of distress, and on necropsy six of the seven ill hamsters had visible cancers, including T-cell lymphomas, plasma cell tumors, hemangiosarcomas, and suspect myeloid leukemias.

Conclusions: None of the hamsters in our colony that were wild-type or heterozygous for KCNQ1 mutations developed cancers indicating that the cancer phenotype is linked to KCNQ1-deficiency. This study is also the first evidence linking KCNQ1-deficiency to blood cancers.

Background: Obesity has frequently been associated with the dyslipidemic state and with the risk of various chronic diseases.

Objective: The objective of this study was to determine the relationship between obesity and blood lipids with a risk of colorectal cancer (CRC).

Methodology: Histologically confirmed CRC patients from five local hospitals were matched with cancer-free controls for age, gender, and ethnicity (n = 140: 280). The study participants underwent physical assessment for the presence of obesity and 10 mL of fasting blood was drawn for blood lipid analysis.

Results: In this study, abdominal obesity significantly doubled the risk of CRC (adjusted odds ratio [AOR] =1.69, 95% confidence interval [CI] = 1-2.83). Hypercholesterolemia and low high-density lipoprotein cholesterol (HDL) increased the risk of CRC more than twofolds (AOR = 2.6, 95% CI = 1.7-3.9 and AOR = 3.8, 95% CI = 2.3-6.3, respectively). Abdominal obesity and hypercholesterolemia synergically doubled the risk of CRC (AOR = 2.0, 95% CI = 1-4). Low-HDL has shown no synergic association with other dyslipidemic states with an increased CRC risk.

Conclusion: Improving abdominal obesity, hypercholesterolemia, and low HDL may be a clinically relevant strategy to reduce the risk of CRC among Malaysians.

Background: Carcinogenesis, a multistep process involves sequential changes during neoplastic transformation. The various hallmarks of cancer aid in cell survival, proliferation, and dissemination. Aberrant glycosylation, a recently defined hallmark of cancer, is influenced by glycosylation enzymes during carcinogenesis. Therefore, the present study measured α-2,3 and α-2,6 sialyltransferase (ST), sialidase, and α-L-fucosidase activity in patients with oral precancerous conditions (OPC) and oral cancer patients.

Subjects: The study enrolled 100 oral cancer patients, 50 patients with OPC, 100 healthy controls, and 46 posttreatment follow-ups of oral cancer patients. Blood and saliva were collected from all the participants.

Materials and methods: Sialidase activity was measured by spectrofluorimetric method, α-2,3 and α-2,6 ST by ELISA using biotinylated lectins, and α-L-fucosidase by spectrophotometric method.

Results: The results depicted increased levels of sialidase, α-2,3 and α-2,6 ST, α-L-fucosidase in patients with OPC and oral cancer patients. Receiver operating characteristic curve indicated significant discriminatory efficacy in distinguishing controls and oral cancer patients for serum and salivary sialidase and α-L-fucosidase activity, and serum α-2,6 ST. Furthermore, serum and salivary α-L-fucosidase activity and serum sialidase activity significantly distinguished controls and patients with OPC. Serum and salivary sialidase, α-L-fucosidase, and serum α-2,3 ST activity were higher in patients with metastasis as compared to nonmetastatic patients. Higher values of serum α-L-fucosidase activity were significantly associated with low-overall survival.

Conclusion: The increased levels of enzymes correlated with tumor initiation, progression, and metastasis in oral cancer patients. The alterations in glycosyltransferases/glycosidases thus support the view of glycosylation as a hallmark of cancer.

Background: The dynamic role of autophagy in cancer development is a topic of considerable research and debate. Previously published studies have shown that anal cancer development can be promoted or prevented with the pharmacologic inhibition or induction, respectively, of autophagy in a human papillomavirus (HPV) mouse model. However, these results are confounded by the fact that the drugs utilized are known to affect other pathways besides autophagy. It has also been shown that autophagic inhibition occurs in the setting of HPV16 oncoprotein expression (E6 and E7) and correlates with increased susceptibility to anal carcinogenesis.

Materials and methods: In this study, we employed a conditional, genetic, autophagic (Atg7) knockout mouse model to determine conclusively that autophagy has a role in anal cancer development, in the absence or presence of E6 and E7.

Results: In mice lacking both HPV16 oncogenes, knockout of autophagy followed by exposure to a carcinogen resulted in a tumor incidence of 40%, compared to 0% in mice treated with a carcinogen alone with an intact autophagic pathway (P = 0.007). In mice expressing either one or both HPV16 oncoproteins, the addition of genetic knockout of autophagy to carcinogen treatment did not lead to a significant difference in tumor incidence compared to carcinogen treatment alone, consistent with the ability of HPV oncogenes to inhibit autophagy in themselves.

Conclusions: These results provide the first conclusive evidence for the distinct role of autophagy in anal carcinogenesis, and suggest that autophagy is a plausible target for therapies aimed at reducing anal dysplasia and anal cancer development.

In recent years, research efforts have been centered on the functional roles of special AT-rich sequence-binding protein (SATB2) in cancer development. Existing studies differ in the types of tumor tissues and cell lines used, resulting in mixed results, which hinder the clear understanding of whether SATB2 acts as a tumor suppressor or promoter. Literature search for this review consisted of a basic search on PubMed using keywords "SATB2" and "special AT-rich sequence-binding protein 2." Each article was then selected for further examination based on relevance of the title. In consideration to possible missing data from a primary PubMed search, after coding for relevant information, articles listed in the references section were filtered for further review. The current literature suggests that SATB2 can act both as a tumor suppressor and as a promoter since it can be regulated by multiple factors and is able to target different downstream genes in various types of cancer cell lines as well as tissues. Future studies should focus on its contradictory roles in different types of tumors. This paper provides a comprehensive review of currently available research on the role of SATB2 in different cancer cells and tissues and may provide some insight into the contradictory roles of SATB2 in cancer development.

Background: African Americans and Hispanics are reported to have higher mortality from esophageal cancer (EC) than Caucasians. In this study, we analyzed the independent effects of race, gender, treatment, and socioeconomic status (SES) on overall survival (OS).

Methods: Data for all EC cases between 2004 and 2010 with follow-up through 2012 were obtained from the California Cancer Registry. We conducted descriptive analyses of clinical variables and survival analyses by Kaplan-Meier and Cox proportional hazards methods.

Results: African Americans and Hispanics were more likely to be in the lower SES strata and less likely to receive surgery than Caucasians in this cohort. The proportion of patients receiving chemotherapy and radiotherapy was similar across different racial/ethnic groups. After adjustment for stage, grade, histology, treatments, and SES in multivariate analyses, the mortality risk in African Americans (hazard ratio [HR] 0.96, 95% confidence interval [CI] 0.85-1.07) and Hispanics (HR 0.96, 95% CI 0.89-1.07) did not differ from Caucasians (HR = 1.00, referent), with histology, SES, and surgery largely accounting for unadjusted OS differences. We also observed that African American men had higher adjusted risk of death relative to Caucasian men (HR 1.24, 95% CI 1.07-1.42), but this effect was not observed for African American women compared to Caucasian women (HR 1.12, 95% CI 0.94-1.35).

Conclusions: Race is not an independent risk factor for OS in our population-based analysis of EC cases. Rather, observed differences in OS by race/ethnicity result from differences in cancer histology, SES, surgery, and gender. Our findings support further health disparities research for this disease.

Background: Matrix Metalloproteinase 13 (MMP13) is a member of collagenase family and it is involved in the degradation of extracellular matrix and basement membrane protein. It is thought to be associated with tumor invasion and metastasis. Elevated MMP13 expression has been found in carcinoma of the breast, urinary bladder, head and neck and others. It is observed that MMP13 gene is also correlated with radiation response in OSCC (Oral squamous cell carcinoma) cell line based study. The present study correlates the MMP13 expressions with clinicopathological parameters and radiation response in OSCC patients.

Materials and methods: The MMP13 mRNA levels were determined by employing qRT-PCR (real-time quantitative reverse transcriptase-polymerase chain reaction).

Results: We observed high expression of MMP13 mRNA in OSCC patients when compared with matched controls. Statistically significant up regulation of MMP13 mRNA expression was found in tobacco chewers, advanced T-stage (p < 0.001) and lymph node metastasis (p < 0.01). MMP13 mRNA levels were also elevated in non responders as compared to responders to radiation treatment.

Conclusions: To the best of our knowledge, this is the first report that indicates role of MMP13 in radiation response in OSCC patients and could be used as potential bio-marker for radiotherapy treatment in OSCC patients.

Since the 1970s, the epidemic of hepatocellular carcinoma (HCC) has spread beyond the Eastern Asian predominance and has been increasing in Northern hemisphere, especially in the United States (US) and Western Europe. It occurs more commonly in males in the fourth and fifth decades of life. Among all cancers, HCC is one of the fastest growing causes of death in the US and poses a significant economic burden on healthcare. Chronic liver disease due to hepatitis B virus or hepatitis C virus and alcohol accounts for the majority of HCC cases. Incidence of nonalcoholic fatty liver disease has been on the risem and it has also been associated with the development of HCC. Its pathogenesis varies based on the underlying etiological factor although majority of cases develop in the setting of background cirrhosis. Carcinogenesis of HCC includes angiogenesis, chronic inflammation, and tumor macroenvironment and microenvironment. There is a significant role of both intrinsic genetic risk factors and extrinsic influences such as alcohol or viral infections that lead to the development of HCC. Understanding its etiopathogenesis helps select appropriate diagnostic tests and treatments.

"Gene amplification causes overexpression" is a longstanding and well-accepted concept in cancer genetics. However, raking the whole literature, we find only statistical analyses showing a positive correlation between gene copy number and expression level, but do not find convincing experimental corroboration for this notion, for most of the amplified oncogenes in cancers. Since an association does not need to be an actual causal relation, in our opinion, this widespread notion still remains a reasonable but unproven assumption awaiting experimental verification.