Cancer Biomarkers - Volume 5, issue 6

Authors: El Awady, Mostafa K. | Karim, Amr M. | Hanna, Laila S. | El Husseiny, Lamia A. | El Sahar, Medhat | Menem, Hanan A. Abdel | Meguid, Nagwa A.

Article Type: Research Article

Abstract: The study was planned as a pilot study to investigate two common polymorphisms in the MTHFR gene c.677C > T and c.1298A > C and their association with enhanced risk of colorectal cancer (CRC) in a sample of Egyptian individuals. Venous blood samples were withdrawn from 35 cases of CRC and 68 healthy controls. Specimens from colonic and rectal carcinoma tissues in addition to cancer free tissues were obtained from all cases. Frequencies of MTHFR677T and 1298C alleles were significantly higher among cases of CRC tumor tissues (50% and 56%, respectively) than germ line alleles in CRC patients (33% and …41%, respectively) and healthy controls (21% and 35%, respectively). Frequencies of heterozygous and homoyzgous polymorphisms of MTHFR at positions 677 and 1298 in carcinoma tissues were always the highest. At position 677, TT and CT genotype frequencies were 17% and 66% with an odds ratio {OR} of 11 [95% confidence interval {CI} 2.39–50.59] and OR 8.34 [95%CI 2.97–23.92], respectively, in carcinoma tissues. While in the germ line of patients the genotype frequencies of 677TT and CT were 6% and 54% with OR 1.57 [95%CI 0.26–9.51] and 2.99 [95%CI 1.25–7.12], respectively, compared to controls (6% and 29%, respectively). The combined genotype MTHFR 1298CC + AC frequencies were 86% with OR 3.71 [95%CI 1.28–10.78] in carcinoma tissues, 69% with OR 1.35 [95%CI 0.57–3.21] in germ line of patients and 62% in controls. The combined genotype 677CT plus any of the following genotypes 1298AA, AC or CC enhanced risk of CRC, when comparing germ line DNA polymorphism of patients versus peripheral blood DNA of control subjects with OR 4.5 [95%CI 0.94–21.56], OR 3.12 [95%CI 0.79–12.36] and OR 18 [95%CI 1.56–207.5], respectively, suggesting strong genetic predisposition of certain Egyptian population to CRC. These results suggested that at least one C to T polymorphism at 677MTHFR gene is required to significantly increase the risk for CRC development. Further large scale studies are required to confirm the present findings. Show more

Keywords: MTHFR, polymorphisms, colorectal cancer, Egyptian

DOI: 10.3233/CBM-2009-0108

Citation: Cancer Biomarkers, vol. 5, no. 6, pp. 233-240, 2009

Authors: Talesa, Vincenzo N. | Antognelli, Cinzia | Del Buono, Chiara | Stracci, Fabrizio | Serva, Maria R. | Cottini, Emanuele | Mearini, Ettore

Article Type: Research Article

Abstract: Prostate cancer (PCa) is a heterogeneous, multifactorial and multifocal disease. Therefore, the search for a combination of assays using a panel of tumor markers is fundamental for a more precise and reliable diagnosis. In the present study we investigated the diagnostic value of five different genes, associated with PCa carcinogenesis, encoding for prostate-specific membrane antigen (PSMA), serine protease Hepsin, PCa antigen 3 (PCA3), UDP-N-acetyl-α-D-galatosamine transferase (GalNAC-T3) and prostate-specific antigen (PSA). Forty-four patients, with previously untreated, histologically verified PCa and forty-six patients with benign prostatic hyperplasia (BPH) were enrolled in this study. Absolute concentration of the transcript levels of each gene …was calculated by quantitative Real-Time PCR analysis in urine sediments of men suffering from PCa or BPH after prostatic massage. The diagnostic value of a concomitant examination of these markers was evaluated by logistic regression analysis. We demonstrated that the diagnostic potential of the combined urinary PSA and PSMA level was significantly better than that of each singularly considered marker, including total serum PSA, the present gold standard test for PCa diagnosis. Show more

Keywords: PCA3/DD3, PSMA, PSA, panel of urinary biomarkers, prostate cancer

DOI: 10.3233/CBM-2009-0109

Citation: Cancer Biomarkers, vol. 5, no. 6, pp. 241-251, 2009

Authors: Sharma, Manoj | Rajappa, Medha | Kumar, Guresh | Sharma, Alpana

Article Type: Research Article

Abstract: Objective: Cancer of posterior one-third of tongue is seen in 0.43% of total world population. Worldwide, cancer of tongue constitutes 5% of the total cancer incidence. Squamous cell cancer of head and neck is the most common cancer encountered in India. Oxidative stress is potentially harmful to cells and ROS are involved in multistage carcinogenesis, in initiation and promotion. Moreover, the extent of ROS-induced oxidative damage can be exacerbated by decreased efficiency of antioxidant defense mechanisms. The aim of this study was to assess the alterations in the circulating lipid peroxide, antioxidant components and the activities of defense enzymes in …patients with cancer of posterior one-third of tongue, with respect to healthy controls in the Indian population. Methods: 60 patients with newly diagnosed, histologically proven cases of locally advanced squamous cell carcinoma (Stage III-IVa) of posterior one-third of tongue were recruited into the study. 60 healthy controls, without history or laboratory evidence of malignancy and inflammatory disorder, were also included in the study, after obtaining informed consent. Single blood samples were taken from patients, before start of therapy and controls. Lipid peroxides, conjugated dienes, reduced glutathione (GSH), vitamin C and E were estimated using standard methods. Glutathione peroxidase (GPx) and superoxide dismutase (SOD) were assayed using commercially available kits from Randox, UK. Results: The pre-treatment levels of plasma lipid peroxide and conjugated dienes were significantly elevated in patients with carcinoma of posterior one-third of tongue, as compared with controls (p=0.001). Significantly lowered levels of GSH, GPx, SOD and antioxidant vitamins were observed in cancer patients, when compared to control subjects (p=0.001). Pearson’s correlation analysis showed a highly statistitically significant negative correlation between pro-oxidant and anti-oxidant levels in patients. Conclusion: Increased levels of oxidative stress markers and decreased levels of antioxidants in carcinoma of posterior one-third of tongue suggest that oxidative stress markers play a significant role in the pathophysiology of tongue cancer. These findings may suggest possible use of antioxidant supplementation as prophylactic agents for prevention and treatment of tongue cancer. A larger patient cohort for therapeutic response after treatment with a longer follow-up period studies might yield more significant data on their probable use as predictors of chemoradiosensitivity of cancer of tongue. Show more

Keywords: Antioxidant enzymes, cancer of posterior one-third of tongue, conjugated dienes, glutathione, lipid peroxide, vitamin C, vitamin E.

DOI: 10.3233/CBM-2009-0110

Citation: Cancer Biomarkers, vol. 5, no. 6, pp. 253-260, 2009

Authors: Krishna, I. Vamshi | Vanaja, G.R. | Kumar, N. Srihari Kirmani | Suman, G.

Article Type: Research Article

Abstract: All the anti-cancer drugs proved to be highly cytotoxic agents to normal cells like lymphocyte cells used in our study which do not come under rapidly dividing cells like bone marrow cells, fetal cells, germ cells, hair follicle cells, intestinal cells, etc. but will proliferate when maintained in growth media with proliferation agents. In this investigation, we determined the effect of anti-cancer drugs on lymphocyte cultures from peripheral blood of healthy non-smoking donors under in vitro conditions by employing MTT assay. All the experiments were carried out with seven anti-cancer drugs; Carboplatin, Avastin, Vinorelbine, Tamoxifen Citrate, Methotrexate, Gemcitabine and Paclitaxel …which are broad-spectrum cancer drugs and being used in six different types of chemotherapy in cancers. We have documented the results that were evaluated by statistical analysis. The MTT assay is now widely adopted by researchers and industry, as it is a rapid spectrophotometric method for determining cell viability in cell lines and in vitro. The initial or dose-finding studies determine the drug toxicity relative to dose and subsequent studies define the spectrum of activity of the drug. And moreover, no anti-neoplastic drug is devoid of side effects. Hence, this investigation determines the lethal concentrations and thereby the dosages at which individual anti-neoplastic drugs and also combinations can bring about certain degree of cytotoxicity in human lymphocytes which with comparative study on cancer cell lines would be useful in defining drug dosages. Show more

Keywords: Anti-cancer drugs, cytotoxicity, in vitro assays, MTT assay

DOI: 10.3233/CBM-2009-0111

Citation: Cancer Biomarkers, vol. 5, no. 6, pp. 261-272, 2009

Authors: Ribeiro, A.L. | Correia, J. | Ribeiro, V.

Article Type: Research Article

Abstract: The hypoxia-inducible factor -1α (HIF-1α) is a transcription factor that plays a crucial role in the cellular response to hypoxia. The C1772T (P582S) and G1790A (A588T) polymorphisms, within the oxygen dependent degradation domain of HIF-1α protein, seem to be important in the oxygen regulation of protein stability, influencing the progression of some hypoxic solid tumors. Despite the numerous reports about the influence of these single-nucleotide polymorphisms (SNPs) on cancer incidence and progression, there are no published data concerning the interethnic variability of these polymorphisms. Here we investigated the SNPs C1772T and G1790A, in four distinct populations from Portugal, Mozambique, Colombia …and Guinea-Bissau. The allelic frequency of the 1772T allele was 0.122 in Portugal, 0.151 in Colombia, 0.246 in Mozambique and 0.08 in Guinea-Bissau. Statistically significant differences were observed when comparing the Portuguese population with the Mozambican one (p=0.020) and the populations from Mozambique and Guinea-Bissau (p< 0.0001). The Mozambican population had an allelic frequency of 0.006 for the 1790A allele, which was not detected among the other studied populations. In conclusion, there is an ethnicity-related variation in the frequency of C1772T and G1790A polymorphisms of the HIF-1α gene that may be relevant in the context of tumor aggressiveness and progression. Show more

Keywords: Hypoxia, polymorphisms, ethnic, cancer

DOI: 10.3233/CBM-2009-0112

Citation: Cancer Biomarkers, vol. 5, no. 6, pp. 273-277, 2009

Authors: White, Nicole M. A. | Mathews, Maria | Yousef, George M. | Prizada, Amrah | Fontaine, Daniel | Ghatage, Prafull | Popadiuk, Catherine | Dawson, Lesa | Doré, Jules J. E.

Article Type: Research Article

Abstract: The current biomarker for ovarian cancer, CA125, lacks the sensitivity and specificity required to detect early stage ovarian cancers. Since several Kallikreins (KLKs) are up regulated in ovarian cancer, they represent a potential pool of biomarkers for ovarian cancer. The purpose of this study is to determine if elevated expression levels of Muc16 (CA125 gene), KLK6 and KLK13 represent a more sensitive test for detection of early stage ovarian cancer than Muc16 alone. Using quantitative real-time PCR, 106 sporadic ovarian tumors and 8 normal ovaries were evaluated for mRNA expression. Analysis for increased expression levels, above controls, of either KLK6, …KLK13 or Muc16 improved overall sensitivity to 93%, from 82% for Muc16 alone. Likewise, the negative predictive value increased from 27% to 50% (Muc16 alone compared to combined). With early stage cancers (n=32), both sensitivity increased 50–56% (individually) to 72% (combined), and negative predictive value increased (30% Muc16 to 58% combined). These results show a combined panel of KLK6, KLK13, and Muc16, is a more sensitive test to detect early stage ovarian cancer than Muc16 alone, indicating assaying for several kallikrein-related peptidases, in addition to CA125, could provide a significant advantage to detect ovarian cancer in the early stages. Show more

Keywords: Human kallikrein related peptidase 6 (KLK6), human kallikrein related peptidase 13 (KLK13), CA125, ovarian cancer, Mucin 16, biomarkers, sensitivity, specificity, positive predictive value, negative predictive value

DOI: 10.3233/CBM-2009-0113

Citation: Cancer Biomarkers, vol. 5, no. 6, pp. 279-287, 2009