Among SNPs of p53 gene, the polymorphism at codon 72 has been widely studied being associated with CRC susceptibility and disease outcome [6, 7, 15]. The rs1625895 was reported to be associated with a high degree of endometrial cancer  and lung cancerrisk , but not associated with breast cancer  and CRC . We find that GG genotype of this polymorphism confers protection; meanwhile, GA genotype and A allele are associated with risk for CRC. Thep53 GA genotype is more frequent whereas the GG genotype is less frequent incancer lot than in controls. These results may be explained by the selection bias or by the fact that G allele may predispose to an increasing rate of mutation’s accumulation, a rapid evolution of malignancies and with apparition of other malignant diseases. The GA genotype may have an opposite effect and may be more common between patients with a single malignant disease.
found in GC with high microsatellite instability . The asso- ciation of some SNPs in TCF7L2 gene with various cancer types was shown in recent studies. Of these SNPs, rs7903146 (C>T) polymorphism was reported to be associated with colorectaland lung cancer  prostate cancerand increased breast can- cer risk . Neverthless, Connor et al  determined three polimorphisms rs3750805, rs7900150 and rs1225404 as well as rs7903146 in TCF7L2 to be associated with breast cancer. Rs12255372 (G>T) was shown to be associated with familial breast cancerrisk  while it was shown to increase prostate cancer aggressiveness in another study . Results of a meta- analysis indicated that there was a signiicant association be- tween TCF7L2 rs7903146 (C>T) polymorphism andtherisk of breast, prostate and colon cancer rather than colorectal, lung and ovarian cancer . Although numer- ous studies have shown diferent genes and variants as genetic risk factors for gastric cancer, revealing the exact molecular mech- anism of GC is still a challenge. The strong candidate TCF7L2 gene, as a transcription factor, may enhance the canceration of gastric epithelial cells by changing the ex- pressions of a variety of genes involved in cell cycle such as c-myc oncogenes. In our country, although it is the second most common type of cancer subsequently breast cancerin women and lung cancerin men , there is no study on the genetic basis of GC. Up to now, the associations between polymorphismsin various genes and GC have been investigated in several studies worldwide, but the association between TC- F7L2 gene polymorphismsandthe GC risk was not investigated in any study to the best of our knowledge. We investigated therisk associated with rs12255372(G>T) and rs7903146(C>T) SNPs in TCF7L2 gene for the irst time in a Turkish population with GC.
The arylamine N-acetyltransferase 2 (NAT2) enzymes detoxify a wide range of naturally occurring xenobiotics in- cluding carcinogens and drugs. Point mutations inthe NAT2 gene result inthe variant alleles M1 (NAT2 *5A), M2 (NAT2*6A), M3 (NAT2*7) and M4 (NAT2 *14A) from the wild-type WT (NAT2 *4) allele. The current study was aimed at screening genetic polymorphisms of NAT2 gene in 49 lung cancerpatients, 54 colorectalcancerpatientsand 99 cancer-free controls, using PCR-RFLP. There were significant differences in allele frequencies between lung cancerpatientsand controls inthe WT, M2 and M3 alleles (p < 0.05). However, only M2 and M3 allele frequencies were dif- ferent between colorectalcancerpatientsand controls (p < 0.05). There was a marginal significant difference inthe distribution of rapid and slow acetylator genotypes between lung cancerpatientsand controls (p = 0.06 and p = 0.05, respectively), but not between colorectalcancerpatientsand controls (p = 1.0 and p = 0.95, respectively). Risk of lung cancer development was found to be lower in slow acetylators [odds ratio (OR): 0.51, 95% confidence interval (95% CI): 0.25, 1.02, p-value = 0.07]. No effect was observed in case of colorectalcancer. Our results showed that NAT2 genotypes and phenotypes might be involved in lung cancer but not colorectalcancer susceptibility in Jordan.
Squamous cell carcinoma of the cervix (SCCC) is one of the leading causes of death in developing countries. Infection with high-risk human papillomavirus (HPV) is the major risk factor to develop malignant lesions inthe cervix. Polymorphisms of the MHC andp53 genes seem to influence the outcome of HPV infection and progres- sion to SCCC, although controversial data have been reported. MHC are highly polymorphic genes that encode molecules involved in antigen presentation, playing a key role in immune regulation, while p53 is a tumor suppressor gene that regulates cell proliferation. The HPV E6 protein from high-risk types binds p53and mediates its degradation by the ubiquitin pathway. The role of these polymor- phisms in genetic susceptibility to HPV infection and to SCCC remains under investigation.
The traditional approach of chemotherapy against cancer targets the several phases of the cell cycle, thereby interfering in cell growth and division and leading to cell death. Many of these treatments act directly or indirectly on the synthesis and replication of DNA, for example: by means of interpolation of DNA, through blockage of components such as purine or antagonistic antifolates, through inhibition of the enzyme topoisomerase (which is necessary for DNA repair), or by inhibiting formation of the mi- crotubules needed for mitosis. The adverse effects of these treatments are caused by the nonspeciicity of these actions on malignant cells (1, 12) .
important factor, which influences the grain size andthe quality of the casting is the amount of modifier introduced into the mould. The amount of cobalt aluminate inthe primary slurry is highly variable, (ranging from 1 to 10% or higher) and depends on the specification requirements, the alloy being casted, the section thickness, and other factors [9-11]. On the grounds of the obtained results it was found that the optimal concentration of cobalt aluminate powder in ceramic mould to produce casting elements made from Inconel 713C superalloy is about 5-6%mass, however in case of S6K - 2%mass. The higher concentration of modifier does not change the grain size significantly and does not improve mechanical properties of castings. So the next step inthestudy is to define what chemical and physical properties should cobalt aluminate characterize in order to archive the best nucleating effect.
Objective: To analyze the immunoexpression of the COX-2, p53, and caspase-3 proteins incolorectal adenomas and non-neoplastic mucosa. Methods: 72 individuals were subjected to colonoscopy, which provided 50 samples of adenomas and 45 samples of non-neoplastic colorectal mucosa. The tissue samples were obtained via the tissue microarray technique and subjected to immunohistochemical analysis using primary anti-p53, anti-COX-2, and anti-caspase-3 antibodies. The positivity and intensity of the immunoreaction were classified. The analyzed variables were as follows: site of the adenomas inthe colon, degree of dysplasia, size, and score of positivity and intensity of immunoexpression of the p-53, caspase-3, and COX-2 proteins. Results: The immunoexpression of mutated protein p53 was positive in 30 (60%) adenoma samples and negative in 20 (40%) adenoma samples. The immunoexpression of mutated protein p53 was negative in 39 (86.6%) samples and positive in 6 (13.3%) samples of the non- neoplastic colorectal mucosa (p<0.0001). Significant differences were seen between both the largest size (p=0.006) andthe highest degree of dysplasia (p<0.0001) of the adenomas andthe intensity of immunoexpression of mutated protein p53. The positivity and intensity of immunoexpression of COX-2 (p=0.14) and caspase-3 (p=0.23) showed no significant differences between the adenomas andthe non-neoplastic colorectal mucosa. Conclusion: Mutated protein p53 was hyperexpressed inthe adenomas compared with the non-neoplastic mucosa. Greater size and greater degree of dysplasia inthe adenomas were associated with higher expression of mutated protein p53. The immunoexpression of COX-2 and caspase-3 inthe adenomas did not exhibit a correlation with the anatomical- pathological features of the tumors and did not differ from the corresponding expression levels inthe non-neoplastic mucosa.
Cervical cancer is a public health problem andthe molecular mechanisms underlying radioresistance are still poorly understood. Here, we evaluated the modulation of key molecules involved in cell proliferation, cell cycle and DNA repair in cervical cancer cell lines (CASKI and C33A) andin malignant tissues biopsied from 10 patients before and after radiotherapy. The expres- sion patterns of epidermal growth factor receptor (EGFR), excision repair cross-complementation group 1 (ERCC1) andp53 were evaluated incancer cell lines by quantitative PCR and western blotting, andin human malignant tissues by immuno- histochemistry. The mutation status of TP53 gene was evaluated by direct sequencing. Among cell lines, absent or weak modulations of EGFR, ERCC1 andp53 were observed after exposure to 1.8 Gy. Conversely, increased expressions of p53 (5/10 patients; P=0.0239), ERCC1 (5/10 patients; P=0.0294) and EGFR (4/10 patients; P=0.1773) were observed in malignant tissues after radiotherapy with the same radiation dose. TP53 mutations were found only in one patient. Here we show that a single dose of radiotherapy induced EGFR, ERCC1 andp53 expression in malignant tissues from cervical cancerpatients but not incancer cell lines, highlighting the gap between in vitro andin vivo experimental models. Studies on larger patient cohorts are needed to allow an interpretation that an upregulation of p53, EGFR and ERCC1 may be part of a radioresistance mechanism. Key words: Cervical cancer; Radiotherapy; Epidermal growth factor receptor (EGFR); p53; Excision repair cross- complementation group 1 (ERCC1)
The repeated elements spread in DNA that are more deeply studied belong to the Alu family, which has this name because most of its members are cleaved by bacterial restriction endonucleases called Alu I, formerly used inthe initial puriication of this DNA. ALU247 has been used incancer investigation and as a genetic marker in studies of human evolution due to its properties, such as speed and facility concerning genotyping, and also because it is selectively neutral 3 .
Inclusion criteria were as follows: a clinical diagnosis of colorectalcancerand admission to a surgical ward for elective surgery. All patients who met the inclusion criteria during the aforementioned period were further evaluated for the following exclusion criteria: age below 40 (in order to exclude inherited genetic conditions), unawareness of colorectalcancer diagnosis, inability to comprehend and fulfill what is required and existence of known metastases at the time of surgery. To minimize confounding factors, patients who underwent neo-adjuvant chemotherapy or radiotherapy, or who had high probability of surgical treatment with subsequent colostomy were also excluded from thestudy.
Tobacco, alcohol, and betel quid are the main causes of squamous cell cancers of the upper aerodigestive tract. These substances can cause multifocal carcinogenesis leading to multiple synchronous or metachronous cancers of the oesophagus, head and neck region, and lungs (‘ield cancerisation’). Globally there are several million people who have survived either head and neck squamous cell cancer (HNSCC) or lung cancer (LC). HNSCC and LC survivors are at increased risk of developing second primary malignancies, including second primary cancers of the oesophagus. Therisk of second primary oesophageal squamous cell cancer (OSCC) ranges from 8-30% in HNSCC patients. LC and HNSCC survivors should be ofered endoscopic surveillance of the oesophagus. Lugol chromoendoscopy is the traditional and best evaluated screening method to detect early squamous cell neoplasias of the oesophagus. More recently, narrow band imaging combined with magnifying endoscopy has been established as an alternative screening method in Asia. Low-dose chest computed tomography (CT) is the best evidence- based screening technique to detect (second primary) LC and to reduce LC-related mortality. Low-dose chest CT screening is therefore recommended in OSCC, HNSCC, and LC survivors. In addition, OSCC survivors should undergo periodic pharyngolaryngoscopy for early detection of second primary HNSCC. Secondary prevention aims at quitting smoking, betel quid chewing, and alcohol consumption. As ield cancerisation involves the oesophagus, the bronchi, andthe head and neck region, thepatients at risk are best surveilled and managed by an interdisciplinary team.
Firms need to attract attention to their products and services. This could prove to be quite a task for the typical Nigeria firm, with a practically unknown brand name and weak advertising dollars. Goldstein and O’Connor (2001) state that “even the best e-marketing strategy does not substitute for traditional media. Indeed, such advertising is normally viewed as an unavoidable sunk cost to establish brand name recognition.” Small firms by themselves will be unable to afford the advertising sunk cost that is necessary for effective market penetration. By engaging in a cooperative effort in marketing, using a Web portal and sharing advertising cost, firms may better penetrate the on-line market. Nigeria government needs to encourage and recognize innovative applications of ICTs and help in instituting mechanisms to spread best practices. Government should create a national demonstration and help desks to assist SMEs in ICTs choice, implementation and maintenance. If possible, provide motivation to encourage SMEs’ use of ICTs through various mechanisms, facilitate, support and encourage e-commerce applications through establishing appropriate frameworks, removing hurdles and leading by example. There is need for education and training. Education institutions in Nigeria should Institute compulsory courses in information and communications technology as early as possible into the curriculum. They should also encourage local hardware shops to collect- refurbish and roll-out computers that are gathering dust in most offices to high schools and elementary schools, at least where there is electricity, so that students will get exposure at an early age.Education administrators must ensure that tertiary education curriculum reflects changes inthe global environment, expand tertiary level information and communications technology education, establish specialized institutions (like the Egyptian Information technology and South African software development institute) to prepare young cadres for the information economy in collaboration with the local private sector and other international institutions.In addition, they should also encourage, recognize, accredit and certify private institutions involved in high level ICTs training, set requirements and (social) obligations for organizations to provide ICTs skills to their staff and provide incentive and motivation.
se of excreta on arable land secures valuable fertilisers for crop production and limits the negative impact on water bodies [29,13, 6]. The environmental impact of excreta disposal usage would always be less than that of the direct use of water bodies as the primary recipient of excreta and greywater . To preserve its fertility, arable land needs to be compensated for the plant nutrients removed. Today, chemical fertilisers produced by fossil resources do mostly this. Inthe long-term perspective the world cannot securely rely on fossil resources, as the recycling of plant nutrients. Another way of compensating soil fertility is from human excreta’s direct application to arable land . Urine has been used as a valuable plant food for centuries in many parts of the world, particularly inthe Far East. It is surprising, therefore, that nearly all the urine produced inthe West andin Africa goes to waste and is lost to agriculture . Urine is known to contribute the major proportion of the nutrients (N, P and K) in domestic wastewater as compared to faeces which even poses a greater health risk when used . Thus, separating the urine which accounts for about 1% of the total wastewater flow, and using it as fertilizer makes it possible to utilize most of the nutrient content of wastewater . Urine is usually collected in a source separating toilet , and nitrogen
A 39-year-old male was admitted to urology clinic because of the complaints of painless clotted hematuria. Ater the urologi- cal examination, he hospitalized for hematuria etiology. A pap- illary tumor with a diameter of 3cm at the right lateral wall of the bladder was determined inthe diagnostic cystoscopy. Tumor was excised. The pathological diagnosis was non-muscle invasive bladder cancer. The patient was followed by control cystoscopies. Ater 9 months, tumor was detected again inthe bladder at the control cystoscopy and it was taken out. The patient’s TCC was classiied as muscle invasive (Figure 1). Cys- tectomy and ileal loop operation was performed for the patient. The patient was recovered and discharged in postoperative
Arg399Gln showed the distribution expected in a Brazilian population. 23-26 Together these observations indicate that our group of patients is adequate for a case-case study. Our study revealed a statistically significant relationship between the Arg194Trp genotype of XRCC1 and Elston grade III, which indicates a poorly differentiated tumor and, consequently, is related to increased aggressiveness of the disease. The role of XRCC1 in efficient BER has already been well determined 6,15,16 and it is acceptable that some gene alterations may change its biological activity and play roles incancer evolution. A recently published meta-analysis of 37 studies suggests that Arg399Gln is associated with a trend of increased breast cancerrisk. 31 Another meta-
when diagnosed early, can be completely healed. Although innumerous studies have addressed the prognostic meaning of various histological and mo- lecular types, as well as clinical characteristics, the pathological stage at the diagnosis is still the best in- dicator of long-term prognosis to both colon and rec- tal cancer. The most important characteristics are pre- sence of distant metastases, local extension of tumor, node positivity (number of lymph nodes involved) and residual disease 7 .
3mg/L, respectively . Furthermore, hs-CRP test is cost effective and has a generally acceptable precision and reproducibility in coronary heart disease risk profiling . de Luka et al also pointed out that high hs-CRP is associated with coronary heart disease independent of traditional risk markers, viral load, CD4 count andthe combination of antiretroviral therapy . Use of hs-CRP inthe HIV-infected population is however subject to debate, since levels may be elevated pre- antiretroviral therapy and during therapy regardless of regimen . hsCRP levels also seem to remain elevated despite normalised CD4 cell count and suppressed viral load . A cohort study done amongst HIV infected patientsin South Africa showed elevated levels of hs-CRP and other biomarkers pre-antiretroviral therapy . hs-CRP levels may be falsely elevated due to tissue injury, recent infection or general inflammation, andin individuals taking non-steroidal inflammatory drugs such as: aspirin, ibuprofen and naproxen . Levels are also elevated in arthritic patients while anti- inflammatory drugs and statins reduce hs-CRP levels . In some studies, changes in regimen have shown to be associated with increases in hs-CRP therefore use of hs-CRP may be more useful in those on stable antiretroviral therapy , . In contrast to some of the editorial commentary that has expressed concerns about the robust predictive value of hs-CRP testing for risk assessment, in a comprehensive 2007 review of available published CRP study data, Ridker supported the use of hs-CRP as a consistently additive and independent inflammatory predictor of future coronary heart events, while refuting some of the critical commentary directed at certain ‘negative’ studies . Results from an analysis in a cohort study done by Boger et al. , also gave evidence for use of hs-CRP as a more reliable estimate of coronary heart disease riskin people with well-controlled HIV infections than standard risk markers . Thestudy also traced significant correlation between hs-CRP and triglycerides, cholesterol, and body mass index (BMI). Thestudy by Boger et al. also showed the following prevalence (as %): hs-CRP >3mg/L (high risk)- 47%, hs-CRP between 1 and 3mg/L (average risk)-26%, and hs-CRP <1mg/L (low risk)-25% . Though BMI were less predictive of coronary heart disease in HIV-infected patients there were indications that higher BMI is correlated with hs- CRP . The aim of the current study was to evaluate therisk of coronary heart disease in both antiretroviral-naïve and antiretroviral-experienced HIV-infected patients using highly- sensitive C-reactive protein and lipid profiles.
Colorectal carcinoma is considered the fourth leading cause of cancer deaths worldwide. Several mi- croorganisms have been associated with carcinogenesis, including Enterococcus spp., Helicobacter pylori, enterotoxigenic Bacteroides fragilis, pathogenic E. coli strains and oral Fusobacterium. Here we qualitatively and quantitatively evaluated the presence of oral and intestinal microorganisms inthe fecal microbiota of colorectalcancerpatientsand healthy controls. Seventeen patients (between 49 and 70 years-old) visiting theCancer Institute of the Sao Paulo State were selected, 7 of whom were diagnosed with colorectal carcinoma. Bacterial detection was performed by qRT-PCR. Al- though all of the tested bacteria were detected inthe majority of the fecal samples, quantitative differ- ences between theCancer Group and healthy controls were detected only for F. nucleatum and C. difficile. The three tested oral microorganisms were frequently observed, suggesting a need for fur- thers studies into a potential role for these bacteria during colorectal carcinoma pathogenesis. Despite the small number of patients included in this study, we were able to detect significantly more F. nucleatum and C. difficile intheCancer Group patients compared to healthy controls, suggesting a possible role of these bacteria in colon carcinogenesis. This finding should be considered when screening for colorectalcancer.
ABSTRACT – Context - Acromegalic patients have better chances to develop colorectal polyps andcancerand, considered a high-risk group, need to undergo frequent screening examinations. Moreover, in acromegalia, the increased bowel length andthe intestinal loop complexity can lead to higher levels of technical difficulties and increase the risks of complications at conventional colonoscopy. Computed tomographic colonography, also known as virtual colonoscopy, is an innovative and secure technology which is revolutionizing the diagnosis of colon and rectum neoplasias. Objective - To analyze computed tomographic colonography performance for the screening of colorectal polyps in acromegalic patients. Methods - A prospective study of 21 asymptomatic acromegalic patients, 12 male and 9 female, average age 49, who underwent computed tomographic colonography and conventional colonoscopy. Computed tomographic colonography was performed with a GE Helical Multislice Computed Tomography Apparatus. Conventional colonoscopy was performed inthe same day, without previous knowledge of the computed tomographic colonography diagnostics. Thestudy evaluated the capacity of computed tomographic colonography to detect patients with colorectal polyps and identify each colorectal lesion described by the colonoscopy. Results - In two patients (2/21), conventional colonoscopy was incomplete. However, in all patients computed tomographic colonography was complete. In Phase I (“per patient”), computed tomographic colonography diagnosed eight of the nine patients with colorectal polyps and showed 88% sensitivity, 75% specificity and 81% accuracy. In Phase II (“per polyp”), out of the 21 acromegalic patients included in this study, 12 presented normal findings at conventional colonoscopy. A total of 19 polyps were identified in 9 patients. Ten of the 19 polyps were smaller than 10 mm, and 9 were equal to or larger than 10 mm. Computed tomographic colonography identified 7 of the 9 polyps ≥10 mm described by conventional colonoscopy and only 6 of the 10 small polyps identified at conventional colonoscopy were detected by computed tomographic colonography. The histological analysis of resected lesions revealed 12 tubular adenomas, 6 hyperplastic polyps and 1 colonic tubulo-villous adenoma with an adenocarcinoma focus. Conclusion - The authors present the first reports of computed tomographic colonography inthe screening of colorectal polyps in acromegalic patients. In this study, computed tomographic colonography was performed without complications and a complete and safe colorectal evaluation was possible in all acromegalic patients. Moreover, computed tomographic colonography presented good sensitivity, specificity and accuracy for the identification of acromegalic patients with polyps of any size and better results inthe diagnosis of large polyps, when they were compared to small polypoid lesions.
Adherence to treatment guidelines could be one of the reasons why high-volume providers have better outcomes. High-volume physicians may use effective treatment strategies more often than low-volume physicians . High-volume surgeons also often adopted multi-disciplinary approaches, while low-volume surgeons were less likely to interact with oncologists or attend multi- disciplinary meetings for breast cancer series . Combined therapy utilization may also be one of the reasons for better outcomes in high-volume physicians who treated cancer. Low- volume physicians in low-volume hospitals may not follow international treatment guidelines. For cancer treatment, the combined effects of low-volume surgeons and low-volume hospitals reached the highest hazard ratio of 1.8 in lung cancer. Resection of lung cancerandthe subsequent intensive care is the corner stone of lung cancer surgery treatment. Lung cancer treatment relies on surgeon experience, hospital hardware and Figure 2. Cancer survival rates by combined effect of surgeon and hospital caseloads (a) Breast cancer (b) Colorectalcancer (c) Lung cancer (d) Prostate cancer (e) Head and neck cancer.