High levels of leptin and non-high molecular weight-adiponectin in patients with colorectal cancer: Association with chemotherapy and common genetic polymorphisms.

Colorectal cancer (CRC) is the third most frequently diagnosed cancer worldwide. Leptin and adiponectin are hormones produced by adipose tissues, which exhibit opposing effects on tumor growth. Leptin promotes tumor development and metastasis, whereas adiponectin attenuates this. The aim of the present study was to assess the possible association between leptin and adiponectin [both high molecular weight (HMW) and non-HMW factions] levels with CRC, CRC response to chemotherapy, and to study the relationship between LEPR (rs6588147), ADIPO (rs266729), LEP (rs2167270), and ADIPO (rs822369) polymorphisms and CRC. A total of 32 blood samples collected from CRC patients were analyzed to identify the serum levels of leptin and adiponectin, and the presence of CRC related polymorphisms. A total of 25 healthy subjects were recruited in the control group. Serum levels of leptin and adiponectin were detected using ELISA whereas DNA from patients and controls was amplified and analyzed using PCR-restriction fragment length polymorphism assay. The results showed that the levels of leptin and non-HMW adiponectin were significantly higher in CRC patients compared with the controls (P<0.05). In addition, HMW adiponectin was significantly higher in patients receiving chemotherapy. The association between LEPR (rs6588147), ADIPO (rs266729), LEP (rs2167270) and ADIPO (rs822369) polymorphisms and CRC was not significant (P>0.05). In conclusion, higher leptin and non-HMW adiponectin levels may be associated with increased CRC. Chemotherapy may positively influence the levels of HMW adiponectin. No association between LEPR (rs6588147), ADIPO (rs266729), LEP (rs2167270) and ADIPO (rs822369) polymorphisms with CRC was found.

The Influence of IL-1B Gene Polymorphisms on H. pylori Infection and Triple Treatment Response Among Jordanian Population.

BACKGROUND: Helicobacter pylori (H. pylori) is considered the main cause of gastritis, peptic ulcer and gastric carcinoma in the human populations. H. pylori infection influences the secretion level of several proinflammatory cytokines including IL-1ß, which encoded by the IL-1B gene. OBJECTIVE: The current study aimed to investigate whether IL-1B gene polymorphisms are associated with H. pylori infection among the Jordanian population and responses to triple therapy. SUBJECTS AND METHODS: The gastroscopic examination was performed on 412 subjects for H. pylori infection diagnosis, 257 subjects were found to be infected by H. Pylori (positive cases), whereas 155 subjects were uninfected (negative controls). The IL-1B gene T-31C and C3954T polymorphisms were genotyped by PCR-RFLP. RESULTS: It was found that the T-31C polymorphism has a significant association with H. pylori infection (P<0.05), and the TT genotype frequency was significantly higher in infected subjects (50.2%) compared to controls (38.7%). On the other hand, no significant association was detected between C3954T SNPs and H. pylori infection among the Jordanian population. In addition, none of the examined polymorphisms were found to influence the responses to triple therapy. CONCLUSION: The IL-1B gene T-31C SNP might be associated with an enhanced risk of H. pylori infection among the Jordanian population.

The Association between ABCB1 C1236T/C3435T SNPs and H. pylori Infection among Jordanians.

Infection with Helicobacter pylori (H. pylori) is very common and affecting about 50% of the worldwide population. Several genetic variations have been implicated in determining the clinical susceptibility to this infection. In the current study, we examined the association between C1236T (rs1045642) and C3435T (rs1045642) single nucleotide polymorphisms (SNPs) in the ABCB1 gene and the prevalence of H. pylori infection among Jordanians. A total of 412 subjects (257 H. pylori-positive cases and 155 H. pylori-negative controls) were recruited and participated in the study, and the genotyping of the ABCB1 gene was performed using RFLP-PCR techniques. A significant association was detected between C1236T and H. pylori infection (p < 0.01). The frequency of CT genotype was significantly higher in the positive cases (40.1%) compared to the controls (21.3%). In addition, the C3435T SNP was weakly associated with H. pylori infection (p = 0.077). Haplotype analysis of C1236T and C3435T SNPs showed that the TT haplotype was present in 22.7% of the positive cases compared to 30.7% of the negative controls (p < 0.05, odds ratio = 0.663, 95% CI: (0.483-0.911)). Consequently, the TT haplotype seems to decrease the risk of H. pylori infection. In conclusion, the current results suggest an association between ABCB1 SNPs and H. pylori infection in the Jordanian population.

Association of a New Germline Variant in the MUTYH DNA Glycosylase Gene with Colorectal Adenoma Transformation into Malignancy

Background: MUTYH DNA glycosylase germline mutations are linked to the recessive inheritance of multiple adenoma. Studies have revealed that germline mutations in this gene are ethnicity related. This study aimed to identify the germline mutations in MUTYH gene and determine their prevalence among Jordanian patients with colorectal adenoma. Methods: In this study, 150 colorectal adenoma patients and 150 cancer-free individuals with no previous history of polyps were recruited. Sanger DNA sequencing of the MUTYH gene (accession number NG_008189.1) was carried out using 3130xL Genetic Analyzer. Sequencing results were analyzed by ChromasPro, and mutational effects were predicted by online bioinformatics tools. Results: Two novel variants, g.87C>T and c.1264G>C, were identified. g.87C>T was also found in 60 (40%) patients and 10 (6.7%) controls. However, c.1264G>C was detected in 90 (60%) patients and 7 (4.7%) controls. Thus, a significant association was observed between these two variants and colorectal adenoma (p value for both variants was <0.0001). Moreover, the newly identified germline variant, c.1264G>C, was found to be significantly associated with colorectal adenoma transformation into malignancy (p < 0.0001). Conclusion: The data showed high prevalence of two germline mutations in MUTYH gene among Jordanians with colorectal adenoma, which may make them as potential early biomarkers for diagnosis of colorectal adenoma.

GRP78 regulates sensitivity of human colorectal cancer cells to DNA targeting agents.

This study was carried out to investigate the activation status of unfolded protein response (UPR) in colorectal cancer (CRC) and its contribution to CRC resistance to chemotherapy-induced apoptosis. Chemotherapy-induced apoptosis was assessed by the propidium iodide method. Activation of UPR was evaluated in CRC cell lines using immunoblotting technique and in CRC tissues using immunohistochemistry. Findings of the present study revealed that the UPR is constitutively activated in CRC cell lines and CRC tissues isolated from patients, as evidenced by relatively high levels of the 78-kDa glucose-regulated protein (GRP78) and spliced X-box-binding protein 1 mRNA in tissue samples. In addition, CRC cell lines differentially responded to clinically relevant DNA-targeting agents including cisplatin, and 5-flourouracil. Moreover, the levels of GRP78 were inversely associated with sensitivity of CRC cells to chemotherapy-induced apoptosis. Inhibition of GRP78 by siRNA resulted in increased sensitivity of CRC cells to chemotherapeutic agents. Collectively, current results appear to provide novel insights into the role of UPR in determining sensitivity of CRC cells to chemotherapeutic agents and might have important implications for personalized CRC treatment.

Laparoscopic cholecystectomy in the elderly and young: a comparative study.

BACKGROUND/AIMS: To assess the safety and effectiveness of simple laparoscopic cholecystectomy in the elderly patients and to compare it with that in younger patients. METHODOLOGY: All patients underwent laparoscopic cholecystectomy in a four year period in a university hospital were retrospectively studied. They were divided in two groups according to the age: group A (65 years and above) and group B (below 65 years). Information about the diagnosis, operation time, intraoperative complications, conversion to open cholecystectomy, length of hospital stay, morbidity and mortality were collected. RESULTS: A total of 1539 patients underwent laparoscopic cholecystectomy during the study period, 234 (15.2%) patients in group A and 1305 (84.8%) patients in group B. Group A experienced higher rates of conversion to laparotomy (9% vs. 2.1%, p<0.005), longer operative time (105.5 vs. 89.7 minutes, p<0.005), longer hospital stay (6.2 vs. 2.1 days, p<0.005) and more morbidity (13.7% vs. 5.1%, p<0.005). The overall mortality was 0.3% with no significant statistical difference between both groups. CONCLUSIONS: Laparoscopic cholecystectomy is feasible in the elderly patients with low mortality and morbidity. However, it is associated with higher conversion rate, longer operation time, longer hospital stay and higher morbidity compared with younger patients.

Prevalence of depression among relatives of cancer patients in Jordan: a cross-sectional survey.

OBJECTIVE: Depression is common among chronically ill patients and their relatives. In this article, we investigated the prevalence of depression among relatives of cancer patients in Jordan, and studied the relation between several socio-demographic, disease- and treatment-related factors, together with the occurrence of depression among those relatives. METHOD: A cross-sectional survey study was conducted at a major university hospital in Jordan. Relatives of cancer patients were interviewed for socio-demographic information, and medical records were checked for information about disease and treatment of patient. Psychological status of the relative was assessed using the Hospital Anxiety & Depression Scale (HADS). RESULTS: The prevalence of depression in our sample was 81.9%. Age and degree of relatedness were significantly correlated with the occurrence of depression among relatives of cancer patients. Significant correlations were also detected between depression among patient's relatives and the stage of the disease. Positive predictive factors for depression included relatives being middle aged, close relatedness, patients being in advanced disease stage, and on chemotherapy or undergoing surgery for cancer treatment. SIGNIFICANCE OF RESULTS: Depression is prevalent among relatives of cancer patients. Therefore, more attention is needed to detect changes in the psychological state of vulnerable relatives of cancer patients, in an effort to reduce the occurrence of depression.

Spontaneous regression in alveolar soft part sarcoma: case report and literature review.

BACKGROUND: Sarcomas are a type of malignant tumors that arise from connective tissue. They are most of the time found in extremities CASE PRESENTATION: We are presenting a case of adult male patient, who was found to have huge abdominal mass and multiple gastric and duodenal polyps. Pathological diagnosis for all lesions was Alveolar soft part sarcoma. Although he complained from metastasis to both lungs and right atrium, all these deposits regressed spontaneously. Patient stated that he used some herbs (Teucrium polium, Cat Thyme) prescribed for him. No chemotherapy or radiotherapy was given. The duration of regression was about 5 months before other lesions appeared. Later on, he died secondary to brain metastasis. CONCLUSION: ASPS is a rare type of sarcomas that affect primarily the lower limbs. This tumor does rarely metastasize to the gastrointestinal tract.