Mansour Al-Moundhri

Coping With a Diagnosis of Breast Cancer-Literature Review and Implications for Developing Countries

Abstract:  Breast cancer is the most common cancer affecting women worldwide. Women are at an increased risk of developing both physical and psychological morbidity after diagnosis; however, many use different strategies to cope with the disease. The aim of this article is to review the available literature on the impact of breast cancer diagnoses and the strategies used by women to cope with this disease. The implications of these emerging findings are extrapolated within the context of health services provided in developing countries. Electronic databases were used to search the relevant literature. The findings showed that women who were diagnosed with breast cancer are at risk of developing several psychological morbidities such as depression, anxiety, fatigue, negative thoughts, suicidal thoughts, fear of dying, sense of aloneness, sexual and body images problems, as well as an overall decrease in the quality of life. Several strategies are used by women with breast cancer to cope with the disease, including positive cognitive restructuring, wishful thinking, emotional expression, disease acceptance, increased religious practice, family and social support, and yoga and exercise. Breast cancer diagnoses have been associated with several devastating psychological consequences; however, many women have used different coping strategies to adjust their lives accordingly. Healthcare professionals in developing countries, who work with women with breast cancer, should be aware of the different coping mechanisms that women use when diagnosed with cancer. Integrating a coping strategy into the treatment regimen would constitute an important milestone in the palliative care of patients with breast cancer.

Amelioration of Cisplatin-Induced Nephrotoxicity in Rats by Tetramethylpyrazine, a Major Constituent of the Chinese Herb Ligusticum wallichi

Nephrotoxicity of the anticancer drug, cisplatin (CP) involves enhanced renal generation of reactive oxygen metabolites and lipid peroxidation caused by decreased levels of antioxidants and antioxidant enzymes. Tetramethylpyrazine (TMP) is known to act as a strong antioxidant. Therefore, in the present work, we aimed at testing the possible protective or palliative effect of TMP on CP nephrotoxicity in rats. TMP was given orally at a dose of 80 mg · kg− 1 · day− 1 for 7 days. Some of these rats were given a single intraperitoneal injection of CP (or vehicle) at a dose of 6 mg/kg on Day 6 of treatment. Animals were sacrificed 6 days after CP (or vehicle) treatment, and blood, urine, and kidneys were obtained. Nephrotoxicity was assessed biochemically by measuring creatinine and urea in serum, reduced glutathione (GSH) concentration in renal cortex, by urinalysis, and histopathologically by light microscopy. CP significantly increased the concentration of urea and creatinine (P < 0.05) by about 128% and 170%, respectively; increased urine volume and N-acetyl-β-D-glucosaminidase (NAG) activity; and significantly decreased osmolality and protein concentrations. CP treatment reduced GSH by about 34% (P < 0.05) and superoxide dismutase (SOD) and total antioxidant activity (TOX) by about 28% and 21%, respectively (P < 0.05). TMP pretreatment significantly mitigated all of these effects. Sections from saline- and TMP-treated rats showed apparently normal proximal tubules. However, kidneys of CP-treated rats had a moderate degree of necrosis. This was markedly reduced when CP was given after pretreatment with TMP. CP cortical concentration was not significantly altered by TMP treatment. The results suggest that TMP ameliorated the histological, physiological, and biochemical indices of nephrotoxicity in rats. Pending further pharmacological and toxicological studies, TMP may potentially be useful as a nephroprotective agent.

Changing trends of breast cancer survival in sultanate of oman.

Breast cancer is the leading cause of cancer-associated mortality in women, with elevated incidence in developing countries. This retrospective study included all 122 patients diagnosed with breast cancer from January 2003 to December 2008 in the Sultanate of Oman. Age at presentation was 47.41 years (SD±12.88), with one-third of patients younger than 40 years. The majority of patients presented with stage III (41.2%) and IV (18.2%) breast cancer. T size (P = .023), skin involvement (P = .003), and stage at presentation (P = .004) were significantly associated with overall survival. Skin involvement at presentation (P = .003), T size (P = .09), lymph node status (P = .013), and stage (P = .003) were strong predictors of relapse-free survival. Patients had a 5-year survival of 78%, compared to 64% of breast cancer patients diagnosed between 1996 and 2002 identified in our previously published study. Thus, despite Omani breast cancer patients continuing to present with advanced breast cancer, survival rates have significantly improved.

The prognostic significance of whole blood global and specific DNA methylation levels in gastric adenocarcinoma

Background Epigenetics, particularly DNA methylation, has recently been elucidated as important in gastric cancer (GC) initiation and progression. We investigated the clinical and prognostic importance of whole blood global and site-specific DNA methylation in GC. Methods Genomic DNA was extracted from the peripheral blood of 105 Omani GC patients at diagnosis. DNA methylation was quantified by pyrosequencing of global DNA and specific gene promoter regions at 5 CpG sites for CDH1, 7 CpG sites for p16, 4 CpG sites for p53, and 3 CpG sites for RUNX3. DNA methylation levels in patients were categorized into low, medium, and high tertiles. Associations between methylation level category and clinicopathological features were evaluated using χ2 tests. Survival analyses were carried out using the Kaplan-Meier method and log rank test. A backward conditional Cox proportional hazards regression model was used to identify independent predictors of survival. Results Older GC patients had increased methylation levels at specific CpG sites within the CDH1, p53, and RUNX-3 promoters. Male gender was significantly associated with reduced global and increased site-specific DNA methylation levels in CDH1, p16, and p53 promoters. Global DNA low methylation level was associated with better survival on univariate analysis. Patients with high and medium methylation vs. low methylation levels across p16 promoter CpG sites, site 2 in particular, had better survival. Multivariate analysis showed that global DNA hypermethylation was a significant independent predictor of worse survival (hazard ratio (HR) = 2.0, 95% CI: 1.1–3.8; p = 0.02) and high methylation mean values across p16 promoter sites 1–7 were associated with better survival with HR of 0.3 (95% CI, 0.1–0.8; p = 0.02) respectively. Conclusions Analysis of global and site-specific DNA methylation in peripheral blood by pyrosequencing provides quantitative DNA methylation values that may serve as important prognostic indicators.

Gastric cancer risk predisposition and prognostic significance of vascular endothelial growth factor (VEGF) gene polymorphisms - a case-control study in an Omani population.

Vascular endothelial growth factor (VEGF) plays a central role in angiogenesis, tumor growth, and metastasis. We investigated the associations between VEGF gene polymorphisms and gastric cancer (GC) risk predisposition and prognostic characteristics in an Omani population, an ethnic group which has not been studied previously. We analyzed three VEGF polymorphisms (+405 G/C, −460 T/C, and +936 C/T) by the extraction of genomic DNA from peripheral blood of 130 GC patients and 130 control subjects followed by VEGF genotyping using polymerase chain reaction restriction fragment length polymorphism (PCR‐RFLP) analysis. There were no significant associations between the VEGF polymorphisms and GC risk. There were significant correlations between the +405 C/C genotype and both poor tumor differentiation (P = 0.007) and lymph node metastasis (P = 0.03) and between the −460 T/T genotype and poor tumor differentiation (P = 0.03) with a statistical trend toward lymph node involvement (P = 0.05). VEGF gene polymorphisms had no significant effects on survival, but the VEGF +405 G/G genotype had a statistical trend toward lower survival rate with a hazard ratio of 1.6 [95% CI, 0.9–2.9] compared with the VEGF +405 CC/GC combined genotype (P = 0.049). Multivariate analysis showed that disease stage at diagnosis and the +405 G/G genotype were independent variables of adverse prognostic significance. There were no associations between the six common haplotypes identified and both GC risk predisposition and survival. The current study suggests that VEGF polymorphisms have no role in GC risk predisposition, but may have prognostic significance in GC patients. Mol. Carcinog.

Combined polymorphism analysis of glutathione S-transferase M1/G1 and interleukin-1B (IL-1B)/interleukin 1-receptor antagonist (IL-1RN) and gastric cancer risk in an Omani Arab population.

Background Host genetics have been implicated in gastric cancer carcinogenesis. Polymorphisms of glutathione S-transferase (GST) M1 and G1 and of interleukin-1B (IL-1B) and interleukin-1 receptor antagonist (IL-1RN) were shown to increase gastric cancer predisposition in several studies. To our knowledge, this is the first report on the combined analysis of polymorphisms GSTM1/G1 and IL-1B/IL-1RN genes in gastric adenocarcinoma. Methods Genomic DNA was extracted from peripheral blood of 107 control subjects and 107 gastric cancer patients. Analysis for the GSTM1 and GSTT1 gene polymorphisms was performed by multiplex polymerase chain reaction. The DNA samples were analyzed using the TaqMan allelic discrimination test for the polymorphism of IL-1B at positions-31. The variable number of tandem repeats of IL-1RN was genotyped using polymerase chain reaction followed by agarose gel electrophoresis. Results There were no statistically significant associations between the GSTM1/G1 or IL-1B-31 genes and gastric cancer risk. There was a statistical association between the presence of the IL-1RN*2 allele and gastric cancer (odds ratio 2.2, 95% confidence interval=1.2-3.7, P=0.01). Combined analysis showed that a combination of the null GSTM1 genotype and carriers of IL-1RN*2 was associated with a statistically significant correlation with gastric cancer (odds ratio=3.6, 95% confidence interval=1.4-9.4, P=0.008). Conclusions The current study suggests that the individual variation in both the cellular inflammatory modulator IL-1RN and the antioxidative property of GSTM1 may predispose individuals to an increased risk of gastric cancer.

Interleukin-1β gene (IL-1B) and interleukin 1 receptor antagonist gene (IL-1RN) polymorphisms and gastric cancer risk in an Omani Arab population

BackgroundGastric cancer (GC) is the most common malignancy in Oman. Interleukin-1β gene (IL-1B) and interleukin-1 receptor antagonist gene (IL-1RN) polymorphisms have been associated with increased GC risk. No previous studies have examined their role in an Arab population. We tested the associations between polymorphisms of IL1B at positions −31, −511, and +3954 and the IL-1RN polymorphism [variable number of tandem repeats (VNTR) and TC polymorphism at the −2018 position] and GC in Omani Arab patients.MethodsGenomic DNA was extracted from peripheral blood of 245 control subjects and 118 gastric cancer patients. The DNA samples were analyzed using the TaqMan allelic discrimination test for IL-1B −31, −511, and +3954 polymorphisms and IL-1RN −2018 polymorphism. The VNTR of IL-1RN was genotyped using the polymerase chain reaction followed by agarose gel electrophoresis.ResultsThere was an association between the presence of IL-1RN*2 allele and gastric cancer [odds ratio (OR) = 2.2, 95% confidence interval (CI) = 1.0–3.3, P = 0.04). The GC risk further increased to OR = 3.5 (95% CI = 1.0–11.9) in Helicobacter pylori-positive patients. No association was found between any of the other polymorphisms studied and GC.ConclusionIL-1RN polymorphism increased the risk of GC in an Omani Arab population, consistent with previous reports. In contrast, the IL-1B −31 polymorphism was not associated with an increased GC risk. These findings underscore the role of cytokine gene polymorphisms in the development of GC and further support the ethnic differences in the effect of IL-1B polymorphism on GC carcinogenesis.

Dietary and lifestyle factors and risk of non-hodgkin's lymphoma in Oman.

BACKGROUND The incidence of various types of cancers including the non-Hodgkins lymphoma (NHL) has increased during the recent years. Diet and lifestyle factors have been reported to play an important role in the etiology of NHL. However, no such data are available from the Middle Eastern countries, including Oman. MATERIALS AND METHODS Forty-three histologically confirmed cases of non-Hodgkins lymphoma (NHL) diagnosed at the Sultan Qaboos University Hospital (SQUH) and the Royal Hospital (RH), Muscat, Oman and forty-three age and gender matched controls were the subjects of this study. Frequency matching was used to select the control population. Information on social and demographic data as well as the dietary intake was collected by personal interviews, using a 117-items semi-quantitative food frequency questionnaire. RESULTS A non-significant increased risk of NHL was observed with higher body mass index (BMI) (OR=1.20, 95%CI: 0.45, 2.93), whereas a significantly decreased risk of NHL was associated with a higher educational level (OR=0.12, 95%CI: 0.03, 0.53). A significantly increased risk was observed for higher intake of energy (OR=2.67, 95%CI: 0.94, 7.57), protein (OR=1.49, 95%CI: 0.54, 4.10) and carbohydrates (OR=5.32, 95%CI: 1.78, 15.86). Higher consumption of daily servings from cereals (OR=3.25, 95%CI: 0.87, 12.09) and meat groups (OR=1.55, 95%CI: 0.58, 4.15) were also found to be associated with risk of NHL, whereas a significantly reduced risk was associated with higher consumption of vegetables (OR=0.24, 95%CI: 0.07, 0.82). The consumption of fruits, milk and dairy products however showed no significant association with the risk of developing NHL. CONCLUSION The results suggest that obesity, high caloric intake, higher consumption of carbohydrate and protein are associated with increased risk of NHL, whereas a significantly reduced risk was observed with higher intake of vegetables.

The Effect of Sildenafil on Cisplatin Nephrotoxicity in Rats

Sildenafil, the first drug for erectile dysfunction, has cardiopulmonary protective actions. A recent study has reported that sildenafil given intraperitoneally (i.p.) attenuated cisplatin (CP)-induced nephrotoxicity. Here, we evaluated whether sildenafil, given by two different routes and at two different doses, can attenuate CP-induced nephrotoxicity and would also affect renal haemodynamics in CP-treated rats. Six groups of rats were treated with saline (controls), CP [5 mg/kg, intraperitoneally (i.p.) once], sildenafil (0.4 mg/kg/day, i.p. for 5 days), sildenafil (0.4 mg/kg/day i.p. for 5 days) plus CP (5 mg/kg, i.p., once), sildenafil [10 mg/kg/day, subcutaneous (s.c.) for 5 days] or sildenafil (10 mg/kg/day, s.c. for 5 days) plus CP (5 mg/kg, i.p. once). Five days after the end of the treatments, urine was collected from all rats, which were then anaesthetized for blood pressure and renal blood flow monitoring. This was followed by intravenous (i.v.) injection of norepinephrine for the measurement of renal vasoconstrictor responses. Thereafter, blood and kidneys were collected for measurement of several biochemical, functional and structural parameters. CP reduced body-weight and renal blood flow but did not affect norepinephrine-induced renal vasoconstriction. It increased the plasma concentrations of urea and creatinine, and reduced creatinine clearance. CP caused extensive renal tubular necrosis, increased urine volume and N-acetyl-β-D-glucosaminidase activity. When sildenafil (0.4 mg/kg/day, i.p. for 5 days) was combined with cisplatin, there was a dramatic improvement in renal histopathology, reduction in N-acetyl-β-D-glucosaminidase and increase in renal blood flow. However, sildenafil (10 mg/kg/day, s.c. for 5 days) did not affect CP nephrotoxicity, suggesting the importance of dose and route selection of sildenafil as a nephroprotectant.

Coping with a diagnosis of breast cancer among Omani women

The aim of this study was to identify coping strategies experienced by Omani women after breast cancer diagnosis. Individual semistructured interviews were conducted with 19 women diagnosed with breast cancer. Several coping strategies were identified including denial, optimism, withdrawal, Islamic beliefs and practices, and the support of family members and health-care providers, but Islamic beliefs and practices were the commonest. Health-care professionals should be aware of and respect women’s coping strategies and encourage them to use to reduce the psychological symptoms. They should also make family members and friends aware of their role in supporting and encouraging coping strategies.