d-Limonene: a bioactive food component from citrus and evidence for a potential role in breast cancer prevention and treatment

Although limited, observations from cell culture, animal, and epidemiological studies support the presence of anti-cancer properties in citrus peel and the primary bioactive food constituent, d-limonene. Early evidence from animal models suggests that when ingested, d-limonene exhibits a wide spectrum of biologic activity including chemotherapeutic and chemopreventive effects. In some of these early models, an analog of d-limonene, perillyl alcohol, demonstrated a more potent effect than d-limonene itself. Yet, when perillyl alcohol advanced to clinical trials, several trials were ended early due to dose-limiting toxicities. Alternatively, oral d-limonene administration in humans is well tolerated even at high doses supporting its investigation as a potential bioactive for cancer prevention. Though the exact mechanisms of action of d-limonene are unclear, immune modulation and anti-proliferative effects are commonly reported. Here, we review the pre-clinical evidence for d-limonene’s anti-cancer mechanisms, bioavailability, and safety, as well as the evidence for anti-cancer effects in humans, focusing on studies relevant to its use in the prevention and treatment of breast cancer.     

HCV-related morbidity in a rural community of Egypt

The origin of the hepatitis C virus (HCV) epidemic in Egypt has been attributed to intravenous schistosomiasis treatment in rural areas in the 1960s to 70s. The objective of this study was to estimate the HCV-related morbidity in a rural area where mass schistosomiasis treatment campaigns took place 20-40 years before. The study sample included 2,425 village residents aged 18-65 years recruited through home-based visits. Overall, HCV antibody prevalence was 448/2,425 = 18.5% (95% CI = 16.9-20.1%), reaching 45% in males over 40 years, and 30% in females over 50 years. Of those with HCV antibodies, 284/448 (63.4%, 95% CI = 58.7-67.9%) had chronic HCV infection, among which 107/266 (40.2%, 95% CI = 34.3-46.4%) had elevated alanine aminotransferase (ALT). As part of pre-treatment screening, 26 consenting patients had a liver biopsy: 13 (50.0%) had a treatment indication. Thus, of all patients with HCV antibodies, 13 (2.9%) were eligible for treatment and willing to be treated. The relatively low level of morbidity observed in this study is discussed in view of co-factors of HCV infection progression, such as young age at infection, absence of alcohol intake, the prevalence of Schistosoma mansoni infection, and the prevalence of chronic hepatitis B.     

The Potential Role of PTPN-22 C1858T Gene Polymorphism in the Pathogenesis of Type 1 Diabetes in Saudi Population

Background: Recent investigations have reported an association between protein tyrosine phosphatase non-receptor type-22 (PTPN-22) gene polymorphism and susceptibility to the development of type 1 diabetes (T1D) in some populations and not in others. In this study, we aimed to investigate the association of PTPN-22 C1858T polymorphism with T1D in Saudi children.

Methods: A cohort of 372 type 1 diabetic children and 372 diabetes-free subjects was enrolled in the current investigation. The PTPN-22 C1858T polymorphism was identified using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method.

Results: Our data showed that the frequency of CT and TT genotypes of PTPN-22 C1858T was higher in T1D children (17.7% and 4.3%, respectively) compared to healthy controls (4.8% and 1.6%, respectively), and both genotypes were statistically associated with T1D patients (OR = 4.4, 95% CI: 2.55–7.58, p < 0.001; and OR = 3.2, 95% CI: 1.23–8.28, p = 0.017, respectively). Moreover, the 1858T allele was significantly associated with T1D patients compared to the C allele (OR = 3.2, 95% CI: 1.59–6.88, p < 0.001). In addition, the T allele was significantly associated with elevated levels of HbA1c, anti-GAD, and anti-insulin antibodies (p < 0.001) and a lower concentration of C-peptide (p < 0.001) in T1D children.

Conclusion: The data presented here suggests that the T allele of PTPN-22 C1858T polymorphism might be a risk factor for T1D development in Saudi children.     

Identifying the molecular signature of the interstitial deletion 7q subgroup of uterine leiomyomata using a paired analysis

Uterine leiomyomata (UL), the most common neoplasm in reproductive‐age women, have recurrent cytogenetic abnormalities including interstitial deletion of 7q. To develop a molecular signature, matched del(7q) and non‐del(7q) tumors identified by FISH or karyotyping from 11 women were profiled with expression arrays. Our analysis using paired t tests demonstrates this matched design is critical to eliminate the confounding effects of genotype and environment that underlie patient variation. A gene list ordered by genome‐wide significance showed enrichment for the 7q22 target region. Modification of the gene list by weighting each sample for percent of del(7q) cells to account for the mosaic nature of these tumors further enhanced the frequency of 7q22 genes. Pathway analysis revealed two of the 19 significant functional networks were associated with development and the most represented pathway was protein ubiquitination, which can influence tumor development by stabilizing oncoproteins and destabilizing tumor suppressor proteins. Array CGH (aCGH) studies determined the only consistent genomic imbalance was deletion of 9.5 megabases from 7q22‐7q31.1. Combining the aCGH data with the del(7q) UL mosaicism‐weighted expression analysis resulted in a list of genes that are commonly deleted and whose copy number is correlated with significantly decreased expression. These genes include the proliferation inhibitor HPB1, the loss of expression of which has been associated with invasive breast cancer, as well as the mitosis integrity‐maintenance tumor suppressor RINT1. This study provides a molecular signature of the del(7q) UL subgroup and will serve as a platform for future studies of tumor pathogenesis. © 2009 Wiley‐Liss, Inc.     

Relationship between child health literacy and body mass index in overweight children

Objective

To test the relationship between child health literacy and body mass index (BMI) Z-score in overweight children.

Methods

Cross-sectional survey of overweight children and parents. Parent and child health literacy was measured by the Short Test of Functional Health Literacy (STOFHLA). Linear regression tested for predictors of childhood BMI Z-score, adjusting for confounders.

Results

Of 171 total children, 107 (62%) participated, of whom 78 (73%) had complete data for analysis. Mean child BMI Z-score (SD) was 2.3 (0.40); median child age (interquartile range) was 11.5 (10–16); 53% were female; 80% were Medicaid recipients. Mean child STOFHLA was 22.9 (9.0); mean parental STOFHLA was 29.1 (8.6). Child STOFHLA correlated negatively with BMI Z-score (r = −0.37, p = 0.0009) and positively with child eating self-efficacy (r = 0.40, p < 0.0001). After adjusting for confounders, child STOFHLA was independently associated with child BMI Z-score (standardized B = −0.43, p < 0.0001). Overall adjusted r-squared for the regression model was 38%. Child STOFHLA contributed 13% to the overall model.

Conclusions

Child health literacy was negatively correlated with BMI Z-scores in overweight children, suggesting the need to consider health literacy in the intersection between self-efficacy and behavior change when planning interventions that aim to improve child BMI.     

The role of systemic steroids and phototherapy in the treatment of stable vitiligo: a randomized controlled trial

Pathogenesis of vitiligo is believed to be multifactorial disease with a wide variety of therapeutic modalities. The aim of this work is to assess the efficacy of oral mini‐pulse steroids (OMP) plus Nb‐U.V.B in comparison to OMP alone and Nb‐U.V.B alone in treating stable vitiligo. A prospective randomized controlled study including 45 patients categorized into three groups receiving therapy for 3 months; Group A received Nb‐U.V.B plus OMP, Group B received OMP alone while Group C received Nb‐U.V.B alone. Clinical assessment and PCR evaluation of bFGF, ICAM1, and ELISA for AMA were done. Patients receiving Nb‐U.V.B plus OMP and using Nb‐U.V.B alone gave statistically significant clinical response than those treated with OMP alone. Statistically significant rise of BFGF was noticed after treatment with Nb‐U.V.B plus OMP and with Nb‐U.V.B alone. Patients treated with OMP alone and with Nb‐U.V.B alone showed statistically significant drop of ICAM‐1 after therapy. NB‐U.V.B plus OMP and Nb‐U.V.B alone were found to be clinically superior over OMP alone in treating stable vitiligo patients, hence suggesting that adding OMP to Nb‐U.V.B can maintain clinical and laboratory success for a longer period of time and with less relapse.     

Phosphorylation levels of BCR-ABL, CrkL, AKT and STAT5 in imatinib-resistant chronic myeloid leukemia cells implicate alternative pathway usage as a survival strategy

Ex-vivo studies have suggested that imatinib-resistance in chronic myeloid leukemia (CML) patients occurs despite adequate suppression of BCR-ABL activity. Whether BCR-ABL phosphorylation levels differ between imatinib-sensitive and -resistant patients is not known. We compared the phosphorylation of BCR-ABL in 54 previously untreated CML patients and 62 imatinib-resistant CML patients with progressive disease. Resistant patients had significantly lower levels of BCR-ABL, CrkL and AKT phosphorylation than previously untreated patients, but STAT5 phosphorylation showed no difference. These observations suggest that imatinib- resistance is not necessarily dependent on higher activity in BCR-ABL-dependent pathways, but is likely due to the activation of other pathways.