BackgroundBeta-catenin is a multifunctional oncogenic protein that contributes fundamentally to cell development and biology. Elevation in expression and activity of β-catenin has been implicated in many cancers and associated with poor prognosis. Beta-catenin is degraded in the cytoplasm by glycogen synthase kinase 3 beta (GSK-3β) through phosphorylation. Cell growth and proliferation is associated with β-catenin translocation from the cytoplasm into the nucleus.This laboratory was the first to demonstrate that selenium-containing compounds can enhance the efficacy and cytotoxicity of anticancer drugs in several preclinical xenograft models. These data provided the basis to identify mechanism of selenium action focusing on β-catenin as a target. This study was designed to: (1) determine whether pharmacological doses of methylseleninic acid (MSeA) have inhibitory effects on the level and the oncogenic activity of β-catenin, (2) investigate the kinetics and the mechanism of β-catenin inhibition, and (3) confirm that inhibition of β-catenin would lead to enhanced cytotoxicity of standard chemotherapeutic drugs.ResultsIn six human cancer cell lines, the inhibition of total and nuclear expression of β-catenin by MSeA was dose and time dependent. The involvement of GSK-3β in the degradation of β-catenin was cell type dependent (GSK-3β-dependent in HT-29, whereas GSK-3β-independent in HCT-8). However, the pronounced inhibition of β-catenin by MSeA was independent of various drug treatments and was not reversed after combination therapy.Knockout of β-catenin by ShRNA and its inhibition by MSeA yielded similar enhancement of cytotoxicity of anticancer drugs.Collectively, the generated data demonstrate that β-catenin is a target of MSeA and its inhibition resulted in enhanced cytotoxicity of chemotherapeutic drugs.ConclusionsThis study demonstrates that β-catenin, a molecule associated with drug resistance, is a target of selenium and its inhibition is associated with increased multiple drugs cytotoxicity in various human cancers. Further, degradation of β-catenin by GSK-3β is not a general mechanism but is cell type dependent.

Introduction Breast cancer represents a traumatic experience with a psychological burden. The prevalence of psychological distress (which include depression and anxiety) among breast cancer patients is estimated to be 15 to 54%, but studies have shown that applying some psychological treatments has contributed to decreasing depression and anxiety. So, it is crucial to diagnose and treat patients with the appropriate means. After reviewing the literature, no studies discussed depression and anxiety among Syrian breast cancer patients. Methods A cross-sectional study in Al-Bairouni hospital in Damascus, Syria carried out using face-to-face interviews based on a structured questionnaire. All breast cancer patients were included, except who refused to participate, and responses with missing data were excluded. The questionnaire consisted of 2 sections: the first included Socio-demographic characteristics, and the other evaluated patients' depression using PHQ-2 and GAD-2 scales. Data were gathered using the Kobo toolbox app and then entered into an Excel sheet. Results Five hundred patients were interviewed. 35.6% of the patients had a GAD-2 score greater than or equal to 3.00, while 35% had a PHQ-2 score greater than or equal to 3.00. There is a significant negative relationship between the age of the patient and the GAD-2 score and PHQ-2 score, which means the older the patient is, the lower the GAD-2 and PHQ-2 scores are. A multivariable regression model showed that younger (age ≤ 45 years) and being widowed were associated with being positive for further evaluation for generalized anxiety disorder. Similarly, patients younger than 45 are significantly associated with the need for further evaluation for major depressive disorder (MDD). Social status had a stronger association with the need for further assessment for MDD, with divorced women showing the strongest association, followed by widowed and married women compared to single women. Conclusion This study showed high anxiety and depression among breast cancer patients. The patient’s age and social status were significant factors in determining the need for further psychological assessment. In General, Younger patients showed higher levels of depression and anxiety, the size of the tumor did not show significant association with psychological distress.

CYP2D6 is a key drug-metabolizing enzyme implicated in the biotransformation of approximately 25% of currently prescribed drugs. Interindividual and interethnic differences in CYP2D6 enzymatic activity, and hence variability in substrate drug efficacy and safety, are attributed to a highly polymorphic corresponding gene. This study aims at reviewing the frequencies of the most clinically relevant CYP2D6 alleles in the Arabs countries. Articles published before May 2021 that reported CYP2D6 genotype and allelic frequencies in the Arab populations of the Middle East and North Africa (MENA) region were retrieved from PubMed and Google Scholar databases. This review included 15 original articles encompassing 2737 individuals from 11 countries of the 22 members of the League of Arab States. Active CYP2D6 gene duplications reached the highest frequencies of 28.3% and 10.4% in Algeria and Saudi Arabia, respectively, and lowest in Egypt (2.41%) and Palestine (4.9%). Frequencies of the loss-of-function allele CYP2D6*4 ranged from 3.5% in Saudi Arabia to 18.8% in Egypt. The disparity in frequencies of the reduced-function CYP2D6*10 allele was perceptible, with the highest frequency reported in Jordan (14.8%) and the lowest in neighboring Palestine (2%), and in Algeria (0%). The reduced-function allele CYP2D6*41 was more prevalent in the Arabian Peninsula countries; Saudi Arabia (18.4%) and the United Arab Emirates (15.2%), in comparison with the Northern Arab-Levantine Syria (9.7%) and Algeria (8.3%). Our study demonstrates heterogeneity of CYP2D6 alleles among Arab populations. The incongruities of the frequencies of alleles in neighboring countries with similar demographic composition emphasize the necessity for harmonizing criteria of genotype assignment and conducting comprehensive studies on larger MENA Arab populations to determine their CYP2D6 allelic makeup and improve therapeutic outcomes of CYP2D6- metabolized drugs.

Background Diagnosis of breast cancer during gestation is a rare occurrence. In addition, the diagnosis of breast cancer in a patient with Crohn’s disease is not common. We present a rare case of gestational breast cancer in a patient with Crohn’s disease, with a concurrent breast cancer diagnosis in her sister. Case presentation A 31-year-old Syrian woman with Crohn’s disease was diagnosed with breast cancer at 30 weeks gestation; she received neoadjuvant chemotherapy during gestation. Incidentally, her 37-year-old sister was also diagnosed concomitantly with breast cancer. Both sisters underwent and successfully completed surgery and adjuvant therapy. At a 5-year review, both patients showed no signs of recurrence. The Crohn’s disease symptoms have also improved after chemotherapy, and the baby born after gestational chemotherapy is currently 5 years old with normal psychomotor development and without any congenital malformations. Conclusions This case report highlights the impact of gestation on breast cancer outcomes, the possibility of giving chemotherapy during gestation, and the effect of chemotherapy on the symptoms of Crohn’s disease.