Targeting Cytochrome P450 Enzymes in Ovarian Cancers: New Approaches to Tumor-Selective Intervention.

Over the past decade, there have been significant developments in treatment for ovarian cancer, yet the lack of targeted therapy with few side effects still represents a major issue. The cytochrome P450 (CYP) enzyme family plays a vital role in the tumorigenesis process and metabolism of drugs and has a negative impact on therapy outcomes. Gaining more insight into CYP expression is crucial to understanding the pathophysiology of ovarian cancer since many isoforms are essential to the metabolism of xenobiotics and steroid hormones, which drive the disease's development. To the best of our knowledge, no review articles have documented the intratumoral expression of CYPs and their implications in ovarian cancer. Therefore, the purpose of this review is to provide a clear understanding of differential CYP expression in ovarian cancer and its implications for the prognosis of ovarian cancer patients, together with the effects of CYP polymorphisms on chemotherapy metabolism. Finally, we discuss opportunities to exploit metabolic CYP expression for the development of novel therapeutic methods to treat ovarian cancer.

Cytochrome 4Z1 Expression Connotes Unfavorable Prognosis in Ovarian Cancers.

Background and Objective: Ovarian cancer is a leading cause of death in females. Since its treatment is challenging and causes severe side effects, novel therapies are urgently needed. One of the potential enzymes implicated in the progression of cancers is Cytochrome 4Z1 (CYP4Z1). Its expression in ovarian cancer remains unknown. Therefore, the current study aims to assess CYP4Z1 expression in different subtypes of ovarian cancers. Materials and Methods: Immunohistochemistry was used to characterize CYP4Z1 expression in 192 cases of ovarian cancers along with eight normal ovarian tissues. The enzyme's association with various clinicopathological characteristics and survival was determined. Results: CYP4Z1 was strongly expressed in 79% of ovarian cancers, compared to negative expression in normal ovarian samples. Importantly, significantly high CYP4Z1 expres-sion was determined in patients with advanced-stage cancer and a high depth of invasion (p < 0.05). Surprisingly, CYP4Z1 expression was significantly associated with a low patient survival rate. Univariate analysis revealed that patient survival was strongly associated with CYP4Z1 expression, tumor stage, depth of invasion, and lymph node metastasis (p < 0.05). Multivariate analysis showed that only CYP4Z1 expression was significantly associated with patient survival (p < 0.05). Conclusions: CYP4Z1 expression is correlated with shorter patient survival and has been identified as an independent indicator of a poor prognosis for ovarian cancer patients.

Glypican-3 Differentiates Intraductal Carcinoma and Paget's Disease from Other Types of Breast Cancer.

Background and Objectives: breast cancer remains the most common health burden affecting females worldwide. Despite developments in breast cancer diagnostic approaches and treatment strategies, the clinical management of metastatic breast cancer remains challenging. Thus, there is a need to identify new biomarkers and novel drug targets for breast cancer diagnosis and therapy. Recently, aberrant glypican-3 (GPC3) expression in cancers has gained considerable interest in cancer research. The studies, however, have yielded contradictory results about GPC3 expression in breast cancer. Therefore, the current study aims to analyse GPC3 expression across a large panel of different breast cancer subtypes. Materials and Methods: GPC3 expression was immunohistochemically evaluated in 230 breast cancer patients along with eight normal tissues and its associations to clinical and demographic characteristics, as well as immunohistochemical biomarkers for breast cancer. Moreover, a public database consisting of breast cancer patients' survival data and GPC3 gene expression information was used to assess the prognostic value of GPC3 in the survival of breast cancer patients. Results: GPC3 expression was only characterised in 7.5% of different histological breast cancer subtypes. None of the normal breast tissues displayed GPC3 expression. Interestingly, all cases of Paget's disease, as well as 42.9% of intraductal and 16.7% of mucinous carcinomas were found to have GPC3 expression, where it was able to significantly discriminate Paget's disease and intraductal carcinoma from other breast cancer subtypes. Importantly, GPC3 expression was found more often in tumours that tested positive for the expression of hormone receptors and human epidermal growth factor receptor 2 (HER2), indicating more favourable histological subtypes of breast cancer. Consequently, longer relapse-free survival (RFS) was significantly correlated with higher GPC3 mRNA expression. Conclusions: Our study proposes that GPC3 is a promising breast cancer subtype-specific biomarker. Moreover, GPC3 may have the potential to be a molecular target for the development of new therapeutics for specific subtypes of breast cancer.

Effect of various abiotic stressors on some biochemical indices of Lepidium sativum plants.

In this study, the regulation of ascorbate peroxidase (APX) specific activity, anthocyanin, carotenoid, hydrogen peroxide, lipid peroxidation, and protein levels in cress leaves in response to different abiotic stresses were investigated. The total APX specific activity was significantly elevated after 9 days of drought treatment, short-term (2 h) exposure to 10, 100 and 370 µE of light, long-term exposure (at least 6 days) to 100 mM NaCl versus the specific APX activity in the controls. Furthermore, a significant change in total APX activity was detected in response to treatment with different temperatures; this change was an early response to 4 °C and 30 °C for a maximum of 4 h, while short-term exposure to 35 °C did not change total APX activity. The results of the present study revealed that plants have a wide range of mechanisms to cope with different stresses that possibly involve morphological changes. The results indicated that Lepidium sativum plants launch common protective pathways only under drought, salinity and high light stresses, while other protective mechanisms/strategies could be responsible for increasing the plants tolerance towards temperature and low light. Future studies will investigate changes in the photosynthetic quantum yield and specific target metabolites, proteins, and nonenzymatic antioxidants.

Methicillin-resistant Staphylococcus aureus nasal carriage among primary school-aged children from Jordan: prevalence, antibiotic resistance and molecular characteristics.

BACKGROUND AND AIM: Colonization with methicillin-resistant Staphylococcus aureus (MRSA) increases the risk for subsequent infections with an increased mortality and morbidity. Children were suggested to be a major asymptomatic reservoir for community-associated (CA) MRSA with an ability to quickly spread the MRSA within community. Therefore, the availability of epidemiological and antibiotic susceptibility data of CA-MRSA will be useful for the infection control and management policies. This study aimed to assess the nasal carriage, molecular characteristics and antibiotic susceptibility of MRSA in primary school-aged children from Jordan. PATIENTS AND METHODS: A total of 210 nasal swabs were collected from children aged 6-11 years. Isolated MRSA and its SCCmec typing, Spa type and PVL (Panton-Valentine Leukociden) toxin were identified following culture, biochemical and PCR. Antibiogram was determined by the disc diffusion method. RESULTS: The prevalence of CA-MRSA was 7.1%. Allergic rhinitis and recent antibiotic exposure were the only significant risk factors for MRSA nasal carriage among children. Resistance to erythromycin, trimethoprim-sulfamethoxazole and tetracycline was 33.4, 20 and 13.4%, respectively. All isolates were susceptible to the remaining non-ß-lactam antibiotics used in this study, in particular linezolid and mupirocin. All MRSA isolates were SCCmec type IV and PVL toxin negative and the majority were Spa type t223. CONCLUSION AND RECOMMENDATIONS: This is the first study to assess the MRSA prevalence among children aged 6-11 years in Jordan. The prevalence in community children is within the range compared with other studies in other countries. The antibiogram, SCCmec and Spa types of the isolated MRSA are much similar to what was found previously in Jordan. However, all isolates were PVL toxin negative. The study recommends increasing the public awareness of MRSA and the proper antibiotics dispensing. Future studies to follow-up on the changing epidemiology of the CA-MRSA in Jordan are also recommended.