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.

Colorectal carcinoma: nucleosomes, carcinoembryonic antigen and ca 19-9 as apoptotic markers; a comparative study.

BACKGROUND: Colorectal carcinoma is a common and often fatal disease in which methods of early detection and monitoring are essential. The present study was conducted for measuring serum levels of nucleosomes, carcinoembryonic antigen (CEA) and CA 19-9 in patients newly diagnosed with colorectal carcinoma and confirmed by clinicopathological study. METHOD: Thirty subjects were included in the current study: six normal subjects as a control group with mean age (45.6 ± 7.9) and twenty four colorectal carcinoma patients with mean age (46.9 ± 15.6), which were classified pathologically according to the degree of malignant cell differentiation into well differentiated (group I), moderately differentiated (group II) and poorly differentiated (group III). Fasting venous blood samples were collected preoperative. RESULTS: The results revealed a significant increase in serum level of nucleosomes in patients with poorly differentiated tumors versus patients with well differentiated tumors (p = 0.041). The levels of CEA and CA19-9 showed no significant increase (p = 0.569 and 0.450, respectively). CONCLUSION: In conclusion, serum level of nucleosomes provides a highly sensitive and specific apoptotic marker for colorectal carcinoma.

Cytochrome 4Z1 Expression is Associated with Unfavorable Survival in Triple-Negative Breast Cancers.

PURPOSE: Triple-negative breast cancer (TNBC) is characterized by high mortality rate, and its clinical management is difficult and complex. Therefore, there is a need for extensive efforts aimed at accelerating the discovery of novel therapies for TNBC. CYP4Z1 has been implicated in the development of breast cancer. The current study aimed at characterizing the expression of CYP4Z1 on TNBC. MATERIALS AND METHODS: Using immunohistochemistry, CYP4Z1 expression was evaluated on 122 TNBC samples, four samples of breast cancers expressing ER, PR, and HER-2, and four samples of normal breast tissues. The association between the enzyme and various histopathological features and survival of patients were determined. RESULTS: CYP4Z1 was strongly expressed in 83.3% of various histopathological subtypes of TNBC, when compared to negative expression in normal breast tissues. Interestingly, there were marked variations in CYP4Z1 expression with respect to histopathology subtype, histological grade, histological stage and tumor diameter. There was a high incidence of CYP4Z1 expression in patients with advanced grades, late stages and larger tumor sizes. Importantly, CYP4Z1 expression was correlated with the survival of TNBC patients, but it was an independent determinant of the poor prognosis of TNBC (p< 0.05). CONCLUSION: CYP4ZI may be a potential biomarker or target for evolving new CYP4Z1-targeted treatments.

Screening of Glypican-6 Expression in Benign, Primary and Metastatic Colon Cancers.

BACKGROUND: The development of colon cancer has been described as a multistep process of carcinogenesis. Understanding molecular and cellular changes underlying this process is required to determine potential biomarkers and therapeutic targets in colon cancers. Several molecular entities, including glypicans, are implicated in cancer development. Among these is glypican-6, which is overexpressed in a limited number of cancers. This study aims to characterise the glypican-6 expression in different types of colon cancer. METHODS: Immunohistochemistry was used to characterise glypican-6 expression in a panel of archived formalin-fixed, paraffin-embedded colon tissue types. These types included 39 normal colon tissues, 10 colon tubular adenomas, 60 colon adenocarcinomas without metastasis and 60 colon adenocarcinomas with metastasis. Glypican-6 expression relation to demographic and clinicopathologic features was also examined. RESULTS: Glypican-6 was strongly expressed in benign, primary and metastatic colon tumours. Normal tissue samples exhibited low to undetectable levels of glypican-6. A significantly high glypican-6 expression was displayed in colon cancers with lymph node metastasis, high depth of invasion, distant metastasis, high histological grades and late stages of the disease (P < 0.05). Importantly, a significant differential in glypican-6 expression was found between normal tissues and different types of colon cancer tissues. Moreover, the highest glypican-6 expression was more frequently found in metastatic tumours, followed by primary tumours and the least in benign tumours (P < 0.05). CONCLUSIONS: Selective expression of glypican-6 may establish a basis for potential use as a tissue biomarker or as a novel therapeutic target in treatment of colon cancer.

Cytochrome 4Z1 Expression is Associated with Poor Prognosis in Colon Cancer Patients.

PURPOSE: Colon cancer is a leading cause of mortality worldwide. It has a relatively poor prognosis; therefore, new therapies are needed. One of the tumour-related enzymes that has gained considerable interest is CYP4Z1. This enzyme has been expressed in many tumours and has been hypothesized as a potential biomarker or target for novel anticancer therapies. PATIENTS AND METHODS: CYP4Z1 overexpression was immunohistochemically examined in a large panel of colon tissue types including normal, benign, primary and metastatic ones, and the enzyme's relation to histopathological features and patient survival was evaluated. RESULTS: A high CYP4Z1 expression was observed in benign, primary and metastatic colon tissues compared to a weak or lack of expression in normal tissues. Importantly, there was a significant differential in CYP4Z1 expression where it was stronger in metastatic, primary and benign, respectively (p < 0.05). A significantly high rate of CYP4Z1 expression was found in high histological grades and late stages of the disease, where its expression was more evident in patients with metastasis in the lymph nodes (p < 0.05). Interestingly, CYP4Z1 expression was identified an independent prognostic predictor of poor overall survival of colon cancer patients (p = 0.003). CONCLUSION: CYP4Z1 was distinctly overexpressed in benign, primary and metastatic colon tissues compared to corresponding normal tissues. This differential in CYP4Z1 expression across different types of colon tissues strongly supports CYP4Z1 as potential biomarker and target for novel anticancer therapy development.

Profiling of CYP4Z1 and CYP1B1 expression in bladder cancers.

Bladder cancer is the tenth most common cancer worldwide, where its burden remains a challenge and needs new novel therapies. Several reports indicate expression of CYP4Z1 and CYP1B1 in many tumours. Their expressions are associated with a poor prognosis, and therefore proposed as promising biomarkers or targets for anticancer therapy. By using immunohistochemistry, expression of CYP4Z1 and CYP1B1 was evaluated in a panel of different types of bladder cancer, and the enzymes' relation to histopathological features were assessed. Results showed an increased expression of CYP4Z1 (54.3%) and CYP1B1 (76.9%) in the majority of bladder cancers compared to weak or lack of expression of both enzymes in normal tissues. CYP4Z1expression was significantly associated with tumour grade and stage where the expression was markedly increased in a high grade and advanced stage of the disease (p < 0.05). Additionally, CYP1B1 expression was also associated with TNM staging (p < 0.05) and its expression was increased in patients with lymph node metastasis. The expression profiles of CYP4Z1 and CYP1B1 suggest that both enzymes have the potential to be biomarkers or targets for novel anticancer therapy for bladder cancer. Nevertheless, further studies are needed to better delineate whether these enzymes are druggable targets.

Screening of cytochrome 4Z1 expression in human non-neoplastic, pre-neoplastic and neoplastic tissues.

BACKGROUND: Cytochromes P450 (CYPs) constitute an enzyme family involved in the oxidative metabolism of a wide variety of endogenous and exogenous compounds, including anti-cancer drugs and carcinogens. Unlike other human CYPs, CYP4Z1 is highly expressed in human breast carcinoma and is associated with poor prognosis. As a result, CYP4Z1 was hypothesised to be a potential biomarker or drug target for the discovery and development of promising anti-cancer therapies. MATERIALS AND METHODS: CYP4Z1 expression was immunohistochemically studied in a set of 100 different human tissues, including normal, benign, malignant and metastatic tissues, which originated from 27 anatomical sites. As a tumour model for CYP4Z1 expression, a panel of different breast cancers was evaluated for CYP4Z1 expression and its relation to histopathological features and prognostic immunohistochemical markers. RESULTS: The immunohistochemical results revealed that CYP4Z1 was expressed in only one (4.3%) of the normal tissues from the mammary glands, while the expression of the enzyme was positive in 1 (11%), 12 (19%) and 2 (40%) of the benign, malignant and metastatic tissues, respectively. Interestingly, several tumour entities showed prominent expressions of CYP4Z1, including carcinomas of adrenal cortex, squamous cells of oesophagus, lung and cervix, as well as seminoma, astrocytoma, melanoma and lastly endometrial adenocarcinoma. In breast cancers, CYP4Z1 was expressed in 82% of the cases. Its expression was significantly associated with the pathology of tumour, histological grade and status of lymph node metastasis. Importantly, it was also significantly associated with the expressions of Her2, P53 and Ki-67. CONCLUSION: These findings greatly support future plans for the use of CYP4Z1 as a biomarker or target for anti-cancer drugs. However, large-scale validation studies are needed to better delineate the potential use of CYP4Z1 for therapeutic purposes.

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.

Studies on synthesis, activity and binding with DNA of a new trinuclear platinum compound [{trans-PtCl(NH3)2}2{trans-Pt(thiazole)2}{H2N(CH2)(6NH2}2]Cl3(NO3).

A new trinuclear platinum compound [{trans-PtCl(NH(3))(2)}(2){trans-Pt(thiazole) (2)}{H(2)N(CH(2))(6)NH(2)}(2)]Cl(3) (NO(3)) has been synthesized and characterized. The activity of the compound against three human ovarian cancer cell lines A2780, A2780(cisR) and A2780(ZD0473R), its cell uptake and level of binding with DNA have been determined. JH5 is found to be less active than cisplatin against parent A2780 cell line but more active than cisplatin against the A2780(cisR) and A2780(ZD0473R) resistant cell lines indicated by the lower resistance factors. The results indicate that at the level of its activity JH5 has been better able to overcome mechanisms of resistance operating in A2780(cisR) and A2780(ZD0473R) cell lines. JH5 has higher cellular accumulation of platinum than cisplatin in the A2780(cisR) and A2780(ZD0473R) resistant cell lines but lower than cisplatin in the parents A2780 cell line. Cisplatin binds with DNA forming mainly bifunctional intrastrand 1,2-Pt(GG) and 1,2-Pt(AG) adducts that cause local bending of DNA strand. In contrast, JH5 is expected to bind with DNA to form mainly interstrand long-range G-Pt..Pt..Pt(G) adducts that would induce more of a global change in DNA conformation.

Studies on two new mixed ligand platinum compounds with a trans-geometry.

In this paper we report the synthesis and in vitro activity of two new mixed ligand platinum complexes: trans-[PtCl2(thiazole)(imidazole) [JH3] and trans-[PtCl2(thiazole)(3-hydroxypyridine) [JH4]. Although the compounds are less active than cisplatin against the parent ovarian cancer cell line A2780, they are more active than cisplatin against the resistant cell lines A2780(cisR) and A2780(ZD0473R), thus indicating that JH3 and JH4 have been better able to overcome mechanisms of resistance operating in A2780(cisR) and A2780(ZD0473R). When Pt-DNA binding levels at 24 h in A2780, A2780(cisR) and A2780(ZD0473R) cell lines are compared it is found that whereas for cisplatin the values in resistant cell lines are significantly lower than that in the parent cell line, for JH3 and JH4 Pt-DNA binding levels in the parent and resistant cell lines are comparable, thus providing an explanation for variations in activity of the compounds in the three cell lines.