Identification of growth suppressive genes as cyclin A1 targets in acute myeloid leukemia by microarray analysis

Das testisspezifische Zyklin A1 wird in leukämischen Blasten exprimiert und induziert in transgenen Mäusen eine AML über bislang unbekannte Mechanismen. In der vorliegenden Arbeit wurden durch Zyklin A1 induzierte Veränderungen der Gen-Expression in myeloischen U937 Zellen mittels Microarray identifiziert. WT1 und EGR1 wurden von Zyklin A1 reprimiert, was durch RT-PCR und Western Blot bestätigt wurde. Eine geringe Expression von WT1 und EGR1 fand sich in den Leukämie-Zelllinien KCL22 und ML1. In Organen und Fibroblasten von Zyklin A1-/- Mäusen waren WT1 und EGR1 höher exprimiert als in Kontrollmäusen. In U937 Kontrollzellen wurde nur eine WT1 Isoform gefunden, wohingegen nach Zyklin A1 Überexpression alle vier Isoformen nachweisbar waren. Eine WT1 Isoform reduzierte die Koloniebildung und Zellzyklusprogression in myeloischen 32D Zellen. Insgesamt führt Zyklin A1 Überexpression zu Veränderungen der Genexpression mit den Tumor-Suppressor-Genen WT1 und EGR1 als putative Zielgene

High-Risk Human Papillomavirus and Colorectal Carcinogenesis

Colorectal, colon and rectal, cancer is the third most common malignancy in both men and women worldwide. Colorectal carcinogenesis is a complex, multistep process implicating environmental and lifestyle factors in addition to gene mutation and viral infections. On the other hand, it is well established that human papillomaviruses (HPVs) infection play a crucial role in certain types of human carcinomas including cervical and head and neck (HN); as roughly 96% and 30% of these cancers are positive for high-risk HPVs, respectively. Moreover, it has been reported that the presence of high-risk HPVs is associated with vascular invasion, lymph node metastases, and tumor size in cervical and HN cancers. Recently, several investigations pointed-out that high-risk HPVs are present in around 70% of human colorectal cancers. Likewise, our group has demonstrated that E6/E7 oncoproteins of HPV type 16 convert noninvasive and nonmetastatic human cancer cells to invasive and metastatic form. Accordingly, it is evident that high-risk HPVs are present in human colorectal cancers where they could play an important role in the development of these malignancies. In this chapter, we will discuss the presence and role of high-risk HPVs in human colorectal carcinogenesis and metastasis; particularly, the interaction between E5 and E6/E7 onco-proteins of high-risk HPVs in colorectal malignancies, which has been linked with the initiation and progression of these tumors

Targeting Insulin and Insulin-Like Growth Factor Pathways in Epithelial Ovarian Cancer

Ovarian cancer is the most lethal of all gynecological malignancies, due in part to the diagnosis at an advanced stage caused by the lack of specific signs and symptoms and the absence of reliable tests for screening and early detection. Most patients will respond initially to treatment but about 70% of them will suffer a recurrence. Therefore, new therapeutic modalities are urgently needed to overcome chemoresistance observed in ovarian cancer patients. Evidence accumulates suggesting that the insulin/insulin growth factor (IGF) pathways could act as a good therapeutic target in several cancers, including ovarian cancer. In this paper, we will focus on the role of insulin/IGF in ovarian cancer tumorigenesis and treatment

Development of Mentorship Module and its Feasibility for Community Midwives in Sindh, Pakistan: A Pilot Study

Numerous articles describe the concept of mentorship for providing professional support in midwifery settings in different countries; however, in Pakistan the concept is under developed. Before implementing the concept in the Pakistani context, it was important to first develop a mentorship module and pilot test the idea. Therefore, the aim of the present study was to develop and test a mentorship module to determine its feasibility for educating community midwives about providing mentoring, so that a formal mentorship program could be established in the future. The training aimed to provide skill focused mentorship training to experienced midwives, so that they could perform the role of mentors for newly graduate midwives, in order to support them and build their confidence. The mentorship module was developed with the help of literature review and experts’ suggestion. A structured questionnaire was given to 50 community midwives after they had been provided mentorship training. Community midwives from nineteen districts of Sindh, Pakistan, were surveyed through purposive sampling. All the community midwives agreed that there was a need for mentorship, that the training module was useful, and that they would be able to integrate it into their practice. Over 80% community midwives rated the content of the module as useful, the majority agreed that the total duration of the training (two days) and the length of each session in the training were appropriate. Similarly, all participants reported that the mentoring strategies were helpful. Hence, the mentorship training module was strongly perceived to be feasible and useful by the community midwives of Sindh, Pakistan

Locking Src/Abl Tyrosine Kinase Activities Regulate Cell Differentiation and Invasion of Human Cervical Cancer Cells Expressing E6/E7 Oncoproteins of High-Risk HPV

In this study, we compared the effects of SKI-606 with Iressa, Src/Abl and EGF-R kinase inhibitors, respectively, on selected parameters in HeLa and SiHa cervical cancer cell lines, which express E6/E7 oncoproteins of high-risk HPV types 18 and 16, respectively. Our results show that SKI-606 and Iressa inhibit cell proliferation and provoke G0-G1 cell cycle arrest and reduction of S and G2-M phase using 2 and 5 μM concentrations of these inhibitors. In contrast, SKI-606 induces differentiation to an epithelial phenotype “mesenchymal-epithelial transition”; thus SKI-606 causes a dramatic decrease in cell motility and invasion abilities of HeLa and SiHa cancer cells, in comparison to untreated cells and Iressa-treated cells in which these parameters are only slightly affected. These changes are accompanied by a regulation of the expression patterns of E-cadherin and catenins. The molecular pathway analysis of Src/Abl inhibitor revealed that SKI-606 blocks the phosphorylation of β-catenin and consequently converts its role from a transcriptional regulator to a cell-cell adhesion molecule. Our findings indicate that SKI-606 inhibits signaling pathways involved in regulating tumor cell migration and invasion genes via β-catenin alteration, suggesting that Src inhibitor, in comparison to EGF-R, is a promising therapeutic agent for human cervical cancer

Co-prevalence of Epstein-Barr virus and high-risk human papillomaviruses in Syrian women with breast cancer.

ABSTRAT We recently performed 2 studies viewing the presence of Epstein-Barr virus (EBV) and high-risk human papillomaviruses (HPVs) types 16, 18, 31, 33 and 35 in human breast cancer in the Syrian population. Herein, we report that EBV and high-risk HPVs are co-present in breast cancer in Syrian women. Therefore, and based on our previous studies and present data, we reveal that 35 (32%) of 108 cancer samples are positive for both EBV and high-risk HPVs and their co-presence is associated with high grade invasive ductal carcinomas (IDCs) with at least one positive lymph nodes, in comparison with EBV and high-risk HPVs-positive samples, which are low to intermediate grade IDCs, respectively. Future studies are needed to confirm the co-presence and the cooperation effect of these onco-viruses in human breast carcinogenesis and metastasis.This work was supported by the Canadian Institutes for Health Research (CIHR) and the Fonds de la Recherche en Santé du Québec (FRSQ- Réseau du Cancer). The new research lab of Dr. Al Moustafa is supported by the College of Medicine at Qatar University

Impact of single-walled carbon nanotubes on the embryo: a brief review

Carbon nanotubes (CNTs) are considered one of the most interesting materials in the 21st century due to their unique physiochemical characteristics and applicability to various industrial products and medical applications. However, in the last few years, questions have been raised regarding the potential toxicity of CNTs to humans and the environment; it is believed that the physiochemical characteristics of these materials are key determinants of CNT interaction with living cells and hence determine their toxicity in humans and other organisms as well as their embryos. Thus, several recent studies, including ours, pointed out that CNTs have cytotoxic effects on human and animal cells, which occur via the alteration of key regulator genes of cell proliferation, apoptosis, survival, cell–cell adhesion, and angiogenesis. Meanwhile, few investigations revealed that CNTs could also be harmful to the normal development of the embryo. In this review, we will discuss the toxic role of single-walled CNTs in the embryo, which was recently explored by several groups including ours.the Canadian Institutes for Health Research, the Cancer Research Society Inc. of Canada, the National Colorectal Cancer Campaign, the Fonds de la Recherche en Santé du Québec (FRSQ-Réseau du Cancer), and by the College of Medicine at Qatar University

Co-Incidence of Epstein-Barr Virus and High-Risk Human Papillomaviruses in Cervical Cancer of Syrian Women.

Epstein-Barr virus (EBV) has been recently shown to be co-present with high-risk human papillomaviruses (HPVs) in human cervical cancer; thus, these oncoviruses play an important role in the initiation and/or progression of this cancer. Accordingly, our group has recently viewed the presence and genotyping distribution of high-risk HPVs in cervical cancer in Syrian women; our data pointed out that HPVs are present in 42/44 samples (95%). Herein, we aim to explore the co-prevalence of EBV and high-risk HPVs in 44 cervical cancer tissues from Syrian women using polymerase chain reaction, immunohistochemistry, and tissue microarray analyses. We found that EBV and high-risk HPVs are co-present in 15/44 (34%) of the samples. However, none of the samples was exclusively EBV-positive. Additionally, we report that the co-expression of LMP1 and E6 genes of EBV and high-risk HPVs, respectively, is associated with poorly differentiated squamous cell carcinomas phenotype; this is accompanied by a strong and diffuse overexpression of Id-1 (93% positivity), which is an important regulator of cell invasion and metastasis. These data imply that EBV and HPVs are co-present in cervical cancer samples in the Middle East area including Syria and their co-presence is associated with a more aggressive cancer phenotype. Future investigations are needed to elucidate the exact role of EBV and HPVs cooperation in cervical carcinogenesis.We would like to thank Mrs. A. Kassab for her critical reading of the manuscript. This work was supported by Qatar University grants # GCC-2017-002 QU/KU and QUCG-CMED-2018\2019-3