Saleh Al-Karim
King Abdulaziz University
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Publication
Featured researches published by Saleh Al-Karim.
Drug Discovery Today | 2015
Ishaq Khan; Saleh Al-Karim; Roop Singh Bora; Adeel Chaudhary; Kulvinder Singh Saini
Despite earlier controversies about their role and existence within tumors, cancer stem cells (CSCs) are now emerging as a plausible target for new drug discovery. Research and development (R&D) efforts are being directed against key gene(s) driving initiation, growth, and metastatic pathways in CSCs and the tumor microenvironment (TME). However, the niche signals that enable these pluripotent CSCs to evade radio- and chemotherapy, and to travel to secondary tissues remain enigmatic. Small-molecule drugs, biologics, miRNA, RNA interference (RNAi), and vaccines, among others, are under active investigation. Here, we examine the feasibility of leveraging current knowhow of the molecular biology of CSCs and their cellular milieu to design futuristic, targeted drugs with potentially lower toxicity that can override the multiple drug-resistance issues currently observed with existing therapeutics.
Oncotarget | 2016
Waqas Iqbal; Saleh Al-Karim; Ahmed M. Al-Hejin; Hasan Mukhtar; Kulvinder Singh Saini
Tumor comprises of heterogeneous population of cells where not all the disseminated cancer cells have the prerogative and “in-build genetic cues” to form secondary tumors. Cells with stem like properties complemented by key signaling molecules clearly have shown to exhibit selective growth advantage to form tumors at distant metastatic sites. Thus, defining the role of cancer stem cells (CSC) in tumorigenesis and metastasis is emerging as a major thrust area for therapeutic intervention. Precise relationship and regulatory mechanisms operating in various signal transduction pathways during cancer dissemination, extravasation and angiogenesis still remain largely enigmatic. How the crosstalk amongst circulating tumor cells (CTC), epithelial mesenchymal transition (EMT) process and CSC is coordinated for initiating the metastasis at secondary tissues, and during cancer relapse could be of great therapeutic interest. The signal transduction mechanisms facilitating the dissemination, infiltration of CSC into blood stream, extravasations, progression of metastasis phenotype and angiogenesis, at distant organs, are the key pathologically important vulnerabilities being elucidated. Therefore, current new drug discovery focus has shifted towards finding “key driver genes” operating in parallel signaling pathways, during quiescence, survival and maintenance of stemness in CSC. Understanding these mechanisms could open new horizons for tackling the issue of cancer recurrence and metastasis-the cause of ~90% cancer associated mortality. To design futuristic & targeted therapies, we propose a multi-pronged strategy involving small molecules, RNA interference, vaccines, antibodies and other biotechnological modalities against CSC and the metastatic signal transduction cascade.
Tissue & Cell | 2015
Ghadeer Ibrahim Alrefaei; Saleh Al-Karim; Nasra Naeim Ayuob; Soad Shaker Ali
BACKGROUND Although the human placenta is considered medical wastes, it has become a main source of stem cells. Due to their easy isolation, ability to resist immune rejection and ability to differentiate into different types of adult cells, placental stem cells are considered superior to other stem cells. OBJECTIVES This study aimed to assess the impact of the maternal age on the expression of mesenchymal stem cell (MSC) markers CD105 and CD29 in different areas of a term human placenta and to identify the differential expression of these markers in different placental areas. SUBJECTS AND METHODS In this comparative cross sectional study, one hundred term placentas were collected after delivery from healthy mothers divided into five groups according to their age. Placentas were processed to assess both immune- and gene-expression of CD105 and CD29 surface antigen markers. Data of the different studied age groups was compared using the Statistical Package of Social Science (SPSS) software. RESULTS CD105 and CD29 immunoexpression in decidua basalis, fetal membrane and placental villi showed significant negative correlations with the maternal age. CD105- and CD29-positive MSCs were significantly abundant in the decidua basalis and placental villi. Real-time polymerase chain reaction results were consistent with those of the immunohistochemical study. CONCLUSION Labeling the placenta-driven MSCs with the specific area from which the cells were taken as well as the mothers age is advised and could be helpful in controlling the quality of the cell banks as well as the favorable outcome of the therapeutic applications.
Folia Histochemica Et Cytobiologica | 2015
Ghadeer Ibrahim Alrefaei; Nasra Naeim Ayuob; Soad Shaker Ali; Saleh Al-Karim
INTRODUCTION Although the human umbilical cord (UC) has been previously considered a medical waste, its use as a main source of fetal stem cells for regenerative medicine applications has increased over the past few years. The aim of the study was to assess the impact of the maternal age on the expression of mesenchymal stem cells (MSC) markers CD105 and CD29 in the different areas of human UC. MATERIAL AND METHODS In this comparative cross sectional study, one hundred term UCs from five maternal age groups (20-45 years) were collected after delivery from healthy mothers and were processed to assess both immuno- and gene expression of CD105 and CD29 surface antigen markers using immunohistochemical and RT-PCR techniques. RESULTS The immunoexpression of CD105 and CD29 in the amniotic membrane (AM) and Whartons jelly (WJ), the umbilical artery (UA) and the umbilical vein (UV) showed significant negative correlation with the maternal age (p < 0.001). Reduced amount of cells as well as the studied MSC markers and their gene expression levels were documented in older age mothers. CD105-positive MSCs were more abundant in the UA, whereas CD29-positive MSCs were more abundant in the AM and WJ. CONCLUSION The decreased expression of CD105 and CD29 MSCs markers with age suggests that selective isolation of MSCs from Whartons jelly, umbilical artery or umbilical vein of younger mothers should be recommended.
Folia Histochemica Et Cytobiologica | 2017
Wafaa S. Ramadan; Ghada A. Abdel-Hamid; Saleh Al-Karim; Aymn T. Abbas
INTRODUCTION Spinal cord injury (SCI) is a life-disrupting condition in which the first few days are the most critical. Secondary conditions remain the main causes of death for people with SCI. The response of different cell types to SCI and their role at different times in the progression of secondary degeneration are not well understood. The aim of this study was to study the histopathological changes of compressed spinal cord injury (CSCI) in a rat model. MATERIAL AND METHODS Forty adult male Sprague-Dawley rats were divided into four groups. In group I, the rats were left without any surgical intervention (control). In group II, the rats were subjected to laminectomy without spinal cord compression (sham-operated). In group III, the rats were sacrificed one day after CSCI. In group IV, the rats were sacrificed seven days after CSCI. The light microscopy was employed to study the morphology using H&E, osmic acid staining and immunohistochemistry to detect glial fibrillary acidic protein (GFAP). The electron microscopy was applied for ultrastructure study. RESULTS Histopathological examination of the posterior funiculus of the white matter revealed minute hemorrhages and localized necrotic areas on day 1, which transformed to areas of cavitation and fibrinoid necrosis surrounded by a demarcating rim of numerous astrocytes by day 7. The mean percentage of area of GFAP expression increased significantly by day 7. Osmic acid staining revealed swollen nerve fibers after one day, while numerous fibers had been lost by day 7. An ultrastructure study revealed swollen redundant thinned myelin and myelin splitting, as well as degeneration of axoplasm on day 1. On day 7, layers of the myelin sheath were folded and wrinkled with partial or complete demyelination areas. The myelin lamellae were disorganized and loose. The G-ratio was significantly greater on day 1 than day 7 after CSCI. CONCLUSIONS In the rat model of CSCI details of the progressive spinal cord injury can be analyzed by morphological methods and may be helpful in the identification of the onset and type of clinical intervention.
Cancer Cell International | 2017
Ishaq Khan; Saleh S. Baeesa; Mohammed Bangash; Hans-Juergen Schulten; Fahad Alghamdi; Hanadi Qashqari; Nawal Madkhali; Angel Carracedo; Mohamad Saka; Awatif Jamal; Jaudah Al-Maghrabi; Mohammed H. Al-Qahtani; Saleh Al-Karim; Ghazi A. Damanhouri; Kulvinder Singh Saini; Adeel Chaudhary; Adel M. Abuzenadah; Deema Hussein
BackgroundMeningioma tumors arise in arachnoid membranes, and are the most reported central nervous system (CNS) tumors worldwide. Up to 20% of grade I meningioma tumors reoccur and currently predictive cancer stem cells (CSCs) markers for aggressive and drug resistant meningiomas are scarce.MethodsMeningioma tissues and primary cell lines were investigated using whole transcriptome microarray analysis, immunofluorescence staining of CSCs markers (including CD133, Sox2, Nestin, and Frizzled 9), and drug treatment with cisplatin or etoposide.ResultsUnsupervised hierarchical clustering of six meningioma samples separated tissues into two groups. Analysis identified stem cells related pathways to be differential between the two groups and indicated the de-regulation of the stem cell associated genes Reelin (RELN), Calbindin 1 (CALB1) and Anterior Gradient 2 Homolog (AGR2). Immunofluorescence staining for four tissues confirmed stemness variation in situ. Biological characterization of fifteen meningioma primary cell lines concordantly separated cells into two functionally distinct sub-groups. Pleomorphic cell lines (NG type) grew significantly faster than monomorphic cell lines (G type), had a higher number of cells that express Ki67, and were able to migrate aggressively in vitro. In addition, NG type cell lines had a lower expression of nuclear Caspase-3, and had a significantly higher number of CSCs co-positive for CD133+ Sox2+ or AGR2+ BMI1+. Importantly, these cells were more tolerant to cisplatin and etoposide treatment, showed a lower level of nuclear Caspase-3 in treated cells and harbored drug resistant CSCs.ConclusionCollectively, analyses of tissues and primary cell lines revealed stem cell associated genes as potential targets for aggressive and drug resistant meningiomas.
Stem Cells International | 2018
Faisal A. Alzahrani; Mohammed Abu El-Magd; Ahmed Abdelfattah-Hassan; Ayman A. Saleh; Islam M. Saadeldin; Eman S. El-Shetry; Abdelnaser Badawy; Saleh Al-Karim
Cross talk, mediated by exosomes, between normal stem cells and cancer stem cells (CSCs) in the tumor microenvironment has been given less attention so far. In addition, no publications are available in the literature that address the in vivo impact of exosomes derived from CSCs and mesenchymal stem cells (MSCs) on progression of long-term hepatocellular carcinoma (HCC). Herein, we hypothesized that transfer of exosomes among the cells in the HCC microenvironment could either induce or inhibit tumor growth and metastasis depending on their source. To check this hypothesis, we investigated the effect of exosomes coming from two different stem cell populations, hepatic CSCs and bone marrow (BM) MSCs, on progression of long-term DEN-induced HCC in rats and the involved underlying mechanisms. CSCs-exosomes induced a significant increase in liver relative weight and serum levels of cancer markers (AFP and GGT) and liver enzymes (ALT, AST, and ALP), intensive immunostaining for the HCC marker GST-P, and an increased number and area of tumor nodules as compared to HCC rats injected by PBS. CSCs-exosomes also decreased apoptosis (marked by downregulation of Bax and p53 and upregulation of Bcl2, and increased immunostaining of PCNA), increased angiogenetic activity (revealed by upregulation of VEGF), enhanced metastasis and invasiveness (indicated by upregulation of P13K and ERK proteins and their downstream target MMP9 and downregulation of TIMP1), and induced epithelial mesenchymal transition (marked by increased serum and hepatic level of TGFβ1 mRNA and protein). Notably, CSCs-exosomes also elevated HCC exosomal microRNA (miR) 21, exosomal long noncoding (lnc) RNA Tuc339, lncHEIH, and the HCC lncHOTAIR and decreased liver miR122 and HCC miRs (miR148a, miR16, and miR125b). All these cellular, functional, and molecular changes were reversed following injection of BM-MSCs-exosomes. However, both CSCs- and MSCs-exosomes failed to change the elevated oxidative stress or the inhibited antioxidant activities induced by HCC. Collectively, our results revealed a tumor stimulatory effect (induction of tumor growth, progression, and metastasis) for exosomes derived from CSCs and an inhibitory effect for exosomes derived from MSCs. These results provide valuable insight on the effect of CSCs- and MSCs-exosomes on HCC growth and progression in vivo, which may be helpful to understand the mechanism of HCC development.
Protein Journal | 2018
Elrashdy M. Redwan; Saleh Al-Karim; Amr A. El-Hanafy; Yasser Saad; Hussein A. Almehdar; Vladimir N. Uversky
The original version of this article contained mistakes in author names and affiliations. The last names of the authors Salah Korim, Amro Samra, and Hussein A. Amhedar were misspelled. The corrected spelling is Saleh A. Alkarim, Amr A. El-Hanafy, and Hussein A. Almehdar. The correct list of author names and affiliations are published with this erratum.
Journal of Ethnopharmacology | 2018
Fareeduddin Quadri Syed; Ayman I. Elkady; Furkhan Ahmed Mohammed; Muqtadir Baig Mirza; Khalid Rehman Hakeem; Saleh Al-Karim
ETHNOPHARMACOLOGICAL RELEVANCE Foeniculum vulgare Mill. (Fennel) is one of the most common herbs used in alternative medicines for its varied range of bioactivity. In Ecuador (South America), use of fennel in traditional cancer treatment is on record. AIM OF THE STUDY The objective of the present study was to demonstrate the anti-proliferative and apoptotic effect of chloroform fraction of fennel (CFF) in MCF-7 cells. MATERIALS AND METHODS Anti-proliferative assay (MTT assay) and colony formation assay were performed to study the growth inhibitory effect of CFF. Various morphological changes of apoptosis were observed using Giemsa, Hoechst and Acridine orange/ ethidium bromide stains in MCF-7 cells. The extent of apoptosis and cell cycle arrest was measured by flow cytometer. Levels of ROS and mitochondrial membrane potential was measured by DCFH-DA and JC-1 respectively. Caspases activity was measured by luminescence and DNA fragmentation by comet assay. RESULTS CFF appeared as a good inhibitor of growth against MCF-7 and MDA-MB-237 in time- and concentration-dependent manners. All the morphological changes of apoptosis were evident in treatment groups. Annexin V/PI-assay of apoptosis gave around 49% of apoptotic cells upon treatment of 0.5 mg/ml of CFF and PI-stained cells showed the G1 phase cell cycle arrest. Elevated levels of ROS, disrupted mitochondrial membrane, increased levels of caspase-9 & caspase-3 and DNA fragmentation were noted in treated MCF-7 cells. CONCLUSION Our findings revealed the proliferation inhibition, cell cycle arrest and apoptosis induction effect of CFF, which may help in exploring the novel anti-cancer drug for therapeutic implications.
Journal of Biosciences | 2018
Wafaa S. Ramadan; Ghada A. Abdel-Hamid; Saleh Al-Karim; Noor Ahmed Mubarak Ben Zakar; M-Zaki Elassouli
The outcomes of compressed spinal cord injury (CSCI) necessitate radical treatment. The therapeutic potential of neuroectodermal stem cells (NESCs) in a rat model of CSCI in acute and subacute stages was assessed. White Wistar rat were divided into control, sham-operated, CSCI untreated model, CSCI grafted with NESCs at 1 day after CSCI, and at 7 days after CSCI. Primary NESC cultures were prepared from brains of embryonic day 10 (E10) mice embryos. NESCs were transplanted at the site of injury using a Hamilton syringe. Locomotor functional assessment, routine histopathology, immunostaining for (GFAP), and ultrastructure techniques for evaluating the CSI were conducted. In CSCI, areas of hemorrhage, cavitation, reactive astrocytosis, upregulated GFAP expression of immunostained areas, degeneration of the axoplasm and demyelination were observed. One day after grafting with NESCs, a decrease in astrocyte reaction and pathological features, quantitative and qualitative enhancement of remyelination and improved locomotor activity were observed. Treatment with NESCs at 7 days after CSCI did not mitigatethe reactive astrocytosis and glial scar formation that hindered the ability of the NESCs to enhance remyelination of axons. In conclusion, the microenvironment and time of NESCs transplantation affect activity of astrocytes and remyelination of axons.