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Article ; Online: Rs10204525 Polymorphism of the Programmed Death (PD-1) Gene Is Associated with Increased Risk in a Saudi Arabian Population with Colorectal Cancer.

Al-Harbi, Nouf / Vaali-Mohammed, Mansoor-Ali / Al-Omar, Suliman / Zubaidi, Ahmed / Al-Obeed, Omar / Abdulla, Maha-Hamadien / Mansour, Lamjed

Medicina (Kaunas, Lithuania)

2022 Volume 58, Issue 10

Abstract: Checkpoint programmed death-1 (PD-1) has been identified as an immunosuppressive molecule implicated in the immune evasion of transformed cells. It is highly expressed in tumor cells in order to evade host immunosurveillance. In this study, we aimed to ... ...

Abstract	Checkpoint programmed death-1 (PD-1) has been identified as an immunosuppressive molecule implicated in the immune evasion of transformed cells. It is highly expressed in tumor cells in order to evade host immunosurveillance. In this study, we aimed to assess the association between single nucleotide polymorphisms (SNP) of
MeSH term(s)	Humans ; Asians ; Case-Control Studies ; Colorectal Neoplasms/genetics ; Colorectal Neoplasms/pathology ; Genetic Predisposition to Disease/genetics ; Genotype ; Polymorphism, Single Nucleotide/genetics ; Programmed Cell Death 1 Receptor/genetics ; Saudi Arabia/epidemiology
Chemical Substances	Programmed Cell Death 1 Receptor ; PDCD1 protein, human
Language	English
Publishing date	2022-10-13
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2188113-3
ISSN	1648-9144 ; 1010-660X
ISSN (online)	1648-9144
ISSN	1010-660X
DOI	10.3390/medicina58101439
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Article: The platinum coordination complex inhibits cell invasion-migration and epithelial-to-mesenchymal transition by altering the TGF-β-SMAD pathway in colorectal cancer.

Abdulla, Maha-Hamadien / Alzailai, Aminah Ahmad / Vaali-Mohammed, Mansoor-Ali / Ahmad, Rehan / Fatima, Sabiha / Zubaidi, Ahmed / Traiki, Thamer Bin / Mahmood, Amer / Hamoud Alrashoudi, Reem / Khan, Zahid

Frontiers in pharmacology

2023 Volume 14, Page(s) 1178190

Abstract: Introduction: ...

Abstract	Introduction:
Language	English
Publishing date	2023-11-08
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2587355-6
ISSN	1663-9812
ISSN	1663-9812
DOI	10.3389/fphar.2023.1178190
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Article ; Online: Upregulation of the proinflammatory cytokine-induced neutrophil chemoattractant-1 and monocyte chemoattractant protein-1 in rats' intestinal anastomotic wound healing--does it matter?

Alzoghaibi, Mohammed A / Zubaidi, Ahmed M

Asian journal of surgery

2014 Volume 37, Issue 2, Page(s) 86–92

Abstract: Background: The proinflammatory cytokines and growth-promoting factor are essential components of the wound healing process. We hypothesized that under healthy conditions, faster healing of intestinal anastomotic wound is due to an early upregulation of ...

Abstract	Background: The proinflammatory cytokines and growth-promoting factor are essential components of the wound healing process. We hypothesized that under healthy conditions, faster healing of intestinal anastomotic wound is due to an early upregulation of proinflammatory cytokines, cytokine-induced neutrophil chemoattractant-1 (CINC-1) that is followed by a quicker upregulation of homeostatic chemokine, monocyte chemoattractant protein-1 (MCP-1) and late upregulation of transforming growth factor (TGF-β). Methods: We characterized the time course of CINC-1, MCP-1 and TGF-β release at four wounds (skin, muscle, small bowel, and colonic anastomosis) after surgery on 38 juvenile male Sprague Dawley rats. The tissue samples of each site were harvested at 0 (control), 1, 3, 5, 7 and 14 days postoperatively (n = 6-8/group) and analyzed by ELISA kits for CINC-1, MCP-1 and TGF-β. Results: CINC-1 expression peaked earlier in muscle and colonic wounds when compared to skin and small bowel. MCP-1 levels were elevated early in skin and muscle wounds, but later expression of MCP-1 was shown in colonic wounds. TGF-β levels were unchanged in all wound sites. Conclusion: An earlier peak in CINC-1 levels and later expression of MCP-1 were seen in colonic wounds, but no significant increase in TGF-β levels was observed. These findings support the early healing process in intestinal anastomotic wounds.
MeSH term(s)	Animals ; Chemokine CCL2/physiology ; Colon/injuries ; Interleukin-8/physiology ; Male ; Rats ; Rats, Sprague-Dawley ; Transforming Growth Factor beta/physiology ; Up-Regulation ; Wound Healing/physiology
Chemical Substances	Chemokine CCL2 ; Interleukin-8 ; Transforming Growth Factor beta
Language	English
Publishing date	2014-04
Publishing country	China
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1068461-x
ISSN	0219-3108 ; 1015-9584
ISSN (online)	0219-3108
ISSN	1015-9584
DOI	10.1016/j.asjsur.2013.07.016
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Article ; Online: Targeting MUCL1 protein inhibits cell proliferation and EMT by deregulating β‑catenin and increases irinotecan sensitivity in colorectal cancer.

Abdulla, Maha / Traiki, Thamer Bin / Vaali-Mohammed, Mansoor-Ali / El-Wetidy, Mohammad S / Alhassan, Noura / Al-Khayal, Khayal / Zubaidi, Ahmed / Al-Obeed, Omar / Ahmad, Rehan

International journal of oncology

2022 Volume 60, Issue 3

Abstract: With >1.85 million cases and 850,000 deaths annually, colorectal cancer (CRC) is the third most common cancer detected globally. CRC is an aggressive malignancy with metastasis and, in spite of advances in improved treatment regimen, distant disease ... ...

Abstract	With >1.85 million cases and 850,000 deaths annually, colorectal cancer (CRC) is the third most common cancer detected globally. CRC is an aggressive malignancy with metastasis and, in spite of advances in improved treatment regimen, distant disease failure rates remain disappointingly high. Mucin‑like 1 (MUCL1) is a small glycoprotein highly expressed mainly in breast cancer. The involvement of the MUCL1 protein in CRC progression and the underlying mechanism have been largely unknown. The aim of the present study was to investigate the MUCL1 expression profile and its functional significance in CRC. The Cancer Genome Atlas dataset revealed that MUCL1 expression was higher in colorectal tumor compared with normal tissues. MUCL1 was also revealed to be expressed in human CRC cell lines. The results demonstrated that MUCL1 promoted cell proliferation and colony formation, confirming its oncogenic potential. Silencing MUCL1 with short interfering RNA inhibited the protein expression of Bcl2 family proteins, such as Bcl2 and BclxL. Targeting MUCL1 resulted in significant inhibition in cell invasive and migratory behavior of HT‑29 and SW620 cells. In addition, the expression of E‑cadherin increased whereas the expression of vimentin decreased in MUCL1‑silenced cells, confirming inhibition of epithelial‑mesenchymal transition (EMT) process. Thus, it was revealed that MUCL1 plays a notable role in cell invasion and migration by inhibiting EMT in CRC. Mechanistically, MUCL1 drives β‑catenin activation by Ser‑552 phosphorylation, nuclear accumulation and transcriptional activation. Targeting MUCL1 increases the drug sensitivity of CRC cells towards irinotecan. These findings thus demonstrated that MUCL1 acts as a modifier of other pathways that play an important role in CRC progression and MUCL1 was identified as a potential target for CRC therapeutics.
MeSH term(s)	Cell Line/drug effects ; Cell Line/physiology ; Cell Movement/genetics ; Cell Proliferation/drug effects ; Colorectal Neoplasms/drug therapy ; Colorectal Neoplasms/physiopathology ; Humans ; Irinotecan/metabolism ; Irinotecan/pharmacology ; Mucins/metabolism ; Mucins/pharmacology ; beta Catenin/drug effects
Chemical Substances	MUCL1 protein, human ; Mucins ; beta Catenin ; Irinotecan (7673326042)
Language	English
Publishing date	2022-01-21
Publishing country	Greece
Document type	Journal Article
ZDB-ID	1154403-x
ISSN	1791-2423 ; 1019-6439
ISSN (online)	1791-2423
ISSN	1019-6439
DOI	10.3892/ijo.2022.5312
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Article ; Online: Quality of Information About Bariatric Surgery on the Internet: A Two-Continent Comparison of Website Content.

Barajas-Gamboa, Juan S / Klingler, Michael / Landreneau, Joshua / Strong, Andrew / Al Zubaidi, Ahmed / Sharadgah, Hala / Del Gobbo, Gabriel Diaz / Abril, Carlos / Kroh, Matthew / Corcelles, Ricard

Obesity surgery

2020 Volume 30, Issue 5, Page(s) 1736–1744

Abstract: Background: Many patients considering bariatric surgery will obtain medical information through the Internet. The type and quality of information patients access may vary significantly by geographic region.: Methods: Searches were performed using ... ...

Abstract	Background: Many patients considering bariatric surgery will obtain medical information through the Internet. The type and quality of information patients access may vary significantly by geographic region. Methods: Searches were performed using commercial search engines in both the United States of America (USA) and United Arab Emirates (UAE) using search terms "bariatric surgery" and "weight loss surgery." Quality was assessed using the scoring systems previously published by DISCERN (United Kingdom (UK)), the Journal of the American Medical Association Benchmark (JAMA; USA), and Expanded Ensuring Quality Information for Patients (EQIP) (UK). Results: Website types were more evenly distributed in UAE, though physician websites were also the most common (n = 25, 25%). Within the USA, most websites analyzed were from physicians (n = 32, 32%), followed by academic sources (n = 26, 26%). Academic websites were the highest average quality in the USA (p < .00001). The overall mean DISCERN scores for all websites in the UAE group and US group had no statistically significance differences (p = .950). The overall mean JAMA Benchmark for all websites in the UAE group and USA had no statistically significance differences (p = 0.202). There were no major differences between the USA and UAE in Expanded EQIP scores. Conclusions: The overall quality of information regarding bariatric surgery is poor to fair in both the USA and UAE. Additionally, there are differences in the types of sites retrieved by the most commonly used search engines in each region. The lack of high-quality, evidence-based, information regarding bariatric surgery online is a potential target to improve public education.
MeSH term(s)	Bariatric Surgery ; Humans ; Internet ; Obesity, Morbid/surgery ; United Arab Emirates ; United Kingdom
Language	English
Publishing date	2020-01-07
Publishing country	United States
Document type	Journal Article
ZDB-ID	1070827-3
ISSN	1708-0428 ; 0960-8923
ISSN (online)	1708-0428
ISSN	0960-8923
DOI	10.1007/s11695-019-04375-5
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Article: Novel quinazoline-based sulfonamide derivative (3D) induces apoptosis in colorectal cancer by inhibiting JAK2-STAT3 pathway.

Al-Obeed, Omar / Vaali-Mohammed, Mansoor-Ali / Eldehna, Wagdy M / Al-Khayal, Khayal / Mahmood, Amer / Abdel-Aziz, Hatem A / Zubaidi, Ahmed / Alafeefy, Ahmed / Abdulla, Maha / Ahmad, Rehan

OncoTargets and therapy

2018 Volume 11, Page(s) 3313–3322

Abstract: Introduction: Colorectal cancer (CRC) is a major worldwide health problem owing to its high prevalence and mortality rate. Developments in screening, prevention, biomarker, personalized therapies and chemotherapy have improved detection and treatment. ... ...

Abstract	Introduction: Colorectal cancer (CRC) is a major worldwide health problem owing to its high prevalence and mortality rate. Developments in screening, prevention, biomarker, personalized therapies and chemotherapy have improved detection and treatment. However, despite these advances, many patients with advanced metastatic tumors still succumb to the disease. New anticancer agents are needed for treating advanced stage CRC as most of the deaths occur due to cancer metastasis. A recently developed novel sulfonamide derivative 4-((2-(4-(dimethylamino) phenyl)quinazolin-4-yl)amino)benzenesulfonamide (3D) has shown potent antitumor effect; however, the mechanism underlying the antitumor effect remains unknown. Materials and methods: 3D-mediated inhibition on cell viability was evaluated by MTT and real-time cell proliferation was measured by xCelligence RTDP instrument. Western blotting was used to measure pro-apoptotic, anti-apoptotic proteins and JAK2-STAT3 phosphorylation. Flow cytometry was used to measure ROS production and apoptosis. Results: Our study revealed that 3D treatment significantly reduced the viability of human CRC cells HT-29 and SW620. Furthermore, 3D treatment induced the generation of reactive oxygen species (ROS) in human CRC cells. Confirming our observation, N-acetylcysteine significantly inhibited apoptosis. This is further evidenced by the induction of p53 and Bax; release of cytochrome c; activation of caspase-9, caspase-7 and caspase-3; and cleavage of PARP in 3D-treated cells. This compound was found to have a significant effect on the inhibition of antiapoptotic proteins Bcl2 and BclxL. The results further demonstrate that 3D inhibits JAK2-STAT3 pathway by decreasing the constitutive and IL-6-induced phosphorylation of STAT3. 3D also decreases STAT3 target genes such as cyclin D1 and survivin. Furthermore, a combination study of 3D with doxorubicin (Dox) also showed more potent effects than single treatment of Dox in the inhibition of cell viability. Conclusion: Taken together, these findings indicate that 3D induces ROS-mediated apoptosis and inhibits JAK2-STAT3 signaling in CRC.
Language	English
Publishing date	2018-06-05
Publishing country	New Zealand
Document type	Journal Article
ZDB-ID	2495130-4
ISSN	1178-6930
ISSN	1178-6930
DOI	10.2147/OTT.S148108
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Article ; Online: Novel derivative of aminobenzenesulfonamide (3c) induces apoptosis in colorectal cancer cells through ROS generation and inhibits cell migration.

Al-Khayal, Khayal / Alafeefy, Ahmed / Vaali-Mohammed, Mansoor-Ali / Mahmood, Amer / Zubaidi, Ahmed / Al-Obeed, Omar / Khan, Zahid / Abdulla, Maha / Ahmad, Rehan

BMC cancer

2017 Volume 17, Issue 1, Page(s) 4

Abstract: Background: Colorectal cancer (CRC) is the 3: Methods: 3c-induced inhibition of proliferation was measured in the absence and presence NAC using MTT in HT-29 and SW620 cells and xCELLigence RTCA DP instrument. 3c-induced apoptotic studies were ... ...

Abstract	Background: Colorectal cancer (CRC) is the 3 Methods: 3c-induced inhibition of proliferation was measured in the absence and presence NAC using MTT in HT-29 and SW620 cells and xCELLigence RTCA DP instrument. 3c-induced apoptotic studies were performed using flow cytometry. 3c-induced redox alterations were measured by ROS production using fluorescence plate reader and flow cytometry and mitochondrial membrane potential by flow cytometry; NADPH and GSH levels were determined by colorimetric assays. Bcl2 family protein expression and cytochrome c release and PARP activation was done by western blotting. Caspase activation was measured by ELISA. Cell migration assay was done using the real time xCELLigence RTCA DP system in SW620 cells and wound healing assay in HT-29. Results: Many anticancer therapeutics exert their effects by inducing reactive oxygen species (ROS). In this study, we demonstrate that 3c-induced inhibition of cell proliferation is reversed by the antioxidant, N-acetylcysteine, suggesting that 3c acts via increased production of ROS in HT-29 cells. This was confirmed by the direct measurement of ROS in 3c-treated colorectal cancer cells. Additionally, treatment with 3c resulted in decreased NADPH and glutathione levels in HT-29 cells. Further, investigation of the apoptotic pathway showed increased release of cytochrome c resulting in the activation of caspase-9, which in turn activated caspase-3 and -6. 3c also (i) increased p53 and Bax expression, (ii) decreased Bcl2 and BclxL expression and (iii) induced PARP cleavage in human colorectal cancer cells. Confirming our observations, NAC significantly inhibited induction of apoptosis, ROS production, cytochrome c release and PARP cleavage. The results further demonstrate that 3c inhibits cell migration by modulating EMT markers and inhibiting TGFβ-induced phosphorylation of Smad2 and Samd3. Conclusions: Our findings thus demonstrate that 3c disrupts redox balance in colorectal cancer cells and support the notion that this agent may be effective for the treatment of colorectal cancer.
MeSH term(s)	Amides/pharmacology ; Antineoplastic Agents/pharmacology ; Apoptosis/drug effects ; Caspase 3/metabolism ; Cell Movement/drug effects ; Cell Proliferation/drug effects ; Colorectal Neoplasms/drug therapy ; Colorectal Neoplasms/metabolism ; Colorectal Neoplasms/pathology ; Cytochromes c/metabolism ; Humans ; Membrane Potential, Mitochondrial/drug effects ; Mitochondria/drug effects ; Mitochondria/metabolism ; Mitochondria/pathology ; Reactive Oxygen Species/metabolism ; Sulfanilic Acids/chemistry ; Tumor Cells, Cultured ; Wound Healing/drug effects
Chemical Substances	Amides ; Antineoplastic Agents ; Reactive Oxygen Species ; Sulfanilic Acids ; Cytochromes c (9007-43-6) ; Caspase 3 (EC 3.4.22.-)
Language	English
Publishing date	2017--03
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	1471-2407
ISSN (online)	1471-2407
DOI	10.1186/s12885-016-3005-7
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Article ; Online: Association of Vitamin D Receptor Gene Polymorphisms with Colorectal Cancer in a Saudi Arabian Population.

Alkhayal, Khayal A / Awadalia, Zainab H / Vaali-Mohammed, Mansoor-Ali / Al Obeed, Omar A / Al Wesaimer, Alanoud / Halwani, Rabih / Zubaidi, Ahmed M / Khan, Zahid / Abdulla, Maha-Hamadien

PloS one

2016 Volume 11, Issue 6, Page(s) e0155236

Abstract: Background: Vitamin D, causally implicated in bone diseases and human malignancies, exerts its effects through binding to the vitamin D receptor (VDR). VDR is a transcription factor modulating the expression of several genes in different pathways. ... ...

Abstract	Background: Vitamin D, causally implicated in bone diseases and human malignancies, exerts its effects through binding to the vitamin D receptor (VDR). VDR is a transcription factor modulating the expression of several genes in different pathways. Genetic variants in the VDR gene have been associated with several cancers in different population including colorectal cancer. Objective: To assess the association of VDR gene polymorphisms in relation with colorectal cancer (CRC) in a Saudi population. Methods: The polymorphisms of VDR gene (BsmI, FokI, ApaI and TaqI) were analyzed by the polymerase chain reaction amplification of segments of interest followed by Sanger sequencing. One hundred diagnosed CRC patients and 100 healthy control subjects that were age and gender matched were recruited. Results: We did not observe significant association of any of the four VDR polymorphisms with colorectal cancer risk in the overall analysis. Although not statistically significant, the AA genotype of BsmI conferred about two-fold protection against CRCs compared to the GG genotype. Stratification of the study subjects based on age and gender suggests statistically significant association of CRC with the 'C' allele of ApaI in patients >57 years of age at disease diagnosis and BsmI polymorphism in females. In addition, statistically significant differences were observed for the genotypic distributions of VDR-BsmI, ApaI and TaqI SNPs between Saudi Arabian population and several of the International HapMap project populations. Conclusion: Despite the absence of correlation of the examined VDR polymorphisms with CRCs in the combined analysis, ApaI and BsmI loci are statistically significantly associated with CRC in elderly and female patients, respectively. These findings need further validation in larger cohorts prior to utilizing these SNPs as potential screening markers for colorectal cancers in Saudi population.
MeSH term(s)	Adult ; Aged ; Aged, 80 and over ; Alleles ; Case-Control Studies ; Colorectal Neoplasms/genetics ; Colorectal Neoplasms/pathology ; Deoxyribonucleases, Type II Site-Specific/chemistry ; Female ; Gene Expression ; Gene Frequency ; Genetic Predisposition to Disease ; Humans ; Linkage Disequilibrium ; Male ; Middle Aged ; Polymorphism, Restriction Fragment Length ; Polymorphism, Single Nucleotide ; Receptors, Calcitriol/genetics ; Saudi Arabia ; Sequence Analysis, DNA
Chemical Substances	Receptors, Calcitriol ; VDR protein, human ; endodeoxyribonuclease BsmI (EC 3.1.21.-) ; endodeoxyribonuclease FokI (EC 3.1.21.-) ; Deoxyribonucleases, Type II Site-Specific (EC 3.1.21.4) ; GGGCCC-specific type II deoxyribonucleases (EC 3.1.21.4) ; TCGA-specific type II deoxyribonucleases (EC 3.1.21.4)
Language	English
Publishing date	2016-06-16
Publishing country	United States
Document type	Journal Article
ZDB-ID	2267670-3
ISSN	1932-6203 ; 1932-6203
ISSN (online)	1932-6203
ISSN	1932-6203
DOI	10.1371/journal.pone.0155236
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Article ; Online: Rs10204525 Polymorphism of the Programmed Death (PD-1) Gene Is Associated with Increased Risk in a Saudi Arabian Population with Colorectal Cancer.

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Article: The platinum coordination complex inhibits cell invasion-migration and epithelial-to-mesenchymal transition by altering the TGF-β-SMAD pathway in colorectal cancer.

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Article ; Online: Upregulation of the proinflammatory cytokine-induced neutrophil chemoattractant-1 and monocyte chemoattractant protein-1 in rats' intestinal anastomotic wound healing--does it matter?

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Article ; Online: Targeting MUCL1 protein inhibits cell proliferation and EMT by deregulating β‑catenin and increases irinotecan sensitivity in colorectal cancer.

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Article ; Online: Quality of Information About Bariatric Surgery on the Internet: A Two-Continent Comparison of Website Content.

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Article: Novel quinazoline-based sulfonamide derivative (3D) induces apoptosis in colorectal cancer by inhibiting JAK2-STAT3 pathway.

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Article ; Online: Novel derivative of aminobenzenesulfonamide (3c) induces apoptosis in colorectal cancer cells through ROS generation and inhibits cell migration.

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Article ; Online: Association of Vitamin D Receptor Gene Polymorphisms with Colorectal Cancer in a Saudi Arabian Population.

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