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Article ; Online: Surveillance Compliance and Quality of Life Assessment Among Surgical Patients with Familial Adenomatous Polyposis Syndrome.

Alhassan, Noura / Helmi, Hadeel / Alzamil, Abdullah / Alshammari, Afraj / Altamimi, Atheer / Alshammari, Sulaiman / Bin Traiki, Thamer / Albanyan, Saleh / AlKhayal, Khayal / Zubaidi, Ahmad / Al-Obeed, Omar

Journal of epidemiology and global health

2024 Volume 14, Issue 1, Page(s) 86–93

Abstract: Background: Familial adenomatous polyposis (FAP) syndrome has a near-100% lifetime risk of colorectal cancer. Early surveillance and prophylactic surgery have been advocated to reduce this risk. However, the surveillance practices among FAP individuals ... ...

Abstract	Background: Familial adenomatous polyposis (FAP) syndrome has a near-100% lifetime risk of colorectal cancer. Early surveillance and prophylactic surgery have been advocated to reduce this risk. However, the surveillance practices among FAP individuals in Saudi Arabia are unknown. We aimed to explore surveillance compliance in our population, as well as the disease impact on their quality of life (QoL). Methods: All patients with FAP who underwent surgical resection at King Saud University Medical City between 2016 and 2022 were included. Demographic data, clinical features, family history, and compliance with surveillance were collected and analyzed. QoL questionnaires: Short-form health survey (SF-36) and European Organization for Research and Treatment (EORTC) were conducted by phone interview. Results: A total of 14 patients were included with an average age of 25 years. Three patients (21.4%) were the first of their family members to develop FAP. Nine patients (64%) were untested for genetic mutation due to lack of referral to geneticists. The compliance rate toward both pre-operative colonoscopy and upper endoscopy were 78%. However, 38% and 27% compliance rates were observed toward initial and post-operative colonoscopy, respectively. The compliance rate was 14% toward thyroid ultrasound. QoL scores varied among patients, with a mean score above 60 across all SF-36 domains. Conclusion: An overall poor compliance was observed among our participants, particularly toward thyroid ultrasound. Increased health awareness and patient education are essential. In addition, the importance of surveillance and genetic counseling should be emphasized among physicians treating these patients.
MeSH term(s)	Humans ; Adenomatous Polyposis Coli/surgery ; Adenomatous Polyposis Coli/psychology ; Adenomatous Polyposis Coli/diagnosis ; Quality of Life ; Male ; Female ; Adult ; Saudi Arabia/epidemiology ; Patient Compliance/statistics & numerical data ; Patient Compliance/psychology ; Young Adult ; Middle Aged ; Surveys and Questionnaires ; Colonoscopy/statistics & numerical data ; Colonoscopy/psychology ; Adolescent ; Population Surveillance/methods
Language	English
Publishing date	2024-01-03
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2645324-1
ISSN	2210-6014 ; 2210-6014
ISSN (online)	2210-6014
ISSN	2210-6014
DOI	10.1007/s44197-023-00171-8
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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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Zs.A 3690: Show issues

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Article ; Online: Robotic general surgery experience: a gradual progress from simple to more complex procedures.

Al-Naami, M / Anjum, M N / Aldohayan, A / Al-Khayal, K / Alkharji, H

The international journal of medical robotics + computer assisted surgery : MRCAS

2013 Volume 9, Issue 4, Page(s) 486–491

Abstract: Background: Robotic surgery was introduced at our institution in 2003, and we used a progressive approach advancing from simple to more complex procedures.: Methods: A retrospective chart review.: Results: Cases included totalled 129. Set-up and ... ...

Abstract	Background: Robotic surgery was introduced at our institution in 2003, and we used a progressive approach advancing from simple to more complex procedures. Methods: A retrospective chart review. Results: Cases included totalled 129. Set-up and operative times have improved over time and with experience. Conversion rates to standard laparoscopic or open techniques were 4.7% and 1.6%, respectively. Intraoperative complications (6.2%), blood loss and hospital stay were directly proportional to complexity. There were no mortalities and the postoperative complication rate (13.2%) was within accepted norms. Conclusion: Our findings suggest that robot technology is presently most useful in cases tailored toward its advantages, i.e. those confined to a single space, those that require performance of complex tasks, and re-do procedures.
MeSH term(s)	Adult ; Female ; General Surgery/statistics & numerical data ; Hospital Mortality ; Humans ; Incidence ; Length of Stay/statistics & numerical data ; Male ; Operative Time ; Postoperative Complications/mortality ; Risk Factors ; Robotics/utilization ; Saudi Arabia/epidemiology ; Surgery, Computer-Assisted/mortality ; Surgery, Computer-Assisted/utilization
Language	English
Publishing date	2013-12
Publishing country	England
Document type	Journal Article
ZDB-ID	2151860-9
ISSN	1478-596X ; 1478-5951
ISSN (online)	1478-596X
ISSN	1478-5951
DOI	10.1002/rcs.1521
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Zs.A 6382: Show issues

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Article ; Online: Urolithin A induces cell cycle arrest and apoptosis by inhibiting Bcl-2, increasing p53-p21 proteins and reactive oxygen species production in colorectal cancer cells.

El-Wetidy, Mohammad S / Ahmad, Rehan / Rady, Islam / Helal, Hamed / Rady, Mohamad I / Vaali-Mohammed, Mansoor-Ali / Al-Khayal, Khayal / Traiki, Thamer Bin / Abdulla, Maha-Hamadien

Cell stress & chaperones

2021 Volume 26, Issue 3, Page(s) 473–493

Abstract: Colorectal cancer (CRC) is the second most common gastrointestinal cancer globally. Prevention of tumor cell proliferation and metastasis is vital for prolonging patient survival. Polyphenols provide a wide range of health benefits and prevention from ... ...

Abstract	Colorectal cancer (CRC) is the second most common gastrointestinal cancer globally. Prevention of tumor cell proliferation and metastasis is vital for prolonging patient survival. Polyphenols provide a wide range of health benefits and prevention from cancer. In the gut, urolithins are the major metabolites of polyphenols. The objective of our study was to elucidate the molecular mechanism of the anticancer effect of urolithin A (UA) on colorectal cancer cells. UA was found to inhibit the cell proliferation of CRC cell lines in a dose-dependent and time-dependent manner in HT29, SW480, and SW620 cells. Exposure to UA resulted in cell cycle arrest in a dose-dependent manner along with alteration in the expression of cell cycle-related protein. Treatment of CRC cell lines with UA resulted in the induction of apoptosis. Treatment of HT29, SW480, and SW620 with UA resulted in increased expression of the pro-apoptotic proteins, p53 and p21. Similarly, UA treatment inhibited the anti-apoptotic protein expression of Bcl-2. Moreover, exposure of UA induced cytochrome c release and caspase activation. Furthermore, UA was found to generate reactive oxygen species (ROS) production in CRC cells. These findings indicate that UA possesses anticancer potential and may be used therapeutically for the treatment of CRC.
MeSH term(s)	Antineoplastic Agents/pharmacology ; Apoptosis/drug effects ; Apoptosis/physiology ; Caspase 3/drug effects ; Caspase 3/metabolism ; Cell Cycle Checkpoints/drug effects ; Cell Death/drug effects ; Cell Line, Tumor ; Cell Proliferation/drug effects ; Colorectal Neoplasms/drug therapy ; Colorectal Neoplasms/metabolism ; Humans ; Proto-Oncogene Proteins c-bcl-2/drug effects ; Proto-Oncogene Proteins c-bcl-2/metabolism ; Reactive Oxygen Species/metabolism ; Tumor Suppressor Protein p53/drug effects ; Tumor Suppressor Protein p53/metabolism
Chemical Substances	Antineoplastic Agents ; BCL2 protein, human ; Proto-Oncogene Proteins c-bcl-2 ; Reactive Oxygen Species ; Tumor Suppressor Protein p53 ; Caspase 3 (EC 3.4.22.-)
Language	English
Publishing date	2021-03-05
Publishing country	Netherlands
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1362749-1
ISSN	1466-1268 ; 1355-8145
ISSN (online)	1466-1268
ISSN	1355-8145
DOI	10.1007/s12192-020-01189-8
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Zs.A 4797: Show issues

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Article ; Online: A novel coordination complex of platinum (PT) induces cell death in colorectal cancer by altering redox balance and modulating MAPK pathway.

Al-Khayal, Khayal / Vaali-Mohammed, Mansoor-Ali / Elwatidy, Mohammed / Bin Traiki, Thamer / Al-Obeed, Omar / Azam, Mohammad / Khan, Zahid / Abdulla, Maha / Ahmad, Rehan

BMC cancer

2020 Volume 20, Issue 1, Page(s) 685

Abstract: Background: Colorectal cancer (CRC) is a heterogeneous tumor having various genetic alterations. The current treatment options had limited impact on disease free survival due to therapeutic resistance. Novel anticancer agents are needed to treat CRC ... ...

Abstract	Background: Colorectal cancer (CRC) is a heterogeneous tumor having various genetic alterations. The current treatment options had limited impact on disease free survival due to therapeutic resistance. Novel anticancer agents are needed to treat CRC specifically metastatic colorectal cancer. A novel coordination complex of platinum, (salicylaldiminato)Pt(II) complex with dimethylpropylene linkage (PT) exhibited potential anti-cancer activity. In this study, we explored the molecular mechanism of PT-induced cell death in colorectal cancer. Methods: Colony formation was evaluated using the clonogenic assay. Apoptosis, cell cycle analysis, reactive oxygen species, mitochondrial membrane potential and caspase-3/- 7 were assessed by flow cytometry. Glutathione level was detected by colorimetric assay. PT-induced alteration in pro-apoptotic/ anti-apoptotic proteins and other signaling pathways were investigated using western blotting. P38 downregulation was performed using siRNA. Results: In the present study, we explored the molecular mechanism of PT-mediated inhibition of cell proliferation in colorectal cancer cells. PT significantly inhibited the colony formation in human colorectal cancer cell lines (HT-29, SW480 and SW620) by inducing apoptosis and necrosis. This platinum complex was shown to significantly increase the reactive oxygen species (ROS) generation, depletion of glutathione and reduced mitochondrial membrane potential in colorectal cancer cells. Exposure to PT resulted in the downregulation of anti-apoptotic proteins (Bcl2, BclxL, XIAP) and alteration in Cyclins expression. Furthermore, PT increased cytochrome c release into cytosol and enhanced PARP cleavage leading to activation of intrinsic apoptotic pathway. Moreover, pre-treatment with ROS scavenger N-acetylcysteine (NAC) attenuated apoptosis suggesting that PT-induced apoptosis was driven by oxidative stress. Additionally, we show that PT-induced apoptosis was mediated by activating p38 MAPK and inhibiting AKT pathways. This was demonstrated by using chemical inhibitor and siRNA against p38 kinase which blocked the cytochrome c release and apoptosis in colorectal cancer cells. Conclusion: Collectively, our data demonstrates that the platinum complex (PT) exerts its anti-proliferative effect on CRC by ROS-mediated apoptosis and activating p38 MAPK pathway. Thus, our findings reveal a novel mechanism of action for PT on colorectal cancer cells and may have therapeutic implication.
MeSH term(s)	Annexin A5/analysis ; Apoptosis/drug effects ; Apoptosis/genetics ; Caspase 3/metabolism ; Caspase 7/metabolism ; Cell Cycle/drug effects ; Cell Death ; Cell Line, Tumor ; Cell Proliferation ; Colorectal Neoplasms/chemistry ; Colorectal Neoplasms/drug therapy ; Colorectal Neoplasms/enzymology ; Colorectal Neoplasms/pathology ; Cyclins/metabolism ; Down-Regulation ; Glutathione/metabolism ; Humans ; Membrane Potential, Mitochondrial/drug effects ; Mitogen-Activated Protein Kinases/metabolism ; Oxidation-Reduction ; Platinum Compounds/pharmacology ; Proto-Oncogene Proteins c-bcl-2/metabolism ; Reactive Oxygen Species/metabolism ; Tumor Stem Cell Assay ; X-Linked Inhibitor of Apoptosis Protein/metabolism ; bcl-X Protein/metabolism ; p38 Mitogen-Activated Protein Kinases/metabolism
Chemical Substances	Annexin A5 ; BCL2L1 protein, human ; Cyclins ; Platinum Compounds ; Proto-Oncogene Proteins c-bcl-2 ; Reactive Oxygen Species ; X-Linked Inhibitor of Apoptosis Protein ; XIAP protein, human ; bcl-X Protein ; Mitogen-Activated Protein Kinases (EC 2.7.11.24) ; p38 Mitogen-Activated Protein Kinases (EC 2.7.11.24) ; Caspase 3 (EC 3.4.22.-) ; Caspase 7 (EC 3.4.22.-) ; Glutathione (GAN16C9B8O)
Language	English
Publishing date	2020-07-23
Publishing country	England
Document type	Journal Article
ISSN	1471-2407
ISSN (online)	1471-2407
DOI	10.1186/s12885-020-07165-w
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Article ; Online: Correction to: A novel coordination complex of platinum (PT) induces cell death in colorectal cancer by altering redox balance and modulating MAPK pathway.

Al-Khayal, Khayal / Vaali-Mohammed, Mansoor-Ali / Elwatidy, Mohammed / Traiki, Thamer Bin / Al-Obeed, Omar / Azam, Mohammad / Khan, Zahid / Abdulla, Maha / Ahmad, Rehan

BMC cancer

2020 Volume 20, Issue 1, Page(s) 834

Abstract: An amendment to this paper has been published and can be accessed via the original article. ...

Abstract	An amendment to this paper has been published and can be accessed via the original article.
Language	English
Publishing date	2020-09-01
Publishing country	England
Document type	Published Erratum
ISSN	1471-2407
ISSN (online)	1471-2407
DOI	10.1186/s12885-020-07245-x
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Article ; Online: Development of 2-oindolin-3-ylidene-indole-3-carbohydrazide derivatives as novel apoptotic and anti-proliferative agents towards colorectal cancer cells.

Eldehna, Wagdy M / Abo-Ashour, Mahmoud F / Al-Warhi, Tarfah / Al-Rashood, Sara T / Alharbi, Amal / Ayyad, Rezk R / Al-Khayal, Khayal / Abdulla, Maha / Abdel-Aziz, Hatem A / Ahmad, Rehan / El-Haggar, Radwan

Journal of enzyme inhibition and medicinal chemistry

2020 Volume 36, Issue 1, Page(s) 319–328

Abstract: Mitochondrial anti-apoptotic Bcl2 and BclxL proteins, are overexpressed in multiple tumour types, and has been involved in the progression and survival of malignant cells. Therefore, inhibition of such proteins has become a validated and attractive ... ...

Abstract	Mitochondrial anti-apoptotic Bcl2 and BclxL proteins, are overexpressed in multiple tumour types, and has been involved in the progression and survival of malignant cells. Therefore, inhibition of such proteins has become a validated and attractive target for anticancer drug discovery. In this manner, the present studies developed a series of novel isatin-indole conjugates (
MeSH term(s)	Antineoplastic Agents/chemical synthesis ; Antineoplastic Agents/chemistry ; Antineoplastic Agents/pharmacology ; Apoptosis/drug effects ; Cell Proliferation/drug effects ; Cell Survival/drug effects ; Colorectal Neoplasms/drug therapy ; Colorectal Neoplasms/pathology ; Dose-Response Relationship, Drug ; Drug Development ; Drug Screening Assays, Antitumor ; Humans ; Hydrazines/chemical synthesis ; Hydrazines/chemistry ; Hydrazines/pharmacology ; Indoles/chemical synthesis ; Indoles/chemistry ; Indoles/pharmacology ; Molecular Structure ; Structure-Activity Relationship ; Tumor Cells, Cultured
Chemical Substances	Antineoplastic Agents ; Hydrazines ; Indoles ; carbohydrazide (W8V7FYY4WH)
Language	English
Publishing date	2020-12-21
Publishing country	England
Document type	Journal Article
ZDB-ID	2082578-X
ISSN	1475-6374 ; 1475-6366
ISSN (online)	1475-6374
ISSN	1475-6366
DOI	10.1080/14756366.2020.1862100
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Zs.A 3004: Show issues

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Article: Novel management of methylene blue extravasation: A case report and review of literature.

Khokhar, Rashid Saeed / Aqil, Mansoor / Al-Zahrani, Tariq / Gelidan, Adnan / Al Khayal, Khayal

Saudi journal of anaesthesia

2015 Volume 9, Issue 2, Page(s) 211–213

Abstract: Methylene blue is a highly irritant drug and has been used intraoperatively. Its accidental extravasation can lead to tissue necrosis. In this report, a unique management is described, and the patient recovered without any morbidity. ...

Abstract	Methylene blue is a highly irritant drug and has been used intraoperatively. Its accidental extravasation can lead to tissue necrosis. In this report, a unique management is described, and the patient recovered without any morbidity.
Language	English
Publishing date	2015-03-29
Publishing country	India
Document type	Case Reports
ZDB-ID	2562174-9
ISSN	0975-3125 ; 1658-354X
ISSN (online)	0975-3125
ISSN	1658-354X
DOI	10.4103/1658-354X.152891
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Article: Evaluation of

Khan, Shahanavaj / Ansari, Anees A / Rolfo, Christian / Coelho, Andreia / Abdulla, Maha / Al-Khayal, Khayal / Ahmad, Rehan

Science and technology of advanced materials

2017 Volume 18, Issue 1, Page(s) 364–373

Abstract: Cerium oxide nanocrystals ( ... ...

Abstract	Cerium oxide nanocrystals (CeO
Language	English
Publishing date	2017-05-31
Publishing country	United States
Document type	Journal Article
ZDB-ID	2027985-1
ISSN	1878-5514 ; 1468-6996
ISSN (online)	1878-5514
ISSN	1468-6996
DOI	10.1080/14686996.2017.1319731
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Article ; Online: Induction of ROS‑mediated cell death and activation of the JNK pathway by a sulfonamide derivative.

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

International journal of molecular medicine

2019 Volume 44, Issue 4, Page(s) 1552–1562

Abstract: The emergence of colorectal cancer in developed nations can be attributed to dietary habits, smoking, a sedentary lifestyle and obesity. Several treatment regimens are available for primary and metastatic colorectal cancer; however, these treatment ... ...

Abstract	The emergence of colorectal cancer in developed nations can be attributed to dietary habits, smoking, a sedentary lifestyle and obesity. Several treatment regimens are available for primary and metastatic colorectal cancer; however, these treatment options have had limited impact on cure and disease‑free survival, and novel agents need to be developed for treating colorectal cancer. Thus, the objective of this study was to explore the anticancer mechanism of a benzo(1,3)dioxol‑based derivative of sulfonamide. The compound's inhibitory effect on cell proliferation was determined using the MTT assay and the xCelligence RTDP machine. Alternations in the expression of Bcl‑2 and inhibitor of apoptosis protein families were detected by western blotting. Apoptotic marker protein expression, including cytochrome c and cleaved poly(ADP‑ribose)polymerase was measured in the cytosolic extract of cells. Apoptosis and necrosis were detected by flow cytometry and immunofluorescence. Reactive oxygen species (ROS), and activation of caspase‑3 and caspase‑7 were measured using flow cytometry. Activation of the JNK pathway was detected by western blotting. We investigated the molecular mechanism of action of the sulfonamide derivative on colorectal cancer cells and found that the compound possesses a potent anticancer effect, which is primarily exerted by inducing apoptosis and necrosis. Interestingly, this compound exhibited little antiproliferative effect against the normal colonic epithelial cell line FHC. Furthermore, our results showed that the compound could significantly increase ROS production. Apoptosis induction could be attenuated by the free oxygen radical scavenger N‑acetyl cysteine (NAC), indicating that the antiproliferative effect of this compound on colorectal cancer cells is at least partially dependent on the redox balance. In addition, JNK signaling was activated by treatment with this derivative, which led to the induction of apoptosis. On the contrary, a JNK inhibitor could suppress the cell death induced by this compound. Our findings thus suggested a novel anticancer mechanism of a benzo(1,3)dioxol‑based derivative of sulfonamide for colorectal cancer cells and may have therapeutic potential for the treatment of colorectal cancer; however, further investigation is required.
MeSH term(s)	Apoptosis/drug effects ; Biomarkers ; Cell Death/drug effects ; Cell Line, Tumor ; Cell Proliferation/drug effects ; Cell Survival/drug effects ; Cytochromes c/metabolism ; Humans ; Immunophenotyping ; MAP Kinase Signaling System/drug effects ; Reactive Oxygen Species/metabolism ; Sulfonamides/pharmacology
Chemical Substances	Biomarkers ; Reactive Oxygen Species ; Sulfonamides ; Cytochromes c (9007-43-6)
Language	English
Publishing date	2019-07-23
Publishing country	Greece
Document type	Journal Article
ZDB-ID	1444428-8
ISSN	1791-244X ; 1107-3756
ISSN (online)	1791-244X
ISSN	1107-3756
DOI	10.3892/ijmm.2019.4284
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Zs.A 4942: Show issues

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