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Interlaced roles of mitochondrial DNA in colorectal cancer:Liquidbiopsy biomarkers,nuclear mtDNA-driven genomic instability,and mito-encoded micro peptide signaling
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作者 Thai-Hau Koo Xue-Bin Leong +2 位作者 Yi-Lin Lee Firdaus Hayati andee dzulkarnaen zakaria 《World Journal of Gastrointestinal Oncology》 2025年第12期24-37,共14页
Colorectal cancer(CRC)is a widely occurring malignancy with significant mortality on a global scale,making up close to 10%of all diagnosed cancers in 2020.While traditional CRC diagnostics and research have focused on... Colorectal cancer(CRC)is a widely occurring malignancy with significant mortality on a global scale,making up close to 10%of all diagnosed cancers in 2020.While traditional CRC diagnostics and research have focused on nuclear genomic alterations,emerging evidence has highlighted the multifaceted roles of mitochondrial DNA(mtDNA)in the pathogenesis and clinical management of CRC.In this review,we examine three interlaced aspects of mtDNA in CRC:(1)Liquid biopsy biomarkers:Cell-free mtDNA circulating in the blood serving as a minimally invasive diagnostic and monitoring tool;(2)Nuclear mtDNA(NUMT)-driven genomic instability:The somatic nuclear incorporation of mtDNA(NUMT segments,or NUMT),contributing to mutational burden and chromosomal disruption in tumours;and(3)Mitochondria-encoded micropeptide signaling-small peptides encoded by the mtDNA that modulate cellular pathways and tumour behaviour.Recent high-impact studies have demonstrated that tumourderived mtDNA in biofluids can augment cancer detection sensitivity,although technical challenges remain due to mtDNA fragmentation and background noise.Meanwhile,genomic analyses have uncovered a significant increase in NUMT insertion events in CRC cells,linking mitochondrial genome escape to nuclear genome instability and identifying potential numtogenesis suppressor genes.A novel dimension of mito-nuclear interactions in cancer was discovered in mitochondrial microproteins,such as humanin and mitochondrial open reading frame of the 12S rRNA type-c.Humanin exhibits both tumour-promoting and cytoprotective properties under specific conditions,while mitochondrial open reading frame of the 12S rRNA type-c possesses tumour-suppressive activities under other conditions.The outcomes of clinical,mechanistic,and translational research,revealing how mtDNA-based biomarkers and involvement contribute towards early detection,prognostication,and treatment of CRC,are presented. 展开更多
关键词 PROTEOMIC Multi-omics Gastrointestinal malignancy Precision oncology Biomarker discovery Therapeutic resistance
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Multi-omics perspectives for gastrointestinal malignancy:A systematic review
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作者 Thai-Hau Koo Yi-Lin Lee +3 位作者 Xue-Bin Leong Firdaus Hayati Mohd Hazeman zakaria andee dzulkarnaen zakaria 《World Journal of Gastrointestinal Surgery》 2025年第7期386-397,共12页
BACKGROUND Gastrointestinal(GI)malignancies,including gastric and colorectal cancers,remain one of the primary contributors to cancer-related illness and death globally.Despite the availability of conventional diagnos... BACKGROUND Gastrointestinal(GI)malignancies,including gastric and colorectal cancers,remain one of the primary contributors to cancer-related illness and death globally.Despite the availability of conventional diagnostic tools,early detection and personalized treatment remain significant clinical challenges.Integrated multi-omics methods encompassing genomic,transcriptomic,proteomic,metabolomic,and microbiome profiles have emerged as powerful tools for advancing precision oncology,improving diagnostic accuracy,and informing therapeutic strategies.AIM To investigate the application of multi-omics approaches in the early detection,risk stratification,treatment optimization,and biomarker discovery of GI malignancies.METHODS The systematic review process was conducted in accordance with the PRISMA 2020 guidelines.Five databases,PubMed,ScienceDirect,Scopus,ProQuest,and Web of Science,were searched for studies published in English from 2015 onwards.Eligible studies involved human subjects and focused on multi-omics integration in GI cancers,including biomarker identification,tumor microenvironment analysis,tumor heterogeneity,organoid modeling,and artificial intelligence(AI)-driven analytics.Data extraction included study characteristics,omics modalities,clinical applications,and evaluation of study quality conducted with the Cochrane risk of bias 2.0 instrument.RESULTS A total of 17196 initially identified articles,20 met the inclusion criteria.The findings highlight the superiority of multi-omics platforms over traditional biomarkers(e.g.,carcinoembryonic antigen and carbohydrate antigen 19-9 in detecting early stage GI cancers.Key applications include the identification of circulating tumor DNA,extracellular vesicles,lipidomic and proteomic signatures,and the adoption of AI algorithms to enhance diagnostic precision.Multi-omics analysis has also revealed the mechanisms of immune modulation,tumor microenvironment regulation,metastatic behavior,and drug resistance.Organoid models and microbiota profiling have contributed to personalized therapeutic strategies and immunotherapy optimization.CONCLUSION Multi-omics approaches offer significant advancements in the early diagnosis,prognostic evaluation,and personalized treatment of GI malignancies.Their integration with AI analytics,organoid biobanking,and microbiota modulation provides a pathway for precision oncology research. 展开更多
关键词 PROTEOMIC Multi-omics Gastrointestinal malignancy Precision oncology Biomarker discovery Therapeutic resistance
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Revolutionizing hepatolithiasis management:Transformative role of DynaCT in imaging and intervention
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作者 Thai-Hau Koo Xue-Bin Leong +3 位作者 Yi-Lin Lee Firdaus Hayati Mohd Hazeman zakaria andee dzulkarnaen zakaria 《World Journal of Gastrointestinal Surgery》 2025年第7期9-12,共4页
In this editorial,we comment on the article by Ye et al.We specifically focused on the novel use of DynaCT biliary soft tissue reconstruction technology in the diagnosis and treatment of hepatolithiasis with bile duct... In this editorial,we comment on the article by Ye et al.We specifically focused on the novel use of DynaCT biliary soft tissue reconstruction technology in the diagnosis and treatment of hepatolithiasis with bile duct stenosis,which is an innovative approach for enhancing the preoperative evaluation and surgical outcomes in hepatolithiasis.This study also highlights the limitations of conventional imaging techniques such as computed tomography and magnetic resonance cholangiopancreatography,which have low sensitivity for small stones and complex biliary strictures.Given the intricate anatomy of the biliary system and the challenges posed by limited visualization using conventional methods,DynaCT addresses these issues by providing high-resolution,three-dimensional reconstruction of the bile ducts,stones,and vascular structures,thus improving anatomical clarity and enabling precise surgical planning.We also focused specifically on the limitations of DynaCT,such as the need for specialized equipment and patient selection criteria,as well as its advantages and disadvantages compared with conventional PTOBF approaches.Overall,DynaCT represents a significant advancement in hepatolithiasis management,with the potential to become a standard imaging modality for safer and more effective biliary procedures. 展开更多
关键词 HEPATOLITHIASIS Biliary stenosis DYNACT One-step percutaneous transhepatic cholangioscopic lithotripsy Editorial
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Transforming biliary surgery:Innovations in fluorescence-guided imaging and indocyanine green application
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作者 Thai-Hau Koo Xue-Bin Leong +3 位作者 Yi-Lin Lee Firdaus Hayati Mohd Hazeman zakaria andee dzulkarnaen zakaria 《World Journal of Gastrointestinal Surgery》 2025年第8期7-11,共5页
In this editorial,we comment on the article by Li et al.We specifically focus on the novel use of multicolor near-infrared fluorescence imaging(MCFI)with indocyanine green in laparoscopic cholecystectomy,which is an i... In this editorial,we comment on the article by Li et al.We specifically focus on the novel use of multicolor near-infrared fluorescence imaging(MCFI)with indocyanine green in laparoscopic cholecystectomy,which is an innovative approach for enhancing biliary visualization during laparoscopic cholecystectomy.This study also highlighted the limitations of conventional single-color fluorescence imaging(SCFI),which relies solely on a green fluorescence signal,leading to challenges such as visual fatigue and difficulty in distinguishing biliary structures from background hepatic tissue.Given the complex anatomy of the biliary system and the challenges of visual fatigue encountered with SCFI,MCFI addresses these issues by enabling the differentiation of biliary structures by mapping the fluorescence intensity across a unique blue-to-purple color spectrum,thus improving the clarity of anatomical structures and reducing the visual strain for surgeons.We also focus specifically on the complications and cautious usage of indocyanine green in this context,as well as the advantages and disadvantages of MCFI and SCFI.Overall,MCFI represents a significant advancement in fluorescence-guided surgery,with the potential to become a standard imaging modality for safer and more effective laparoscopic procedures. 展开更多
关键词 Indocyanine green Near-infrared fluorescence Fluorescence imaging Multicolor fluorescence imaging Laparoscopic cholecystectomy
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Effects of preoperative immunonutrition vs standard oral nutrition in patients undergoing colorectal surgery:A randomized controlled trial
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作者 Manivaasan Pannirselvam Zaidi zakaria +4 位作者 Michael Pak-Kai Wong Mohd Hady Shukri Abdul Satar Nor Syarahani Jusoh andee dzulkarnaen zakaria Muhammad Faeid Othman 《World Journal of Gastrointestinal Surgery》 2025年第9期333-342,共10页
BACKGROUND Current guidelines recommend providing malnourished individuals immunonutrition before major gastrointestinal surgery.Nonetheless,the advantages of preoperative immunonutrition remain controversial.AIM To a... BACKGROUND Current guidelines recommend providing malnourished individuals immunonutrition before major gastrointestinal surgery.Nonetheless,the advantages of preoperative immunonutrition remain controversial.AIM To analyses the effects of preoperative immunonutrition and standard oral nutrition supplements on colorectal surgery outcomes.METHODS This study employed a prospective single-center randomized double-blinded comparative approach and was conducted at Hospital Universiti Sains Malaysia between September 2023 and September 2024.In this study,the participants in the experimental group were supplied with a specialized oral supplement enriched with immune-modulating nutrients.Meanwhile,a conventional oral nutrition supplement was provided to the control group.The time to first flatus and the time to first bowel evacuation were the primary outcomes recorded.Incidence of nosocomial infections,surgical site infections,and the total length of hospital stay were considered secondary data.RESULTS This study involved 58 patients who were allocated into two groups.No dropouts were documented.The mean age of the participants was 61.20±12.96,and most were males(63.38%).All participants’baseline and surgical characteristics in both arms were also generally comparable.The participants in this study underwent colorectal surgery,where most had laparoscopic surgery(58%).Based on the results,no significant statistical differences were observed regarding the duration from the first flatus to the first bowel evacuation,the onset of a normal diet,and hospital stay between the experimental and control groups.Both groups also recorded 10(17.24%)infectious complications.CONCLUSION The findings indicated no notable variations in the primary and secondary endpoints despite the theoretical benefits of immune-modulating nutrients.Conclusively,routine preoperative immunonutrition may not provide additional advantages over standard nutrition in this demographic. 展开更多
关键词 Cancer surgery Colorectal surgery Gastrointestinal surgery IMMUNONUTRITION Postoperative complication
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Laparoscopic intracorporeal anastomosis is the future standard for ileostomy reversal in Crohn’s disease
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作者 Thai-Hau Koo Xue-Bin Leong +3 位作者 Yi-Lin Lee Mohd Hazeman zakaria Firdaus Hayati andee dzulkarnaen zakaria 《World Journal of Gastrointestinal Surgery》 2025年第10期1-4,共4页
In this editorial,we comment on an article by Liu et al.We focus specifically on the novel use of laparoscopic intracorporeal anastomosis(LIA)compared with open ileostomy reversal in patients with Crohn’s disease(CD)... In this editorial,we comment on an article by Liu et al.We focus specifically on the novel use of laparoscopic intracorporeal anastomosis(LIA)compared with open ileostomy reversal in patients with Crohn’s disease(CD),which is an innovative approach for improving postoperative outcomes and accelerating recovery in ileostomy reversal procedures.This study also highlights the limitations of the conventional open surgical technique,which is associated with higher rates of feeding intolerance,prolonged hospital stays,and delayed initiation of enteral nutrition.The chronic and recurrent nature of CD and the challenges posed by traditional surgical methods are issues addressed by LIA,which offers a minimally invasive approach that reduces surgical trauma,shortens recovery time,and improves tolerance to enteral nutrition,thereby enhancing postoperative outcomes.However,while LIA shows great promise,further prospective multicenter trials are needed to validate these findings and assess their broader application in other surgical scenarios.Overall,LIA represents a significant advancement in minimally invasive surgery for CD and has the potential to become the preferred standard approach for ileostomy reversal in patients requiring bowel reanastomosis. 展开更多
关键词 Crohn’s disease Ileostomy reversal Laparoscopic intracorporeal anastomosis Enteral nutrition intolerance
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Cancer-associated fibroblasts of colorectal cancer: Translationalprospects in liquid biopsy and targeted therapy
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作者 ELYN AMIELA SALLEH YEONG YEH LEE +2 位作者 andee dzulkarnaen zakaria NUR ASYILLA CHE JALIL MARAHAINI MUSA 《BIOCELL》 SCIE 2023年第10期2233-2244,共12页
Colorectal cancer (CRC) is a major global health concern. Accumulation of cancer-associated fibroblasts(CAFs) in CRC is associated with poor prognosis and disease recurrence. CAFs are the main cellular component ofthe... Colorectal cancer (CRC) is a major global health concern. Accumulation of cancer-associated fibroblasts(CAFs) in CRC is associated with poor prognosis and disease recurrence. CAFs are the main cellular component ofthe tumor microenvironment. CAF-tumor cell interplay, which is facilitated by various secretomes, drives colorectalcarcinogenesis. The complexity of CAF populations contributes to the heterogeneity of CRC and influences patientsurvival and treatment response. Due to their significant roles in colorectal carcinogenesis, different clinicalapplications utilizing or targeting CAFs have been suggested. Circulating CAFs (cCAFs) which can be detected inblood samples, have been proposed to help in determining patient prognosis and enables the detection of cancerthrough liquid biopsy. Liquid biopsy is gaining traction as it is non-invasive, allows frequent and easy sampling, andshows concordance to tissue biopsy analysis. In addition, CAF-targeted therapy is currently being studied extensivelyto be used as one of the treatment avenues for CRC. Various mechanisms of CAF-targeted therapy have beenreported, including blocking the signaling pathways involving CAFs and cancer cells, thus abolishing the CAF-tumorcell crosstalk and subsequently hindering tumorigenesis. These translational applications of cCAFs and utilization ofCAFs as key targets for CRC therapy, although still in the early phases of development, will potentially improve CRCpatient management in the future. 展开更多
关键词 Activated fibroblast Colon cancer Liquid biopsy Precision medicine
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A Multidisciplinary Approach in Management of Breast Cancer: Case Study and Literature Reviews
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作者 andee dzulkarnaen zakaria Nur Farhana Abd Salam +1 位作者 Wan Zainira Wan Zain Mohd Nizam Hashim 《Journal of Cancer Therapy》 2013年第7期7-11,共5页
The diagnosis of breast cancer can cause a significant anxiety in someone’s life. The care of the breast cancer patient requires in many centres. The care of breast cancer patient is undertaken as a joint venture bet... The diagnosis of breast cancer can cause a significant anxiety in someone’s life. The care of the breast cancer patient requires in many centres. The care of breast cancer patient is undertaken as a joint venture between the surgeon, medical oncologist, radiotherapist, pathologist and allied health professionals such as the clinical nurse specialist as well as counsellors. This is a case of a 39-years-old Malay woman presented to HUSM with a history of ulcerating breast lump with bloody pus discharge on the right breast. An initial mammogram study showed lesion suspicious of malignancy, and histopathological examination was consistent with invasive ductal carcinoma. She received neoadjuvant chemotherapy before proceeding to right modified radical mastectomy with axillary clearance and immediate chest wall reconstruction. Detailed discussion on the diagnosis, treatment, surgical intervention and progress of the patient with reference to available literature reviews are presented. 展开更多
关键词 BREAST CANCER MULTIDISCIPLINARY Approach RECONSTRUCTIVE SURGERY
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