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| 1 | Novel therapeutic diiminoquinone exhibits anticancer effects on human colorectal cancer cells in two-dimensional and threedimensional in vitro models显示文摘BACKGROUND Colorectal cancer(CRC) is the second leading cause of cancer-related mortality.Cancer stem cells(CSCs) in CRC, which are spared by many chemotherapeutics,have tumorigenic capacity and are believed to be the reason behind cancer relapse. So far, there have been no effective drugs to target colon CSCs. Diiminoquinone(DIQ) has shown promising effects on targeting colon cancer.However, there is limited research on the effects of DIQ on eradicating CSCs in CRC.AIM To investigate the anticancer potential of DIQ on colon CSCs in two-dimensional(2D) and three-dimensional(3D) models using colonospheres and patient-derived organoids.METHODS Various 2D methods have been used to assess the effect and the mechanism of DIQ on HCT116and HT29 cell lines including cell proliferation and viability assays, migration and invasion assays,immunofluorescence staining, and flow cytometry. The potency of DIQ was also assessed in 3D culture using the sphere formation assay and colon cancer patient-derived organoid model.RESULTS Our results showed that DIQ significantly inhibited cell proliferation, migration, and invasion in HCT116 and HT29 cell lines. DIQ treatment induced apoptosis along with an accumulation of HCT116 and HT29 cancer cells in the sub-G1 region and an increase in reactive oxygen species in both CRC cell lines. DIQ reduced sphere-forming and self-renewal ability of colon cancer HCT116and HT29 stem/progenitor cells at sub-toxic doses of 1 μmol/L. Mechanistically, DIQ targets CSCs by downregulating the main components of stem cell-related-catenin, AKT, and ERK oncogenic signaling pathways. Potently, DIQ displayed a highly significant decrease in both the count and the size of the organoids derived from colon cancer patients as compared to control and 5-fluorouracil conditions.CONCLUSION This study is the first documentation of the molecular mechanism of the novel anticancer therapeutic DIQ via targeting CSC, a promising compound that needs further investigation. | Alissar Monzer Kevork Wakimian Farah Ballout Samar Al Bitar Amani Yehya Mariam Kanso Nour Saheb Ayman Tawil Samer Doughan Maher Hussein Deborah Mukherji Walid Faraj Hala Gali-Muhtasib Wassim Abou-Kheir | 2022 | World Journal of Gastroenterology2022，28，33： | 1 |
| 2 | Molecular mechanisms targeting drug-resistance and metastasis in colorectal cancer:Updates and beyond显示文摘Colorectal cancer(CRC)is the third most diagnosed malignancy and a major leading cause of cancer-related deaths worldwide.Despite advances in therapeutic regimens,the number of patients presenting with metastatic CRC(mCRC)is increasing due to resistance to therapy,conferred by a small population of cancer cells,known as cancer stem cells.Targeted therapies have been highly successful in prolonging the overall survival of patients with mCRC.Agents are being developed to target key molecules involved in drug-resistance and metastasis of CRC,and these include vascular endothelial growth factor,epidermal growth factor receptor,human epidermal growth factor receptor-2,mitogen-activated extracellular signal-regulated kinase,in addition to immune checkpoints.Currently,there are several ongoing clinical trials of newly developed targeted agents,which have shown considerable clinical efficacy and have improved the prognosis of patients who do not benefit from conventional chemotherapy.In this review,we highlight recent developments in the use of existing and novel targeted agents against drug-resistant CRC and mCRC.Furthermore,we discuss limitations and challenges associated with targeted therapy and strategies to combat intrinsic and acquired resistance to these therapies,in addition to the importance of implementing better preclinical models and the application of personalized therapy based on predictive biomarkers for treatment selection. | Samar Al Bitar Marwan El-Sabban Samer Doughan Wassim Abou-Kheir | 2023 | World Journal of Gastroenterology2023，29，9： | 1 |
| 3 | Potential role of micro ribonucleic acids in screening for anal cancer in human papilloma virus and human immunodeficiency virus related malignancies显示文摘Despite advances in antiretroviral treatment(ART),human immunodeficiency virus(HIV)continues to be a major global public health issue owing to the increased mortality rates related to the prevalent oncogenic viruses among people living with HIV(PLWH).Human papillomavirus(HPV)is the most common sexually transmitted viral disease in both men and women worldwide.High-risk or oncogenic HPV types are associated with the development of HPV-related malignancies,including cervical,penile,and anal cancer,in addition to oral cancers.The incidence of anal squamous cell cancers is increasing among PLWH,necessitating the need for reliable screening methods in this population at risk.In fact,the currently used screening methods,including the Pap smear,are invasive and are neither sensitive nor specific.Investigators are interested in circulatory and tissue micro ribonucleic acids(miRNAs),as these small non-coding RNAs are ideal biomarkers for early detection and prognosis of cancer.Multiple miRNAs are deregulated during HIV and HPV infection and their deregulation contributes to the pathogenesis of disease.Here,we will review the molecular basis of HIV and HPV co-infections and focus on the pathogenesis and epidemiology of anal cancer in PLWH.The limitations of screening for anal cancer and the need for a reliable screening program that involves specific miRNAs with diagnostic and therapeutic values is also discussed. | Samar Al Bitar Tala Ballouz Samer Doughan Hala Gali-Muhtasib Nesrine Rizk | 2021 | World Journal of Gastrointestinal Pathophysiology2021，12，4： | 0 |
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