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(...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.展开更多
The occurrence of intussusception in adults is rare,accounting for less than 5% of all cases of intussusceptions and almost 1%-5% of bowel obstruction.The condition is found in less than 1 in 1300 abdominal operations...The occurrence of intussusception in adults is rare,accounting for less than 5% of all cases of intussusceptions and almost 1%-5% of bowel obstruction.The condition is found in less than 1 in 1300 abdominal operations and 1 in 100 patients operated for intestinal obstruction.The child to adult ratio is more than 20:1.We report a rare case of ileocolic intussusception in an adult secondary to an ileal lipoma.展开更多
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...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.展开更多
AIM:To assess the outcomes of laparoscopic colorectal cancer resection in the octogenarian population at our institution.METHODS:Retrospective analysis of registry data accumulated prospectively were used in conjuncti...AIM:To assess the outcomes of laparoscopic colorectal cancer resection in the octogenarian population at our institution.METHODS:Retrospective analysis of registry data accumulated prospectively were used in conjunction with the data obtained from patient notes to identify outcome data for octogenarians who had undergone elective laparoscopic colorectal cancer resection.RESULTS:Laparoscopic colorectal cancer resections were performed in 68 octogenarians between 2003 and 2011 at our institution.Four operations(6%) were converted to an open technique.There were twelve cases of morbidity(18%) and two cases of mortality(3%).The overall median hospital stay was 8 d.The median time for a patient to be deemed surgically fit for discharge was 5 d reflecting a delay in provision of social care or stoma education.CONCLUSION:Our results support the view that laparoscopic surgery in octogenarians is safe,feasible and with a reduced length of stay.This is well reflected in our results which are compatible with United Kingdom national figures.展开更多
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 a...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.展开更多
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.
文摘The occurrence of intussusception in adults is rare,accounting for less than 5% of all cases of intussusceptions and almost 1%-5% of bowel obstruction.The condition is found in less than 1 in 1300 abdominal operations and 1 in 100 patients operated for intestinal obstruction.The child to adult ratio is more than 20:1.We report a rare case of ileocolic intussusception in an adult secondary to an ileal lipoma.
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.
文摘AIM:To assess the outcomes of laparoscopic colorectal cancer resection in the octogenarian population at our institution.METHODS:Retrospective analysis of registry data accumulated prospectively were used in conjunction with the data obtained from patient notes to identify outcome data for octogenarians who had undergone elective laparoscopic colorectal cancer resection.RESULTS:Laparoscopic colorectal cancer resections were performed in 68 octogenarians between 2003 and 2011 at our institution.Four operations(6%) were converted to an open technique.There were twelve cases of morbidity(18%) and two cases of mortality(3%).The overall median hospital stay was 8 d.The median time for a patient to be deemed surgically fit for discharge was 5 d reflecting a delay in provision of social care or stoma education.CONCLUSION:Our results support the view that laparoscopic surgery in octogenarians is safe,feasible and with a reduced length of stay.This is well reflected in our results which are compatible with United Kingdom national figures.
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.
