Esophageal cancer (EC) presents a high mortality rate, mainly due to its aggressive nature. Squamous cell carcinoma is the most common histological type world-wide, though, a continuous increase in esophageal adenocar...Esophageal cancer (EC) presents a high mortality rate, mainly due to its aggressive nature. Squamous cell carcinoma is the most common histological type world-wide, though, a continuous increase in esophageal adenocarcinomas has been noted in the past decades. Common risk factors associated with EC include smoking, alcohol consumption, gastroesophageal reflux disease, Barrett's esophagus and obesity. In an effort to overcome chemotherapy resistance in oncology, it was discovered that histone acetylation/deacetylation equilibrium is altered in carcinogenesis, leading to changes in chromatin structure and altering expression of genes important in the cell cycle, differentiation and apoptosis. Based on this knowledge, histone acetylation was addressed as a potential novel chemotherapy drug target to repress cancer cell proliferation. There are four classes of histone deacetylases (HDACs) inhibitors with a variety of different mechanisms of actions that render them possible anticancer drugs. They arrest the cell cycle, inhibit differentiation and angiogenesis and induce apoptosis. They do not necessarily act on histone proteins, since they can also exert indirect anti-cancer effects, by modifying various cellular proteins.In addition,HDACs have also been associated with increased chemotherapy resistance.Based on the literature,HDACs have been associated with EC,with surveys revealing that increased expression of certain HDACs correlates with advanced TNM stages,tumor grade,metastatic potential and decreased 5-year overall and disease-free survival.The aim of this survey is to elucidate the molecular identity and mechanism of action of HDAC inhibitors as well as verify their potential utility as anti-cancer agents in esophageal cancer.展开更多
BACKGROUND Desmoid tumors(DT) are locally advanced but histologically benign monoclonal neoplasms that can occur from any musculoaponeurotic structure. The aim of this report is to analyze a rare clinical case of an a...BACKGROUND Desmoid tumors(DT) are locally advanced but histologically benign monoclonal neoplasms that can occur from any musculoaponeurotic structure. The aim of this report is to analyze a rare clinical case of an aggressive intra-abdominal DT successfully treated with sorafenib.CASE SUMMARY A 36-year-old man presented with increasing colicky abdominal pain and a selfpalpable mass in his left abdomen. Fourteen years earlier he was diagnosed with a large intra-abdominal tumor, which adhered to the left colonic flexure, part of the major gastric curvature and the spleen. Subsequent exploratory laparotomy revealed a voluminous mass in the epigastrium, arising from the posterior surface of the stomach and invading the superior mesenteric vessels, transverse mesocolon and the small bowel mesentery. As the tumor was unresectable, a jejunojejunal bypass was performed. Traditional therapeutic interventions proved insufficient, and the patient was started on sorafenib with a subsequent fulldisease response.CONCLUSIONDT's pathogenesis has been associated with mutations in the adenomatous polyposis coli(APC) gene or beta-catenin gene CTNNB1, sex steroids or previous surgical trauma. Local treatment modalities, such as surgery or radiotherapy, are implemented in aggressively progressing or symptomatic patients. Sorafenib is a hopeful therapeutic option against DTs, while several pharmacological agents have been successfully used.展开更多
July coincides with the beginning of the academic year in teaching hospitals across the United States of America (USA).The increased responsibility assumed by trainees transitioning to a higher role in the healthcare ...July coincides with the beginning of the academic year in teaching hospitals across the United States of America (USA).The increased responsibility assumed by trainees transitioning to a higher role in the healthcare team is hypothesized to lead to poorer patient outcomes,termed the“July Effect”.The consequence of a“July Effect”might be more severe in critical care settings,where the complexity of patients requires a higher level of experience and training.The only studies evaluating the“July Effect”in the ICU were published in the early 2000’s.;Since that time,several resident work-hour regulations have been implemented by the Accreditation Council for Graduate Medical Education (ACGME).;These regulations have resulted in more frequent sign-outs,reduced continuity of care,and less clinical time for trainees,which in theory could increase the risk of errors among young trainees at the time they are most vulnerable.展开更多
文摘Esophageal cancer (EC) presents a high mortality rate, mainly due to its aggressive nature. Squamous cell carcinoma is the most common histological type world-wide, though, a continuous increase in esophageal adenocarcinomas has been noted in the past decades. Common risk factors associated with EC include smoking, alcohol consumption, gastroesophageal reflux disease, Barrett's esophagus and obesity. In an effort to overcome chemotherapy resistance in oncology, it was discovered that histone acetylation/deacetylation equilibrium is altered in carcinogenesis, leading to changes in chromatin structure and altering expression of genes important in the cell cycle, differentiation and apoptosis. Based on this knowledge, histone acetylation was addressed as a potential novel chemotherapy drug target to repress cancer cell proliferation. There are four classes of histone deacetylases (HDACs) inhibitors with a variety of different mechanisms of actions that render them possible anticancer drugs. They arrest the cell cycle, inhibit differentiation and angiogenesis and induce apoptosis. They do not necessarily act on histone proteins, since they can also exert indirect anti-cancer effects, by modifying various cellular proteins.In addition,HDACs have also been associated with increased chemotherapy resistance.Based on the literature,HDACs have been associated with EC,with surveys revealing that increased expression of certain HDACs correlates with advanced TNM stages,tumor grade,metastatic potential and decreased 5-year overall and disease-free survival.The aim of this survey is to elucidate the molecular identity and mechanism of action of HDAC inhibitors as well as verify their potential utility as anti-cancer agents in esophageal cancer.
文摘BACKGROUND Desmoid tumors(DT) are locally advanced but histologically benign monoclonal neoplasms that can occur from any musculoaponeurotic structure. The aim of this report is to analyze a rare clinical case of an aggressive intra-abdominal DT successfully treated with sorafenib.CASE SUMMARY A 36-year-old man presented with increasing colicky abdominal pain and a selfpalpable mass in his left abdomen. Fourteen years earlier he was diagnosed with a large intra-abdominal tumor, which adhered to the left colonic flexure, part of the major gastric curvature and the spleen. Subsequent exploratory laparotomy revealed a voluminous mass in the epigastrium, arising from the posterior surface of the stomach and invading the superior mesenteric vessels, transverse mesocolon and the small bowel mesentery. As the tumor was unresectable, a jejunojejunal bypass was performed. Traditional therapeutic interventions proved insufficient, and the patient was started on sorafenib with a subsequent fulldisease response.CONCLUSIONDT's pathogenesis has been associated with mutations in the adenomatous polyposis coli(APC) gene or beta-catenin gene CTNNB1, sex steroids or previous surgical trauma. Local treatment modalities, such as surgery or radiotherapy, are implemented in aggressively progressing or symptomatic patients. Sorafenib is a hopeful therapeutic option against DTs, while several pharmacological agents have been successfully used.
文摘July coincides with the beginning of the academic year in teaching hospitals across the United States of America (USA).The increased responsibility assumed by trainees transitioning to a higher role in the healthcare team is hypothesized to lead to poorer patient outcomes,termed the“July Effect”.The consequence of a“July Effect”might be more severe in critical care settings,where the complexity of patients requires a higher level of experience and training.The only studies evaluating the“July Effect”in the ICU were published in the early 2000’s.;Since that time,several resident work-hour regulations have been implemented by the Accreditation Council for Graduate Medical Education (ACGME).;These regulations have resulted in more frequent sign-outs,reduced continuity of care,and less clinical time for trainees,which in theory could increase the risk of errors among young trainees at the time they are most vulnerable.
