| 1 | Hematopoietic stem cell-derived adipocytes and fibroblasts in the tumor microenvironment显示文摘The tumor microenvironment(TME) is complex and constantly evolving. This is due, in part, to the crosstalk between tumor cells and the multiple cell types that comprise the TME, which results in a heterogeneous population of tumor cells and TME cells. This review will focus on two stromal cell types, the cancerassociated adipocyte(CAA) and the cancer-associated fibroblast(CAF). In the clinic, the presence of CAAs and CAFs in the TME translates to poor prognosis in multiple tumor types. CAAs and CAFs have an activated phenotype and produce growth factors, inflammatory factors, cytokines, chemokines, extracellular matrix components, and proteases in an accelerated and aberrant fashion. Through this activated state, CAAs and CAFs remodel the TME, thereby driving all aspects of tumor progression, including tumor growth and survival, chemoresistance, tumor vascularization, tumor invasion, and tumor cell metastasis. Similarities in the tumorpromoting functions of CAAs and CAFs suggest that a multipronged therapeutic approach may be necessary to achieve maximal impact on disease. While CAAs and CAFs are thought to arise from tissues adjacent to the tumor, multiple alternative origins for CAAs and CAFs have recently been identified. Recent studies from our lab and others suggest that the hematopoietic stem cell, through the myeloid lineage, may serve as a progenitor for CAAs and CAFs. We hypothesize that the multiple origins of CAAs and CAFs may contribute to the heterogeneity seen in the TME. Thus, a better understanding of the origin of CAAs and CAFs, how this origin impacts their functions in the TME, and thetemporal participation of uniquely originating TME cells may lead to novel or improved anti-tumor therapeutics. | Ying Xiong Lindsay T Mc Donald Dayvia L Russell Ryan R Kelly Katie R Wilson Meenal Mehrotra Adam C Soloff Amanda C LaRue | 2015 | World Journal of Stem Cells2015，7，2： | 6 |
| 2 | Old vs new: Risk factors predicting early onset colorectal cancer显示文摘BACKGROUND Colorectal cancer(CRC)is the second leading cause of all cancer related deaths in the United States and Europe.Although the incidence has been decreasing for individuals’≥50,it has been on the rise for individuals<50.AIM To identify potential risk factors for early-onset CRC.METHODS A population-based cohort analysis using a national database,Explorys,screened all patients with an active electronic medical record from January 2012 to December 2016 with a diagnosis of CRC.Subgroups were stratified based on age(25–49 years vs≥50 years).Demographics,comorbidities,and symptom profiles were recorded and compared between both age groups.Furthermore,the younger group was also compared with a control group consisting of individuals aged 25-49 years within the same timeframe without a diagnosis of CRC.Twentydata points for CRC related factors were analyzed to identify potential risk factors specific to early-onset CRC.RESULTS A total of 68860 patients were identified with CRC,of which 5710(8.3%)were younger than 50 years old,with 4140(73%)between 40-49 years of age.Multivariable analysis was reported using odds ratio(OR)with 95%CI and demonstrated that several factors were associated with an increased risk of CRC in the early-onset group versus the later-onset group.These factors included:African-American race(OR 1.18,95%CI:1.09-1.27,P<0.001),presenting symptoms of abdominal pain(OR 1.82,95%CI:1.72-1.92,P<0.001),rectal pain(OR 1.50,95%CI:1.28-1.77,P<0.001),altered bowel function(OR 1.12,95%CI:1.05-1.19,P=0.0005),having a family history of any cancer(OR 1.78,95%CI:1.67-1.90,P<0.001),gastrointestinal(GI)malignancy(OR 2.36,95%CI:2.18-2.55,P<0.001),polyps(OR 1.41,95%CI:1.08-1.20,P<0.001),and obesity(OR 1.14,95%CI:1.08-1.20,P<0.001).Comparing the early-onset cohort versus the control group,factors that were associated with an increased risk of CRC were:male gender(OR 1.34,95%CI:1.27-1.41),P<0.001),Caucasian(OR 1.48,95%CI:1.40-1.57,P<0.001)and African-American race(OR 1.25,95%CI:1.17-1.35,P<0.001),presenting symptoms of abdominal pain(OR 4.73,95%CI:4.49-4.98,P<0.001),rectal pain(OR 7.48,95%CI:6.42-8.72,P<0.001),altered bowel function(OR 5.51,95%CI:5.19-5.85,P<0.001),rectal bleeding(OR 9.83,95%CI:9.12-10.6,P<0.001),weight loss(OR 7.43,95%CI:6.77-8.15,P<0.001),having a family history of cancer(OR 11.66,95%CI:10.97-12.39,P<0.001),GI malignancy(OR 28.67,95%CI:26.64-30.86,P<0.001),polyps(OR 8.15,95%CI:6.31-10.52,P<0.001),tobacco use(OR 2.46,95%CI:2.33-2.59,P<0.001),alcohol use(OR 1.71,95%CI:1.62-1.80,P<0.001),presence of colitis(OR 4.10,95%CI:3.79-4.43,P<0.001),and obesity(OR 2.88,95%CI:2.74-3.04,P<0.001).CONCLUSION Pending further investigation,these potential risk factors should lower the threshold of suspicion for early CRC and potentially be used to optimize guidelines for early screening. | Aslam R Syed Payal Thakkar Zachary D Horne Heitham Abdul-Baki Gursimran Kochhar Katie Farah Shyam Thakkar | 2019 | World Journal of Gastrointestinal Oncology2019，11，11： | 6 |
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