Induction and Analysis of Epithelial to Mesenchymal Transition

Epithelial to mesenchymal transition (EMT) is essential for proper morphogenesis during development. Misregulation of this process has been implicated as a key event in fibrosis and the progression of carcinomas to a metastatic state. Understanding the processes that underlie EMT is imperative for the early diagnosis and clinical control of these disease states. Reliable induction of EMT in vitro is a useful tool for drug discovery as well as to identify common gene expression signatures for diagnostic purposes. Here we demonstrate a straightforward method for the induction of EMT in a variety of cell types. Methods for the analysis of cells pre- and post-EMT induction by immunocytochemistry are also included. Additionally, we demonstrate the effectiveness of this method through antibody-based array analysis and migration/invasion assays.     

Cancer incidence among Canadian Veterans: A matched cohort study

IntroductionOccupational exposures related to military service may increase the risk of cancer for military Veterans, while high levels of fitness during service may decrease risk. However, few studies have compared this post-career cancer risk directly to the employed general population.MethodsThis retrospective cohort study used linked administrative data. Canadian Armed Forces and Royal Canadian Mounted Police Veterans in Ontario, Canada were matched 1:4 on age, sex, geography, and community-level income to a group of non-Veterans most likely to have been employed during a period similar to the Veterans’ military service. Cancer diagnoses were identified using the Ontario Cancer Registry.ResultsDuring the study period, 642 of 30 576 included Veterans (2.1%) and 3408 of the 122 293 matched general population cohort (2.8%) experienced at least one cancer diagnosis. The crude rate of cancer was 153.5 per 100 000 person-years among Veterans vs. 205.9 per 100 000 person-years for the general population cohort. After adjusting for rurality and matching variables, Veterans had an 27% lower risk of developing any cancer than their matched comparators [hazard ratio = 0.73 (95% CI: 0.67–0.80)]. Among specific cancer types, the risk of lung and colorectal cancer was significantly lower for Veterans relative to the general population cohort; the risk of breast and prostate cancer was similar.DiscussionThis study adds to the growing international evidence suggesting that risk of many cancers among Veterans is lower or similar to the general population. Further understanding of the complex relationships among occupational exposures, environmental factors, and lifestyle factors is needed.     

Further development of local IL-2 therapy of cancer: multiple versus single IL-2 treatment of transplanted murine colon carcinoma

We have compared the effect of one and up to four local IL-2 treatments of transplanted MC38 colon carcinoma. A single IL-2 treatment prolonged the survival time (p=0.015), but no cure was obtained. One local IL-2 treatment inhibited tumor growth for about 1 week. After the start of tumor regrowth, a further IL-2 injection was given. After four IL-2 injections 6 out of 13 mice were cured. Histological studies show that IL-2 induced a local vascular leakage syndrome leading to massive peritumoral edema and subsequent necrosis of tumor tissue. IL-2 also attracted infiltrating cells, mainly macrophages. Subsequent IL-2 injections led to complete tumor regression. We believe that the combination of necrotic tumor debris and the IL-2–induced macrophage reaction enhanced a tumor-specific immune response. This local IL-2 application was not toxic.     

兔脑种植VX2肿瘤动物模型的建立

目的建立兔VX2肿瘤脑内种植动物模型,观察其生长特性。方法采用兔脑内VX2肿瘤组织块种植法将VX2肿瘤组织块种植入24只成年New Zealand大白兔右侧大脑皮质内,用B超检测肿瘤的生长情况,在实验兔在肿瘤种植后第13、171、9、21、232、5天取材,进行组织学观察。并观察实验兔在种植VX2肿瘤后的生存期及出现厌食、偏瘫等神经系统体征和死亡的时间。结果VX2肿瘤组织块种植入脑内后荷瘤兔的中位生存期为24.5 d,平均生存期为24.8 d,肿瘤体积随种植后的时间在对数坐标中接近一条直线。VX2肿瘤种植入兔脑17 d后血供较丰富、呈鱼肉状生长,与正常脑组织边缘界限不清楚,第17~19天肿瘤中心出现坏死并出现腹腔内转移。光镜下从VX2肿瘤种植后第17天开始肿瘤细胞向正常脑组织浸润,并形成瘤巢,瘤周脑组织形成水肿带。结论在缺乏兔源性脑肿瘤的情况下,采用兔VX2肿瘤组织块颅内种植能较好模拟颅内肿瘤生长,为对脑肿瘤的某些实验研究提供条件。     

Stem cell biology in thyroid cancer: Insights for novel therapies

Currently, thyroid cancer is one of the most common endocrine cancer in the United States. A recent involvement of sub-population of stem cells, cancer stem cells, has been proposed in different histological types of thyroid cancer. Because of their ability of self-renewal and differentiation into various specialized cells in the body, these putative cells drive tumor genesis, metastatic activity and are responsible to provide chemo- and radioresistant nature to the cancer cells in the thyroid gland. Our Review was conducted from previously published literature to provide latest apprises to investigate the role of embryonic, somatic and cancer stem cells, and discusses the hypothesis of epithelial-mesenchymal transition. Different methods for their identification and isolation through stemness markers using various in vivo and in vitro methods such as flow cytometry, thyrosphere formation assay, aldehyde dehydrogenase activity and ATP-binding cassette sub-family G member 2 efflux-pump mediated Hoechst 33342 dye exclusion have been discussed. The review also outlines various setbacks that still remain to target these tumor initiating cells. Future perspectives of therapeutic strategies and their potential to treat advanced stages of thyroid cancer are also disclosed in this review.     

全数字化X线摄影联合MR 动态增强检查诊断早期乳腺癌的 临床价值研究

摘要目的：分析早期乳腺癌的全数字X 线摄影与MRI影像学表现,评价全数字X 线摄影联合MRI 检查在早期乳腺癌诊断中的 临床价值。方法：回顾性分析2009 年10 月至2012 年5月在我院经穿刺或手术病理证实为早期乳腺癌的42例患者的临床资料, 术前均行数字X线及动态增强MR 检查,比较两种方法单独使用和联合使用的诊断乳腺癌的准确率。结果：全数字化X 线摄片 诊断早期乳腺癌的准确率为69.0%(29/42),动态增强MR 检查为95.2%(40/42),两者比较差异有统计学意义(P<0.05);两者联合使 用诊断早期乳腺癌的准确率为97.6%(41/42)。结论：动态增强MR 检查对早期乳腺癌的诊断价值明显优于全数字X线摄影,但后 者对微小钙化显示较好,两者联合可提高诊断正确率,尤其对多腺体型和致密型乳腺的早期乳腺癌的检出具有重要的价值。     

贝伐珠单抗的疗效预测研究现状

抗血管生成的贝伐珠单抗已被广泛应用于多种恶性肿瘤的治疗。但因其受益人群有限及逐渐出现的获得性耐药,也限制了其对患者总生存的改善。迫切需要寻找有效的预测贝伐珠单抗疗效的预测因子指导临床应用。人们在生物标记物、影像学方面进行了大量探索,但目前尚没有一个公认的普遍适用的临床预测指标,仍需要从多角度出发,进行进一步的基础研究及临床研究去发现和验证有效的疗效预测指标。     

Isolation and characterization of temperature-sensitivelethal(2)giant larva alleles

Summary In this paper we present an analysis of the behavior ofl(2)gl ^tsimaginal wing discs during culture in adult hosts. Thel(2)gl ^tslarvae reared at 29° C contain two types of wing discs, those that are morphologically normal and those that are abnormal. When discs of both types are cultured in adult hosts at 29° C, the restrictive temperature, they give rise to transplantable neoplastic tissue. However, when the 29° C reared discs are cultured at 15° C, the permissive temperature, the morphologically normal discs maintain their morphology, but the morphologically abnormal discs give rise to neoplasms. Thel(2)gl ^tslarvae reared at 15° C contain only morphologically normal discs. When these discs are cultured in adult hosts at 29° C they give rise to neoplasms, however if the discs are cultured at 15° C they maintain their normal morphology. These results demonstrate: (1) that all wing imaginal discs obtained from 29° C rearedl(2)gl ^tslarvae are competent to undergo neoplastic development, (2) the morphologically abnormal discs obtained from the 29° C rearedl(2)gl ^tslarvae are committed to neoplastic development, (3) the neoplastic development of the morphologically normal discs is temperature dependent, (4) once the neoplastic development of thel(2)gl ^tsdiscs has been initiated the process is not readily reversible. In addition, the ability ofl(2)gl ^tswing discs to perform epimorphic regulation was tested by amputating morphologically normal permissively rearedl(2)gl ^tswing discs and culturing both fragiments at the permissive temperature. Fragments of control wild-type discs maintained their morphology during culture at the permissive temperature. However, both fragments of txel(2)gl ^tsdiscs became neoplastic. This result is discussed with respect to a possible role for thel(2)gl ⁺function in epimorphic regulation and with respect to the phenomena of tumor promotion in vertebrates.     

Colonoscopy screening and surveillance disparities during the COVID-19 pandemic

BackgroundThe COVID-19 pandemic has increased barriers to accessing preventive healthcare. This study identifies populations disproportionately underrepresented in screening and surveillance colonoscopies during the COVID-19 pandemic.MethodsIn this single-center cohort study, colonoscopy procedures were reviewed during 6-month intervals before the pandemic (July 1, 2019 - December 31, 2019) and during the pandemic (July 1, 2020 - December 31, 2020 and January 1, 2021 - June 30, 2021). 7095 patients were categorized based on procedure indication, demographics, Charlson Comorbidity Index and Social Vulnerability Index (SVI). Statistics performed using VassarStats.Results2387 (2019) colonoscopies pre-pandemic and 2585 (2020) and 2123 (2021) during the pandemic were identified. There was a decrease in colonoscopies performed during months when COVID-19 cases peaked. The total number of average CRC risk patients presenting for first colonoscopy declined during the pandemic: 232 (10 %) pre-pandemic to 190 (7 %) in 2020, 145 (7 %) in 2021 (p < 0.001). Fewer of these patients presented from highly vulnerable communities, SVI > 0.8, during the pandemic, 39 in 2019 vs 16 in 2020 and 22 in 2021. Of all screening and surveillance patients, fewer presented from communities with SVI > 0.8 during the pandemic, 106 in 2019 versus 67 in 2020 and 77 in 2021.ConclusionIt is important to address the decline in CRC preventive care during this pandemic among average CRC risk first-time screeners and vulnerable community patients. An emphasis on addressing social determinants of health and establishing patients in gastroenterology clinics is imperative to promote future health in these populations.     

High-risk Population for Gastric Cancer Development Based on Serum Pepsinogen Status and Lifestyle Factors

Background: Gastric atrophy is a major risk factor for non-cardiac gastric cancer. Serum pepsinogen status could identify people at high-risk for gastric cancer development during our previous cohort study. However, lifestyle-related factors may additionally affect this risk.
Materials and methods: A total of 6983 Japanese were followed up by annual endoscopy in the previous study, and 43 cases of gastric cancer including two cardiac cancers developed. In most subjects, the body length and weight were measured and a questionnaire was applied to gather information regarding life habits. The risk of non-cardiac gastric cancer development during surveillance was re-analyzed based on serum pepsinogen, sex, age, body mass index (BMI), alcohol, and smoking habit.
Results: A total of 6158 subjects with 37 non-cardiac gastric cancer development (male/female = 4259/1899, mean age = 49.0, mean follow-up period = 4.79 years) were entered into analysis. In a multivariate analysis, old age (by 10 years; (odds ratio) OR, 2.8; p  < .001), alcohol (weekly; OR, 2.4; p  = .03), smoking (current; OR, 5.6; p  = .006 and past; OR, 3.9; p  = .04), and pepsinogen status ("atrophic"; OR, 6.2; p  < .001) were independent risk factors, whereas BMI was not. The annual incidence of gastric cancer was 1.2% in the older subjects aged ≥ 60 years with "atrophic" pepsinogen status. Moreover, it was as high as 2.9% when they had both alcohol and current smoking habits.
Conclusions: Old age, alcohol, and smoking habits additionally promoted the risk for gastric cancer in subjects with gastric atrophy.