Apoptosis inducing factor is decreased in metastatic colon cancer in ex-vivo models of colon carcinogenesis by tissue microarray

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 14539-14539 ◽  
Author(s):  
S. Huerta ◽  
R. H. Amirkhan ◽  
A. A. Siddiqui ◽  
E. H. Livingston ◽  
S. Huerta-Yepez
Keyword(s):  
Colon Cancer ◽  
Tissue Microarray ◽  
Ex Vivo ◽  
Expression Patterns ◽  
Stage I ◽  
Stage Iii ◽  
Metastatic Colon Cancer ◽  
Primary Tumors ◽  
Apoptosis Inducing Factor

14539 Background: In vitro studies suggest that apoptosis inducing factor (AIF) expression is decreased in metastatic cells relative to those derived from primary tumors. This study was undertaken to determine AIF expression patterns in patients with stage I/II vs. stage III/IV colorectal cancers. Methods: Colon cancer specimens were prospectively collected (11/05–6/06) from 12 patients from 3 different sites: tumor, adjacent to tumor, and tissue 2 cm from the tumor. Paraffin-embedded specimens were examined by tissue microarray with AIF-specific antibodies. Total AIF expression as well as cytoplasmic and nuclear expression was assessed by an investigator blinded to the tissue site and patient stage. Staining was assessed as: 1=absent, 2=mild, 3=moderate, 4=high and 5=very high. The clinical characteristics and tumor stage of all patients were analyzed. Results: All patients were male. Eight patients had non-metastatic disease at the time of laparotomy, four had metastasis to: lymph nodes (n=3) and liver (n=1). Stage I/II patients (n=8) were of similar age compared to stage III/IV patients (n=4) [61.3±4.2 vs. 54.4±6.0 y.o.; p=0.6] had similar tumor size (3.81±0.7 vs. 4.08±1.4 cm; p=0.4). There was no difference in the level of expression of AIF in normal tissue collected 2-cm away from the tumor site in stage I/II vs. stage III/IV colon cancers in the cytoplasm (3.81±0.17 vs. 3.30±0.38; p=0.4), nucleus (3.19±0.43 vs. 2.49±0.46; p=0.8) or overall (4.06±0.27 vs. 3.37±0.8). A significant decrease in AIF expression was observed in stage III/IV tumors compared to stage I/II tumors in tissue collected adjacent to the tumor in the cytoplasm (3.12±0.22 vs. 4.46±0.25; p=0.03), the nucleus (2.10±0.44 vs. 3.63±0.32; p=0.03) and overall (3.12±0.22 vs. 4.46±0.25; p=0.03). There was a trend towards a decrease in AIF expression between stage III/IV vs. I/II tumors in tissue collected directly from the tumor in the cytoplasm (2.55±0.24 vs. 3.56±0.26; p=0.12), the nucleus (1.39±0.25 vs. 2.73±0.63; p=0.14) and overall (2.79±0.38 vs. 3.90±0.37; p=0.22). Conclusion: AIF expression is decreased in metastatic colon cancer. The main differences occur in the normal mucosa adjacent to the tumor. No significant financial relationships to disclose.

Down expression of activin A receptor type 2A in relation to metastatic potential and prognosis of patients with colon cancer.

2018 ◽  
Vol 36 (4_suppl) ◽  
pp. 712-712
Author(s):  
Changhua Zhuo ◽  
Dan Hu ◽  
Xiandong Lin ◽  
Ying Chen ◽  
Xiongwei Zheng ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Cell Proliferation ◽  
Cell Migration ◽  
Mrna Expression ◽  
Tissue Microarray ◽  
Validation Cohort ◽  
Activin A ◽  
Receptor Type ◽  
Primary Tumors

712 Background: The ACVR2A (activin A receptor type 2A) is a membrane receptor in TGF-β signal pathway, which is involved in the regulation of cell proliferation, migration and apoptosis. The expression profiles and biological functions of ACVR2A in colon cancer is largely unknown so far. Methods: ACVR2A expression was investigated using GSE39582 database and two validation cohorts. The in vitro study of the cell proliferation and migration of human colon cell lines was also performed. Results: In GSE39582 database (n = 497), lower mRNA expression of ACVR2A was identified as an inferior prognostic factor by linear regression analysis. In one validation cohort of 15 stage IV patients, the mRNA expression of ACVR2A was significantly reduced in metastatic lesions and primary tumors compared with adjacent normal controls (P = 0.001). In another validation cohort of tissue microarray (TMA) cohort consisting 193 cases, reduced ACVR2A expression was correlated with advanced N stage (P = 0.001) and positive lymphovascular invasion (P = 0.005). Strong correlations between lower ACVR2A mRNA or protein expression and worse survival were also observed in GSE39582 database and TMA validation cohort (all P< 0.05). Moreover, our in vitro studies showed a remarkable increase of cell migration in cell ACVR2A knockdown cells. Conclusions: Taken together, our findings indicate that loss of ACVR2A has an important role in cancer progression and distant metastasis, and may serve as a prognostic marker in patients with colon cancer. Keywords: Activin a receptor type 2A (ACVR2A), Colon Cancer, tissue microarray, Metastasis, Cell proliferation, Cell migration

Identification of biomarkers and functional modules from genomic data in stage-wise breast cancer

2020 ◽  
Vol 15 ◽  
Author(s):  
Athira K ◽  
Vrinda C ◽  
Sunil Kumar P V ◽  
Gopakumar G
Keyword(s):  
Breast Cancer ◽  
Expression Patterns ◽  
Differential Expression Analysis ◽  
Predictive Biomarkers ◽  
Stage I ◽  
Stage Ii ◽  
Stage Iii ◽  
Functional Modules ◽  
Incidence And Mortality ◽  
Multiple Stages

Background: Breast cancer is the most common cancer in women across the world, with high incidence and mortality rates. Being a heterogeneous disease, gene expression profiling based analysis plays a significant role in understanding breast cancer. Since expression patterns of patients belonging to the same stage of breast cancer vary considerably, an integrated stage-wise analysis involving multiple samples is expected to give more comprehensive results and understanding of breast cancer. Objective: The objective of this study is to detect functionally significant modules from gene co-expression network of cancerous tissues and to extract prognostic genes related to multiple stages of breast cancer. Methods: To achieve this, a multiplex framework is modelled to map the multiple stages of breast cancer, which is followed by a modularity optimization method to identify functional modules from it. These functional modules are found to enrich many Gene Ontology terms significantly that are associated with cancer. Result and Discussion: predictive biomarkers are identified based on differential expression analysis of multiple stages of breast cancer. Conclusion: Our analysis identified 13 stage-I specific genes, 12 stage-II specific genes, and 42 stage-III specific genes that are significantly regulated and could be promising targets of breast cancer therapy. That apart, we could identify 29, 18 and 26 lncRNAs specific to stage I, stage II and stage III respectively.

scholarly journals Conditional Survival and Cure of Patients With Colon or Rectal Cancer: A Population-Based Study

2020 ◽  
Vol 18 (9) ◽  
pp. 1230-1237 ◽  
Author(s):  
Seyed M. Qaderi ◽  
Paul W. Dickman ◽  
Johannes H.W. de Wilt ◽  
Rob H.A. Verhoeven
Keyword(s):  
Rectal Cancer ◽  
Colon Cancer ◽  
Population Based ◽  
Stage I ◽  
Stage Iii ◽  
Disease Stage ◽  
Conditional Survival ◽  
Population Based Study ◽  
Pathologic Stage ◽  
Number Of Patients

Background: The increasing number of colorectal cancer (CRC) survivors need survival estimates that account for the time already survived. The aim of this population-based study was to determine conditional survival, cure proportions, and time-to-cure (TTC) of patients with colon or rectal cancer. Materials and Methods: All patients with pathologic stage I–III CRC treated with endoscopy or surgery, diagnosed and registered in the Netherlands Cancer Registry between 1995 and 2016, and aged 18 to 99 years were included. Conditional survival was calculated for those diagnosed before and after 2007. Cure proportions were calculated using flexible parametric models. Results: A total of 175,384 patients with pathologic stage I (25%), II (38%), or III disease (37%) were included. Conditional 5-year survival of patients with stage I, II, and III colon cancer having survived 5 years was 98%, 94%, and 92%, respectively. For patients with stage I–III rectal cancer, this was 96%, 89%, and 85%, respectively. Statistical cure in patients with colon cancer was reached directly after diagnosis (stage I) to 6 years (stage III) after diagnosis depending on age, sex, and disease stage. Patients with rectal cancer reached cure 0.5 years after diagnosis (stage I) to 9 years after diagnosis (stage III). In 1995, approximately 42% to 46% of patients with stage III colon or rectal cancer, respectively, were considered cured, whereas in 2016 this percentage increased to 73% to 78%, respectively. Conclusions: The number of patients with CRC reaching cure has increased substantially over the years. This study’s results provide valuable insights into trends of CRC patient survival and are important for patients, clinicians, and policymakers.

scholarly journals Inflammatory Mediators and Gut Microbial Toxins Drive Colon Tumorigenesis by IL-23 Dependent Mechanism

Cancers ◽  
2021 ◽  
Vol 13 (20) ◽  
pp. 5159
Author(s):  
Janani Panneerselvam ◽  
Venkateshwar Madka ◽  
Rajani Rai ◽  
Katherine T. Morris ◽  
Courtney W. Houchen ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Dendritic Cells ◽  
Tumor Progression ◽  
Inflammatory Mediators ◽  
Ex Vivo ◽  
Colon Tumor ◽  
Colonic Tumor ◽  
Colon Tumorigenesis ◽  
Microbial Toxins

Obesity-associated chronic inflammation predisposes colon cancer risk development. Interleukin-23 (IL-23) is a potential inflammatory mediator linking obesity to chronic colonic inflammation, altered gut microbiome, and colon carcinogenesis. We aimed to elucidate the role of pro-inflammatory eicosanoids and gut bacterial toxins in priming dendritic cells and macrophages for IL-23 secretion to promote colon tumor progression. To investigate the association of IL-23 with obesity and colon tumorigenesis, we utilized TCGA data set and colonic tumors from humans and preclinical models. To understand IL-23 production by inflammatory mediators and gut microbial toxins, we performed several in vitro mechanistic studies to mimic the tumor microenvironment. Colonic tumors were utilized to perform the ex vivo experiments. Our findings showed that IL-23 is elevated in obese individuals, colonic tumors and correlated with reduced disease-free survival. In vitro studies showed that IL-23 treatment increased the colon tumor cell self-renewal, migration, and invasion while disrupting epithelial barrier permeability. Co-culture experiments of educated dendritic cells/macrophages with colon cancer cells significantly increased the tumor aggression by increasing the secretory levels of IL-23, and these observations are further supported by ex vivo rat colonic tumor organotypic experiments. Our results demonstrate gut microbe toxins and eicosanoids facilitate IL-23 production, which plays an important role in obesity-associated colonic tumor progression. This newly identified nexus represents a potential target for the prevention and treatment of obesity-associated colon cancer.

A National Cancer Database (NCDB) analysis of the impact of nonmetastatic colon cancer sidedness on survival.

2021 ◽  
Vol 39 (3_suppl) ◽  
pp. 139-139
Author(s):  
Deven Patel ◽  
Timothy DiPeri ◽  
Brian Cox ◽  
Andrew Eugene Hendifar ◽  
Arsen Osipov ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Logistic Regression ◽  
Adjuvant Chemotherapy ◽  
Large Population ◽  
Stage I ◽  
Prognostic Impact ◽  
Metastatic Colon Cancer ◽  
Prognostic Features ◽  
Binomial Logistic Regression ◽  
The Impact

139 Background: Differences in embryological origin and tumor biology distinguish right-sided colon cancer (RCC) from left-sided colon cancer (LCC). Previous studies characterizing the prognostic impact of colon cancer laterality on clinical outcomes in non-metastatic colon cancer have been conflicting, thus closer examination is needed. Methods: Using the NCDB, patients with stage I-III colon cancer between 2004-2014 were stratified according to tumor location; RCC vs. LCC. Patient (pt) and tumor characteristics were compared in univariate analysis, survival (OS) was estimated by Kaplan-Meier (KM) curves and Cox proportional hazards modeling. Binomial logistic regression analysis was utilized to identify variables associated with colon cancer laterality. Results: Of the 342,735 pts who met inclusion criteria, 210,343 (61.4%) were diagnosed with RCC, and 132,392 (38.6%) with LCC. Pts with RCC were older (mean 71.6 vs. 66.4 years, p< 0.001) and predominantly female (65% vs. 35%, p< 0.001) compared to those with LCC. A trend towards poorer OS was seen in pts with RCC (mean 91.0 mos [95% CI: 90.2-91.8]) compared to LCC (112.2 mos [95% CI: 110.9-113.6]) in unadjusted analysis. On Cox multivariable adjusted analyses there was a significant but minimal impact on OS and laterality (hazard ratio or HR [LCC as ref] 0.978, 95% CI 0.967-0.989 p< 0.0001). Multiple unadjusted KM survival analyses showed RCC with T4 disease, high-grade, LVI/PNI, positive margins, N0-N2 disease, tumor deposits, and receipt of adjuvant chemotherapy had poorer OS than those features in LCC (all p < 0.0001). Binomial logistic regression showed RCCs were significantly more likely to be higher grade (odds ratio or OR 2.024) and MSI-H (OR 2.010) with trends (nonsignificant) towards more likely having N1-2 positive disease, LVI, less receipt of adjuvant chemotherapy, and fewer tumor deposits. Conclusions: The impact of sidedness on prognosis in stage I-III colon cancer is complex. In this large, population-based study, RCC tends to be associated with more adverse prognostic features than LCC. More investigation into the biologic differences between RCC and LCC is warranted and how they impact phenotype and survival.

scholarly journals Iroquois Homeobox Protein 2 Identified as a Potential Biomarker for Parkinson’s Disease

2020 ◽  
Vol 21 (10) ◽  
pp. 3455
Author(s):  
Hyuna Sim ◽  
Joo-Eun Lee ◽  
Hee Min Yoo ◽  
Sunwha Cho ◽  
Hana Lee ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Ex Vivo ◽  
Expression Patterns ◽  
Cell Types ◽  
Motor Symptoms ◽  
Intestinal Organoids ◽  
Potential Biomarker ◽  
Homeobox Protein

The diagnosis of Parkinson’s disease (PD) is initiated after the occurrence of motor symptoms, such as resting tremors, rigidity, and bradykinesia. According to previous reports, non-motor symptoms, notably gastrointestinal dysfunction, could potentially be early biomarkers in PD patients as such symptoms occur earlier than motor symptoms. However, connecting PD to the intestine is methodologically challenging. Thus, we generated in vitro human intestinal organoids from PD patients and ex vivo mouse small intestinal organoids from aged transgenic mice. Both intestinal organoids (IOs) contained the human LRRK2 G2019S mutation, which is the most frequent genetic cause of familial and sporadic PD. By conducting comprehensive genomic comparisons with these two types of IOs, we determined that a particular gene, namely, Iroquois homeobox protein 2 (IRX2), showed PD-related expression patterns not only in human pluripotent stem cell (PSC)-derived neuroectodermal spheres but also in human PSC-derived neuronal cells containing dopaminergic neurons. We expected that our approach of using various cell types presented a novel technical method for studying the effects of multi-organs in PD pathophysiology as well as for the development of diagnostic markers for PD.

Single-Incision Laparoscopic Colectomy for Colon Cancer: Experiences with 308 Consecutive Cases

2018 ◽  
Vol 84 (4) ◽  
pp. 565-569 ◽  
Author(s):  
Yasumitsu Hirano ◽  
Masakazu Hattori ◽  
Kenji Douden ◽  
Chikashi Hiranuma ◽  
Yasuo Hashizume ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Single Incision ◽  
Survival Rates ◽  
Stage Iv ◽  
Stage I ◽  
Stage Ii ◽  
Stage Iii ◽  
Oncologic Outcomes ◽  
Single Incision Laparoscopic Surgery ◽  
Intention To Treat

Single-incision laparoscopic surgery (SILS) has been developed with the aim to further reduce the invasiveness of conventional laparoscopy. Our experiences with more than 300 consecutive patients with SILS for colon cancer are reviewed, and its outcomes are evaluated to determine the midterm clinical and oncologic safety of SILS for colon cancer in a community hospital. A single surgeon's consecutive experience of SILS for colon cancer is presented. Three hundred and eight patients were treated with the SILS procedure for colon cancer between December 2010 and March 2015. Data were analyzed according to intention to treat. Of these 308 patients, 19 (6.2%) were converted to laparotomy. Intraoperative injury occurred in five patients. Postoperative complications occurred in 19 patients (6.2%). The 2-year relapse-free survival rates of patients with Stage I, Stage II, and Stage III were 97.8, 92.2, and 80.4 per cent, respectively, and the 2-year overall survival rates of patients with Stage I, Stage II, Stage III, and Stage IV were 100, 95.7, 93.0, and 74.4 per cent, respectively. Our initial experiences showed that SILS colectomy for cancer can be performed safely and with good short-term oncologic outcomes by a skilled surgeon.

QIM19-124: Does Virtual Navigation Improve Care Continuity and Compliance in Patients With Early Stage Colon Cancer?

2019 ◽  
Vol 17 (3.5) ◽  
pp. QIM19-124
Author(s):  
Dayna Crawford ◽  
Brook Blackmore ◽  
Jeremy Ortega ◽  
Erica Williams
Keyword(s):  
Colon Cancer ◽  
Cancer Patients ◽  
Early Stage ◽  
Stage I ◽  
Stage Iii ◽  
Nccn Guidelines ◽  
Care Continuity ◽  
Colon Cancers ◽  
Follow Up Care

Background: Colon cancer is the 3rd most common cancer in men and women combined, with an occurrence rate of 4.49% for men and 4.15% for women. The 2018 expectation is 50,630 deaths related to colon cancer in the United States (American Cancer Society Facts and Figures 2018). Early detection is increasing with nearly 45% of colon cancers diagnosed as stage I/II (Sarah Cannon Cancer Registry 2015). Treatment for early stage I/II colon cancer patients usually involves surgery then surveillance. On-site navigators perform their duties by patient need and barriers to care. Late stage III/IV colon cancer patients require more assistance and face more barriers, which often leaves early stage I/II patients without an advocate. This disparity can lead to lower rates of follow-up care for early stage I/II patients. Sarah Cannon created a program for virtual colon navigation (VCN) to determine if early stage I/II patients benefit from a virtual navigator who offers support by phone throughout their disease process. Objectives: The goal was to increase early stage I/II patients’ knowledge of their cancer and convey the importance of compliance with follow-up care, such as repeat colonoscopy as recommended by their physician and NCCN Guidelines. Methods: By developing software that utilizes artificial intelligence, Sarah Cannon created an automated process to identify colon cancer patients at the time of diagnosis. This technology then routes positive pathology reports to a VCN who contacts the early stage I/II patients by telephone, ensuring patient connection to the suitable physician for treatment. The VCN helps patients understand their diagnosis, provides education, assesses barriers to care, connects to resources, provides emotional support, and offers assistance with follow-up for physician visits, imaging and procedures such as colonoscopies, based upon NCCN Guidelines and physician guidelines. The VCN also connects stage III/IV patients with an on-site navigator in their region for more hands-on navigation. Results: Through September 2018, Sarah Cannon navigated 734 colon cancers, 332 stage I/II and 402 stage III/IV. With our increased capacity, Sarah Cannon/HCA maintained a 98% rate of follow-up care with new diagnoses of all stages of colon cancer. Conclusions: The VCN program allowed Sarah Cannon/HCA to improve care continuity and compliance based upon NCCN Guidelines for early stage I/II colon cancer patients throughout 5 regions and 37 facilities.

Efficacy of Abbreviated Stanford V Chemotherapy and Involved Field Radiotherapy in Early Stage Hodgkin's Disease: Mature Results of the G4 Trial.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 1670-1670 ◽  
Author(s):  
Ranjana H Advani ◽  
Richard T Hoppe ◽  
David M. Baer ◽  
Joseph Mason ◽  
Saul A Rosenberg ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Hodgkin's Disease ◽  
Early Stage ◽  
Hodgkin’S Disease ◽  
Stage I ◽  
Metastatic Colon Cancer ◽  
Eortc Criteria ◽  
Grade 3 ◽  
Involved Field ◽  
Involved Field Radiotherapy

Abstract Abstract 1670 Poster Board I-696 The standard management for early stage Hodgkin's disease (HD) is combined modality therapy. In the G4 protocol, patients (pts) with non-bulky, supra-diaphragmatic stage I-IIA disease received 8 weeks of Stanford V chemotherapy + 30 Gy involved field radiotherapy (IFRT). 87 pts were enrolled and treated between 4/1996 and 4/2001. Median age was 30 years (16-59) and stages were IA (n=23), IIA (n=64). Unfavorable risk factors were present in 47 patients (54%) according to German Hodgkin Study Group (GHSG) criteria (> 2 AA sites, ESR > 50 or EN involvement) and 38 (44%) according to EORTC criteria (> 3 AA sites, ESR > 50). Therapy was well tolerated with grade 3-4 non-hematologic toxic events in 7 % of pts. These included constipation (n=3), peripheral neuropathy (n=1), generalized weakness (n=2), chest pain (n=1), mylagias (n=1), abdominal pain (n=1) and an allergic reaction to etoposide (n=1). 42 patients received cytokine support for grade 3-4 neutropenia however only 2 pts developed fever with neutropenia. No cases of clinical bleomycin toxicity or radiation pneumonitis were observed. At a median follow-up of 9 (2-12) years, freedom from progression (FFP) and survival (OS) are 94% and 96% respectively. FFP was 100% for favorable and 89% for unfavorable patients by GHSG criteria (p=0.04) with no differences in OS (96.9% versus 95.7%). All relapses (n=5) occurred in the RT field: limited in 2 patients and combined with distant disease in 3 pts. All relapses were in “unfavorable” risk patients: 5 per GHSG and 4 per EORTC criteria. Secondary therapy included chemotherapy followed by high dose therapy and stem cell support (n=3) and ABVD (n=2). Three pts died, 2 due to disease progression after second-line therapy and one due to metastatic colon cancer. 5 patients developed a second cancer (2 breast, 2 melanomas at unirradiated sites and 1 colon cancer). The cases of breast cancer were considered unrelated to RT as both occurred within 5-years of therapy in women who were > 30 yrs at time of treatment. No secondary AML and no late cardiac or pulmonary toxicities have been observed. In conclusion, for pts with non-bulky stage I/II A HD, abbreviated Stanford V with 8 weeks of chemotherapy and 30 Gy IFRT is a safe and highly effective regimen. It is still too early to assess potential RT-related complications. Our outcomes in “unfavorable” stage I-IIA patients without bulky or symptomatic disease compare favorably with more intensive or prolonged regimens employed by the GHSG and EORTC. Disclosures No relevant conflicts of interest to declare.

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