scholarly journals The Chemokine CXCL7 Is Related to Angiogenesis and Associated With Poor Prognosis in Colorectal Cancer Patients

2021 ◽  
Vol 11 ◽  
Author(s):  
Longhai Li ◽  
Kai Jiang ◽  
Dongpeng Li ◽  
Dongxiao Li ◽  
Zitong Fan ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Proportional Hazards ◽  
Rank Correlation ◽  
Cox Proportional Hazards ◽  
Vegf Expression ◽  
Spearman’S Rank Correlation ◽  
Spearman’S Rank Correlation Coefficient ◽  
Tumor Tissues ◽  
Colorectal Cancer Patients

ObjectiveThe present study was designed to investigate the role of the chemokine CXCL7 in angiogenesis and explore its prognostic value in colorectal cancer (CRC).MethodsA total of 160 CRC patients who had undergone surgery were included in this study, and staged according to the guidelines of the AJCC, 7th Edition. Expression of CXCL7 and VEGF was detected by immunohistochemical (IHC) staining and divided into high and low expression subgroups. The correlation between CXCL7 and VEGF expression was evaluated by Spearman’s rank-correlation coefficient. Prognosis based on CXCL7 and VEGF was evaluated using the Cox proportional hazards regression model and a nomogram of 5-year overall survival (OS) time.ResultsCXCL7 was highly expressed in tumor tissues (65.63% vs 25.00% in paracancerous tissue, P < 0.001), as was VEGF. CXCL7 and VEGF expression correlated well with N and TNM stage cancers (all P < 0.001). Importantly, CXCL7 was positively correlated with VEGF expression in CRC tissues. CXCL7 was an independent predictor of poor OS of CRC patients (HR = 2.216, 95% CI: 1.069-4.593, P = 0.032), and co-expression of CXCL7 and VEGF of predicted poor OS of 56.96 months.ConclusionExpression of CXCL7 correlated with VEGF and was associated with poor clinical outcomes in CRC patients.

A pooled analysis of the secondary resection for colorectal cancer liver metastases: Comparison of bevacizumab (Bmab) and anti-EGFRs.

2016 ◽  
Vol 34 (4_suppl) ◽  
pp. 610-610
Author(s):  
Wataru Ichikawa ◽  
Yu Sunakawa ◽  
Hirofumi Nakayama ◽  
Toshikazu Ikusue ◽  
Toshikado Kaneta ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Liver Metastases ◽  
Rank Correlation ◽  
Positive Association ◽  
Pooled Analysis ◽  
Clear Correlation ◽  
Colorectal Cancer Liver Metastases ◽  
Spearman’S Rank Correlation ◽  
Secondary Resection ◽  
Spearman’S Rank Correlation Coefficient

610 Background: Systemic chemotherapies can convert irresectable liver metastases (LM) to resectable in some cases of metastatic colorectal cancer (mCRC). Secondary surgical resection is now considered to be a worthwhile therapeutic aim in mCRC with LM. There is a clear correlation between radiological response and secondary resection rate (SRR) (Jones RP et al. Eur J Cancer 2014). However, it remains unclear which monoclonal antibodies contribute the improvement of SRR, Bmab or anti-EGFRs. Methods: We performed a systematic review of literature published between Jan 1998 and Aug 2015 to analyze the relationship between SRR and antibodies in mCRC treated with 1st-line chemotherapy. Phase II or III trials which obtained the information of response rate (RR) and resection of LM were included in this analysis. The RR, SRR, and R0 SRR were compared between Bmab- and anti-EGFR (cetuximab or panitumumab)-containing regimen groups using Mann–Whitney U test. The correlation between RR and R0 SRR was assessed by Spearman's rank correlation coefficient. Results: A total of 40 studies were enrolled: 33 treatment arms from 16 trials for liver-limited disease (LLD) and 31 arms from 24 trials for non-LLD. The result is shown below. No difference was observed in SRR and R0 SRR between Bmab and anti-EGFR groups. In addition, a preliminary analysis showed that RR had significantly positive association with R0 SRR in anti-EGFR group (R2 0.74, P=0.027 for non-LLD; R2 0.88, P=0.018 for LLD) but not in Bmab group (P=0.27 for non-LLD, P=0.12 for LLD). Conclusions: The SRR and R0 SRR were comparable between Bmab and anti-EGFRs, even in mCRC with LLD, while RR correlated with R0 SSR in anti-EGFRs but not in Bmab. These findings warrant validation in ongoing trials to compare the targeted-agents. [Table: see text]

scholarly journals Racial disparity in survival of patients diagnosed with early-onset colorectal cancer

2020 ◽  
Vol 9 (3) ◽  
pp. CRC32
Author(s):  
Kristin Wallace ◽  
Hong Li ◽  
Chrystal M Paulos ◽  
David N Lewin ◽  
Alexander V Alekseyenko
Keyword(s):  
Colorectal Cancer ◽  
Racial Differences ◽  
Proportional Hazards ◽  
Age Groups ◽  
Tumor Location ◽  
Cox Proportional Hazards ◽  
Risk Of Death ◽  
Study Materials ◽  
Caucasian Americans

Background: Survival is reduced in African–Americans (AAs) diagnosed with colorectal cancer (CRC), especially in those <50 years old, when compared with Caucasian Americans (CAs). Yet, the role of clinicopathologic features of CRCs on racial differences in survival needs further study. Materials & methods: Over 1000 individuals (CA 709, AA 320) diagnosed with CRC were studied for survival via the Cox proportional hazards regression analysis based on race and risk of death in two age groups (<50 or 50+). Results: Risk of death for younger AAs (<50) was elevated compared with younger CAs (hazard ratio [HR] 1.98 [1.26–3.09]). Yet no racial differences in survival was observed in older cohort (50+ years), HR 1.07 (0.88–1.31); p for interaction = 0.01. In younger AAs versus CAs only, colonic location attenuated the risk of death. Conclusion: The tumor location and histology influence the poorer survival observed in younger AAs suggesting these may also influence treatment responses.

Over-Expression of Flt3 Induces the Expression of NFkB Target Genes, cIAP-1 and IL-6.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 2051-2051
Author(s):  
Shinichiro Takahashi ◽  
Hideo Harigae ◽  
Mitsue Inomata ◽  
Keiko Kumura Ishii ◽  
Jonathan D. Licht ◽  
...  
Keyword(s):  
Tyrosine Kinases ◽  
Target Genes ◽  
Rank Correlation ◽  
Positive Influence ◽  
Over Expression ◽  
Real Time Quantitative Pcr ◽  
Spearman’S Rank Correlation ◽  
Spearman’S Rank Correlation Coefficient ◽  
Nfkb Pathway

Abstract Nuclear factor kappa B (NFkB) regulates transcription of many genes involved in the immune response, including cytokines (e.g. IL-6) and growth factors. NFkB suppresses apoptosis as well, through various mechanisms including activation of cellular inhibitor of apoptosis-1 (cIAP-1). NFkB can be activated by the activation of Ras/phosphatidylinositol 3′-kinase (PI3K)/protein kinase B pathway in acute myeloblastic leukemia (AML). It was reported that in large proportion of primary AML cells, NFkB is constitutively activated, and the target genes are upregulated. Flt3 is a member of receptor tyrosine kinases. Flt3 receptor phosphorylation/activation results in the activation of downstream kinase pathways, like Ras, PI3K, leading to abnormal cell growth and aberrant gene regulation. Increased levels of Flt3 transcript are observed in a large number of AML specimens, and the over-expression of Flt3 contributes to the phosphorylation of Flt3 and activation of this pathway. In this study, we addressed the role of Flt3 over-expression in the activation of NFkB, which is a target molecule of various kinase pathways. We first tested the effect of Flt3 expression to NFkB responsive reporter by transient transfection and revealed the significant induction of the reporter. Next, we generated Flt3 transgenic BaF3 (BaF3-Flt3) cells that stably over-expressing Flt3 to confirm this effect. The introduction of NFkB-responsive reporter, as well as serum response element (SRE)-luciferase fused reporter into these cells resulted in the activation of the reporters. These results suggest that Flt3 over-expression mediated signal transduction activates NFkB pathways and affects growth factor pathways as well. Real time quantitative PCR demonstrated that in BaF3-Flt3 cells, mRNA expression of IL-6 and cIAP-1, both known target genes of NFkB, were increased. AG1296 or PDTC, potent inhibitors of Flt3 and NFkB respectively, completely abrogated the induction of these genes, suggesting the importance of Flt3-NFkB pathway to these effects. Moreover, we measured the expression level of Flt3 and NFkB target genes in 24 primary AML samples. As a result, there was a tendency of moderate to weak positive correlation between Flt3 and NFkB target genes. (Flt3 vs IL-6 [Spearman’s rank correlation coefficient: r= 0.35], Flt3 vs cIAP-1 [r=0.16]). These facts may also indicate the positive influence of Flt3 over-expression to NFkB target genes. Overall, these suggest a role of Flt3 over-expression in the activation of NFkB pathway in AML.

scholarly journals Role of β-defensins in immune response in tuberculosis patients

2020 ◽  
Vol 7 (2) ◽  
pp. 102-106
Author(s):  
O. Pohorielova ◽  
O. Shevchenko
Keyword(s):  
Immune Response ◽  
Immune Cells ◽  
Rank Correlation ◽  
Lesion Volume ◽  
Tuberculosis Patients ◽  
Research Results ◽  
Spearman’S Rank Correlation ◽  
Spearman’S Rank Correlation Coefficient ◽  
Healthy Persons

ROLE OF Β-DEFENSINS IN IMMUNE RESPONSE IN TUBERCULOSIS PATIENTS Shevchenko O., Pohorielova O. Expanding of tuberculosis drug-resistance makes host-directed treatment an important part of tuberculosis treatment. Host-directed treatment is aimed at stimulating the production of antimicrobial peptides by the patient's immune cells. The use of β-defensins is very interesting in this field because of their pronounced bactericidal and bacteriostatic effects, as well as the ability to stimulate the chemotaxis of immune cells. The article presents a review on the immunological properties of the defensin family and the possibility of their use in practice. To complete the review 114 articles from “PubMed” resource were analyzed to perform the study. 34 of them were chosen to review immunomodulatory and antimicrobial action of β-defensins. The own research results on Human-beta-defensine-1 use as tuberculosis severity marker are also added to the research. To obtain our own research results, 100 TB patients and 20 healthy persons were included in the study. Human-beta-defensin-1 level in serum was investigated in all the patients at the treatment onset and in healthy persons. Mann-Whitney U test (for comparison of 2 independent groups) and Spearman's rank correlation coefficient were used for statistical data processing. It was found that Human-beta-defensin-1 level was significantly higher in TB patients than in healthy persons. A correlation of medium strength (r=+0.53, p<0.05) between Human-beta-defensin-1 and tuberculosis lesion volume was revealed. The data obtained allows to use human β-defensin-1 as a diagnostic marker of tuberculosis. Key words: tuberculosis, β-defensins, immunity, prognostic marker   Резюме. РОЛЬ Β-ДЕФЕНЗИНІВ В ІМУННІЙ ВІДПОВІДІ У ХВОРИХ НА ТУБЕРКУЛЬОЗ Шевченко О.С., Погорєлова О.О. Розширення лікарської стійкості туберкульозу робить лікування, спрямоване на активацію власних резервів організму-хазяїна, важливою частиною терапії. Таке лікування спрямоване на стимулювання продукції антимікробних пептидів імунними клітинами пацієнта. Використання β-дефензинів в даній області є перспективним через їх виражену бактерицидну і бактеріостатичну дію, а також здатність стимулювати хемотаксис імунних клітин. У статті представлений огляд імунологічних властивостей сімейства дефензинів і можливостей їх використання на практиці. Для створення огляду було проаналізовано 114 статей з ресурсу «PubMed». З них 34 були обрані для вивчення імуномодулюючої і антимікробної дії β-дефензинів. Результати власного дослідження можливостей використання β-дефензину-1 також були включені в роботу. Для отримання власних результатів у дослідження було включено 100 хворих на туберкульоз і 20 здорових людей. Рівень β-дефензіну-1 в сироватці крові був досліджений у всіх пацієнтів на початку лікування і у здорових людей. U-критерій Манна-Уїтні (для порівняння 2 незалежних груп) і коефіцієнт кореляції застосовувалися для статистичної обробки даних. Було виявлено, що рівень β-дефензину-1 був значно вищим у хворих на туберкульоз, ніж у здорових людей. Виявлено кореляцію середньої сили (r = + 0,53, р <0,05) між рівнем β-дефензину-1 і об’ємом туберкульозного ураження. Отримані дані дозволяють використовувати β-дефензин-1 в якості діагностичного маркеру перебігу туберкульозу. Ключові слова: туберкульоз, β-дефензини, імунітет, прогностичний маркер   Резюме. РОЛЬ Β-ДЕФЕНЗИНОВ В ИММУННОМ ОТВЕТЕ У БОЛЬНЫХ ТУБЕРКУЛЕЗОМ Шевченко О.С., Погорелова О.А. Расширение лекарственной устойчивости туберкулеза делает лечение, направленное на активацию резервов организма-хозяина, важной частью терапии. Такое лечение направлено на стимулирование производства антимикробных пептидов иммунными клетками пациента. Использование β-дефензинов в данной области является перспективным из-за их выраженного бактерицидного и бактериостатического действия, а также способности стимулировать хемотаксис иммунных клеток. В статье представлен обзор иммунологических свойств семейства дефензинов и возможности их использования на практике. Для создания обзора было проанализировано 114 статей из ресурса «PubMed». 34 из них были выбраны для изучения иммуномодулирующего и антимикробного действия β-дефензинов. Собственные результаты исследования возможностей использования β-дефензина-1 в качестве маркера тяжести туберкулеза также были включены в работу. Для получения собственных результатов в исследование были включены 100 больных туберкулезом и 20 здоровых людей. Уровень β-дефензина-1 в сыворотке был исследован у всех пациентов в начале лечения и у здоровых людей. U-критерий Манна-Уитни (для сравнения 2 независимых групп) и коэффициент корреляции Спирмена были использованы для статистической обработки данных. Было обнаружено, что уровень β-дефензина-1 был значительно выше у больных туберкулезом, чем у здоровых людей. Выявлена ​​корреляция средней силы (r = + 0,53, р <0,05) между уровнем β-дефензина-1 и туберкулезного поражения. Полученные данные позволяют использовать β-дефензин-1 в качестве диагностического маркера течения туберкулеза. Ключевые слова: туберкулез, β-дефензины, иммунитет, прогностический маркер

scholarly journals Asparagine metabolism in tumors is linked to poor survival in females with colorectal cancer: A cohort study

2021 ◽  
Author(s):  
Xinyi Shen ◽  
Yuping Cai ◽  
Lingeng Lu ◽  
Huang Huang ◽  
Hong Yan ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Proportional Hazards ◽  
Cox Proportional Hazards ◽  
Poor Survival ◽  
Free Survival ◽  
Polyamine Synthesis ◽  
Tumor Tissues ◽  
Metabolite Profiles ◽  
Improve Patient ◽  
Asparagine Metabolism

Abstract Background The interplay between the sex-specific differences in tumor metabolome and colorectal cancer (CRC) prognosis has never been studied and represents an opportunity to improve patient outcomes. This study aims to examine the link between tumor metabolome and prognosis by sex for CRC patients. Methods Using untargeted metabolomics analysis, abundances of 91 metabolites were obtained from primary tumor tissues from 197 patients (N=95 females, N=102 males) after surgical colectomy for stage I-III CRC. Cox Proportional Hazards (PH) regression models were applied to estimate the associations between tumor metabolome and 5-year overall survival (OS) and 5-year recurrence-free survival (RFS), and their interactions with sex. Results Eleven metabolites had significant sex differences in their associations with 5-year OS, and five metabolites for 5-year RFS (Pinteraction < .05). The metabolites asparagine and serine had sex interactions for both OS and RFS. Furthermore, sex-specific differences were found in the associations between prognosis and metabolic pathways. Notably, in the asparagine synthetase (ASNS)-catalyzed asparagine synthesis pathway, asparagine was associated with substantially poorer OS (hazard ratio [HR] = 6.39, 95% confidence interval [CI] = 1.78-22.91, P = .004) and RFS (HR = 4.36, 95% CI = 1.39-13.68, P = .01) for female patients only (Pinteraction, OS = .02, Pinteraction, RFS = .003). Similar prognostic disadvantages in females were seen in lysophospholipid and polyamine synthesis. Conclusions Unique metabolite profiles indicated increased asparagine synthesis was associated with poorer prognosis for females only, providing insights into precision medicine for CRC treatment stratified by sex.

Patterns of care and survival trends in elderly metastatic colorectal cancer patients: A SEER-Medicare analysis.

2011 ◽  
Vol 29 (4_suppl) ◽  
pp. 520-520
Author(s):  
V. Shankaran ◽  
S. J. Beck ◽  
D. K. Blough ◽  
Y. Yim ◽  
E. Yu ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Hepatic Resection ◽  
Metastatic Colorectal Cancer ◽  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model ◽  
New Drugs ◽  
Hazards Model ◽  
Colorectal Cancer Patients

520 Background: Over the last decade, the treatment of metastatic colorectal cancer (mCRC) has changed dramatically as new drugs and hepatic resection have been incorporated into practice. The goal of this study is to examine treatment patterns and survival trends for older patients (pts) with mCRC. Methods: Pts ≥ age 65 with mCRC diagnosed (dx) 2001-2005 were identified from the SEER-Medicare database. Pts were excluded for lack of Medicare parts A and B in the year prior to dx, second malignancy, or non- adenocarcinoma histology. First-line (1L) chemotherapy (CTx) use was identified by claims within 3 months of dx. Metastatectomy was identified by various claims for liver resection. Comorbidity was assessed by Klabunde index. A Cox proportional hazards regression model was used to assess the effect of demographic and treatment factors on survival. Results: A total of 5,725 pts (median age 77) met inclusion criteria. 274 pts (5%) underwent hepatic resection and 2,647 (46%) received CTx. From 2001-2003, 43% of pts received 1L CTx (34% and 1% with regimens containing irinotecan (Iri) and oxaliplatin (Ox) and 49% with 5-FU/cap alone). From 2004-2005, 51% of pts received 1L CTx (25%, 14%, and 37% with regimens containing bevacizumab (Bv), Iri, and Ox and 40% with 5-FU/cap alone). In the multivariate analysis using the Cox proportional hazards model, survival was significantly improved in pts receiving CTx or hepatic resection and in pts dx 2004-2005 (Table). Conclusions: In an older mCRC population, hepatic resection, CTx use, and mCRC dx in 2004-2005 are associated with improved survival. Improved survival of pts dx in 2004-2005 coincides with the 2004 approval dates and uptake of Bv and Ox, and may be associated with the use of these therapies. Further analysis will examine the associations between specific Ctx regimens, Bv, and survival and will include pts dx through 2007. [Table: see text] [Table: see text]

VEGF-A polymorphisms affect the pharmacologic effect of bevacizumab on VEGF-A levels in patients with metastatic colorectal cancer.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e15505-e15505
Author(s):  
Apostolos Papachristos ◽  
Polychronis Kemos ◽  
Haralabos Kalofonos ◽  
Gregory Sivolapenko
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Rank Correlation ◽  
Progression Free Survival ◽  
Strong Negative Correlation ◽  
Spearman’S Rank Correlation ◽  
Spearman’S Rank Correlation Coefficient ◽  
Bevacizumab Treatment ◽  
Individualized Dosing ◽  
Pharmacologic Effect

e15505 Background: Bevacizumab treatment presents large interpatient variability in efficacy. Mutations in VEGF-A rs699947 are associated with longer overall survival and progression free survival in bevacizumab-treated metastatic colorectal cancer (mCRC) patients. The aim of the present study was to investigate correlations between VEGF-A polymorphisms and VEGF-A levels in patients receiving bevacizumab for mCRC. Methods: 46 patients were studied. Blood samples were collected for VEGF-A (rs2010963, 1570360, rs699947) genotyping, and measurement of bevacizumab and VEGF-A levels. The Spearman's rank correlation coefficient was used to study the correlation between VEGF-A and bevacizumab levels. For the multiple analysis, we used linear regression with residual analysis and considering multicollinearity while the effects are reported with 95% confidence intervals. Results: In total 171 samples for VEGF-A and 157 for bevacizumab levels were analyzed. A very strong negative correlation between bevacizumab and VEGF-A levels (coef. = -0.625, p < 0.000001) was noted. Interestingly, VEGF-A rs699947 plays an important role in the model (p = 0.0002, 95% CI 32.5-58.1) and as VEGF-A levels were found to be significantly lower in patients with mutant rs699947 (p < 0.0001, 95% CI 25.2 - 53.8). Conclusions: In conclusion, genetic factors significantly affected the effect of bevacizumab on VEGF-A levels. Significantly lower VEGF levels were measured in carriers of mutant rs699947. These results may explain the favorable clinical outcomes reported in this sub-group of patients. These findings might enable clinicians to distinguish patients, who may benefit more and in a long-term. Finally, can be used to design individualized dosing schemes for bevacizumab.

scholarly journals Inferring Multiple Metagenomic Association Networks based on Variation of Environmental Factors

2020 ◽  
Author(s):  
Yuqing Yang ◽  
Xin Wang ◽  
Kaikun Xie ◽  
Congmin Zhu ◽  
Ning Chen ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Environmental Factors ◽  
Environmental Factor ◽  
Environmental Conditions ◽  
Synthetic Data ◽  
Rank Correlation ◽  
Cancer Dataset ◽  
Spearman’S Rank Correlation ◽  
Spearman’S Rank Correlation Coefficient ◽  
Irritable Bowel

AbstractIdentifying significant biological relationships or patterns is central to many metagenomic studies. Methods that estimate association networks have been proposed for this purpose, but they assume that associations are static, neglecting the fact that relationships in a microbial ecosystem may vary with changes in environmental factors, which can result in inaccurate estimations. We propose a computational model, k-Lognormal-Dirichlet-Multinomial model (kLDM), which estimates multiple association networks that correspond to specific environmental conditions according to values of environmental factors (EFs), and simultaneously infers microbe-microbe and environmental factor-microbe associations for each network. We showed the effectiveness of kLDM on synthetic data, a colorectal cancer dataset, as well as the TARA Oceans and American Gut project datasets. The results showed that the widely used Spearman’s rank correlation coefficient (SCC) performed much worse than other methods, indicating the importance of separating samples by environmental conditions. We compared cancer fecal samples with cancer-free samples, and our estimation showed fewer associations among microbes but stronger associations between specific bacteria such as five colorectal cancer (CRC)-associated OTUs, indicating gut microbe translocation in cancer patients. Some environmental-factor-dependent associations were found within marine eukaryotic community, and gut microbial heterogeneity of irritable bowel disease (IBD) patients was detected. Results demonstrated that kLDM could successfully unravel the underlying biological associations. In summary, our study presents a computational framework that can elucidate the complex associations within microbial ecosystems. The kLDM program, R, and python scripts, together with all experimental datasets are all accessible at Github (https://github.com/tinglab/kLDM.git).

Venous Thromboembolism in Patients With Colorectal Cancer: Incidence and Effect on Survival

2006 ◽  
Vol 24 (7) ◽  
pp. 1112-1118 ◽  
Author(s):  
Allison Alcalay ◽  
Ted Wun ◽  
Vijay Khatri ◽  
Helen K. Chew ◽  
Danielle Harvey ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Venous Thromboembolism ◽  
Cancer Patients ◽  
Metastatic Disease ◽  
Proportional Hazards ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Models ◽  
Major Operation ◽  
Regional Disease ◽  
Colorectal Cancer Patients

Purpose To describe the incidence and outcomes associated with venous thromboembolism (VTE) among patients with colorectal cancer. Methods This was a retrospective analysis of all colorectal cancer patients diagnosed in California between 1993 and 1995 and 1997 to 1999. Principal outcomes were incident symptomatic VTE events and death. Associations between specific risk factors and principal outcomes were analyzed using Cox proportional hazards models. Results Among 68,142 colorectal cancer patients, 50% were women, mean age was 70 ± 15 years, and approximately 70% underwent a major operation. The 2-year cumulative incidence of VTE was 2,100 patients (3.1%), with an incidence rate that decreased significantly over time from 5.0% (events/100 patient-years) in months 0 to 6 to 1.4% during months 7 to 12 to 0.6% during the second year. Significant predictors of VTE included metastatic stage (hazard ratio [HR] = 3.2; 95% CI, 2.8 to 3.8) and three or more comorbid conditions (HR = 2.0; 95% CI, 1.7 to 2.3). The risk of VTE was significantly reduced among Asians/Pacific Islanders (HR = 0.4; 95% CI, 0.3 to 0.5.) and patients who underwent an abdominal operation (HR = 0.4; 95% CI, 0.3 to 0.4). In risk-adjusted models, VTE was a significant predictor of death within 1 year of cancer diagnosis among patients with local- (HR = 1.8; 95% CI, 1.4 to 2.3) or regional-stage disease (HR = 1.5; 95% CI, 1.3 to 1.8) but not among patients with metastatic disease (HR = 1.1; 95% CI, 1.0 to 1.2). Conclusion The incidence of VTE among colorectal cancer patients was highest in the first 6 months after diagnosis and decreased rapidly thereafter. Metastatic disease and the number of medical comorbidities were the strongest predictors of VTE. Incident VTE reduced survival among patients with local or regional disease, suggesting that, in these patients, VTE may reflect the presence of a biologically more aggressive cancer.

Role of Regulatory Oncogenic or Tumor Suppressor miRNAs of PI3K/AKT Signaling Axis in the Pathogenesis of Colorectal Cancer

2019 ◽  
Vol 24 (39) ◽  
pp. 4605-4610 ◽  
Author(s):  
Atena Soleimani ◽  
Farzad Rahmani ◽  
Gordon A. Ferns ◽  
Mikhail Ryzhikov ◽  
Amir Avan ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Tumor Suppressor ◽  
Current Knowledge ◽  
Akt Signaling ◽  
Tumor Tissues ◽  
Radio Therapy ◽  
Signaling Axis ◽  
Cancer Tumor ◽  
Novel Biomarkers

Colorectal cancer (CRC) is the leading cause of cancer death worldwide and its incidence is increasing. In most patients with CRC, the PI3K/AKT signaling axis is over-activated. Regulatory oncogenic or tumor suppressor microRNAs (miRNAs) for PI3K/AKT signaling regulate cell proliferation, migration, invasion, angiogenesis, as well as resistance to chemo-/radio-therapy in colorectal cancer tumor tissues. Thus, regulatory miRNAs of PI3K/AKT/mTOR signaling represent novel biomarkers for new patient diagnosis and obtaining clinically invaluable information from post-treatment CRC patients for improving therapeutic strategies. This review summarizes the current knowledge of miRNAs’ regulatory roles of PI3K/AKT signaling in CRC pathogenesis.

Sign in / Sign up

Export Citation Format

Share Document