Efficacy of Vedolizumab Induction and Maintenance Therapy in Patients With Ulcerative Colitis, Regardless of Prior Exposure to TNF Antagonists
- Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association
- Published almost 3 years ago
The efficacy and safety of vedolizumab, a humanized immunoglobulin G1 monoclonal antibody against the integrin α4β7, was demonstrated in multicenter, phase 3, randomized, placebo-controlled trials in patients with moderately to severely active ulcerative colitis (UC) or Crohn’s disease. We analyzed data from 1 of these trials to determine the effects of vedolizumab therapy in patients with UC, based on past exposure to anti-tumor necrosis factor (TNF) agents.
fifteen percent of patients with Crohn’s disease (CD) are elderly; they are less likely to have complications and more likely to have colonic disease.
In 114 cases of the transverse colon isolated from cadavers (50 male, 64 female), anatomical examinations of the arterial system of the colon were performed. Arteriograms were obtained after dissecting and contrasting the colonic vessels with Mixobar contrast. In one case, on arteriography of the colon with its mesentery isolated from a 55-year-old male cadaver, a rare anatomical variant was found. The third mesenteric artery originated directly from the aorta-halfway between the superior and inferior mesenteric arteries and ascended obliquely in the direction of the hepatic flexure of the colon. Supply area of the artery was typical for the middle colic branch of the superior mesenteric artery: the distal segment of the ascending colon and the transverse colon. Such a variation, although very rare, may have particular impact on diagnosis and even the method and range of surgery.
The employment of anti-epidermal growth factor receptor (EGFR) antibodies represents a backbone of the therapeutic options for the treatment of metastatic colorectal cancer (mCRC). However, this therapy is poorly effective or ineffective in unselected patients. Mutations in KRAS, BRAF and PIK3CA genes have recently emerged as the best predictive factors of low/absent response to EGFR-targeted therapy. Due to the need for efficacious treatment options for mCRC patients bearing these mutations, in this short report we examined the antitumoral activity of the protease inhibitor gabexate mesilate, alone and in combination with the anti-EGFR monoclonal antibody cetuximab, in a panel of human CRC cell lines harbouring a different expression pattern of wild-type/mutated KRAS, BRAF and PIK3CA genes. Results obtained showed that gabexate mesilate significantly inhibited the growth, invasive potential and tumour-induced angiogenesis in all the CRC cells employed in this study (including those ones harbouring dual KRAS/PIK3CA or BRAF/PIK3CA mutation), while cetuximab affected these parameters only in CRC cells with KRAS, BRAF and PIK3CA wild-type. Notably, the antitumoral efficacy of gabexate mesilate and cetuximab in combination was found to be not superior than that observed with gabexate mesilate as single agent. Overall, these preliminary findings suggest that gabexate mesilate could represent a promising therapeutic option for mCRC patients, particularly for those harbouring KRAS, BRAF and PIK3CA mutations, either as mono-therapy or in addition to standard chemotherapy regimens. Further studies to better elucidate gabexate mesilate mechanism of action in CRC cells are therefore warranted.
To investigate the survival of individuals with colorectal cancer (CRC) with inflammatory bowel disease (IBD-associated CRC) compared to that of individuals without IBD diagnosed with CRC.
Local relapse and peritoneal carcinomatosis (PC) for pT4 colon cancer is estimated in 15,6% and 36,7% for 12 months and 36 months from surgical resection respectively, achieving a 5 years overall survival of 6%. There are promising results using prophylactic HIPEC in this group of patients, and it is estimated that up to 26% of all T4 colon cancer could benefit from this treatment with a minimal morbidity. Adjuvant HIPEC is effective to avoid the possibility of peritoneal seeding after surgical resection. Taking into account these results and the cumulative experience in HIPEC use, we will lead a randomized controlled trial to determine the effectiveness and safety of adjuvant treatment with HIPEC vs. standard treatment in patients with colon cancer at high risk of peritoneal recurrence (pT4).
Ulcerative colitis (UC) is a chronic relapsing-remitting form of inflammatory bowel disease (IBD) that increases the risk of colorectal cancer, the third most common malignancy in humans. Oxidative stress is a risk factor for the development of UC. The Keap1-Nrf2-ARE pathway is one of the most important defensive mechanisms against oxidative and/or electrophilic stresses. In this study, we identified CPUY192018 as a potent small-molecule inhibitor of the Keap1-Nrf2 PPI, investigated the cyto-protective effects of CPUY192018 on the NCM460 colonic cells and evaluated whether treatment with the inhibitor of the Keap1-Nrf2 PPI exerts protection on an established experimental model of UC induced by dextran sodium sulfate (DSS). Our study clearly demonstrated that CPUY192018 had a cytoprotective effect against DSS in both NCM460 cells and mouse colon via the activation of Nrf2 signaling. These results suggested that activation of Nrf2 by directly inhibiting the Keap1-Nrf2 PPI may be beneficial as a treatment for UC.
Colorectal cancer is the third most widely diagnosed cancer. Extracts from snails may modulate growth and development of colorectal cancer cells. The objective of this study was to determine the chemical composition of tissues derived fromHelix aspersaMüller and red-ox properties of tissue extracts. Then, the influence of extracts and their fractions of different molecular weights on viability of Caco-2 cells was examined. Tissue lyophilisates contained antioxidants that could be important in the prevention of colorectal cancer. Moreover, we confirmed the presence of a wide array of compounds that might be used in treatment of this disease. The decrease of cell viability after the application of extracts from lyophilized mucus and foot tissues was affirmed. The effect of extract from mucus could be related to the content of some proteins and peptides, proper essential amino acids (EAA)/non-essential amino acids (NEAA) ratio, Met restriction and the presence of Cu, Ca, Zn, Se. The influence of the extract from foot tissues could be assigned additionally to the presence of eicosapentaenoic, α-linolenic, linoleic and γ-linolenic acids. The opposite effect was demonstrated by extract from lyophilized shells which increased cell viability. Further studies are needed to know whether dietary supplying ofH. aspersaMüller tissues can be used as an approach in colorectal cancer management.
Colorectal cancer (CRC) is one of the most common malignancies in the United States. Every 3 years, the American Cancer Society provides an update of CRC incidence, survival, and mortality rates and trends. Incidence data through 2013 were provided by the Surveillance, Epidemiology, and End Results program, the National Program of Cancer Registries, and the North American Association of Central Cancer Registries. Mortality data through 2014 were provided by the National Center for Health Statistics. CRC incidence rates are highest in Alaska Natives and blacks and lowest in Asian/Pacific Islanders, and they are 30% to 40% higher in men than in women. Recent temporal patterns are generally similar by race and sex, but differ by age. Between 2000 and 2013, incidence rates in adults aged ≥50 years declined by 32%, with the drop largest for distal tumors in people aged ≥65 years (incidence rate ratio [IRR], 0.50; 95% confidence interval [95% CI], 0.48-0.52) and smallest for rectal tumors in ages 50 to 64 years (male IRR, 0.91; 95% CI, 0.85-0.96; female IRR, 1.00; 95% CI, 0.93-1.08). Overall CRC incidence in individuals ages ≥50 years declined from 2009 to 2013 in every state except Arkansas, with the decrease exceeding 5% annually in 7 states; however, rectal tumor incidence in those ages 50 to 64 years was stable in most states. Among adults aged <50 years, CRC incidence rates increased by 22% from 2000 to 2013, driven solely by tumors in the distal colon (IRR, 1.24; 95% CI, 1.13-1.35) and rectum (IRR, 1.22; 95% CI, 1.13-1.31). Similar to incidence patterns, CRC death rates decreased by 34% in among individuals aged ≥50 years during 2000 through 2014, but increased by 13% in those aged <50 years. Progress against CRC can be accelerated by increasing initiation of screening at age 50 years (average risk) or earlier (eg, family history of CRC/advanced adenomas) and eliminating disparities in high-quality treatment. In addition, research is needed to elucidate causes for increasing CRC in young adults. CA Cancer J Clin 2017. © 2017 American Cancer Society.
The appendix may modulate colon microbiota and bowel inflammation. We investigated whether appendectomy alters colorectal cancer risk.