Bacterial biofilm in colorectal cancer: What is the real mechanism of action?

2020 ◽  
Vol 142 ◽  
pp. 104052 ◽  
Author(s):  
Rasoul Mirzaei ◽  
Hamed Mirzaei ◽  
Mohammad Yousef Alikhani ◽  
Mohammad Sholeh ◽  
Mohammad Reza Arabestani ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Mechanism Of Action ◽  
Bacterial Biofilm ◽  
The Real

scholarly journals Alemtuzumab in the long-term treatment of relapsing-remitting multiple sclerosis: an update on the clinical trial evidence and data from the real world

2017 ◽  
Vol 10 (10) ◽  
pp. 343-359 ◽  
Author(s):  
Tjalf Ziemssen ◽  
Katja Thomas
Keyword(s):  
Multiple Sclerosis ◽  
Adverse Events ◽  
Mechanism Of Action ◽  
Real World ◽  
Continuous Treatment ◽  
The Real ◽  
Relapsing Remitting ◽  
Remitting Multiple Sclerosis ◽  
Relapsing Remitting Multiple Sclerosis

Alemtuzumab is a humanized monoclonal antibody approved for the treatment of relapsing-remitting multiple sclerosis (RRMS), given as two annual courses on five consecutive days at baseline and on three consecutive days 12 months later. Here we provide an update on the long-term efficacy and safety of alemtuzumab in RRMS, including real-world experience, and advances in our understanding of its mechanism of action. Recent data from the phase II/III extension study have demonstrated that alemtuzumab reduces relapse rates, disability worsening, and the rate of brain volume loss over the long term, with many patients achieving no evidence of disease activity. In high proportions of patients, preexisting disability remained stable or improved. Alemtuzumab is associated with a consistent safety profile over the long term, with no new safety signals emerging and the overall annual incidence of reported adverse events decreasing after the first year on treatment. Acyclovir prophylaxis reduces herpetic infections, and monitoring has been shown to mitigate the risk of autoimmune adverse events, allowing early detection and overall effective management. Data from clinical practice and ongoing observational studies are providing additional information on the real-world use of alemtuzumab. Recent evidence on the mechanism of action of alemtuzumab indicates that in addition to its previously known effects of inducing depletion and repopulation of T and B lymphocytes, it also results in a relative increase of cells with memory and regulatory phenotypes and a decrease in cells with a proinflammatory signature, and may further promote an immunoregulatory environment through an impact on other innate immune cells (e.g. dendritic cells) that play a role in MS. These effects may allow preservation of innate immunity and immunosurveillance. Together, these lines of evidence help explain the durable clinical efficacy of alemtuzumab, in the absence of continuous treatment, in patients with RRMS.

The real-world use of regorafenib for metastatic colorectal cancer: multicentre analysis of treatment pattern and outcomes in Hong Kong

2016 ◽  
Vol 93 (1101) ◽  
pp. 395-400 ◽  
Author(s):  
Ka-On Lam ◽  
Kin-Chung Lee ◽  
Joanne Chiu ◽  
Victor Ho-Fun Lee ◽  
Roland Leung ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Hong Kong ◽  
Metastatic Colorectal Cancer ◽  
Real World ◽  
Treatment Pattern ◽  
The Real

Survival among metastatic colorectal patients in clinical trials compared to the real world.

2015 ◽  
Vol 33 (3_suppl) ◽  
pp. 673-673
Author(s):  
Ziwei Wang ◽  
Lindsay Hwang ◽  
James Don Murphy
Keyword(s):  
Colorectal Cancer ◽  
Clinical Trial ◽  
Clinical Trials ◽  
Metastatic Colorectal Cancer ◽  
Median Survival ◽  
Real World ◽  
Randomized Clinical Trials ◽  
Phase Iii ◽  
The Real ◽  
Clinical Trial Results

673 Background: Randomized clinical trials play a central role in clinical research though only a small fraction of patients partake in clinical studies. Questions thus arise regarding the generalizability of clinical trial results to the remainder of the population. This study evaluated whether patient survival from randomized clinical trials in metastatic colorectal cancer reflects real world outcomes. Methods: A Pubmed search was used to identify randomized phase III clinical trials of first-line treatment for metastatic colorectal cancer published between 2005 and 2010. We excluded secondary or pooled analyses, second-line treatments, non-metastatic patients, non-English language, and non-randomized studies. Thirty-one clinical trials met these criteria, comprised of 79 distinct clinical trial arms. Overall survival among clinical trial patients was compared to metastatic colorectal cancer patients within the Surveillance, Epidemiology, and End Results (SEER) program. Within SEER, we restricted the analysis time-period and age of patients to match the enrollment period and age of patients within each individual clinical trial. Results: The clinical trials enrolled a total of 16,614 patients. Among all clinical trial arms the median survival ranged from 6.7-62 months, 1-year survival ranged from 30-97%, and 2-year survival ranged from 6-88%. Compared to SEER, the median survival was higher in 95% of the individual clinical trial arms by an average of 5.4 months (p<0.0001). The 1-year survival was higher in 94% of the clinical trial arms by an average of 16.7% (p<0.0001). The 2-year survival was higher in 71% of the clinical trial arms by an average of 7.2% (p<0.0001). Conclusions: This study found substantially improved survival among clinical trial participants compared to patients in the SEER database suggesting that survival estimates from clinical trials may not generalize to the “real world.” Potential patient factors such as differences in underlying comorbidity, performance status, disease burden, as well as variation in treatment could not be addressed in this study, though these factors likely explain some of the observed survival differences.

scholarly journals The real-word impact of breast and colorectal cancer surgery during the SARS-CoV-2 pandemic

2022 ◽  
Author(s):  
Pasquale Losurdo ◽  
Natasa Samardzic ◽  
Francesca Di Lenarda ◽  
Nicolò de Manzini ◽  
Fabiola Giudici ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cancer Surgery ◽  
Real Word ◽  
Colorectal Cancer Surgery ◽  
The Real

scholarly journals Computational Identification of Stearic Acid as a Potential PDK1 Inhibitor and In Vitro Validation of Stearic Acid as Colon Cancer Therapeutic in Combination with 5-Fluorouracil

2021 ◽  
Vol 20 ◽  
pp. 117693512110659
Author(s):  
Jonathan Mitchel ◽  
Pratima Bajaj ◽  
Ketki Patil ◽  
Austin Gunnarson ◽  
Emilie Pourchet ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Drug Design ◽  
Stearic Acid ◽  
Mechanism Of Action ◽  
Colorectal Adenocarcinoma ◽  
Metabolic Reprogramming ◽  
Colorectal Cancers ◽  
Structure Based Drug Design ◽  
Computational Structure ◽  
Efficacious Treatment

Background: Colorectal cancer is the third largest cause of cancer-related mortality worldwide. Although current treatments with chemotherapeutics have allowed for management of colorectal cancer, additional novel treatments are essential. Intervening with the metabolic reprogramming observed in cancers called “Warburg Effect,” is one of the novel strategies considered to combat cancers. In the metabolic reprogramming pathway, pyruvate dehydrogenase kinase (PDK1) plays a pivotal role. Identification and characterization of a PDK1 inhibitor is of paramount importance. Further, for efficacious treatment of colorectal cancers, combinatorial regimens are essential. To this end, we opted to identify a PDK1 inhibitor using computational structure-based drug design FINDSITEcomb and perform combinatorial studies with 5-FU for efficacious treatment of colorectal cancers. Methods: Using computational structure-based drug design FINDSITEcomb, stearic acid (SA) was identified as a possible PDK1 inhibitor. Elucidation of the mechanism of action of SA was performed using flow cytometry, clonogenic assays. Results: When the growth inhibitory potential of SA was tested on colorectal adenocarcinoma (DLD-1) cells, a 50% inhibitory concentration (IC50) of 60 µM was recorded. Moreover, SA inhibited the proliferation potential of DLD-1 cells as shown by the clonogenic assay and there was a sustained response even after withdrawal of the compound. Elucidation of the mechanism of action revealed, that the inhibitory effect of SA was through the programmed cell death pathway. There was increase in the number of apoptotic and multicaspase positive cells. SA also impacted the levels of the cell survival protein Bcl-2. With the aim of achieving improved treatment for colorectal cancer, we opted to combine 5-fluorouracil (5-FU), the currently used drug in the clinic, with SA. Combining SA with 5-FU, revealed a synergistic effect in which the IC50 of 5-FU decreased from 25 to 6 µM upon combination with 60 µM SA. Further, SA did not inhibit non-tumorigenic NIH-3T3 proliferation. Conclusions: We envision that this significant decrease in the IC50 of 5-FU could translate into less side effects of 5-FU and increase the efficacy of the treatment due to the multifaceted action of SA. The data generated from the current studies on the inhibition of colorectal adenocarcinoma by SA discovered by the use of the computational program as well as synergistic action with 5-FU should open up novel therapeutic options for the management of colorectal adenocarcinomas.

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