Drug repurposing to overcome resistance to various therapies for colorectal cancer.

Drug repurposing to overcome resistance to various therapies for colorectal cancer. Cell Mol Life Sci. 2019 May 13;: Authors: Fong W, To KKW Abstract Emergence of novel treatment modalities provides effective therapeutic options, apart from conventional cytotoxic chemotherapy, to fight against colorectal cancer. Unfortunately, drug resistance remains a huge challenge in clinics, leading to invariable occurrence of disease progression after treatment initiation. While novel drug development is unfavorable in terms of time frame and costs, drug repurposing is one of the promising strategies to combat resistance. This approach refers to the application of clinically available drugs to treat a different disease. With the well-established safety profile and optimal dosing of these approved drugs, their combination with current cancer therapy is suggested to provide an economical, safe and efficacious approach to overcome drug resistance and prolong patient survival. Here, we review both preclinical and clinical efficacy, as well as cellular mechanisms, of some extensively studied repurposed drugs, including non-steroidal anti-inflammatory drugs, statins, metformin, chloroquine, disulfiram, niclosamide, zoledronic acid and angiotensin receptor blockers. The three major treatment modalities in the management of colorectal cancer, namely classical cytotoxic chemotherapy, molecular targeted therapy and immunotherapy, are covered in this review. PMID: 3108711...
Source: Cellular and Molecular Life Sciences : CMLS - Category: Cytology Authors: Tags: Cell Mol Life Sci Source Type: research

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Publication date: Available online 13 June 2019Source: Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of LipidsAuthor(s): Bhoomika Sharma, Vikas Gupta, Divya Dahiya, Hemanth Kumar, Kim Vaiphei, Navneet AgnihotriAbstractAccumulation of cholesterol is a well-known feature in cancer. Preclinical studies suggest the contribution of various cholesterol regulators in CRC. However, their clinical relevance remains poorly understood. The aim of the present study is to evaluate the expression of these modulators in CRC and elucidate their diagnostic and prognostic value. mRNA levels of HMGCR, SREBF2, NR1H3 and NR1...
Source: Biochimica et Biophysica Acta (BBA) Molecular and Cell Biology of Lipids - Category: Lipidology Source Type: research
Abstract Monacolin K (MK) is the principal active substance in Monascus-fermentation products (e.g. red yeast rice). MK is effective in reducing cholesterol levels in humans and has been widely used as a lipid-lowering drug. The mechanism for this is through a high degree of competitive inhibition of the rate-limiting enzyme HMG-CoA reductase (HMGR) in the cholesterol synthesis pathway. In addition to lowering blood lipid levels, MK also prevents colon cancer, acute myeloid leukemia and neurological disorders such as Parkinson's disease and type I neurofibromatosis. The aim of this manuscript is to comprehensively...
Source: Food and Chemical Toxicology - Category: Food Science Authors: Tags: Food Chem Toxicol Source Type: research
Aims: Noninvasive tools for the prognosis of colorectal cancer (CRC) are in urgent need. Lipids and proteins have been studied in CRC several years, thus a prognostic indicator based on preoperative serum high-density lipoprotein cholesterol (HDL-C) and serum albumin (ALB) levels (HA score) in CRC patients and to compare the correlation with survival to that of the Glasgow prognostic score.Patient and methods: In the present study, the patient characteristics, clinicopathological factors, and the level of pre-treatment serum markers (HDL-C, ALB, CEA and CA19-9) were analyzed retrospectively in 248 patients with CRC.Results...
Source: Journal of Cancer - Category: Cancer & Oncology Authors: Tags: Research Paper Source Type: research
Conclusions: Our result suggests that, among CRC patients with MetS, taking metformin and statins may improve overall survival, whereas being on insulin may negatively impact CRC prognosis. Further studies are warranted to determine the exact mechanism through which metformin, statins, and insulin exert their effects on CRC survival. PMID: 31139216 [PubMed]
Source: Journal of Cancer Epidemiology - Category: Epidemiology Tags: J Cancer Epidemiol Source Type: research
ConclusionsHigh statin users with hypercholesterolemia were associated with lower risk of overall colorectal cancer, especially proximal colon cancer in men and rectal cancer in both sexes.
Source: Nutrition, Metabolism and Cardiovascular Diseases - Category: Nutrition Source Type: research
Taking statins before or after cancer diagnosis cuts all - cause and cancer - related deaths
Source: The Doctors Lounge - Oncology - Category: Cancer & Oncology Tags: Cardiology, Family Medicine, Gastroenterology, Internal Medicine, Oncology, Pharmacy, Journal, Source Type: news
Authors: Momtazi-Borojeni AA, Nik ME, Jaafari MR, Banach M, Sahebkar A Abstract Introduction: Inhibition of proprotein convertase subtilisin/kexin 9 (PCSK9) is an effective therapeutic tool for lowering low-density lipoprotein cholesterol (LDL-C). There is no available evidence on the efficacy and safety of PCSK9 inhibitors in non-cardiovascular diseases, particularly cancer. The present study aimed to evaluate the effect of PCSK9 inhibition on cancer endpoints in mice bearing colon carcinoma, using a nanoliposomal antiPCSK9 vaccine. Material and methods: The prepared nanoliposomal antiPCSK9 vaccine was subcuta...
Source: Archives of Medical Science - Category: General Medicine Tags: Arch Med Sci Source Type: research
Publication date: Available online 16 May 2019Source: Nanomedicine: Nanotechnology, Biology and MedicineAuthor(s): Mitra Korani, Solmaz Ghaffari, Hossein Attar, Mohammad Mashreghi, Mahmoud Reza JaafariAbstractThree Bortezomib (BTZ) liposomal formulations including of HSPC/Cholesterol/DSPE-mPEG2000 (F1), HSPC/DSPG/Cholesterol (F2), and HSPC/DSPG/Cholesterol/DSPE-mPEG2000 (F3) were prepared and characterized. Results demonstrated that the size of formulations ranged 72–92 nm. The DSPE-mPEG2000 containing formulations (F1 and F3) had higher BTZ encapsulation compared to F2 formulation. The size of the liposomal for...
Source: Nanomedicine: Nanotechnology, Biology and Medicine - Category: Nanotechnology Source Type: research
This article describes HAPPI's collaborative efforts to enhance local capacity by training personnel from community health centers (CHCs) and community-based organizations (CBOs), implementing a small grants program, and forming a community advisory council. HAPPI demonstrates that existing resources in the region can be successfully linked and leveraged to increase awareness and receipt of CPS. Five CHCs expanded quality improvement efforts and eight CBOs reached 2,730 older African Americans and Latinos through locally tailored educational programs that encouraged community-clinic linkages. A community council assumed le...
Source: The Gerontologist - Category: Geriatrics Authors: Tags: Gerontologist Source Type: research
In this study, we utilized drift tube IMS (DTIMS) coupled with MS to characterize 56 different unlabeled BA standards and 16 deuterated versions. In the DTIMS-MS analyses of 12 isomer groups, BAs with smaller m/z values were easily separated in either their deprotonated or sodiated forms (or both). However, as the BAs grew in m/z value, they became more difficult to separate with two isomer groups being inseparable. Metal ions such as copper and zinc were then added to the overlapping BAs, and due to different binding sites, the resulting complexes were separable. Thus, the rapid structural measurements possible with DTIMS...
Source: Analytical and Bioanalytical Chemistry - Category: Chemistry Authors: Tags: Anal Bioanal Chem Source Type: research
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