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      Delivering curcumin and gemcitabine in one nanoparticle platform for colon cancer therapy

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          Abstract

          As gemcitabine and curcumin have different targets in colon cancer cells, combination of them may bring benefits.

          Abstract

          As gemcitabine and curcumin have different targets in colon cancer cells, combination of them may bring benefits. Here, curcumin and gemcitabine were formulated into a biodegradable polymer platform for combination therapy for treatment of colon cancer. In doing so, a FDA approved biodegradable polymer mPEG-PLA (methoxyl-polyethylen glycol- block-polylactide) was chosen as a drug carrier. At first, a mPEG-PLA/Gem conjugate was designed. Thereafter, simply using this drug conjugate to encapsulate curcumin, polymeric micelles loaded with both curcumin and gemcitabine were obtained. Varying the feed ratio of the two drugs, a series of micelles with different ratios of curcumin and gemcitabine could be prepared. The as-prepared dual drug loaded nanoparticles showed spherical structures with mean diameters ranging from 118 nm to 149 nm by DLS. In vitro, M(Cur/Gem) almost showed greater synergy than free combination of curcumin/gemcitabine. In vivo, better antitumor effect and lower systemic toxicity of M(Cur/Gem) were observed on a murine xenograft model. The present study provides the possibility of combining curcumin and gemcitabine in a nanoparticle formulation, and translation of this combination may bring benefits for future clinical use.

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          Most cited references 28

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          Drug combination studies and their synergy quantification using the Chou-Talalay method.

          This brief perspective article focuses on the most common errors and pitfalls, as well as the do's and don'ts in drug combination studies, in terms of experimental design, data acquisition, data interpretation, and computerized simulation. The Chou-Talalay method for drug combination is based on the median-effect equation, derived from the mass-action law principle, which is the unified theory that provides the common link between single entity and multiple entities, and first order and higher order dynamics. This general equation encompasses the Michaelis-Menten, Hill, Henderson-Hasselbalch, and Scatchard equations in biochemistry and biophysics. The resulting combination index (CI) theorem of Chou-Talalay offers quantitative definition for additive effect (CI = 1), synergism (CI 1) in drug combinations. This theory also provides algorithms for automated computer simulation for synergism and/or antagonism at any effect and dose level, as shown in the CI plot and isobologram, respectively.
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            Colorectal cancer statistics, 2014.

            Colorectal cancer is the third most common cancer and the third leading cause of cancer death in men and women in the United States. This article provides an overview of colorectal cancer statistics, including the most current data on incidence, survival, and mortality rates and trends. Incidence data were provided by the National Cancer Institute's Surveillance, Epidemiology, and End Results program and the North American Association of Central Cancer Registries. Mortality data were provided by the National Center for Health Statistics. In 2014, an estimated 71,830 men and 65,000 women will be diagnosed with colorectal cancer and 26,270 men and 24,040 women will die of the disease. Greater than one-third of all deaths (29% in men and 43% in women) will occur in individuals aged 80 years and older. There is substantial variation in tumor location by age. For example, 26% of colorectal cancers in women aged younger than 50 years occur in the proximal colon, compared with 56% of cases in women aged 80 years and older. Incidence and death rates are highest in blacks and lowest in Asians/Pacific Islanders; among males during 2006 through 2010, death rates in blacks (29.4 per 100,000 population) were more than double those in Asians/Pacific Islanders (13.1) and 50% higher than those in non-Hispanic whites (19.2). Overall, incidence rates decreased by approximately 3% per year during the past decade (2001-2010). Notably, the largest drops occurred in adults aged 65 and older. For instance, rates for tumors located in the distal colon decreased by more than 5% per year. In contrast, rates increased during this time period among adults younger than 50 years. Colorectal cancer death rates declined by approximately 2% per year during the 1990s and by approximately 3% per year during the past decade. Progress in reducing colorectal cancer death rates can be accelerated by improving access to and use of screening and standard treatment in all populations. © 2014 American Cancer Society, Inc.
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              Colorectal cancer epidemiology: incidence, mortality, survival, and risk factors.

              In this article, the incidence, mortality, and survival rates for colorectal cancer are reviewed, with attention paid to regional variations and changes over time. A concise overview of known risk factors associated with colorectal cancer is provided, including familial and hereditary factors, as well as environmental lifestyle-related risk factors such as physical inactivity, obesity, smoking, and alcohol consumption.
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                Author and article information

                Journal
                RSCACL
                RSC Adv.
                RSC Adv.
                Royal Society of Chemistry (RSC)
                2046-2069
                2014
                2014
                : 4
                : 106
                : 61948-61959
                Affiliations
                [1 ]Medical and Health Center
                [2 ]Beijing Friendship Hospital
                [3 ]Capital University of Medical Sciences
                [4 ]Beijing, China
                10.1039/C4RA10431E
                © 2014
                Product
                Self URI (article page): http://xlink.rsc.org/?DOI=C4RA10431E

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