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Takumu Hasebe, Jun Matsukawa, Daina Ringus, Jun Miyoshi, John Hart, Atsushi Kaneko, Masahiro Yamamoto, Toru Kono, Mikihiro Fujiya, Yutaka Kohgo, Chong-Zi Wang, Chun-Su Yuan, Marc Bissonnette, Mark W Musch, Eugene B Chang
Chemopreventative properties of traditional medicines and underlying mechanisms of action are incompletely investigated. This study demonstrates that dietary daikenchuto (TU-100), comprised of ginger, ginseng, and Japanese pepper effectively suppresses intestinal tumor development and progression in the azoxymethane (AOM) and APC(min/+) mouse models. For the AOM model, TU-100 was provided after the first of six biweekly AOM injections. Mice were sacrificed at 30 weeks. APC(min/+) mice were fed diet without or with TU-100 starting at 6 weeks, and sacrificed at 24 weeks...
October 12, 2016: Phytotherapy Research: PTR
Fatemeh Nabavizadeh, Hafseh Fanaei, Alireza Imani, Jalal Vahedian, Fahimeh Asadi Amoli, Jamal Ghorbi, Hamid Sohanaki, Seyed Mehdi Mohammadi, Ravieh Golchoobian
Capecitabine, an effective anticancer drug in colorectal cancer chemotherapy, may create adverse side effects on healthy tissues. In the present study, we first induced colon adenocarcinoma with azoxymethane, a carcinogen agent, and then investigated the potentiality of polyamidoamine (PAMAM) dendrimer to improve capecitabine therapeutic index and decrease its adverse side effects on healthy tissues like liver and bone marrow. Other variables such as nanoparticle concentrations have also been investigated. Drug loading concentration (DLC) and encapsulation efficiency (EE) were calculated for capecitabine/dendrimer complex...
August 2016: Acta Medica Iranica
Sun-A Im, Ji-Wan Kim, Hee-Suk Kim, Chan-Su Park, Eunju Shin, Seon-Gil Do, Young In Park, Chong-Kil Lee
The preventive effect of a processed Aloe vera gel (PAG) on colon carcinogenesis was examined using an azoxymethane (AOM)-initiated and dextran sodium sulfate (DSS)-promoted mouse colon carcinogenesis model. Oral administration of PAG (200, or 400mg/kg/day) significantly reduced the multiplicity of colonic adenomas and adenocarcinomas compared with the AOM/DSS only-treated mice. In the mice treated with 400mg/kg of PAG, adenoma and adenocarcinoma development was reduced to 80% and 60%, respectively, compared to 100% in the PAG-untreated AOM/DSS-treated mice...
September 30, 2016: International Immunopharmacology
Agustina Tri Endharti, Adisti Wulandari, Anik Listyana, Eviana Norahmawati, Sofy Permana
BACKGROUND: Indonesian mistletoe grows on various trees. Mango Mistletoes (Dendrophthoe pentandra) is one type of mistletoe that grown on mango tree (.benalu mangga in bahasa Indonesia). Our study used mistletoe as a parasitic plant that has been used for traditional medicine. It has been known that Dendrophtoe pentandra extract (DPE) anti-inflammatory and anticancer. Furthermore, it is necessary to follow-up study in vivo to evaluate the response to treatment of new cancer therapeutic agents...
September 26, 2016: BMC Complementary and Alternative Medicine
Luca Di Martino, Maneesh Dave, Paola Menghini, Wei Xin, Kristen Arseneau, Theresa Pizarro, Fabio Cominelli
Inflammatory bowel disease causes chronic, relapsing intestinal inflammation that can lead to the development of colorectal cancer. Members of the TNF superfamily are key regulators of intestinal inflammation. In particular, TNF-like weak inducer of apoptosis (TWEAK) and its receptor, Fn14, are involved in normal and pathologic intestinal tissue remodeling. In this study, we show that the TWEAK/Fn14 signaling complex plays a protective role during the acute stage of intestinal inflammation and contributes to the prevention of colitis-associated cancer during chronic inflammation through its pro-apoptotic effects...
September 9, 2016: Cancer Research
Richard K Le Leu, Benjamin L Scherer, Mark T Mano, Jean M Winter, Tamsin Lannagan, Richard J Head, Trevor Lockett, Julie M Clarke
O(6)-methyl guanine (O(6)MeG) adducts are major toxic, promutagenic, and procarcinogenic adducts involved in colorectal carcinogenesis. Resistant starch and its colonic metabolite butyrate are known to protect against oncogenesis in the colon. In this study, we hypothesized that a dietary intervention that specifically delivers butyrate to the large bowel (notably butyrylated high-amylose maize starch [HAMSB]) would reduce colonic levels of O(6)MeG in rats shortly after exposure to the deoxyribonucleic acid (DNA) alkylating agent azoxymethane (AOM) when compared with a low-amylose maize starch (LAMS)...
September 2016: Nutrition Research
Mónica García-Barros, Nicolas Coant, Toshihiko Kawamori, Masayuki Wada, Ashley J Snider, Jean-Philip Truman, Bill X Wu, Hideki Furuya, Christopher J Clarke, Agnieszka B Bialkowska, Amr Ghaleb, Vincent W Yang, Lina M Obeid, Yusuf A Hannun
Alterations in sphingolipid metabolism, especially ceramide and sphingosine 1-phosphate, have been linked to colon cancer, suggesting that enzymes of sphingolipid metabolism may emerge as novel regulators and targets in colon cancer. Neutral ceramidase (nCDase), a key enzyme in sphingolipid metabolism that hydrolyzes ceramide into sphingosine, is highly expressed in the intestine; however, its role in colon cancer has not been defined. Here we show that molecular and pharmacological inhibition of nCDase in colon cancer cells increases ceramide, and this is accompanied by decreased cell survival and increased apoptosis and autophagy, with minimal effects on noncancerous cells...
September 8, 2016: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
Kandy T Velazquez, Reilly T Enos, Meredith S Carson, Taryn L Cranford, Jackie Bader, Ioulia Chatzistamou, Udai Singh, Prakash S Nagarkatti, Mitzi Nagarkatti, J Mark Davis, James A Carson, E Angela Murphy
Obesity presents a significant public health concern given its association with increased cancer incidence, unfavorable prognosis, and metastasis. However, there is very little literature on the effects of weight-loss, following obesity, on risk for colon cancer or liver cancer. Therefore, we sought to study whether intentional weight loss through diet manipulation was capable of mitigating colon and liver cancer in mice. We fed mice with a high-fat diet (HFD) comprised of 47% carbohydrates, 40% fat, and 13% protein for 20 weeks to mimic human obesity...
September 8, 2016: American Journal of Physiology. Gastrointestinal and Liver Physiology
Nancy Lévesque, Karen E Christensen, Lauren Van Der Kraak, Ana F Best, Liyuan Deng, Don Caldwell, Amanda J MacFarlane, Nicole Beauchemin, Rima Rozen
The common R653Q variant (∼20% homozygosity in Caucasians) in the synthetase domain of the folate-metabolizing enzyme MTHFD1 reduces purine synthesis. Although this variant does not appear to affect risk for colorectal cancer, we questioned whether it would affect growth of colorectal tumors. We induced tumor formation in a mouse model for MTHFD1-synthetase deficiency (Mthfd1S(+/-) ) using combined administration of azoxymethane (AOM) and dextran sodium sulfate (DSS) in male and female wild-type and Mthfd1S(+/-) mice...
September 6, 2016: Molecular Carcinogenesis
Aline Van Acker, Els Louagie, Jessica Filtjens, Sylvie Taveirne, Els Van Ammel, Tessa Kerre, Dirk Elewaut, Tom Taghon, Bart Vandekerckhove, Jean Plum, Georges Leclercq
Ly49E is a member of the Ly49 family of NK receptors and is distinct from other members of this family on the basis of its structural properties, expression pattern and ligand recognition. Importantly, Ly49E receptor expression is high on small intestinal and colonic intraepithelial lymphocytes (IELs). Intestinal IELs are regulators of the mucosal immune system and contribute to front-line defense at the mucosal barrier, including anti-tumor immune response. Whereas most Ly49 receptors have MHC class-I ligands, we showed that Ly49E is instead triggered by urokinase plasminogen activator (uPA)...
September 1, 2016: Cancer Immunology, Immunotherapy: CII
Young-Min Han, Migyeung Jeong, Jong-Min Park, Mi-Young Kim, Eun-Jin Go, Ji Young Cha, Kyung Jo Kim, Ki Baik Hahm
Numerous studies have demonstrated that diets containing an increased ratio of ω-6 : ω-3 polyunsaturated fatty acids (PUFAs) are a risk factor for colon cancer and might affect tumorigenesis. Therefore, dietary ω-3 PUFA administration may be a preventive strategy against colon cancer. Until now, the exact molecular mechanisms and required dietary doses of ω-3 PUFAs for cancer prevention were unknown. In this study, we explored the anti-tumorigenic mechanisms of ω-3 PUFAs against a colitis-associated cancer (CAC) model...
August 23, 2016: Oncotarget
Xiaowei Huo, Dongyu Liu, Li Gao, Liyong Li, Li Cao
Inflammatory bowel disease (IBD) is generally considered as a major risk factor in the progression of colitis-associated carcinogenesis (CAC). Thus, it is well accepted that ameliorating inflammation creates a potential to achieve an inhibitory effect on CAC. Licorice flavonoids (LFs) possess strong anti-inflammatory activity, making it possible to investigate its pharmacologic role in suppressing CAC. The purpose of the present study was to evaluate the anti-tumor potential of LFs, and further explore the underlying mechanisms...
2016: International Journal of Molecular Sciences
Mari Masuda, Yuko Uno, Naomi Ohbayashi, Hirokazu Ohata, Ayako Mimata, Mutsuko Kukimoto-Niino, Hideki Moriyama, Shigeki Kashimoto, Tomoko Inoue, Naoko Goto, Koji Okamoto, Mikako Shirouzu, Masaaki Sawa, Tesshi Yamada
Canonical Wnt/β-catenin signalling is essential for maintaining intestinal stem cells, and its constitutive activation has been implicated in colorectal carcinogenesis. We and others have previously identified Traf2- and Nck-interacting kinase (TNIK) as an essential regulatory component of the T-cell factor-4 and β-catenin transcriptional complex. Consistent with this, Tnik-deficient mice are resistant to azoxymethane-induced colon tumorigenesis, and Tnik(-/-)/Apc(min/+) mutant mice develop significantly fewer intestinal tumours...
August 26, 2016: Nature Communications
Matthew McMillin, Stephanie Grant, Gabriel Frampton, Sarah Andry, Adam Brown, Sharon DeMorrow
BACKGROUND: Acute liver failure is associated with numerous systemic consequences including neurological dysfunction, termed hepatic encephalopathy, which contributes to mortality and is a challenge to manage in the clinic. During hepatic encephalopathy, microglia activation and neuroinflammation occur due to dysregulated cell signaling and an increase of toxic metabolites in the brain. Fractalkine is a chemokine that is expressed primarily in neurons and through signaling with its receptor CX3CR1 on microglia, leads to microglia remaining in a quiescent state...
2016: Journal of Neuroinflammation
Gang Chen, Yang Yang, Chunping Hu, Xiaolan Cheng, Yuehua Xu, Xueting Cai, Min Wang, Chung S Yang, Peng Cao
Individuals with ulcerative colitis (UC) are at a high risk for developing colorectal cancer (CRC). Huangqin Decoction (HQD), a traditional Chinese medicinal formula chronicled in the Shang Han Lun, is commonly used to treat gastrointestinal symptoms. However, experimental evidence for supporting the clinical practice is lacking. This study used modern biomedical approaches to investigate the protective/preventive effects of HQD in dextran sulfate sodium (DSS)-induced acute/chronic UC and azoxymethane (AOM)/DSS-induced CRC in mice...
August 19, 2016: Oncotarget
Weston A Welge, Jennifer K Barton
BACKGROUND AND OBJECTIVE: Colorectal cancer (CRC) remains the second deadliest cancer in the United States. Several screening methods exist; however, detection of small polyps remains a challenge. Optical coherence tomography (OCT) has been demonstrated to be capable of detecting lesions as small as 1 mm in the mouse colon, but detection is based on measuring a doubling of the mucosa thickness. The colon microvasculature may be an attractive biomarker of early tumor development because tumor vessels are characterized by irregular structure and dysfunction...
August 22, 2016: Lasers in Surgery and Medicine
Maria Vittoria Sepporta, Raffaela Fuccelli, Patrizia Rosignoli, Giovanni Ricci, Maurizio Servili, Roberto Fabiani
Previous studies have shown that the precursor of olive oil secoiridoids, Oleuropein (OL) has several in vitro chemopreventive properties. OL inhibits proliferation and induces apoptosis in breast, thyroid, prostate, and colorectal cancer (CRC) cells. Much less is known about the effects of OL on animal models of carcinogenesis. In this study, we investigated the ability of OL to prevent the azoxymethane (AOM)-induced colon cancer upset and DNA damage in mice. Animals, fed with a basal diet either enriched or not with OL (125 mg/kg), were injected with AOM (10 mg/kg, once a week for 6 weeks) and sacrificed after either 7 weeks for histological analysis of colon crypt dysplasia and evaluation of DNA damage in leukocytes or 17 weeks for counting the macroscopically observable colon tumors...
August 19, 2016: Journal of Medicinal Food
Tzu-Tang Wei, Yi-Ting Lin, Ruo-Yu Tseng, Chia-Tung Shun, Yu-Chin Lin, Ming-Shiang Wu, Jim-Min Fang, Ching-Chow Chen
PURPOSE: Colorectal cancer is a worldwide cancer with rising annual incidence. Inflammation is a well-known cause of colorectal cancer carcinogenesis. Metabolic inflammation (metaflammation) and altered gut microbiota (dysbiosis) have contributed to colorectal cancer. Chemoprevention is an important strategy to reduce cancer-related mortality. Recently, various polypharmacologic molecules that dually inhibit histone deacetylases (HDAC) and other therapeutic targets have been developed...
August 15, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Latifah Saiful Yazan, Muhamad Firdaus Shyfiq Muhamad Zali, Razana Mohd Ali, Nurul Amira Zainal, Nurulaidah Esa, Sarah Sapuan, Yong Sze Ong, Yin Sim Tor, Banulata Gopalsamy, Fui Ling Voon, Sharifah Sakinah Syed Alwi
Ethnopharmacological Relevance. Colon cancer has been a major problem worldwide. Kelulut honey (KH) is produced by the stingless bees from Trigona species and has strong antioxidant activities that could be one of the potential chemopreventive agents from natural resources. Aim of This Study. This study investigated the chemopreventive properties and toxicity of KH in Sprague Dawley rats induced with azoxymethane (AOM). Material and Method. Twenty-four male Sprague Dawley rats aged 5 weeks were divided into 4 groups: (G1) untreated group not induced with AOM, (G2) untreated group induced with AOM, (G3) treated group induced with AOM, and (G4) treated group not induced with AOM...
2016: BioMed Research International
Sareeya Reungpatthanaphong, Chaiyavat Chaiyasut, Sasithorn Sirilun, Prasit Suwannalert
Colorectal cancer (CRC) is a major cause of morbidity and mortality throughout the world, with chronic inflammation and diet as major causes in its development. Chemopreventive effects of natural dietary products have been the focus of studies for prevention over the past decade. This study was conducted to determine the effects of unpolished Thai rice during precancerous stage through the involvement of ?catenin, cyclooxygenase2 (COX2) expression and inflammatory cytokines focusing on azoxymethane (AOM)induced aberrant crypt foci (ACF)related to CRC...
2016: Asian Pacific Journal of Cancer Prevention: APJCP
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