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Michael Devos, Barbara Gilbert, Geertrui Denecker, Kirsten Leurs, Conor Mc Guire, Kelly Lemeire, Tino Hochepied, Marnik Vuylsteke, Jo Lambert, Caroline Van Den Broecke, Louis Libbrecht, Jody Haigh, Geert Berx, Saskia Lippens, Peter Vandenabeele, Wim Declercq
Unlike its family member p53, the p63 gene is rarely mutated in human cancer. However, ΔNp63α protein levels are often elevated in tumors of epithelial origin, such as squamous cell carcinoma and cholangiocarcinoma. In order to study the oncogenic properties of ΔNp63α in vivo, we generated transgenic mice overexpressing ΔNp63α from the Rosa26 locus promoter controlled by K5Cre. We found that these mice spontaneously develop epidermal cysts and ectopic ΔNp63α expression in the bile duct epithelium that leads to dilatation of the intrahepatic biliary ducts, to hepatic cyst formation and bile duct adenoma...
October 7, 2016: Journal of Investigative Dermatology
Evie H Carchman, Kristina A Matkowskyj, Louise Meske, Paul F Lambert
INTRODUCTION: Autophagy is an intracellular catabolic process that removes and recycles unnecessary/dysfunctional cellular components, contributing to cellular health and survival. Autophagy is a highly regulated cellular process that responds to several intracellular signals, many of which are deregulated by human papillomavirus (HPV) infection through the expression of HPV-encoded oncoproteins. This adaptive inhibitory response helps prevent viral clearance. A strong correlation remains between HPV infection and the development of squamous cell carcinoma (SCC) of the anus, particularly in HIV positive and other immunosuppressed patients...
2016: PloS One
S Balakrishnan, F A Bhat, P Raja Singh, S Mukherjee, P Elumalai, S Das, C R Patra, J Arunakaran
OBJECTIVES: Epidermal growth factor plays a critical role in breast malignancies by enhancing cell proliferation, invasion, angiogenesis and metastasis. Epithelial-mesenchymal transition (EMT) is a crucial process by which epithelial cells lose polarity and acquire migratory mesenchymal properties. Gold nanoparticles are an efficient drug delivery vehicle for carrying chemotherapeutic agents to target cancer cells and quercetin is an anti-oxidative flavonoid known with potent anti-malignant cell activity...
September 18, 2016: Cell Proliferation
Mahmoud T Abo-Elfadl, Amira M Gamal-Eldeen, Mostafa M Elshafey, Gamil M Abdalla, Shawkey S Ali, Moustafa R K Ali, Mahmoud F M Zawrah
BACKGROUND: The photothermal properties of gold nanoparticles (GNPs) are promising therapeutic modality for cancer. The study objective is to evaluate the therapeutic effect of the prepared PEGylated gold nano-semicubes (PEG-GNSCs) in skin cancer. The synthesized PEG-GNSCs were intermediate between cubic and rod shapes (low aspect ratio- rods). METHODS: In vitro toxicity was investigated in human skin melanoma Sk-Mel-28 cells, and skin squamous cell carcinoma was induced in CD1 mice by dimethylbenzanthracene (DMBA) and 12-O-tetradecanoyl-phorbol-13-acetate (TPA)...
September 13, 2016: Journal of Photochemistry and Photobiology. B, Biology
Leena Hilakivi-Clarke, Anni Wärri, Kerrie B Bouker, Xiyuan Zhang, Katherine L Cook, Lu Jin, Alan Zwart, Nguyen Nguyen, Rong Hu, M Idalia Cruz, Sonia de Assis, Xiao Wang, Jason Xuan, Yue Wang, Bryan Wehrenberg, Robert Clarke
BACKGROUND: Responses to endocrine therapies vary among patients with estrogen receptor (ER+) breast cancer. We studied whether in utero exposure to endocrine-disrupting compounds might explain these variations. METHODS: We describe a novel ER+ breast cancer model to study de novo and acquired tamoxifen (TAM) resistance. Pregnant Sprague Dawley rats were exposed to 0 or 0.1 ppm ethinyl estradiol (EE2), and the response of 9,12-dimethylbenz[a]anthracene (DMBA)-induced mammary tumors to 15 mg/kg TAM, with (n = 17 tumors in the controls and n = 20 tumors in EE2 offspring) or without 1...
January 2017: Journal of the National Cancer Institute
Luiz Gustavo A Chuffa, Luiz Antonio Lupi Júnior, Fábio R F Seiva, Marcelo Martinez, Raquel F Domeniconi, Patricia Fernanda F Pinheiro, Lucilene D Dos Santos, Francisco Eduardo Martinez
To obtain more information into the molecular mechanisms underlying ovarian cancer (OC), we proposed a comparative proteomic analysis in animals receiving long-term melatonin as therapy or only vehicle using multidimensional protein identification combined with mass spectrometry. To induce tumor, a single dose of 100 μg 7,12-dimethylbenz(a)anthracene (DMBA) dissolved in 10 μL of sesame oil was injected under the left ovarian bursa of 20 Fischer 344 rats. The right ovaries were injected with sesame oil only...
October 7, 2016: Journal of Proteome Research
Zhengxue Liu, Tanima Kundu-Roy, Isao Matsuura, Guannan Wang, Yong Lin, You-Rong Lou, Nicola J Barnard, Xiao-Fan Wang, Mou-Tuan Huang, Nanjoo Suh, Fang Liu
Previous studies based on cell culture and xenograft animal models suggest that Smad3 has tumor suppressor function for breast cancer during early stages of tumorigenesis. In this report, we show that DMBA (7,12-dimethylbenz[a]anthracene), a chemical carcinogen, induces mammary tumor formation at a significantly higher frequency in the Smad3 heterozygous mice than in the Smad3 wild type mice. This is the first genetic evidence showing that Smad3 inhibits mammary tumor formation in a mouse model. Our findings support the notion that Smad3 has important tumor suppressor function for breast cancer...
August 30, 2016: Oncotarget
Martín C Abba, Yi Zhong, Jaeho Lee, Hyunsuk Kil, Yue Lu, Yoko Takata, Melissa S Simper, Sally Gaddis, Jianjun Shen, C Marcelo Aldaz
Controversy always existed on the utility of chemically induced mouse mammary carcinogenesis models as valid equivalents for the study of human breast cancer. Here, we performed whole exome and RNA sequencing on long latency mammary tumors (218 ± 27 days) induced by the carcinogen 7,12-Dimethylbenzathracene (DMBA) and short latency tumors (65 ± 11 days) induced by the progestin Medroxyprogesterone Acetate (MPA) plus DMBA in CD2F1 mice. Long latency tumors displayed a high frequency of Pi3kca and/or Pten mutations detected in 11 of 13 (85%) long latency cases (14/22, 64% overall)...
August 31, 2016: Oncotarget
Camelia Oprean, Florin Borcan, Ioana Pavel, Alis Dema, Corina Danciu, Codruta Soica, Cristina Dehelean, Andreea Nicu, Anamaria Ardelean, Mirabela Cristea, Alexandra Ivan, Calin Tatu, Florina Bojin
BACKGROUND/AIM: Oleanolic and ursolic acids (OA and UA) are two pentacyclic triterpenes, ubiquitously spread in plants, previously known for their chemopreventive capacity on different types of cancer. The major pharmacological disadvantage of these phytocompounds is their poor water solubility, which often limits their applicability. MATERIALS AND METHODS: Using the interfacial polycondensation combined with spontaneous emulsification technique, polyurethane nanostructures (PU) were synthetized in order to improve this problem...
September 2016: In Vivo
Muthusamy Rajasekar, Kathiresan Suresh, Kathiresan Sivakumar
Diosmin is naturally found flavanoid in many citrus fruits known to have anti-inflammatory, antihyperglycemic, antioxidant and antimutagenic properties. Effects of Diosmin on IL-6/STAT-3 expression in hamster buccal pouch carcinogenesis remain unclear. Alterations in many genes encode crucial proteins, which regulate cell proliferation, differentiation and apoptosis have been implicated in oral cancer. In the present study, we investigated the effect of dietary Diosmin on IL-6/STAT-3 signaling in the 7,12-dimethylbenz[a]anthracene (DMBA)-induced hamster buccal pouch (HBP) carcinogenesis by examining the protein expression of IL-6/STAT-3 and its related genes...
August 18, 2016: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Indu Pal Kaur, Tranum Kaur, Rishi Bhardwaj, Parneet Kaur Deol, Vandita Kakkar, Kim Vaiphei, S N Sanyal
BACKGROUND: Chemoprevention using natural agents has emerged as a new and promising strategy for reducing cancer burden. Sesamol, a water soluble lignin, is a potent antioxidant with potential anticancer activities. Its small size (molecular weight: 138.34g) coupled with easy permeability (log P: 1.29) results in its excessive systemic loss therefore, compromising local bioavailability. Furthermore, irritant nature of sesamol limits its application on skin per se. OBJECTIVE: Present study aims to evaluate chemopreventive efficacy of free and encapsulated (SLNs) sesamol, at gross and molecular level, in DMBA induced skin cancer animal model...
August 19, 2016: Anti-cancer Agents in Medicinal Chemistry
Snehal S Patel, Surender Nakka
BACKGROUND: Studies have shown the renin angiotensin system via angiogenesis is involved in tumor development. OBJECTIVE: Therefore, the objective of present study was to examine the effect of perindopril on tumor growth and angiogenesis in animal model of breast cancer. METHODS: In the present study, we investigated the effect of perindopril on tumor development of mammary gland cancer induced by 7,12-dimethylbenz[a]anthracene, mouse tumor xenograft and corneal micropocket model...
August 17, 2016: Anti-cancer Agents in Medicinal Chemistry
Juan Luis Callejas-Valera, Ramiro Iglesias-Bartolome, Panomwat Amornphimoltham, Julia Palacios-Garcia, Daniel Martin, Joseph A Califano, Alfredo A Molinolo, J Silvio Gutkind
The rising incidence of human papillomavirus (HPV)-associated malignancies, especially for oropharyngeal cancers, has highlighted the urgent need to understand how the interplay between high-risk HPV oncogenes and carcinogenic exposure results in squamous cell carcinoma (SCC) development. Here, we describe an inducible mouse model expressing high risk HPV-16 E6/E7 oncoproteins in adults, bypassing the impact of these viral genes during development. HPV-16 E6/E7 genes were targeted to the basal squamous epithelia in transgenic mice using a doxycycline inducible cytokeratin 5 promoter (cK5-rtTA) system...
October 2016: Carcinogenesis
Somdutta Sinha Roy, Shyamali Mukherjee, Billy R Ballard, Salil K Das
Consumption of α-lactalbumin as dietary protein offers a beneficial effect on breast cancer development. Breast cancer was developed by gavage administration of single dose of dimethylbenz(a)anthracene (DMBA) in female rats, maintained on AIN-76A diet with either 20% casein or α-lactalbumin (a component of whey protein). All tumors were detected by palpation. After approximately 130 days of DMBA administration, the animals were euthanized. There was a delay in the development of breast tumor in the α-lactalbumin group in comparison to the casein group...
2016: International Journal of Cancer and Oncology
Khaled Waleed Zaid, Bander Mossa Nhar, Salman Mohammed Ghadeer Alanazi, Rashad Murad, Ahmad Domani, Awadh Jamman Alhafi
Recombinant human bone morphogenetic protein2 (rhBMP2 ), a member of the TGF? family, has been used widely in recent years to regenerate defects of the maxillary and mandible bones. Such defects are sometimes caused by resection of oral squamous cell carcinoma (OSCC) yet the biologic effects of rhBMP2 on these carcinomas are not fully clear. The objective of this study was to determine histologically whether rhBMP2 produces adverse effects on angiogenesis during induction of OSCC, a biologic process critical for tumor formation in an experimental model in the buccal pouch of golden Syrian hamsters...
2016: Asian Pacific Journal of Cancer Prevention: APJCP
Yingai Jane Jin, Sally Wang, Joshua Cho, M Angelica Selim, Tim Wright, George Mosialos, Jennifer Y Zhang
The deubiquitinase-encoding gene Cyld displays a dominant genetic linkage to a wide spectrum of skin-appendage tumors, which could be collectively designated as CYLD mutant-syndrome (CYLD(m)-syndrome). Despite recent advances, little is understood about the molecular mechanisms responsible for this painful and difficult-to-treat skin disease. Here, we generated a conditional mouse model with epidermis-targeted expression of a catalytically deficient CYLD(m) through K14-Cre-mediated deletion of exon 9 (hereafter refer to Cyld(EΔ9/Δ9) )...
July 21, 2016: JCI Insight
Hanumappa Ananda, Kothanahally S Sharath Kumar, Mahesh Hegde, Kanchugarakoppal S Rangappa
Isoxazole derivatives are an important group of chemotherapeutic prototypes. In the current study, we have synthesized few isoxazole derivatives and tested them for their antiproliferative properties in cancer cell lines such as MCF7 and HeLa. The lead compound, 3-(3,4-dimethoxyphenyl)-5-(thiophen-2-yl)isoxazole (2b), showed considerable inhibition of proliferation of MCF7 and HeLa cells with the IC50 values of 19.5 and 39.2 µM, respectively. Cell cycle analyses and annexin-FITC staining in 2b-treated breast adenocarcinoma cells (MCF7) showed increased sub-G1 population and apoptosis...
September 2016: Molecular and Cellular Biochemistry
Elisa E Baracco, Federico Pietrocola, Aitziber Buqué, Norma Bloy, Laura Senovilla, Laurence Zitvogel, Erika Vacchelli, Guido Kroemer
The loss-of-function mutation of formyl peptide receptor 1 (FPR1) has a negative impact on the progression-free and overall survival of breast cancer patients treated with anthracycline-based adjuvant chemotherapy. This effect may be attributed to the fact that chemotherapy-induced antitumor immunity requires FPR1 and that such anticancer immune responses are responsible for the long-term effects of chemotherapy. Here, we investigated the possible contribution of FPR1 to the efficacy of a combination of mitoxantrone (MTX) and cyclophosphamide (CTX) for the treatment of hormone-induced breast cancer...
June 2016: Oncoimmunology
Soha M Hamdy, Ola N Sayed, Abdel Karim M Abdel Latif, Ayman M Abdel-Aziz, Alshimaa M Amin
Nutritional studies recommend the regular consumption of fruits and vegetables to favor a healthy quality of life. This study was carried out to evaluate the efficacy of hesperidin and tiger nut against the carcinogenic activity of DMBA in female rats. 72 adult Sprague Dawley female rats were divided equally into six groups: control group (I); Hesperidin treated group (II); Tiger Nut treated group (III); DMBA treated group (IV); HES-DMBA treated group (V); and TN-DMBA treated group (VI). There was a significant increase in serum levels of carcinoembryonic antigen, total sialic acid, progesterone, estradiol, ALT, AST, LDH, urea and creatinine, and significant decrease in reduced glutathione level, superoxide dismutase, catalase and glutathione peroxidase activities of DMBA treated group compared to control...
July 28, 2016: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Abhishek Kumar, S Jha, Shakti P Pattanayak
Cancer is a faction of disorders that conjugated primarily with oxidative imbalance. In mammary carcinoma, oxidative stress secondarily changes various gene expressions and signalling pathways that bring genomic instability and mutagenic alterations that fascinating carcinogenesis. Several coumarin compounds are active against various malignancies. Among them, daphnetin (DAP) exhibits valuable safety and bioactivity profile that contributes towards its efficacy against cancer. In this study, the antioxidative and chemotherapeutic potential of DAP against 7,12-dimethylbenz(a)anthracene (DMBA)- induced mammary carcinogenesis was evaluated in female Sprague-Dawley rats...
August 2016: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
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