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DMBA carcinogenesis

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
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
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
I Thurlings, L M Martínez-López, B Westendorp, M Zijp, R Kuiper, P Tooten, L N Kent, G Leone, H J Vos, B Burgering, A de Bruin
E2F transcription factors are important regulators of the cell cycle, and unrestrained activation of E2F-dependent transcription is considered to be an important driver of tumor formation and progression. Although highly expressed in normal skin and skin cancer, the role of the atypical E2Fs, E2F7 and E2F8, in keratinocyte homeostasis, regeneration and tumorigenesis is unknown. Surprisingly, keratinocyte-specific deletion of E2F7 and E2F8 in mice did not interfere with skin development and wound healing. However, the rate for successful isolation and establishment of E2f7/8-deficient primary keratinocyte cultures was much higher than for wild-type keratinocytes...
July 25, 2016: Oncogene
Liu Peiqi, Guo Zhaozhong, Yin Yaotian, Jia Jun, Guo Jihua, Jia Rong
OBJECTIVE: Oral squamous cell carcinoma (OSCC) is the most common malignancy of head and neck with high mortality rates. The mechanisms of initiation and development of OSCC remain largely unknown. Dysregulated alternative splicing of pre-mRNA has been associated with OSCC. Splicing factor SRSF3 is a proto-oncogene and overexpressed in multiple cancers. The aim of this study was to uncover the relationship between SRSF3 and carcinogenesis and progression of oral squamous cell carcinoma...
2016: International Journal of Medical Sciences
Y-Q Hu, J Wang, J-H Wu
OBJECTIVE: Resveratrol (RES), present in fruits and plants, is a natural compound that has been shown various medicinal properties, including protection of cardiovascular disease and cancer risk. However, the effects of RES on skin cancer have not been investigated. The present work was designed to explore the anticancer potential of RES against chemical-induced skin carcinogenesis in rats. MATERIALS AND METHODS: Skin carcinogenesis were induced in male Wistar rats by a single topical application of 7,12-dimethylbenz(a)anthracene (DMBA) and 2 weeks later, 12-O-tetradecanoylphorbol-13-acetate (TPA) were topically applied thrice a week to promote skin carcinogenesis...
July 2016: European Review for Medical and Pharmacological Sciences
Cristina A Dehelean, Codruta Soica, Iulia Pinzaru, Dorina Coricovac, Corina Danciu, Ioana Pavel, Florin Borcan, Demetrios A Spandidos, Aristidis M Tsatsakis, Flavia Baderca
The increased susceptibility of men as compared to women to develop different types of cancer, including skin cancer, is well known; however, the mechanisms involved in this process are still a matter of debate. This study aimed to obtain animal models of photo-chemically-induced skin carcinogenesis by exposure to ultraviolet radiation B (UVB) coupled with topical applications of a tumor initiator (7,12-dimethylbenz(a)anthracene, DMBA) and a tumor promoter (12-O-tetradecanoylphorbol-13-acetate, TPA) in order to characterize the gender disparities regarding the skin lesions developed by the female and male SKH-1 hairless mice included in this study...
September 2016: Food and Chemical Toxicology
Jasmine Sati, Biraja Prasad Mohanty, Mohan Lal Garg, Ashwani Koul
Silibinin, a major bioactive flavonolignan in Silybum marianum, has received considerable attention in view of its anticarcinogenic activity. The present study examines its anticancer potential against 7, 12-dimethylbenz(a)anthracene (DMBA) and 12-O-tetradecanoylphorbol-13-acetate (TPA) induced skin cancer. Male LACA mice were randomly segregated into 4 groups: Control, DMBA/TPA, Silibinin and Silibinin+DMBA/TPA. Tumors in DMBA/TPA and Silibinin+DMBA/TPA groups were histologically graded as squamous cell carcinoma...
2016: PloS One
Markus Winter, Dmitri Lodygin, Berlinda Verdoodt, Heiko Hermeking
The p53-inducible cell cycle regulator 14-3-3σ exhibits tumor suppressive functions and is highly expressed in differentiating layers of the epidermis and hair follicles. 14-3-3σ/SFN/stratifin is frequently silenced in human epithelial cancers, and experimental down-regulation of 14-3-3σ expression immortalizes primary human keratinocytes. In the repeated-epilation (ER) mouse model, a heterozygous nonsense mutation of 14-3-3σ causes repeated hair-loss, hyper-proliferative epidermis, and spontaneous development of papillomas and squamous cell carcinomas in aging mice...
July 7, 2016: Oncotarget
Abdul Basit Baba, Jaganathan Kowshik, Jayaraman Krishnaraj, Josephraj Sophia, Madhulika Dixit, Siddavaram Nagini
Aberrant activation of oncogenic signaling pathways plays a pivotal role in tumor initiation and progression. The purpose of the present study was to investigate the chemopreventive and therapeutic efficacy of blueberry in the hamster buccal pouch (HBP) carcinogenesis model based on its ability to target TGF-β, PI3K/Akt, MAPK and NF-κB signaling and its impact on invasion and angiogenesis. Squamous cell carcinomas were induced in the HBP by 7,12-dimethylbenz[a]anthracene (DMBA). The effect of blueberry on the oncogenic signaling pathways and downstream events was analyzed by quantitative real-time PCR and immunoblotting...
September 2016: Journal of Nutritional Biochemistry
Wen-Chen Wang, Ching-Yi Chen, Hseng-Kuang Hsu, Li-Min Lin, Yuk-Kwan Chen
OBJECTIVE: Toona sinensis leaf extract (TSL) has been shown to have anti-tumor effects on cancer cell lines. This study aimed to investigate the chemopreventive potential and the underlying mechanism of TSL during 7,12-dimethylbenz[a]anthracene (DMBA)-induced hamster buccal pouch (HBP) carcinogenesis. METHODS: One hundred hamsters were divided into control (n=30), carcinogenic (n=20), preventive (n=42), and therapeutic (n=8) groups. The animals in carcinogenic and preventive groups were administered reverse osmosis water (carcinogenic group) or TSL (1g/kg bw) (preventive group) by gavage daily for 4 weeks, and their bilateral pouches were painted with a 0...
June 15, 2016: Archives of Oral Biology
Ângela Valéria Farias Alves, Danielle Rodrigues Ribeiro, Sonia Oliveira Lima, Francisco Prado Reis, Andréa Ferreira Soares, Margarete Zanardo Gomes, Ricardo Luiz Cavalcanti de Albuquerque
OBJECTIVE: to evaluate the influence of Ki-67 and P16INK4a proteins immunohistochemical expressions on the clinical and morphological parameters of perioral squamous cell carcinoma induced with 9,10-dimethyl-1,2-benzanthracene (DMBA) in mice. METHODS: we topically induced the lesions in the oral commissure of ten Swiss mice for 20 weeks, determining the time to tumors onset and the average tumor volume up to 26 weeks. In histopathological analysis, the variables studied were histological malignancy grade and the immunohistochemical expression of Ki-67 and P16INK4a proteins...
March 2016: Revista do Colégio Brasileiro de Cirurgiões
Luiza N Guido, Camile C Fontelles, Mariana P Rosim, Vanessa C Pires, Silvia M F Cozzolino, Inar A Castro, Francisco Bolaños-Jiménez, Luis F Barbisan, Thomas P Ong
Breast cancer is a global public health problem and accumulating evidence indicates early-life exposures as relevant factors in the disease risk determination. Recent studies have shown that paternal nutrition can influence offspring health including breast cancer risk. Selenium is a micronutrient with essential role in central aspects of embryogenesis, male fertility and cancer and that has been extensively studied as a chemopreventive agent in several breast cancer experimental models. Thus, we designed an animal study to evaluate whether paternal selenium deficiency or supplementation during preconception could affect the female offspring mammary gland development and breast cancer susceptibility...
October 15, 2016: International Journal of Cancer. Journal International du Cancer
Siddavaram Nagini, Jaganathan Kowshik
The hamster buccal pouch (HBP) carcinogenesis model is one of the most well-characterized animal tumor models used as a prelude to investigate multistage oral carcinogenesis and to assess the efficacy of chemointervention. Hamster buccal pouch carcinomas induced by 7,12-dimethylbenz[a]anthracene (DMBA) show extensive similarities to human oral squamous cell carcinomas. The HBP model offers a number of advantages including a simple and predictable tumor induction procedure, easy accessibility for examination and follow-up of lesions, and reproducibility...
2016: Methods in Molecular Biology
Oukseub Lee, Mi-Ran Choi, Konstantin Christov, David Ivancic, Seema A Khan
PURPOSE: Blockade of the progestogen-progesterone receptor (PR) axis is a novel but untested strategy for breast cancer prevention. We report preclinical data evaluating telapristone acetate (TPA), ulipristal acetate (UPA), and mifepristone. METHODS: Tumors were induced with medroxyprogesterone acetate (MPA) plus 7,12-dimethylbenz[a]anthracene (DMBA) in mice, and MPA or progesterone plus N-methyl-N-nitrosourea (MNU) in rats. Mammary gland histology, tumor incidence, latency, multiplicity, burden and histology were evaluated, along with immunohistochemical labeling of pHH3 (proliferation), CD34 (angiogenesis), and estrogen and progesterone receptors (ER and PR)...
July 1, 2016: Cancer Letters
Deepalakshmi Krishnamoorthy, Mirunalini Sankaran
BACKGROUND: Worldwide, breast cancer is the second most prevalent cancer among women and its incidence is increasing alarmingly. AIM: To determine a dose-response effect of Pleurotus ostreatus on oxidant/antioxidant status in 7,12-dimethylbenz. (a) antheracene induced. (DMBA) mammary carcinoma in experimental rats. MATERIALS AND METHODS: Cancer bearing female Sprague Dawley rats were orally treated with Pleurotus ostreatus ethanolic extract (POEet) (150, 300 and 600 mg/kg body weight) for 16 weeks...
January 2016: Journal of Cancer Research and Therapeutics
Cristina Vantaggiato, Giulia Dell'Omo, Balaji Ramachandran, Isabella Manni, Enrico Radaelli, Eugenio Scanziani, Giulia Piaggio, Adriana Maggi, Paolo Ciana
Estrogen receptors (ER) are known to play an important regulatory role in mammary gland development as well as in its neoplastic transformation. Although several studies highlighted the contribution of ER signaling in the breast transformation, little is known about the dynamics of ER state of activity during carcinogenesis due to the lack of appropriate models for measuring the extent of receptor signaling in time, in the same animal. To this aim, we have developed a reporter mouse model for the non-invasive in vivo imaging of ER activity: the ERE-Luc reporter mouse...
2016: American Journal of Nuclear Medicine and Molecular Imaging
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