Modulation of DMBA- induced biochemical and histopathological changes by Syzygium cumini seed extract during skin carcinogenesis

Aim & Method: The current study was designed to elucidate the protective effect of Syzygium cumini seed extract (SCE) on skin carcinogenesis induced by a single topical application of 7,12-dimethylbenz(a)anthracene (100 μg/100 μl of acetone) and 2 weeks later promoted by repeated application of croton oil (1% in acetone/three times a week) till the end of the experiment (16 weeks). Result: Oral administration of SCE at a dose of 125 mg/kg b.wt./day for 15 days at the peri-initiational stage (i.e., 7 days before & 7 days after DMBA application) and for 14 weeks at the promotional stage (i.e., from the time of croton oil application), revealed a significant reduction in lipid peroxidation (p<0.05-0.001) along with an elevation in the activities of enzymatic antioxidants (superoxide dismutase, p<0.05-0.001 & catalase, p<0.05-0.001), non-enzymatic antioxidant (reduced glutathione, p<0.05-0.01 & vitamin-C, p<0.01-0.001) and total proteins levels (p<0.01-0.001) when compared to the carcinogen treated control animals. Histopathological study revealed that dyskeratosis of the epidermis, deposition of keratinous pearl and epidermal hyperplasia in skin tumors of DMBA treated control and the same were found to be of lesser degree in both the SCE treated experimental animals. Conclusions: These results demonstrate that SCE ameliorate the DMBA/croton oil induced adverse biochemical and histopathological alterations during skin carcinogenesis in mice

The synthesis and some properties of nylon 4,T

The synthesis of nylon 4,T from tetramethylenediamine and a terephthalic acid derivative was studied in a two step-process: prepolymerization, followed by postcondensation in the solid state (4 h, 290°C). The prepolymers were prepared by the nylon salt method, ester polymerization method, interfacial method, and a low temperature solution method. A maximum ηinh of 1.52 was obtained. From a solution in trifluoroacetic acid, films were cast and on these films we studied its IR spectrum, WAXS, and melting behavior with DSC. A boiled up sample had a double melting transition at 434 and 475°C and a ΔH0 of 130 J/g

Enhanced skin carcinogenesis and lack of thymus hyperplasia in transgenic mice expressing human cyclin D1b (CCND1b)

Cyclin D1b is an alternative transcript of the cyclin D1 gene (CCND1) expressed in human tumors. Its abundance is regulated by a single base pair polymorphism at the exon 4/intron 4 boundary (nucleotide 870). Epidemiological studies have shown a correlation between the presence of the G870A allele (that favors the splicing for cyclin D1b) with increased risk and less favorable outcome in several forms of cancer. More recently, it has been shown that, unlike cyclin D1a, the alternative transcript D1b by itself has the capacity to transform fibroblasts in vitro. In order to study the oncogenic potential of cyclin D1b, we developed transgenic mice expressing human cyclin D1b under the control of the bovine K5 promoter (K5D1b mice). Seven founders were obtained and none of them presented any significant phenotype or developed spontaneous tumors. Interestingly, K5D1b mice do not develop the fatal thymic hyperplasia, which is characteristic of the cyclin D1a transgenic mice (K5D1a). Susceptibility to skin carcinogenesis was tested in K5D1b mice using two-stage carcinogenesis protocols. In two independent experiments, K5D1b mice developed higher papilloma multiplicity as compared with wild-type littermates. However, when K5D1b mice were crossed with cyclin D1KO mice, the expression of cyclin D1b was unable to rescue the carcinogenesis-resistant phenotype of the cyclin D1 KO mice. To further explore the role of cyclin D1b in mouse models of carcinogenesis we carried out in silico analysis and in vitro experiments to evaluate the existence of a mouse homologous of the human cyclin D1b transcript. We were unable to find any evidence of an alternatively spliced transcript in mouse Ccnd1. These results show that human cyclin D1b has different biological functions than cyclin D1a and confirm its oncogenic properties.Fil: Rojas, Paola Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina. University of Texas; Estados UnidosFil: Benavides, Fernando. University of Texas; Estados UnidosFil: Blando, Jorge. University of Texas; Estados UnidosFil: Pérez, Carlos. University of Texas; Estados UnidosFil: Cardenas, Kim. University of Texas; Estados UnidosFil: Richie, Ellen. University of Texas; Estados UnidosFil: Knudsen, Erik S.. Thomas Jefferson University; Estados UnidosFil: Johnson, David G.. University of Texas; Estados UnidosFil: Senderowicz, Adrian M.. Department of Health and Human Services. Food and Drug Administration. Center for Drug Evaluation and Research; Estados UnidosFil: Rodriguez Puebla, Marcelo L.. University of North Carolina; Estados UnidosFil: Conti, Claudio. University of Texas; Estados Unido

Multicolour lineage tracing reveals clonal dynamics of squamous carcinoma evolution from initiation to metastasis.

Tumour cells are subjected to evolutionary selection pressures during progression from initiation to metastasis. We analysed the clonal evolution of squamous skin carcinomas induced by DMBA/TPA treatment using the K5CreER-Confetti mouse and stage-specific lineage tracing. We show that benign tumours are polyclonal, but only one population contains the Hras driver mutation. Thus, benign papillomas are monoclonal in origin but recruit neighbouring epithelial cells during growth. Papillomas that never progress to malignancy retain several distinct clones, whereas progression to carcinoma is associated with a clonal sweep. Newly generated clones within carcinomas demonstrate intratumoural invasion and clonal intermixing, often giving rise to metastases containing two or more distinct clones derived from the matched primary tumour. These data demonstrate that late-stage tumour progression and dissemination are governed by evolutionary selection pressures that operate at a multicellular level and, therefore, differ from the clonal events that drive initiation and the benign-malignant transition

Black Cumin Seed Oil Increase Leucocyte and CD4Thelper Number in Sprague-dawley Rats Induced with Dimethylbenzanthracene

Cigarette smoke contains 7, 12 dimethylbenzanthracene (DMBA). Metabolic of DMBA is immunosuppressive. Black cumin seed oil (BCSO) is an immunomodulation. The aim of this study was to determine the effect of BCSO on leukocyte, CD4Th and CD4CD25Treg in Sprague-Dawley (SD) mice induced with DMBA. The 96 SD rats were divided into 8 groups of 12. Group I received aquabidest and standard feeding. Groups II, III and IV received BCSO (an equivalent of 6.8, 68 and 136 mg/kg BW / day thymoquinone, respectively). Group V received thymoquinone (50 mg / kg BW / day) and group VI received tamoxifen (60 mg / kg BW). Group VII (DMBA) was induced with DMBA (10x20mg / kg BW for 5 weeks). Group VIII received standard feeding and corn oil treatment. In the third week, all groups began to be induced with DMBA (20 mg/kg BW twice per week for five weeks). Data collection of leukocytes, CD4Th and CD4CD25Treg was performed at week 27th. The mean difference of CD4Th and CD4CD25Treg counts between groups was calculated with one way ANOVA. Results: The administration of BCSO, thymoquinone, and tamoxifen had increased leukocytes and CD4 Th cell count. The CD4Th cell count of the treatment groups was higher than that of the DMBA group (p &lt;0.05). BCSO equivalent doses of 6.8 and 68 mg/kg BW / day thymoquinone showed immunoprotective effects. Conclusion: It can be concluded that the BCSO administration at doses of 6.8 and 68 mg/kg BW / day shows immunoprotective effects due to DMBA induction

Reduction in squamous cell carcinomas in mouse skin by dietary zinc supplementation.

Inadequate dietary Zn consumption increases susceptibility to esophageal and other cancers in humans and model organisms. Since Zn supplementation can prevent cancers in rodent squamous cell carcinoma (SCC) models, we were interested in determining if it could have a preventive effect in a rodent skin cancer model, as a preclinical basis for considering a role for Zn in prevention of human nonmelanoma skin cancers, the most frequent cancers in humans. We used the 7,12-dimethyl benzanthracene carcinogen/phorbol myristate acetate tumor promoter treatment method to induce skin tumors in Zn-sufficient wild-type and Fhit (human or mouse protein) knockout mice. Fhit protein expression is lost in \u3e50% of human cancers, including skin SCCs, and Fhit-deficient mice show increased sensitivity to carcinogen induction of tumors. We hypothesized that: (1) the skin cancer burdens would be reduced by Zn supplementation; (2) Fhit(-/-) (Fhit, murine fragile histidine triad gene) mice would show increased susceptibility to skin tumor induction versus wild-type mice. 30 weeks after initiating treatment, the tumor burden was increased ~2-fold in Fhit(-/-) versus wild-type mice (16.2 versus 7.6 tumors, P \u3c 0.001); Zn supplementation significantly reduced tumor burdens in Fhit(-/-) mice (males and females combined, 16.2 unsupplemented versus 10.3 supplemented, P = 0.001). Most importantly, the SCC burden was reduced after Zn supplementation in both strains and genders of mice, most significantly in the wild-type males (P = 0.035). Although the mechanism(s) of action of Zn supplementation in skin tumor prevention is not known in detail, the Zn-supplemented tumors showed evidence of reduced DNA damage and some cohorts showed reduced inflammation scores. The results suggest that mild Zn supplementation should be tested for prevention of skin cancer in high-risk human cohorts

The administration of multipotent stromal cells at precancerous stage precludes tumor growth and epithelial dedifferentiation of oral squamous cell carcinoma

Multipotent stromal cells (MSCs) are envisioned as a powerful therapeutic tool. As they home into tumors, secrete trophic and vasculogenic factors, and suppress immune response their role in carcinogenesis is a matter of controversy. Worldwide oral squamous cell carcinoma (OSCC) is the fifth most common epithelial cancer. Our aim was to determine whether MSC administration at precancerous stage modifies the natural progression of OSCC. OSCC was induced in Syrian hamsters by topical application of DMBA in the buccal pouch. At papilloma stage, the vehicle or 3 × 106 allogenic bone marrow-derived MSCs were locally administered. Four weeks later, the lesions were studied according to: volume, stratification (histology), proliferation (Ki-67), apoptosis (Caspase 3 cleaved), vasculature (ASMA), inflammation (Leukocyte infiltrate), differentiation (CK1 and CK4) and gene expression profile (mRNA). Tumors found in individuals that received MSCs were smaller than those presented in the vehicle group (87 ± 80 versus 54 ± 62 mm3, p < 0.05). The rate of proliferation was two times lower and the apoptosis was 2.5 times higher in lesions treated with MSCs than in untreated ones. While the laters presented dedifferentiated cells, the former maintained differentiated cells (cytokeratin and gene expression profile similar to normal tissue). Thus, MSC administration at papilloma stage precludes tumor growth and epithelial dedifferentiation of OSCC.Fil: Bruna, Flavia Alejandra. Universidad del Desarrollo; Chile. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; ArgentinaFil: Arango Rodríguez, Martha. Universidad del Desarrollo; ChileFil: Plaza, Anita. Universidad del Desarrollo; ChileFil: Espinoza, Iris. Universidad del Desarrollo; ChileFil: Conget, Paulette. Universidad del Desarrollo; Chil

Aspects of a supersymmetric Brans-Dicke theory

We consider a locally supersymmetric theory where the Planck mass is replaced by a dynamical superfield. This model can be thought of as the Minimal Supersymmetric extension of the Brans-Dicke theory (MSBD). The motivation that underlies this analysis is the research of possible connections between Dark Energy models based on Brans-Dicke-like theories and supersymmetric Dark Matter scenarios. We find that the phenomenology associated with the MSBD model is very different compared to the one of the original Brans-Dicke theory: the gravitational sector does not couple to the matter sector in a universal metric way. This feature could make the minimal supersymmetric extension of the BD idea phenomenologically inconsistent.Comment: 6 pages, one section is adde

Macromolecular organic acids in the Murchison meteorite

This study has detected bound organic acids within the Murchison meteorite organic macromolecule. Benzoic acid was the most abundant compound; other abundant compounds include C1 and C2 benzoic acids. Their origin and significance will be discussed