The Development of an Advanced Model for Multilayer Human Skin Reconstruction In Vivo.

Human skin reconstruction on immune-deficient mice has become indispensable for in vivo studies performed in basic research and translational laboratories. Further advancements in making sustainable, prolonged skin equivalents to study new therapeutic interventions rely on reproducible models utilizing patient-derived cells and natural three-dimensional culture conditions mimicking the structure of living skin. Here, we present a novel step-by-step protocol for grafting human skin cells onto immunocompromised mice that requires low starting cell numbers, which is essential when primary patient cells are limited for modeling skin conditions.

Loss of TP63 Promotes the Metastasis of Head and Neck Squamous Cell Carcinoma by Activating MAPK and STAT3 Signaling.

TP63 is frequently amplified or overexpressed in primary head and neck squamous cell carcinomas (HNSCC). Nevertheless, the role of TP63 in the initiation and progression of HNSCCs is not known. Using archival HNSCC tissue sections, we found that TP63 expression is often downregulated in late-stage human HNSCCs.

Grape seed extract efficacy against azoxymethane-induced colon tumorigenesis in A/J mice: interlinking miRNA with cytokine signaling and inflammation.

Colorectal cancer (CRC) is the second leading cause of cancer-associated deaths, suggesting that additional strategies are needed to prevent/control this malignancy. As CRC growth and progression involve a large window (10-15 years), chemopreventive intervention could be a practical/translational strategy. Azoxymethane (AOM)-induced colon tumorigenesis in mice resembles human CRC in terms of progression of ACF to polyps, adenoma, and carcinomas and associated molecular mechanisms.

Inhibitory effect of silibinin against azoxymethane-induced colon tumorigenesis in A/J mice.

Purpose: Colorectal cancer is the second leading cause of cancer-associated deaths, which suggests that more effort is needed to prevent/control this disease. Herein, for the first time, we investigate in vivo the efficacy of silibinin against azoxymethane-induced colon tumorigenesis in A/J mice.

Experimental Design: Five-week-old male mice were gavaged with vehicle or silibinin (250 and 750 mg/kg) for 25 weeks starting 2 weeks before initiation with azoxymethane (pretreatment regime) or for 16 weeks starting 2 weeks after the last azoxymethane injection (posttreatment regime).

Silibinin exerts sustained growth suppressive effect against human colon carcinoma SW480 xenograft by targeting multiple signaling molecules.

Purpose: Earlier, we reported the strong preventive efficacy of silibinin against colorectal cancer (CRC), but its usefulness against established CRC or effect of its withdrawal on CRC growth remained unknown. Present study focused on these important issues by employing two different treatment protocols in advanced human CRC SW480 xenograft in nude mice.

Methods: In the first treatment protocol, silibinin was fed for 28 days (200 mg/kg body weight, 5 days/week) to mice with growing SW480 xenograft; thereafter, tumor growth was monitored for additional 3 weeks without silibinin treatment.

Dietary-feeding of grape seed extract prevents azoxymethane-induced colonic aberrant crypt foci formation in fischer 344 rats.

Chemoprevention by dietary agents/supplements has emerged as a novel approach to control various malignancies, including colorectal cancer (CRC). This study assessed dietary grape seed extract (GSE) effectiveness in preventing azoxymethane (AOM)-induced aberrant crypt foci (ACF) formation and associated mechanisms in Fischer 344 rats. Six-week-old rats were injected with AOM, and fed control diet or the one supplemented with 0.

Silibinin suppresses growth of human colorectal carcinoma SW480 cells in culture and xenograft through down-regulation of beta-catenin-dependent signaling.

Mutations in APC/beta-catenin resulting in an aberrant activation of Wnt/beta-catenin pathway are common in colorectal cancer (CRC), suggesting that targeting the beta-catenin pathway with chemopreventive/anticancer agents could be a potential translational approach to control CRC. Using human CRC cell lines harboring mutant (SW480) versus wildtype (HCT116) APC gene and alteration in beta-catenin pathway, herein we performed both in vitro and in vivo studies to examine for the first time whether silibinin targets beta-catenin pathway in its efficacy against CRC. Silibinin treatment inhibited cell growth, induced cell death, and decreased nuclear and cytoplasmic levels of beta-catenin in SW480 but not in HCT116 cells, suggesting its selective effect on the beta-catenin pathway and associated biologic responses.

Chemoprevention of intestinal tumorigenesis in APCmin/+ mice by silibinin.

Chemoprevention is a practical and translational approach to reduce the risk of various cancers including colorectal cancer (CRC), which is a major cause of cancer-related deaths in the United States. Accordingly, here we assessed chemopreventive efficacy and associated mechanisms of long-term silibinin feeding on spontaneous intestinal tumorigenesis in the APC(min/+) mice model. Six-week-old APC(min/+) mice were p.

Dietary feeding of grape seed extract prevents intestinal tumorigenesis in APCmin/+ mice.

Chemopreventive effects and associated mechanisms of grape seed extract (GSE) against intestinal/colon cancer development are largely unknown. Herein, we investigated GSE efficacy against intestinal tumorigenesis in APC(min/+) mice. Female APC(min/+) mice were fed control or 0.

Silibinin suppresses spontaneous tumorigenesis in APC min/+ mouse model by modulating beta-catenin pathway.

Purpose: Here we assessed whether silibinin, a nontoxic chemopreventive agent, inhibits spontaneous intestinal tumorigenesis in APC ( min/+) mouse model, a genetically predisposed animal model of human familial adenomatous polyposis (FAP).

Materials And Methods: Six-week-old APC (min/+) mice were divided into four groups and orally gavaged with 0.2 ml vehicle, or 250, 500 and 750 mg silibinin/kg body weight in 0.

Silibinin suppresses growth and induces apoptotic death of human colorectal carcinoma LoVo cells in culture and tumor xenograft.

Colorectal cancer is one of the leading causes of cancer-related morbidity and mortality. The use of nontoxic phytochemicals in the prevention and intervention of colorectal cancer has been suggested as an alternative to chemotherapy. Here we assessed the anticancer efficacy of silibinin against advanced colorectal cancer LoVo cells both in vitro and in vivo.

Gallic acid, an active constituent of grape seed extract, exhibits anti-proliferative, pro-apoptotic and anti-tumorigenic effects against prostate carcinoma xenograft growth in nude mice.

Purpose: Gallic acid, a natural agent present in a wide-range of fruits and vegetables, has been of potential interest as an anti-cancer agent; herein, we evaluated its efficacy in androgen-independent DU145 and androgen-dependent-22Rv1 human prostate cancer (PCa) cells.

Materials And Methods: Cell viability was determined by MTT and apoptosis by Annexin V-PI assays. In vivo anti-cancer efficacy was assessed by DU145 and 22Rv1 xenograft growth in nude mice given normal drinking water or one supplemented with 0.

Inhibition of azoxymethane-induced colonic aberrant crypt foci formation by silibinin in male Fisher 344 rats.

Chemoprevention is a practical approach to control colorectal cancer, which is one of the major causes of cancer mortality in the United States. Based on our recent silibinin efficacy studies in human colorectal cancer cells, we investigated the effects of its dietary feeding on azoxymethane (AOM)-induced aberrant crypt foci (ACF) formation and associated biomarkers in male Fisher 344 rats. Five-week-old male Fisher 344 rats were fed control or silibinin-supplemented (0.

Protective effect of tomato against N-methyl-N'-nitro-N-nitrosoguanidine-induced in vivo clastogenicity and oxidative stress.

Objective: Chemoprevention by dietary constituents has emerged as a cost-effective approach to control the incidence of gastric cancer, the second most common malignancy worldwide, and a major cause of mortality in Chennai, India. Identification of dietary agents with chemopreventive potential requires prescreening in animal models. We evaluated the modifying effects of tomato paste against N-methyl-N'-nitro-N-nitrosoguanidine (MNNG)-induced genetic damage and oxidative stress in male Swiss mice.

Protective effect of S-allylcysteine and lycopene in combination against N-methyl-N'-nitro-N-nitrosoguanidine-induced genotoxicity.

Chemoprotection by diet-derived antioxidants has emerged as a cost-effective approach in preventing genotoxicity and carcinogenicity. In this study, we investigated the protective effects of S-allylcysteine (SAC) and lycopene against N-methyl-N'-nitro-N-nitrosoguanidine (MNNG)-induced genotoxicity. Quantification of bone marrow micronuclei and chromosomal aberrations in male Wistar rats was used to monitor the protective effects of SAC and lycopene.

Effect of S-allylcysteine on oxidant-antioxidant status during N-methyl-N'-nitro-N-nitrosoguanidine and saturated sodium chloride-induced gastric carcinogenesis in Wistar rats.

We investigated the chemopreventive effect of S-allylcysteine (SAC), a water-soluble garlic constituent against gastric carcinogenesis induced in male Wistar rats by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) and saturated sodium chloride (S-NaCl). The animals were divided into four groups of six animals. Rats in groups 1 and 2 were administered MNNG (200 mg/kg body weight) on days 0 and 14 as well as S-NaCl (1 mL/rat) three days during weeks 0 to 3, and thereafter placed on basal diet until the end of the experiment.