EFFECT OF DIALLYL TRISULFIDE ON HEDGEHOG SIGNALING IN PANCREATIC CANCER CELLS

With an increasing global cancer burden, new methods of cancer prevention are desired to improve overall survival. In particular, pancreatic cancer (PC) is in desperate need of new strategies to improve the dismal 8% overall 5-year survival rate. Studies have shown aberrant activation of the Hedgehog pathway to be associated with very poor prognosis in multiple cancer types, including pancreatic. Prevention strategies utilizing dietary agents have been shown to regulate multiple cancer hallmark pathways, but little is known regarding their effect on Hedgehog. Here we observed diallyl trisulfide (DATS), an anti-cancer agent found in garlic, reduced colony formation and inhibited Hedgehog signaling in PC cells. Treatment of AsPC-1 PC cells with DATS resulted in inhibition of mRNA and protein expression of the transcription factor Gli1. Protein levels of the Sonic Hedgehog pathway initiating ligand as well as the Patched receptor were increased following DATS treatment. Additionally, DATS reduced ectopic expression of Gli1. These results give further support for the anti-cancer role of DATS and provide rationale for future investigation into its use as a chemopreventive agent in PC

Redox Modulation at Work: Natural Phytoprotective Polysulfanes From Alliums Based on Redox-Active Sulfur

Purpose of review: This article provides a brief overview of natural phytoprotective products of allium with a special focus on the therapeutic potential of diallyl polysulfanes from garlic, their molecular targets and their fate in the living organisms. A comprehensive overview of antimicrobial and anticancer properties of published literature is presented for the reader to understand the effective concentrations of polysulfanes and their sensitivity towards different human pathogenic microbes, fungi, and cancer cell lines. Recent findings: The article finds polysulfanes potentials as new generation novel antibiotics and chemo preventive agent. The effective dose rates of polysulfanes for antimicrobial properties are in the range of 0.5–40 mg/L and for anticancer 20–100 μM. The molecular targets for these redox modulators are mainly cellular thiols as well as inhibition and/or activation of certain cellular proteins in cancer cell lines. Summary: Antimicrobial and anticancer activities of polysulfanes published in the literature indicate that with further development, they could be promising candidates for cancer prevention due to their selectivity towards abnormal cells

Dietary Bioactive Diallyl Trisulfide in Cancer Prevention and Treatment

Bioactive dietary agents have been shown to regulate multiple cancer hallmark pathways. Epidemiologic studies have linked consumption of Allium vegetables, such as garlic and onions, to decreased incidence of cancer. Diallyl trisulfide (DATS), a bioactive compound derived from Allium vegetables, has been investigated as an anti-cancer and chemopreventive agent. Preclinical studies provide ample evidence that DATS regulates multiple cancer hallmark pathways including cell cycle, apoptosis, angiogenesis, invasion, and metastasis. DATS has been shown to arrest cancer cells at multiple stages of the cell cycle with the G2/M arrest being the most widely reported. Additionally, increased pro-apoptotic capacity as a result of regulating intrinsic and extrinsic apoptotic pathway components has been widely reported following DATS treatment. Invasion, migration, and angiogenesis represent emerging targets of DATS and support its anti-cancer properties. This review summarizes DATS mechanisms of action as an anti-cancer and chemopreventive agent. These studies provide rationale for future investigation into its use as a cancer chemopreventive agent

Dietary Bioactive Diallyl Trisulfide in Cancer Prevention and Treatment

Bioactive dietary agents have been shown to regulate multiple cancer hallmark pathways. Epidemiologic studies have linked consumption of Allium vegetables, such as garlic and onions, to decreased incidence of cancer. Diallyl trisulfide (DATS), a bioactive compound derived from Allium vegetables, has been investigated as an anti-cancer and chemopreventive agent. Preclinical studies provide ample evidence that DATS regulates multiple cancer hallmark pathways including cell cycle, apoptosis, angiogenesis, invasion, and metastasis. DATS has been shown to arrest cancer cells at multiple stages of the cell cycle with the G2/M arrest being the most widely reported. Additionally, increased pro-apoptotic capacity as a result of regulating intrinsic and extrinsic apoptotic pathway components has been widely reported following DATS treatment. Invasion, migration, and angiogenesis represent emerging targets of DATS and support its anti-cancer properties. This review summarizes DATS mechanisms of action as an anti-cancer and chemopreventive agent. These studies provide rationale for future investigation into its use as a cancer chemopreventive agent

Therapist adherence in brief strategic family therapy for adolescent drug abusers

Therapist adherence has been shown to predict clinical outcomes in family therapy. In prior studies, adherence has been represented broadly by core principles and a consistent family (vs. individual) focus. To date, these studies have not captured the range of clinical skills that are represented in complex family-based approaches or examined how variations in these skills predict different clinically relevant outcomes over the course of treatment. In this study, the authors examined the reliability and validity of an observational adherence measure and the relationship between adherence and outcome in a sample of drug-using adolescents who received brief strategic family therapy within a multisite effectiveness study. Participants were 480 adolescents (age 12-17) and their family members, who were randomized to the Brief Strategic Family Therapist treatment condition (J. Szapocznik, U. Hervis, & S. Schwartz, 2003) or treatment as usual. The adolescents were mostly male (377 vs. 103 female) and Hispanic (213), whereas 148 were White, and 110 were Black. Therapists were also randomly assigned to treatment condition within agencies. Results supported the proposed factor structure of the adherence measure, providing evidence that it is possible to capture and discriminate between distinct dimensions of family therapy. Analyses demonstrated that the mean levels of the factors varied over time in theoretically and clinically relevant ways and that therapist adherence was associated with engagement and retention in treatment, improvements in family functioning, and reductions in adolescent drug use. Clinical implications and future research directions are discussed, including the relevance of these findings on training therapists and studies focusing on mechanisms of action in family therapy

Equivalence of family functioning and externalizing behaviors in adolescent substance users of different race/ethnicity

The Brief Strategic Family Therapy for Adolescent Drug Abuse clinical trial of 480 adolescents boys and girls aged 12 to 17 years and their parents was designed to maximize the chance that a sufficient number of Hispanic and Black adolescents would be included to allow valid subgroup comparisons. Examination of measurement invariance is an important step to ensure valid analysis. Two construct areas important to the analysis of trial results, adolescent problem behaviors, and family functioning showed a high degree of measurement invariance, which allowed valid comparisons of mean baseline differences across groups. Results showed that Black families had significantly higher initial levels of family functioning and lower levels of adolescent externalizing behaviors than either Hispanic or White non-Hispanic families. This pattern is consistent with an increased likelihood of referral of Black adolescents with more severe problems to restricted setting rather than to outpatient drug abuse treatment. This possibility highlights the importance of considering differing baseline characteristics of subgroups prior to assessing differential treatment effectiveness to prevent confounding

Retailer Marketing Communications in the Digital Age::Getting the Right Message to the Right Shopper at the Right Time

The evolving retail landscape in the digital age has resulted in opportunities and novel capabilities for retailers. This paper identifies four key challenges facing retailers based on insights from practitioners and academics using the customer journey framework as a guide. It then considers evidence from both practice and theory on how contemporary retailers might best innovate in the face of these challenges, to get “the right message to the right shopper at the right time.” Historically, retail was largely constrained to focus on individual touchpoints as manufacturers drove the majority of communication decisions. More recently, with the ability of e-commerce to capture the shopper decision journey more comprehensively, retailers are better able to understand what the right message would be as well as where, when, and how to deliver it to reach the most responsive shoppers to achieve the retailer’s strategic objectives in each phase of the journey. It is within this context that this paper considers the following key challenges: 1) When is the right time to communicate with a given shopper?, 2) What is the right way to communicate with a given shopper?, 3) What is the right way to leverage in-store collateral?, and 4) How do we cultivate the right long-term relationship with a shopper