Variability in firearm injury among major pediatric trauma centers across the USA.

Objectives: In 2020, firearm injuries surpassed automobile collisions as the leading cause of death in US children. Annual automobile fatalities have decreased during 40 years through a multipronged approach. To develop similarly targeted public health interventions to reduce firearm fatalities, there is a critical need to first characterize firearm injuries and their outcomes at a granular level. We sought to compare firearm injuries, outcomes, and types of shooters at trauma centers in four pediatric health systems across the USA. Methods: We retrospectively extracted data from each institution's trauma registry, paper and electronic health records. Study included all patients less than 19 years of age with a firearm injury between 2003 and 2018. Variables collected included demographics, intent, resources used, and emergency department and hospital disposition. Descriptive statistics were reported using medians and IQRs for continuous data and counts with percentages for categorical data. χ2 test or Fisher's exact test was conducted for categorical comparisons. Results: Our cohort (n=1008, median age 14 years) was predominantly black and male. During the study period, there was an overall increase in firearm injuries, driven primarily by increases in the South (S) site (ß=0.11 (SE 0.02), p=<0.001) in the setting of stable rates in the West and decreasing rates in the Northeast and Mid-Atlantic sites (ß=-0.15 (SE 0.04), p=0.002; ß=-0.19 (SE0.04), p=0.001). Child age, race, insurance type, resource use, injury type, and shooter type all varied by regional site. Conclusion: The incidence of firearm-related injuries seen at four sites during 15 years varied by site and region. The overall increase in firearm injuries was predominantly driven by the S site, where injuries were more often unintentional. This highlights the need for region-specific data to allow for the development of targeted interventions to impact the burden of injury.Level of Evidence: II, retrospective study.

Multi-ancestral origin of intestinal tumors: Impact on growth, progression, and drug efficacy.

BACKGROUND: Data are steadily accruing that demonstrate that intestinal tumors are frequently derived from multiple founding cells, resulting in tumors comprised of distinct ancestral clones that might cooperate or alternatively compete, thereby potentially impacting different phases of the disease process. AIM: We sought to determine whether tumors with a multi-ancestral architecture involving at least two distinct clones show increased tumor number, growth, progression, or resistance to drug intervention. METHODS: Mice carrying the Min allele of Apc were generated that were mosaic with only a subset of cells in the intestinal epithelium expressing an activated form of PI3K, a key regulatory kinase affecting several important cellular processes. These cells were identifiable as they fluoresced green, whereas all other cells fluoresced red. RESULTS: Cell lineage tracing revealed that many intestinal tumors from our mouse model were derived from at least two founding cells, those expressing the activated PI3K (green) and those which did not (red). Heterotypic tumors with a multi-ancestral architecture as evidenced by a mixture of green and red cells exhibited increased tumor growth and invasiveness. Clonal architecture also had an impact on tumor response to low-dose aspirin. Aspirin treatment resulted in a greater reduction of heterotypic tumors derived from multiple founding cells as compared to tumors derived from a single founding cell. CONCLUSION: These data indicate that genetically distinct tumor-founding cells can contribute to early intratumoral heterogeneity. The coevolution of the founding cells and their progeny enhances colon tumor progression and impacts the response to aspirin. These findings are important to a more complete understanding of tumorigenesis with consequences for several distinct models of tumor evolution. They also have practical implications to the clinic. Mouse models with heterogenous tumors are likely better for predicting drug efficacy as compared to models in which the tumors are highly homogeneous. Moreover, understanding how interactions among different populations in a single heterotypic tumor with a multi-ancestral architecture impact response to a single agent and combination therapies are necessary to fully develop personalized medicine.

Severe Agitation in a Teenager With Spastic Cerebral Palsy: A Clinical Challenge.

Neuroleptic malignant syndrome is a challenging diagnosis because it mimics many other conditions. We present a case of a 16-year-old boy with spastic cerebral palsy who presented with severe agitation, hyperthermia, and autonomic dysfunction. He arrived to a community pediatric hospital without a caregiver to provide a detailed history, which further complicated his management.

Fisetin and 5-fluorouracil: Effective combination for PIK3CA-mutant colorectal cancer.

The normal colon epithelium is transformed into its neoplastic counterpart through a series of genetic alterations in driver genes including activating mutations in PIK3CA. Treatment often involves surgery followed by 5-fluorouracil (5-FU) based therapy, which has limited efficiency and serious side effects. We sought to determine whether fisetin, a dietary flavonoid, alone or in combination with 5-FU affected tumorigenesis in the mammalian intestine. We first determined the effect of fisetin, 5-FU or their combination on PIK3CA-mutant and PIK3CA wild-type colon cancer cells by assessing cell viability, colony formation, apoptosis and effects on PI3K/AKT/mTOR signaling. Treatment of PIK3CA-mutant cells with fisetin and 5-FU reduced the expression of PI3K, phosphorylation of AKT, mTOR, its target proteins, constituents of mTOR signaling complex and this treatment increased the phosphorylation of AMPKα. We then determined whether fisetin and 5-FU together or singly affected tumorigenesis in ApcMin/+ mice that also express constitutively active PI3K in the distal small intestine and colon. Tumor incidence was markedly lower in fisetin-treated FC1 3K1 ApcMin/+ mice that also express constitutively active PI3K in distal small intestine and colon, as compared to control animals, indicating that fisetin is a strong preventive agent. In addition, the combination of fisetin and 5-FU also reduced the total number of intestinal tumors. Fisetin could be used as a preventive agent plus an adjuvant with 5-FU for the treatment of PIK3CA-mutant colorectal cancer.

Effects of Anodal Transcranial Direct Current Stimulation Over the Ventrolateral Prefrontal Cortex on Episodic Memory Formation and Retrieval.

In the past decade, several studies have investigated the effects of transcranial direct current stimulation (tDCS) on episodic memory abilities. However, the specific conditions under which tDCS affects memory remain largely unclear. Here, we report data from 4 experiments aimed at investigating the effects of anodal tDCS over the left ventrolateral prefrontal cortex (VLPFC) on verbal episodic memory. We evaluated tDCS-induced effects as a function of time of administration, nature of the memory encoding task, and age of the participants. A robust enhancement of memory performance was only found when anodal tDCS was delivered during intentional memorization. This enhancement was evident in young and older adults. tDCS applied during incidental memorization or during retrieval did not induce any modulation of memory performance, and memory was unaffected by offline administration before encoding or retrieval. These results show that the modulation of episodic memory functions by anodal tDCS over the left VLPFC is dependent upon the time of administration and the nature of the memory task. The findings may help profile the optimal stimulation protocols for neurorehabilitation interventions on individuals with memory decline.

Tea Polyphenols in Promotion of Human Health.

Tea is the most widely used beverage worldwide. Japanese and Chinese people have been drinking tea for centuries and in Asia, it is the most consumed beverage besides water. It is a rich source of pharmacologically active molecules which have been implicated to provide diverse health benefits. The three major forms of tea are green, black and oolong tea based on the degree of fermentation. The composition of tea differs with the species, season, leaves, climate, and horticultural practices. Polyphenols are the major active compounds present in teas. The catechins are the major polyphenolic compounds in green tea, which include epigallocatechin-3-gallate (EGCG), epigallocatechin, epicatechin-3-gallate and epicatechin, gallocatechins and gallocatechin gallate. EGCG is the predominant and most studied catechin in green tea. There are numerous evidences from cell culture and animal studies that tea polyphenols have beneficial effects against several pathological diseases including cancer, diabetes and cardiovascular diseases. The polyphenolic compounds present in black tea include theaflavins and thearubigins. In this review article, we will summarize recent studies documenting the role of tea polyphenols in the prevention of cancer, diabetes, cardiovascular and neurological diseases.

Sestrin-3 modulation is essential for therapeutic efficacy of cucurbitacin B in lung cancer cells.

Many purified compounds from dietary sources have been investigated for their anticancer activities. The main issue with most agents is their effectiveness at high doses which generally could not be delivered to humans through dietary consumption. Here, we observed that cucurbitacin B, a tetracyclic triterpenoid present in pumpkins, gourds and squashes, exhibits antiproliferative effects on human non-small cell lung cancer (NSCLC) cells at nanomolar concentrations. Treatment with cucurbitacin B (0.2-0.6 µM; 24 h) was found to result in decrease in the viability of EGFR-wild type (A549 and H1792) and EGFR-mutant lung cancer cells (H1650 and H1975) and reduction in cell-colonies but had only minimal effect on normal human bronchial epithelial cells. Treatment with cucurbitacin B also caused inhibition of PI3K/mTOR and signal transducer and activator of transcription (STAT)-3 signaling along with simultaneous activation of AMPKα levels in both EGFR-wild type and EGFR-mutant lung cancer cells. Cucurbitacin B caused specific increase in the protein and mRNA expression of sestrin-3 in EGFR-mutant lung cancer cells, but not in EGFR-wild type cells. Treatment with cucurbitacin B to sestrin-3 siRNA treated EGFR-mutant cells further amplified the decrease in cell-viability and caused more sustained G2-phase cell cycle arrest, suggesting that these effects are mediated partly through sestrin-3. We also found that sestrin-3 has a role in the induction of apoptosis by cucurbitacin B in both EGFR-wild type and EGFR-mutant lung cancer cells. These findings suggest novel mechanism by the modulation of sestrin-3 for the action of cucurbitacin B and suggest that it could be developed as an agent for therapy of NSCLC.

Improving Discharge Instructions in a Pediatric Emergency Department: Impact of a Quality Initiative.

BACKGROUND: Effective communication between physician and patient is essential to optimize care after discharge from the emergency department (ED). Written discharge care instructions (DCI) complement verbal instructions and have been shown to improve communication and patient management. In 2012, Centers for Medicare and Medicaid Services proposed a quality measure (OP-19) that assesses compliance with key elements considered essential for high-quality written DCI. OBJECTIVE: To evaluate the impact of a QI intervention on improving quality of written DCI in a pediatric emergency department (PED). METHODS: A QI initiative was conducted at a tertiary PED with greater than 60,000 annual visits. Based on Centers for Medicare and Medicaid Services OP-19 measure and group consensus, 8 elements were defined a priori as requisites for good quality DCI. These elements are:Providers reviewed a random sample of DCI of patients. Proportion of DCI that had each element documented was compared between preintervention phase (PRE) and postintervention phase (POST). RESULTS: Three hundred twenty-nine DCI (PRE) and 1434 DCI (POST) were reviewed. The POST DCI showed statistically significant improvement for each of the 8 elements. The bundle measure (proportion containing all 8 elements) increased from 23% (PRE) to 79% (POST) (P < 0.001). CONCLUSIONS: The ED DCI improved in all 8 elements after a QI intervention. A detailed DCI at ED discharge enhances the patient's ability to comply with postdischarge treatment plan. Further studies are needed to evaluate the impact of improving DCI on ED return rates and other outcomes.

Exploring the molecular targets of dietary flavonoid fisetin in cancer.

The last few decades have seen a resurgence of interest among the scientific community in exploring the efficacy of natural compounds against various human cancers. Compounds of plant origin belonging to different groups such as alkaloids, flavonoids and polyphenols evaluated for their cancer preventive effects have yielded promising data, thereby offering a potential therapeutic alternative against this deadly disease. The flavonol fisetin (3,3',4',7-tetrahydroxyflavone), present in fruits and vegetables such as strawberries, apple, cucumber, persimmon, grape and onion, was shown to possess anti-microbial, anti-inflammatory, anti-oxidant and more significantly anti-carcinogenic activity when assessed in diverse cell culture and animal model systems. The purpose of this review is to update and discuss key findings obtained till date from in vitro and in vivo studies on fisetin, with special focus on its anti-cancer role. The molecular mechanism(s) described in the observed growth inhibitory effects of fisetin in different cancer cell types is also summarized. Moreover, an attempt is made to delineate the direction of future studies that could lead to the development of fisetin as a potent chemopreventive/chemotherapeutic agent against cancer.

Emergency Department Return Visits Resulting in Admission: Do They Reflect Quality of Care?

Prior studies have suggested that emergency department (ED) return visits resulting in admission may be a more robust quality indicator than all 72-hour returns. The objective was to evaluate factors that contribute to admission within 72 hours of ED discharge. Each return visit resulting in admission was independently reviewed by 3 physicians. Analysis was by descriptive statistics. Of 45 071 ED discharges, 4.1% returned within 72 hours; 0.96% returned for related reasons and were admitted to wards (91.2%), intensive care units (6.5%), or operating rooms (1.2%). Management was acceptable in 92.6%, suboptimal in 7.4%. Admissions were illness (94.9%), patient (1.6%), and physician related (3.5%). Almost all admissions within 72 hours after ED discharge are illness related, including all intensive care unit admissions and the majority of operating room admissions. Deficiencies in ED care are rarely the reason for admission on return. ED return visits resulting in admission may not be reflective of ED quality of care.

Dietary agents for prevention and treatment of lung cancer.

Lung cancer is a prominent cause of cancer-associated mortality worldwide. The main reason for high mortality due to lung cancer is attributable to the fact that the diagnosis is generally made when it has spread beyond a curable stage and cannot be treated surgically or with radiation therapy. Therefore, new approaches like dietary modifications could be extremely useful in reducing lung cancer incidences. Several fruits and vegetables offer a variety of bioactive compounds to afford protection against several diseases, including lung cancer. A number of research studies involving dietary agents provide strong evidence for their role in the prevention and treatment of lung cancer, and have identified their molecular mechanisms of action and potential targets. In this review article, we summarize data from in-vitro and in-vivo studies and where available, in clinical trials, on the effects of some of the most promising dietary agents against lung cancer.

Prodifferentiation, anti-inflammatory and antiproliferative effects of delphinidin, a dietary anthocyanidin, in a full-thickness three-dimensional reconstituted human skin model of psoriasis.

BACKGROUND: Psoriasis is a chronic inflammatory disorder of skin and joints for which conventional treatments that are effective in clearing the moderate-to-severe disease are limited due to long-term safety issues. This necessitates exploring the usefulness of botanical agents for treating psoriasis. We previously showed that delphinidin, a diet-derived anthocyanidin endowed with antioxidant and anti-inflammatory properties, induces normal epidermal keratinocyte differentiation and suggested its possible usefulness for the treatment of psoriasis [1]. OBJECTIVES: To investigate the effect of delphinidin (0-20 µM; 2-5 days) on psoriatic epidermal keratinocyte differentiation, proliferation and inflammation using a three-dimensional reconstructed human psoriatic skin equivalent (PSE) model. METHODS: PSEs and normal skin equivalents (NSEs) established on fibroblast-contracted collagen gels with respective psoriatic and normal keratinocytes and treated with/without delphinidin were analyzed for histology, expression of markers of differentiation, proliferation and inflammation using histomorphometry, immunoblotting, immunochemistry, qPCR and cultured supernatants for cytokine with a Multi-Analyte ELISArray Kit. RESULTS: Our data show that treatment of PSE with delphinidin induced (1) cornification without affecting apoptosis and (2) the mRNA and protein expression of markers of differentiation (caspase-14, filaggrin, loricrin, involucrin). It also decreased the expression of markers of proliferation (Ki67 and proliferating cell nuclear antigen) and inflammation (inducible nitric oxide synthase and antimicrobial peptides S100A7-psoriasin and S100A15-koebnerisin, which are often induced in psoriatic skin). ELISArray showed increased release of psoriasis-associated keratinocyte-derived proinflammatory cytokines in supernatants of the PSE cultures, and this increase was significantly suppressed by delphinidin. CONCLUSIONS: These observations provide a rationale for developing delphinidin for the management of psoriasis.

Excellent anti-proliferative and pro-apoptotic effects of (-)-epigallocatechin-3-gallate encapsulated in chitosan nanoparticles on human melanoma cell growth both in vitro and in vivo.

Earlier we demonstrated the anti-proliferative and pro-apoptotic effects of green tea polyphenol epigallocatechin-3-gallate (EGCG) on human melanoma cells (Int J Cancer. 2005; 114(4): 513-21). The doses used in this study were not physiologically attainable and for chemoprevention the preferred route of administration is oral consumption. To overcome these shortcomings, and taking advantage of our novel concept of nanochemoprevention (Cancer Res. 2009;69(5):1712-6), we developed a nanotechnology based oral delivery system to encapsulate EGCG. Here, using human melanoma Mel 928 cells we demonstrate 8-fold dose advantage of this nanoformulation over native EGCG. Further, nano-EGCG treated cells showed marked induction of apoptosis and cell cycle inhibition along with the growth of Mel 928 tumor xenograft. Nano-EGCG also inhibited proliferation (Ki-67 and PCNA) and induced apoptosis (Bax, PARP) in tumors harvested from the treated mice. These observations warrant further in vivo efficacy studies of nano-EGCG in robust animal models of human melanoma. FROM THE CLINICAL EDITOR: This team of investigators developed a nanotechnology based oral delivery system to encapsulate EGCG, a green tea-derived polyphenol in chitosan nanoparticles. Using human melanoma cells, an eight-fold dose advantage was demonstrated over native EGCG, leading to measurable apoptosis induction and proliferation inhibition, warranting further in vivo investigations.

Oral administration of naturally occurring chitosan-based nanoformulated green tea polyphenol EGCG effectively inhibits prostate cancer cell growth in a xenograft model.

In preclinical animal models, several phytochemicals have shown excellent potential to be used as effective agents in preventing and treating many cancers. However, the limited bioavailability of active agents could be one reason for their restricted usefulness for human consumption. To overcome this limitation, we recently introduced the concept of nanochemoprevention by encapsulating useful bioactive food components for their slow and sustained release. Here, we report the synthesis, characterization and efficacy assessment of a nanotechnology-based oral formulation of chitosan nanoparticles encapsulating epigallocatechin-3-gallate (Chit-nanoEGCG) for the treatment of prostate cancer (PCa) in a preclinical setting. Chit-nanoEGCG with a size of <200nm diameter and encapsulating EGCG as determined by dynamic light scattering and transmission electron microscope showed slow release of EGCG in simulated gastric juice acidic pH and faster release in simulated intestinal fluid. The antitumor efficacy of Chit-nanoEGCG was assessed in subcutaneously implanted 22Rν1 tumor xenografts in athymic nude mice. Treatment with Chit-nanoEGCG resulted in significant inhibition of tumor growth and secreted prostate-specific antigen levels compared with EGCG and control groups. In tumor tissues of mice treated with Chit-nanoEGCG, compared with groups treated with EGCG and controls, there was significant (i) induction of poly (ADP-ribose) polymerases cleavage, (ii) increase in the protein expression of Bax with concomitant decrease in Bcl-2, (iii) activation of caspases and (iv) reduction in Ki-67 and proliferating cell nuclear antigen. Through this study, we propose a novel preventive and therapeutic modality for PCa using EGCG that addresses issues related to bioavailability.

Delphinidin, a dietary antioxidant, induces human epidermal keratinocyte differentiation but not apoptosis: studies in submerged and three-dimensional epidermal equivalent models.

Delphinidin (Del), [3,5,7,3'-,4'-,5'-hexahydroxyflavylium], an anthocyanidin and a potent antioxidant abundantly found in pigmented fruits and vegetables exhibits proapoptotic effects in many cancer cells. Here, we determined the effect of Del on growth, apoptosis and differentiation of normal human epidermal keratinocytes (NHEKs) in vitro in submerged cultures and examined its effects in a three-dimensional (3D) epidermal equivalent (EE) model that permits complete differentiation reminiscent of in vivo skin. Treatment of NHEKs with Del (10-40 µm; 24-48 h) significantly enhanced keratinocyte differentiation. In Del-treated cells, there was marked increase in human involucrin (hINV) promoter activity with simultaneous increase in the mRNA and protein expressions of involucrin and other epidermal differentiation markers including procaspase-14 and transglutaminase-1 (TGM1), but without any effect on TGM2. Del treatment of NHEKs was associated with minimal decrease in cell viability, which was not associated with apoptosis as evident by lack of modulation of caspases, apoptosis-related proteins including Bcl-2 family of proteins and poly(ADP-ribose) polymerase cleavage. To establish the in vivo relevance of our observations in submerged cultures, we then validated these effects in a 3D EE model, where Del was found to significantly enhance cornification and increase the protein expression of cornification markers including caspase-14 and keratin 1. For the first time, we show that Del induces epidermal differentiation using an experimental system that closely mimics in vivo human skin. These observations suggest that Del could be a useful agent for dermatoses associated with epidermal barrier defects including aberrant keratinization, hyperproliferation or inflammation observed in skin diseases like psoriasis and ichthyoses.

Tea and health: studies in humans.

Tea, next to water is the cheapest beverage humans consume. Drinking the beverage tea has been considered a healthpromoting habit since ancient times. The modern medicinal research is providing a scientific basis for this belief. The evidence supporting the health benefits of tea drinking grows stronger with each new study that is published in the scientific literature. Tea plant Camellia sinensis has been cultivated for thousands of years and its leaves have been used for medicinal purposes. Tea is used as a popular beverage worldwide and its ingredients are now finding medicinal benefits. Encouraging data showing cancer-preventive effects of green tea from cell-culture, animal and human studies have emerged. Evidence is accumulating that black tea may have similar beneficial effects. Tea consumption has also been shown to be useful for prevention of many debilitating human diseases that include maintenance of cardiovascular and metabolic health. Various studies suggest that polyphenolic compounds present in green and black tea are associated with beneficial effects in prevention of cardiovascular diseases, particularly of atherosclerosis and coronary heart disease. In addition, anti-aging, antidiabetic and many other health beneficial effects associated with tea consumption are described. Evidence is accumulating that catechins and theaflavins, which are the main polyphenolic compounds of green and black tea, respectively, are responsible for most of the physiological effects of tea. This article describes the evidences from clinical and epidemiological studies in the prevention of chronic diseases like cancer and cardiovascular diseases and general health promotion associated with tea consumption.

The use of ondansetron for nausea and vomiting after head injury and its effect on return rates from the pediatric ED.

BACKGROUND: The use of ondansetron in children with vomiting after a head injury has not been well studied. Concern about masking serious injury is a potential barrier to its use. OBJECTIVE: The aim of this study was to evaluate the use of ondansetron in children with head injury and symptoms of vomiting in the pediatric emergency department (PED) and its effect on return rates and masking of more serious injuries. DESIGN/METHODS: Visits to 2 PEDs from 2003 to 2010 with a diagnosis of head injury were evaluated retrospectively. Patients discharged home after a head computed tomography (CT) are the primary cohort for the study. A logistic regression model was used to analyze ondansetron's effects on the likelihood of return to the PED within 72 hours for persistent symptoms. A secondary analysis was performed on patients with a diagnoses of head injury who did not receive a head CT and were discharged. RESULTS: A total of 6311 patients had a diagnosis of head injury, had a head CT performed, and were discharged from the PED. The use of ondansetron increased significantly from 3.7% in 2003 to 22% in 2010 (P < .001). After controlling for demographic/acuity differences, receiving ondansetron in the PED was associated with a lower likelihood of returning within 72 hours (0.49, 95% confidence interval [0.26-0.92]). In patients with head injury who did not have a head CT performed and were sent home, the use of ondansetron in the PED was not associated with an increased risk of missed diagnoses. CONCLUSION: Ondansetron use in children with a CT scan who are dispositioned home is relatively safe, does not appear to mask any significant conditions, and significantly reduces return visits to the PED.

Modulation of signaling pathways in prostate cancer by green tea polyphenols.

Prostate cancer (PCa) is the most common malignancy found in American men and the risk factors for PCa include age, family history, ethnicity, hormonal status, diet and lifestyle. For the successful development of cancer-preventive/therapeutic approaches, consumption of dietary agents capable of inhibiting or delaying the growth and proliferation of cancer cells without significantly affecting normal cells could be an effective strategy. Polyphenols derived from green tea, termed as green tea polyphenols (GTP) have received great attention in recent years for their beneficial effects, in particular, their significant involvement in cancer chemoprevention and chemotherapy. Several studies have reported beneficial effects of GTP using in vitro and in vivo approaches and in human clinical trials. Among green tea catechins, epigallocatechin-3-gallate (EGCG) is best studied for its cancer preventive properties. In this review article, we present available scientific literature about the effects of GTP and EGCG on signaling pathways in PCa.

Fisetin: a dietary antioxidant for health promotion.

SIGNIFICANCE: Diet-derived antioxidants are now being increasingly investigated for their health-promoting effects, including their role in the chemoprevention of cancer. In general, botanical antioxidants have received much attention, as they can be consumed for longer periods of time without any adverse effects. Flavonoids are a broadly distributed class of plant pigments that are regularly consumed in the human diet due to their abundance. One such flavonoid, fisetin (3,3',4',7-tetrahydroxyflavone), is found in various fruits and vegetables, such as strawberry, apple, persimmon, grape, onion, and cucumber. RECENT ADVANCES: Several studies have demonstrated the effects of fisetin against numerous diseases. It is reported to have neurotrophic, anticarcinogenic, anti-inflammatory, and other health beneficial effects. CRITICAL ISSUES: Although fisetin has been reported as an anticarcinogenic agent, further in-depth in vitro and in vivo studies are required to delineate the mechanistic basis of its observed effects. In this review article, we describe the multiple effects of fisetin with special emphasis on its anticancer activity as investigated in cell culture and animal models. FUTURE DIRECTIONS: Additional research focused toward the identification of molecular targets could lead to the development of fisetin as a chemopreventive/chemotherapeutic agent against cancer and other diseases.

Apoptosis and autophagy induction as mechanism of cancer prevention by naturally occurring dietary agents.

Nontoxic naturally occurring compounds, especially those from dietary sources, are receiving increasing consideration for prevention and treatment of diseases including cancer. There is a growing need for innovative anticancer therapies and therefore search for natural compounds with novel biological activities or antineoplastic potential is currently an important area in drug discovery. Support for this interest also comes from increasing concern over the efficacy and safety of many conventional therapies, especially those that run over a long course of time. Laboratory studies in different in vitro and in vivo systems have shown that many natural compounds possess the capacity to regulate response to oxidative stress and DNA damage, suppress angiogenesis, inhibit cell proliferation and induce autophagy and apoptosis. This review discusses the induction of apoptosis and autophagy as a mechanism of cancer prevention by some of the most studied naturally occurring dietary compounds.