Chemoprevention

 Invasive fungal infection (IFI) following liver transplant is associated with significant morbidity and mortality. Antifungal prophylaxis is rational for liver transplant patients at high IFI risk.  In this open-label, noninferiority study, patients were randomized 1:1 to receive intravenous micafungin 100 mg or center-specific standard care (fluconazole, liposomal amphotericin B, or caspofungin) posttransplant. The primary endpoint was clinical success (absence of a proven/probable IFI and no need for additional antifungals) at end of prophylaxis (EOP). Noninferiority (10% margin) of micafungin vs standard care was assessed in the per protocol and full analysis sets. Safety assessments included adverse events and liver and kidney function tests.  The full analysis set comprised 344 patients (172 micafungin; 172 standard care). Mean age was 51.2 years; 48.0% had a Model for End-Stage Liver Disease score ≥20. At EOP (mean treatment duration, 17 days), clinical success was 98.6% for ...

Fruit and vegetable consumption has consistently been associated with decreased risk of a number of aerodigestive tract cancers, including esophageal cancer. We have taken a "food-based" chemopreventive approach to evaluate the inhibitory potential of lyophilized black raspberries (LBRs) against N-nitrosomethylbenzylamine (NMBA)-induced esophageal tumorigenesis in the F344 rat, during initiation and postinitiation phases of carcinogenesis. Anti-initiation studies included a 30-week tumorigenicity bioassay, quantification of DNA adducts, and NMBA metabolism study. Feeding 5 and 10% LBRs, for 2 weeks prior to NMBA treatment (0.25 mg/kg, weekly for 15 weeks) and throughout a 30-week bioassay, significantly reduced tumor multiplicity (39 and 49%, respectively). In a short-term bioassay, 5 and 10% LBRs inhibited formation of the promutagenic adduct O(6)-methylguanine (O(6)-meGua) by 73 and 80%, respectively, after a single dose of NMBA at 0.25 mg/kg. Feeding 5% LBRs also signif...

Epidemiological studies showing a protective effect of diets rich in fruits and vegetables against cancer have focused attention on the possibility that biologically-active plant secondary metabolites exert anti-carcinogenic activity. This huge group of compounds, now collectively termed ‘phytochemicals’, provides much of the flavour and colour of edible plants and the beverages derived from them. Many of these compounds also exert anti-carcinogenic effects in animal models of cancer, and much progress has been made in defining their many biological activities at the molecular level. Such mechanisms include the detoxification and enhanced excretion of carcinogens, the suppression of inflammatory processes such as cyclooxygenase-2 expression, inhibition of mitosis and the induction of apoptosis at various stages in the progression and promotion of cancer. However, much of the research on phytochemicals has been conducted in vitro, with little regard to the bioavailability and metabol...

Individuals in contact with patients who have leprosy have an increased risk of disease exposure, which reinforces the need for chemoprophylactic measures, such as the use of rifampicin. The objective of the review was to synthesize the best available evidence regarding the effectiveness of rifampicin chemoprophylaxis for contacts with patients with leprosy, and to synthesize the best available evidence on the experience and acceptability of rifampicin chemoprophylaxis as reported by the contacts and health professionals involved in the treatment of leprosy or Hansen's disease. In the quantitative component, individuals in contact with leprosy patients were included. In the qualitative component, in addition to contacts, health professionals who were in the practice of treating leprosy were included. The quantitative component considered as an intervention rifampicin at any dose, frequency and mode of administration, and rifampicin combination regimens.The qualitative component ...

Moringa oleifera Lam (Moringaceae) is promising plant for biomedicine applications because it has an impressive
range of medicinal purposes with high nutritional value. Therefore, we investigated the therapeutic effect of
Moringa oleifera leaf extract (MOLE) on Ehrlich's solid tumor implanted mice (EST-mice). Swiss male albino mice
were implanted intramuscularly with Ehrlich ascites carcinoma (EAC). Three doses of MOLE extract (125, 250 and
500mg kg-1) were administrated to EST-mice for 14 days. The standard drug vincristine (VCR) was i.p injected (0.1
mg kg1-) after the implantation of EST. The antitumor activity of MOLE was assessed using several tumor markers.
Modulating activity of MOLE against EST was evaluated using comet assay, micronucleus test and morphological
apoptotic changes as well as DNA fragmentation assay. The expression analysis of the inducible nitric oxide
synthase (iNOS), vascular endothelial growth factor (VEGF) and apoptosis related genes (p53, p21 and bcl2) were
evaluated. Treatment of EST-mice with the highest dose of MOLE exhibited inhibition of tumor growth and the
tumor markers in solid tumor. MOLE inhibited the apoptotic/necrotic cells, decrease of micronucleus formation and
DNA damage in EST-mice. Expression of iNOS, VEGF, p53 mutation, p21 and bcl2 genes in EST-mice were
significantly over-expressed compared with control group. These observations were markedly inhibited with the
highest dose of extract. Moringa oleifera leaf extract revealed antitumor, antigenotoxic and anticytotoxic activities
in EST-mice. The biological activities of Moringa oleifera leaf extract were discussed.

A wide variety of phenolic compounds derived from spices possess potent antioxidant, anti-inflammatory, antimutagenic, and anticarcinogenic activities. [6]-gingerol (1-[4′-hydroxy-3′-methoxyphenyl]-5-hydroxy-3-decanone) is the major pungent principle of ginger, with numerous pharmacological properties including antioxidant, anti-inflammation, and antitumor promoting properties. It could decrease inducible nitric oxide synthase (iNOS) and tumor necrosis factor alpha (TNF-α) expression through suppression of I-kappaB alpha (IκBα) phosphorylation, nuclear factor kappa B (NF-κB) nuclear translocation. Other antiproliferative mechanisms of [6]-gingerol include the release of Cytochrome c, Caspases activation, and increase in apoptotic protease-activating factor-1 (Apaf-1) as mechanism of apoptosis induction. Taken together, the chemopreventive potentials of [6]-gingerol present a promising future alternative to therapeutic agents that are expensive, toxic, and might even be carcinogenic.

Cancer chemoprevention is a new approach in cancer prevention, in which chemical agents are used to prevent cancer in normal and/or high-risk populations. Although chemoprevention has shown promise in some epithelial cancers, currently available preventive agents are limited and the agents are costly, generally with side effects. Natural products, such as grape seed, green tea, and certain herbs have demonstrated anti-cancer effects. To find a natural product that can be used in chemoprevention of cancer, we tested Arizona cactus fruit solution, the aqueous extracts of cactus pear, for its anti-cancer effects in cultured cells and in an animal model. Aqueous extracts of cactus pear were used to treat immortalized ovarian and cervical epithelial cells, as well as ovarian, cervical, and bladder cancer cells. Aqueous extracts of cactus pear were used at six concentrations (0, 0.5, 1, 5, 10 or 25%) to treat cells for 1, 3, or 5 days. Growth inhibition, apoptosis induction, and cell cycl...

Influenza is a global health concern, causing death, morbidity, and economic losses. Chemotherapeutics that target influenza virus are available; however, rapid emergence of drug-resistant strains is common. Therapeutic targeting of host proteins hijacked by influenza virus to facilitate replication is an antiviral strategy to reduce the development of drug resistance. Nuclear export of influenza virus ribonucleoprotein (vRNP) from infected cells has been shown to be mediated by exportin 1 (XPO1) interaction with viral nuclear export protein tethered to vRNP. RNA interference screening has identified XPO1 as a host proinfluenza factor where XPO1 silencing results in reduced influenza virus replication. The Streptomyces metabolite XPO1 inhibitor leptomycin B (LMB) has been shown to limit influenza virus replication in vitro; however, LMB is toxic in vivo, which makes it unsuitable for therapeutic use. In this study, we tested the anti-influenza virus activity of a new class of orally...

Aberrantly regulated apoptosis is involved in the pathogenesis of several diseases and defective apoptosis leads to uncontrolled cell proliferation and tumorigenesis. Cancer is an example of a pathologic condition where the normal mechanisms of cell cycle regulation are dysfunctional either by excessive cell proliferation, inhibited/suppressed apoptosis or both. Dietary habits are estimated to contribute to, at least, one third of all human cancers, showing that dietary components can exacerbate or interfere with carcinogenesis. However, several epidemiological studies have revealed that some dietary factors can decrease the risk of different types of cancer. Apoptosis is suggested to be a crucial mechanism for the chemopreventive properties associated with several dietary factors by eliminating potentially deleterious (damaged/mutated) cells. Food, a readily available item, contains several promising chemopreventive agents. Polyphenols are serious candidates since they are responsible for the cancer protective properties of a diet rich in vegetables and fruits: numerous phenolic compounds showed antiproliferative and cytotoxic effects and, more specifically, pro-apoptotic activities, in several cancer cells lines and animal tumor models. The aim of the present review is to analyze and summarize several aspects related to the molecular mechanisms of apoptosis induced by dietary factors with particular emphasis on polyphenols. Dietary factors that can activate cell death signals and induce apoptosis, preferentially in precancerous or malignant cells, and the study of their apoptotic inducing targets can represent a mean to devise new strategies for cancer prevention in the future.

Since its advent in the field of cancer, nanotechnology has provided researchers with expertise to explore new avenues for diagnosis, prevention, and treatment of the disease. Utilization of nanotechnology has enabled the development of devices in nanometer (nm) sizes which could be designed to encapsulate useful agents that have shown excellent results but otherwise are generally toxic due to the doses intended for extended use. In addition, examples are also available where these devices are easily conjugated with several purposeful moieties for better localization and targeted delivery. We introduced a novel concept in which nanotechnology was utilized for enhancing the outcome of chemoprevention. This idea, which we termed as "nanochemoprevention," was subsequently exploited by several laboratories worldwide and has now become an advancing field in chemoprevention research. This review examines some of the up and coming applications of nanotechnology for cancer detecti...

This article reviews the mechanisms by which glucosinolate breakdown products are thought to inhibit carcinogenesis. It describes how isothiocyanates, thiocyanates, nitriles, cyano-epithioalkanes and indoles are produced from glucosinolates through the actions of myrosinase, epithiospecifier protein and epithiospecifier modifier protein released from cruciferous vegetables during injury to the plant. The various biological activities displayed by these phytochemicals are described. In particular, their abilities to induce cytoprotective genes, mediated by the Nrf2 (NF-E2 related factor 2) and AhR (arylhydrocarbon receptor) transcription factors, and their abilities to repress NF-κB (nuclear factor-κB) activity, inhibit histone deacetylase, and inhibit cytochrome P450 are outlined. Isothiocyanates appear to alter gene expression through modification of critical thiols in regulatory proteins such as Keap1 (Kelch-like ECH-associated protein 1) or IKK (IκB kinase), causing activation of Nrf2 and inactivation of NF-κB, respectively. Certain indoles act as ligands for AhR. Isothiocyanates and indoles are also capable of affecting cell cycle arrest and stimulating apoptosis. The mechanisms responsible for these anti-proliferative responses are discussed.

Despite advances in drug discovery programs and molecular approaches for identifying drug targets, incidence and mortality rates due to melanoma continue to rise at an alarming rate. Existing preventive strategies generally involve mole screening followed by surgical removal of the benign nevi and abnormal moles. However, due to lack of effective programs for screening and disease recurrence after surgical resection, there is a need for better chemopreventive agents. Although sunscreens have been used extensively for protecting from UV-induced melanomas, results of correlative population-based studies are controversial, with certain studies suggest increased skin cancer risk in sunscreen users. Therefore, these studies require further authentication to conclusively confirm the chemoprotective efficacy of sunscreens. This chapter reviews the current understanding regarding melanoma chemoprevention and the various strategies used to accomplish this objective.

Prostate cancer (PC) is one of the most common and leading cancer amongst the males all around the world. Depending upon it long latency and cost involved in its management and
treatment, there is extensive need for more personalized and economical therapeutic approach for its effective therapy. The current review here discusses agents from natural dietary sources and drug class Non-Steroidal Antinflammatory (NSAIDS) that bears chemopreventive potential to regulate PC progression & tumour development and therefore could be devised into effective future treatment strategy against PC along with its metastatic castration-resistant form. Based on the literature search the therapeutic scope of selected agents are delineated, sighting their previous activity and prospects as epigenetic moderators in specific to particular PC causing biomarkers like over expression of AKR1C3, lost intracellular glutathione/ glutathione stranferases  (GSH/GST) expression, DNA hypermethylation, aberrant cell proliferation and other related factors that are thought to potentiate and aggravate the onset of PC like smoking and use of other narcotics products.