The need for contraception in patients taking prescription drugs: a review of FDA warning labels, duration of effects, and mechanisms of action.

: This review provides a guide for the rational use of prescription drugs in patients of reproductive age. : A comprehensive retrieval of the labels of FDA-approved drugs was performed to identify drugs where the label recommends contraceptive use during and/or after treatment. The acquired data were analyzed and organized into a table.

FDA-approved drugs that are spermatotoxic in animals and the utility of animal testing for human risk prediction.

Purpose: This study reviews FDA-approved drugs that negatively impact spermatozoa in animals, as well as how these findings reflect on observations in human male gametes.

Methods: The FDA drug warning labels included in the DailyMed database and the peer-reviewed literature in the PubMed database were searched for information to identify single-ingredient, FDA-approved prescription drugs with spermatotoxic effects.

Results: A total of 235 unique, single-ingredient, FDA-approved drugs reported to be spermatotoxic in animals were identified in the drug labels.

FDA-approved medications that impair human spermatogenesis.

We herein provide an overview of the single-ingredient U.S. Food and Drug Administration (FDA)-approved drugs that affect human spermatogenesis, potentially resulting in a negative impact on male fertility.

FDA-approved drugs that interfere with laboratory tests: A systematic search of US drug labels.

Drug-related laboratory test interference or drug/laboratory test interactions (DLTI) are a major source of laboratory errors. DLTI is of concern with regard to both the clinical diagnosis and the monitoring of patients. Although there have been numerous reports about specific drugs that interfere with laboratory tests, there has not been a recent review on the topic.

KCN1, a novel synthetic sulfonamide anticancer agent: in vitro and in vivo anti-pancreatic cancer activities and preclinical pharmacology.

The purpose of the present study was to determine the in vitro and in vivo anti-cancer activity and pharmacological properties of 3,4-dimethoxy-N-[(2,2-dimethyl-2H-chromen-6-yl)methyl]-N-phenylbenzenesulfonamide, KCN1. In the present study, we investigated the in vitro activity of KCN1 on cell proliferation and cell cycle distribution of pancreatic cancer cells, using the MTT and BrdUrd assays, and flow cytometry. The in vivo anti-cancer effects of KCN1 were evaluated in two distinct xenograft models of pancreatic cancer.

Development and validation of an HPLC method for quantitation of BA-TPQ, a novel iminoquinone anticancer agent, and an initial pharmacokinetic study in mice.

We herein describe the development and validation of an HPLC method for the quantitation of 7-(benzylamino)-1,3,4,8-tetrahydropyrrolo [4,3,2-de]quinolin-8(1H)-one (BA-TPQ), a newly synthesized iminoquinone anticancer agent. BA-TPQ was extracted from plasma and tissue samples by first precipitating proteins with acetonitrile followed by a liquid-liquid extraction with ethyl acetate. Chromatographic separation was carried out using a gradient flow rate on a Zorbax SB C(18) column, and the effluent was monitored by UV detection at 346 nm.

Preclinical pharmacology of BA-TPQ, a novel synthetic iminoquinone anticancer agent.

Marine natural products and their synthetic derivatives represent a major source of novel candidate anti-cancer compounds. We have recently tested the anti-cancer activity of more than forty novel compounds based on an iminoquinone makaluvamine scaffold, and have found that many of the compounds exert potent cytotoxic activity against human cancer cell lines. One of the most potent compounds, BA-TPQ [(11,12),7-(benzylamino)-1,3,4,8-tetrahydropyrrolo[4,3,2-de]quinolin-8(1H)-one], was active against a variety of human cancer cell lines, and inhibited the growth of breast and prostate xenograft tumors in mice.

A novel synthetic iminoquinone, BA-TPQ, as an anti-breast cancer agent: in vitro and in vivo activity and mechanisms of action.

Herein, we report our examination of the anti-breast cancer activity of a novel synthetic compound, 7-(benzylamino)-1, 3, 4, 8-tetrahydropyrrolo [4, 3, 2-de]quinolin-8(1H)-one (BA-TPQ). This agent is an analog of a naturally occurring marine compound, and was found to be the most active out of more than 40 related compounds. We investigated the in vitro activity of BA-TPQ on the survival, proliferation, and apoptosis of breast cancer cells using the MTT and BrdUrd assays, and Annexin/Annexin-PI staining and flow cytometry.

Recent advances in validating MDM2 as a cancer target.

The MDM2 oncogene is overexpressed in various human cancers. Its expression correlates with the phenotypes of high-grade, late-stage, and more resistant tumors. The auto-regulatory loop between MDM2 and the tumor suppressor p53 has long been considered the epitome of a rational target for cancer therapy.

In vitro and in vivo anticancer activity of novel synthetic makaluvamine analogues.

Purpose: The present study was designed to determine biological structure-activity relationships for four newly synthesized analogues of natural compounds (makaluvamines). The compounds, 7-(4-fluorobenzylamino)-1,3,4,8-tetrahydropyrrolo[4,3,2-de]quinolin-8(1H)-one (FBA-TPQ); 7-(phenethylamino)-1,3,4,8-tetrahydropyrrolo[4,3,2-de]quinolin-8(1H)-one (PEA-TPQ); 7-(3,4-methylenedioxyphenethylamino)-1,3,4,8-tetrahydropyrrolo[4,3,2-de]quinolin-8(1H)-one (MPA-TPQ); and 7-(3,4-dimethoxyphenethylamino)-1,3,4,8-tetrahydropyrrolo[4,3,2-de]quinolin-8(1H)-one (DPA-TPQ), were synthesized and purified, and their chemical structures were elucidated on the basis of physicochemical constants and nuclear magnetic resonance spectra.

Experimental Design: The structure-activity relationship of the compounds was initially evaluated by comparing their in vitro cytotoxicity against 14 human cell lines.

Synthesis and in vitro anti-lung cancer activity of novel 1, 3, 4, 8-tetrahydropyrrolo [4, 3, 2-de]quinolin-8(1H)-one alkaloid analogs.

The high mortality rate and lack of effective therapies make lung cancer an ideal target for novel therapeutic agents. The present study was designed to implement a novel chemical synthesis pathway and to determine the biological activities of synthetic makaluvamine analogs in human lung cancer. Seventeen compounds were synthesized and purified, and their chemical structures were elucidated on the basis of physicochemical constants and NMR spectra.

FBA-TPQ, a novel marine-derived compound as experimental therapy for prostate cancer.

We recently synthesized a series of novel makaluvamine compounds, and found that the most potent was FBA-TPQ. The effects of FBA-TPQ on human (LNCaP and PC3) and murine (TRAMP C1) prostate cancer cells were evaluated. Potential mechanisms of action of the compound were also determined.

Novel ginsenosides 25-OH-PPD and 25-OCH3-PPD as experimental therapy for pancreatic cancer: anticancer activity and mechanisms of action.

We recently isolated and characterized two novel ginsenosides, 25-OH-PPD and 25-OCH(3)-PPD. We investigated whether these ginsenosides could represent safe and effective therapeutic agents for pancreatic cancer. In vitro and in vivo studies demonstrated that both compounds inhibited proliferation, caused cell cycle arrest, and induced apoptosis.

Anti-lung cancer effects of novel ginsenoside 25-OCH(3)-PPD.

20(S)-25-methoxyl-dammarane-3beta, 12beta, 20-triol (25-OCH(3)-PPD), a newly identified natural product from Panax notoginseng, exhibits activity against a variety of cancer cells. Herein, we report the effects of this compound on human A549, H358, and H838 lung cancer cells, and compare these effects with a control lung epithelial cell line, BEAS-2B. 25-OCH(3)-PPD decreased survival, inhibited proliferation, and induced apoptosis and G1 cell cycle arrest in the lung cancer cell lines.

Anti-Inflammatory Agents for Cancer Therapy.

Inflammation is closely linked to cancer, and many anti-cancer agents are also used to treat inflammatory diseases, such as rheumatoid arthritis. Moreover, chronic inflammation increases the risk for various cancers, indicating that eliminating inflammation may represent a valid strategy for cancer prevention and therapy. This article explores the relationship between inflammation and cancer with an emphasis on epidemiological evidence, summarizes the current use of anti-inflammatory agents for cancer prevention and therapy, and describes the mechanisms underlying the anti-cancer effects of anti-inflammatory agents.

RYBP stabilizes p53 by modulating MDM2.

The mouse double minute 2 (MDM2)-p53 interaction regulates the activity of p53 and is a potential target for human cancer therapy. Here, we report that RYBP (RING1- and YY1-binding protein), a member of the polycomb group (PcG), interacts with MDM2 and decreases MDM2-mediated p53 ubiquitination, leading to stabilization of p53 and an increase in p53 activity. RYBP induces cell-cycle arrest and is involved in the p53 response to DNA damage.

Antisense, RNAi, and gene silencing strategies for therapy: mission possible or impossible?

Antisense oligonucleotides can regulate gene expression in living cells. As such, they regulate cell function and division, and can modulate cellular responses to internal and external stresses and stimuli. Although encouraging results from preclinical and clinical studies have been obtained and significant progress has been made in developing these agents as drugs, they are not yet recognized as effective therapeutics.

Experimental therapy of prostate cancer with novel natural product anti-cancer ginsenosides.

Background: Ginseng and its components exert various biological effects, including antioxidant, anti-carcinogenic, anti-mutagenic, and anti-tumor activity, and recent research has focused on their value in human cancer prevention and treatment. We recently isolated 25-hydroxyprotopanaxadiol (25-OH-PPD) and 25-hydroxyprotopanaxatriol (25-OH-PPT) from Panax ginseng and evaluated their anti-cancer activity in vitro.

Methods: We compared the effects of the two compounds on human prostate cancer LNCaP and PC3 cells in vitro and in a mouse PC3 xenograft tumor model.

Experimental therapy for colon cancer: anti-cancer effects of TLR9 agonism, combination with other therapeutic modalities, and dependence upon p53.

The present study demonstrates the efficacy of utilizing TLR9 (toll-like receptor 9) agonism as a potential therapy for colon cancer. We examined the effects of two types of TLR9 agonists: a traditional CpG oligonucleotide and a novel immunomodulatory oligonucleotide in models of colon cancer, both alone and in combination with conventional cancer therapies. Because the tumor suppressor p53 is involved in many anti-cancer pathways, and is mutated in more than 50% of cancers, we determined whether p53 is necessary for the anti-tumor effects observed following treatment with TLR9 agonists.

Extracellular activity of cyclic AMP-dependent protein kinase as a biomarker for human cancer detection: distribution characteristics in a normal population and cancer patients.

The overexpression of cyclic AMP (cAMP)-dependent protein kinase (PKA) has been reported in patients with cancer, and PKA inhibitors have been tested in clinical trials as a novel cancer therapy. The present study was designed to characterize the population distribution of extracellular activity of cAMP-dependent protein kinase (ECPKA) and its potential value as a biomarker for cancer detection and monitoring of cancer therapy. The population distribution of ECPKA activity was determined in serum samples from a Chinese population consisting of a total of 603 subjects (374 normal healthy volunteers and 229 cancer patients).

Dexamethasone as a chemosensitizer for breast cancer chemotherapy: potentiation of the antitumor activity of adriamycin, modulation of cytokine expression, and pharmacokinetics.

Dexamethasone (DEX) is mainly used as an anti-emetic agent in cancer therapy. We have recently demonstrated that DEX pretreatment increases the antitumor activity of the cancer chemotherapeutic agents carboplatin and gemcitabine, and decreases host toxicity in nude mouse xenograft models of human cancer. However, the underlying mechanisms are not fully understood.

Immunomodulatory oligonucleotides as novel therapy for breast cancer: pharmacokinetics, in vitro and in vivo anticancer activity, and potentiation of antibody therapy.

Oligonucleotides containing CpG motifs and immunomodulatory oligonucleotides (IMO) containing a synthetic immunostimulatory dinucleotide and a novel DNA structure have been suggested to have potential for the treatment of various human diseases. In the present study, a newly designed IMO was evaluated in several models of human (MCF-7 and BT474 xenograft) and murine (4T1 syngeneic) breast cancer. Pharmacokinetics studies of the IMO administered by s.

Experimental therapy of prostate cancer with an immunomodulatory oligonucleotide: effects on tumor growth, apoptosis, proliferation, and potentiation of chemotherapy.

Background: The present study was designed to demonstrate the therapeutic efficacy of a novel immunomodulatory oligonucleotide (IMO) for prostate cancer.

Methods: We evaluated the effects of the IMO in xenograft (PC-3) and syngeneic (TRAMP C1) models of prostate cancer, and in prostate cancer cells. The IMO was also evaluated in combination with chemotherapy, and the in vitro expression of TLR9 was examined.

In vitro anti-cancer activity and structure-activity relationships of natural products isolated from fruits of Panax ginseng.

Purpose: Panax ginseng and its extracts have long been used for medical purposes; there is increasing interest in developing ginseng products as cancer preventive or therapeutic agents. The present study was designed to determine biological structure-activity relationships (SAR) for saponins present in Panax ginseng fruits.

Methods: Eleven saponins were extracted from P.

Chemotherapy and chemosensitization of non-small cell lung cancer with a novel immunomodulatory oligonucleotide targeting Toll-like receptor 9.

Lung cancer is a leading cause of death world-wide and the long-term survival rate for lung cancer patients is one of the lowest for any cancer. New therapies are urgently needed. The present study was designed to evaluate an immunomodulatory oligonucleotide as a novel type of therapy for lung cancer.