Phase I Study of Aurora A Kinase Inhibitor Alisertib (MLN8237) in Combination With Selective VEGFR Inhibitor Pazopanib for Therapy of Advanced Solid Tumors.

Objectives: Pazopanib is a multikinase angiogenesis inhibitor. Alisertib is a highly selective inhibitor of mitotic Aurora A kinase. There is preclinical evidence that mitosis-targeting agents exhibit antiangiogenic effects.

Caffeine Accelerates Emergence from Isoflurane Anesthesia in Humans: A Randomized, Double-blind, Crossover Study.

What We Already Know About This Topic: WHAT THIS ARTICLE TELLS US THAT IS NEW: BACKGROUND:: There are currently no drugs clinically available to reverse general anesthesia. We previously reported that caffeine is able to accelerate emergence from anesthesia in rodents. This study was carried out to test the hypothesis that caffeine accelerates emergence from anesthesia in humans.

The Role of Forkhead Box Protein M1 in Breast Cancer Progression and Resistance to Therapy.

The Forkhead box M1 (FOXM1) is a transcription factor that has been implicated in normal cell growth and proliferation through control of cell cycle transition and mitotic spindle. It is implicated in carcinogenesis of various malignancies where it is activated by either amplification, increased stability, enhanced transcription, dysfunction of regulatory pathways, or activation of PI3K/AKT, epidermal growth factor receptor, Raf/MEK/MAPK, and Hedgehog pathways. This review describes the role of FOXM1 in breast cancer.

Treatment of multiple unresectable basal cell carcinomas from Gorlin-Goltz syndrome: a case report.

Background: Nevoid basal cell carcinoma syndrome (NBCCS), which is also known by other names, including Gorlin-Goltz syndrome and multiple basal-cell carcinoma (BCC) syndrome, is a rare multi-systemic disease inherited in a dominant autosomal manner with complete penetrance and variable expressivity. The main clinical manifestations include multiple BCCs, odontogenic keratocysts of the jaw, hyperkeratosis of the palms and soles, skeletal abnormalities, intracranial calcifications and facial deformities.

Patients And Methods: A 31-year-old male diagnosed with Gorlin-Goltz syndrome with multiple unresectable facial BCCs was treated with the Hedgehog inhibitor vismodegib.

Methylnaltrexone: its pharmacological effects alone and effects on morphine in healthy volunteers.

Rationale: Methylnaltrexone bromide (MTNX) is a peripherally acting mu-opioid receptor antagonist, prescribed for the treatment of opioid-induced constipation in patients with advanced illness who are receiving palliative care. Studies have used this drug to determine if other opioid-induced effects besides constipation are altered by MTNX in humans and have suggested, based on their results, that these other effects are altered by peripheral opioid actions.

Objective: The primary objective of this report is to present results that provide indirect evidence that MTNX has centrally mediated effects, albeit slight, and secondarily to describe the effects of MTNX on psychopharmacological effects of morphine.

Abuse liability measures for use in analgesic clinical trials in patients with pain: IMMPACT recommendations.

Assessing and mitigating the abuse liability (AL) of analgesics is an urgent clinical and societal problem. Analgesics have traditionally been assessed in randomized clinical trials (RCTs) designed to demonstrate analgesic efficacy relative to placebo or an active comparator. In these trials, rigorous, prospectively designed assessment for AL is generally not performed.

Modulating roles of smoking status and sex on oxycodone-induced nausea and drug liking.

Two prominent and important risk factors for nonmedical use of prescription opioids (NMUPO) identified in epidemiological studies are smoking status and sex (i.e., there is a greater likelihood of NMUPO in smokers and in men, relative to nonsmokers and women).

Core outcome measures for opioid abuse liability laboratory assessment studies in humans: IMMPACT recommendations.

A critical component in development of opioid analgesics is assessment of their abuse liability (AL). Standardization of approaches and measures used in assessing AL have the potential to facilitate comparisons across studies, research laboratories, and drugs. The goal of this report is to provide consensus recommendations regarding core outcome measures for assessing the abuse potential of opioid medications in humans in a controlled laboratory setting.

Research design considerations for clinical studies of abuse-deterrent opioid analgesics: IMMPACT recommendations.

Opioids are essential to the management of pain in many patients, but they also are associated with potential risks for abuse, overdose, and diversion. A number of efforts have been devoted to the development of abuse-deterrent formulations of opioids to reduce these risks. This article summarizes a consensus meeting that was organized to propose recommendations for the types of clinical studies that can be used to assess the abuse deterrence of different opioid formulations.

Separate and combined psychopharmacological effects of alprazolam and oxycodone in healthy volunteers.

Background: There are epidemiological data indicating that medical and/or nonmedical use of prescription opioids oftentimes involves concurrent use of other substances. One of those substances is benzodiazepines. It would be of relevance to characterize the effects of an opioid and a benzodiazepine when taken together to determine if measures related to abuse liability-related effects and psychomotor performance impairment are increased compared to when the drugs are taken alone.

Subjective, psychomotor, and physiological effects of pregabalin alone and in combination with oxycodone in healthy volunteers.

Pregabalin is an anticonvulsant drug indicated for neuropathic disorders and fibromyalgia. Some chronic pain patients suffering from these disorders take both this drug and an opioid for pain relief. Pregabalin is a scheduled drug under the Controlled Substances Act.

Characterizing the subjective and psychomotor effects of carisoprodol in healthy volunteers.

Carisoprodol is a centrally acting drug used to relieve skeletal muscle spasms and associated pain in acute musculoskeletal conditions. There is evidence from different sources that this oral muscle relaxant is abused and that it is associated with impairment leading to arrests for "driving under the influence" as well as increased risk of automobile accidents. Its subjective and psychomotor effects in healthy volunteers at therapeutic and supratherapeutic doses have not been well-characterized, and form the basis of this report.

Subjective and psychomotor effects of carisoprodol in combination with oxycodone in healthy volunteers.

Background: Some chronic pain patients on long-term opioid therapy also take centrally active skeletal muscle relaxants. One of those muscle relaxants is carisoprodol, a drug that is abused and capable of producing impairment. It would be of relevance to characterize the effects of an opioid and carisoprodol when taken together to determine if abuse liability-related measures and psychomotor impairment are increased compared to when the drugs are taken alone.

Subjective, psychomotor, and physiological effects of oxycodone alone and in combination with ethanol in healthy volunteers.

Rationale: Nonmedical use of prescription opioids is sometimes accompanied by the ingestion of ethanol. Whether ethanol increases the abuse liability-related effects of prescription opioids has not been determined.

Objective: The purpose of this study was to characterize the subjective, psychomotor, and physiological effects of oxycodone, a widely prescribed and abused opioid, and ethanol, alone and in combination.

Psychopharmacological effects of oxycodone in volunteers with and without generalized anxiety disorder.

A number of studies have documented a relationship between anxiety disorders and opioid misuse and abuse, and there is some data to suggest that some people use opioids in an attempt to reduce their anxiety. We tested the hypothesis that volunteers with an anxiety disorder would report a more positive spectrum of subjective effects (i.e.

Lack of sex differences to the subjective effects of nitrous oxide in healthy volunteers.

Background: Although numerous studies have assessed subjective effects of nitrous oxide, few studies have analyzed for sex differences. Since sex differences have been reported in subjective effects of several drugs such as opioids, nicotine and alcohol, we sought to determine if sex modulates the subjective effects of the inhalant, nitrous oxide, in healthy volunteers.

Methods: Thirty-eight females and seventy-two males from nine studies that were conducted in our laboratory were included in this retrospective analysis.

A possible link between sensation-seeking status and positive subjective effects of oxycodone in healthy volunteers.

Sensation-seeking is a personality trait that is linked to use and abuse of drugs. Laboratory studies have established that high sensation seekers, as measured by different instruments, are more likely to report abuse liability-related subjective effects from drugs such as nicotine, alcohol, and d-amphetamine than low sensation seekers. One class of drugs that has not been studied to date in this fashion is opioids.

Psychopharmacological effects of oxycodone in healthy volunteers: roles of alcohol-drinking status and sex.

Background: Studies have shown that alcohol-drinking status modulates psychopharmacological effects of several drugs. We sought to determine if drinking status modulates the effects of a prescription opioid, oxycodone, in healthy volunteers. We included sex of the volunteer in the statistical analyses since this is a factor that is known to alter several pharmacodynamic effects of opioids in nonhumans and humans.

The prescription opioid, oxycodone, does not alter behavioral measures of impulsivity in healthy volunteers.

This study examined the effects of oral oxycodone, a prescription opioid, on several measures of impulsive behavior in healthy volunteers. Volunteers (n=12) participated in a four-session, double-blind, randomized design in which they received capsules containing oxycodone (5, 10, and 20 mg) or placebo. From 70 min to approximately 120 min after ingesting the capsules, subjects completed five impulsivity tasks: delay and probability discounting task, balloon analogue risk task (BART), go/no-go task, stop task, and simple reaction time test.

Within-subject comparison of the psychopharmacological profiles of oral hydrocodone and oxycodone combination products in non-drug-abusing volunteers.

Background: Non-medical use and abuse of prescription opioids is a significant problem in the United States. Little attention has been paid to assessing the relative psychopharmacological profile (including abuse liability-related effects) of specific prescription opioids. The purpose of this study was to directly compare the psychopharmacological profile of two widely prescribed and abused oral opioid combination products within the same subject.

Choice of nitrous oxide and its subjective effects in light and moderate drinkers.

Background: Alcohol-drinking status has been shown to modulate the reinforcing and subjective effects of a number of drugs. We have previously published two studies on the modulating effects of alcohol-drinking status on choice for, and subjective effects of, nitrous oxide, but the results were equivocal. Using a methodology different from our previous studies, we sought to determine in a more definitive fashion the degree to which the choice of nitrous oxide and its subjective effects were modulated by drinking status.

Subjective, psychomotor, and physiological effects profile of hydrocodone/acetaminophen and oxycodone/acetaminophen combination products.

Objectives: To compare within the same individuals two typically prescribed doses of hydrocodone/acetaminophen and oxycodone/acetaminophen products for their subjective, psychomotor, and physiological effects in healthy volunteers.

Design: A randomized, placebo-controlled, double-blind, crossover, six-session clinical laboratory study, enrolling 16 healthy participants (27.2 +/- 4.

Nonmedical use of prescription opioids: motive and ubiquity issues.

Unlabelled: Two issues relating to prescription opioid nonmedical use that to our knowledge have not been comprehensively addressed in the peer-reviewed literature are discussed: Motives for nonmedical use and the extent of nonmedical use of prescription opioids in other countries. The United States' national annual survey on illicit drug use in the general population (National Survey on Drug Use and Health) asks respondents whether they have used prescription opioids for nonmedical purposes but does not assess motives for such use. By not assessing motives, nonmedical users who use only for pain relief and nonmedical users who have other motives for use are grouped together, but 2 recent epidemiological studies suggest that these 2 groups may differ in a propensity to have substance use-related problems.

Choice of sevoflurane and its subjective and psychomotor effects in light and moderate drinkers.

Background: Sevoflurane, an inhalant of the volatile anesthetic class, has neurobiological and behavioral effects in common with abused inhalants and ethanol. We sought to determine if choice for subanesthetic doses of sevoflurane, and its subjective and psychomotor effects, would differ as a function of alcohol-drinking status in healthy volunteers.

Methods: The effects of four concentrations of sevoflurane (0, 0.

Within-subject comparison of the psychopharmacological profiles of oral oxycodone and oral morphine in non-drug-abusing volunteers.

Rationale: Nonmedical use and abuse of prescription opioids is a significant problem in the USA. Little attention has been paid to assessing the relative psychopharmacological profile (including abuse liability-related effects) of specific prescription opioids.

Objectives: The aim of this study is to directly compare the psychopharmacological profile of two oral opioids within the same subject.