18 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

("drug-induced" OR "drug-related") AND ("adverse events" OR "side effects" OR "side-effects")

These pubmed results were generated on 2017/03/16

PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

Dysregulation of BET proteins in levodopa-induced dyskinesia.

Neurobiol Dis. 2017 Mar 09;:

Authors: Figge D, Standaert DG

Abstract
Levodopa (L-DOPA) remains the most effective pharmacological treatment for Parkinson's Disease (PD) but its use is limited by the development of debilitating drug-related side effects, particularly L-DOPA induced dyskinesia (LID). LID is a consequence of long-term L-DOPA use, and in model systems is characterized by a "priming effect", whereby initial administrations of L-DOPA trigger a sensitized biochemical and transcriptional response upon subsequent dopaminergic stimulation. Preliminary studies into the mechanisms underlying this cellular memory have indicated an important role for epigenetic change but many of the downstream mechanisms remain unknown. The family of bromodomain and extraterminal (BET) proteins, which bind acetylated histones, play a critical effector role in the regulation of transcription. BET proteins have been implicated in several forms of neural plasticity, but their potential relevance to LID remains unexplored. Using the 6-OHDA rodent model of LID, we show that dyskinesia development induces alterations in BET protein expression along with enhanced occupation of sites at the promoter and enhancer regions of genes dysregulated during dyskinesia development. When BET function was blocked using the pharmacologic inhibitor JQ1, LID was prevented. In addition, we found that JQ1 treatment blocked the transcriptional upregulation of several immediate-early genes known to participate in the pathogenesis of dyskinesia. Together, these results demonstrate an essential role for BET protein activity as an epigenetic "reader" of the altered histone acetylation required for LID development and suggest that modulation of BET protein function is a potential therapeutic avenue for the treatment prevention or reversal of LID in PD.

PMID: 28286180 [PubMed - as supplied by publisher]

The insect repellents: A silent environmental chemical toxicant to the health.

Environ Toxicol Pharmacol. 2017 Mar;50:91-102

Authors: Roy DN, Goswami R, Pal A

Abstract
In recent years, a large number of insect repellents have been developed with the idea of consumer benefits. In addition to already known advantageous application of insect repellents, there is increasing concern about the potential toxicity in environment leading to health caused by random use of these compounds. An increasing number of evidence suggests that insect repellents may trigger undesirable hazardous interactions with biological systems with a potential to generate harmful effects including intermediate metabolites. Biotransformation followed by bioaccumulation (vice e versa) may be an important phenomenon for toxic response of this chemicals. In this review, we have summarized the current state of knowledge on the insect repellent toxicity, including biochemical pathway alteration under in vitro and in vivo conditions considering different classes of organisms, from lower to higher vertebrate. Furthermore, we have tried to incorporate the effects of insect repellent in light of some clinical reports. We hope this review would provide useful information on potential side effects of uncontrolled use of insect repellents.

PMID: 28171823 [PubMed - indexed for MEDLINE]

Antimalarial activity of the terpene nerolidol.

Int J Antimicrob Agents. 2016 Dec;48(6):641-646

Authors: Saito AY, Marin Rodriguez AA, Menchaca Vega DS, Sussmann RA, Kimura EA, Katzin AM

Abstract
Malaria, an infectious disease that kills more than 438,000 people per year worldwide, is a major public health problem. The emergence of strains resistant to conventional therapeutic agents necessitates the discovery of new drugs. We previously demonstrated that various substances, including terpenes, have antimalarial activity in vitro and in vivo. Nerolidol is a sesquiterpene present as an essential oil in several plants that is used in scented products and has been approved by the US Food and Drug Administration as a food-flavouring agent. In this study, the antimalarial activity of nerolidol was investigated in a mouse model of malaria. Mice were infected with Plasmodium berghei ANKA and were treated with 1000 mg/kg/dose nerolidol in two doses delivered by the oral or inhalation route. In mice treated with nerolidol, parasitaemia was inhibited by >99% (oral) and >80% (inhalation) until 14 days after infection (P <0.0001). On Day 30 post-infection, the survival rate of orally treated mice was 90% compared with 16% in controls (P <0.0001). In contrast, inhalation-treated mice showed a survival rate of 50% vs. 42% in controls (P > 0.05). The toxicity of nerolidol administered by either route was not significant, whilst genotoxicity was observed only at the highest dose tested. These results indicate that combined use of nerolidol and other drugs targeting different points of the same isoprenoid pathway may be an effective treatment for malaria.

PMID: 27742206 [PubMed - indexed for MEDLINE]

Assessing Natural Product-Drug Interactions: An End-to-End Safety Framework.

Regul Toxicol Pharmacol. 2016 Apr;76:1-6

Authors: Roe AL, Paine MF, Gurley BJ, Brouwer KR, Jordan S, Griffiths JC

Abstract
The use of natural products (NPs), including herbal medicines and other dietary supplements, by North Americans continues to increase across all age groups. This population has access to conventional medications, with significant polypharmacy observed in older adults. Thus, the safety of the interactions between multi-ingredient NPs and drugs is a topic of paramount importance. Considerations such as history of safe use, literature data from animal toxicity and human clinical studies, and NP constituent characterization would provide guidance on whether to assess NP-drug interactions experimentally. The literature is replete with reports of various NP extracts and constituents as potent inhibitors of drug metabolizing enzymes, and transporters. However, without standard methods for NP characterization or in vitro testing, extrapolating these reports to clinically-relevant NP-drug interactions is difficult. This lack of a clear definition of risk precludes clinicians and consumers from making informed decisions about the safety of taking NPs with conventional medications. A framework is needed that describes an integrated robust approach for assessing NP-drug interactions; and, translation of the data into formulation alterations, dose adjustment, labelling, and/or post-marketing surveillance strategies. A session was held at the 41st Annual Summer Meeting of the Toxicology Forum in Colorado Springs, CO, to highlight the challenges and critical components that should be included in a framework approach.

PMID: 26776752 [PubMed - indexed for MEDLINE]

Adverse outcome pathways: From research to regulation scientific workshop report.

Regul Toxicol Pharmacol. 2016 Apr;76:39-50

Authors: Kleinstreuer NC, Sullivan K, Allen D, Edwards S, Mendrick DL, Embry M, Matheson J, Rowlands JC, Munn S, Maull E, Casey W

Abstract
An adverse outcome pathway (AOP) helps to organize existing knowledge on chemical mode of action, starting with a molecular initiating event such as receptor binding, continuing through key events, and ending with an adverse outcome such as reproductive impairment. AOPs can help identify knowledge gaps where more research is needed to understand the underlying mechanisms, aid in chemical hazard characterization, and guide the development of new testing approaches that use fewer or no animals. A September 2014 workshop in Bethesda, Maryland considered how the AOP concept could improve regulatory assessments of chemical toxicity. Scientists from 21 countries, representing industry, academia, regulatory agencies, and special interest groups, attended the workshop, titled Adverse Outcome Pathways: From Research to Regulation. Workshop plenary presentations were followed by breakout sessions that considered regulatory acceptance of AOPs and AOP-based tools, criteria for building confidence in an AOP for regulatory use, and requirements to build quantitative AOPs and AOP networks. Discussions during the closing session emphasized a need to increase transparent and inclusive collaboration, especially with disciplines outside of toxicology. Additionally, to increase impact, working groups should be established to systematically prioritize and develop AOPs. Multiple collaborative projects and follow-up activities resulted from the workshop.

PMID: 26774756 [PubMed - indexed for MEDLINE]

Defibrotide for Patients with Hepatic Veno-Occlusive Disease/Sinusoidal Obstruction Syndrome (VOD/SOS): Interim Results From a Treatment IND Study.

Biol Blood Marrow Transplant. 2017 Mar 08;:

Authors: Richardson PG, Smith AR, Triplett BM, Kernan NA, Grupp SA, Antin JH, Lehmann L, Shore T, Iacobelli M, Miloslavsky M, Hume R, Hannah AL, Nejadnik B, Soiffer RJ, Defibrotide Study Group

Abstract
Hepatic veno-occlusive disease, or sinusoidal obstruction syndrome (VOD/SOS), is a serious and potentially fatal complication of conditioning for hematopoietic stem cell transplantation (HSCT) or of chemotherapy regimens alone. Defibrotide is a complex mixture of single-stranded polydeoxyribonucleotides that is approved in the United States for treatment of hepatic VOD/SOS with renal or pulmonary dysfunction post-HSCT and in the European Union, Israel, and South Korea for treatment of severe hepatic VOD/SOS post-HSCT. Defibrotide was previously available in the United States as an investigational drug through a treatment protocol (treatment IND) study. Interim results of that large, treatment IND study of patients with VOD/SOS and with or without multi-organ dysfunction (MOD, also known as multi-organ failure) are presented here. Defibrotide was administered intravenously at 6.25 mg/kg every 6 hours (25 mg/kg/day), with a recommended treatment duration of at least 21 days. Enrolled patients (N=681) were diagnosed with VOD/SOS according to Baltimore or modified Seattle criteria or liver biopsy. For patients who had received HSCT (n=573), 50.3% (n=288; 95% confidence interval [CI], 46.2% to 54.4%) were alive at day +100 post-HSCT. Day +100 survival for the pediatric (≤16 years) and adult (>16 years) subgroups was 54.5% (n=174/319; 95% CI, 49.1% to 60.0%) and 44.9% (n=114/254; 95% CI, 38.8% to 51.0%), respectively. In the MOD subgroup (n=351), 45.3% (n=159; 95% CI, 40.1% to 50.5%) of patients were alive at day +100 post-HSCT. Treatment with defibrotide was generally well tolerated, and drug-related toxicities were consistent with prior studies. Adverse events were reported in 69.6% (399/573) of safety-evaluable patients. Other than VOD/SOS and associated MOD symptoms, the most commonly reported treatment-emergent adverse event was hypotension (13.8%). Day +100 survival results observed in this trial were consistent with results seen in previous trials of defibrotide for VOD/SOS in adult and pediatric patients. These data support the potential benefit of defibrotide in treating a VOD/SOS patient population that includes those with or without MOD.

PMID: 28285079 [PubMed - as supplied by publisher]

16 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

("drug-induced" OR "drug-related") AND ("adverse events" OR "side effects" OR "side-effects")

These pubmed results were generated on 2017/03/11

PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

Meta-analysis of pemetrexed plus carboplatin doublet safety profile in first-line nonsquamous non-small cell lung cancer studies.

Curr Med Res Opin. 2017 Feb 20;:1-11

Authors: Okamoto I, Schuette WH, Stinchcombe TE, Rodrigues-Pereira J, San Antonio B, Chen J, Liu J, John WJ, Zinner RG

Abstract
OBJECTIVES: This meta-analysis compared safety profiles (selected drug-related treatment-emergent adverse events [TEAEs]) of first-line pemetrexed plus carboplatin (PCb) area under the concentration-time curve 5 mg/min·mL (PCb5) or 6 mg/min·mL (PCb6), two widely used regimens in clinical practice for advanced nonsquamous non-small cell lung cancer.
METHODS: All patients received pemetrexed 500 mg/m(2) every 21 days with either of two carboplatin doses for up to 4 to 6 cycles. Safety profiles of PCb doses were compared using three statistical analysis methods: frequency table analysis (FTA), generalized linear mixed effect model (GLMM), and the propensity score method. Efficacy outcomes of PCb5 and PCb6 regimens were summarized.
RESULTS: A total of 486 patients mainly from the United States, Europe, and East Asia were included in the analysis; 22% (N = 105) received PCb5 in one trial and 78% (N = 381) received PCb6 in four trials. The FTA comparison demonstrated that PCb5 versus PCb6 was associated with a statistically significantly lower incidence of TEAEs, including all-grade thrombocytopenia, anemia, fatigue, and vomiting, and grade 3/4 thrombocytopenia. In the GLMM analysis, PCb5 patients were numerically less likely to experience all-grade and grade 3/4 neutropenia, anemia, and thrombocytopenia. The propensity score regression analysis showed PCb5 group patients were significantly less likely than PCb6 group patients to experience all-grade hematologic TEAEs and grade 3/4 thrombocytopenia and anemia. After applying propensity score 1:1 matching, FTA analysis showed that the PCb5 group had significantly less all-grade and grade 3/4 hematologic toxicities. Overall efficacy outcomes, including overall survival, progression-free survival, and response rate, were similar between the two carboplatin doses.
CONCLUSIONS: Acknowledging the limitations of this meta-analysis of five trials, heterogeneous in patient's characteristics and trial designs, our results show that the PCb5 regimen was generally associated with a better safety profile than PCb6 across three statistical approaches, with no apparent impact on survival outcomes.

PMID: 28277871 [PubMed - as supplied by publisher]

How I manage the toxicities of myeloma drugs.

Blood. 2017 Mar 08;:

Authors: Delforge M, Ludwig H

Abstract
The treatment of multiple myeloma is considered a continuously evolving paradigm as a result of the growing availability of new and highly effective drugs, including first-and second-generation proteasome inhibitors, immunomodulatory agents and monoclonal antibodies. Clinical trials advocate long-term rather than short-term treatment schedules with combinations of these new anti-myeloma drug classes. Although the overall toxicity profile of the recommended regimens can be considered favorable, their increasing complexity and prolonged use warrants a heightened vigilance for early and late side-effects, a priori because real-life patients can be more frail or present with one or more comorbidities. The treatment decision process -at diagnosis and at relapse- therefore requires myeloma physicians to carefully balance efficacy and toxicity profiles for each individual patient. Early and/or unneccesary tapering or treatment discontinuation for drug-related adverse events may not only reduce patients their quality of life, but can also negatively impact their outcome. Accurate knowledge in recognizing and managing the potential side-effects of present-day treatment regimens is therefore a cornerstone in myeloma care. Using 5 case vignettes, we discuss how to prevent and manage the most common non-hematological adverse events of anti-myeloma treatment regimens containing proteasome inhibitors, immunomodulatory drugs and monoclonal antibodies.

PMID: 28275090 [PubMed - as supplied by publisher]

Long-term safety and efficacy of combined tiotropium and olodaterol in Japanese patients with chronic obstructive pulmonary disease.

Respir Investig. 2017 Mar;55(2):121-129

Authors: Ichinose M, Kato M, Takizawa A, Sakamoto W, Grönke L, Tetzlaff K, Fukuchi Y

Abstract
BACKGROUND: The efficacy and safety of once-daily tiotropium+olodaterol (T+O) (2.5/5µg or 5/5µg) for treating chronic obstructive pulmonary disease (COPD) have been demonstrated in the large, multinational, randomized, Phase III studies TONADO(®) 1 and 2, which included 413 Japanese patients (~80 in each group). This study was conducted to supplement the TONADO(®) study data to assess long-term safety in ≥100 Japanese patients treated for 1 year in compliance with International Conference on Harmonisation guidelines. Efficacy was evaluated descriptively as a secondary end point.
METHODS: Patients were randomized to 52 weeks of double-blind treatment with once-daily T+O (2.5/5 or 5/5µg) or O (5µg) monotherapy via the Respimat(®) inhaler. We report the safety and efficacy data descriptively.
RESULTS: The incidence of adverse events (AEs) was comparable in the T+O 2.5/5µg (75.0%), T+O 5/5µg (85.4%), and O 5µg (80.5%) groups, with drug-related AEs being reported in 5.0%, 7.3%, and 4.9% of patients, respectively. Serious AEs were reported in 14 patients (11.5%). The change from baseline in forced expiratory volume in 1s (FEV1) area under the curve from 0 to 3h and trough FEV1 were numerically higher in the T+O treatment groups than in the O monotherapy group throughout the study period. Overall safety of T+O was comparable to that in the TONADO(®) studies.
CONCLUSIONS: No safety concerns for long-term T+O treatment were identified in Japanese patients with COPD. A numerical improvement in lung function was observed with T+O treatment compared to O monotherapy.

PMID: 28274527 [PubMed - in process]

Liver Effects of Clinical Drugs Differentiated in Human Liver Slices.

Int J Mol Sci. 2017 Mar 07;18(3):

Authors: Vickers AE, Ulyanov AV, Fisher RL

Abstract
Drugs with clinical adverse effects are compared in an ex vivo 3-dimensional multi-cellular human liver slice model. Functional markers of oxidative stress and mitochondrial function, glutathione GSH and ATP levels, were affected by acetaminophen (APAP, 1 mM), diclofenac (DCF, 1 mM) and etomoxir (ETM, 100 μM). Drugs targeting mitochondria more than GSH were dantrolene (DTL, 10 μM) and cyclosporin A (CSA, 10 μM), while GSH was affected more than ATP by methimazole (MMI, 500 μM), terbinafine (TBF, 100 μM), and carbamazepine (CBZ 100 μM). Oxidative stress genes were affected by TBF (18%), CBZ, APAP, and ETM (12%-11%), and mitochondrial genes were altered by CBZ, APAP, MMI, and ETM (8%-6%). Apoptosis genes were affected by DCF (14%), while apoptosis plus necrosis were altered by APAP and ETM (15%). Activation of oxidative stress, mitochondrial energy, heat shock, ER stress, apoptosis, necrosis, DNA damage, immune and inflammation genes ranked CSA (75%), ETM (66%), DCF, TBF, MMI (61%-60%), APAP, CBZ (57%-56%), and DTL (48%). Gene changes in fatty acid metabolism, cholestasis, immune and inflammation were affected by DTL (51%), CBZ and ETM (44%-43%), APAP and DCF (40%-38%), MMI, TBF and CSA (37%-35%). This model advances multiple dosing in a human ex vivo model, plus functional markers and gene profile markers of drug induced human liver side-effects.

PMID: 28272341 [PubMed - in process]

Sarcoidosis associated with infliximab therapy in ulcerative colitis: A case report.

Medicine (Baltimore). 2017 Mar;96(10):e6156

Authors: Gîlcă GE, Diaconescu S, Bălan GG, Timofte O, Ştefănescu G

Abstract
RATIONALE: Although immunomodulatory therapy has been clearly stated as an important landmark in treatment of ulcerative colitis, significantly improving the quality of life for patients with inflammatory bowel disease, there are several aspects to be considered regarding the possible side-effects of anti-TNF alpha agents. In spite of a good safety profile, biologic TNF antagonists may induce paradoxical inflammation, which can manifest as sarcoid-like granulomatosis, consisting of noncaseating granulomas in the affected organs.
PATIENT CONCERNS: We report the case of a 30-year-old male patient, with no personal or familial history of lung disease, with a personal history of ulcerative colitis (UC), under clinical remission following infliximab therapy in maintenance dose, who was admitted for treatment administration, but also for dyspnea, nocturnal sweating, and nonproductive cough.
DIAGNOSES: Based on clinical manifestations, biological landmarks excluding various infections, CT scan, fibrobronchoscopy with bronchoalveolar lavage for culture and immunohistochemical examination, followed by mediastinoscopy with sampling of paratracheal lymph node, which underwent histopathological examination, the patient was diagnosed with drug- induced stage II pulmonary sarcoidosis.
INTERVENTIONS: Since the patient had developed severe allergic reaction after being administered Infliximab at admission, the biological treatment was immediately discontinued. Following the diagnosis of pulmonary sarcoidosis, corticotherapy was initiated.
PATIENT OUTCOMES: After corticotherapy was initiated, the patient had a favorable outcome at 3 months reevaluation, both regarding the course of ulcerative colitis and sarcoidosis.
LESSONS: Patients under biological therapy using anti-TNF alpha agents must be carefully monitored, in order to early identify potential paradoxical inflammation (such as sarcoidosis) as a side-effect. The drug-related pulmonary disease tends to improve upon withdrawal of the drug, with occasional requirement of steroid treatment. However, a thorough strategy should be assembled in the case of UC relapse in this patient category, with switching to adalimumab or surgical approach as main possibilities.

PMID: 28272203 [PubMed - in process]

[A 20-year-old woman with ulcerative colitis and acute liver failure].

Internist (Berl). 2017 Mar 07;:

Authors: Forker R, Escher M, Stange EF

Abstract
A 20-year-old woman presented with acute exacerbation of ulcerative colitis. After treatment with infliximab, she developed a fulminant liver failure. Under supportive therapy and steroid medication, recovery of symptoms and transaminases occurred. A few case reports about hepatic side effects of anti-TNF-α antibodies in patients with inflammatory bowel disease have been published. These side effects ranged from asymptomatic increase of transaminases to fulminant liver failure necessitating transplantation. The pathomechanism is not fully understood; in some case reports autoimmune phenomena have been described.

PMID: 28271269 [PubMed - as supplied by publisher]

Cytokine biomarkers to predict antitumor responses to nivolumab suggested in a phase II study for advanced melanoma.

Cancer Sci. 2017 Mar 07;:

Authors: Yamazaki N, Kiyohara Y, Uhara H, Iizuka H, Uehara J, Otsuka F, Fujisawa Y, Takenouchi T, Isei T, Iwatsuki K, Uchi H, Ihn H, Minami H, Tahara H

Abstract
Promising anti-tumor activities of nivolumab, a fully humanized IgG4 inhibitor antibody against the programmed death-1 protein, were suggested in previous phase 1 studies. The present phase 2, single-arm study (JAPIC-CTI #111681) evaluated the anti-tumor activities of nivolumab and explored its predictive correlates in advanced melanoma patients at 11 sites in Japan. Intravenous nivolumab 2 mg/kg was given repeatedly at 3-week intervals to 35 of 37 patients enrolled from December 2011 to May 2012 until they experienced unacceptable toxicity, disease progression, or complete response. The primary endpoint was objective response rate. Serum levels of immune modulators were assessed at multiple time points. As of 21 October 2014, the median response duration, median progression-free survival, and median overall survival were 463 days, 169 days, and 18.0 months, respectively. The overall response rate and 1- and 2-year survival rates were 28.6%, 54.3%, and 42.9%, respectively. Thirteen patients remained alive at the end of the observation period and no deaths were drug related. Grade 3-4 drug-related adverse events were observed in 31.4% of patients. Pre-treatment serum interferon-γ, and interleukin-6 and -10 levels were significantly higher in the patients with objective tumor responses than in those with tumor progression. In conclusion, repeated intravenous administration of nivolumab had potent and durable anti-tumor effects and a manageable safety profile in advanced melanoma patients, strongly suggesting the usefulness of nivolumab for advanced melanoma and the usefulness of pre-treatment serum cytokine profiles as correlates for predicting treatment efficacy. This article is protected by copyright. All rights reserved.

PMID: 28266140 [PubMed - as supplied by publisher]

Efficacy and safety of morinidazole in pelvic inflammatory disease: results of a multicenter, double-blind, randomized trial.

Eur J Clin Microbiol Infect Dis. 2017 Mar 06;:

Authors: Cao C, Luo A, Wu P, Weng D, Zheng H, Wang S

Abstract
This multicenter, double-blind, randomized, parallel-group, non-inferiority study compared the efficacy and safety of morinidazole with those of ornidazole in women with pelvic inflammatory disease. Women from 18 hospitals in China received a 14-day course of either intravenous morinidazole, 500 mg twice daily (n = 168), or intravenous ornidazole, 500 mg twice daily (n = 170). A total of 312 of 338 patients in the full analysis set (FAS) (92.3%) were included in the per protocol set (PPS) analyses, 61 (19.6%) of whom were included in the microbiologically valid (MBV) population. The clinical resolution rates in the PPS population at the test of cure (TOC, primary efficacy end point, 7-30 days post-therapy) visit were 96.86% (154/159) for morinidazole and 96.73% (148/153) for ornidazole (95% CI: -3.79% to 4.03%). The bacteriological success rates in the MBV population at the TOC visit were 100% (32/32) for morinidazole and 89.66% (26/29) for ornidazole (95% CI: -16.15% to 11.21%). Drug-related adverse events occurred less frequently with morinidazole (32.74%, 55/168) than with ornidazole (47.06%, 80/170) (p < 0.01). For women with pelvic inflammatory disease, twice-daily morinidazole for 14 days was clinically and bacteriologically as efficacious as twice-daily ornidazole for 14 days, while the former was associated with fewer drug-related adverse events than the latter.

PMID: 28265816 [PubMed - as supplied by publisher]

Interventional Analgesic Management of Lung Cancer Pain.

Front Oncol. 2017;7:17

Authors: Hochberg U, Elgueta MF, Perez J

Abstract
Lung cancer is one of the four most prevalent cancers worldwide. Comprehensive patient care includes not only adherence to clinical guidelines to control and when possible cure the disease but also appropriate symptom control. Pain is one of the most prevalent symptoms in patients diagnosed with lung cancer; it can arise from local invasion of chest structures or metastatic disease invading bones, nerves, or other anatomical structures potentially painful. Pain can also be a consequence of therapeutic approaches like surgery, chemotherapy, or radiotherapy. Conventional medical management of cancer pain includes prescription of opioids and coadjuvants at doses sufficient to control the symptoms without causing severe drug effects. When an adequate pharmacological medical management fails to provide satisfactory analgesia or when it causes limiting side effects, interventional cancer pain techniques may be considered. Interventional pain management is devoted to the use of invasive techniques such as joint injections, nerve blocks and/or neurolysis, neuromodulation, and cement augmentation techniques to provide diagnosis and treatment of pain syndromes resistant to conventional medical management. Advantages of interventional approaches include better analgesic outcomes without experiencing drug-related side effects and potential for opioid reduction thus avoiding central side effects. This review will describe various pain syndromes frequently described in lung cancer patients and those interventional techniques potentially indicated for those cases.

PMID: 28261561 [PubMed - in process]

A case-based discussion of clinical problems in the management of patients treated with ruxolitinib for myelofibrosis.

Intern Med J. 2017 Mar;47(3):262-268

Authors: Ho PJ, Bajel A, Burbury K, Dunlop L, Durrant S, Forsyth C, Perkins AC, Ross DM

Abstract
Ruxolitinib is a dual janus kinase 1 (JAK1)/JAK2 inhibitor used to treat splenomegaly and symptoms associated with myelofibrosis (MF). Current therapeutic options for symptomatic MF include supportive care, myelosuppressive therapy (such as hydroxycarbamide) and janus kinase (JAK) inhibitors (in particular ruxolitinib). Allogeneic stem cell transplantation remains the only potentially curative treatment for MF, and younger transplant-eligible patients should still be considered for allogeneic stem cell transplantation; however, this is applicable only to a small proportion of patients. There is now increasing and extensive experience of the efficacy and safety of ruxolitinib in MF, both in clinical trials and in 'real-world' practice. The drug has been shown to be of benefit in intermediate-1 risk patients with symptomatic splenomegaly or other MF-related symptoms, and higher risk disease. Optimal use of the drug is required to maximise clinical benefit, requiring an understanding of the balance between dose-dependent responses and dose-limiting toxicities. There is also increasing experience in the use of ruxolitinib in the pre-transplantation setting. This paper aims to utilise several 'real-life' cases to illustrate several strategies that may help to optimise clinical practice.

PMID: 28260257 [PubMed - in process]

Protein Kinase CK2: Intricate Relationships within Regulatory Cellular Networks.

Pharmaceuticals (Basel). 2017 Mar 05;10(1):

Authors: Nuñez de Villavicencio-Diaz T, Rabalski AJ, Litchfield DW

Abstract
Protein kinase CK2 is a small family of protein kinases that has been implicated in an expanding array of biological processes. While it is widely accepted that CK2 is a regulatory participant in a multitude of fundamental cellular processes, CK2 is often considered to be a constitutively active enzyme which raises questions about how it can be a regulatory participant in intricately controlled cellular processes. To resolve this apparent paradox, we have performed a systematic analysis of the published literature using text mining as well as mining of proteomic databases together with computational assembly of networks that involve CK2. These analyses reinforce the notion that CK2 is involved in a broad variety of biological processes and also reveal an extensive interplay between CK2 phosphorylation and other post-translational modifications. The interplay between CK2 and other post-translational modifications suggests that CK2 does have intricate roles in orchestrating cellular events. In this respect, phosphorylation of specific substrates by CK2 could be regulated by other post-translational modifications and CK2 could also have roles in modulating other post-translational modifications. Collectively, these observations suggest that the actions of CK2 are precisely coordinated with other constituents of regulatory cellular networks.

PMID: 28273877 [PubMed - in process]

Drug target identification using network analysis: Taking active components in Sini decoction as an example.

Sci Rep. 2016 Apr 20;6:24245

Authors: Chen S, Jiang H, Cao Y, Wang Y, Hu Z, Zhu Z, Chai Y

Abstract
Identifying the molecular targets for the beneficial effects of active small-molecule compounds simultaneously is an important and currently unmet challenge. In this study, we firstly proposed network analysis by integrating data from network pharmacology and metabolomics to identify targets of active components in sini decoction (SND) simultaneously against heart failure. To begin with, 48 potential active components in SND against heart failure were predicted by serum pharmacochemistry, text mining and similarity match. Then, we employed network pharmacology including text mining and molecular docking to identify the potential targets of these components. The key enriched processes, pathways and related diseases of these target proteins were analyzed by STRING database. At last, network analysis was conducted to identify most possible targets of components in SND. Among the 25 targets predicted by network analysis, tumor necrosis factor α (TNF-α) was firstly experimentally validated in molecular and cellular level. Results indicated that hypaconitine, mesaconitine, higenamine and quercetin in SND can directly bind to TNF-α, reduce the TNF-α-mediated cytotoxicity on L929 cells and exert anti-myocardial cell apoptosis effects. We envisage that network analysis will also be useful in target identification of a bioactive compound.

PMID: 27095146 [PubMed - indexed for MEDLINE]