APN/CD13 inhibitor Ubenimex: A molecular chaperone of antineoplastic chemotherapeutic drugs / 中国药理学通报

Cytotoxic anti-neoplastic drugs are a kind of chemotherapeutic drugs that directly kill or inhibit the growth and proliferation of tumor cells, and it is one of the main drugs for the treatment of malignant tumors. These drugs may have toxic side effects on normal cells of human body (especially those with strong division and proliferation) when they are used to kill tumor cells. And patients may usually have adverse reactions even at a normal dose when using this kind of drugs. Due to the strong toxic side effects of cytotoxic chemotherapeutic drugs, their clinical application is limited. In recent years it has been found that aminopeptidase N inhibitor Ubenimex has a significant synergistic effect with anti-neoplastic chemotherapeutic drugs, which has the advantages of enhancing the therapeutic effect of drugs and reducing the toxic side effects of chemotherapeutic drugs. This review enumerates that the combination of Ubenimex and a variety of cytotoxic drugs can enhance the anti-tumor effect of cytotoxic drugs and reduce the occurrence of adverse reactions. In addition, the mechanism of combined use of Ubenimex in reversing drug resistance is also introduced. At the same time, is is further confirmed the clinical value of Ubenimex as an effective adjuvant in the treatment of malignant tumors, so as to provide a basis for clinical application.

Knowledge and associated factors towards cytotoxic drug handling among University of Gondar Comprehensive Specialized Hospital health professionals, institutional-based cross-sectional study

BACKGROUND@#Currently, cancer is among the leading causes of morbidity and mortality in the world. Exposure to CDs may occur during drug preparation and mixing, during drug administration, during transport, and cleaning spills and waste disposal. Healthcare workers who prepare or administer antineoplastic drugs, or who work in areas where these drugs are used, can be exposed to these agents. This also affects the public around the exposed area if appropriate disposal system is not known. Several studies reported increased risks of leukemia and breast cancer among nurses handling CDs and not following safety guidelines. Because of the absence of studies in Ethiopia, the current study was conducted to determine the knowledge level of cytotoxic drug handling and associated factors among health professionals in the University of Gondar Comprehensive Specialized Hospital.@*METHODS@#The institutional-based cross-sectional study was conducted from June to August 2019. Epi info 7.1 was used for data entry and then exported into SPSS version 20 for computing, recording, and statistical analysis. Logistic regression was used to explain the relationship with independent variables.@*RESULTS@#Four hundred and twelve health professionals participated in the study with 53.4% males. The participants' mean age was 29.9 (± 5.43) years ranging from 20-60. Two hundred and twenty-three (54.1%) health professionals heard about cytotoxic drugs, and 52.7% (95% UI 47.8-57.8%) had good knowledge of cytotoxic drug handling. Being male sex (AOR = 1.84, 95% CI (1.13-3.00)), age of 29-31 (AOR = 1.99, 95% CI (1.03-3.84)), hearing information about cytotoxic drug handling (AOR = 2.53, 95% CI (1.43-4.47)), ever attended training on cytotoxic drug handling (AOR = 3.15, 95% CI (1.13-8.79)), ever taking courses related to cytotoxic drugs (AOR = 2.03, 95% CI (1.15-3.59)), and good practice (AOR = 3.24, 95% CI (1.95-5.37)) were significantly associated with knowledge towards cytotoxic drug handling. It is therefore imperative to train health professionals and to incorporate CDs handling related course contents while revising curricula to raise the knowledge of health professionals about proper cytotoxic drug handling.@*CONCLUSION@#Above half of the study participants scored higher than the median of the cytotoxic drug handling knowledge questions. Sex, age, information about cytotoxic drug handling, training, taking courses related to cytotoxic drugs, and good practice were significantly associated with knowledge towards cytotoxic drugs handling.

Improve the effect of nurses on the occupational protection of cytotoxic drugs / 中华劳动卫生职业病杂志

Objective@#Evaluation of improving the occupational protective effect of nurses in cytotoxic drugs.@*Methods@#The occupational hazards of cytotoxic drugs in Qingdao Central hospital were taken as samples. Compare the occupational hazards of cytotoxic drugs before and after improvement.@*Results@#From Sept.2017 to Aug.2018, the number of occupational hazards of cytotoxic drugs decreased by 90.38%; Sharp injuries, drug spillovers, distribution errors and excessive air diffusivity were decreased by 70%~100%.@*Conclusion@#Targeted occupational protection can significantly reduce the hazards of cytotoxic drugs and ensure the health of the medicinal staff.

Duxorubicin-induced cardiotoxicity.

The survival rate of cancer patients has greatly increased over the last 20 years. However, to achieve this result, a considerable price has been paid in terms of the side-effects associated with the intensive anticancer treatment. Cardiotoxicity of anticancer drugs is a serious problem. It is defined, by the National Cancer Institute, as the “toxicity that affects the heart.” This definition not only includes a direct effect of the drug on the heart, but also an indirect effect due to enhancement of hemodynamic flow alterations or due to thrombotic events. Cardiotoxicity can develop in a subacute, acute, or chronic manner. The risk for such effects depends upon: cumulative dose, rate of drug administration, mediastinal radiation, advanced age, younger age, female gender, pre-existing heart disease and hypertension. Anthracyclines, such as doxorubicin (DOX), cause serious cardiac side-effects. Acute tachyarrhythmias and acute heart failure (HF) may occur after high doses, but these reactions are now rare due to changed dosage schemes (e.g. slower infusion) with the aim to prevent this. However, the sub-acute or chronic cardiac effects of anthracyclines remain a clinical problem. Clinically, anthracycline induced cardiotoxicity manifests itself as left ventricular failure, which develops insidiously over months to years after completion of the anthracycline based chemotherapy and may result in congestive HF. The mechanism of anthracyclin induced cardiotoxicity is not totally unraveled. It is likely that the decline in myocardial function is related to apoptosis of cardiac myocytes that occurs apparently at random in the myocardium. Anthracyclin induced formation of reactive oxygen species (ROS) in the presence of intracellular iron, impaired homeostasis of intracellular iron and calcium (that may facilitate the apoptosis induced by the ROS) have been put forward as mechanisms. Cardiac protection can be achieved by limitation of the cumulative dose. Further, addition of the antioxidant and iron chelator dexrazoxane to anthracycline therapy has shown to be effective in lowering the incidence of anthracycline induced cardiotoxicity.

The Role of Pharmacoethnicity in the Development of Cytotoxic and Molecular Targeted Drugs in Oncology

The effective and toxic ranges of anticancer drugs are very narrow and, in some cases, inverted. Thus determination of the most appropriate dosage and schedule of administration is crucial for optimal chemotherapy. In common arm trials conducted in Japan and by Southwest Oncology Group (SWOG) that used the same doses and schedules for the administration of carboplatin plus paclitaxel, the frequency of hematological toxicity was significantly higher in the Japanese trials than in the SWOG trial, despite demonstrating similar response rates. The frequency of epidermal growth factor receptor (EGFR) mutations in tumors was significantly higher among East Asian populations, and these populations are also reported to demonstrate a higher response rates to epidermal growth factor receptor tyrosine-kinase inhibitors (EGFR-TKIs). The prevalence of interstitial lung disease induced by treatment with EGFR-TKIs has been shown to be quite high in the Japanese population. Clinical trials of cetuximab against non-small cell lung cancer and of bevacizumab against stomach cancer have shown that these agents are only active in Caucasians. In a trial examining the use of sorafenib after transarterial chemoembolization in Korean and Japanese patients with advanced hepatocellular carcinoma, the compliance and dose intensity of the drug were quite low compared with other trials. Although not only identified pharmacogenomics differences but also differences in social environment, and regional medical care, including pharmacoeconomics strongly influence ethnic differences in treatment response, further identification and understanding of the pharmacogenomics underlying ethnic differences will be essential to timely and reliable global development of new anticancer drugs.

Nefropatía por Inmunoglobulina A: Guía de práctica clínica / Immunoglobulin A nephropathy: Clinical Practice Guidelines

La nefropatía por Inmunoglobulina A (N.IgA) es la causa más frecuente de enfermedad glomerular a nivel mundial, 15-50% de los pacientes presentan pérdida progresiva de la función renal en 10-20 años; el resto remisión clínica o hematuria/ proteinuria persistente. Su tratamiento óptimo es incierto. Nuestro objetivo fue desarrollar recomendaciones basadas en la evidencia a través de búsqueda en bases de datos Medline, Embase, Lilacs, Cochrane Trials Register. Los investigadores analizaron la calidad de los estudios independientemente, usando la Cochrane Renal Group checklist: aleatorización, carácter ciego, intención de tratar y pérdidas en el seguimiento. La evidencia se clasificó en niveles y la recomendación en grados, según el Centre for Evidence-Based Medicine, Oxford, con dos enfoques principales: Terapia inmunosupresora (corticoides, citostáticos, ciclosporina A y micofenolato mofetilo): Nivel I a, grado A. Terapia combinada con inmunosupresores en adultos: Nivel II b, grado B. Corticoides más ciclofosfamida o azatioprina en niños: Nivel II b, grado C. Ciclosporina y micofenolato-mofetilo: Nivel II b, grado B. Terapia no inmunosupresora: inhibidores del sistema renina-angiotensina (IEAC) y/o bloqueantes del receptor de angiotensina II (BRAII), aceite de pescado, estatinas, antiplaquetarios y tonsilectomía: Nivel I a, grado A. Niños: IECA y BRAII con monitoreo de función renal y de nivel sérico de potasio: Nivel I b, grado B. En nefropatía progresiva, antiplaquetarios como tratamiento coadyuvante: Nivel I, grado C. Aceite de pescado como soporte adicionado de BRAII e IECA en pacientes con lesiones histológicas leves y baja reducción de la filtración glomerular: Nivel II b, grado B (no en niños). No hay evidencias para recomendar estatinas en niños; en mayores de 5 años con síndrome nefrótico e hipercolesterolemia usar sólo con monitoreo de fosfocreatin-kinasa sérica. No hay evidencias para recomendar la tonsilectomía.

Immunoglobulin A nephropathy (N.IgA) is the world most common glomerular disease; 15-50% of patients develop loss of renal function in 10-20 years, and the rest remission or mild proteinuria/ hematuria. The optimal treatment is uncertain. Our aim was to develop evidence-based recommendations through research in Medline, Embasse, Lilacs and Cochrane Central Register of Controlled Trials. The study-quality was independently assessed by the reviewers following the Cochrane Renal Group checklist: randomization, blinding, intention-to-treat analysis and follow-up period. Levels of evidence and grades of recommendation were assigned according to Center for Evidence-Based Medicine, Oxford. Two approaches were considered: Immunosuppressive therapy (corticosteroids, cytostatics, cyclosporine A, mycophenolate-mofetil): Level I a, grade A. -Combined suppressive therapy in adults. Corticosteroids plus cytotoxics drugs (cyclophosphamide/azathioprine): Level II b, grade B. In children with severe IgA nephropathy: Level II b, grade D. Cyclosporine and mycophenolate- mophetil: Level II b, grade C. Cyclosporine and mycophenolate-mophetil: Level ll b, grade C. -Non immunosuppressive therapy: reninangiotensin converting enzyme inhibitors (ACEI) and/or angiotensin II receptor blockers (ARB), fish oil, statins, antiplatelets and tonsillectomy. ACEI and/or ARB, in patients with proteinuria =1 g: Level I a, grade A. In children with moderate proteinuria: ACEI and/or ARB with close monitoring of renal function and serum potassium level: Level II b, grade B. Antiplatelet as supportive treatment: Level I a, grade C. Fish oil in addition to ACEI or ARB in patients with mild histological lesions: Level II b, grade B (Not in children). Statins: no evidence to recommend these drugs in children. In patients > 5 years with nephrotic syndrome and hyper-cholesterolemia, use statins with close monitoring of serum creatine-kinase. There is no evidence to recommend tonsillectomy.

Systemic Cytotoxic Drugs Depletes Epidermal Langerhans Cells in Guinea Pigs

No abstract available.