Glucocorticoids
Cancer Biol Ther. 2007 Feb;6(2):278-87. Epub 2007 Feb 27. Clinical and mechanistic aspects of glucocorticoid-induced chemotherapy resistance in the majority of solid tumors. Zhang C, Wenger T, Mattern J, Ilea S, Frey C, Gutwein P, Altevogt P, Bodenmüller W, Gassler N, Schnabel PA, Dienemann H, Marmé A, Hohenfellner M, Haferkamp A, Pfitzenmaier J, Gröne HJ, Kolb A, Büchler P, Büchler M, Friess H, Rittgen W, Edler L, Debatin KM, Krammer PH, Rutz HP, Herr I. Research Group Molecular OncoSurgery, University of Heidelberg, Im Neuenheimer Feld 365, Heidelberg 69120, Germany. BACKGROUND: Glucocorticoids have been used widely in conjunction with cancer therapy due to their ability to induce apoptosis in hematological cells and to prevent nausea and emesis. However, recent data including ours, suggest induction of therapy-resistance by glucocorticoids in solid tumors, although it is unclear whether this happens only in few carcinomas or is a more common cell type specific phenomenon. MATERIAL AND METHODS: We performed an overall statistical analysis of our new and recent data with 157 tumor probes evaluated in vitro, ex vivo and in vivo. The effect of glucocorticoids on apoptosis, viability and cell cycle progression under diverse clinically important questions was examined. RESULTS: New in vivo results demonstrate glucocorticoid-induced chemotherapy resistance in xenografted prostate cancer. In an overall statistical analysis we found glucocorticoid-induced resistance in 89% of 157 analysed tumor samples. Resistance is common for several cytotoxic treatments and for several glucocorticoid-derivatives and due to an inhibition of apoptosis, promotion of viability and cell cycle progression. Resistance occurred at clinically achievable peak plasma levels of patients under anti-emetic glucocorticoid therapy and below, lasted for a long time, after one single dose, but was reversible upon removal of glucocorticoids. Two nonsteroidal alternative anti-emetic agents did not counteract anticancer treatment and may be sufficient to replace glucocorticoids in cotreatment of carcinoma patients. CONCLUSION: These data demonstrate the need for prospective clinical studies as well as for detailed mechanistic studies of GC-induced cell-type specific pro- and anti-apoptotic signalling. PMID: 17224649 [PubMed - indexed for MEDLINE] 10 page PDF of full text: http://www.landesbioscience.com/jour.../article/3652/ Excerpts: Quote:
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Cell cycle arrest by glucocorticoids may protect normal tissue and solid tumors from cancer therapy. Mattern J, Büchler MW, Herr I. Molecular OncoSurgery, Department of Surgery, University and German Cancer Research Center (DKFZ), Heidelberg, Germany. Glucocorticoids have been widely used as cotreatment for patients with cancer due to potent pro-apoptotic properties in lymphoid cells, reduction of nausea and diminishing acute toxicity on normal tissue. There are now data from preclinical and, to some extent, clinical studies, demonstrating that these medicaments are highly suspicious to induce therapy resistance in the majority of malignant solid tumors-irrespective of tumor origin and the nature of specific anticancer drugs or irradiation used for treatment. Despite these huge amounts of data, the underlying mechanisms of cell type-specific signaling by these steroid hormones are just beginning to be described. This review summarizes our present understanding of a relationship between glucocorticoid-induced reversible cell cycle arrest and therapy resistance in solid tumors. We give a summary of our current knowledge of decreased proliferation rates in response to glucocorticoid pre and combination treatment which are suspicious to be involved not only in protection of normal tissues, but also in protection of solid tumors from cytotoxic effects of anticancer agents. The inhibition of cell cycle progression by pretreatment with GCs may be crucially involved in switching the balance of several interacting pathways to survival upon treatment with GCs. PMID: 18087223 [PubMed - indexed for MEDLINE] PDF of full text available: http://www.landesbioscience.com/jour.../article/4765/ excerpts: Quote:
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2009 Oct 28. [Epub ahead of print] Estrogen Receptor, Progesterone Receptor, and Glucocorticoid Receptor Expression in Normal Breast Tissue, Breast In Situ Carcinoma, and Invasive Breast Cancer. Buxant F, Engohan-Aloghe C, Noël JC. *Gynecology daggerPathology, Erasme Hospital, Free University of Brussels (ULB), Belgium. Glucocorticoids (GCs) are used in cancer treatment to induce programmed cell death in transformed cells of the hematopoietic system and to lessen side effects. Moreover, GCs have been described not only as inhibitors of some chemotherapy or radiation-induced apoptosis, but also as inhibitors of cancer progression by down-regulation or up-regulation of different gene expressions. Recently, it has been suggested that GCs can attenuate estrogen responses through induction of expression and activity of the sulfotransferase. The presence or absence of glucocorticoid receptor (GR) in normal and abnormal breast tissue is thus interesting, and the aim of this study was to analyze the expression of GR during the progression of breast tissue. We tested by immunohistochemistry the expression status of estrogen receptor (ER), progesterone receptor (PR), and GR in normal breast parenchyma (n=49), ductal intraepithelial neoplasia (DIN) 1a (n=9), DIN 1b-1c (n=15), DIN 2-3 (n=21), and invasive breast carcinoma (n=39). The evaluation of GR expression was made by using the Allred score. All the normal parenchyma, DIN 1a, DIN 1b, and DIN 1c were ER-positive (ER) and PR-positive (PR). Seventeen of 21 DIN 2-3 and 30 of 39 invasive carcinomas were ER/PR. The other samples were ER-negative (ER) and PR-negative (PR). Moreover, all the ER/PR samples were GR-negative. Interestingly, we found a significant correlation between the histologic grade and the GR-negative tumors, and a percentage of positive patients presented with nuclear immunoreaction to GR, which decreases significantly with tumor histologic grade. Understanding the role of GCs in breast carcinoma is thus essential before continuing the widespread use of GCs combined with antineoplastic drugs or agents in the clinical management of women with breast cancer. PMID: 19875955 [PubMed - as supplied by publisher] |
Re: Glucocorticoids
Endocr Relat Cancer. 2009 Sep 23. [Epub ahead of print]
Dexamethasone enhances cell resistance to chemotherapy through increasing adhesion to extracellular matrix in human ovarian cancer cells. Chen YX, Wang Y, Fu CC, Diao F, Song LN, Li ZB, Yang R, Lu J. Y Chen, Department of Pathophysiology, the Second Military Medical University, Shanghai, China. Glucocorticoids (GCs) are widely used as co-medication in therapy of solid malignant tumors to relieve some of the side effects of chemotherapy drugs. However, recent studies have shown that GCs could render cancer cells more resistant to cytotoxic drug-induced apoptosis, but the mechanism is largely unknown. In the present study, we found that the treatment of human ovarian cancer cell lines HO-8910 and SKOV3 with synthetic GCs Dexamethasone (Dex) significantly increased their adhesion to extracellular matrix (ECM) and their resistance to apoptosis induced by cytotoxic drugs cisplatin and paclitaxel. Dex also increased the protein levels of adhesion molecules integrin beta1, alpha4 and alphaV in HO-8910 cells. The neutralizing antibody against integrin beta1 prevented Dex-induced adhesion and significantly abrogated the protective effect of Dex toward cytotoxic agents. We further found that TGF-beta1 alone not only increased cell adhesion and cell survival of HO-8910 cells in the presence of cisplatin, but also has synergistic pro-adhesion and pro-survival effects with Dex. Moreover, TGF-beta1 neutralizing antibody that could block TGF-beta1-induced cell adhesion and apoptosis resistance markedly abrogated the synergistic pro-adhesion and pro-survival effects of Dex and TGF-beta1. Finally, we further demonstrated that Dex could up-regulate the expression of TGF-beta receptor type II (TbetaRII) and enhance the responsiveness of cells to TGF-beta1. In conclusion, our results indicate that increased adhesion to ECM through enhancing integrin beta1 signaling and TGF-beta1 signaling plays an important role in chemoresistance induced by GCs in ovarian cancer cells. PMID: 19776289 [PubMed - as supplied by publisher] Int J Oncol. 2006 Feb;28(2):551-8. Glucocorticoid-mediated inhibition of chemotherapy in ovarian carcinomas. Zhang C, Marmé A, Wenger T, Gutwein P, Edler L, Rittgen W, Debatin KM, Altevogt P, Mattern J, Herr I. Molecular Urooncology, German Cancer Research Center, Heidelberg, Germany. The glucocorticoid dexamethasone is frequently used as a co-treatment in cytotoxic cancer therapy, e.g. to prevent nausea, to protect normal tissue or for other reasons. While the potent pro-apoptotic properties and supportive effects of glucocorticoids to tumour therapy in lymphoid cells are well studied, the impact on the cytotoxic treatment of ovarian carcinoma is unknown. We tested apoptosis-induction, viability, tumour growth and protein expression using established cell lines, primary cell lines freshly isolated from patient material and a xenograft on nude mice. We found a general induction of resistance toward cytotoxic therapy by DEX-co-treatment in most of the examined ovarian cancer cells treated in vitro, ex vivo or in vivo. Resistance occurred independently of cell density and was found at peak plasma levels of dexamethasone and below. Mechanistically, the dexamethasone-induced expression of survival genes may be involved in the resistance. These data show that glucocorticoid-induced resistance is common in ovarian carcinomas implicating that the use of glucocorticoids may be harmful for cancer patients. PMID: 16391812 [PubMed - indexed for MEDLINE] Administration of Glucocorticoids to Ovarian Cancer Patients Is Associated with Expression of the Anti-apoptotic Genes SGK1 and MKP1/DUSP1 in Ovarian Tissues
Abstract Purpose: To prevent chemotherapy-related side effects, synthetic glucocorticoids, for example, dexamethasone, are routinely administered to patients with ovarian cancer. However, preclinical data implicate glucocorticoids in suppressing chemotherapy-mediated apoptosis in epithelial tumors. The anti-apoptotic mechanisms underlying this increased survival have been shown to require up-regulation of prosurvival genes, including serum and glucocorticoid-regulated kinase 1 (SGK1) and map kinase phosphatase 1 (MKP1)/dual specificity phosphatase 1 (DUSP1). Despite abundant preclinical data, there are no correlative studies in patients. We therefore evaluated anti-apoptotic gene expression in tumor samples from patients randomized to dexamethasone or normal saline. Experimental Design: Eighteen patients were randomized before exploratory laparotomy for suspected ovarian cancer. Dexamethasone or normal saline was administered i.v. following anesthesia. Ovarian and omental tumor samples were collected intra-operatively before and after infusion. Samples were analyzed for histology and glucocorticoid receptor expression by immunohistochemistry. SGK1 and MKP1/DUSP1 mRNA levels were determined using quantitative real-time PCR. Results: Ten patients were evaluable. At 30 min postinfusion, tumor samples from five patients receiving dexamethasone revealed an average SGK1 mRNA induction of 6.1-fold (SEM, ±2.6) compared with only 1.5-fold (SEM, ±0.4) in tumor samples from five patients receiving normal saline (P = 0.028). Average MKP1/DUSP1 mRNA expression was increased by 8.2-fold (SEM, ±2.9) following dexamethasone versus 1.1-fold (SEM, ±0.4) following normal saline (P = 0.009). All samples expressed glucocorticoid receptor. Conclusion: Glucocorticoid administration to patients is associated with rapid up-regulation of SGK1 and MKP1 expression in ovarian tumors. This finding supports the hypothesis that pharmacologic doses of glucocorticoids may decrease chemotherapy effectiveness in ovarian cancer patients through increased anti-apoptotic gene expression. Cancer Biol Ther. 2006 Aug;5(8):933-40. Epub 2006 Aug 2. Dexamethasone decreases xenograft response to Paclitaxel through inhibition of tumor cell apoptosis. Pang D, Kocherginsky M, Krausz T, Kim SY, Conzen SD. Department of Medicine and Committee on Cancer Biology, University of Chicago, Chicago, Illinois 60637, USA. Comment in: Glucocorticoid receptor (GR) activation has recently been implicated in the initiation of anti-apoptotic signaling pathways in epithelial cell lines grown in culture. However, the evidence that GR-mediated inhibition of tumor cell apoptosis is the mechanism that diminishes chemotherapy effectiveness in vivo is limited. We therefore initiated a breast cancer xenograft study to examine whether or not pretreatment with glucocorticoids (GCs) decreases tumor response to chemotherapy by inhibiting tumor cell apoptosis. Here we report a significant decrease in paclitaxel-induced apoptosis in xenografts from mice pretreated with dexamethasone (Dex). A significant difference in apoptosis in xenografts from Dex/paclitaxel versus paclitaxel treated animals was seen eight days following initiation of chemotherapy. Nine days later, mice treated with Dex/paclitaxel had significantly larger tumors compared with those that received paclitaxel alone (p = 0.032). Dex pretreatment did not significantly affect tumor cell proliferation rates. Taken together, these results demonstrate that systemic Dex administration results in significantly reduced breast cancer xenograft apoptosis in the context of chemotherapy treatment. We also found that systemic Dex treatment results in upregulation of the anti-apoptotic gene MKP-1 and downregulation of pro-apoptotic Bid and TRAIL genes in tumor cells six hours following Dex treatment. These in vivo gene expression changes correlated with significant inhibition of chemotherapy-induced apoptosis. Interestingly, the decreased chemotherapeutic response of Dex-pretreated tumors persisted for several weeks following treatment. These data suggest that GR-mediated transcriptional regulation of pro- and anti-apoptotic genes contributes to the mechanism through which GCs decrease paclitaxel-induced apoptosis. PMID: 16775428 [PubMed - indexed for MEDLINE] J Biol Chem. 2005 Feb 11;280(6):4117-24. Epub 2004 Dec 7. Glucocorticoid receptor-induced MAPK phosphatase-1 (MPK-1) expression inhibits paclitaxel-associated MAPK activation and contributes to breast cancer cell survival. Wu W, Pew T, Zou M, Pang D, Conzen SD. Department of Medicine and the Committee on Cancer Biology, University of Chicago, Chicago, Illinois 60637, USA. Glucocorticoid receptor (GR) activation has recently been shown to inhibit apoptosis in breast epithelial cells. We have previously described a group of genes that is rapidly up-regulated in these cells following dexamethasone (Dex) treatment. In an effort to dissect the mechanisms of GR-mediated breast epithelial cell survival, we now examine the molecular events downstream of GR activation. Here we show that GR activation leads to both the rapid induction of MAPK phosphatase-1 (MKP-1) mRNA and its sustained expression. Induction of the MKP-1 protein in the MCF10A-Myc and MDA-MB-231 breast epithelial cell lines was also seen. Paclitaxel treatment resulted in MAPK activation and apoptosis of MDA-MB-231 breast cancer cells, and both processes were inhibited by Dex pretreatment. Furthermore, induction of MKP-1 correlated with the inhibition of extracellular signal-regulated kinase (ERK1/2) and c-Jun N-terminal kinase (JNK) activity, whereas p38 activity was minimally affected. Blocking Dex-induced MKP-1 induction using small interfering RNA increased ERK1/2 and JNK phosphorylation and decreased cell survival. ERK1/2 and JNK inactivation was associated with Ets-like transcription factor-1 (ELK-1) dephosphorylation. To explore the gene expression changes that occur downstream of ELK-1 dephosphorylation, we used a combination of temporal gene expression data and promoter element analyses. This approach revealed a previously unrecognized transcriptional target of ELK-1, the human tissue plasminogen activator (tPA). We verified the predicted ELK-1--> tPA transcriptional regulatory relationship using a luciferase reporter assay. We conclude that GR-mediated MAPK inactivation contributes to cell survival and that the potential transcriptional targets of this inhibition can be identified from large scale gene array analysis. PMID: 15590693 [PubMed - indexed for MEDLINE] |
Re: Glucocorticoids
Autophagy. 2009 Nov 18;5(8). [Epub ahead of print]
Autophagy as the main means of cytotoxicity by glucocorticoids in hematological malignancies. Grandér D, Kharaziha P, Laane E, Pokrovskaja K, Panaretakis T. Department of Oncology/Pathology, Cancer Centre Karolinska (CCK) R8:03, Karolinska Institutet and Karolinska University Hospital, Stockholm, Sweden. Glucocorticoids are fundamental drugs used in the treatment of lymphoid malignancies with apoptotic cell death as the hitherto proposed mechanism of action. We have recently shown that dexamethasone induces autophagy in lymphoid leukemia cells and in this particular setting this cell death modality is a prerequisite for the efficient killing of the leukemic cells by dexamethasone.(1) Hence, inhibition of autophagy by siRNA-mediated silencing of Beclin 1, as well as chemical inhibition of type III PtdIns3K, inhibits apoptosis, demonstrating an important role of autophagy in dexamethasone-induced cell death. In this brief report, we review these findings and introduce the multiple myeloma cells as a novel system to study autophagy in response to dexamethasone. PMID: 19855186 [PubMed - as supplied by publisher] |
Re: Glucocorticoids
Related to Fluoxetine (Prozac)?
Ann N Y Acad Sci. 2009 Oct;1179(1Glucocorticoids and Mood Clinical Manifestations, Risk Factors, and Molecular Mechanisms):86-105. Cytokines and Glucocorticoid Receptor Signaling. Pace TW, Miller AH. Department of Psychiatry and Behavioral Sciences, Winship Cancer Institute, Emory University School of Medicine, Atlanta, Georgia, USA. Data suggest that the activation of immune responses and the release of inflammatory cytokines may play a role in the pathophysiology of major depression. One mechanism by which cytokines may contribute to depression is through their effects on the glucocorticoid receptor (GR). Altered GR function in depression has been demonstrated by neuroendocrine challenge tests that reliably reveal reduced GR sensitivity as manifested by nonsuppression of cortisol following dexamethasone administration in vivo and lack of immune suppression following administration of glucocorticoids in vitro. Relevant to the GR, cytokines have been shown to decrease GR expression, block translocation of the GR from cytoplasm to nucleus, and disrupt GR-DNA binding through nuclear protein-protein interactions. In addition, cytokines have been shown to increase the expression of the relatively inert GR beta isoform. Specific cytokine signaling molecules that have been shown to be involved in the disruption of GR activity include p38 mitogen-activated protein kinase, which is associated with reduced GR translocation, and signal transducer and activator of transcription (STAT)5, which binds to GR in the nucleus. Nuclear factor-kappaB (NF-kappaB) also has been shown to lead to GR suppression through mutually inhibitory GR-NF-kappaB nuclear interactions. Interestingly, several antidepressants have been shown to enhance GR function, as has activation of protein kinase A (PKA). Antidepressants and PKA activation have also been found to inhibit inflammatory cytokines and their signaling pathways, suggesting that drugs that target both inflammatory responses and the GR may have special efficacy in the treatment of depression. PMID: 19906234 [PubMed - as supplied by publisher] Patient thread on psychological effects of Decadron: LINK |
Re: Glucocorticoids
Available Alternatives 5-HT3 antagonists: http://en.wikipedia.org/wiki/5-HT3_antagonist
Certain prokinetic drugs such as cisapride, renzapride and metoclopramide, although not 5-HT<sub>3</sub> antagonists proper, possess some weak antagonist effect at the 5-HT<sub>3</sub> receptor. Galanolactone, a diterpenoid found in ginger, is a 5-HT<sub>3</sub> antagonist and is believed to at least partially mediate the anti-emetic activity of this plant.<sup id="cite_ref-31" class="reference">[32]</sup><sup id="cite_ref-32" class="reference">[33]</sup> Mirtazapine (trade name Remeron) is a tetracyclic antidepressant with 5-HT<sub>3</sub> antagonist effects and strong anti-emetic properties. Studies show mirtazapine as equally effective in treating chemotherapy-related nausea and vomiting as standard treatments; it is also cheaper and has fewer side effects than typical anti-emetics, and its antidepressant qualities may be an added benefit for cancer populations.<sup id="cite_ref-Kast_33-0" class="reference">[34]</sup> Mirtazapine has also been used in the treatment of the motility disorder gastroparesis due to its anti-emetic effects.<sup id="cite_ref-34" class="reference">[35]</sup> Olanzapine (trade name Zyprexa), an atypical antipsychotic with anti-emetic properties similar to those of mirtazapine, also shows promise in treating chemotherapy-induced nausea and vomiting.<sup id="cite_ref-Kast_33-1" class="reference">[34]</sup>
http://kytril.com/ Kytril is Granisetron available as IV, tablets or liquid. http://www.sancuso.com/hcp/efficacy/...FYJx5QodFy7jqQ SANCUSO is the first and only patch (Granisetron) for the prevention of chemotherapy-induced nausea and vomiting in patients receiving moderately and/or highly emetogenic chemotherapy regimens (MEC and/or HEC) of up to 5 consecutive days' duration.<sup>1</sup> Preventing CINV can make a positive impact on a patient's emotional and physical recovery Read more about the occurrence of CINV, patient fear, and problems with adherence to CINV medication below. SANCUSO—a selective 5-HT<sub>3</sub> receptor antagonist The SANCUSOpatch delivers 34.3 mg of granisetron, a selective 5-HT<sub>3</sub> receptor antagonist, at a rate of 3.1 mg per day through the skin and into the bloodstream.<sup>1</sup>. It’s an optimal choice for patients at risk for CINV, and those who would benefit from 5 continuous days of coverage. SANCUSO starts working before chemotherapy begins One key to successful CINV prevention is to address the situation before it even begins and to offer continuous CINV prevention at a steady state during and after each round of chemotherapy. SANCUSO is applied a minimum of 24 to 48 hours before chemotherapy and provides up to 5 days of continuous coverage for the prevention of chemotherapy-induced nausea and vomiting.<sup>1</sup> Coverage prior to symptoms on a long-term basis can relieve your patients' anxieties and help them stay positive about their treatment overall. http://www.sancuso.com/images/chart-apply_5_days.jpg Masui. 1996 Sep;45(9):1096-9. Treatment of postoperative nausea and vomiting with ondansetron in patients administered anti-neoplastic agents [Article in Japanese] Morimoto Y, Nakamura M, Tamura T, Kunii T, Shimizu K, Miyauchi Y. Department of Anesthesiology and Critical Care, Tokuyama Central Hospital. The antiemetic effect of ondansetron (a 5-HT3 antagonist) was evaluated in patients treated with intraperitoneally administered anti-neoplastic agents (cisplatin and mitomycin-C) during surgery for ovarian cancer. Anesthesia was induced with intravenous thiopental 5 mg x kg-1 and maintained with nitrous oxide 66% in oxygen and isoflurane. After surgery, 6 patients received a single intravenous dose of ondansetron 4 mg (group O), 6 others did not receive ondansetron (group C). Both groups received an intravenous dose of methyl-prednisolone 500 mg. An intravenous dose of metoclopramide 10 mg was provided in case of continued vomiting or at the patient's request as a rescue antiemetic. The incidence of vomiting was 13% in group O and 87% in group C (P < 0.05). Nausea scores (range 1-4) were significantly lower in group O as compared with group C at 4 h and 8 h after surgery. Total dose of metoclopramide was 20 +/- 13 mg (mean +/- SD) in group C and 2 +/- 4 mg in group O. Administration of anti-neoplastic agents during surgery caused severe nausea and vomiting after surgery and ondansetron prevented the occurrence of nausea and vomiting almost completely. We conclude that ondansetron is an effective antiemetic for preventing postoperative nausea and vomiting in patients administered anti-neoplastic agents. PMID: 8905945 [PubMed - indexed for MEDLINE] http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(09)70109-3/abstract Efficacy and safety of casopitant mesylate, a neurokinin 1 (NK1)-receptor antagonist, in prevention of chemotherapy-induced nausea and vomiting in patients receiving cisplatin-based highly emetogenic chemotherapy: a randomised, double-blind, placebo-controlled trial http://www.webmd.com/cancer/aprepitant Aprepitant Examples <table class="drug_info_fmt" rules="all" frame="box"> <col> <col> <tbody><tr> <th>Generic Name</th> <th>Brand Name</th> </tr> <tr> <td>aprepitant</td> <td>Emend</td> </tr> </tbody></table> Emend is available as a capsule you can swallow in either 80 mg or 125 mg doses. How It Works Aprepitant prevents and controls nausea and vomiting by blocking the effects of a chemical in the brain. That chemical is called P/neurokinin 1 (NK1) receptor antagonist. note: may interfere with Tamoxifen/CYP450 pathway Why It Is Used Aprepitant is used to prevent and control nausea and vomiting caused by chemotherapy. It is always used in combination with serotonin antagonists (such as ondansetron) and dexamethasone. Aprepitant is not approved for the treatment of chronic nausea or vomiting. It is most often used when the other drugs used to treat nausea and vomiting have not worked well enough. How Well It Works Aprepitant, when combined with ondansetron and dexamethasone as part of a 3-day regimen, prevents both acute and delayed nausea and vomiting caused by chemotherapy. Side Effects Side effects can occur with aprepitant and may include:
What To Think About Aprepitant should be used only under the supervision of a medical oncologist or hematologist. It is approved for use only in combination with ondansetron and dexamethasone for the treatment of nausea and vomiting caused by chemotherapy. It also may do a better job than other drugs at controlling nausea and vomiting that occurs more than 1 day after treatment. Aprepitant interacts with many other drugs. Be sure that your doctor knows all the prescription and over-the-counter drugs you are taking. Blood-thinning drugs, such as warfarin, may not work as well when you take aprepitant. If you are taking a blood thinner, you will need frequent blood tests to make sure that your dose is high enough. Aprepitant decreases the effectiveness of birth control pills. If you are taking birth control pills, your doctor will help you choose another method of birth control. Study: Ginger can help reduce nausea after chemotherapy By Liz Szabo, USA TODAY Ginger capsules can relieve the nausea caused by chemotherapy, a new study shows. Up to 70% of patients become nauseated after chemo, according to a study of 644 people released Thursday, in advance of the annual meeting of the <kwd href="http://content.usatoday.com/topics/topic/American+Society+of+Clinical+Oncology">American Society of Clinical Oncology</kwd>, which begins in two weeks in <kwd href="http://content.usatoday.com/topics/topic/Places,+Geography/Towns,+Cities,+Counties/Orlando">Orlando</kwd>. Although drugs such as Kytril can prevent vomiting, they don't always relieve nausea, says author Julie Ryan, assistant professor of dermatology and radiation oncology at the <kwd href="http://content.usatoday.com/topics/topic/Organizations/Schools/University+of+Rochester">University of Rochester</kwd> Medical Center. Ginger, however, reduced patients' nausea levels by half, according to the study, funded by the National Cancer Institute. On a scale of one to seven — in which seven represents the worst nausea — chemo patients given placebos rated their nausea as a 5 or 6, or very nauseous. Those given ginger, however, rated their nausea level as only 2 or 3, Ryan says. Patients took ginger three days before and three days after getting chemo, Ryan says. Patients took three capsules, twice a day. The most effective doses were 1 gram and 0.5 gram a day, which are equal to half a teaspoon or one-quarter of a teaspoon of ground ginger. All patients also got standard drugs to prevent vomiting, Ryan says. Significantly, ginger caused no side effects. Doctors were careful to monitor patients' platelet levels, because some earlier research suggested that ginger might act like a blood thinner, Ryan says. "That's why we're so excited. This is something that people have access to, that won't harm them," says Ryan, who notes that ginger capsules are commonly sold in health food stores. Although ginger has been used as a folk remedy for nausea for centuries, this is the first time that it has been so rigorously tested for chemo patients, says Richard Schilsky, oncology society president, who wasn't involved in the study. He describes the trial's results as "conclusive." Several studies have shown that ginger can relieve morning sickness during pregnancy, says Linda Lee, director of the <kwd href="http://content.usatoday.com/topics/topic/Organizations/Schools/Johns+Hopkins">Johns Hopkins</kwd> Integrative Medicine & Digestive Center. Doctors don't yet understand exactly why it works. Lee notes that the Food and Drug Administration doesn't regulate supplements such as ginger the same way as it regulates drugs. "One of the challenges about recommending a ginger supplement is that not all brands are created equal," Lee says. "One study looked at several ginger supplements on the market, only to find a few of them did not contain gingerol, one of the active compounds in ginger." And Schilsky notes that, because researchers didn't test powdered or fresh ginger, they don't know if these types of ginger are as effective as capsules. "How do you translate ginger in a capsule to the ginger in your spice rack?" Schilsky asks. "Can you drink a six pack of ginger ale?" Douglas Blayney, incoming president of the oncology society, says cancer patients should resist the temptation to indulge in too much ginger soda or cookies, however. Some studies show that cancer patients who gain weight are more likely to relapse. Studies show up to two-thirds of cancer patients try herbal remedies or other alternative therapies. Cancer researchers are increasingly interested in testing these approaches. In 2007, researchers at the cancer society meeting showed that ginseng could help relieve cancer patients' fatigue. After eight weeks of treatment in that study, roughly 27% of those who took the two highest ginseng doses rated their fatigue as "moderately" or "very much" better, she says. Only 10% of those who took placebos or the lowest ginseng dose improved that much. And while alternative therapies can relieve some treatment-related symptoms, researchers haven't shown the these folk remedies actually treat cancer. At the 2007 meeting, researchers found that shark cartilage had no effect on lung cancer. |
Re: Glucocorticoids
Masui. 1996 Sep;45(9):1096-9.
Treatment of postoperative nausea and vomiting with ondansetron in patients administered anti-neoplastic agents [Article in Japanese] Morimoto Y, Nakamura M, Tamura T, Kunii T, Shimizu K, Miyauchi Y. Department of Anesthesiology and Critical Care, Tokuyama Central Hospital. The antiemetic effect of ondansetron (a 5-HT3 antagonist) was evaluated in patients treated with intraperitoneally administered anti-neoplastic agents (cisplatin and mitomycin-C) during surgery for ovarian cancer. Anesthesia was induced with intravenous thiopental 5 mg x kg-1 and maintained with nitrous oxide 66% in oxygen and isoflurane. After surgery, 6 patients received a single intravenous dose of ondansetron 4 mg (group O), 6 others did not receive ondansetron (group C). Both groups received an intravenous dose of methyl-prednisolone 500 mg. An intravenous dose of metoclopramide 10 mg was provided in case of continued vomiting or at the patient's request as a rescue antiemetic. The incidence of vomiting was 13% in group O and 87% in group C (P < 0.05). Nausea scores (range 1-4) were significantly lower in group O as compared with group C at 4 h and 8 h after surgery. Total dose of metoclopramide was 20 +/- 13 mg (mean +/- SD) in group C and 2 +/- 4 mg in group O. Administration of anti-neoplastic agents during surgery caused severe nausea and vomiting after surgery and ondansetron prevented the occurrence of nausea and vomiting almost completely. We conclude that ondansetron is an effective antiemetic for preventing postoperative nausea and vomiting in patients administered anti-neoplastic agents. PMID: 8905945 [PubMed - indexed for MEDLINE] Study: Ginger can help reduce nausea after chemotherapy By Liz Szabo, USA TODAY Ginger capsules can relieve the nausea caused by chemotherapy, a new study shows. Up to 70% of patients become nauseated after chemo, according to a study of 644 people released Thursday, in advance of the annual meeting of the <kwd href="http://content.usatoday.com/topics/topic/American+Society+of+Clinical+Oncology">American Society of Clinical Oncology</kwd>, which begins in two weeks in <kwd href="http://content.usatoday.com/topics/topic/Places,+Geography/Towns,+Cities,+Counties/Orlando">Orlando</kwd>. Although drugs such as Kytril can prevent vomiting, they don't always relieve nausea, says author Julie Ryan, assistant professor of dermatology and radiation oncology at the <kwd href="http://content.usatoday.com/topics/topic/Organizations/Schools/University+of+Rochester">University of Rochester</kwd> Medical Center. Ginger, however, reduced patients' nausea levels by half, according to the study, funded by the National Cancer Institute. On a scale of one to seven — in which seven represents the worst nausea — chemo patients given placebos rated their nausea as a 5 or 6, or very nauseous. Those given ginger, however, rated their nausea level as only 2 or 3, Ryan says. Patients took ginger three days before and three days after getting chemo, Ryan says. Patients took three capsules, twice a day. The most effective doses were 1 gram and 0.5 gram a day, which are equal to half a teaspoon or one-quarter of a teaspoon of ground ginger. All patients also got standard drugs to prevent vomiting, Ryan says. Significantly, ginger caused no side effects. Doctors were careful to monitor patients' platelet levels, because some earlier research suggested that ginger might act like a blood thinner, Ryan says. "That's why we're so excited. This is something that people have access to, that won't harm them," says Ryan, who notes that ginger capsules are commonly sold in health food stores. Although ginger has been used as a folk remedy for nausea for centuries, this is the first time that it has been so rigorously tested for chemo patients, says Richard Schilsky, oncology society president, who wasn't involved in the study. He describes the trial's results as "conclusive." Several studies have shown that ginger can relieve morning sickness during pregnancy, says Linda Lee, director of the <kwd href="http://content.usatoday.com/topics/topic/Organizations/Schools/Johns+Hopkins">Johns Hopkins</kwd> Integrative Medicine & Digestive Center. Doctors don't yet understand exactly why it works. Lee notes that the Food and Drug Administration doesn't regulate supplements such as ginger the same way as it regulates drugs. "One of the challenges about recommending a ginger supplement is that not all brands are created equal," Lee says. "One study looked at several ginger supplements on the market, only to find a few of them did not contain gingerol, one of the active compounds in ginger." And Schilsky notes that, because researchers didn't test powdered or fresh ginger, they don't know if these types of ginger are as effective as capsules. "How do you translate ginger in a capsule to the ginger in your spice rack?" Schilsky asks. "Can you drink a six pack of ginger ale?" Douglas Blayney, incoming president of the oncology society, says cancer patients should resist the temptation to indulge in too much ginger soda or cookies, however. Some studies show that cancer patients who gain weight are more likely to relapse. Studies show up to two-thirds of cancer patients try herbal remedies or other alternative therapies. Cancer researchers are increasingly interested in testing these approaches. In 2007, researchers at the cancer society meeting showed that ginseng could help relieve cancer patients' fatigue. After eight weeks of treatment in that study, roughly 27% of those who took the two highest ginseng doses rated their fatigue as "moderately" or "very much" better, she says. Only 10% of those who took placebos or the lowest ginseng dose improved that much. And while alternative therapies can relieve some treatment-related symptoms, researchers haven't shown the these folk remedies actually treat cancer. At the 2007 meeting, researchers found that shark cartilage had no effect on lung cancer. http://www.webmd.com/cancer/aprepitant Aprepitant Examples <table class="drug_info_fmt" rules="all" frame="box"> <col> <col> <tbody><tr> <th>Generic Name</th> <th>Brand Name</th> </tr> <tr> <td>aprepitant</td> <td>Emend</td> </tr> </tbody></table> Emend is available as a capsule you can swallow in either 80 mg or 125 mg doses. How It Works Aprepitant prevents and controls nausea and vomiting by blocking the effects of a chemical in the brain. That chemical is called P/neurokinin 1 (NK1) receptor antagonist. Why It Is Used Aprepitant is used to prevent and control nausea and vomiting caused by chemotherapy. It is always used in combination with serotonin antagonists (such as ondansetron) and dexamethasone. Aprepitant is not approved for the treatment of chronic nausea or vomiting. It is most often used when the other drugs used to treat nausea and vomiting have not worked well enough. How Well It Works Aprepitant, when combined with ondansetron and dexamethasone as part of a 3-day regimen, prevents both acute and delayed nausea and vomiting caused by chemotherapy. Side Effects Side effects can occur with aprepitant and may include:
What To Think About Aprepitant should be used only under the supervision of a medical oncologist or hematologist. It is approved for use only in combination with ondansetron and dexamethasone for the treatment of nausea and vomiting caused by chemotherapy. It also may do a better job than other drugs at controlling nausea and vomiting that occurs more than 1 day after treatment. Aprepitant interacts with many other drugs. Be sure that your doctor knows all the prescription and over-the-counter drugs you are taking. Blood-thinning drugs, such as warfarin, may not work as well when you take aprepitant. If you are taking a blood thinner, you will need frequent blood tests to make sure that your dose is high enough. Aprepitant decreases the effectiveness of birth control pills. If you are taking birth control pills, your doctor will help you choose another method of birth control. |
Re: Glucocorticoids
Well, Rich, I hated those damn 'roids, and now I know with good reason...
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Re: Glucocorticoids
<meta http-equiv="Content-Type" content="text/html; charset=utf-8"><meta name="ProgId" content="Word.Document"><meta name="Generator" content="Microsoft Word 10"><meta name="Originator" content="Microsoft Word 10"><link rel="File-List" href="file:///C:%5CDOCUME%7E1%5CUSERSE%7E1%5CLOCALS%7E1%5CTemp%5 Cmsohtml1%5C01%5Cclip_filelist.xml"><!--[if gte mso 9]><xml> <w:WordDocument> <w:View>Normal</w:View> <w:Zoom>0</w:Zoom> <w:Compatibility> <w:BreakWrappedTables/> <w:SnapToGridInCell/> <w:WrapTextWithPunct/> <w:UseAsianBreakRules/> </w:Compatibility> <w:BrowserLevel>MicrosoftInternetExplorer4</w:BrowserLevel> </w:WordDocument> </xml><![endif]--><style> <!-- /* Style Definitions */ p.MsoNormal, li.MsoNormal, div.MsoNormal {mso-style-parent:""; margin:0in; margin-bottom:.0001pt; mso-pagination:widow-orphan; font-size:12.0pt; font-family:"Times New Roman"; mso-fareast-font-family:"Times New Roman";} @page Section1 {size:8.5in 11.0in; margin:1.0in 1.25in 1.0in 1.25in; mso-header-margin:.5in; mso-footer-margin:.5in; mso-paper-source:0;} div.Section1 {page:Section1;} --> </style><!--[if gte mso 10]> <style> /* Style Definitions */ table.MsoNormalTable {mso-style-name:"Table Normal"; mso-tstyle-rowband-size:0; mso-tstyle-colband-size:0; mso-style-noshow:yes; mso-style-parent:""; mso-padding-alt:0in 5.4pt 0in 5.4pt; mso-para-margin:0in; mso-para-margin-bottom:.0001pt; mso-pagination:widow-orphan; font-size:10.0pt; font-family:"Times New Roman";} </style> <![endif]--> Doesn’t u think these poor Indians are suffering from inferiority complex. Frustrated minds really afraid of Islam...Look at the face of this soldier LOLz, a pet dog of So-called Indian liberalism...
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