Rich66
12-09-2009, 01:45 AM
(Triple neg, metronomic, w/glycolysis & mTOR inhib, w/Roglitazone, w/cranberry, oral Satraplatin, Lipoplatin, newer versions on way,w/resveratrol,w/honokiol,w/Quercetin, w/Acetyl-L-carnitine, theophylline to prevent renal damage)
Eur J Gynaecol Oncol. (http://javascript%3Cb%3E%3C/b%3E:AL_get%28this,%20%27jour%27,%20%27Eur%20J%20G ynaecol%20Oncol.%27%29;) 2009;30(4):449-51.
Prolonged clinical benefit from platinum-based chemotherapy in a patient with metastatic triple negative breast cancer.
Krockenberger M (http://www.ncbi.nlm.nih.gov/pubmed?term=%22Krockenberger%20M%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsP anel.Pubmed_RVAbstract), Engel JB (http://www.ncbi.nlm.nih.gov/pubmed?term=%22Engel%20JB%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsP anel.Pubmed_RVAbstract), Häusler S (http://www.ncbi.nlm.nih.gov/pubmed?term=%22H%C3%A4usler%20S%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsP anel.Pubmed_RVAbstract), Dietl J (http://www.ncbi.nlm.nih.gov/pubmed?term=%22Dietl%20J%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsP anel.Pubmed_RVAbstract), Honig A (http://www.ncbi.nlm.nih.gov/pubmed?term=%22Honig%20A%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsP anel.Pubmed_RVAbstract).
Department for Obstetrics and Gynecology, University of Würzburg, Würzburg, Germany.
Triple negative breast cancer is a recently defined subgroup of tumors which do not express receptors for estrogen or progesterone and which do not show any overexpression of HER2 receptors. Tumors with these histopathologic features have an unfavorable prognosis and at present there is no standard chemotherapy regimen available. However, experimental studies and very recently some clinical data showed a benefit from platinum-based chemotherapy. We treated a 52-year-old caucasian female with metastatic triple negative breast cancer. She suffered from extensive liver disease resistant to taxane treatment and yttrium radiotherapy. Cisplatin/ifosfamide (12 cycles) induced regression of the liver metastasis from over 30 cm to 6 cm as revealed by CT scan. Dose-limiting toxicity was impairment of renal function and pancytopenia. The patient has now been stable for over ten months on a metronomic regimen of oral cyclophosphamide. This case report adds to recent evidence suggesting good clinical benefits of platinum-based regimens in early and advanced triple negative breast cancers.
PMID: 19761144 [PubMed - indexed for MEDLINE]
Int J Exp Pathol. (http://javascript%3Cb%3E%3C/b%3E:AL_get%28this,%20%27jour%27,%20%27Int%20J%20E xp%20Pathol.%27%29;) 2010 Feb;91(1):10-6.
Low-dose metronomic chemotherapy with cisplatin: can it suppress angiogenesis in H22 hepatocarcinoma cells?
Shen FZ (http://www.ncbi.nlm.nih.gov/pubmed?term=%22Shen%20FZ%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsP anel.Pubmed_RVAbstract), Wang J (http://www.ncbi.nlm.nih.gov/pubmed?term=%22Wang%20J%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsP anel.Pubmed_RVAbstract), Liang J (http://www.ncbi.nlm.nih.gov/pubmed?term=%22Liang%20J%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsP anel.Pubmed_RVAbstract), Mu K (http://www.ncbi.nlm.nih.gov/pubmed?term=%22Mu%20K%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsP anel.Pubmed_RVAbstract), Hou JY (http://www.ncbi.nlm.nih.gov/pubmed?term=%22Hou%20JY%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsP anel.Pubmed_RVAbstract), Wang YT (http://www.ncbi.nlm.nih.gov/pubmed?term=%22Wang%20YT%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsP anel.Pubmed_RVAbstract).
Department of Oncology, Affiliated Hospital of Medical College, Qingdao University, Qingdao, China. fangzhenshen@126.com
Low-dose chemotherapy drugs can suppress tumours by restraining tumour vessel growth and preventing the repair of damaged vascular endothelial cells. Cisplatin is a broad-spectrum, cell cycle-non-specific drug, but has serious side effects if used at high doses. There have been few reports on the anti-angiogenic effects of low-dose cisplatin and hence the effect of low-dose metronomic (LDM) chemotherapy on the proliferation and neovascularization of H22 hepatocarcinoma cells is discussed in this research. The influence of LDM chemotherapy with cisplatin on human umbilical vascular endothelial cells (HUVECs) and proliferation of the HepG(2) human hepatocarcinoma cell line were measured using MTT assays. The LDM group was treated with cisplatin 0.6 mg/kg/day; the control group with saline 0.2 ml; the maximum tolerated dose (MTD) group with cisplatin 9 mg/kg/day. Vascular endothelial growth factor (VEGF) and matrix metallopeptidase 2 (MMP-2) were detected using immunohistochemical staining. A chicken chorio-allantoic membrane (CAM) model was used to check the inhibitory effect of LDM chemotherapy with cisplatin on neovascularization in vivo. Low-dose cisplatin inhibited HUVEC proliferation in a dose- and time-dependent manner, but was ineffective in inhibiting HepG(2) cell proliferation. Tumour growth was delayed in mice receiving LDM cisplatin, without apparent body weight loss, compared with mice that received MTD cisplatin. Microvessel density and expression of VEGF and MMP-2 were much lower in mice receiving LDM cisplatin than in the control and MTD groups. Continuous low-dose cisplatin suppressed CAM angiogenesis in vivo. LDM chemotherapy with cisplatin can inhibit the growth of blood vessel endothelial cells in vitro and shows anti-angiogenic ability in vivo.
PMID: 20096070 [PubMed - in process]
Another example of benefits of simultaneously targeting glycolysis and mTOR (http://her2support.org/vbulletin/showthread.php?t=41857) and why Metformin (http://her2support.org/vbulletin/showthread.php?t=39740) (and other diabetes drugs) is especially helpful in triple neg BC:
Am J Obstet Gynecol. (http://javascript%3Cb%3E%3C/b%3E:AL_get%28this,%20%27jour%27,%20%27Am%20J%20Ob stet%20Gynecol.%27%29;) 2010 Feb 4. [Epub ahead of print]
Inhibition of glycolysis enhances cisplatin-induced apoptosis in ovarian cancer cells.
Loar P (http://www.ncbi.nlm.nih.gov/pubmed?term=%22Loar%20P%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsP anel.Pubmed_RVAbstract), Wahl H (http://www.ncbi.nlm.nih.gov/pubmed?term=%22Wahl%20H%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsP anel.Pubmed_RVAbstract), Kshirsagar M (http://www.ncbi.nlm.nih.gov/pubmed?term=%22Kshirsagar%20M%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsP anel.Pubmed_RVAbstract), Gossner G (http://www.ncbi.nlm.nih.gov/pubmed?term=%22Gossner%20G%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsP anel.Pubmed_RVAbstract), Griffith K (http://www.ncbi.nlm.nih.gov/pubmed?term=%22Griffith%20K%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsP anel.Pubmed_RVAbstract), Liu JR (http://www.ncbi.nlm.nih.gov/pubmed?term=%22Liu%20JR%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsP anel.Pubmed_RVAbstract).
Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of Michigan Medical School, Ann Arbor, MI.
OBJECTIVE: Up-regulation of glycolysis has been demonstrated in multiple tumor types and is believed to originate as an adaptive response to the selective pressure of the tumor microenvironment. We hypothesized that ovarian cancer cells are dependent on the glycolytic pathway for adenosine triphosphate generation and that this phenotype could be exploited for therapeutic intervention. STUDY DESIGN: Expression of glucose transporter 1 (Glut1), phosphorylated protein kinase B (pPKB/pAkt), and phosphorylated mammalian target of rapamycin (pmTOR) was assessed in ovarian carcinoma tumors and cell lines. Cells were incubated with 2-deoxyglucose and rapamycin; growth inhibition, viability, and mechanism of cell death were determined. RESULTS: Ovarian carcinoma cells overexpress Glut1, pAkt, and pmTOR compared with benign ovarian epithelial cells. 2-Deoxyglucose and rapamycin markedly enhance apoptotic and nonapoptotic cell death in ovarian cancer cells. CONCLUSION: The glycolytic phenotype of ovarian cancer cells can be targeted for therapeutic intervention. Combined treatment modalities that target multiple cellular pathways hold promise for the treatment of chemoresistant ovarian cancer cells. Copyright © 2010 Mosby, Inc. All rights reserved.
PMID: 20138251 [PubMed - as supplied by publisher]
MONDAY, May 7 (HealthDay News) -- The diabetes drug rosiglitazone (brand name Avandia) dramatically increases the potency of platinum-based cancer drugs, U.S. researchers report.
In research with mice, scientists at the Dana-Farber Cancer Institute in Boston found that combining a platinum chemotherapy agent with rosiglitazone was as much as three times more effective at halting or shrinking tumors than using either of the drugs alone.
For more see:
http://news.yahoo.com/s/hsn/20070508...seffectiveness (http://news.yahoo.com/s/hsn/20070508/hl_hsn/diabetesdrugboostschemoseffectiveness)
BMC Cancer. (http://javascript%3Cb%3E%3C/b%3E:AL_get%28this,%20%27jour%27,%20%27BMC%20Cance r.%27%29;) 2009 Apr 8;9:107.
Rosiglitazone synergizes anticancer activity of cisplatin and reduces its nephrotoxicity in 7, 12-dimethyl benz{a}anthracene (DMBA) induced breast cancer rats.
Tikoo K (http://www.ncbi.nlm.nih.gov/pubmed?term=%22Tikoo%20K%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsP anel.Pubmed_RVAbstract), Kumar P (http://www.ncbi.nlm.nih.gov/pubmed?term=%22Kumar%20P%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsP anel.Pubmed_RVAbstract), Gupta J (http://www.ncbi.nlm.nih.gov/pubmed?term=%22Gupta%20J%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsP anel.Pubmed_RVAbstract).
Laboratory of Chromatin Biology, Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER), Sector 67, SAS Nagar, Punjab, India. tikoo.k@gmail.com
BACKGROUND: Antineoplastic drug cisplatin remains the drug of choice for various solid tumours including breast cancer. But dose dependent nephrotoxicity is the major drawback in majority of platinum based chemotherapy regimens. Recent reports have shown that inflammatory pathways are the main offender for cisplatin induced nephrotoxicity. The present study was undertaken to assess the effect of rosiglitazone, a PPARgamma agonist and an anti-inflammatory agent, on cisplatin induced nephrotoxicity, and its anticancer activity in DMBA induced breast cancer rats. METHODS: Mammary tumours were induced in female Sprague-Dawley rats by feeding orally with dimethylbenz [a]anthracene (DMBA) (60 mg/kg). Cisplatin induced nephropathy was assessed by measurements of blood urea nitrogen, albumin and creatinine levels. Posttranslational modifications of histone H3, mitogen-activated protein (MAP) kinase p38 expression and PPAR-gamma expression were examined by western blotting. RESULTS: Our data shows involvement of TNF-alpha in preventing cisplatin induced nephrotoxicity by rosiglitazone. Rosiglitazone pre-treatment to cisplatin increases the expression of p38, PPAR-gamma in mammary tumours and shows maximum tumour reduction. Furthermore, cisplatin induced changes in histone acetylation, phosphorylation and methylation of histone H3 in mammary tumours was ameliorated by pre-treatment of rosiglitazone. Suggesting, PPAR-gamma directly or indirectly alters aberrant gene expression in mammary tumours by changing histone modifications. CONCLUSION: To best of our knowledge this is the first report which shows that pre-treatment of rosiglitazone synergizes the anticancer activity of cisplatin and minimizes cisplatin induced nephrotoxicity in DMBA induced breast cancer.
PMID: 19356226 [PubMed - indexed for MEDLINE]
Phytother Res. (http://javascript%3cb%3e%3c/b%3E:AL_get%28this,%20%27jour%27,%20%27Phytother%2 0Res.%27%29;) 2009 Aug;23(8):1066-74.
Cranberry proanthocyanidins are cytotoxic to human cancer cells and sensitize platinum-resistant ovarian cancer cells to paraplatin.
Singh AP (http://www.ncbi.nlm.nih.gov/pubmed?term=%22Singh%20AP%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsP anel.Pubmed_RVAbstract), Singh RK (http://www.ncbi.nlm.nih.gov/pubmed?term=%22Singh%20RK%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsP anel.Pubmed_RVAbstract), Kim KK (http://www.ncbi.nlm.nih.gov/pubmed?term=%22Kim%20KK%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsP anel.Pubmed_RVAbstract), Satyan KS (http://www.ncbi.nlm.nih.gov/pubmed?term=%22Satyan%20KS%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsP anel.Pubmed_RVAbstract), Nussbaum R (http://www.ncbi.nlm.nih.gov/pubmed?term=%22Nussbaum%20R%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsP anel.Pubmed_RVAbstract), Torres M (http://www.ncbi.nlm.nih.gov/pubmed?term=%22Torres%20M%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsP anel.Pubmed_RVAbstract), Brard L (http://www.ncbi.nlm.nih.gov/pubmed?term=%22Brard%20L%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsP anel.Pubmed_RVAbstract), Vorsa N (http://www.ncbi.nlm.nih.gov/pubmed?term=%22Vorsa%20N%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsP anel.Pubmed_RVAbstract).
Department of Plant Biology and Plant Pathology, Rutgers University, New Brunswick, NJ 08019, USA.
Polyphenolic extracts of the principal flavonoid classes present in cranberry were screened in vitro for cytotoxicity against solid tumor cells lines, identifying two fractions composed principally of proanthocyanidins (PACs) with potential anticancer activity. Matrix-Assisted Laser Desorption/Ionization Time-Of-Flight Mass Spectrometry (MALDI-TOF-MS) analysis of the proanthocyanidins (PACs) fractions indicated the presence of A-type PACs with 1-4 linkages containing between 2-8 epicatechin units with a maximum of 1 epigallocatechin unit. PACs exhibited in vitro cytotoxicity against platinum-resistant human ovarian, neuroblastoma and prostate cancer cell lines (IC50 = 79-479 microg/mL) but were non-cytotoxic to lung fibroblast cells (IC50 > 1000 microg/ml). SKOV-3 ovarian cancer cells treated with PACs exhibited classic apoptotic changes. PACs acted synergistically with paraplatin in SKOV-3 cells. Pretreatment of SKOV-3 cells with PACs (106 microg/ml) resulted in a significant reduction of the paraplatin IC50 value. Similarly, in a BrdU incorporation assay, co-treatment of SKOV-3 cells with PACs and paraplatin revealed reduced cell proliferation at lower concentrations than with either individually. In SKOV-3 cell cultures co-treated with PAC-1 and paraplatin, an HPLC analysis indicated differential quantitative presence of various PAC oligomers such as DP-8, -9, -11 and -14 indicating either selective binding or uptake. Cranberry proanthocyanidins exhibit cell-line specific cytotoxicity, induce apoptotic markers and augment cytotoxicity of paraplatin in platinum-resistant SKOV-3 ovarian cancer cells. Copyright 2009 John Wiley & Sons, Ltd.
PMID: 19172579 [PubMed - indexed for MEDLINE]
Expert Opin Investig Drugs. (http://javascript%3Cb%3E%3C/b%3E:AL_get%28this,%20%27jour%27,%20%27Expert%20Op in%20Investig%20Drugs.%27%29;) 2009 Nov;18(11):1787-97.
Satraplatin: leading the new generation of oral platinum agents.
Bhargava A (http://www.ncbi.nlm.nih.gov/pubmed?term=%22Bhargava%20A%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsP anel.Pubmed_RVAbstract), Vaishampayan UN (http://www.ncbi.nlm.nih.gov/pubmed?term=%22Vaishampayan%20UN%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsP anel.Pubmed_RVAbstract).
Department of Medicine, Division of Hematology/Oncology, Wayne State University, Barbara Ann Karmanos Cancer Institute, Detroit, MI, USA.
BACKGROUND: In recent years, JM-216/satraplatin (GPC Biotech, Inc.) has emerged as a novel oral platinum analogue with a better toxicity profile than cisplatin. Since satraplatin is more hydrophobic than cisplatin or oxaliplatin, it appears to demonstrate efficacy in cisplatin-resistant cell lines. The preclinical and clinical evaluation of satraplatin stimulated this review of the pharmacology and clinical trial data of this agent. METHODS: A literature review was conducted in the MEDLINE database from 1985 to present using the keywords 'satraplatin' or 'JM-216'. The abstracts regarding satraplatin reported at the 2007 - 2009 American Society of Clinical Oncology meetings were also reviewed. RESULTS/CONCLUSION: Satraplatin has a favorable toxicity profile, and appears to have clinical activity against a variety of malignancies such as breast, prostate and lung cancer. The oral route of administration and the intermittent schedule makes it very convenient for clinical use. Despite this, a FDA-approved indication has not yet been achieved. The only Phase III trial with satraplatin was conducted in pretreated metastatic castrate-resistant prostate cancer (CRPC), revealing an improvement in progression-free survival but no overall survival benefit. Future development would have to include designing trials in docetaxel-refractory metastatic CRPC, or in other malignancies where cisplatin is of benefit.
PMID: 19888874 [PubMed - in process]
Chemother Res Pract. (http://www.ncbi.nlm.nih.gov/pubmed/22295201#) 2011;2011:125192. Epub 2010 Dec 21.
Lipoplatin treatment in lung and breast cancer.
Fantini M (http://www.ncbi.nlm.nih.gov/pubmed?term=%22Fantini%20M%22%5BAuthor%5D), Gianni L (http://www.ncbi.nlm.nih.gov/pubmed?term=%22Gianni%20L%22%5BAuthor%5D), Santelmo C (http://www.ncbi.nlm.nih.gov/pubmed?term=%22Santelmo%20C%22%5BAuthor%5D), Drudi F (http://www.ncbi.nlm.nih.gov/pubmed?term=%22Drudi%20F%22%5BAuthor%5D), Castellani C (http://www.ncbi.nlm.nih.gov/pubmed?term=%22Castellani%20C%22%5BAuthor%5D), Affatato A (http://www.ncbi.nlm.nih.gov/pubmed?term=%22Affatato%20A%22%5BAuthor%5D), Nicolini M (http://www.ncbi.nlm.nih.gov/pubmed?term=%22Nicolini%20M%22%5BAuthor%5D), Ravaioli A (http://www.ncbi.nlm.nih.gov/pubmed?term=%22Ravaioli%20A%22%5BAuthor%5D).
Free PMC Article (http://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22295201/?tool=pubmed)
Source
Department of Oncology and Oncohematology, Infermi Hospital, 2 Settembrini Street, 47900 Rimini, Italy.
Abstract
The introduction of cisplatin in cancer treatment represents an important achievement in the oncologic field. Many types of cancers are now treated with this drug, and in testicular cancer patients major results are reached. Since 1965, other compounds were disovered and among them carboplatin and oxaliplatin are the main Cisplatin analogues showing similar clinical efficacy with a safer toxicity profile. Lipoplatin is a new liposomal cisplatin formulation which seems to have these characteristics. Lipoplatin was shown to be effective in NSCLC both in phase 2 and phase 3 trials, with the same response rate of Cisplatin, a comparable overall survival but less toxicity. A new protocol aiming to elucidate the double capacity of Lipoplatin to act as a chemotherapeutic and angiogenetic agent in triple-negative breast cancer patients is upcoming.
<dl class="rprtid"><dt>PMID:</dt><dd>22295201</dd><dd> [PubMed - in process] </dd><dd>
</dd><dt>PMCID:</dt><dd>PMC3265256</dd><dd>
</dd></dl>[/URL]
LINK (http://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22295201/?tool=pubmed)
New Class of Platinum-Based Anti-Tumor Drugs, Bisplatinates, Demonstrates Potent Anti-Tumor Activity and Ability to Overcome Resistance to Currently Available Platinum-Based Agents
CTI targeting starting human clinical trials as early as year end 2010
SEATTLE, Nov. 30 /PRNewswire-FirstCall/ -- Cell Therapeutics, Inc. (CTI) (Nasdaq and MTA: CTIC) announced today that its new class of platinum-based anti-tumor compounds, termed bis-platinates, demonstrated a stronger anti-tumor potency and activity compared to currently available platinum-based compounds as well as the ability to overcome cisplatin-resistance in cancer cell lines. The results were presented in a paper titled "Novel Bis-platinum Complexes Endowed with an Improved Pharmacological Profile," by Laura Gatti et al. that was published in the online edition of the journal Molecular Pharmaceutics. Platinum-based compounds, such as cisplatin and oxaliplatin, are the cornerstone in the treatment of testicular, ovarian, colorectal, lung and other cancers but their effectiveness is limited by the relatively low therapeutic ratio, the ratio of the maximally tolerated dose of the drug to the effective dose, and the frequent occurrence of drug resistance leading to cancer recurrence. The novel bis-platinum compounds represent a completely new class of platinum-based drugs called bisplatinates.
The bis-platinum based compounds, unlike the currently approved platinum-based compounds, contain two platinum atoms and work by binding to and damaging both strands of DNA making it much more difficult for cancer cells to repair the damage. The research demonstrated through cancer cell assaysand animal tumor models that the bis-platinum complexes exhibited greater cytotoxic potency and anti-tumor effect compared to cisplatin and oxaliplatin. There was more than a 200-fold increase in percent accumulation in tumor cells of the bisplatinum compounds compared to cisplatin and oxaliplatin. The bisplatinates were substantially more active against human tumors grown in an immunodeficient preclinical model than the standard palatinate compounds, oxaliplatin, carboplatin and cisplatin. Furthermore, the bis-platinum compounds demonstrated the ability to overcome tumor resistance to cisplatin mediated by DNA mismatch repair defects. The complexes showed marked anti-tumor efficacy in platinum refractory tumors, with significant activity in terms of tumor growth inhibition and tumor growth delay.
"Platinum-based compounds are cornerstone agents in the treatment of very common cancers such as cancers of the lung, colon, and ovary and are also widely used in other gynecological tumors, testicular cancers, and cancers of the esophagus, head and neck. They are increasingly being used for salvage therapy in lymphoma. However, resistance to palatinate compounds is common. The current results are encouraging as they demonstrate that the bisplatinates are not only more effective in human tumor models than the current agents, but also capable of overcoming some forms of palatinate resistance," said Jack Singer, M.D., Chief Medical Officer of CTI.
About Cell Therapeutics, Inc.
Headquartered in Seattle, CTI is a biopharmaceutical company committed to developing an integrated portfolio of oncology products aimed at making cancer more treatable. For additional information, please visit www.CellTherapeutics.com (http://www.celltherapeutics.com/).
Sign up for email alerts and get RSS feeds at our Web site, http://www.celltherapeutics.com/investors_alert
Cancer Biother Radiopharm. (http://javascript%3cb%3e%3c/b%3E:AL_get%28this,%20%27jour%27,%20%27Cancer%20Bi other%20Radiopharm.%27%29;) 2009 Dec;24(6):675-80.
Resveratrol protects against Cisplatin-induced cardiotoxicity by alleviating oxidative damage.
Wang J (http://www.ncbi.nlm.nih.gov/pubmed?term=%22Wang%20J%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsP anel.Pubmed_RVAbstract), He D (http://www.ncbi.nlm.nih.gov/pubmed?term=%22He%20D%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsP anel.Pubmed_RVAbstract), Zhang Q (http://www.ncbi.nlm.nih.gov/pubmed?term=%22Zhang%20Q%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsP anel.Pubmed_RVAbstract), Han Y (http://www.ncbi.nlm.nih.gov/pubmed?term=%22Han%20Y%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsP anel.Pubmed_RVAbstract), Jin S (http://www.ncbi.nlm.nih.gov/pubmed?term=%22Jin%20S%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsP anel.Pubmed_RVAbstract), Qi F (http://www.ncbi.nlm.nih.gov/pubmed?term=%22Qi%20F%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsP anel.Pubmed_RVAbstract).
Department of Medical Oncology, Tumor Hospital of Harbin Medical University, Haping, Harbin, China.
The clinical use of cisplatin, a potent antineoplastic agent, is limited by its severe adverse effects. The present study was designed to evaluate the effects of resveratrol on cisplatin-induced cardiac injury. Resveratrol is a potent free radical scavenger. In the present study, we tested whether resveratrol would prevent cisplatin-induced cardiotoxicity in rats. Plasma-enzyme activities and histologic myocardial changes were examined. The anticancer role of resveratrol and/or cisplatin were measured by MTT. Our data showed that cisplatin led to cardiac-function deterioration, myocardial injury, increased lactate dehydrogenase, creatine kinase, malondialdehyde activities, and decreased activities of superoxide dismutase, glutathione, glutathione peroxidase, and catalase. Treatment with [U]resveratrol effectively hindered the adverse effects of cisplatin in a dose-dependent manner, such as myocardial injury and impaired heart function. An in vitro cytotoxic study showed that resveratrol could increase the antineoplastic activity of cisplatin to A549 adenocarcinoma cells. All the above lines of evidence suggest that resveratrol protects cardiomyocytes from cisplatin-induced cardiotoxicity via the suppression of oxidative stress.
PMID: 20025547 [PubMed - indexed for MEDLINE]
<input name="EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.P ubmed_ResultsController.ResultCount" sid="1" value="1" type="hidden"><input name="EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.P ubmed_ResultsController.RunLastQuery" sid="1" type="hidden">
J Cancer Res Clin Oncol. (http://javascript%3Cb%3E%3C/b%3E:AL_get%28this,%20%27jour%27,%20%27J%20Cancer% 20Res%20Clin%20Oncol.%27%29;) 2008 Sep;134(9):937-45. Epub 2008 Mar 19.
Liposomal honokiol, a promising agent for treatment of cisplatin-resistant human ovarian cancer.
Luo H (http://www.ncbi.nlm.nih.gov/pubmed?term=%22Luo%20H%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsP anel.Pubmed_RVAbstract), Zhong Q (http://www.ncbi.nlm.nih.gov/pubmed?term=%22Zhong%20Q%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsP anel.Pubmed_RVAbstract), Chen LJ (http://www.ncbi.nlm.nih.gov/pubmed?term=%22Chen%20LJ%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsP anel.Pubmed_RVAbstract), Qi XR (http://www.ncbi.nlm.nih.gov/pubmed?term=%22Qi%20XR%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsP anel.Pubmed_RVAbstract), Fu AF (http://www.ncbi.nlm.nih.gov/pubmed?term=%22Fu%20AF%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsP anel.Pubmed_RVAbstract), Yang HS (http://www.ncbi.nlm.nih.gov/pubmed?term=%22Yang%20HS%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsP anel.Pubmed_RVAbstract), Yang F (http://www.ncbi.nlm.nih.gov/pubmed?term=%22Yang%20F%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsP anel.Pubmed_RVAbstract), Lin HG (http://www.ncbi.nlm.nih.gov/pubmed?term=%22Lin%20HG%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsP anel.Pubmed_RVAbstract), Wei YQ (http://www.ncbi.nlm.nih.gov/pubmed?term=%22Wei%20YQ%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsP anel.Pubmed_RVAbstract), Zhao X (http://www.ncbi.nlm.nih.gov/pubmed?term=%22Zhao%20X%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsP anel.Pubmed_RVAbstract).
Department of Gynecology and Obstetrics, West China Second Hospital and State Key Laboratory of Biotherapy, West China Medical School, Sichuan University, Chengdu, Sichuan, People's Republic of China. luohongcd1969@163.com
PURPOSE: Honokiol has been receiving attention as an anticancer agent because of its anti-tumor effect. In the current study, we encapsulated honokiol with liposome and tested it on cisplatin-sensitive (A2780s) and -resistant (A2780cp) human ovarian cancer models. METHODS: The anti-tumor activity of liposomal honokiol (Lipo-HNK) was evaluated in nude mice bearing A2780s and A2780cp s.c. tumors. Mice were treated twice weekly with i.v. administration of Lipo-HNK (10 mg/kg), control liposome (10 mg/kg), 0.9% NaCl solution or weekly with intraperitoneally administered cisplatin (5 mg/kg) for 3 weeks. Tumor volume and survival time were observed. Assessment of apoptotic cells by TUNEL assay was conducted in tumor tissue. Microvessel density within tumor tissue was determined by CD34 immunohistochemistry. For in vitro study, induction of apoptosis by Lipo-HNK was examined by PI staining fluorescence microscopy, DNA fragmentation assay and flow cytometric analysis. RESULTS: Administration of Lipo-HNK resulted in significant inhibition (84-88% maximum inhibition relative to controls) in the growth of A2780s and A2780cp tumor xenografts and prolonged the survival of the treated mice. These anti-tumor responses were associated with marked increases in tumor apoptosis, and reductions in intratumoral microvessel density. CONCLUSIONS: The present findings suggest that Lipo-HNK may provide an effective approach to inhibit tumor growth in both cisplatin sensitive and -resistant human ovarian cancer with minimal side effects.
Int J Gynecol Cancer. (http://javascript%3Cb%3E%3C/b%3E:AL_get%28this,%20%27jour%27,%20%27Int%20J%20G ynecol%20Cancer.%27%29;) 2008 Jul-Aug;18(4):652-9. Epub 2007 Sep 24.
Enhancement of therapeutic effectiveness by combining liposomal honokiol with cisplatin in ovarian carcinoma.
Liu Y (http://www.ncbi.nlm.nih.gov/pubmed?term=%22Liu%20Y%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsP anel.Pubmed_RVAbstract), Chen L (http://www.ncbi.nlm.nih.gov/pubmed?term=%22Chen%20L%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsP anel.Pubmed_RVAbstract), He X (http://www.ncbi.nlm.nih.gov/pubmed?term=%22He%20X%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsP anel.Pubmed_RVAbstract), Fan L (http://www.ncbi.nlm.nih.gov/pubmed?term=%22Fan%20L%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsP anel.Pubmed_RVAbstract), Yang G (http://www.ncbi.nlm.nih.gov/pubmed?term=%22Yang%20G%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsP anel.Pubmed_RVAbstract), Chen X (http://www.ncbi.nlm.nih.gov/pubmed?term=%22Chen%20X%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsP anel.Pubmed_RVAbstract), Lin X (http://www.ncbi.nlm.nih.gov/pubmed?term=%22Lin%20X%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsP anel.Pubmed_RVAbstract), DU L (http://www.ncbi.nlm.nih.gov/pubmed?term=%22DU%20L%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsP anel.Pubmed_RVAbstract), Li Z (http://www.ncbi.nlm.nih.gov/pubmed?term=%22Li%20Z%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsP anel.Pubmed_RVAbstract), Ye H (http://www.ncbi.nlm.nih.gov/pubmed?term=%22Ye%20H%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsP anel.Pubmed_RVAbstract), Mao Y (http://www.ncbi.nlm.nih.gov/pubmed?term=%22Mao%20Y%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsP anel.Pubmed_RVAbstract), Zhao X (http://www.ncbi.nlm.nih.gov/pubmed?term=%22Zhao%20X%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsP anel.Pubmed_RVAbstract), Wei Y (http://www.ncbi.nlm.nih.gov/pubmed?term=%22Wei%20Y%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsP anel.Pubmed_RVAbstract).
Department of Gynecology and Obstetrics, Second West China Hospital, West China Medical School, Sichuan University, Chengdu, Sichuan, People's Republic of China.
Honokiol, a well-tolerated natural product, can inhibit the proliferation of cancer cells. But its water insolubility hampers its systemic administration for therapy of cancer. As a drug delivery system, the pegylated liposome (PEGL) can increase the water solubility and targeting of the drug. Honokiol has been successfully encapsulated by PEGL in our laboratory. We wondered whether the combination treatment with pegylated liposomal honokiol (H-PEGL) and cisplatin (DDP) could improve the antitumor efficacy in ovarian carcinoma. H-PEGL could introduce apoptosis of SKOV3 cells in vitro, which was quantified by flow cytometric analysis, and the cellular morphologic changes were determined by propidium iodide staining. In a human ovarian carcinoma mouse model, combination treatment with H-PEGL (0.4 mg/day for 30 days; intraperitoneal) and DDP (5 mg/kg on days 7, 11, 15, 19; intraperitoneal) acted synergistically to inhibit tumor growth by 91.48% without notable toxicity, but H-PEGL and DDP alone only inhibit tumor growth by 66.83% and 52.5% as compared to the NaCl solution control, respectively. Assessment of microvessel density and apoptosis index by CD31 and terminal deoxynucleotidyl transferase-mediated nick end labeling immunohistochemistry respectively suggested that the antitumor activity of H-PEGL is mediated by angiogenesis inhibition and introduction of apoptosis. Our results showed us a splendid prospect of the clinical application of combination treatment on patients suffering from ovarian cancer with H-PEGL and DDP.
PMID: 17892458 [PubMed - indexed for MEDLINE]
Mutagenesis. (http://javascript%3Cb%3E%3C/b%3E:AL_get%28this,%20%27jour%27,%20%27Mutagenesis .%27%29;) 2010 Feb 15. [Epub ahead of print]
The impact of quercetin on cisplatin-induced clastogenesis and apoptosis in murine marrow cells.
Attia SM (http://www.ncbi.nlm.nih.gov/pubmed?term=%22Attia%20SM%22%5BAuthor%5D).
Department of Pharmacology, College of Pharmacy, King Saud University, PO 2457, Riyadh 11451, Saudi Arabia.
The aim of the present investigation is to determine whether the quercetin in combination with cisplatin can ameliorate cisplatin-induced clastogenesis and apoptosis in the bone marrow cells of mice. The scoring of chromosomal aberrations, micronuclei and mitotic activity were undertaken in the current study as markers of clastogenicity. Apoptosis was analysed by the Annexin V-propidium iodide assay and the occurrence of a hypodiploid DNA peak. Oxidative stress markers such as bone marrow lipid peroxidation and reduced glutathione were assessed as a possible mechanism underlying this amelioration. Quercetin was neither clastogenic nor apoptogenic in mice at doses equivalent to 50 or 100 mg/kg for 2 days. Pre-treatment of mice with quercetin significantly reduced cisplatin-induced clastogenesis and apoptosis in the bone marrow cells and these effects were dose and time dependent. Prior administration of quercetin ahead of cisplatin challenge ameliorated oxidative stress markers. Overall, this study provides for the first time that quercetin has a protective role in the abatement of cisplatin-induced clastogenesis and apoptosis in the bone marrow cells of mice that resides, at least in part, in its antioxidant effects. Therefore, quercetin can be a good candidate to decrease the deleterious effects of cisplatin in the bone marrow cells of cancer patients treated with this drug.
PMID: 20156843 [PubMed - as supplied by publisher]
Clin Cancer Res. (http://javascript%3Cb%3E%3C/b%3E:AL_get%28this,%20%27jour%27,%20%27Clin%20Canc er%20Res.%27%29;) 2010 Jun 18. [Epub ahead of print]
Metabolic Approach to the Enhancement of Antitumor Effect of Chemotherapy: A Key Role of Acetyl-L-Carnitine.
Pisano C (http://www.ncbi.nlm.nih.gov/pubmed?term=%22Pisano%20C%22%5BAuthor%5D), Vesci L (http://www.ncbi.nlm.nih.gov/pubmed?term=%22Vesci%20L%22%5BAuthor%5D), Milazzo FM (http://www.ncbi.nlm.nih.gov/pubmed?term=%22Milazzo%20FM%22%5BAuthor%5D), Guglielmi MB (http://www.ncbi.nlm.nih.gov/pubmed?term=%22Guglielmi%20MB%22%5BAuthor%5D), FoderÃ* R (http://www.ncbi.nlm.nih.gov/pubmed?term=%22Foder%C3%A0%20R%22%5BAuthor%5D), Barbarino M (http://www.ncbi.nlm.nih.gov/pubmed?term=%22Barbarino%20M%22%5BAuthor%5D), D'Incalci M (http://www.ncbi.nlm.nih.gov/pubmed?term=%22D%27Incalci%20M%22%5BAuthor%5D), Zucchetti M (http://www.ncbi.nlm.nih.gov/pubmed?term=%22Zucchetti%20M%22%5BAuthor%5D), Petrangolini G (http://www.ncbi.nlm.nih.gov/pubmed?term=%22Petrangolini%20G%22%5BAuthor%5D), Tortoreto M (http://www.ncbi.nlm.nih.gov/pubmed?term=%22Tortoreto%20M%22%5BAuthor%5D), Perego P (http://www.ncbi.nlm.nih.gov/pubmed?term=%22Perego%20P%22%5BAuthor%5D), Zuco V (http://www.ncbi.nlm.nih.gov/pubmed?term=%22Zuco%20V%22%5BAuthor%5D), Orlandi A (http://www.ncbi.nlm.nih.gov/pubmed?term=%22Orlandi%20A%22%5BAuthor%5D), Passeri D (http://www.ncbi.nlm.nih.gov/pubmed?term=%22Passeri%20D%22%5BAuthor%5D), Carminati P (http://www.ncbi.nlm.nih.gov/pubmed?term=%22Carminati%20P%22%5BAuthor%5D), Cavazza C (http://www.ncbi.nlm.nih.gov/pubmed?term=%22Cavazza%20C%22%5BAuthor%5D), Zunino F (http://www.ncbi.nlm.nih.gov/pubmed?term=%22Zunino%20F%22%5BAuthor%5D).
Oncology - R & D, Sigma-Tau S.p.A.
http://www.ncbi.nlm.nih.gov/corehtml/query/egifs/http:--highwire.stanford.edu-icons-externalservices-pubmed-standard-clincanres_full.gif (http://clincancerres.aacrjournals.org/cgi/pmidlookup?view=long&pmid=20562210)
Abstract
PURPOSE: Acetyl-L-carnitine (ALC) plays a relevant role in energy metabolism and stress response, because its function in the complex metabolic system regulating the acetyl-CoA levels which provide a source of acetyl groups for metabolic and acetylation-regulated processes. Since acetylation may influence p53 activity/stability and, therefore, the response to platinum compounds, this study was designed to investigate the effect of ALC in combination with platinum compounds.EXPERIMENTAL DESIGN: The antiproliferative and antitumor activity studies were performed in a panel of human tumor cell lines with functional or defective p53. The antimetastatic drug efficacy was investigated in the subcutaneously-growing H460/M tumor subline, which is able to generate lung metastases.RESULTS: ALC enhanced sensitivity to cisplatin of tumor cells with functional p53. The sensitization by ALC was reflected in an improved in vivo antitumor efficacy of the combination over cisplatin alone in wild-type p53 lung tumors. ALC did not increase the cisplatin efficacy in the p53-mutant SW620 tumor. ALC exhibited a significant antimetastatic activity and this effect was better exploited in combination with the histone deacetylase inhibitor, ST3595. The in vivo acetyl-L-carnitine/cisplatin combination caused activation of p53, associated with protein acetylation and induction of target genes. CONCLUSIONS: ALC was effective in enhancing the antitumor potential of platinum compounds in wild-type p53 tumors. ALC, alone and in combination with an histone deacetylase inhibitor, exhibited an outstanding antimetastatic activity. Both effects, likely mediated by protein acetylation, may have implications for platinum-based therapy and combinations with histone deacetylase inhibitors.
J Am Soc Nephrol. (http://www.ncbi.nlm.nih.gov/pubmed/15590762#) 2005 Feb;16(2):452-8. Epub 2004 Dec 8.
Nephroprotection by theophylline in patients with cisplatin chemotherapy: a randomized, single-blinded, placebo-controlled trial.
Benoehr P (http://www.ncbi.nlm.nih.gov/pubmed?term=%22Benoehr%20P%22%5BAuthor%5D), Krueth P (http://www.ncbi.nlm.nih.gov/pubmed?term=%22Krueth%20P%22%5BAuthor%5D), Bokemeyer C (http://www.ncbi.nlm.nih.gov/pubmed?term=%22Bokemeyer%20C%22%5BAuthor%5D), Grenz A (http://www.ncbi.nlm.nih.gov/pubmed?term=%22Grenz%20A%22%5BAuthor%5D), Osswald H (http://www.ncbi.nlm.nih.gov/pubmed?term=%22Osswald%20H%22%5BAuthor%5D), Hartmann JT (http://www.ncbi.nlm.nih.gov/pubmed?term=%22Hartmann%20JT%22%5BAuthor%5D).
LINK (http://jasn.asnjournals.org/cgi/pmidlookup?view=long&pmid=15590762)
Source
Department of Nephrology and Rheumatology, Georg-August-University, Robert-Koch Strasse 40, 37075 Göttingen, Germany. pbenoeh@gwdg.de
Abstract
The aim of the present study was to assess the possible prevention of cisplatin-induced impairment of GFR by theophylline in patients with various malignancies. The trial design was parallel, randomized, single blinded, and placebo controlled. Patients received cisplatin at a dosage of 50 mg/m(2) either combined with etoposide, ifosfamide, and epirubicin or with paclitaxel and 5-fluorouracil/folinic acid with the usual precautions, including a standard hydration scheme before application of cisplatin in both arms. In the control arm, placebo was administered; in the verum arm, patients received theophylline in a loading dose of 4 mg/kg intravenously over 30 min before cisplatin, followed by 0.4 mg/kg per min over a minimum of 6 h, and then 350 mg three times daily orally for 4 consecutive days after completion of chemotherapy. GFR of each patient was assessed by renal clearance of inulin within 3 d before and at day 5 after cisplatin chemotherapy. Despite usual precautions, patients in the placebo group had a 21% decrease (range, 11 to 31%) of inulin clearance after a single cycle of cisplatin-containing chemotherapy (92.9 +/- 3.4 versus 71.8 +/- 3.5 ml/min; P < 0.01). Patients who received theophylline had no deterioration of GFR (91.5 +/- 3.7 versus 90.0 +/- 3.8 ml/min; P > 0.05). No adverse effects have been observed during theophylline application. Conventional precautions such as hydration and osmotic diuresis cannot prevent a significant decrease of GFR after a single cycle of cisplatin-containing chemotherapy. The prophylactic application of theophylline as an intravenous loading dose and oral maintenance regimen may preserve kidney function in terms of GFR.
<dl class="rprtid"><dt>PMID:</dt><dd>15590762</dd><dd> [PubMed - indexed for MEDLINE] </dd><dd>
</dd></dl>Free full text
Eur J Gynaecol Oncol. (http://javascript%3Cb%3E%3C/b%3E:AL_get%28this,%20%27jour%27,%20%27Eur%20J%20G ynaecol%20Oncol.%27%29;) 2009;30(4):449-51.
Prolonged clinical benefit from platinum-based chemotherapy in a patient with metastatic triple negative breast cancer.
Krockenberger M (http://www.ncbi.nlm.nih.gov/pubmed?term=%22Krockenberger%20M%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsP anel.Pubmed_RVAbstract), Engel JB (http://www.ncbi.nlm.nih.gov/pubmed?term=%22Engel%20JB%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsP anel.Pubmed_RVAbstract), Häusler S (http://www.ncbi.nlm.nih.gov/pubmed?term=%22H%C3%A4usler%20S%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsP anel.Pubmed_RVAbstract), Dietl J (http://www.ncbi.nlm.nih.gov/pubmed?term=%22Dietl%20J%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsP anel.Pubmed_RVAbstract), Honig A (http://www.ncbi.nlm.nih.gov/pubmed?term=%22Honig%20A%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsP anel.Pubmed_RVAbstract).
Department for Obstetrics and Gynecology, University of Würzburg, Würzburg, Germany.
Triple negative breast cancer is a recently defined subgroup of tumors which do not express receptors for estrogen or progesterone and which do not show any overexpression of HER2 receptors. Tumors with these histopathologic features have an unfavorable prognosis and at present there is no standard chemotherapy regimen available. However, experimental studies and very recently some clinical data showed a benefit from platinum-based chemotherapy. We treated a 52-year-old caucasian female with metastatic triple negative breast cancer. She suffered from extensive liver disease resistant to taxane treatment and yttrium radiotherapy. Cisplatin/ifosfamide (12 cycles) induced regression of the liver metastasis from over 30 cm to 6 cm as revealed by CT scan. Dose-limiting toxicity was impairment of renal function and pancytopenia. The patient has now been stable for over ten months on a metronomic regimen of oral cyclophosphamide. This case report adds to recent evidence suggesting good clinical benefits of platinum-based regimens in early and advanced triple negative breast cancers.
PMID: 19761144 [PubMed - indexed for MEDLINE]
Int J Exp Pathol. (http://javascript%3Cb%3E%3C/b%3E:AL_get%28this,%20%27jour%27,%20%27Int%20J%20E xp%20Pathol.%27%29;) 2010 Feb;91(1):10-6.
Low-dose metronomic chemotherapy with cisplatin: can it suppress angiogenesis in H22 hepatocarcinoma cells?
Shen FZ (http://www.ncbi.nlm.nih.gov/pubmed?term=%22Shen%20FZ%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsP anel.Pubmed_RVAbstract), Wang J (http://www.ncbi.nlm.nih.gov/pubmed?term=%22Wang%20J%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsP anel.Pubmed_RVAbstract), Liang J (http://www.ncbi.nlm.nih.gov/pubmed?term=%22Liang%20J%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsP anel.Pubmed_RVAbstract), Mu K (http://www.ncbi.nlm.nih.gov/pubmed?term=%22Mu%20K%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsP anel.Pubmed_RVAbstract), Hou JY (http://www.ncbi.nlm.nih.gov/pubmed?term=%22Hou%20JY%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsP anel.Pubmed_RVAbstract), Wang YT (http://www.ncbi.nlm.nih.gov/pubmed?term=%22Wang%20YT%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsP anel.Pubmed_RVAbstract).
Department of Oncology, Affiliated Hospital of Medical College, Qingdao University, Qingdao, China. fangzhenshen@126.com
Low-dose chemotherapy drugs can suppress tumours by restraining tumour vessel growth and preventing the repair of damaged vascular endothelial cells. Cisplatin is a broad-spectrum, cell cycle-non-specific drug, but has serious side effects if used at high doses. There have been few reports on the anti-angiogenic effects of low-dose cisplatin and hence the effect of low-dose metronomic (LDM) chemotherapy on the proliferation and neovascularization of H22 hepatocarcinoma cells is discussed in this research. The influence of LDM chemotherapy with cisplatin on human umbilical vascular endothelial cells (HUVECs) and proliferation of the HepG(2) human hepatocarcinoma cell line were measured using MTT assays. The LDM group was treated with cisplatin 0.6 mg/kg/day; the control group with saline 0.2 ml; the maximum tolerated dose (MTD) group with cisplatin 9 mg/kg/day. Vascular endothelial growth factor (VEGF) and matrix metallopeptidase 2 (MMP-2) were detected using immunohistochemical staining. A chicken chorio-allantoic membrane (CAM) model was used to check the inhibitory effect of LDM chemotherapy with cisplatin on neovascularization in vivo. Low-dose cisplatin inhibited HUVEC proliferation in a dose- and time-dependent manner, but was ineffective in inhibiting HepG(2) cell proliferation. Tumour growth was delayed in mice receiving LDM cisplatin, without apparent body weight loss, compared with mice that received MTD cisplatin. Microvessel density and expression of VEGF and MMP-2 were much lower in mice receiving LDM cisplatin than in the control and MTD groups. Continuous low-dose cisplatin suppressed CAM angiogenesis in vivo. LDM chemotherapy with cisplatin can inhibit the growth of blood vessel endothelial cells in vitro and shows anti-angiogenic ability in vivo.
PMID: 20096070 [PubMed - in process]
Another example of benefits of simultaneously targeting glycolysis and mTOR (http://her2support.org/vbulletin/showthread.php?t=41857) and why Metformin (http://her2support.org/vbulletin/showthread.php?t=39740) (and other diabetes drugs) is especially helpful in triple neg BC:
Am J Obstet Gynecol. (http://javascript%3Cb%3E%3C/b%3E:AL_get%28this,%20%27jour%27,%20%27Am%20J%20Ob stet%20Gynecol.%27%29;) 2010 Feb 4. [Epub ahead of print]
Inhibition of glycolysis enhances cisplatin-induced apoptosis in ovarian cancer cells.
Loar P (http://www.ncbi.nlm.nih.gov/pubmed?term=%22Loar%20P%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsP anel.Pubmed_RVAbstract), Wahl H (http://www.ncbi.nlm.nih.gov/pubmed?term=%22Wahl%20H%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsP anel.Pubmed_RVAbstract), Kshirsagar M (http://www.ncbi.nlm.nih.gov/pubmed?term=%22Kshirsagar%20M%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsP anel.Pubmed_RVAbstract), Gossner G (http://www.ncbi.nlm.nih.gov/pubmed?term=%22Gossner%20G%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsP anel.Pubmed_RVAbstract), Griffith K (http://www.ncbi.nlm.nih.gov/pubmed?term=%22Griffith%20K%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsP anel.Pubmed_RVAbstract), Liu JR (http://www.ncbi.nlm.nih.gov/pubmed?term=%22Liu%20JR%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsP anel.Pubmed_RVAbstract).
Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of Michigan Medical School, Ann Arbor, MI.
OBJECTIVE: Up-regulation of glycolysis has been demonstrated in multiple tumor types and is believed to originate as an adaptive response to the selective pressure of the tumor microenvironment. We hypothesized that ovarian cancer cells are dependent on the glycolytic pathway for adenosine triphosphate generation and that this phenotype could be exploited for therapeutic intervention. STUDY DESIGN: Expression of glucose transporter 1 (Glut1), phosphorylated protein kinase B (pPKB/pAkt), and phosphorylated mammalian target of rapamycin (pmTOR) was assessed in ovarian carcinoma tumors and cell lines. Cells were incubated with 2-deoxyglucose and rapamycin; growth inhibition, viability, and mechanism of cell death were determined. RESULTS: Ovarian carcinoma cells overexpress Glut1, pAkt, and pmTOR compared with benign ovarian epithelial cells. 2-Deoxyglucose and rapamycin markedly enhance apoptotic and nonapoptotic cell death in ovarian cancer cells. CONCLUSION: The glycolytic phenotype of ovarian cancer cells can be targeted for therapeutic intervention. Combined treatment modalities that target multiple cellular pathways hold promise for the treatment of chemoresistant ovarian cancer cells. Copyright © 2010 Mosby, Inc. All rights reserved.
PMID: 20138251 [PubMed - as supplied by publisher]
MONDAY, May 7 (HealthDay News) -- The diabetes drug rosiglitazone (brand name Avandia) dramatically increases the potency of platinum-based cancer drugs, U.S. researchers report.
In research with mice, scientists at the Dana-Farber Cancer Institute in Boston found that combining a platinum chemotherapy agent with rosiglitazone was as much as three times more effective at halting or shrinking tumors than using either of the drugs alone.
For more see:
http://news.yahoo.com/s/hsn/20070508...seffectiveness (http://news.yahoo.com/s/hsn/20070508/hl_hsn/diabetesdrugboostschemoseffectiveness)
BMC Cancer. (http://javascript%3Cb%3E%3C/b%3E:AL_get%28this,%20%27jour%27,%20%27BMC%20Cance r.%27%29;) 2009 Apr 8;9:107.
Rosiglitazone synergizes anticancer activity of cisplatin and reduces its nephrotoxicity in 7, 12-dimethyl benz{a}anthracene (DMBA) induced breast cancer rats.
Tikoo K (http://www.ncbi.nlm.nih.gov/pubmed?term=%22Tikoo%20K%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsP anel.Pubmed_RVAbstract), Kumar P (http://www.ncbi.nlm.nih.gov/pubmed?term=%22Kumar%20P%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsP anel.Pubmed_RVAbstract), Gupta J (http://www.ncbi.nlm.nih.gov/pubmed?term=%22Gupta%20J%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsP anel.Pubmed_RVAbstract).
Laboratory of Chromatin Biology, Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER), Sector 67, SAS Nagar, Punjab, India. tikoo.k@gmail.com
BACKGROUND: Antineoplastic drug cisplatin remains the drug of choice for various solid tumours including breast cancer. But dose dependent nephrotoxicity is the major drawback in majority of platinum based chemotherapy regimens. Recent reports have shown that inflammatory pathways are the main offender for cisplatin induced nephrotoxicity. The present study was undertaken to assess the effect of rosiglitazone, a PPARgamma agonist and an anti-inflammatory agent, on cisplatin induced nephrotoxicity, and its anticancer activity in DMBA induced breast cancer rats. METHODS: Mammary tumours were induced in female Sprague-Dawley rats by feeding orally with dimethylbenz [a]anthracene (DMBA) (60 mg/kg). Cisplatin induced nephropathy was assessed by measurements of blood urea nitrogen, albumin and creatinine levels. Posttranslational modifications of histone H3, mitogen-activated protein (MAP) kinase p38 expression and PPAR-gamma expression were examined by western blotting. RESULTS: Our data shows involvement of TNF-alpha in preventing cisplatin induced nephrotoxicity by rosiglitazone. Rosiglitazone pre-treatment to cisplatin increases the expression of p38, PPAR-gamma in mammary tumours and shows maximum tumour reduction. Furthermore, cisplatin induced changes in histone acetylation, phosphorylation and methylation of histone H3 in mammary tumours was ameliorated by pre-treatment of rosiglitazone. Suggesting, PPAR-gamma directly or indirectly alters aberrant gene expression in mammary tumours by changing histone modifications. CONCLUSION: To best of our knowledge this is the first report which shows that pre-treatment of rosiglitazone synergizes the anticancer activity of cisplatin and minimizes cisplatin induced nephrotoxicity in DMBA induced breast cancer.
PMID: 19356226 [PubMed - indexed for MEDLINE]
Phytother Res. (http://javascript%3cb%3e%3c/b%3E:AL_get%28this,%20%27jour%27,%20%27Phytother%2 0Res.%27%29;) 2009 Aug;23(8):1066-74.
Cranberry proanthocyanidins are cytotoxic to human cancer cells and sensitize platinum-resistant ovarian cancer cells to paraplatin.
Singh AP (http://www.ncbi.nlm.nih.gov/pubmed?term=%22Singh%20AP%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsP anel.Pubmed_RVAbstract), Singh RK (http://www.ncbi.nlm.nih.gov/pubmed?term=%22Singh%20RK%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsP anel.Pubmed_RVAbstract), Kim KK (http://www.ncbi.nlm.nih.gov/pubmed?term=%22Kim%20KK%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsP anel.Pubmed_RVAbstract), Satyan KS (http://www.ncbi.nlm.nih.gov/pubmed?term=%22Satyan%20KS%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsP anel.Pubmed_RVAbstract), Nussbaum R (http://www.ncbi.nlm.nih.gov/pubmed?term=%22Nussbaum%20R%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsP anel.Pubmed_RVAbstract), Torres M (http://www.ncbi.nlm.nih.gov/pubmed?term=%22Torres%20M%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsP anel.Pubmed_RVAbstract), Brard L (http://www.ncbi.nlm.nih.gov/pubmed?term=%22Brard%20L%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsP anel.Pubmed_RVAbstract), Vorsa N (http://www.ncbi.nlm.nih.gov/pubmed?term=%22Vorsa%20N%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsP anel.Pubmed_RVAbstract).
Department of Plant Biology and Plant Pathology, Rutgers University, New Brunswick, NJ 08019, USA.
Polyphenolic extracts of the principal flavonoid classes present in cranberry were screened in vitro for cytotoxicity against solid tumor cells lines, identifying two fractions composed principally of proanthocyanidins (PACs) with potential anticancer activity. Matrix-Assisted Laser Desorption/Ionization Time-Of-Flight Mass Spectrometry (MALDI-TOF-MS) analysis of the proanthocyanidins (PACs) fractions indicated the presence of A-type PACs with 1-4 linkages containing between 2-8 epicatechin units with a maximum of 1 epigallocatechin unit. PACs exhibited in vitro cytotoxicity against platinum-resistant human ovarian, neuroblastoma and prostate cancer cell lines (IC50 = 79-479 microg/mL) but were non-cytotoxic to lung fibroblast cells (IC50 > 1000 microg/ml). SKOV-3 ovarian cancer cells treated with PACs exhibited classic apoptotic changes. PACs acted synergistically with paraplatin in SKOV-3 cells. Pretreatment of SKOV-3 cells with PACs (106 microg/ml) resulted in a significant reduction of the paraplatin IC50 value. Similarly, in a BrdU incorporation assay, co-treatment of SKOV-3 cells with PACs and paraplatin revealed reduced cell proliferation at lower concentrations than with either individually. In SKOV-3 cell cultures co-treated with PAC-1 and paraplatin, an HPLC analysis indicated differential quantitative presence of various PAC oligomers such as DP-8, -9, -11 and -14 indicating either selective binding or uptake. Cranberry proanthocyanidins exhibit cell-line specific cytotoxicity, induce apoptotic markers and augment cytotoxicity of paraplatin in platinum-resistant SKOV-3 ovarian cancer cells. Copyright 2009 John Wiley & Sons, Ltd.
PMID: 19172579 [PubMed - indexed for MEDLINE]
Expert Opin Investig Drugs. (http://javascript%3Cb%3E%3C/b%3E:AL_get%28this,%20%27jour%27,%20%27Expert%20Op in%20Investig%20Drugs.%27%29;) 2009 Nov;18(11):1787-97.
Satraplatin: leading the new generation of oral platinum agents.
Bhargava A (http://www.ncbi.nlm.nih.gov/pubmed?term=%22Bhargava%20A%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsP anel.Pubmed_RVAbstract), Vaishampayan UN (http://www.ncbi.nlm.nih.gov/pubmed?term=%22Vaishampayan%20UN%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsP anel.Pubmed_RVAbstract).
Department of Medicine, Division of Hematology/Oncology, Wayne State University, Barbara Ann Karmanos Cancer Institute, Detroit, MI, USA.
BACKGROUND: In recent years, JM-216/satraplatin (GPC Biotech, Inc.) has emerged as a novel oral platinum analogue with a better toxicity profile than cisplatin. Since satraplatin is more hydrophobic than cisplatin or oxaliplatin, it appears to demonstrate efficacy in cisplatin-resistant cell lines. The preclinical and clinical evaluation of satraplatin stimulated this review of the pharmacology and clinical trial data of this agent. METHODS: A literature review was conducted in the MEDLINE database from 1985 to present using the keywords 'satraplatin' or 'JM-216'. The abstracts regarding satraplatin reported at the 2007 - 2009 American Society of Clinical Oncology meetings were also reviewed. RESULTS/CONCLUSION: Satraplatin has a favorable toxicity profile, and appears to have clinical activity against a variety of malignancies such as breast, prostate and lung cancer. The oral route of administration and the intermittent schedule makes it very convenient for clinical use. Despite this, a FDA-approved indication has not yet been achieved. The only Phase III trial with satraplatin was conducted in pretreated metastatic castrate-resistant prostate cancer (CRPC), revealing an improvement in progression-free survival but no overall survival benefit. Future development would have to include designing trials in docetaxel-refractory metastatic CRPC, or in other malignancies where cisplatin is of benefit.
PMID: 19888874 [PubMed - in process]
Chemother Res Pract. (http://www.ncbi.nlm.nih.gov/pubmed/22295201#) 2011;2011:125192. Epub 2010 Dec 21.
Lipoplatin treatment in lung and breast cancer.
Fantini M (http://www.ncbi.nlm.nih.gov/pubmed?term=%22Fantini%20M%22%5BAuthor%5D), Gianni L (http://www.ncbi.nlm.nih.gov/pubmed?term=%22Gianni%20L%22%5BAuthor%5D), Santelmo C (http://www.ncbi.nlm.nih.gov/pubmed?term=%22Santelmo%20C%22%5BAuthor%5D), Drudi F (http://www.ncbi.nlm.nih.gov/pubmed?term=%22Drudi%20F%22%5BAuthor%5D), Castellani C (http://www.ncbi.nlm.nih.gov/pubmed?term=%22Castellani%20C%22%5BAuthor%5D), Affatato A (http://www.ncbi.nlm.nih.gov/pubmed?term=%22Affatato%20A%22%5BAuthor%5D), Nicolini M (http://www.ncbi.nlm.nih.gov/pubmed?term=%22Nicolini%20M%22%5BAuthor%5D), Ravaioli A (http://www.ncbi.nlm.nih.gov/pubmed?term=%22Ravaioli%20A%22%5BAuthor%5D).
Free PMC Article (http://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22295201/?tool=pubmed)
Source
Department of Oncology and Oncohematology, Infermi Hospital, 2 Settembrini Street, 47900 Rimini, Italy.
Abstract
The introduction of cisplatin in cancer treatment represents an important achievement in the oncologic field. Many types of cancers are now treated with this drug, and in testicular cancer patients major results are reached. Since 1965, other compounds were disovered and among them carboplatin and oxaliplatin are the main Cisplatin analogues showing similar clinical efficacy with a safer toxicity profile. Lipoplatin is a new liposomal cisplatin formulation which seems to have these characteristics. Lipoplatin was shown to be effective in NSCLC both in phase 2 and phase 3 trials, with the same response rate of Cisplatin, a comparable overall survival but less toxicity. A new protocol aiming to elucidate the double capacity of Lipoplatin to act as a chemotherapeutic and angiogenetic agent in triple-negative breast cancer patients is upcoming.
<dl class="rprtid"><dt>PMID:</dt><dd>22295201</dd><dd> [PubMed - in process] </dd><dd>
</dd><dt>PMCID:</dt><dd>PMC3265256</dd><dd>
</dd></dl>[/URL]
LINK (http://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22295201/?tool=pubmed)
New Class of Platinum-Based Anti-Tumor Drugs, Bisplatinates, Demonstrates Potent Anti-Tumor Activity and Ability to Overcome Resistance to Currently Available Platinum-Based Agents
CTI targeting starting human clinical trials as early as year end 2010
SEATTLE, Nov. 30 /PRNewswire-FirstCall/ -- Cell Therapeutics, Inc. (CTI) (Nasdaq and MTA: CTIC) announced today that its new class of platinum-based anti-tumor compounds, termed bis-platinates, demonstrated a stronger anti-tumor potency and activity compared to currently available platinum-based compounds as well as the ability to overcome cisplatin-resistance in cancer cell lines. The results were presented in a paper titled "Novel Bis-platinum Complexes Endowed with an Improved Pharmacological Profile," by Laura Gatti et al. that was published in the online edition of the journal Molecular Pharmaceutics. Platinum-based compounds, such as cisplatin and oxaliplatin, are the cornerstone in the treatment of testicular, ovarian, colorectal, lung and other cancers but their effectiveness is limited by the relatively low therapeutic ratio, the ratio of the maximally tolerated dose of the drug to the effective dose, and the frequent occurrence of drug resistance leading to cancer recurrence. The novel bis-platinum compounds represent a completely new class of platinum-based drugs called bisplatinates.
The bis-platinum based compounds, unlike the currently approved platinum-based compounds, contain two platinum atoms and work by binding to and damaging both strands of DNA making it much more difficult for cancer cells to repair the damage. The research demonstrated through cancer cell assaysand animal tumor models that the bis-platinum complexes exhibited greater cytotoxic potency and anti-tumor effect compared to cisplatin and oxaliplatin. There was more than a 200-fold increase in percent accumulation in tumor cells of the bisplatinum compounds compared to cisplatin and oxaliplatin. The bisplatinates were substantially more active against human tumors grown in an immunodeficient preclinical model than the standard palatinate compounds, oxaliplatin, carboplatin and cisplatin. Furthermore, the bis-platinum compounds demonstrated the ability to overcome tumor resistance to cisplatin mediated by DNA mismatch repair defects. The complexes showed marked anti-tumor efficacy in platinum refractory tumors, with significant activity in terms of tumor growth inhibition and tumor growth delay.
"Platinum-based compounds are cornerstone agents in the treatment of very common cancers such as cancers of the lung, colon, and ovary and are also widely used in other gynecological tumors, testicular cancers, and cancers of the esophagus, head and neck. They are increasingly being used for salvage therapy in lymphoma. However, resistance to palatinate compounds is common. The current results are encouraging as they demonstrate that the bisplatinates are not only more effective in human tumor models than the current agents, but also capable of overcoming some forms of palatinate resistance," said Jack Singer, M.D., Chief Medical Officer of CTI.
About Cell Therapeutics, Inc.
Headquartered in Seattle, CTI is a biopharmaceutical company committed to developing an integrated portfolio of oncology products aimed at making cancer more treatable. For additional information, please visit www.CellTherapeutics.com (http://www.celltherapeutics.com/).
Sign up for email alerts and get RSS feeds at our Web site, http://www.celltherapeutics.com/investors_alert
Cancer Biother Radiopharm. (http://javascript%3cb%3e%3c/b%3E:AL_get%28this,%20%27jour%27,%20%27Cancer%20Bi other%20Radiopharm.%27%29;) 2009 Dec;24(6):675-80.
Resveratrol protects against Cisplatin-induced cardiotoxicity by alleviating oxidative damage.
Wang J (http://www.ncbi.nlm.nih.gov/pubmed?term=%22Wang%20J%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsP anel.Pubmed_RVAbstract), He D (http://www.ncbi.nlm.nih.gov/pubmed?term=%22He%20D%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsP anel.Pubmed_RVAbstract), Zhang Q (http://www.ncbi.nlm.nih.gov/pubmed?term=%22Zhang%20Q%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsP anel.Pubmed_RVAbstract), Han Y (http://www.ncbi.nlm.nih.gov/pubmed?term=%22Han%20Y%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsP anel.Pubmed_RVAbstract), Jin S (http://www.ncbi.nlm.nih.gov/pubmed?term=%22Jin%20S%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsP anel.Pubmed_RVAbstract), Qi F (http://www.ncbi.nlm.nih.gov/pubmed?term=%22Qi%20F%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsP anel.Pubmed_RVAbstract).
Department of Medical Oncology, Tumor Hospital of Harbin Medical University, Haping, Harbin, China.
The clinical use of cisplatin, a potent antineoplastic agent, is limited by its severe adverse effects. The present study was designed to evaluate the effects of resveratrol on cisplatin-induced cardiac injury. Resveratrol is a potent free radical scavenger. In the present study, we tested whether resveratrol would prevent cisplatin-induced cardiotoxicity in rats. Plasma-enzyme activities and histologic myocardial changes were examined. The anticancer role of resveratrol and/or cisplatin were measured by MTT. Our data showed that cisplatin led to cardiac-function deterioration, myocardial injury, increased lactate dehydrogenase, creatine kinase, malondialdehyde activities, and decreased activities of superoxide dismutase, glutathione, glutathione peroxidase, and catalase. Treatment with [U]resveratrol effectively hindered the adverse effects of cisplatin in a dose-dependent manner, such as myocardial injury and impaired heart function. An in vitro cytotoxic study showed that resveratrol could increase the antineoplastic activity of cisplatin to A549 adenocarcinoma cells. All the above lines of evidence suggest that resveratrol protects cardiomyocytes from cisplatin-induced cardiotoxicity via the suppression of oxidative stress.
PMID: 20025547 [PubMed - indexed for MEDLINE]
<input name="EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.P ubmed_ResultsController.ResultCount" sid="1" value="1" type="hidden"><input name="EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.P ubmed_ResultsController.RunLastQuery" sid="1" type="hidden">
J Cancer Res Clin Oncol. (http://javascript%3Cb%3E%3C/b%3E:AL_get%28this,%20%27jour%27,%20%27J%20Cancer% 20Res%20Clin%20Oncol.%27%29;) 2008 Sep;134(9):937-45. Epub 2008 Mar 19.
Liposomal honokiol, a promising agent for treatment of cisplatin-resistant human ovarian cancer.
Luo H (http://www.ncbi.nlm.nih.gov/pubmed?term=%22Luo%20H%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsP anel.Pubmed_RVAbstract), Zhong Q (http://www.ncbi.nlm.nih.gov/pubmed?term=%22Zhong%20Q%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsP anel.Pubmed_RVAbstract), Chen LJ (http://www.ncbi.nlm.nih.gov/pubmed?term=%22Chen%20LJ%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsP anel.Pubmed_RVAbstract), Qi XR (http://www.ncbi.nlm.nih.gov/pubmed?term=%22Qi%20XR%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsP anel.Pubmed_RVAbstract), Fu AF (http://www.ncbi.nlm.nih.gov/pubmed?term=%22Fu%20AF%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsP anel.Pubmed_RVAbstract), Yang HS (http://www.ncbi.nlm.nih.gov/pubmed?term=%22Yang%20HS%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsP anel.Pubmed_RVAbstract), Yang F (http://www.ncbi.nlm.nih.gov/pubmed?term=%22Yang%20F%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsP anel.Pubmed_RVAbstract), Lin HG (http://www.ncbi.nlm.nih.gov/pubmed?term=%22Lin%20HG%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsP anel.Pubmed_RVAbstract), Wei YQ (http://www.ncbi.nlm.nih.gov/pubmed?term=%22Wei%20YQ%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsP anel.Pubmed_RVAbstract), Zhao X (http://www.ncbi.nlm.nih.gov/pubmed?term=%22Zhao%20X%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsP anel.Pubmed_RVAbstract).
Department of Gynecology and Obstetrics, West China Second Hospital and State Key Laboratory of Biotherapy, West China Medical School, Sichuan University, Chengdu, Sichuan, People's Republic of China. luohongcd1969@163.com
PURPOSE: Honokiol has been receiving attention as an anticancer agent because of its anti-tumor effect. In the current study, we encapsulated honokiol with liposome and tested it on cisplatin-sensitive (A2780s) and -resistant (A2780cp) human ovarian cancer models. METHODS: The anti-tumor activity of liposomal honokiol (Lipo-HNK) was evaluated in nude mice bearing A2780s and A2780cp s.c. tumors. Mice were treated twice weekly with i.v. administration of Lipo-HNK (10 mg/kg), control liposome (10 mg/kg), 0.9% NaCl solution or weekly with intraperitoneally administered cisplatin (5 mg/kg) for 3 weeks. Tumor volume and survival time were observed. Assessment of apoptotic cells by TUNEL assay was conducted in tumor tissue. Microvessel density within tumor tissue was determined by CD34 immunohistochemistry. For in vitro study, induction of apoptosis by Lipo-HNK was examined by PI staining fluorescence microscopy, DNA fragmentation assay and flow cytometric analysis. RESULTS: Administration of Lipo-HNK resulted in significant inhibition (84-88% maximum inhibition relative to controls) in the growth of A2780s and A2780cp tumor xenografts and prolonged the survival of the treated mice. These anti-tumor responses were associated with marked increases in tumor apoptosis, and reductions in intratumoral microvessel density. CONCLUSIONS: The present findings suggest that Lipo-HNK may provide an effective approach to inhibit tumor growth in both cisplatin sensitive and -resistant human ovarian cancer with minimal side effects.
Int J Gynecol Cancer. (http://javascript%3Cb%3E%3C/b%3E:AL_get%28this,%20%27jour%27,%20%27Int%20J%20G ynecol%20Cancer.%27%29;) 2008 Jul-Aug;18(4):652-9. Epub 2007 Sep 24.
Enhancement of therapeutic effectiveness by combining liposomal honokiol with cisplatin in ovarian carcinoma.
Liu Y (http://www.ncbi.nlm.nih.gov/pubmed?term=%22Liu%20Y%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsP anel.Pubmed_RVAbstract), Chen L (http://www.ncbi.nlm.nih.gov/pubmed?term=%22Chen%20L%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsP anel.Pubmed_RVAbstract), He X (http://www.ncbi.nlm.nih.gov/pubmed?term=%22He%20X%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsP anel.Pubmed_RVAbstract), Fan L (http://www.ncbi.nlm.nih.gov/pubmed?term=%22Fan%20L%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsP anel.Pubmed_RVAbstract), Yang G (http://www.ncbi.nlm.nih.gov/pubmed?term=%22Yang%20G%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsP anel.Pubmed_RVAbstract), Chen X (http://www.ncbi.nlm.nih.gov/pubmed?term=%22Chen%20X%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsP anel.Pubmed_RVAbstract), Lin X (http://www.ncbi.nlm.nih.gov/pubmed?term=%22Lin%20X%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsP anel.Pubmed_RVAbstract), DU L (http://www.ncbi.nlm.nih.gov/pubmed?term=%22DU%20L%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsP anel.Pubmed_RVAbstract), Li Z (http://www.ncbi.nlm.nih.gov/pubmed?term=%22Li%20Z%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsP anel.Pubmed_RVAbstract), Ye H (http://www.ncbi.nlm.nih.gov/pubmed?term=%22Ye%20H%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsP anel.Pubmed_RVAbstract), Mao Y (http://www.ncbi.nlm.nih.gov/pubmed?term=%22Mao%20Y%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsP anel.Pubmed_RVAbstract), Zhao X (http://www.ncbi.nlm.nih.gov/pubmed?term=%22Zhao%20X%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsP anel.Pubmed_RVAbstract), Wei Y (http://www.ncbi.nlm.nih.gov/pubmed?term=%22Wei%20Y%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsP anel.Pubmed_RVAbstract).
Department of Gynecology and Obstetrics, Second West China Hospital, West China Medical School, Sichuan University, Chengdu, Sichuan, People's Republic of China.
Honokiol, a well-tolerated natural product, can inhibit the proliferation of cancer cells. But its water insolubility hampers its systemic administration for therapy of cancer. As a drug delivery system, the pegylated liposome (PEGL) can increase the water solubility and targeting of the drug. Honokiol has been successfully encapsulated by PEGL in our laboratory. We wondered whether the combination treatment with pegylated liposomal honokiol (H-PEGL) and cisplatin (DDP) could improve the antitumor efficacy in ovarian carcinoma. H-PEGL could introduce apoptosis of SKOV3 cells in vitro, which was quantified by flow cytometric analysis, and the cellular morphologic changes were determined by propidium iodide staining. In a human ovarian carcinoma mouse model, combination treatment with H-PEGL (0.4 mg/day for 30 days; intraperitoneal) and DDP (5 mg/kg on days 7, 11, 15, 19; intraperitoneal) acted synergistically to inhibit tumor growth by 91.48% without notable toxicity, but H-PEGL and DDP alone only inhibit tumor growth by 66.83% and 52.5% as compared to the NaCl solution control, respectively. Assessment of microvessel density and apoptosis index by CD31 and terminal deoxynucleotidyl transferase-mediated nick end labeling immunohistochemistry respectively suggested that the antitumor activity of H-PEGL is mediated by angiogenesis inhibition and introduction of apoptosis. Our results showed us a splendid prospect of the clinical application of combination treatment on patients suffering from ovarian cancer with H-PEGL and DDP.
PMID: 17892458 [PubMed - indexed for MEDLINE]
Mutagenesis. (http://javascript%3Cb%3E%3C/b%3E:AL_get%28this,%20%27jour%27,%20%27Mutagenesis .%27%29;) 2010 Feb 15. [Epub ahead of print]
The impact of quercetin on cisplatin-induced clastogenesis and apoptosis in murine marrow cells.
Attia SM (http://www.ncbi.nlm.nih.gov/pubmed?term=%22Attia%20SM%22%5BAuthor%5D).
Department of Pharmacology, College of Pharmacy, King Saud University, PO 2457, Riyadh 11451, Saudi Arabia.
The aim of the present investigation is to determine whether the quercetin in combination with cisplatin can ameliorate cisplatin-induced clastogenesis and apoptosis in the bone marrow cells of mice. The scoring of chromosomal aberrations, micronuclei and mitotic activity were undertaken in the current study as markers of clastogenicity. Apoptosis was analysed by the Annexin V-propidium iodide assay and the occurrence of a hypodiploid DNA peak. Oxidative stress markers such as bone marrow lipid peroxidation and reduced glutathione were assessed as a possible mechanism underlying this amelioration. Quercetin was neither clastogenic nor apoptogenic in mice at doses equivalent to 50 or 100 mg/kg for 2 days. Pre-treatment of mice with quercetin significantly reduced cisplatin-induced clastogenesis and apoptosis in the bone marrow cells and these effects were dose and time dependent. Prior administration of quercetin ahead of cisplatin challenge ameliorated oxidative stress markers. Overall, this study provides for the first time that quercetin has a protective role in the abatement of cisplatin-induced clastogenesis and apoptosis in the bone marrow cells of mice that resides, at least in part, in its antioxidant effects. Therefore, quercetin can be a good candidate to decrease the deleterious effects of cisplatin in the bone marrow cells of cancer patients treated with this drug.
PMID: 20156843 [PubMed - as supplied by publisher]
Clin Cancer Res. (http://javascript%3Cb%3E%3C/b%3E:AL_get%28this,%20%27jour%27,%20%27Clin%20Canc er%20Res.%27%29;) 2010 Jun 18. [Epub ahead of print]
Metabolic Approach to the Enhancement of Antitumor Effect of Chemotherapy: A Key Role of Acetyl-L-Carnitine.
Pisano C (http://www.ncbi.nlm.nih.gov/pubmed?term=%22Pisano%20C%22%5BAuthor%5D), Vesci L (http://www.ncbi.nlm.nih.gov/pubmed?term=%22Vesci%20L%22%5BAuthor%5D), Milazzo FM (http://www.ncbi.nlm.nih.gov/pubmed?term=%22Milazzo%20FM%22%5BAuthor%5D), Guglielmi MB (http://www.ncbi.nlm.nih.gov/pubmed?term=%22Guglielmi%20MB%22%5BAuthor%5D), FoderÃ* R (http://www.ncbi.nlm.nih.gov/pubmed?term=%22Foder%C3%A0%20R%22%5BAuthor%5D), Barbarino M (http://www.ncbi.nlm.nih.gov/pubmed?term=%22Barbarino%20M%22%5BAuthor%5D), D'Incalci M (http://www.ncbi.nlm.nih.gov/pubmed?term=%22D%27Incalci%20M%22%5BAuthor%5D), Zucchetti M (http://www.ncbi.nlm.nih.gov/pubmed?term=%22Zucchetti%20M%22%5BAuthor%5D), Petrangolini G (http://www.ncbi.nlm.nih.gov/pubmed?term=%22Petrangolini%20G%22%5BAuthor%5D), Tortoreto M (http://www.ncbi.nlm.nih.gov/pubmed?term=%22Tortoreto%20M%22%5BAuthor%5D), Perego P (http://www.ncbi.nlm.nih.gov/pubmed?term=%22Perego%20P%22%5BAuthor%5D), Zuco V (http://www.ncbi.nlm.nih.gov/pubmed?term=%22Zuco%20V%22%5BAuthor%5D), Orlandi A (http://www.ncbi.nlm.nih.gov/pubmed?term=%22Orlandi%20A%22%5BAuthor%5D), Passeri D (http://www.ncbi.nlm.nih.gov/pubmed?term=%22Passeri%20D%22%5BAuthor%5D), Carminati P (http://www.ncbi.nlm.nih.gov/pubmed?term=%22Carminati%20P%22%5BAuthor%5D), Cavazza C (http://www.ncbi.nlm.nih.gov/pubmed?term=%22Cavazza%20C%22%5BAuthor%5D), Zunino F (http://www.ncbi.nlm.nih.gov/pubmed?term=%22Zunino%20F%22%5BAuthor%5D).
Oncology - R & D, Sigma-Tau S.p.A.
http://www.ncbi.nlm.nih.gov/corehtml/query/egifs/http:--highwire.stanford.edu-icons-externalservices-pubmed-standard-clincanres_full.gif (http://clincancerres.aacrjournals.org/cgi/pmidlookup?view=long&pmid=20562210)
Abstract
PURPOSE: Acetyl-L-carnitine (ALC) plays a relevant role in energy metabolism and stress response, because its function in the complex metabolic system regulating the acetyl-CoA levels which provide a source of acetyl groups for metabolic and acetylation-regulated processes. Since acetylation may influence p53 activity/stability and, therefore, the response to platinum compounds, this study was designed to investigate the effect of ALC in combination with platinum compounds.EXPERIMENTAL DESIGN: The antiproliferative and antitumor activity studies were performed in a panel of human tumor cell lines with functional or defective p53. The antimetastatic drug efficacy was investigated in the subcutaneously-growing H460/M tumor subline, which is able to generate lung metastases.RESULTS: ALC enhanced sensitivity to cisplatin of tumor cells with functional p53. The sensitization by ALC was reflected in an improved in vivo antitumor efficacy of the combination over cisplatin alone in wild-type p53 lung tumors. ALC did not increase the cisplatin efficacy in the p53-mutant SW620 tumor. ALC exhibited a significant antimetastatic activity and this effect was better exploited in combination with the histone deacetylase inhibitor, ST3595. The in vivo acetyl-L-carnitine/cisplatin combination caused activation of p53, associated with protein acetylation and induction of target genes. CONCLUSIONS: ALC was effective in enhancing the antitumor potential of platinum compounds in wild-type p53 tumors. ALC, alone and in combination with an histone deacetylase inhibitor, exhibited an outstanding antimetastatic activity. Both effects, likely mediated by protein acetylation, may have implications for platinum-based therapy and combinations with histone deacetylase inhibitors.
J Am Soc Nephrol. (http://www.ncbi.nlm.nih.gov/pubmed/15590762#) 2005 Feb;16(2):452-8. Epub 2004 Dec 8.
Nephroprotection by theophylline in patients with cisplatin chemotherapy: a randomized, single-blinded, placebo-controlled trial.
Benoehr P (http://www.ncbi.nlm.nih.gov/pubmed?term=%22Benoehr%20P%22%5BAuthor%5D), Krueth P (http://www.ncbi.nlm.nih.gov/pubmed?term=%22Krueth%20P%22%5BAuthor%5D), Bokemeyer C (http://www.ncbi.nlm.nih.gov/pubmed?term=%22Bokemeyer%20C%22%5BAuthor%5D), Grenz A (http://www.ncbi.nlm.nih.gov/pubmed?term=%22Grenz%20A%22%5BAuthor%5D), Osswald H (http://www.ncbi.nlm.nih.gov/pubmed?term=%22Osswald%20H%22%5BAuthor%5D), Hartmann JT (http://www.ncbi.nlm.nih.gov/pubmed?term=%22Hartmann%20JT%22%5BAuthor%5D).
LINK (http://jasn.asnjournals.org/cgi/pmidlookup?view=long&pmid=15590762)
Source
Department of Nephrology and Rheumatology, Georg-August-University, Robert-Koch Strasse 40, 37075 Göttingen, Germany. pbenoeh@gwdg.de
Abstract
The aim of the present study was to assess the possible prevention of cisplatin-induced impairment of GFR by theophylline in patients with various malignancies. The trial design was parallel, randomized, single blinded, and placebo controlled. Patients received cisplatin at a dosage of 50 mg/m(2) either combined with etoposide, ifosfamide, and epirubicin or with paclitaxel and 5-fluorouracil/folinic acid with the usual precautions, including a standard hydration scheme before application of cisplatin in both arms. In the control arm, placebo was administered; in the verum arm, patients received theophylline in a loading dose of 4 mg/kg intravenously over 30 min before cisplatin, followed by 0.4 mg/kg per min over a minimum of 6 h, and then 350 mg three times daily orally for 4 consecutive days after completion of chemotherapy. GFR of each patient was assessed by renal clearance of inulin within 3 d before and at day 5 after cisplatin chemotherapy. Despite usual precautions, patients in the placebo group had a 21% decrease (range, 11 to 31%) of inulin clearance after a single cycle of cisplatin-containing chemotherapy (92.9 +/- 3.4 versus 71.8 +/- 3.5 ml/min; P < 0.01). Patients who received theophylline had no deterioration of GFR (91.5 +/- 3.7 versus 90.0 +/- 3.8 ml/min; P > 0.05). No adverse effects have been observed during theophylline application. Conventional precautions such as hydration and osmotic diuresis cannot prevent a significant decrease of GFR after a single cycle of cisplatin-containing chemotherapy. The prophylactic application of theophylline as an intravenous loading dose and oral maintenance regimen may preserve kidney function in terms of GFR.
<dl class="rprtid"><dt>PMID:</dt><dd>15590762</dd><dd> [PubMed - indexed for MEDLINE] </dd><dd>
</dd></dl>Free full text