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Cancer Biology & Therapy Apr 2007Mucositis is a common, costly and unpleasant side effect of cancer chemotherapy and radiotherapy. Velafermin (FGF-20) has shown the potential to reduce these side...
Mucositis is a common, costly and unpleasant side effect of cancer chemotherapy and radiotherapy. Velafermin (FGF-20) has shown the potential to reduce these side effects. Irinotecan is a chemotherapeutic agent which is commonly used in solid tumors, and causes GI mucositis manifested by severe diarrhea. Therefore the primary aim of this study was to investigate whether velafermin reduces the GI mucositis induced by irinotecan. The secondary aim was to test varying schedules of administration of velafermin. Groups of tumor-bearing DA rats (6 per group) were treated with varying doses (4, 8 or 16 mg/kg) of velafermin intraperitoneally either prior to, prior to and during, or after chemotherapy treatment. Rats received a single dose of 200 mg/kg irinotecan intraperitoneally. Rats were monitored closely for the incidence and severity of diarrhea and mortality before being killed 192 h following treatment. Mortality, diarrhea and histopathology were assessed throughout the gastrointestinal tract. Severe or moderate diarrhea occurred in approximately 40% of rats treated with irinotecan alone. This was associated with a 50% mortality rate 96 h following chemotherapy. Velafermin administered at 16 mg/kg prior to irinotecan improved gastrointestinal mucositis as measured by reduced diarrhea and mortality following irinotecan chemotherapy in the DA rat. Rats that received velafermin prior to, or prior to and during irinotecan treatment did develop severe or moderate diarrhea, however it occurred later, in fewer rats and was not associated with mortality. Other dosing regimens were not as effective. This has important implications for the use of velafermin in GI mucositis in humans, and should be further studied.
Topics: Animals; Antineoplastic Agents, Phytogenic; Body Weight; Camptothecin; Diarrhea; Fibroblast Growth Factors; Gastroenteritis; Irinotecan; Mucositis; Rats; Rats, Inbred Strains
PubMed: 17457046
DOI: 10.4161/cbt.6.4.3848 -
Current Opinion in Investigational... Nov 2005CuraGen is developing velafermin (CG-53135), human fibroblast growth factor-20 administered intravenously, for the potential treatment and prevention of oral mucositis...
CuraGen is developing velafermin (CG-53135), human fibroblast growth factor-20 administered intravenously, for the potential treatment and prevention of oral mucositis (OM). By December 2004, phase II trials for the prevention of OM in cancer patients undergoing bone marrow transplant had been initiated, and in September 2005 CuraGen indicated that results from this study will be reported during the first quarter of 2006.
Topics: Animals; Disease Models, Animal; Drug Evaluation, Preclinical; Fibroblast Growth Factors; Humans; Infusions, Intravenous; Patents as Topic; Radiation-Protective Agents; Radiotherapy; Randomized Controlled Trials as Topic; Stomatitis
PubMed: 16312140
DOI: No ID Found -
International Journal of Radiation... May 2008Velafermin (recombinant human fibroblast growth factor-20, rhFGF-20) has been shown to reduce the severity and duration of mucositis in preclinical acute (single dose)...
PURPOSE
Velafermin (recombinant human fibroblast growth factor-20, rhFGF-20) has been shown to reduce the severity and duration of mucositis in preclinical acute (single dose) radiation and chemotherapy/radiation models of oral mucositis. Our present study assessed the impact of velafermin on the severity and duration of oral mucositis that occurred as a consequence of fractionated radiation.
EXPERIMENTAL DESIGN
Male Golden Syrian hamsters were exposed to eight doses of radiation (7.5 Gy/dose) to the cheek pouch on days 0, 1, 2, 3, 6, 7, 8 and 9 that resulted in severe mucositis. Velafermin (4 mg/kg intraperitoneally) was administered on days 3 and 9; days 2, 3, 8 and 9; days 3, 4, 9 and 10; or days 4, 5, 10 and 11.
RESULTS
Although all velafermin-treated groups showed some reduction in the degree of mucositis relative to the vehicle control, the most significant reduction (p < 0.001) was observed in the groups treated on days 3 and 9 or on days 4, 5, 10 and 11. Further histological analysis of resected buccal mucosa revealed improvements in epithelial tissue degradation, connective tissue degradation and inflammation severity after velafermin treatment. Most notably, velafermin treatment reduced inflammatory cytokines interleukin-6 (IL-6) and tumor necrosis factor (TNF) production possibly through nuclear factor-kappaB (NF-kappaB) mediation. The detection of increased NF-E2-related factor-2 (NRF-2) expression in the early onset stage of mucositis in the buccal mucosa suggested additional protective benefits from reactive oxygen species (ROS) generated as a consequence of fractionated radiation treatment.
CONCLUSION
Thus, velafermin provided therapeutic benefit in a hamster model of oral mucositis induced by fractionated radiation therapy.
Topics: Animals; Cheek; Cricetinae; Epithelium; Fibroblast Growth Factors; Humans; Inflammation; Interleukin-6; Male; Mouth Mucosa; NF-E2-Related Factor 2; NF-kappa B; Radiation Injuries; Stomatitis; Tumor Necrosis Factor-alpha
PubMed: 18464069
DOI: 10.1080/09553000802007601 -
Supportive Care in Cancer : Official... May 2008The objective of this study was to evaluate the safety and tolerability of velafermin in patients at risk of developing severe oral mucositis (OM) from chemotherapy.
GOALS OF WORK
The objective of this study was to evaluate the safety and tolerability of velafermin in patients at risk of developing severe oral mucositis (OM) from chemotherapy.
MATERIALS AND METHODS
This study was a single-center, open-label, single-dose escalation, phase I trial in patients undergoing high-dose chemotherapy (HDCT) and autologous peripheral blood stem cell transplant (PBSCT). Velafermin was administered 24 h after stem cell infusion as a single intravenous dose infused over 15 min. Clinical safety variables were assessed and OM status scored daily for 30 days using the World Health Organization (WHO) grading scale.
MAIN RESULTS
Thirty patients were treated with velafermin at doses of 0.03 (n = 10), 0.1 (n = 10), 0.2 (n = 8), or 0.33 mg/kg (n = 2). Patients were diagnosed with multiple myeloma (n = 16), non-Hodgkin's lymphoma (n = 12), acute myelogenous leukemia (n = 1), or desmoplasmic round cell tumor (n = 1). Velafermin was well tolerated at doses up to 0.2 mg/kg. There were no drug-related serious adverse events. No patient discontinued because of adverse events; however, two patients administered 0.33 mg/kg developed adverse reactions immediately after infusion of the study drug. No other patients were treated at this dose level. The most frequent (>35% of patients) treatment-emergent adverse events were diarrhea, fatigue, pyrexia, vomiting, and nausea. Most adverse events were mild or moderate and resolved the same day without sequelae. Eight (27%) patients developed WHO grade 3 or 4 OM during the study; seven of these patients received high-dose melphalan as a conditioning regimen.
CONCLUSION
Velafermin was well tolerated by autologous PBSCT patients at doses up to 0.2 mg/kg.
Topics: Adult; Aged; Antineoplastic Agents; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Fibroblast Growth Factors; Hematologic Neoplasms; Humans; Male; Middle Aged; Peripheral Blood Stem Cell Transplantation; Stomatitis; Treatment Outcome
PubMed: 17710442
DOI: 10.1007/s00520-007-0325-9 -
Methods and Findings in Experimental... 2007Gateways to Clinical Trials are a guide to the most recent clinical trials in current literature and congresses. The data the following tables have been retrieved from...
Gateways to Clinical Trials are a guide to the most recent clinical trials in current literature and congresses. The data the following tables have been retrieved from the Clinical Trials Knowledge Area of Prous Science Integrity, the drug discovery and development portal, http://integrity.prous.com. This issues focuses on the following selection of drugs: 4'-Thio-ara-C, 5-methyltetrahydrofolate; ABT-089, AD-237, AF-37702, alvocidib hydrochloride, apricitabine, armodafinil, atrasentan, AVE-5883, avian influenza vaccine, azimilide hydrochloride; Banoxantrone, BIBF-1120; CD34+ cells, certolizumab pegol, CHIR-258, cilansetron, CoFactor, CX-3543, cystemustine; D-003, dexloxiglumide, DMXB-anabaseine; Ecogramostim, elcometrine, elcometrine/ethinylestradiol, etravirine; Fenretinide, fingolimod hydrochloride, fospropofol disodium; Gaboxadol, gestodene, glutamine; Human insulin, hyaluronic acid; Incyclinide, indacaterol, ispronicline, istradefylline; Labradimil, lamifiban, lapatinib, L-arginine hydrochloride, liposomal cisplatin, liposome encapsulated paclitaxel, LY-517717; Manidipine hydrochloride/delapril hydrochloride, maraviroc, MBP(82-98), MD-0727, MDX-214, melanotan I, MMR vaccine; Nacystelyn, nalfurafine hydrochloride, nibentan, nilotinib, NK-105; OBI-1, oblimersen sodium, olmesartan medoxomil, olmesartan medoxomil/hydrochlorothiazide, oregovomab; Pexelizumab, PG-116800, PG-CPT, PHA-794428, prasugrel; RC-3095, rDNA insulin, RFB4(dsFv)-PE38, rhEndostatin, rhenium Re-186 etidronate, rhGM-CSF, roflumilast, romidepsin; Sarcosine, SGLU1, SGN-40, succinobucol; TAU, teduglutide, telatinib, tesofensine, tipifarnib, tirapazamine, TKA-731, tolvaptan, trabectedin; Vaccimel, vatalanib succinate, velafermin, vildagliptin, vinflunine; XP-19986; YM-155.
Topics: Clinical Trials as Topic; Humans
PubMed: 17344945
DOI: No ID Found -
Methods and Findings in Experimental... 2008(-)-Epigallocatechin gallate, 501516, 89-12; Abatacept, Adalimumab, Adefovir dipivoxil, AG-701, Agatolimod sodium, Alefacept, Aliskiren fumarate, Apixaban, Atazanavir...
(-)-Epigallocatechin gallate, 501516, 89-12; Abatacept, Adalimumab, Adefovir dipivoxil, AG-701, Agatolimod sodium, Alefacept, Aliskiren fumarate, Apixaban, Atazanavir sulfate, Atrasentan, Axitinib; BI-1744-CL, BIBF-1120, BIBW-2992, Bortezomib; Carboxyamidotriazole, Caspofungin acetate, CBP-501, Cediranib, Ceftobiprole, Certolizumab pegol, Cetuximab, Cholesteryl hydrophobized polysaccharide-Her2 protein complex, CHP-NY-ESO-1, Cypher; Dalbavancin, Dalcetrapib, Daptomycin, Darapladib, Deferasirox, Deforolimus, Denosumab, DNA-HIV-C, Dovitinib, DR-5001, Dronedarone hydrochloride, DT388IL3; E75, EC-17/EC-90, Ecogramostim, Efungumab, Entecavir, EP HIV-1090, EP-2101, Everolimus, Ezetimibe, Ezetimibe/simvastatin; Faropenem daloxate, Fluticasone furoate, Fondaparinux sodium, Fospropofol disodium, Fulvestrant; Golimumab, GSK-089, GW-590735; HO/03/03, hTERT572, hTERT572Y; Iloperidone; Immunoglobulin intravenous (human), Ispinesib mesylate, Istradefylline, Ixabepilone; JR-031, JX-594; KLH; Laropiprant, Lecozotan hydrochloride, Lenalidomide, Lestaurtinib, Linezolid; MGCD-0103, MK-0646, MVA-BN Measles; NI-0401, Niacin/laropiprant, NSC-719239, NYVAC-C; Ospemifene; Paliperidone palmitate, PAN-811, PCV7, Pegfilgrastim, Peginterferon alfa-2a, PEGirinotecan, Perifosine, Pertuzumab, PF-00299804, Picoplatin, Pimavanserin tartrate, Pitavastatin calcium, Pomalidomide, Prasterone, Pratosartan, Prucalopride, PSMA27/pDOM, Pyridoxal phosphate; QS-21, Quercetin; Rebimastat, Rimonabant, Rolofylline, Romidepsin, Rosuvastatin calcium, RTS,S/SBAS2; SCH-530348, SN-29244, Soblidotin, Sodium dichloroacetate, Solifenacin succinate, Sorafenib, Spheramine, SU-6668, Succinobucol; Taranabant, Taxus, Telaprevir, Telavancin hydrochloride, Telbivudine, Tenofovir disoproxil fumarate, Tigecycline, Tiotropium bromide, Tocilizumab, Triphendiol; UC-781, Udenafil, UNIL-025; V-5 Immunitor, Valsartan/amlodipine besylate, Varenicline tartrate, Velafermin, Vernakalant hydrochloride, Vinflunine, Vitespen, Vorinostat, VX-001; Xience V, XRP-0038; Yttrium Y90 Epratuzumab; Z-360, Ziconotide, Ziprasidone hydrochloride, Zotarolimus, Zotarolimus-eluting stent.
Topics: Clinical Trials as Topic; Humans
PubMed: 18850047
DOI: No ID Found -
Cellular Signalling Jan 2022Macrophages, which are the main regulators of the tumor-associated microenvironment, play a crucial role in the progression of various tumors. The anti-inflammatory role...
Macrophages, which are the main regulators of the tumor-associated microenvironment, play a crucial role in the progression of various tumors. The anti-inflammatory role of β-catenin in macrophages has been extensively studied in recent years. However, the association between macrophages and β-catenin with regards to the development of glioma has not yet been investigated, at least to the best of our knowledge. The present study found that fibroblast growth factor 20 (FGF20), as a paracrine cytokine, was secreted by glioma cells and acted on macrophages. FGF20 treated macrophages exhibited a decreased pro-inflammatory phenotype upon LPS and IFN-γ stimulation, characterized by the decreased the level of M1 macrophage markers and the reduced production of pro-inflammatory cytokines. Mechanistic analysis revealed that FGF20 interacted with FGF receptor 1 isoform of macrophages, and subsequently increased the stability of β-catenin via phosphorylating GSK3β, which suppressed macrophage polarization to the M1-phenotype. Finally, it was found that FGF20 of glioma cells expression was upregulated by the glucocorticoids (GCs) treatment, and decreased FGF20 expression of glioma cells markedly blocked the effects of GCs on the polarization of macrophages. On the whole, the present study demonstrates that FGF20, secreted from glioma cells, participates the GCs regulated macrophage function and exerts anti-inflammatory effects during the treatment of glioma by GCs. Moreover, a molecular link was identified between glioma cells and macrophages, demonstrating that FGF20 modulates the GCs-induced dysfunction of macrophages during glioma development.
Topics: Fibroblast Growth Factors; Glioma; Humans; Macrophage Activation; Macrophages; Tumor Microenvironment; beta Catenin
PubMed: 34757019
DOI: 10.1016/j.cellsig.2021.110181 -
Neurological Research Apr 2017Many studies have investigated the association between fibroblast growth factor 20(FGF20) rs12720208(C/T) polymorphism and the susceptibility of Parkinson's disease... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
Many studies have investigated the association between fibroblast growth factor 20(FGF20) rs12720208(C/T) polymorphism and the susceptibility of Parkinson's disease (PD). However, published data are still controversial. Here, we performed a meta-analysis to evaluate the association of rs12720208 polymorphism with the risk of PD.
METHODS
Up to April 2016, Pubmed, EMbase, Web of science, the Chinese National Knowledge Infrastructure, and Wanfang Medicine were reviewed to identify appropriate documents. A total of seven papers involving 11 studies with 3360 PD cases and 3681 controls were included based on the strict inclusion and exclusion standards. And STATA 12.0 statistics software was used to calculate available data from each study. The pooled odds ratios (OR) and 95% confidence interval (CI) were calculated to assess the association between FGF20 rs12720208 polymorphism and PD risk.
RESULTS
When all studies were pooled into this meta-analysis, neither the minor T allele frequencies nor the genotypic distributions were different between PD cases and controls. But the subgroup analysis stratified by ethnicity showed FGF20 rs12720208 polymorphism was associated with increased risk in the allele model (T vs. C:OR = 1.167, 95% CI = 1.020-1.335) and dominant model (TT + TC vs. CC:OR = 1.156, 95% CI = 1.001-1.335) in Caucasians but not in Asians.
CONCLUSIONS
This meta-analysis indicates that rs12720208 C/T variant might be associated with PD susceptibility in Caucasians.
Topics: Animals; Fibroblast Growth Factors; Genetic Predisposition to Disease; Humans; Parkinson Disease; Polymorphism, Single Nucleotide; White People
PubMed: 28191856
DOI: 10.1080/01616412.2017.1286542 -
Journal of Orthopaedic Research :... Jul 2021Musculoskeletal malignancy is often accompanied by aberrant bone remodeling, leading to tumor cell invasion into skeletal tissues and causing severe pain. BMPs, FGF-2,...
Musculoskeletal malignancy is often accompanied by aberrant bone remodeling, leading to tumor cell invasion into skeletal tissues and causing severe pain. BMPs, FGF-2, and RANKL have been identified as promising regulators in physiological bone remodeling. In this study, we explored the expressional profile of BMPs, FGF-2, and RANKL in 1361 patients with 22 varieties of musculoskeletal tumors. Notably, the expression of FGF-2 and RANKL was under detected in all patients. Among BMP1 to BMP15, we found that BMP1, BMP2, BMP4, BMP5, BMP6, and BMP7 were prevalent. In comparison with normal bones, osteosarcoma highly expressed BMP1, BMP2, BMP4, and BMP7 with statistical significance. Synovial sarcoma upregulated BMP4, BMP5, and BMP7; rhabdomyosarcoma increased BMP1 and BMP4; and alveolar soft part sarcoma upregulated BMP1, BMP4, and BMP7. To visualize the BMP-oriented interactions in a bone tumor microenvironment, we have developed novel software that analyzes numerous cell-to-cell and ligand-to-receptor interactions, that is, Environmentome, delineating that osteosarcoma-secreted BMP-4 and synovial sarcoma-secreted BMP7 potently interact with osteoblasts, osteocytes, osteoclast precursors, and mature osteoclasts. Specifically, quantification analysis revealed that the relationship between osteosarcoma and mature osteoclast/precursor, BMP4-BMPR2 and BMP4-ACVR2A interactions were most potent. Regarding the association between osteosarcoma and osteocyte/osteoblast, BMP4-ACVR1 and BMP4-BMPR2 were the key interactions. In the connection between synovial sarcoma and mature osteoclast/precursor, BMP7-ACVR2A and BMP7-BMPR2 interactions were most remarkable. With regard to the cellular link between synovial sarcoma and osteocyte/osteoblast, BMP7-BMPR2 was identified as a potent interaction. In conclusion, our new outlook suggests delivering the pathological events that clinically underlie behind severe skeletal pain or fracture in musculoskeletal tumors.
Topics: Bone Morphogenetic Proteins; Bone Neoplasms; Bone Remodeling; Bone and Bones; Chondrosarcoma; Fibroblast Growth Factors; Humans; Multiple Myeloma; Muscle Neoplasms; Osteosarcoma; RANK Ligand; Tumor Microenvironment
PubMed: 33034913
DOI: 10.1002/jor.24879 -
CNS Neuroscience & Therapeutics Jan 2022
Topics: Asian People; Female; Fibroblast Growth Factors; GTP Cyclohydrolase; Genetic Predisposition to Disease; Humans; Male; Middle Aged; Parkinson Disease; Synaptotagmins
PubMed: 34674384
DOI: 10.1111/cns.13745