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Biology of Blood and Marrow... Jan 2016The purpose of our study was to compare long-term safety outcomes (overall survival, disease progression, and incidence of secondary malignancies) between palifermin and... (Randomized Controlled Trial)
Randomized Controlled Trial
Long-Term Safety Outcomes in Patients with Hematological Malignancies Undergoing Autologous Hematopoietic Stem Cell Transplantation Treated with Palifermin to Prevent Oral Mucositis.
The purpose of our study was to compare long-term safety outcomes (overall survival, disease progression, and incidence of secondary malignancies) between palifermin and placebo in the prevention of oral mucositis in patients with hematological malignancies undergoing autologous hematopoietic stem cell transplantation (HSCT). Patients were enrolled between 1997 and 2005 into 4 phase I to III studies (3 double-blind placebo-controlled and 1 open-label) conducted at 31 sites in Australia, Europe, and the United States. Survival outcomes (overall survival, progression-free survival) were compared using hazard ratios (HRs) estimated with a Cox model that included treatment group, baseline age, disease type, Eastern Cooperative Oncology Group performance status, country, and presence of prior radiotherapy as covariates. The incidence of secondary malignancies was compared with a chi-square test. A total of 672 patients were randomized into the studies (428 palifermin and 244 placebo). The median follow-up time for subjects alive at last visit was 7.9 years (range, .1 to 14.9) for palifermin and 8.8 years (range, .1 to 14.8) for placebo. Palifermin-treated patients had overall survival (HR, 1.01; 95% confidence interval [CI], .78 to 1.31; P = .921) and progression-free survival times (HR, 1.04; 95% CI, .83 to 1.31; P = .733) that were comparable with placebo-treated patients. Secondary malignancies were reported by 13% of palifermin-treated patients versus 11% of placebo patients (P = .477). Breakdown into secondary hematological malignancies (7% versus 6%) or solid tumors (6% versus 6%) did not suggest any differences between the treatment groups. After a follow-up of up to 15 years, comparable long-term safety outcomes (overall survival, progression-free survival, and incidence of secondary malignancies) were observed for palifermin- and placebo-treated patients undergoing autologous HSCT.
Topics: Adult; Autografts; Disease-Free Survival; Female; Fibroblast Growth Factor 7; Follow-Up Studies; Hematologic Neoplasms; Hematopoietic Stem Cell Transplantation; Humans; Male; Middle Aged; Stomatitis; Survival Rate
PubMed: 26303102
DOI: 10.1016/j.bbmt.2015.08.018 -
International Journal of Molecular... Jul 2023The objective of this study was to investigate the potential effects of a formulation derived from the bioactive fraction of nanostructured (BFNB) on the promotion of...
The objective of this study was to investigate the potential effects of a formulation derived from the bioactive fraction of nanostructured (BFNB) on the promotion of hair growth in C57BL/6 mice. The characterization of the follicular phases and histomorphological analysis showed that the topical application of the formulation for 15 days significantly increased pigmentation and hair growth on the dorsum and head of the mice. Additionally, an acceleration of the follicular cycle phases was observed, along with an increase in the number of follicles, hair length, and diameter, compared to mice treated with minoxidil. In silico analysis and molecular characterization demonstrated that BFNB enhances the expression of epidermal growth factor (EGF) and fibroblast growth factor 7 (FGF7), activating the PI3K-AKT-β-catenin signaling pathway, as well as the expression of PCNA, KI-67, Cyclin D1, and Cyclin E, regulating the cell cycle and cell proliferation, crucial events for hair regeneration. Our results strongly suggest the utility of BFNB as a therapeutic alternative to stimulate hair growth and promote hair health.
Topics: Animals; Mice; beta Catenin; Catenins; Cell Proliferation; Epidermal Growth Factor; Fibroblast Growth Factor 7; Hair; Hair Follicle; Mice, Inbred C57BL; Phosphatidylinositol 3-Kinases; Proto-Oncogene Proteins c-akt
PubMed: 37569486
DOI: 10.3390/ijms241512110 -
Annals of Oncology : Official Journal... Sep 2008Oral mucositis is a frequent problem after high-dose methotrexate (HD-MTX), impairing patient's quality of life, leading to higher rates of infections and delaying...
BACKGROUND
Oral mucositis is a frequent problem after high-dose methotrexate (HD-MTX), impairing patient's quality of life, leading to higher rates of infections and delaying subsequent chemotherapy. This report describes the effect of palifermin in patients treated within the GMALL-B-ALL 2002 protocol containing HD-MTX who developed a severe mucositis in cycle A1/B1.
PATIENTS AND METHODS
Ten patients, all with World Health Organization grades III-IV oral mucositis in cycles A1/B1, obtained palifermin with subsequent similar or identical cycles to reduce mucositis. Thus, patients serve as their own control for efficacy of palifermin.
RESULTS
All 10 patients developed grades III-IV mucositis in cycles A1/B1 without palifermin, whereas only two of 10 developed grades III-IV mucositis in corresponding cycles A2/B2 with palifermin. Only four of 10 patients showed infections in the cycles with palifermin compared with 10 of 10 patients without palifermin. The duration of mucositits in patients who acquired a higher grade mucositis despite treatment with palifermin could be reduced from 12.9 days (median) without to 11 days with palifermin. The amount of i.v. opioid analgetics could be significantly reduced.
CONCLUSION
Palifermin might reduce the incidence, severeness and duration of oral mucositis in HD-MTX-based chemotherapy and may influence clinical sequelae such as infection and quality of life.
Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Fibroblast Growth Factor 7; Follow-Up Studies; Humans; Lymphoma, B-Cell; Male; Methotrexate; Middle Aged; Pain Measurement; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Reference Values; Retrospective Studies; Risk Assessment; Severity of Illness Index; Statistics, Nonparametric; Stomatitis; Treatment Outcome
PubMed: 18453519
DOI: 10.1093/annonc/mdn179 -
International Journal of Environmental... Aug 2020Most patients with thyroid cancer suffer from salivary gland (SG) dysfunctions after radioiodine (RI) therapy. We investigated the effects of keratinocyte growth factor...
BACKGROUND
Most patients with thyroid cancer suffer from salivary gland (SG) dysfunctions after radioiodine (RI) therapy. We investigated the effects of keratinocyte growth factor (KGF)-1 on RI-induced SG dysfunction in an animal model.
METHODS
Six C57BL/6 mice were assigned to each of the following groups: treatment naïve control group, RI group, and RI+KGF-1 group. Body and SG weights, salivary flow rates, salivary lag times and changes in 99mTc pertechnetate uptake and excretion were measured, and histologic changes were noted. Amylase activities and epidermal growth factor (EGF) concentrations in saliva were also measured. In addition, TUNEL assays were performed and apoptosis-related protein expressions were assessed.
RESULTS
RI-induced reductions in salivary flow rates and increases in salivary lag times observed in the RI group were not observed in RI+KGF-1 group. Mice in RI group had higher HIF1a levels than controls, but HIF1a levels in RI+KGF-1 group were similar to those in control group. Furthermore, mice in RI+KGF-1 group had more mucin stained acini and decreased periductal fibrosis than mice in RI group, and tissue remodeling of many salivary epithelial cells (AQP5) and endothelial cells (CD31) were observed in RI+KGF-1 group. Amylase activity and expression in saliva were greater in RI+KGF-1 group than in RI group, and fewer apoptotic cells were observed in RI+KGF-1 group. Furthermore, BCLxl (anti-apoptotic) expression was higher, and Bax (pro-apoptotic) expression was lower in RI+KGF-1 group than in RI group.
CONCLUSIONS
Local delivery of KGF-1 might prevent RI-induced SG damage by reducing apoptosis.
Topics: Animals; Apoptosis; Endothelial Cells; Female; Fibroblast Growth Factor 7; Iodine Radioisotopes; Mice; Mice, Inbred C57BL; Salivary Glands
PubMed: 32878050
DOI: 10.3390/ijerph17176322 -
Antioxidants & Redox Signaling Aug 2011Peroxiredoxin 6 (Prdx6) is the prototype and the only mammalian 1-Cys member of the Prdx family. Major differences from 2-Cys Prdxs include the use of glutathione (GSH)... (Review)
Review
Peroxiredoxin 6 (Prdx6) is the prototype and the only mammalian 1-Cys member of the Prdx family. Major differences from 2-Cys Prdxs include the use of glutathione (GSH) instead of thioredoxin as the physiological reductant, heterodimerization with πGSH S-transferase as part of the catalytic cycle, and the ability either to reduce the oxidized sn-2 fatty acyl group of phospholipids (peroxidase activity) or to hydrolyze the sn-2 ester (alkyl) bond of phospholipids (phospholipase A(2) [PLA(2)] activity). The bifunctional protein has separate active sites for peroxidase (C47, R132, H39) and PLA(2) (S32, D140, H26) activities. These activities are dependent on binding of the protein to phospholipids at acidic pH and to oxidized phospholipids at cytosolic pH. Prdx6 can be phosphorylated by MAP kinases at T177, which markedly increases its PLA(2) activity and broadens its pH-activity spectrum. Prdx6 is primarily cytosolic but also is targeted to acidic organelles (lysosomes, lamellar bodies) by a specific targeting sequence (amino acids 31-40). Oxidant stress and keratinocyte growth factor are potent regulators of Prdx6 gene expression. Prdx6 has important roles in both antioxidant defense based on its ability to reduce peroxidized membrane phospholipids and in phospholipid homeostasis based on its ability to generate lysophospholipid substrate for the remodeling pathway of phospholipid synthesis.
Topics: Amino Acid Sequence; Animals; Antioxidants; Catalytic Domain; Fibroblast Growth Factor 7; Gene Expression Regulation; Glutathione Peroxidase; Glutathione Transferase; Humans; Molecular Sequence Data; Oxidative Stress; Peroxiredoxin VI; Phospholipases A2; Phospholipids; Protein Structure, Tertiary
PubMed: 20919932
DOI: 10.1089/ars.2010.3412 -
Cell Proliferation Aug 2002The epithelium of the oral cavity and small intestine of the gastrointestinal tract have a high rate of cell renewal and as such, are sensitive to cytotoxic therapies... (Review)
Review
The epithelium of the oral cavity and small intestine of the gastrointestinal tract have a high rate of cell renewal and as such, are sensitive to cytotoxic therapies that kill rapidly dividing cells. Mucositis is a complication of cancer therapy where impairment of the regenerative capacity of the epithelium leads to atrophy, ulceration and a loss of barrier function. Keratinocyte growth factor (KGF) is an epithelial cell-specific growth and differentiation factor that is trophic for the mucosal epithelium of the gastrointestinal tract. In this study, KGF in normal animals caused epithelial thickening in the squamous epithelium of the oral cavity and increased crypt depth and villus height of the small intestine. It also appeared to regulate gene expression in these tissues including that of some antioxidant enzymes and intestinal trefoil protein. KGF has been shown to be efficacious in several preclinical models of mucositis where KGF pretreatment reduced weight loss typically seen during and after the course of therapy and significantly improved survival. At a tissue level KGF reduced atrophy, accelerated regrowth, and decreased ulcer formation of the oral epithelium after irradiation, and improved crypt survival and prevented villus atrophy in the small intestine of irradiated or chemotherapy-treated mice. Preliminary studies suggest that its efficacy may be partly a consequence of the growth and differentiation effect, and also partly due to regulation of the expression of genes that play a role in mucosal protection. These data suggest that KGF may be useful for the prevention or treatment of mucositis in patients treated with regimens of cancer therapy that have gastrointestinal toxicity.
Topics: Animals; Disease Models, Animal; Fibroblast Growth Factor 7; Fibroblast Growth Factors; Mouth Mucosa; Radiation Injuries, Experimental; Stomatitis
PubMed: 12139710
DOI: 10.1046/j.1365-2184.35.s1.8.x -
PloS One 2023To investigate human corneal epithelial cell and fibroblast migration and growth factor secretion after rose bengal photodynamic therapy (RB-PDT) and the effect of...
PURPOSE
To investigate human corneal epithelial cell and fibroblast migration and growth factor secretion after rose bengal photodynamic therapy (RB-PDT) and the effect of conditioned medium (CM).
METHODS
A human corneal epithelial cell line (HCE-T), human corneal fibroblasts (HCF) and keratoconus fibroblasts (KC-HCF) have been used. Twenty-four hours after RB-PDT (0.001% RB concentration, 565 nm wavelength illumination, 0.17 J/cm2 fluence) cell migration rate using scratch assay and growth factor concentrations in the cell culture supernatant using ELISA have been determined. In addition, the effect of CM has been observed.
RESULTS
RB-PDT significantly reduced migration rate in all cell types, compared to controls (p≤0.02). Migration rate of HCE-T cultures without RB-PDT (untreated) was significantly higher using HCF CM after RB-PDT, than using HCF CM without RB-PDT (p<0.01). Similarly, untreated HCF displayed a significantly increased migration rate with HCE-T CM after RB-PDT, compared to HCE-T CM without treatment (p<0.01). Furthermore, illumination alone and RB-PDT significantly decreased keratinocyte growth factor (KGF) concentration in HCF and KC-HCF supernatant, and RB-PDT significantly decreased soluble N-Cadherin (SN-Cad) concentration in HCF supernatant, compared to controls (p<0.01 for all). In HCE-T CM, RB-PDT increased hepatocyte growth factor (HGF) and basic fibroblast growth factor (FGFb) concentration (p≤0.02), while decreasing transforming growth factor β (TGF-β) concentration (p<0.01). FGFb concentration increased (p<0.0001) and TGF-β concentration decreased (p<0.0001) in HCF CM, by RB-PDT. Epidermal growth factor (EGF), HGF, and TGF-β concentration decreased (p≤0.03) and FGFb concentration increased (p<0.01) in KC-HCF CM, using RB-PDT.
CONCLUSIONS
HCE-T, HCF and KC-HCF migration rate is reduced 24 hours after RB-PDT. In contrast, HCE-T migration is enhanced using HCF CM after RB-PDT, and HCF migration rate is increased through HCE-T CM following RB-PDT. Modulation of EGF, KGF, HGF, FGFb, TGF-β and N-Cadherin secretion through RB-PDT may play an important role in corneal wound healing.
Topics: Humans; Epidermal Growth Factor; Culture Media, Conditioned; Rose Bengal; Cells, Cultured; Fibroblasts; Cell Movement; Transforming Growth Factor beta; Photochemotherapy; Epithelial Cells; Cadherins; Fibroblast Growth Factor 7
PubMed: 38150488
DOI: 10.1371/journal.pone.0296022 -
American Journal of Hematology Oct 2011A previously conducted randomized, double-blind, placebo-controlled study from 2000-2003 tested peri-transplant palifermin (KGF) in 100 recipients of T-replete matched... (Randomized Controlled Trial)
Randomized Controlled Trial
A previously conducted randomized, double-blind, placebo-controlled study from 2000-2003 tested peri-transplant palifermin (KGF) in 100 recipients of T-replete matched related donor allogeneic hematopoietic transplant (MRD allo-HCT). The use of KGF in preclinical transplant models, including an autologous non-human primate model, has been associated with improved immune reconstitution. Therefore, we investigated whether palifermin treated patients (n = 69) had improved absolute lymphocyte counts (ALCs) at days 30, 60 and 100 after transplant compared to placebo treated patients (n = 31). No statistically significant difference in ALC was noted at these time points. Additionally, there was no difference in ALC between patients who received low (240μg/kg) vs. high (720μg/kg) dose palifermin. Patients with a day 30 ALC of >600 ×10/L had a trend towards improved progression-free survival (49% vs. 29%, p=0.07), lower transplant-related mortality (18% vs. 35%, p=0.1) and grade II-IV aGvHD (31% vs. 47%, p=0.14), but this was not influenced by palifermin therapy. We conclude that following myeloablation and a T-replete MSD allogeneic graft, peri-transplant palifermin does not accelerate early lymphocyte recovery. Studies combining palifermin with other agents (as in pre-clinical models) may be required to improve immune reconstitution after allo-HCT.
Topics: Adolescent; Adult; Aged; Child; Cohort Studies; Double-Blind Method; Female; Fibroblast Growth Factor 7; Graft vs Host Disease; Hematologic Neoplasms; Hematopoietic Stem Cell Transplantation; Humans; Male; Middle Aged; Retrospective Studies; T-Lymphocytes; Transplantation, Homologous; Young Adult
PubMed: 21922528
DOI: 10.1002/ajh.22136 -
International Journal of Biological... 2021Fibroblast growth factors (FGFs) include a large family of growth factors that play a critical role in maintaining bone homeostasis, but the specific role of its members...
Fibroblast growth factors (FGFs) include a large family of growth factors that play a critical role in maintaining bone homeostasis, but the specific role of its members such as FGF7 does not well understand. Osteoblasts are a kind of major cells essential for bone formation. Osteoblasts interact with one another to create the unique structure of osteons. The well-connected osteons constitute the cortical bone. As an early osteocyte marker that triggers actin cytoskeleton dynamics, E11 is essential for osteoblasts' dendrites formation. However, the upstream which regulates E11 is mainly unknown. The purpose of this study was to examine the influence of FGF7 on the expression and the distribution of E11 in osteoblasts, which mediated osteoblasts' processes formation and gap junctional intercellular communication (GJIC) partly through connexin43 (Cx43). We first demonstrated that FGF7 increased the expression of E11 in osteoblasts. We then showed that FGF7 promoted osteoblasts' dendrites elongation and functional gap junctions formation. Furthermore, E11 interacted directly with Cx43 in primary osteoblasts. MAPK pathway and PI3K-AKT pathway were involved in the effect of FGF7. Our results shed light on the unique role of FGF7 on osteoblasts, which may indicate that FGF7 plays a more significant role in the later stages of bone development and homeostasis.
Topics: 3T3 Cells; Animals; Cell Communication; Connexin 43; Fibroblast Growth Factor 7; Ligands; MAP Kinase Signaling System; Membrane Glycoproteins; Mice; Osteoblasts
PubMed: 34671204
DOI: 10.7150/ijbs.65240 -
Transplantation and Cellular Therapy Oct 2021The incidence of debilitating oral mucositis (OM) can be as high as 99% after myeloablative conditioning regimens preparing patients with hematologic malignancies for...
The incidence of debilitating oral mucositis (OM) can be as high as 99% after myeloablative conditioning regimens preparing patients with hematologic malignancies for hematopoietic cell transplantation (HCT). Palifermin (KGF) is a recombinant human keratinocyte growth factor that reduces the incidence and duration of severe OM. The long-term safety of KGF has not been well established, however. In this long-term prospective matched-cohort study, patients who received KGF (cases) and underwent autologous or allogeneic HCT for hematologic malignancies between 2006 and 2013 were matched 1:1 to patients who did not receive KGF (controls). The primary outcome was overall survival (OS). Other outcomes were disease relapse, new malignancies, pancreatitis, renal failure requiring dialysis, pulmonary complications, cataract surgery, and acute and chronic graft-versus-host disease (GVHD). The analysis population comprised 2191 matched pairs with a wide range of diseases and donor types that received diverse conditioning and GVHD preventive regimens, representing contemporary practice patterns. The median duration of follow-up was 8 years (range, 1 to 12.5 years). In multivariate analyses, the probabilities of OS (relative risk [RR], 1.01; 95% confidence interval [CI], 0.91 to 1.12), relapse (RR, 1.06; 95% CI, 0.94 to 1.18), new malignancies (RR, 0.89; 95% CI, 0.67 to 1.18), and cataract surgery (RR, 1.05; 95% CI, 0.74 to 1.50) were not statistically significantly different between cases and controls. In univariate analyses, no increased risks were observed for renal failure requiring dialysis, pancreatitis, acute GVHD, chronic GVHD, interstitial pneumonitis/acute respiratory distress syndrome/idiopathic pneumonia syndrome, or bronchiolitis obliterans/cryptogenic organizing pneumonia/bronchiolitis obliterans organizing pneumonia among cases compared with controls. This long-term prospective safety cohort study demonstrates that the KGF group had no increased risk of overall mortality, relapse, new malignancies, or any other key outcome. The broad inclusion criteria allow the results to be generalized to contemporary practice for patients with a wide range of diseases and receiving a wide range of HCT conditioning regimens and graft sources from diverse donor types.
Topics: Cohort Studies; Fibroblast Growth Factor 7; Hematologic Neoplasms; Hematopoietic Stem Cell Transplantation; Humans; Neoplasm Recurrence, Local; Prospective Studies
PubMed: 34224914
DOI: 10.1016/j.jtct.2021.06.028