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Cutis Aug 2023
Topics: Humans; Fibroblast Growth Factor 7; Antineoplastic Agents; Cisplatin; Neck; Exanthema; Stomatitis
PubMed: 37820333
DOI: 10.12788/cutis.0835 -
Journal of Reconstructive Microsurgery Oct 2022Radiation-associated soft tissue injury is a potentially devastating complication for head and neck cancer patients. The damage can range from minor sequelae such as... (Review)
Review
BACKGROUND
Radiation-associated soft tissue injury is a potentially devastating complication for head and neck cancer patients. The damage can range from minor sequelae such as xerostomia, which requires frequent daily maintenance, to destructive degenerative processes such as osteoradionecrosis, which can contribute to flap failure and delay or reverse oral rehabilitation. Despite the need for effective radioprotectants, the literature remains sparse, primarily focused on interventions beyond the surgeon's control, such as maintenance of good oral hygiene or modulation of radiation dose.
METHODS
This narrative review aggregates and explores noninvasive, systemic treatment modalities for prevention or amelioration of radiation-associated soft tissue injury.
RESULTS
We highlighted nine modalities with the most clinical potential, which include amifostine, melatonin, palifermin, hyperbaric oxygen therapy, photobiomodulation, pentoxifylline-tocopherol-clodronate, pravastatin, transforming growth factor-β modulators, and deferoxamine, and reviewed the benefits and limitations of each modality. Unfortunately, none of these modalities are supported by strong evidence for prophylaxis against radiation-associated soft tissue injury.
CONCLUSION
While we cannot endorse any of these nine modalities for immediate clinical use, they may prove fruitful areas for further investigation.
Topics: Amifostine; Deferoxamine; Fibroblast Growth Factor 7; Humans; Melatonin; Pravastatin; Soft Tissue Injuries; Transforming Growth Factors
PubMed: 35213927
DOI: 10.1055/s-0042-1742731 -
Endocrine, Metabolic & Immune Disorders... 2020Despite significant progress in the diagnosis of contact dermatitis, the identification by specific tests or biomarkers remains an unsolved issue, particularly when...
BACKGROUND
Despite significant progress in the diagnosis of contact dermatitis, the identification by specific tests or biomarkers remains an unsolved issue, particularly when needed for the confirmation of the occupational origin of the disease.
OBJECTIVE
To characterize the plasma proteome profile in occupational dermatitis in workers of paint industry.
METHODS
The study has a case-control design, comparing exposed workers with and without occupational contact dermatitis, matched for age, gender, occupational history, and comorbidities. An immunological assay (Human XL Cytokine Array Kit - ARY022B, R&D Systems) was used to measure the plasma levels of 105 cytokines and chemokines in a pooled sample of the cases and a pooled sample of the controls.
RESULTS
A 1.5-fold increase was noticed for interleukin 3, interleukin 10, and leptin in cases, as compared to controls. Fibroblast growth factor-7 and growth/differentiation factor-15 showed a 1.4-fold increase, while interleukin 19, interleukin 31, and macrophage inflammatory protein 3a.had only a 1.3- fold increase. The leukemia inhibitory factor was the only plasma cytokine that showed a 1.3-fold decrease. All other cytokines had a variation of less than 1.2-fold between cases and controls.
CONCLUSION
The recognition of the molecular signatures is very important for an accurate and indisputable diagnosis of occupational contact dermatitis. In workers from the paint industry, plasma levels of interleukins 3, 10, 13 and 19, fibroblast growth factor-7, and growth/differentiation factor-15, together with leukemia inducible factor, may differentiate subjects with contact dermatitis from those without skin lesions.
Topics: Adult; Biomarkers; Case-Control Studies; Cytokines; Dermatitis, Occupational; Female; Humans; Male; Middle Aged; Paint
PubMed: 32515314
DOI: 10.2174/1871530320666200607194021 -
Physiological Reports Apr 2022Although full-length fibroblast growth factor 7 (FGF7) blocks cyclophosphamide-induced urothelial apoptosis in mice, limitations include high production costs because of...
Although full-length fibroblast growth factor 7 (FGF7) blocks cyclophosphamide-induced urothelial apoptosis in mice, limitations include high production costs because of its large size. We previously identified a small peptide derived from FGF2 that mitigated acute radiation syndrome as well as full-length FGF2. Based on the sequence of the FGF2 peptide, we synthesized a corresponding 19 amino acid FGF7 peptide (FGF7p). Our objectives were to determine if systemic FGF7p triggered the downstream targets and protected against cyclophosphamide bladder injury similar to full-length FGF7. We administered FGF7p or vehicle subcutaneously (SQ) to mice subjected to no injury or intraperitoneal (IP) cyclophosphamide and harvested bladders 1 day after injury. We then performed hematoxylin and eosin, TUNEL and immunofluorescence (IF) staining. In uninjured mice, a 20 mg/kg threshold FGF7p dose induced expression of phosphorylated (activated) FRS2α (pFRS2α), and pAKT in urothelium (consistent with cytoprotective effects of FGF7). We then gave FGF7p (20 mg/kg) or vehicle at 72 and 48 h prior to cyclophosphamide. One day after injury, TUNEL staining revealed many more apoptotic urothelial cells with vehicle treatment versus FGF7p treatment. IF for pAKT and readouts of two anti-apoptotic AKT targets (BAD and mTORC1) revealed minimal staining with vehicle treatment, but strong urothelial expression for all markers with FGF7p treatment. In conclusion, FGF7p appears to block bladder urothelial apoptosis via AKT and its targets, similar to FGF7. FGF7p is much more inexpensive to make and has a longer shelf life and higher purity than FGF7.
Topics: Animals; Cyclophosphamide; Fibroblast Growth Factor 2; Fibroblast Growth Factor 7; Mice; Peptides; Proto-Oncogene Proteins c-akt; Urinary Bladder; Urothelium
PubMed: 35388988
DOI: 10.14814/phy2.15241 -
Journal of Translational Medicine Mar 2024Ovarian cancer (OC) is distinguished by its aggressive nature and the limited efficacy of current treatment strategies. Recent studies have emphasized the significant...
BACKGROUND
Ovarian cancer (OC) is distinguished by its aggressive nature and the limited efficacy of current treatment strategies. Recent studies have emphasized the significant role of cancer-associated fibroblasts (CAFs) in OC development and progression.
METHODS
Employing sophisticated machine learning techniques on bulk transcriptomic datasets, we identified fibroblast growth factor 7 (FGF7), derived from CAFs, as a potential oncogenic factor. We investigated the relationship between FGF7 expression and various clinical parameters. A series of in vitro experiments were undertaken to evaluate the effect of CAFs-derived FGF7 on OC cell activities, such as proliferation, migration, and invasion. Single-cell transcriptomic analysis was also conducted to elucidate the interaction between FGF7 and its receptor. Detailed mechanistic investigations sought to clarify the pathways through which FGF7 fosters OC progression.
RESULTS
Our findings indicate that higher FGF7 levels correlate with advanced tumor stages, increased vascular invasion, and poorer prognosis. CAFs-derived FGF7 significantly enhanced OC cell proliferation, migration, and invasion. Single-cell analysis and in vitro studies revealed that CAFs-derived FGF7 inhibits the ubiquitination and degradation of hypoxia-inducible factor 1 alpha (HIF-1α) via FGFR2 interaction. Activation of the FGF7/HIF-1α pathway resulted in the upregulation of mesenchymal markers and downregulation of epithelial markers. Importantly, in vivo treatment with neutralizing antibodies targeting CAFs-derived FGF7 substantially reduced tumor growth.
CONCLUSION
Neutralizing FGF7 in the medium or inhibiting HIF-1α signaling reversed the effects of FGF7-mediated EMT, emphasizing the dependence of FGF7-mediated EMT on HIF-1α activation. These findings suggest that targeting the FGF7/HIF-1α/EMT axis may offer new therapeutic opportunities to intervene in OC progression.
Topics: Humans; Female; Cancer-Associated Fibroblasts; Fibroblast Growth Factor 7; Cell Line, Tumor; Signal Transduction; Ovarian Neoplasms; Hypoxia-Inducible Factor 1, alpha Subunit; Epithelial-Mesenchymal Transition; Cell Movement
PubMed: 38491511
DOI: 10.1186/s12967-024-05085-y -
Physiological Reports Jun 2022We previously identified a peptide derived from human fibroblast growth factor 7 (FGF7p) that blocks urothelial apoptosis similar to full-length FGF7, although effects...
We previously identified a peptide derived from human fibroblast growth factor 7 (FGF7p) that blocks urothelial apoptosis similar to full-length FGF7, although effects of FGF7p on urothelial repair are unknown. Also, while urothelial AKT activation downstream of FGF7p correlated with the anti-apoptotic effects, we have not directly interrogated the role of AKT in mediating the cytoprotection. Our goal was to assess effects of FGF7p on urothelial repair and the role of AKT signaling in mediating the cytoprotective effects of FGF7p. We performed hematoxylin and eosin (H&E), TUNEL, and/or immunofluorescence (IF) staining for various markers in FGF7p-treated mice 28 days after giving cyclophosphamide or after co-administering a systemic AKT antagonist with FGF7p 24 h after cyclophosphamide. Vehicle-treated and injured mice had hyperplastic urothelium, incomplete return of mature superficial cell markers, ongoing proliferation, and continued presence of basal progenitor markers 28 days after injury; conversely, FGF7p-treated mice had normal numbers of urothelial cell layers, nearly complete return of superficial cell markers, limited proliferation and fewer basal progenitor cells 28 days post-injury. Vehicle-treated mice also had ectopic lumenal basal progenitor cell markers, while FGF7p had none 28 days after cyclophosphamide. Co-administration of an AKT inhibitor largely abrogated FGF7p-driven AKT activation and cytoprotection in urothelium 24 h after injury. Thus, FGF7p drives faster and higher fidelity urothelial repair by limiting apoptotic injury via AKT signaling, similar to full-length FGF7. Finally, FGF7p is much less expensive to synthesize and has a longer shelf life and higher purity than FGF7.
Topics: Animals; Apoptosis; Cyclophosphamide; Cytoprotection; Mice; Proto-Oncogene Proteins c-akt; Urothelium
PubMed: 35748317
DOI: 10.14814/phy2.15358 -
Anticancer Research Nov 2020Oral mucositis (OM) is considered to be one of the worst and most debilitating complications of conditioning for hematopoietic cell transplantation (HCT). Prevention and...
BACKGROUND
Oral mucositis (OM) is considered to be one of the worst and most debilitating complications of conditioning for hematopoietic cell transplantation (HCT). Prevention and treatment of this complication is one of the utmost priorities of supportive therapy during transplant procedure. The objective of this study was the analysis of the influence of palifermin, keratinocyte growth factor (KGF), on transplant outcomes in patients undergoing allo-HCT.
PATIENTS AND METHODS
A total of 253 allo-HCTs performed between 2003-2018 in patients aged 0-19 years at a single center were analyzed. KGF was administered in 161 HCTs. Uni- and multivariate risk factor analyses were performed.
RESULTS
In spite of reducing the duration and grade of mucositis, no prognostic impact of KGF was shown for overall survival, event-free survival, relapse incidence, acute and chronic graft-versus-host disease (GVHD), nor GVHD-free relapse-free survival.
CONCLUSION
Palifermin had no impact on transplant outcomes in children and adolescents undergoing allo-HCT.
Topics: Adolescent; Adult; Child; Child, Preschool; Female; Fibroblast Growth Factor 7; Graft vs Host Disease; Hematopoietic Stem Cell Transplantation; Hematopoietic Stem Cells; Humans; Male; Progression-Free Survival; Stomatitis; Transplantation, Homologous; Treatment Outcome; Young Adult
PubMed: 33109594
DOI: 10.21873/anticanres.14677 -
Molecular Oncology Aug 2022We have recently demonstrated that fibroblast growth factor receptor 2 (FGFR2)-mediated signalling alters progesterone receptor (PR) activity and response of oestrogen...
We have recently demonstrated that fibroblast growth factor receptor 2 (FGFR2)-mediated signalling alters progesterone receptor (PR) activity and response of oestrogen receptor α (ER)-positive (ER+) breast cancer (BCa) cell lines to anti-ER agents. Little is known about whether the crosstalk between ER and PR, shown to be modulated by the hormonal background, might also be affected by FGFR2. Here, PR-dependent behaviour of ER+ BCa cells was studied in the presence of oestrogen (E2) and progesterone (P4) and/or FGF7. In vitro analyses showed that FGF7/FGFR2 signalling: (a) abolished the effect of P4 on E2-promoted 3D cell growth and response to tamoxifen; (b) regulated ER and PR expression and activity; (c) increased formation of ER-PR complexes; and (d) reversed P4-triggered deregulation of ER-dependent genes. Analysis of clinical data demonstrated that the prognostic value of FGFR2 varied between patients with different menopausal status; that is, high expression of FGFR2 was significantly associated with longer progression-free survival (PFS) in postmenopausal patients, whereas there was no significant association in premenopausal patients. FGFR2 was found to positively correlate with the expression of JunB proto-oncogene, AP-1 transcription factor subunit (JUNB), an ER-dependent gene, only in premenopausal patients. Molecular analyses revealed that the presence of JunB was a prerequisite for FGFR2-mediated abrogation of P4-induced inhibition of cell growth. Our results demonstrate for the first time that the FGF7/FGFR2-JunB axis abolishes the modulatory effects of PR on ER-associated biological functions in premenopausal ER+ BCa. This may provide foundations for a better selection of patients for FGFR-targeting therapeutic strategies.
Topics: Breast Neoplasms; Female; Fibroblast Growth Factor 7; Humans; Progesterone; Receptor, Fibroblast Growth Factor, Type 2; Receptors, Progesterone; Signal Transduction; Tamoxifen; Transcription Factors
PubMed: 35726195
DOI: 10.1002/1878-0261.13274 -
Drug Development Research May 2024Oral mucositis (OM) remains a significant toxicity among patients being treated with radiotherapy (RT) alone or with concomitant chemotherapy (CRT) for cancers of the... (Comparative Study)
Comparative Study
Comparisons of successful and failed Phase III trials of drugs and biologicals tested for mitigation of oral mucositis in patients being treated with radiotherapy with or without concomitant chemotherapy for cancers of the head and neck.
Oral mucositis (OM) remains a significant toxicity among patients being treated with radiotherapy (RT) alone or with concomitant chemotherapy (CRT) for cancers of the head and neck (HNC). Given its clinical significance as an unmet need and its potential commercial viability, the pharmaceutical industry has been actively pursuing an effective intervention. Despite this interest and activity, only a few agents have been studied in Phase III trials (n = 6). The objective of this study was to identify common features that differentiate successful and failed Phase III OM trials. We used the United States Patent and Trademark Office Patent Public Search database to search patents with "oral mucositis" in the claims. We then searched ClinicalTrials.gov and PubMed to determine if Phase III or Phase II trial data for identified biologics/drugs had been published. We assessed each Phase III and Phase II trial for characteristics that may be associated with trial success or failure. We considered a study as a "success" if the primary endpoint reached statistical significance, and we considered a study as "failure" if the primary endpoint did not reach statistical significance. Of the three successful Phase III trials, one investigated avasopasem manganese (Galera Therapeutics) and two examined palifermin (Amgen). The three failed trials included those evaluating dusquetide (Soligenix), iseganan hydrochloride (IntraBiotics Pharmaceuticals), and clonidine (Monopar Therapeutics). We found that differences in the level of sponsor funding, patient inclusion criteria including radiation source and concomitant chemotherapy regimen, and concordance of primary efficacy outcomes between Phase II and Phase III trials influenced outcomes. To properly design clinical trials for OM in HNC patients, it is important that researchers and sponsors take note of specific study characteristics associated with success or failure, particularly with Phase III trials where the risks and costs are the highest.
Topics: Humans; Head and Neck Neoplasms; Stomatitis; Clinical Trials, Phase III as Topic; Biological Products; Chemoradiotherapy; Clinical Trials, Phase II as Topic; Antineoplastic Agents
PubMed: 38678547
DOI: 10.1002/ddr.22188 -
Molecular Biology Reports Sep 2022Helicobacter pylori as the causative agent of the most common chronic bacterial infectious disease in human still involves a range of clinical challenging complications....
BACKGROUND
Helicobacter pylori as the causative agent of the most common chronic bacterial infectious disease in human still involves a range of clinical challenging complications. In this meantime, the survey of the interaction between H. pylori virulence genes expression and its consequences on gastric antral epithelial cells is Controversial. This study surveyed the correlations between H. pylori cag Pathogenicity Island and virulence factors genes with Fgf7 gene expression as an angiogenic factor in developing gastric cancer in gastric antral epithelial cells of patients with H. pylori infection.
METHOD
Gastric antral biopsy samples collected from patients out of exclusion criteria, including consumption of tobacco, alchohol and anti-H. pylori drugs, were categorized into gastric cancer (case group n:53) and gastritis (control group n:50) with and without H. pylori infection to detect changes in cDNA of fgf7 in gastric antral epithelial cells by using Real Time RT PCR. Extracted total RNA from gastric antral biopsy samples was used to synthesize cDNA for real time PCR. Furthermore, the cDNA of H. pylori cag Pathogenicity Island and other virulence factors genes were detected by using specific designed primers and simple PCR.
RESULTS
Fgf7 gene expression revealed a significantly increase in gastric antral epithelial cells of gastric cancer and H. pylori-positive patients in contrast with gastritis and H. pylori-negative patients (p < 0.05). In the meanwhile, cag Pathogenicity Island and hopQ genotypes showed a positive correlation with Fgf7 gene expression (fold changes of cDNA) in gastric antral epithelial cells (p < 0.05).
CONCLUSION
This study revealed an obvious correlation between Fgf7 gene expression in gastric antral epithelial cells of patients with H. pylori carcinogenic genotypes infection and some host factors including age.
Topics: Bacterial Proteins; DNA, Complementary; Fibroblast Growth Factor 7; Gastric Mucosa; Gastritis; Gene Expression; Genotype; Helicobacter Infections; Helicobacter pylori; Humans; Stomach Neoplasms; Virulence Factors
PubMed: 35799083
DOI: 10.1007/s11033-022-07732-3