Paradoxical cancer cell proliferation after FGFR inhibition through decreased p21 signaling in FGFR1-amplified breast cancer cells.

Fibroblast growth factors (FGFs) control various cellular functions through fibroblast growth factor receptor (FGFR) activation, including proliferation, differentiation, migration, and survival. FGFR amplification in ER + breast cancer patients correlate with poor prognosis, and FGFR inhibitors are currently being tested in clinical trials. By comparing three-dimensional spheroid growth of ER + breast cancer cells with and without FGFR1 amplification, our research discovered that FGF2 treatment can paradoxically decrease proliferation in cells with FGFR1 amplification or overexpression. In contrast, FGF2 treatment in cells without FGFR1 amplification promotes classical FGFR proliferative signaling through the MAPK cascade. The growth inhibitory effect of FGF2 in FGFR1 amplified cells aligned with an increase in p21, a cell cycle inhibitor that hinders the G1 to S phase transition in the cell cycle. Additionally, FGF2 addition in FGFR1 amplified cells activated JAK-STAT signaling and promoted a stem cell-like state. FGF2-induced paradoxical effects were reversed by inhibiting p21 or the JAK-STAT pathway and with pan-FGFR inhibitors. Analysis of patient ER + breast tumor transcriptomes from the TCGA and METABRIC datasets demonstrated a strong positive association between expression of FGF2 and stemness signatures, which was further enhanced in tumors with high FGFR1 expression. Overall, our findings reveal a divergence in FGFR signaling, transitioning from a proliferative to stemness state driven by activation of JAK-STAT signaling and modulation of p21 levels. Activation of these divergent signaling pathways in FGFR amplified cancer cells and paradoxical growth effects highlight a challenge in the use of FGFR inhibitors in cancer treatment.

The effect of fibroblast growth factor-2 on the outcomes of tooth replantation: A systematic review of animal studies.

Background/Aim: The ideal treatment of tooth avulsion is replantation. However, replanting teeth may lead to root resorption. Fibroblast growth factor-2 (FGF-2) is a cytokine that plays an important role in wound repair and tissue regeneration. Recently, FGF-2 has been studied a potential regenerative agent to prevent root resorption and ankylosis. The aim of this review is to analyze and summarize the currently available literature focusing on using FGF-2 based regenerative modalities to improve the outcomes of tooth replantation. Materials and Methods: An electronic search was conducted via PubMed/Medline, Google Scholar and ISI Web of Knowledge, using the Medical Subject Headings (MeSH) terms "Basic fibroblast growth factor," "Fibroblast growth factor-2," "tooth replantation," and "replantation" for studies published between January 2001 and June 2021. Data was extracted and quality assessment was carried using the ARRIVE guidelines. Results: Nine animal studies were included in this review. In six studies, FGF-2 had a favorable effect on the tissue regeneration around roots of replanted teeth when compared to other treatment groups. However, quality assessment of the studies revealed many sources of bias and deficiencies in the studies. Conclusions: Within the limitations of this study, it may be concluded that FGF-2 may improve the outcomes of delayed replantation of avulsed teeth. However, more long-term animal studies, with improved experimental designs, and clinical trials are required to determine the clinical potential of the growth factor in improving the outcomes of delayed tooth replantation.

Predictive factors of periodontal regeneration outcomes using rhFGF-2: A case-control study.

OBJECTIVE: This study aimed to investigate the factors influencing the clinical outcomes of regenerative therapy using recombinant human fibroblast growth factor-2 (rhFGF-2). BACKGROUND: rhFGF-2 promotes periodontal regeneration, and identifying the factors influencing this regeneration is important for optimizing the effectiveness of rhFGF-2. METHODS AND MATERIALS: This study used a hospital information-integrated database to identify patients who underwent periodontal regenerative therapy with rhFGF-2. Factors included age, smoking status, diabetes mellitus (DM), periodontal inflamed surface area (PISA) at the initial visit, whether the most posterior tooth was involved or not, and preoperative radiological bone defect angle. Periodontal regenerative therapy outcomes were defined as good if radiographic bone fill ≥35% or periodontal pocket closure at 9-15 months after surgery. Bone fill rate (%) and periodontal pocket depth (mm) were also used as outcome measures. Factors were evaluated by simple regression analysis, and then the association between factors and the outcomes was determined by multivariate analysis. RESULTS: PISA and age at the first visit did not significantly influence the success or failure of bone fill rate byrhFGF-2. However, DM, radiographic bone defect angle, and the most posterior tooth significantly influenced the regenerative effect (success/failure in bone fill) of rhFGF-2. The most posterior tooth was significantly associated with bone fill rate by rhFGF-2. Examination of the association between pocket closure and factors shows that the most posterior tooth significantly influenced. The most posterior tooth and preoperative PPD were significantly associated with pocket reduction depth. For the most posterior tooth, a significantly higher bone regeneration rate (p < .05) was observed with a combination of autologous bone graft and rhFGF-2 than with rhFGF-2 alone, and the effect was significant in multivariate analysis. CONCLUSIONS: The radiographic bone defect angle, the involvement of most posterior teeth, and the presence of DM influenced the effectiveness of rhFGF-2 in periodontal regeneration. However, PISA values and age at the initial visit had no significant effect.

Appropriate dosage, timing, and site of intramuscular injections of brain-derived neurotrophic factor (BDNF) promote motor recovery after facial nerve injury in rats.

INTRODUCTION/AIMS: Daily intramuscular injections of fibroblast growth factor 2 (FGF2) but not of brain-derived neurotrophic factor (BDNF) significantly improve whisking behavior and mono-innervation of the rat levator labii superioris (LLS) muscle 56 days after buccal nerve transection and suture (buccal-buccal anastomosis, BBA). We explored the dose-response of BDNF, FGF2, and insulin growth factor 2 (IGF2) on the same parameters, asking whether higher doses of BDNF would promote recovery. METHODS: After BBA, growth factors were injected (30 µL volume) daily into the LLS muscle over 14, 28, or 56 days. At 56 days, video-based motion analysis of vibrissal whisking was performed and the extent of mono- and poly-reinnervation of the reinnervated neuromuscular junctions (NMJs) of the muscle determined with immunostaining of the nerve with ß-tubulin and histochemical staining of the endplates with Alexa Fluor 488-conjugated α-bungarotoxin. RESULTS: The dose-response curve demonstrated significantly higher whisking amplitudes and corresponding increased mono-innervation of the NMJ in the reinnervated LLS muscle at concentrations of 20-30 µg/mL BDNF administered daily for 14-28 days after BBA surgery. In contrast, high doses of IGF2 and FGF2, or doses of 20 and 40 µg/mL of BDNF administered for 14-56 days had no effect on either whisking behavior or in reducing poly-reinnervation of endplates in the muscle. DISCUSSION: These data suggest that the re-establishment of mono-innervation of whiskerpad muscles and the improved motor function by injections of BDNF into the paralyzed vibrissal musculature after facial nerve injury have translation potential and promote clinical application.

The use of basic fibroblast growth factor to treat intractable Bell's palsy administered via transcanal endoscopic ear surgery.

PURPOSE: Facial nerve decompression surgery is an invasive procedure which has hitherto been the main option for patients with severe intractable Bell's palsy which is resistant to drug treatment. We have developed a new salvage treatment for such patients by using minimally invasive transcanal endoscopic ear surgery (TEES) to deliver the biological regenerative agent, basic fibroblast growth factor (bFGF), to the damaged facial nerve. MATERIALS AND METHODS: An endoscopic salvage treatment group was studied prospectively and was made up of severe intractable Bell's palsy patients who did not respond to high dose steroid treatment and had an ENoG value of 5 % or less. This surgery group was retrospectively compared to a similar control group who had received high dose steroid only. RESULTS: Complete recovery to House-Brackmann (HB) Grade I was achieved by 44.8 % of the endoscopic salvage treatment group which was significantly higher than the 21.2 % of the control group at one-year follow up. Patients with an ENoG value of 1 % to 5 % exhibited a significantly higher complete recovery rate of 71.4 % in the endoscopic salvage treatment group than the 28.6 % of the control group. In addition, no complications were observed including hearing loss. CONCLUSIONS: bFGF delivered via TEES shows considerable promise as a new salvage treatment of severe intractable Bell's palsy that is resistant to high dose steroid treatment without the risks presented by facial nerve decompression surgery.

Clinical Observation of Recombinant Bovine Basic Fibroblast Growth Factor as an Adjuvant Therapy for Patients with Atrophic Acne Scar / 中国医学科学院学报

Objective To study the influence of recombinant bovine basic fibroblast growth factor as an adjuvant therapy on scar alleviation and inflammatory cytokines in patients with atrophic acne scar. Methods The random number table was employed to randomly assign 120 patients with atrophic acne scar into a test group and a control group.Both groups of patients were treated with CO2 lattice laser.After the operation,the control group was routinely smeared with erythromycin ointment and the test group was coated with recombinant bovine basic fibroblast growth factor gel.The clinical efficacy,clinical indicators,scar alleviation,and inflammatory cytokine levels before and after treatment were compared,and adverse reactions were counted. Results The test group had higher total effective rate(P=0.040) and lower total incidence of adverse reactions(P=0.028) than the control group.Compared with the control group,the test group showcased short erythema duration after treatment(P=0.025),early scab forming(P=0.002),and early edema regression(P<0.001).After treatment,the proportion of grade 1 scars graded by Goodman and Baron's acne scar grading system in the test group and control group increased(P=0.001,P=0.027),and the proportion of grade 4 scars decreased(P<0.001,P=0.034).Moreover,the proportion of grade 1 scars in the test group was higher than that in the control group(P=0.031) after treatment,and the proportion of grade 4 scars presented an opposite trend(P=0.031).After treatment,the levels of tumor necrosis factor-α(TNF-α) and interleukin-1β(IL-1β) in both groups declined(all P<0.001),and the test group had lower TNF-α and IL-1β levels than the control group(all P<0.001). Conclusion The recombinant bovine basic fibroblast growth factor gel as an adjuvant therapy of CO2 lattice laser can effectively alleviate the atrophic acne scar,relieve local inflammatory reaction,and has good curative effect and less adverse reactions.

Enriquecimiento de injerto autologo con concentrado de factores de crecimiento / Autologous graft combined with growth factors concentrate

Introducción: Debido a los cambios recientes en torno al tratamiento de las fracturas, en los últimos años se ha priorizado una combinación de métodos no sólo mecánicos sino también biológicos. En este estudio se evalúan los resultados de un tratamiento combinado mediante osteosíntesis y aplicación de injerto enriquecido con agregado plaquetario, con resultados alentadores. Materiales y métodos: Nuestra serie comprendió 29 pacientes tratados entre 1999 y 2006, laboralmente activos, con una edad promedio de 42 años (rango, 26 a 62 años). En todos los casos se efectuó osteosíntesis con el agregado plaquetario rico en factores de crecimiento plaquetario. Los resultados se analizaron en función de la formación de callo fracturario a los 6 meses. La obtención de injerto esponjoso fue dificultosa en los pacientes reintervenidos. Resultados: La obtención y preparación del agregado plaquetario no presentó inconvenientes. La consolidación clínica y radiológica se alcanzó en los 29 casos al término de 4 meses (2-6 meses); en 2 casos fue necesario repetir el procedimiento de aporte sin recambio del implante a los 2 meses de la primera intervención. Conclusiones: El injerto autólogo enriquecido con plasma rico en factores de crecimiento pudo haber contribuido de manera favorable a la consolidación de estos casos complejos, con gran ausencia biológica, en los que habían fracasado otros métodos(AU)

Enriquecimiento de injerto autologo con concentrado de factores de crecimiento / Autologous graft combined with growth factors concentrate

Introducción: Debido a los cambios recientes en torno al tratamiento de las fracturas, en los últimos años se ha priorizado una combinación de métodos no sólo mecánicos sino también biológicos. En este estudio se evalúan los resultados de un tratamiento combinado mediante osteosíntesis y aplicación de injerto enriquecido con agregado plaquetario, con resultados alentadores. Materiales y métodos: Nuestra serie comprendió 29 pacientes tratados entre 1999 y 2006, laboralmente activos, con una edad promedio de 42 años (rango, 26 a 62 años). En todos los casos se efectuó osteosíntesis con el agregado plaquetario rico en factores de crecimiento plaquetario. Los resultados se analizaron en función de la formación de callo fracturario a los 6 meses. La obtención de injerto esponjoso fue dificultosa en los pacientes reintervenidos. Resultados: La obtención y preparación del agregado plaquetario no presentó inconvenientes. La consolidación clínica y radiológica se alcanzó en los 29 casos al término de 4 meses (2-6 meses); en 2 casos fue necesario repetir el procedimiento de aporte sin recambio del implante a los 2 meses de la primera intervención. Conclusiones: El injerto autólogo enriquecido con plasma rico en factores de crecimiento pudo haber contribuido de manera favorable a la consolidación de estos casos complejos, con gran ausencia biológica, en los que habían fracasado otros métodos

Plasma Rico en Plaquetas y su utilización en implantología dental / PPR and his utilization in oral implantology

Se presenta una revisión sobre la utilización del Plasma Rico en Plaquetas en el ámbito de la implantología. El trabajo comienza con la definición de varios conceptos básicos sobre Regeneración Tisular Guiada. A continuación se explican los factores de crecimiento y su participación en los concentrados de plaquetas. Se hace hincapié en los estudios realizados con PRP e implantes y se describe la aparición de unos posibles efectos negativos con el empleo de esta técnica. Por último se exponen las conclusiones del trabajo (AU)

A review about using Platelet Rich Plasma in Implantology is presented. It begins with the basic concepts of Bone Guided Regeneration. Then, growth factors and its implication in Platelet Rich Plasma are described. We want to highlight the experiments with dental implants and PRP. It is also described the probably negative efects of PRP. Finally, we show the rewiev conclusions (AU)

Neuromodulación farmacológica en la enfermedad cerebrovascular / Pharmacological neuromodulation in cerebrovascular disease

La enfermedad cerebrovascular representa la tercera causa de muerte en los países desarrollados y en vías de desarrollo y sus secuelas se comportan como la primera causa de invalidez en los adultos. Las orientaciones terapéuticas más importantes en estos pacientes consisten en mejorar el flujo sanguíneo cerebral y reducir o bloquear las consecuencias metabólicas a nivel subcelular y celular. Los importantes avances producidos en los últimos años en el conocimiento de los mecanismos fisiopatológicos de la isquemia cerebral y en el desarrollo de nuevos fármacos han planteado las expectativas reales de tratamiento y el rechazo de actitudes nihilistas. Se hizo una breve revisión del concepto de plasticidad neuronal y neuromodulación farmacológica. Se expuso un grupo de fármacos neuroprotectores y neurotróficos, algunos de forma experimental, usados en la enfermedad cerebrovascular aguda y crónica(AU)

La utilización de los factores de crecimiento plasmáticos en cirugía oral, maxilofacial y periodoncia [P.R.G.F.] / The use of plasma rich in growth factors in oral and maxillofacial surgery and periodontics [P.R.G.F.]

Se presenta un protocolo para la obtención de un plasma autólogo rico en factores de crecimiento (P.R.G.F) obtenido de forma ambulatoria así como diferentes técnicas de aplicación, para obtener un coágulo rico en factores de crecimiento. Algunas de las ventajas observadas de su uso, son el favorecer la epitelización de una herida, acelerar y favorecer la neoformación ósea, compactar y retener los injertos, relleno de un alveolo post-extracción, ser un excelente osteoconductor y un largo etcetera (AU)