RESUMO
Actinic keratoses (AKs) and squamous cell carcinoma in situ (SCCIS) are precursor lesions for cutaneous squamous cell carcinoma (cSCC), the second most common form of cancer. Current topical therapies for AKs and SCCIS promote skin inflammation to eradicate lesions and do not directly target the biological mechanisms driving growth. We hypothesized that topical small molecule inhibitors targeting kinases promoting keratinocyte growth in AKs and SCCIS could induce regression of these lesions with less inflammation. To test this hypothesis, we determined the efficacy of topical dasatinib, 5-fluorouracil and BEZ-235 in inducing regression of cSCCs in the K14-Fyn Y528 transgenic mouse model. Topical dasatinib induced regression of cSCC with less inflammation, no ulceration and no mortality compared to 5-fluorouracil. Topical BEZ-235 induced cSCC regression similar to dasatinib without erythema or ulceration. These data indicate that topical small molecule kinase inhibitors targeting drivers of AK/SCCIS/cSCC growth represent a promising therapeutic approach to treat these common skin lesions.
Assuntos
Carcinoma de Células Escamosas/tratamento farmacológico , Ceratose Actínica/tratamento farmacológico , Inibidores de Proteínas Quinases/administração & dosagem , Neoplasias Cutâneas/tratamento farmacológico , Administração Tópica , Animais , Dasatinibe/administração & dosagem , Fluoruracila/administração & dosagem , Humanos , Imidazóis/administração & dosagem , Inflamação , Queratinócitos/patologia , Camundongos , Camundongos Transgênicos , Quinolinas/administração & dosagem , Resultado do TratamentoRESUMO
BACKGROUND: Ablative fractional laser-assisted therapy is increasingly used to facilitate drug delivery and intensify clinical efficacy of topically applied drugs. OBJECTIVE: To evaluate the effectiveness of combined ablative fractional CO2 laser and topically applied 5-fluorouracil (5-FU) or verapamil hydrochloride in the treatment of hypertrophic scars (HTSs) and keloids and to examine their possible effects on TGF-ß1 expression. PATIENTS AND METHODS: Thirty patients with HTSs and keloids were randomly treated with combined CO2 laser followed by topical verapamil or 5-FU application or CO2 laser monotherapy. All patients received 4 treatments at 1-month intervals. Subjective and objective assessment was obtained using the Vancouver Scar Scale (VSS). Histological changes and immunohistochemical staining for TGF-ß1 were performed. RESULTS: Compared with baseline, there was a significant reduction in the VSS 1 month after the last treatment session in all groups (p < .05). Laser-assisted 5-FU delivery tended to show a higher extent of improvement in scar characteristics than laser-assisted verapamil hydrochloride delivery, without significance. No significant side effects were reported in all patient groups. TGF-ß1 expression was significantly decreased after laser sessions. CONCLUSION: Combined fractional CO2 laser and topical 5-FU or verapamil hydrochloride offer a safe therapy for HTSs and keloids.
Assuntos
Cicatriz Hipertrófica/terapia , Fluoruracila/administração & dosagem , Queloide/terapia , Terapia a Laser , Lasers de Gás/uso terapêutico , Verapamil/administração & dosagem , Administração Tópica , Cicatriz Hipertrófica/metabolismo , Terapia Combinada , Fracionamento da Dose de Radiação , Humanos , Imuno-Histoquímica , Queloide/metabolismo , Fator de Crescimento Transformador beta1/biossíntese , Resultado do TratamentoRESUMO
Human papilloma virus infection may be self-limiting; however, some cases may spread. There are no factors predicting the prognosis of such infections. The present study aimed to evaluate the significance of TLR4 expression in predicting the response of warts to candida immunotherapy. A total of 60 patients with different types of warts were included in the present study. A total volume of 2 ml venous blood was collected and real-time polymerase chain reaction was used to determine expression of TLR4. Patients were subjected to intralesional injection of Candida antigen into the largest wart at 2-week intervals until complete clearance or for a maximum of six sessions. Of the total 58 patients available for analysis of study results, 44 patients (75.9%) showed complete resolution with better response in younger ages. The TLR4 expression in patients with complete and partial response was significantly higher than that in patients who had no response (p = .006). Among our patients, 48.3% showed no side effects, 44.8% showed local reactions, and 6.9% showed systemic side effects. Only four patients showed recurrence after 6 months. Using receiver operating characteristic curve analysis, at cutoff of expression level >12 is accompanied by 100% specificity of TLR4 in predicting treatment response to candida immunotherapy. Candida immunotherapy is an effective warts treatment, especially in young patients. Higher PMBC TLR4 levels can predict response to candida immunotherapy.
Assuntos
Antígenos de Fungos/uso terapêutico , Candida/imunologia , RNA Mensageiro/sangue , Receptor 4 Toll-Like/genética , Verrugas/sangue , Verrugas/terapia , Adolescente , Adulto , Antígenos de Fungos/administração & dosagem , Antígenos de Fungos/efeitos adversos , Criança , Feminino , Expressão Gênica , Humanos , Imunoterapia , Injeções Intralesionais , Leucócitos Mononucleares , Masculino , Valor Preditivo dos Testes , Curva ROC , Recidiva , Verrugas/genética , Adulto JovemRESUMO
Background: Infantile hemangioma (IH) in most cases can be a self-limited condition; however, it may be ulcerated, infected, causing organ function disability and even death. Vascular endothelial growth factor (VEGF) has a role in IH. Bevacizumab is a monoclonal antibody against VEGF-A.Objectives: We aimed to evaluate and compare the efficacy of intralesional injection of bevacizumab versus triamcinolone acetonide (TAC) in IH.Methods: Thirty patients with IH were included in this study, divided into two equal groups, and treated with intralesional injection; the first group by bevacizumab and the second group by TAC. The injections in both groups were given every 4 weeks for six sessions. Assessment of the clinical response was done by the hemangioma activity score (HAS) and visual analog scale (VAS).Results: Both treatment modalities gave similar initial improvement after three sessions. However, with continuing injection sessions, bevacizumab reached a response's plateau and TAC gave better significant results after six injection sessions reading both HAS (p = .0017) and VAS (p ≤.001).Conclusion: Both intralesional injection of bevacizumab and TAC were safe and effective treatments in early proliferative IH after three sessions, however, TAC injection was significantly better than bevacizumab after six sessions.
Assuntos
Anti-Inflamatórios/uso terapêutico , Antineoplásicos Imunológicos/uso terapêutico , Bevacizumab/uso terapêutico , Hemangioma/tratamento farmacológico , Triancinolona Acetonida/uso terapêutico , Feminino , Hemangioma/patologia , Humanos , Lactente , Injeções Intralesionais , Masculino , Resultado do TratamentoRESUMO
BACKGROUND: The microdeletion events that occur in the Y chromosome-azoospermia factor (AZF) region may lead to dyszoospermia. Also, the deleted azoospermia (DAZ) gene on AZFc and autosomal deleted azoospermia like gene (DAZL) are suggested to represent impairment, so it is interesting to determine the independency pattern of the AZF region and DAZL gene in azoospermic patients. AIM: To study the molecular characterization of AZFc and DAZL in 64 idiopathic non-obstructed azoospermia patients and 30 sexually reproductive men. METHODS: SYBR Green I (Q-PCR) and AZF-STS analysis was used for DAZ gene, and SNV-PCR and confirmative Sanger sequencing for DAZL gene. RESULTS: The present study observed that 15.6% had AZFc microdeletion, out of which 10% had DAZ1/2 deletion, and no T54A variant in the DAZL gene was found. CONCLUSION: In the current work, the novelty is that spermatogenic impairment phenotype, present with AZFc microdeletions, is independent of the T54A variant in the DAZL gene, and AZFc microdeletions could be a causative agent in spermatogenic impairment.
RESUMO
OBJECTIVES: To study the relationship between sperm DNA fragmentation (SDF) and reactive oxygen species (ROS) levels in infertile patients with varicocele, and to examine the beneficial effect of varicocelectomy and elucidate predictors of improvement after repair. PATIENTS SUBJECTS AND METHODS: We prospectively studied 60 patients with varicocele and abnormal semen variables who attended the outpatient clinic complaining of infertility for ≥12 months. In all, 25 patients (41.7%) had bilateral varicoceles and 35 (58.3%) had left varicoceles. The DNA fragmentation index (DFI%, percentage of sperm with denatured nuclei), ROS and total non-enzymatic antioxidant capacity (TAC) were measured. Inguinal varicocelectomy was performed in all patients. At 3-6 months postoperatively, all measurements were repeated. A control group, comprised of 20 normozoospermic fertile men, was included. Regression analysis was used to examine predictors of improvement. RESULTS: The mean (SD) DFI% in the 60 infertile patients with varicocele was 29.9 (8.3) and 7.56 (2.84)% in the controls; ROS levels were 4.49 (0.9) in patients and 2.62 (0.8) photons/min in controls; and the TAC was 0.97 (0.4) in patients and 1.5 (0.5) mM in controls; with highly significant differences between the patients and controls. The DFI% showed a positive correlation with ROS levels, whilst the total motile sperm count (TMSC) had a significant negative correlation with DFI%, ROS levels and grade of varicocele, whilst there was significant positive correlation with TAC. The grade of varicocele and duration of infertility were related to the presence of higher levels of ROS and increased of DFI%. Postoperatively, improvement (measured as a >50% increase in TMSC) occurred in 40 of 55 (73%) patients available at follow-up, with a significant reduction in the mean (SD) DFI% from 29.49 (8.58) to 18.78 (7.23)%, ROS levels from 4.49 (0.88) to 3.27 (1.3) photons/min (both P < 0.001), and a significant increase in the mean (SD) TAC from 1.01 (0.44) to 2.05 (0.51) mM (P < 0.001). Responders had a shorter infertility duration and lower preoperative DFI% and ROS levels. Regression analysis showed that DFI% is a predictor of improvement after varicocelectomy. CONCLUSION: SDF was shown to have a negative impact on improvement after varicocelectomy. Hence, DFI% could be recommended as a prognostic test in infertile patients with varicocele to help decision-making as regards the necessity and the anticipated outcome of varicocelectomy in patients with infertility.