Résumé
BACKGROUND@#Triple-negative breast cancer (TNBC) is an aggressive type of breast cancer associated with poor prognosis and limited treatment options. The androgen receptor (AR) has emerged as a potential therapeutic target for luminal androgen receptor (LAR) TNBC. However, multiple studies have claimed that anti-androgen therapy for AR-positive TNBC only has limited clinical benefits. This study aimed to investigate the role of AR in TNBC and its detailed mechanism.@*METHODS@#Immunohistochemistry and TNBC tissue sections were applied to investigate AR and nectin cell adhesion molecule 4 (NECTIN4) expression in TNBC tissues. Then, in vitro and in vivo assays were used to explore the function of AR and estrogen receptor beta (ERβ) in TNBC. Chromatin immunoprecipitation sequencing (ChIP-seq), co-immunoprecipitation (co-IP), molecular docking method, and luciferase reporter assay were performed to identify key molecules that affect the function of AR.@*RESULTS@#Based on the TNBC tissue array analysis, we revealed that ERβ and AR were positive in 21.92% (32/146) and 24.66% (36/146) of 146 TNBC samples, respectively, and about 13.70% (20/146) of TNBC patients were ERβ positive and AR positive. We further demonstrated the pro-tumoral effects of AR on TNBC cells, however, the oncogenic biology was significantly suppressed when ERβ transfection in LAR TNBC cell lines but not in AR-negative TNBC. Mechanistically, we identified that NECTIN4 promoter -42 bp to -28 bp was an AR response element, and that ERβ interacted with AR thus impeding the AR-mediated NECTIN4 transcription which promoted epithelial-mesenchymal transition in tumor progression.@*CONCLUSIONS@#This study suggests that ERβ functions as a suppressor mediating the effect of AR in TNBC prognosis and cell proliferation. Therefore, our current research facilitates a better understanding of the role and mechanisms of AR in TNBC carcinogenesis.
Sujets)
Humains , Androgènes/usage thérapeutique , Récepteur bêta des oestrogènes/métabolisme , Récepteurs aux androgènes/usage thérapeutique , Tumeurs du sein triple-négatives/métabolisme , Simulation de docking moléculaire , Lignée cellulaire tumoraleRésumé
Objective:To analyze clinical features of 78 infants with scabies and their causes of misdiagnosis.Methods:A retrospective analysis was performed on infants aged < 6 months with confirmed scabies at Department of Dermatology in Zhengzhou Children′s Hospital, Jingjiang People′s Hospital, Tangdu Hospital of the Fourth Military Medical University, Second Affiliated Hospital of Soochow University and Henan Provincial People′s Hospital from January 1, 2016 to December 31, 2018. Then, epidemiological features, skin lesion characteristics, treatment and causes of misdiagnosis of infantile scabies were analyzed.Results:A total of 78 infants with scabies were collected. Their age of onset and duration from onset to diagnosis [ M ( P25, P75) ] were 8.5 (7, 12) and 4 (3.5, 5) weeks respectively. At the time of diagnosis, 45 (57.7%) patients showed lower body weight than the first quartile [ P25] of body weight of age- and gender-matched healthy peers, 40 (47.4%) had fussiness and irritation, and 68 (87.2%) had sleep disorders like night crying and increased frequency of night waking. Infantile scabies more frequently occurred in autumn (30 cases [38.5%]) and winter (22 cases [28.2%]) , and least frequently occurred in summer (8 cases [10.3%]) . In the case of 58 patients, there was at least 1 member with scabies at the same time, who had resided with the patients in their families for a long time; in the case of 12 patients, scabies was transmitted through previous contact with temporary residents with scabies in their families. Scabies lesions most commonly occurred on the chest and abdominal regions (80.8%) , followed by the limbs (76.9%) ; skin lesions were polymorphic, and lesions at different stages could coexist; the rashes mainly manifested as edematous red or non-edematous brown papules, blisters, papulovesicles and nodules, and some burrows could be characterized by an oval, linear, serpiginous, comma- or J-shaped appearance. All the patients had visited the clinic for 1 - 4 times with an average of 2.38 visits. Forty-eight (61.5%) patients initially visited non-dermatology departments, and 30 (38.5%) initially visited dermatological outpatient clinics. Incorrect diagnoses included infantile eczema, papular urticaria, impetigo, miliaria, prurigo, urticaria pigmentosa, infantile acropustulosis, herpes simplex and varicella. All the patients received topical sulfur 5% ointment. Nine (11.5%) patients experienced a sudden exacerbation of skin lesions after the topical treatment, and 20 (25.6%) needed 2 - 3 sessions of treatment. No recurrence was observed in all the patients at 2, 4 and 8 weeks after the end of treatment. Conclusions:Infantile scabies lesions are polymorphic, widely distributed, and easily misdiagnosed. To prevent misdiagnosis and improve the early diagnosis rate, a detailed clinical interrogation with clinical-epidemiological examination should be performed.
Résumé
Objective To develop a new strategy for preparing large-area full-thickness skin grafts with donor incisions small enough to allow direct suture under low pressure.Methods A geometrical analysis was carried out to design the best strategy to obtain skin grafts with minimal donor defect.In this strategy,two semicircular donor skin grafts are subjected to a malpositioned joining to form a circle which is equal in size to the large-area skin defect.Seven patients with cutaneous malignancy were managed by this operation regimen,including three cases of basal cell carcinoma,three cases of squamous cell carcinoma,and one case of malignant melanoma.Tumors were located in the face or head in five patients,and in feet in two patients.Results The width of donor incisions was significantly reduced by this strategy,and donor defects were sutured directly with the minimal loss of donor graft.Of the five patients with malignancies of the head or face,three achieved complete survival of skin grafts,two experienced mild erosion at the margin of skin grafts.A 10%-20% necrosis of skin graft was observed in the sole of feet in 2 patients,which healed 1-2 months after dressing changes.Conclusion Joined grafts of equal size may be an effective approach to the repair of large skin defect.