RESUMEN
Pyoderma gangrenosum (PG) is a rare neutrophilic dermatosis characterized by rapidly developing and painful skin ulcers with distinctive features. As far as we are concerned, there is no previous case report on facial PG in East-Asia. In this case, we describe a case of a 79-year-old man with a 3-month history of progressive painful ulcers on his cheek and upper lip. Initial suspicion of atypical mycobacterium infection led to an ineffective treatment regimen. Comprehensive infectious testing yielded negative results, and a positive pathergy test indicated a potential diagnosis of PG. A skin biopsy confirmed the diagnosis, and the patient showed significant improvement with intravenous methylprednisolone and oral cyclosporine treatment. After three months, complete resolution of the lesions was achieved without recurrence. The case highlights the diagnostic challenges associated with PG, which is often misdiagnosed due to its resemblance to other conditions. Thorough evaluation is crucial to exclude alternative diagnoses, particularly cutaneous infections. Clinical morphology, tissue biopsy, and culture are essential for accurate diagnosis. The presence of pathergy, the development of new lesions following minor trauma, can also be a diagnostic clue.
RESUMEN
Human epidermal growth factor receptor (EGFR) has been established as a therapeutic target of lung cancer and other diverse tumors. The antibody drug Cetuximab has been developed to target the third subdomain III (TSDIII) of EGFR extracellular domain (ECD) by competitively inhibiting epidermal growth factor binding. In this study, we performed systematic investigation on the crystal complex structure of EGFR ECD domain with Cetuximab to create a residue importance profile for the TSDIII subdomain, based on which a number of U-shaped, double-stranded linear peptides were derived and cyclized to orthogonally thread through most hotspot residues and many responsible residues within the TSDIII ß-sheet plane; they represent mimotopes of the key antibody-recognition site of TSDIII subdomain. Computational analyses revealed that these linear peptides cannot spontaneously fold to the desired conformation in free state due to their intrinsic flexibility. Cell-free assays confirmed that the stapling can considerably improve the binding affinity of linear peptides to Cetuximab by up to 18-fold. The cOrt1 [3-18] cyclic peptide was measured to have the highest affinity in all designed linear and cyclic peptides.
Asunto(s)
Anticuerpos Monoclonales , Neoplasias Pulmonares , Humanos , Cetuximab/uso terapéutico , Anticuerpos Monoclonales/farmacología , Anticuerpos Monoclonales Humanizados/uso terapéutico , Conformación Proteica en Lámina beta , Receptores ErbB/metabolismo , Neoplasias Pulmonares/tratamiento farmacológico , Péptidos/química , Línea Celular TumoralRESUMEN
OBJECTIVE: To investigate the effects of 8-methoxypsoralen on human melanocytes [Ca(2+)]i and cytoskeleton actin organization in vitro. METHODS: Human melanocytes were obtained from normal foreskins. Laser confocal microscope was employed to measure [Ca(2+)]i and rhodamine-conjugated phalloidin was used to visualize the cytoskeleton actin. RESULTS: 8-methoxypsoralen increased [Ca(2+)]i and induced organization of actin stress fiber cytoskeleton. CONCLUSION: 8-methoxypsoralen might influence the migration of melanocytes by increasing the intracellular free Ca(2+) concentration and cytoskeleton actin reorganization.
Asunto(s)
Actinas/biosíntesis , Calcio/metabolismo , Proteínas del Citoesqueleto/biosíntesis , Melanocitos/efectos de los fármacos , Metoxaleno/farmacología , Actinas/genética , Movimiento Celular/efectos de los fármacos , Células Cultivadas , Proteínas del Citoesqueleto/genética , Humanos , Melanocitos/citología , Melanocitos/metabolismo , Piel/citologíaRESUMEN
OBJECTIVE: To observe the effect of basic fibroblast growth factor (bFGF) and alpha-melanocyte stimulating hormone (alpha-MSH) on adhesion and migration of melanocytes in vitro. METHODS: Human melanocytes were obtained from normal human foreskins. Culture dishes covered with fibronectin were used to perform melanocytes adhesion assay, and cell motility was assessed using the Transwell micropore filter method. RESULT: bFGF and alpha-MSH increased melanocytes adhesion on culture dishes covered with fibronectin. bFGF stimulated melanocytes migration through micropore filter while alpha-MSH had no significant effects. CONCLUSION: bFGF and alpha-MSH could promote the adhesion and migration of melanocytes, which suggests that two agents may play a role in the repigmentation of vitiligo.
Asunto(s)
Movimiento Celular/efectos de los fármacos , Factor 2 de Crecimiento de Fibroblastos/farmacología , Melanocitos/citología , alfa-MSH/farmacología , Adhesión Celular/efectos de los fármacos , Células Cultivadas , HumanosRESUMEN
OBJECTIVE: To investigate the effect of endothelin-1 (ET-1) on the adhesion and migration of melanocyte in vitro. METHODS: Human epidermal melanocytes that had been cultured and purified were treated with ET-1 and observed for adhesion to bovine serum fibronectin-coated culture dishes. Stem cell factor (SCF) and ET-1 treated cells were also examined for migration into micropore filters coated with the same protein. RESULTS: Compared with the SCF group, ET-1 treated melanocytes were easier to adhere to the dishes and to be moved into the filters, especially when the concentration was 32 nmol/L. When the concentration of ET-1 was 128 nmol/L or more, it could inhibit the adhesion and migration of melanocyte. At any concentration of ET-1 except at 2 nmol/L, there was a significant difference between ET-1-treated and untreated melanocytes (P < 0.01) when the adhesion test was carried out. However, even at 2 nmol/ L ET-1, there was obviously increased migration compared with those of ET-1 untreated melanocytes and SCF-treated cells (P < 0.01). CONCLUSION: ET-1 may influence the adhesion and migration of melanocyte, which can partly explain the capacity of ET-1 to regulate the melanocyte function in vitiligo lesions.
Asunto(s)
Adhesión Celular/efectos de los fármacos , Movimiento Celular/efectos de los fármacos , Endotelina-1/farmacología , Melanocitos/citología , Células Cultivadas , Humanos , Piel/citología , Vitíligo/terapiaRESUMEN
OBJECTIVE: To investigate the Malytea Scurfpea fruit (MSF) on melanocyte adhesion and migration. METHOD: Human epidermal melanocytes were treated with MSF and Ginger respectively, then adhesion to bovine serum fibronectin-coated culture dishes was checked. Control and treated cells were also examined for migration into micropore filters coated with the same protein. RESULT: Compared with control, MSF treated melanocytes were obviously easier to adhere to the dishes and move into the filters in a dose-dependent manner. When the dose of MSF was 200 mg x L(-1), it could not reincrease melanocyte adhesion and migration. At 10 mg x L(-1), under every other concentrations of MSF, there was no marked difference among MSF-treated, Ginger-treated and untreated melanocytes (P < 0.05) when adhesion test were studied. But to migration, even at 10 mg x L(-1) MSF, there was obvious increased migration compared with MSF-untreated or Ginger-treated melanocytes (P < 0.01). CONCLUSION: MSF has effect on melanocyte adhesion and migration, which can explain, in part, the capacity of MSF to modulate melanocyte function in vitiligo lesions.