Wang H.-W.,Shanghai Skin Diseases Hospital |
Zhang L.-L.,Shanghai Skin Diseases Hospital |
Miao F.,Shanghai Skin Diseases Hospital |
Lv T.,Shanghai Skin Diseases Hospital |
And 3 more authors.
Photochemistry and Photobiology | Year: 2012
The aim of this study was to investigate the efficacy of 5-aminolaevulinic acid (ALA)-mediated photodynamic therapy (PDT) in treatment of human papillomavirus (HPV)-associated cervical condylomata. A total of 56 patients with cervical and external condylomata lesions were recruited for this open-label study. HPV genotyping of exfoliated cells collected from the cervix and external lesions was performed. Cervical lesions were treated with PDT by applying ALA gel (10%) to the surface of the cervix for 4 h followed by irradiating with a 635 nm laser at 100 J cm -2. PDT was repeated at 2-week intervals if lesion and HPV infection remained. Patients were followed up for 6-24 months. Genotyping analysis revealed four HPV subtypes (HPV6, 11, 16 and 18). The overall complete remission rate of 1-4 sessions of treatments was 98.2% and the corresponding HPV clearance rate was 83.9%. Ten cases showed complete removal of cervical lesions and HPV infection after a single treatment. Recurrence rate was 3.6%. Adverse effects were minimal and no structural complications were reported. In conclusion, topical ALA PDT is safe and effective for eradicating cervical HPV infection and eliminating condylomata lesion. Its definitive role in treating cervical condylomata deserves further investigation. Condylomata acuminata (CA) are the most prevalent sexually transmitted disease and closely associated with human papillomavirus (HPV) infections. Although CA mainly occur in the external genital and perianal area, HPV infection in these areas in women can lead to further infections in the vaginal and cervical mucosal epithelia. This clinical study investigated the efficacy of ALA PDT in treatment of HPV-associated cervical condylomata. We demonstrated that topical ALA PDT could effectively eradicate cervical HPV infection and ablate warty lesion (illustrated). © 2011 The American Society of Photobiology.
Sun H.,Jining First Peoples Hospital |
Yu T.,Jining Medical University |
Li J.,Shanghai Skin Diseases Hospital
Cancer Letters | Year: 2011
Here we report an oral alkylphospholipid perifosine dramatically sensitizes chemo-resistant ovarian cancer cells to paclitaxel induced cell death and apoptosis in vitro. We found that co-administration perifosine with paclitaxel in human ovarian cancer cells led to the inhibition of AKT/mTOR complex 1 (mTORC1), a marked increase in ceramide and reactive oxygen species (ROS) production, and a striking increase in the activation of pro-apoptosis pathways, including caspase 3, c-Jun N-terminal kinases (JNK) and AMP-activated protein kinase (AMPK). These signaling events together caused a marked increase of cancer cell apoptosis. Combining paclitaxel with perifosine may represent a novel anti-ovarian cancer strategy. © 2011 Elsevier Ireland Ltd.
Wang H.,Shanghai Skin Diseases Hospital |
Wang H.,Shanghai Huadong Hospital |
Li J.,Shanghai Skin Diseases Hospital |
Lv T.,Shanghai Skin Diseases Hospital |
And 5 more authors.
Experimental Dermatology | Year: 2013
The therapeutic effects of 5-aminolevulinic acid (ALA)-mediated photodynamic therapy (PDT) on cutaneous squamous cell carcinoma (SCC) are not fully understood, and the usefulness of topical PDT in the treatment of SCC is still debatable. The most interesting aspect in SCC PDT is perhaps its potential in inducing antitumor immune responses. In this study, cutaneous SCCs were established by UVB irradiation of hairless mice and treated with multiple ALA PDT. Immunohistochemistry assays showed that ALA PDT could induce quick apoptosis, overexpression of TNFα and marked increases in DCs, CD4+ and CD8+ cells in tumor interstitium and subcutaneous connective tissues. However, a complete response was only achieved for small SCCs. The clinical value of ALA PDT-induced specific antitumor immune responses in long-term control of SCCs deserves further study. © 2013 John Wiley & Sons A/S.
PubMed | University of Sichuan, Nanjing Medical University, Shanghai Skin Diseases Hospital, Jiangsu Province Official Hospital and Peking Union Medical College
Type: | Journal: World journal of surgical oncology | Year: 2016
Delayed first medical consultation (patients delay) is quite common in cases of penile carcinoma (PC), but its reasons and impacts remain unclear. We conducted this study to ascertain risk factors resulting in delayed treatment seeking and evaluate its influence on prognosis.From 2004 to 2010 at 4 centers, 254 patients were enrolled into this study from 262 consecutive PC cases. Patients sexual performance was investigated using the International Index of Erectile Function (IIEF)-15 at the sixth-month end after treatment. Data for prognostic analyses was obtained via a 5-year follow-up.A multivariate model ascertained 4 risk factors (single, living in rural areas, heavy drinking alcohol, and aspecific initial symptoms) and 1 protective factor (history of condyloma) significantly associated with patients delay. Delay >3 months led to significant risks for adverse clinical characteristics, low penis-sparing rate, and poor sexual function restoration. Although patients delay was not found to impact on postoperative relapses and 5-year overall survival (OS), patients with delay >6 months had significantly inferior 2-year OS.Single, living in rural areas, heavy drinking alcohol, and aspecific initial symptoms are significant risk factors of PC associated with patients delay. Delay >3 months will lead to significantly inferior clinical consequences. Minimizing patients delay is the key to avoid amputation and retain superior sexual potency. Improving patient education on initial symptoms of PC is necessary in men of >40 years old.
Mitra D.,University of Colorado at Denver |
Fernandez P.,University of Colorado at Denver |
Bian L.,Kunming Medical University |
Song N.,Shanghai Skin Diseases Hospital |
And 4 more authors.
Journal of Investigative Dermatology | Year: 2013
Smad4 loss occurs frequently in human skin squamous cell carcinoma (SCC), but it is unknown whether this loss increases UV-induced carcinogenesis, a major etiological factor in skin cancer. In the present study, mice with keratinocyte-specific Smad4 deletion (K14.Smad4-/-) and wild-type (WT) littermates were chronically UV-irradiated. Compared with WT, K14.Smad4-/-mice exhibited increased DNA damage and increased susceptibility to UV-induced skin cancer. Among genes involved in repairing UV-induced DNA damage, Excision repair cross-complementation group 1 (Ercc1) messenger RNA was significantly reduced in UV-treated K14.Smad4-/-skin compared with WT skin. Further analysis revealed that Smad4 loss confers reduced Snail binding to the Ercc1 regulatory elements, resulting in reduced Ercc1 transcription. Consistently, transient transfection of Snai1 into Smad4-/-keratinocytes led to increased repair of UV-induced DNA lesions. Transfection of Ercc1 into Smad4-/-keratinocytes restored repair of UV-induced DNA damage. Further, immunostaining revealed that the presence of Smad4 protein is associated with the presence of Snail and Ercc1 proteins in human skin SCC and precancerous actinic keratoses. Collectively, Smad4 loss-associated Snail reduction compromises Ercc1-mediated DNA repair, contributing to increased UV-induced skin carcinogenesis. Thus, we identified a role for Snail in UV-induced DNA repair. © 2013 The Society for Investigative Dermatology.
Ding H.-L.,Shanghai Skin Diseases Hospital |
Wang X.-L.,Shanghai Skin Diseases Hospital |
Wang H.-W.,Shanghai Skin Diseases Hospital |
Huang Z.,University of Colorado at Denver
Photodiagnosis and Photodynamic Therapy | Year: 2011
Acne vulgaris is a common dermatological disorder. Topical photodynamic therapy (PDT)-mediated with aminolevulinic acid (ALA) or methyl aminolevulinic acid (MAL) has been successfully used in the treatment of moderate to severe acne. The purpose of this case report is to highlight the feasibility of using a repeat weekly short-cycle ALA-PDT to treat severe facial acne lesions refractory to systemic retinoid and antibiotics. © 2011 Elsevier B.V.
Wu Z.-S.,Shanghai Skin Diseases Hospital |
Wu Z.-S.,Anhui Medical University |
Cheng X.-W.,Anhui Medical University |
Wang X.-N.,Anhui Medical University |
Song N.-J.,Shanghai Skin Diseases Hospital
Melanoma Research | Year: 2011
Cutaneous malignant melanoma is one of the most common and aggressive forms of human cancers and has a poor prognosis. Activation of signal transducer and activator of transcription 3 (STAT3) has been found in several human cancers and is thought to correlate aggressive disease and poor response. In this study, we investigated the clinical role of STAT3 and its natural inhibitor, suppressor of cytokine signaling 3 (SOCS3), in human cutaneous melanoma development and progression. Immunohistochemical analysis of pSTAT3, SOCS3, matrix metalloproteinase (MMP)-2, and MMP-9 expression was performed on 90 primary melanomas and 43 common melanocytic nevi specimens. The expression of STAT3 mRNA was further detected by in-situ hybridization in the same cohort of patients. The association of STAT3 mRNA, pSTAT3, and SOCS3 protein expression with clinicopathological parameters and patient survival was analyzed. Altered expression of STAT3 mRNA, pSTAT3, and SOCS3 protein was observed in melanoma specimens, compared with benign melanocytic nevi. High expression of pSTAT3 was correlated to large tumor diameter, depth of tumor invasion, tumor lymph node metastasis, MMP-2 and MMP-9 expression, and poor patient survival. Decreased expression of SOCS3 was correlated to depth of tumor invasion, tumor lymph node metastasis, the expression of MMP-2, MMP-9, and pSTAT3, and poor patient survival. Moreover, the expression of pSTAT3 was conversely correlated to SOCS3 expression in melanoma. Our results indicate that deregulated expression of pSTAT3 and SOCS3 might possess potential roles in the development and progression of human cutaneous melanoma. © 2011 Wolters Kluwer Health | Lippincott Williams & Wilkins.
Wang X.,Shanghai Skin Diseases Hospital
Photonics and Lasers in Medicine | Year: 2015
Our research group started to utilize 5-aminolevulinic acid (ALA)-mediated photodynamic therapy (ALA-PDT) as a possible treatment of skin cancers in 1995. Nowadays, ALA-PDT has become one of the most popular modalities in dermatology and venereology in China. In particular, the pioneering work done by our group in ALA-PDT of urethral condylomata acminata helped Shanghai Fudan Zhangjiang Bio-Pharmaceutical Co., Ltd.To obtain the regulatory approval from the China Food and Drug Administration (CFDA) for ALA to be used in the topical PDT of Condyloma acuminatum in 2007. Since then, ALA and dermatological PDT have been rapidly developed in China. To date, ALA-PDT has been carried out routinely in over 600 clinics across China. Approved and off-label indications include condylomata acminata, acne, flat warts, photoaging, actinic kerotosis, folliculitis, extramammary Paget's disease, lichen sclerosus, and superficial skin cancers. Meanwhile, numerous research teams have been actively engaged in basic researches of ALA-PDT. This presentation will provide an overview on clinical and basic researches carried out by our group and other groups in China.
Yang X.,Fudan University |
Yang J.,Fudan University |
Xing X.,Fudan University |
Wan L.,Shanghai Skin Diseases Hospital |
Li M.,Fudan University
Arthritis Research and Therapy | Year: 2014
Introduction: Although immune dysfunction plays a role in the pathogenesis of systemic sclerosis (SSc), involvement of T helper 17 (Th17) and T regulatory (Treg) cells remains unclear. We aimed to investigate the presence of Th17 and Treg cells in SSc patients and the role of Th17 cells in collagen production in SSc fibroblasts.Methods: We analyzed inflammatory cell profiles in the skin of 13 SSc patients by immunohistochemistry, the percentage of Th17 and Treg cells in peripheral blood mononuclear cells (PBMCs) of 45 SSc patients and 24 healthy controls by flow cytometry, gene expression in PBMCs by real-time reverse transcription-polymerase chain reaction and interleukin-17 (IL-17) in sera and culture supernatants by enzyme-linked immunosorbent assay. We also investigated the effect of Th17 cell-derived IL-17 on fibroblast growth and collagen production.Results: Infiltration of inflammatory cells including IL-17+ and Foxp3+ lymphocytes was detected in the skin of patients with early SSc. The percentages of circulating Th17 cells and IL-17 production were elevated in samples from patients with active SSc, whereas the percentage of circulating Treg cells was not affected. The number of Th17 cells was closely related to disease activity. IL-17 from SSc patients promoted fibroblast growth and collagen production, whereas IL-17 neutralizing antibody effectively blocked collagen production.Conclusion: SSc progression might be linked to expansion of circulating Th17 cells and increased infiltration of IL-17+ cells in skin. Th17-derived IL-17 is involved in fibroblast growth and collagen production. IL-17 blocking antibody may be a useful tool for intervention in the fibrotic course of SSc. © 2014 Yang et al.; licensee BioMed Central Ltd.
Zhang L.,Fudan University |
Fu X.-H.,Shanghai Pudong Gongli Hospital |
Yu Y.,Fudan University |
Shui R.-H.,Fudan University |
And 5 more authors.
Laboratory Investigation | Year: 2015
Cathepsin B (CB) is involved in the turnover of proteins and has various roles in maintaining the normal metabolism of cells. In our recent study, CB is increased in the muscles of polymyositis/dermatomyositis (PM/DM). However, the role of CB in interstitial lung disease (ILD) has not been reported. ILD is a frequent complication of PM/DM, which is the leading cause of death in PM/DM. It carries high morbidity and mortality in connective tissue diseases, characterized by an overproduction of inflammatory cytokines and induced fibrosis, resulting in respiratory failure. The etiology and pathogenesis of ILD remain incompletely understood. This study investigated whether treatment with CA-074Me, a specific inhibitor of CB, attenuates ILD in PM. CB expression, inflammation, and fibrosis were analyzed in the lung tissues from patients with PM/DM. The animal model of PM was induced in guinea pigs with Coxsackie virus B1 (CVB1). CA-074Me was given 24 h after CVB1 injection for 7 consecutive days. At the end of the experiment, the animals were killed and lung tissues were collected for the following analysis. Inflammation, fibrosis and apoptosis cells, and cytokines were assessed by histological examinations and immunohistochemical analyses, western blot analysis and transferase-mediated dUTP nick-end labeling assay. In patients with PM/DM, the protein levels of CB were significantly elevated in lung tissues compared with healthy controls, which correlated with increases in inflammation and fibrosis. Similarly, the expression of CB, inflammation and fibrosis, CD8+ T cell, CD68+ cell, tumor necrosis factor-alpha, transforming growth factor-beta1 infiltrations, and apoptotic cell death were significantly increased in lung tissues of the guinea-pig model of CVB1-induced PM. These changes were attenuated by the administration of CA-074Me. In conclusion, this study demonstrates that PM/DM increases CB expression in lung tissues and inhibition of CB reduces ILD in a guinea-pig model of CVB1-induced PM. This finding suggests that CB may be a potential therapeutic target for ILD. © 2015 USCAP, Inc All rights reserved.