[Show abstract][Hide abstract] ABSTRACT: Mycosis fungoides (MF) often mimics the common chronic inflammatory skin diseases and is difficult to be diagnosed with certainty, partly because of the lack of well-characterized molecular markers. Previously, we discovered that TOX, a key T cell development regulator,was aberrantly over-expressed in early stage MF. In the current multi-center study involving two independent patient cohorts, we determined the prevalence of TOX over-expression in the full spectrum of MF skin biopsies, and tested if TOX expression levels correlated with long term clinical outcomes. We examined TOX expression levels in 113 MF biopsies. We found that the MF biopsies expressed higher TOX mRNA than the controls in both cohorts (17.9 fold in cohort 1, P = 0.002; 5.8 fold in cohort 2, P < 0.0001). In addition, thicker skin lesions such as plaques and tumors expressed even higher TOX levels than thinner patches. Further, TOX over-expression differentiated MF from the controls (area under the curve [AUC]=0.87, P < 0.0001). Finally, high TOX mRNA levels correlated with increased risks of disease progression (P = 0.003) and disease-specific mortality (P = 0.008). In conclusion, TOX may be a useful marker for improving MF diagnosis and prognostication.
[Show abstract][Hide abstract] ABSTRACT: Cutaneous CD30+ lymphoproliferative disease (CD30+LPD), characterized by the presence of CD30+ anaplastic large T cells, comprises the second most common group of cutaneous T cell lymphoma (CTCL). However, little is known about the pathobiology of the CD30+ lymphoma cells, as well as the mechanisms of disease progression. Here we report that Special AT-rich region binding protein 1 (SATB1), a thymocyte specific chromatin organizer, is over-expressed in CD30+ lymphoma cells in most CD30+LPDs, and its expression is up-regulated during disease progression. Our findings show that SATB1 silencing in CD30+LPD cells leads to G1 cell cycle arrest mediated by p21 activation. Using chromatin immunoprecipitation, luciferase assays, and mutational analysis, we demonstrate that SATB1 directly regulates the transcription of p21 in a p53 independent manner. Moreover, DNA demethylation on a specific CpG rich region of the SATB1 promoter is associated with the up-regulation of SATB1 during disease progression. These experiments define a novel SATB1-p21 pathway in malignant CD30+ T lymphocytes, which provides novel molecular insights into the pathogenesis of CD30+LPDs and possibly leads to new therapies.
[Show abstract][Hide abstract] ABSTRACT: To investigate the clinical and histopathological characteristics of basal cell carcinoma (BCC) in Chinese patients.
Clinical and pathological data of BCC confirmed by histology from 2010 to 2012 in Peking University First Hospital were retrospectively analyzed.
Among 418 patients enrolled, the male/female ratio was 0.77:1. The average age was (65.39±13.51) years. Among the patients younger than 60 years who occupied 29% of all the cases, the male/female ratio was 1.16:1. In terms of the histology subtypes of the BCCs, 81.8% were nodular, followed by superficial (9.8%), and the others were in very small proportion. The head and face were the most common sites of BCC (86.6%). All morpheaform subtypes, and the majority of the nodular subtypes were located on the head and face, whereas the trunk and extremities were the most common locations for the others. Clinically, 86.6% of the BCC were pigmented and 80.4% were not ulcerated. The diagnostic accordance rates of BCC on the head and face (84.7%) and on the trunk (79.1%) were higher than those on the extremities (46.2%, P<0.05).
The most clinical and histopathological characteristics of our cases were similar to those of Caucasian. This study displays some unique characteristics. The young and middle aged patients occupied relative higher proportion, and their gender ration was different from that of the aged group. Tumor with hyperpigmentation was popular and few cases were ulcerated. In this study, multiple BCC cases were seldom, and the BCC patients with nevus sebaceous were older than those in other reports. The research of the diagnostic accordance rates of BCC revealed that both doctors and patients should pay more attention to BCC.
Beijing da xue xue bao. Yi xue ban = Journal of Peking University. Health sciences 04/2014; 46(2):195-9.
[Show abstract][Hide abstract] ABSTRACT: BCL11B is a Kruppel-like C2H2-type zinc finger transcription factor, which has been associated with several human malignancies. Recent evidence showed that overexpressed BCL11B conferred chemoresistance to malignant T cells and that inhibiting BCL11B led to increased apoptosis, suggesting its potential pathogenic relevance in cutaneous T-cell lymphomas (CTCL), which were characterized by the resistance to chemotherapy-induced apoptosis. To investigate the expression pattern of BCL11B in different stages of mycosis fungoides (MF), quantitative reverse transcription polymerase chain reaction and immunohistochemistry were performed to compare the mRNA and protein expression among different stages of MF and benign inflammatory dermatoses (BID), respectively. BCL11B demonstrated significant upregulation in all stages of MF, compared with BID, in both mRNA expression level and protein level. In addition, BCL11B expression increased with advancing lesion tumor stage and overall disease stage. Further, to evaluate the dynamic expression of BCL11B under CTCL-directed treatment, BCL11B expression and cell apoptosis were evaluated after interferon (IFN)-α-2b and methotrexate treatment on CTCL cell line Hut78 cells. IFN-α-2b, but not methotrexate, induced BCL11B inhibition and cell apoptosis, suggesting that BCL11B may play important roles in the anti-CTCL effect of IFN-α-2b. In conclusion, our study demonstrated the overexpression of BCL11B in MF lesions and its potential relevance to disease progression. In addition, we provided evidence for BCL11B inhibitory approaches as a potential treatment to target chemoresistant tumor cells in advanced MF.
The Journal of Dermatology 05/2013; · 2.35 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Methods for quantitatively evaluate the efficacy of photodynamic therapy (PDT) for port-wine stains (PWS) are still needed for clinical practice and studies.
50 pairs of pictures before and after PDT of 40 PWS patients were selected. Each PWS lesion was labeled with a marker of red color graded 0-9. These pictures were taken without assistance of instruments to keep same position or distance and were referred to as 'experimental' images. 70 labels were photographed at a fixed position and distance with the assistance of a bracket and the images obtained were referred to as 'standardized' ones. An independent group of three experts viewed the photos and assessed the efficacy. The images were processed and measured for erythema index (EI) with the ImageJ freeware. The EI difference (ΔEI) and the percent change of ΔEI (ratioΔEI(%)) of the labels and the PWS lesions was computed separately.
Significant differences of EI, ΔEI and ratioΔEI(%) were found between each two grades of the color markers in both standardized and experimental images. ΔEI of lesions achieved 'almost cured' and 'great improvement' after PDT was significantly reduced than before PDT. Significantly greater percentages of lesions were assessed as 'response' and 'significant response' in those of beforeΔEI≥35 compared to those of beforeΔEI<35. The ratioΔEI(%) decrease of lesions assessed as 'almost cured', 'great improvement' and 'some improvement' was significantly reduced sequentially.
The EI image analysis is a valid method for quantitatively evaluating efficacy of PDT for PWS.
Photodiagnosis and photodynamic therapy 05/2013; 10(2):96-102.
[Show abstract][Hide abstract] ABSTRACT: Background The epidemiological and clinical characterization data of skin malignancies and premalignancies in Chinese population is scarce and inadequate. Objective To systematically investigate the clinical features and the trend of skin malignancies and premalignancies in 1420 Chinese cases. Methods A total of 1398 patients (presenting 1420 skin tumours) were included. Clinical and demographic information for every individual was collected, including age, age of onset, sex, lesion location, disease duration and tumour histology, which was analyzed for each type of skin tumours. Results The number of skin malignancies and premalignancies increased over time, with Basal cell carcinoma (BCC) as the most common type (30.5%). The majority of the patients were above 60 years of age both at onset and at diagnosis (52.8% and 62.9%, respectively), yet around one-third of patients were between 35-59 years (35.3% and 31.2%, respectively). Skin malignancies and premalignancies were mainly located in the head and neck (58.6%), followed by the trunk (18.3%) and the extremities (15.0%). Of all BCCs, nodular BCC was the most common histologic subtype (62.8%), while 15.8% were classified as aggressive subtypes. Malignant melanoma (MM) comprised the lowest proportion of 3.7%, with 75% located on extremities. The diagnostic accordance rates varied from 49.5% to 90.4%, with BCC being 67.9%. Conclusions The clinical features of skin malignancies and premalignancies in this study showed some similarities with those observed in Caucasian and other Asian populations, with several distinguished features in Chinese patients also being recognized. Closer attention to suspicious lesions in young and middle-aged people is needed.
Journal of the European Academy of Dermatology and Venereology 08/2012; · 2.69 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background Alterations of the PTCH1 gene have been found to contribute to both familial and sporadic basal cell carcinoma (BCC), especially in Caucasian patients. Furthermore, the majority of PTCH1 gene mutations in sporadic BCCs in Caucasian patients carry ultraviolet (UV) signatures, suggesting the key role of UV light in BCC development. However, sporadic BCC in non-Caucasian population has a lower incidence, and the pathogenesis remains largely unknown. To date, there has been no mutation analysis on PTCH1 gene in Chinese patients with sporadic BCCs. Objective To investigate genetic alterations of the PTCH1 gene in Chinese sporadic BCCs. Methods Direct sequencing was used to screen for mutations in PTCH1 in 31 microdissected samples in Chinese sporadic BCCs. In addition, single nucleotide polymorphisms (SNPs) were studied for loss of heterozygosity (LOH). Results Nineteen PTCH1 mutations in 17 of the 31 BCCs (54.8%) were identified. SNP analysis revealed LOH of PTCH1 in 10 of 23 BCCs (43.5%). Interestingly, the majority of mutations identified (63.2%) were insertion/deletion, which was different from the results in Caucasian cases whose mutations are predominantly point mutations. Only two (10.5%) of the remaining seven mutations were UV-specific C → T transition or tandem CC → TT transitions. All mutations occurred evenly throughout the entire PTCH1 protein domain without a hot-spot detected. Conclusion Mutations and LOH in PTCH1 were also highly prevalent in Chinese sporadic BCCs. However, UV light plays a less role in causing these mutations, suggesting other potential mechanisms in the development of sporadic BCC in Chinese patients.
Journal of the European Academy of Dermatology and Venereology 02/2012; · 2.69 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: This phase IIa study aimed to study the efficacy and safety of hemoporfin in photodynamic therapy (PDT) with a 532 nm continuous laser for port-wine stain (PWS).
In this 8-week open-labeled study in three centers, three different laser exposure times (532 nm continuous laser for 20, 30 and 40 min) were used in stage I, group A, stage II, group B and stage III, group C, respectively. Primary efficacy assessment was performed by an independent group of experts, who reviewed the standardized photos. Secondary efficacy assessment consisted of the subjective grading of the PWS fading by the investigators and the patients. Treatment reactions and adverse events (AE) were recorded separately.
Forty patients were initially enrolled in the study, but stage III had to be cancelled eventually for the safety of the patients. Patients in groups A and B showed similar satisfactory results in efficacy assessments, the total 'response' rate being 80.0% and 94.7% in groups A and B, respectively. The AE rates were also similar in the two groups. Self-limiting photosensitive dermatitis and hyperpigmentation were the most frequently observed AE.
Hemoporfin-PDT is effective and safe for patients with PWS aged 16-50.
Photodermatology Photoimmunology and Photomedicine 02/2011; 27(1):17-23. · 1.52 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Sézary syndrome (SS) is an aggressive subtype of cutaneous T-cell lymphoma that is characterized by circulating leukemic Sézary cells. The accumulation of these malignant cells has been shown to be the result of the resistance to apoptosis, in particular, activation-induced cell death. However, the mechanism of apoptosis resistance remains unknown. By characterizing the gene transcription profiles of purified CD4(+)CD7(-) Sézary cells from patients with SS and cultured Sézary cells, it was found that Sézary cells are deficient in the expression of special AT-rich region binding protein 1 (SATB1), a key regulator of T-cell development and maturation. Retrovirus-mediated gene transduction revealed that SATB1 restoration in cultured Sézary cells (Hut78) triggered spontaneous cell death and sensitized Hut78 cells to activation-induced cell death, with associated activation of caspase 8 and caspase 3. Furthermore, endogenous expression of FasL in Sézary cells was increased in transcriptional and translational levels on restoration of SATB1 expression in cultured Sézary cells. These results suggest that deficiency in SATB1 expression in Sézary cells plays an important role in SS pathogenesis by causing apoptosis resistance. Thus, restoration of SATB1 expression may represent a potential molecular targeted therapy for SS, which does not have a cure at present.
[Show abstract][Hide abstract] ABSTRACT: Tacrolimus has shown promising results in the treatment of various dermatological diseases, including hair loss. The direct effect of tacrolimus on hair follicles and its underlying mechanisms have rarely been investigated. In this study, we investigated the effects of topical tacrolimus on anagen in the hair cycle and on the expression of vascular endothelial growth factor (VEGF) and insulin-like growth factor-1 (IGF-1) mRNAs in mouse skin. Topical tacrolimus 0.1% ointment was applied to one side of the skin of depilated C57BL/6 mice. Skin samples from both sides were taken during the study. Vegf and Igf-1 mRNA were determined by quantitative RT-PCR. No obvious difference in skin colour, hair cycling or histological features was found between the treated and untreated skin, but the levels of Vegf mRNA and Igf-1 mRNA were markedly decreased in the treated skin in late anagen, compared with those in untreated skin.
Clinical and Experimental Dermatology 12/2009; 34(8):e937-40. · 1.33 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Autosomal recessive lamellar ichthyosis (LI) is a severe skin disorder characterized by generalized hyperkeratosis. Gene mutation in transglutaminase 1 (TGM1), which mediates cross-links in the formation of the cell envelope during terminal differentiation of epidermis, has been identified as a cause of LI.
To determine mutations of TGM1 gene in three Chinese families with LI.
The TGM1 gene was sequenced to identify disease-causing mutations in the three families with LI. One of the results was confirmed by using reverse transcriptase PCR and in situ hybridization. An in situ transglutaminase (TGase) 1 assay was performed to estimate TGase 1 activity in the patients' skin.
Four novel mutations of keratinocyte TGase1 (Q203X, D254N, R687H and IVS4 + 1G-->T) were found in the three families. No TGase 1 mRNA was detected in patient skin using RT-PCR and in situ hybridization, and the in situ TGase assay showed that there was no or decreased TGase 1 activity in patient skin.
Our findings suggest that four novel mutations in TGM1 gene result in decrease or absence of TGase activity in the skin and, as a consequence, cause the phenotype of LI.
Clinical and Experimental Dermatology 05/2009; 34(8):904-9. · 1.33 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Netherton's syndrome is a rare autosomal recessive disorder caused by mutations of the SPINK5 gene, which encodes the lymphoepithelial Kazal-type-related inhibitor (LEKTI) protein. We observed microstructural changes and detected LEKTI activity and SPINK5 gene mutation in three Chinese patients with Netherton's syndrome. Decreased LEKTI activity was found in the skin of patients. Lamellar bodies and foci of electron-dense material were detected in the intercellular spaces of the stratum corneum. A novel homozygous splicing mutation of 1430+2 T-->G was found in the SPINK5 gene in one proband. No mutation was found in the other family.
Clinical and Experimental Dermatology 09/2007; 32(5):564-7. · 1.33 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Castleman tumor, a rare lymphoproliferative disorder, is one of the associated tumors in paraneoplastic pemphigus. We analyzed the characteristics of a group of patients with Castleman tumor to clearly understand and to improve the prognosis of the disease.
Ten cases of paraneoplastic pemphigus associated with Castleman tumor treated in the Department of Dermatology, Peking University First Hospital, Beijing, China, from May 1, 1999, to March 31, 2004, were analyzed for clinical aspects, characteristics and histologic features of the tumors, and computed tomographic findings. Literature was reviewed and data were compared with our cases. Castleman tumor was a frequently reported neoplasm in association with paraneoplastic pemphigus in China. The disease was found to be caused by an autoimmune reaction originating from the B lymphocytes in the Castleman tumor.
Castleman tumor in association with paraneoplastic pemphigus is a commonly reported subtype of paraneoplastic pemphigus in China. Early detection and removal of the Castleman tumor are crucial for the treatment of this tumor-associated autoimmune disease.
Archives of Dermatology 11/2005; 141(10):1285-93. · 4.79 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To identify the DSRAD gene; mutations in three Chinese families with dyschromatosis symmetrica hereditaria.
All exons of DSRAD gene were analyzed in each person of these families with PCR-DNA sequencing. DNA samples from 100 unrelated, normally pigmented adult individuals were also included as control.
We identified a missense mutation of C3220T (R1074C) in DSRAD gene in family A, and another missense mutation of G3325T (D1109Y) in DSRAD gene in family B and C. No same mutation was found in unaffected individuals in the families and the controls.
We found two special missense mutations in DSRAD gene in three families of dyschromatosis symmetrica hereditaria. These mutations may impair DSRAD protein function, and as a consequence, cause skin dyschromatosis.
Beijing da xue xue bao. Yi xue ban = Journal of Peking University. Health sciences 11/2004; 36(5):466-8.