Ping Tu

Peking University, Peping, Beijing, China

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Publications (17)65.35 Total impact

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    Y Zhao · C M Wen · N N Zhou · Q Feng · P Tu
    Journal of the European Academy of Dermatology and Venereology 06/2014; DOI:10.1111/jdv.12568 · 3.11 Impact Factor
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    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.
    Oncotarget 05/2014; 5(12). · 6.63 Impact Factor
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    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.
    Blood 04/2014; 123(22). DOI:10.1182/blood-2013-10-534693 · 10.43 Impact Factor
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    04/2014; 24(3). DOI:10.1684/ejd.2014.2308
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    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; 40(8). DOI:10.1111/1346-8138.12160 · 2.35 Impact Factor
  • Yi Zhao · Jining Tao · Ping Tu
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    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. DOI:10.1016/j.pdpdt.2012.10.001 · 2.52 Impact Factor
  • Yang Wang · Jin Yu · Ping Tu
    The Journal of Dermatology 12/2012; 40(2). DOI:10.1111/1346-8138.12037 · 2.35 Impact Factor
  • Yang Wang · Haizhen Yang · Ping Tu
    11/2012; 22(6):814-5. DOI:10.1684/ejd.2012.1869
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    ABSTRACT: Olmsted syndrome (OS) is a rare congenital disorder characterized by palmoplantar and periorificial keratoderma, alopecia in most cases, and severe itching. The genetic basis for OS remained unidentified. Using whole-exome sequencing of case-parents trios, we have identified a de novo missense mutation in TRPV3 that produces p.Gly573Ser in an individual with OS. Nucleotide sequencing of five additional affected individuals also revealed missense mutations in TRPV3 (which produced p.Gly573Ser in three cases and p.Gly573Cys and p.Trp692Gly in one case each). Encoding a transient receptor potential vanilloid-3 cation channel, TRPV3 is primarily expressed in the skin, hair follicles, brain, and spinal cord. In transfected HEK293 cells expressing TRPV3 mutants, much larger inward currents were recorded, probably because of the constitutive opening of the mutants. These gain-of-function mutations might lead to elevated apoptosis of keratinocytes and consequent skin hyperkeratosis in the affected individuals. Our findings suggest that TRPV3 plays essential roles in skin keratinization, hair growth, and possibly itching sensation in humans and selectively targeting TRPV3 could provide therapeutic potential for keratinization or itching-related skin disorders.
    The American Journal of Human Genetics 03/2012; 90(3):558-64. DOI:10.1016/j.ajhg.2012.02.006 · 10.99 Impact Factor
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    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.
    Blood 04/2011; 117(14):3826-35. DOI:10.1182/blood-2010-07-294819 · 10.43 Impact Factor
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    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. DOI:10.1111/j.1600-0781.2010.00555.x · 1.30 Impact Factor
  • International journal of dermatology 03/2010; 49(3):337-9. DOI:10.1111/j.1365-4632.2009.04186.x · 1.23 Impact Factor
  • Journal of Dermatological Science 07/2007; 46(3):211-3. DOI:10.1016/j.jdermsci.2007.01.004 · 3.34 Impact Factor
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    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. DOI:10.1001/archderm.141.10.1285 · 4.31 Impact Factor
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    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.
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    ABSTRACT: Dyskeratosis congenita (DKC) is a rare and fatal congenital syndrome characterized by the triad of reticular skin pigmentation, nail dystrophy and mucosal leukoplakia, and the predisposition to bone marrow failure and malignancies. Mutations in DKC1 gene encoding dyskerin are responsible for the X-linked dyskeratosis congenita. Here we report mutation analysis of two Chinese pedigrees with dyskeratosis congenita. The 15 coding exons of DKC1 and their flanking regions were amplified from genomic DNA by PCR. DNA sequencing and restriction endonuclease digestion were used for mutation detection. Transition mutation of 1226C-->T (P409L) found in the first pedigree is a novel mutation. In the second pedigree, the proband's mother phenotypically normal carried a de novo transition mutation of 1058C-->T (A353 V) in one allele, and transmitted the mutant allele to her two sons who had typical manifestations of dyskeratosis congenita.
    Journal of Investigative Dermatology 09/2004; 123(3):470-3. DOI:10.1111/j.0022-202X.2004.23228.x · 6.37 Impact Factor
  • Yong Yang · Dingfang Bu · Ke Wang · Ping Tu · Xuejun Zhu
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    ABSTRACT: To clone and express xeroderma pigmentosum, complementation group A (XPA) cDNA and to identify its recombinant protein. Coding region of XPA cDNA was amplified from human tonsil cDNA by reverse transcription and nested PCR. The PCR product was cloned into pBluescript vector, confirmed by DNA sequencing, cloned in frame into a prokaryotic expression vector pTrcHis C and expressed in E. coli. TOP10. The recombinant fusion protein was identified by immunoblotting. The entire coding region of XPA cDNA was cloned and expressed. The fusion XPA protein was identified by anti-XPA monoclonal antibody on western blot. Cloning of human XPA cDNA and successful expression of recombinant XPA protein will be useful for the construction of a viral gene transfer vector for the gene therapy of XPA.
    Beijing da xue xue bao. Yi xue ban = Journal of Peking University. Health sciences 09/2003; 35(4):426-8.

Publication Stats

153 Citations
65.35 Total Impact Points

Institutions

  • 2011–2014
    • Peking University
      Peping, Beijing, China
  • 2003–2014
    • Beijing Medical University
      • Department of Dermatology
      Peping, Beijing, China