Publications by authors named "Xuyou Zhu"

23 Publications

  • Page 1 of 1

A potential mechanism of the onset of immune-related pneumonitis triggered by anti-PD-1 treatment in a patient with advanced adenocarcinoma lung cancer: case report.

BMC Pulm Med 2021 Sep 14;21(1):291. Epub 2021 Sep 14.

Department of Respiratory Medicine, Shanghai East Hospital, Affiliated to Tongji University, Shanghai, 200120, China.

Background: In recent years, the application of immunotherapy combined with chemotherapy in the first-line lung cancer has showed significant benefit in improving long-term survival. Immunotherapy also has risks of immune-related pneumonitis (IRP) after long-term treatment. Despite the treatment strategy of the IRP has been very clear. However, the mechanism is unclear.

Case Presentation: A 73-year-old male patient was diagnosed with left lung adenocarcinoma IVa, EGFR, ALK, ROS1 negative. The patient received anti-PD1 antibody combined with pemetrexed and cisplatin. After 5 cycles of treatment, partial response was obtained. Subsequently, the patient continued the treatment of anti-PD1 antibody combined with pemetrexed. Before the 7th cycle, the CT found a new lesion in the basal segment of the right lower lobe. It was diagnosed with IRP and pneumocystis jirovecii. The patient did not give trimethoprim-sulphamethoxazole (TMP-SMX) and corticosteroids, symptoms and radiological lesions had improved. We describe the report of immune-related pneumonitis trigged by anti PD-1 and monitored the dynamic changes of CD, CD T lymphocytes, MDSC and Treg cells in the bilateral bronchoalveolar alveolar lavage fluid. From the point of view of immune cells, the mechanism of immune reconstitution inflammatory syndrome is confirmed. Based on the current case report and literature, this study proposes a potential mechanism of the onset.

Conclusion: Immune reconstitution inflammatory syndrome may be potential mechanism of IRP. This study may improve our understanding of the pathogenesis underlying IRP. We believe the detection and dynamic monitoring CD4, CD8 T lymphocytes, MDSC and Treg cells can provide more accurate procedures.
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http://dx.doi.org/10.1186/s12890-021-01649-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8438889PMC
September 2021

Rupture and hemorrhage of a seminoma mixed with yolk sac tumors in 46XY partial gonadal dysgenesis: a case report and literature review.

BMC Surg 2021 Jul 3;21(1):307. Epub 2021 Jul 3.

General Surgery Department, Tongji Hospital, Tongji University School of Medicine, Shanghai, 200065, China.

Background: 46XY partial gonadal dysgenesis (PGD) is a rare subtype of disorder of sex development (DSD). 46YY PGD is a congenital disease with atypical chromosomal, gonadal, or anatomical sex development. The patient in this case report had male and female genitalia simultaneously. We created a flowchart of the differential diagnosis for clinicians.

Case Presentation: A 41-year-old male was admitted to the hospital complaining of lower quadrant abdominal pain for 1 day. Physical examination revealed that his penis size was normal, but a urethral orifice was located in the perineum area between the scrotum and anus. One small testicle was in the left scrotum, but no testicle was present on the right. The patient's abdomen was bulging, and he had lower abdominal pain. According to the emergency CT scan, a lesion (74*65 mm) was found in the right pelvis between the bladder and rectum. The lesion showed an unclear boundary and hematocele appearance. The lesion was removed by emergency surgery, and the pathology report indicated a mixed germ cell tumor with a seminoma and yolk sac tumors.

Conclusion: This article is a case report of germ cell tumors in 46XY PGD patients. The literature review summarizes the clinical diagnosis, and a flowchart is provided for physicians in future practice. The importance of this report is that it will help acquaint physicians with this rare disease and make the right initial clinical decision quickly through the use of this flowchart. However, the variants of special subtypes of 46XY DSD are myriad, and all the diagnoses could not be covered in one flowchart.
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http://dx.doi.org/10.1186/s12893-021-01302-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8254990PMC
July 2021

Tracing steroidogenesis in prostate biopsy samples to unveil prostate tissue androgen metabolism characteristics and potential clinical application.

J Steroid Biochem Mol Biol 2021 06 4;210:105859. Epub 2021 Mar 4.

State Key Laboratory of Cell Biology, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, University of Chinese Academy of Sciences, 320 Yueyang Road, Shanghai, 200031, China. Electronic address:

Androgens are essential for prostate cancer development. However, steroidogenesis has mainly been investigated in a limited number of prostate cancer cell lines, leading to varied conclusions and elusive clinical significance. Here, we established an ex vivo research platform with fresh biopsy samples transiently cultured with tritium- labelled androgens to trace steroidogenesis in prostate tissues and investigate its potential clinical application. DHEA was confirmed as the major precursor for androgen synthesis in the prostate. Significant amounts of oxidized DHEA and 5α-androstanedione were generated from DHEA in prostate biopsy samples. Prostatic steroidogenesis was independent of other clinical factors. Furthermore, prostatic steroidogenesis was suppressed after androgen deprivation therapy but increased upon treatment resistance, indicating that prostatic steroidogenesis was affected by clinical treatments. Overall, we provide an accessible research platform to characterize steroidogenesis in prostate tissue and indicate the correlation between prostatic steroidogenesis and disease progression.
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http://dx.doi.org/10.1016/j.jsbmb.2021.105859DOI Listing
June 2021

Performance Evaluation of and Methylation for the Aid in Diagnosis of Lung Cancer Based on the Analysis of FFPE Specimen.

Front Oncol 2020 14;10:565780. Epub 2020 Dec 14.

Department of Pathology, Tongji Hospital, Tongji University, Shianghai, China.

Emerging molecular diagnostic methods are more sensitive and objective, which can overcome the intrinsic failings of morphological diagnosis. Here, a RT-PCR-based diagnostic test kit (LungMe) was developed and characterized to simultaneously quantify the DNA methylation of and in FFPE tissue specimens. The clinical manifestations were evaluated in 251 FFPE samples with specificity and sensitivity of 90.4 and 89.8%, respectively. Furthermore, the quantitative analysis shows that the degree of methylation was correlated with the stages of lung cancer, but not in the case of . Our observation indicated that the DNA methylation of and may play different roles in cancer development. Comparison of the methylation levels of and between cancer and cancer-adjacent specimens (n = 30), showed they have "epigenetic field defect". As additional clinical validation, the hypermethylation of and was detected not only in surgical operative specimens, but also in histopathological negative puncture biopsies. and methylation detection can be used to increase sensitivity and NPV, which provide us with a more accurate method of differential diagnosis and are likely to be rapidly applied in clinical examinations.
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http://dx.doi.org/10.3389/fonc.2020.565780DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7793934PMC
December 2020

Identification of H7N9 hemagglutinin novel protein epitopes that elicit strong antibody-dependent, cell-mediated cytotoxic activities with protection from influenza infection in mouse model.

Cell Immunol 2021 01 6;359:104255. Epub 2020 Dec 6.

Department of Pathology, Tongji Hospital, Tongji University School of Medicine, Shanghai 200065, PR China. Electronic address:

Background: Antibody-dependent cell-mediated cytotoxicity (ADCC) is one of the mechanisms connecting humoral immunity and cellular immunity and has been well-demonstrated in recent studies. Neutralizing antibodies and antibodies can mediate ADCC effects and both build a strong defense against H7N9 influenza virus infection. In our previous study, we found that H7N9 patients' plasma displayed low neutralizing activities that were not sufficient for host protection; however, the plasma of some patients can mediate strong ADCC effects.

Methods: Based on the plasma samples of H7N9 infected patients collected, we measured the ADCC activities of these samples and selected the best to locate the dominant epitopes on H7N9 hemagglutinin (HA) protein that can elicit antibodies and strong ADCC activities. We constructed a yeast surface-display H7N9 HA protein epitope library and screened this library against plasma samples with different potencies in mediating ADCC effects.

Results: Two dominant epitopes were selected from the screening. Plasma samples with depleted antibodies that were specific to the epitopes showed reduced ADCC activities. The serum of mice immunized with the epitopes elicited strong ADCC activities. Three monoclonal antibodies were isolated which showed high ADCC effects in vitro. Vaccination with isolated ADCC activating epitopes can provide partial protection from influenza infection in mouse model. And mice with vaccinated with combination of epitopes and extracellular domain can provide full protection from influenza infection in the same mouse model.

Conclusions: In this study, the epitopes isolated on H7N9 HA were immunogenic and elicited antibodies and strong ADCC activities in mice. Although the protective effect of the epitopes is partial, the combination of epitopes and extracellular domain can provide 100% protection from influenza virus infection in the same mouse model. Our study provides information on the potential use of epitope vaccine design against H7N9 viral infection.
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http://dx.doi.org/10.1016/j.cellimm.2020.104255DOI Listing
January 2021

GPRC5A reduction contributes to pollutant benzo[a]pyrene injury via aggravating murine fibrosis, leading to poor prognosis of IIP patients.

Sci Total Environ 2020 Oct 3;739:139923. Epub 2020 Jun 3.

Department of Pathology, Tongji University Affiliated Tongji Hospital, Tongji University School of Medicine, Shanghai 200065, China; Tongji University School of Medicine, Tongji University, Shanghai 200092, China. Electronic address:

Air pollution exposure is recently reported to be one of the drivers of exacerbation in idiopathic pulmonary fibrosis (IPF). But there was a lack of direct evidence between pollution and lung fibrosis. Here, our data show effects of pollutant benzo[a]pyrene (BaP) and protein G-protein-coupled receptor family C group 5 type A (GPRC5A) on pulmonary fibrosis, which might help limit potential pollutant injury and disease progression. We cross-referenced epithelial differentially-expressed-genes (DEGs) from pollutant injury and published experimental fibrosis and IPF patients' data, top common-DEG (CO-DEG) GPRC5A was identified as a potential link between exposure-damage and fibrogenesis. The role of GPRC5A was evaluated under BaP exposure, in idiopathic interstitial pneumonia (IIP) tissue-array and via CRISPR/Cas9 knockout mice (Gprc5a). BaP exposure enhanced bleomycin (BLM)-induced murine pulmonary fibrosis with increased Fibronectin and α-SMA expression in primary fibroblasts, thickened respiratory membrane and damaged alveolar type II cell, combined with Gprc5a decline in fibrotic mass. GPRC5A mRNA reduced after 10-14 days' BaP exposure in human epithelial cell A549. GPRC5A protein was further found to decrease in IIP epithelium, especially hyperplastic regions. A high epithelial GPRC5A expression score was positively associated with long survival time (R = 0.34) while negatively with high age (R = -0.4) and IIP type IPF (R = -0.5). Low GPRC5A expression predicts poor prognosis (HR = 4.5). Gprc5a depletion aggravated mortality rate (50%) with increased collagen deposition and myofibroblast activation under BLM treatment and exacerbated BaP injury in lung remodeling. Vitamin metabolic imbalance and Mitofusion2 (Mfn2) or Opa1-regulated mitochondrial dynamics were deduced to contribute to Gprc5a depletion and fibrogenesis. Pollutant BaP exposure worsens murine fibrosis and myofibroblast activation via GPRC5A reduction in the damaged epithelium. GPRC5A deficiency was first confirmed to contribute to both poor prognosis of IIP patients and fibrogenesis in murine model; thus, GPRC5A could serve as a novel therapeutic target in pollutant injury and pulmonary fibrosis.
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http://dx.doi.org/10.1016/j.scitotenv.2020.139923DOI Listing
October 2020

Salicylate sensitizes oral squamous cell carcinoma to chemotherapy through targeting mTOR pathway.

Oral Dis 2020 Apr 8. Epub 2020 Apr 8.

Department of Pathology, Tongji Hospital, Tongji University, Shanghai, China.

Oral squamous cell carcinoma (OSCC) is an extremely aggressive neoplasm, which is usually diagnosed in the advanced stage of the disease. Extensive studies have shown a link between chronic inflammation and various types of cancer, including OSCC. Salicylate is a biotransformation product of aspirin, with similar anti-inflammatory ability to aspirin but lacks aspirin's inhibitory effect on the isolated cyclooxygenase activity. Our study indicates that salicylate sensitizes OSCC to anti-cancer drugs, but the mechanisms of its action are unclear. Here, OSCC cells were used to evaluate the cytotoxicity of salicylate alone or in combination with cisplatin (CDDP). RPPA proteomic array and Western blotting were employed to determine the signaling pathways affected by salicylate. Salicylate decreased cell survival rate and induced cell apoptosis in OSCC cells but not human normal oral mucosal epithelial cells (hTERT-OME). The use of sodium salicylate (SS) dramatically sensitized OSCC cells to CDDP. RPPA array showed that SS reduced many oncogenes such as PI3K/mTOR signaling and cancer stem cell (CSC)-related genes versus control. Western and transcriptional analyses substantiated that salicylate down-regulated these CSC-associated genes and the mTOR pathway dose dependently. Salicylate preferentially repressed the ability of sorted ALDH1+ cells to form tumor spheres. Finally, salicylate suppressed tumor growth in vivo, and the combination of salicylate and CDDP further synergistically reduced the growth of tumors. Salicylate hinders OSCC cell growth and sensitizes OSCC cells to CDDP through targeting CSCs and the mTOR signaling pathway. We propose that salicylate is beneficial for OSCC patients, and salicylate may be combined with chemotherapies to effectively treat OSCC patients.
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http://dx.doi.org/10.1111/odi.13345DOI Listing
April 2020

Functional Silencing of in Prostate Cancer Promotes Disease Progression.

Clin Cancer Res 2019 02 18;25(4):1291-1301. Epub 2018 Sep 18.

State Key Laboratory of Cell Biology, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai, P.R. China.

Purpose: Steroidogenic enzymes are essential for prostate cancer development. Enzymes inactivating potent androgens were not investigated thoroughly, which leads to limited interference strategies for prostate cancer therapy. Here we characterized the clinical relevance, significance, and regulation mechanism of enzyme in prostate cancer development.

Experimental Design: expression was detected with patient specimens and prostate cancer cell lines. Function of in steroidogenesis, androgen receptor (AR) signaling, and tumor growth was investigated with prostate cancer cell lines and a xenograft model. DNA methylation and mRNA alternative splicing were investigated to unveil the mechanisms of regulation.

Results: expression was reduced as prostate cancer progressed. 17βHSD2 decreased potent androgen production by converting testosterone (T) or dihydrotestosterone (DHT) to each of their upstream precursors. overexpression suppressed androgen-induced cell proliferation and xenograft growth. Multiple mechanisms were involved in functional silencing including DNA methylation and mRNA alternative splicing. DNA methylation decreased the mRNA level. Two new catalytic-deficient isoforms, generated by alternative splicing, bound to wild-type 17βHSD2 and promoted its degradation. Splicing factors SRSF1 and SRSF5 participated in the generation of new isoforms.

Conclusions: Our findings provide evidence of the clinical relevance, significance, and regulation of in prostate cancer progression, which might provide new strategies for clinical management by targeting the functional silencing mechanisms of .See related commentary by Mostaghel, p. 1139.
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http://dx.doi.org/10.1158/1078-0432.CCR-18-2392DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6377858PMC
February 2019

Lymphangiomatosis involving the pulmonary and extrapulmonary lymph nodes and surrounding soft tissue: A rare case report.

Medicine (Baltimore) 2017 Dec;96(49):e9032

Department of ENT, Children's Medical Center, Shanghai Jiao Tong University, Shanghai Department of Pathology, Shanghai Tongji Hospital, Tongji Hospital Affiliated to Tongji University, Shanghai Department of Pathology, Chongqing Medical University, Chongqing Department of Pathology, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China.

Background: Diffuse pulmonary lymphangiomatosis (DPL) mainly affects the lung and pleura. There are very few pathological reports of lung damage accompanied by diffuse involvement of the extrapulmonary lymph nodes and surrounding soft tissue. The clinicopathological significance of coexistence of pulmonary and extrapulmonary lesions is unknown.

Methods: Here, we report a 16-year-old male patient. The pathological specimens of the supraclavicular lymph node and soft tissue together with the lung biopsy were analyzed by pathological observation and immunohistochemical staining. Literatures were reviewed and clinical and imaging findings were discussed.

Results: The patient presented with coughing and expectoration for 1 year and intermittent hemoptysis for 4 months. Ultrasound revealed swollen lymph nodes in bilateral neck, left armpit, and pubic symphysis. Chest CT scan showed diffuse grid and linear shadows, bilateral pleural thickening, and nodule formation. Multiple enlarged lymph nodes were mainly investigated in bilateral hilar, mediastinal, para-aortic, lesser curvature, and retroperitoneal. Supraclavicular lymph node biopsy confirmed the lymphatic hyperplasia and expansion in the capsule and surrounding soft tissue. The thoracoscopic examination found bloody chylothorax on the left chest. And lung biopsy showed the lymphatic vessel hyperplasia and expansion on the pleura and adjacent lung tissue. Immunohistochemical stains showed that the lymphatic endothelial cells were positive for D2-40 and CD31. Lymphangiomatosis involving the pulmonary and extrapulmonary lymph nodes and surrounding soft tissue was diagnosed based on the aforementioned histological findings.

Conclusion: Lymphangiomatosis of superficial lymph node mainly involves the capsule of lymph nodes and its surrounding soft tissue. The information obtained from the lymph node biopsy can prompt and assist the diagnosis of DPL.
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http://dx.doi.org/10.1097/MD.0000000000009032DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5728910PMC
December 2017

Reduced expression of BMP3 contributes to the development of pulmonary fibrosis and predicts the unfavorable prognosis in IIP patients.

Oncotarget 2017 Oct 9;8(46):80531-80544. Epub 2017 Aug 9.

Department of Pathology, Tongji Hospital, Tongji University School of Medicine, Shanghai 200065, China.

Idiopathic pulmonary fibrosis (IPF) and idiopathic nonspecific interstitial pneumonia (INSIP) are two related diseases involving varying degrees of pulmonary fibrosis with no effective cure. Bone morphogenetic protein 3 (BMP3) is a member of the transforming growth factor-β (TGF-β) super-family, which has not been implicated in pulmonary fibrosis previously. In this study, we aimed to investigate the potential role of BMP3 playing in pulmonary fibrosis from clinical diagnosis to molecular signaling regulation. RNA sequencing was performed to explore the potential biomarker of IIP patients. The expression of BMP3 was evaluated in 83 cases of IPF and INSIP by immunohistochemistry. The function of BMP3 was investigated in both fibroblast cells and a bleomycin-induced murine pulmonary fibrosis model. The clinical relevance of BMP3 expression were analyzed in 47 IIP patients, which were included in 83 cases and possess more than five-year follow-up data. Both RNA-sequencing and immunohistochemistry staining revealed that BMP3 was significantly down-regulated in lung tissues of patients with IPF and INSIP. Consistently, lower expression of BMP3 also was found in pulmonary fibrotic tissues of bleomycin-induced mice model. Up-regulation of BMP3 prevented pulmonary fibrosis processing through inhibiting cellular proliferation of fibroblasts as well as TGF-β1 signal transduction. Finally, the relatively higher expression of BMP3 in IPF patients was associated with less/worse mortality. Intravenous injection of recombinant BMP3. Taken together, our results suggested that the low expression level of BMP3 may indicate the unfavorable prognosis of IPF patients, targeting BMP3 may represent a novel potential therapeutic method for pulmonary fibrosis management.
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http://dx.doi.org/10.18632/oncotarget.20083DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5655218PMC
October 2017

Analysis of Microarray-Identified Genes and MicroRNAs Associated with Idiopathic Pulmonary Fibrosis.

Mediators Inflamm 2017 14;2017:1804240. Epub 2017 May 14.

Department of Pathology, Tongji Hospital, Tongji University School of Medicine, Shanghai 200065, China.

The aim of this study was to identify potential microRNAs and genes associated with idiopathic pulmonary fibrosis (IPF) through web-available microarrays. The microRNA microarray dataset GSE32538 and the mRNA datasets GSE32537, GSE53845, and GSE10667 were downloaded from the Gene Expression Omnibus (GEO) database. Differentially expressed miRNAs (DE-miRNAs)/genes (DEGs) were screened with GEO2R, and their associations with IPF were analyzed by comprehensive bioinformatic analyses. A total of 45 DE-microRNAs were identified between IPF and control tissues, whereas 67 common DEGs were determined to exhibit the same expression trends in all three microarrays. Furthermore, functional analysis indicated that microRNAs in cancer and ECM-receptor interaction were the most significant pathways and were enriched by the 45 DE-miRNAs and 67 common DEGs. Finally, we predicted potential microRNA-target interactions between 17 DE-miRNAs and 17 DEGs by using at least three online programs. A microRNA-mediated regulatory network among the DE-miRNAs and DEGs was constructed that might shed new light on potential biomarkers for the prediction of IPF progression.
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http://dx.doi.org/10.1155/2017/1804240DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5446886PMC
March 2018

Lower expression of platelet derived growth factor is associated with better overall survival rate of patients with idiopathic nonspecific interstitial pneumonia.

J Thorac Dis 2017 Mar;9(3):519-528

Department of Pathology, Tongji Hospital, Tongji University School of Medicine, Shanghai 200065, China.

Background: Idiopathic nonspecific interstitial pneumonia (INSIP) presents with varying degrees of interstitial inflammation and fibrosis exhibiting a uniform appearance. Lack of knowledge on the underlying mechanisms of INSIP has contributed to few effective treatment strategies. Our study is designed to explore aberrantly expressed cytokines involvement in INSIP development.

Methods: Oligo GEArray was employed to detect the expression of cytokines in INSIP patients, and idiopathic pulmonary fibrosis (IPF) was setup as isotype control. Real-time PCR and immunohistochemistry analysis were used to further confirm the expression of abnormally expressed cytokines. The correlationship between cytokines expression and overall survival rate of patients with IPF and INSIP were analyzed.

Results: From microarray detection, transforming growth factor-beta-1 (TGF-β1), fibroblast growth factor 10 (FGF10), and platelet derived growth factor (PDGF) were predominantly up-regulated in patients with INSIP. Real-time PCR and immunohistochemistry also showed these cytokines was abnormally expressed in INSIP. In addition to, the clinical relevance analysis demonstrated relatively lower expression of PDGF patients had longer overall survival rate than those with higher expression of PDGF.

Conclusions: Our study suggests that TGF-β1, FGF10, and PDGF are required for the pathogenesis of INSIP, and may therefore be ideal targets in INSIP treatment. Moreover, INSIP patients with lower expression of PDGF had better survival rate.
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http://dx.doi.org/10.21037/jtd.2017.02.50DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5394091PMC
March 2017

The expression and clinical relevance of PD-1, PD-L1, and TP63 in patients with diffuse large B-cell lymphoma.

Medicine (Baltimore) 2017 Apr;96(15):e6398

Department of Hematology Deparment of Pathology, Tongji Hospital, Tongji University School of Medicine, Shanghai, China Division of Hematology and Internal Medicine, Mayo Clinic, Rochester, MN Department of Laboratory, Shanghai Zhongliu Hospital, Shanghai Fudan University School of Medicine, Shanghai, China.

Latest study showed that a novel translocation between programmed cell death ligand 1 (PD-L1) (cluster of differentiation 274) and TP63 (tumor protein 63) can be found in diffuse large B-cell lymphoma (DLBCL), resulting in their conjunct overexpression in tumor cells at RNA level. However, the expressed pattern of these 2 genes at protein level in DLBCL remains largely unknown, and the clinical relevance of PD-L1 and TP63 expression in DLBCL are also unclear.Tumor tissues from 76 Chinese DLBCL patients were immunostained for programmed cell death 1 (PD-1), PD-L1, and TP63 using the EnVision system. Clinical relevance of PD-1, PD-L1, and TP63 in 74 DLBCL were analyzed by chi-square test, the Kaplan-Meier curves with log rank test, and Cox's proportional hazards regression model.PD-1 was mainly expressed in tumor-infiltrating lymphocytes (TILs) of 39.5% patients. PD-L1 was expressed in tumor cells of 26.3% patients, and TP63 was immunostained in nucleoli of tumor cells of 31.6% cases. PD-1 expression was significantly associated with the patients' gender and B symptoms (P = 0.032, P = 0.026). DLBCL with PD-L1 or TP63 expression in tumor cells showed low International Prognostic Index (IPI) score (P = 0.007, P = 0.009). PD-1 TILs was related to prolonged overall survival rate (OS) of DLBCL patients (P = 0.02), whereas PD-L1 expression was associated with worse clinical outcome of patients (P = 0.049). Immunoreactivity of TP63 was not correlated with patients' survival time. Besides, PD-1 expression, patients' age, Ann Arbor stage, and IPI score were significant prognostic markers for OS, but PD-L1 and TP63 had no prognostic significance.PD-1, PD-L1, and TP63 are frequently expressed in DLBCL. PD-1/PD-L1/TP63 blockade may be a potential therapeutic strategy for some patients.
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http://dx.doi.org/10.1097/MD.0000000000006398DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5403068PMC
April 2017

[Value of DNA image cytometry in diagnosis of malignant pleural effusion].

Zhonghua Bing Li Xue Za Zhi 2015 Sep;44(9):653-4

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September 2015

Clinical significance of programmed death ligand-1 (PD-L1) in colorectal serrated adenocarcinoma.

Int J Clin Exp Pathol 2015 1;8(8):9351-9. Epub 2015 Aug 1.

Department of Pathology, Tongji Hospital, Tongji University School of Medicine Shanghai, China.

Preliminary research results with antibody of the negative costimulatory molecule programmed cell death ligand-1 (PD-L1) suggested its expression on tumor cells associated with various tumor grade and postoperative prognosis. However, to date, there is no information of PD-L1 expression in colorectal serrated adenocarcinoma (SAC) and its clinical relevance. Therefore, the purpose of this study is to investigate the clinical significance of PD-L1 expression in a large cohort of patients with SAC. Here, we first retrospectively identified all SAC collected at our institution between August 2008 and May 2013. The expression levels of PD-L1 were examined by immunohistochemistry in 120 patients with SAC. We further evaluated the correlation between expression data and clinical parameters, including patient age, sex, tumor size, location, grade, primary tumor classification (pT), lymph node metastasis (pN), distant metastases (pM), and vascular invasion. Strong PD-L1 expression was detected in 25% of SAC. Higher expression of PD-L1 was significantly associated with pN (P=0.003) and pM (P=0.014). Survival analysis showed that patients with higher expression of PD-L1 had a poorer prognosis (P=0.045). However, multivariate regression analysis did not support PD-L1 as an independent prognostic factor (P=0.430). Our data suggest that PD-L1 may represent a new biomarker of metastasis and prognosis for patients with SAC, but as a target in the treatment of SAC is less certain.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4583920PMC
August 2016

Histology subtypes and polyp size are associated with synchronous colorectal carcinoma of colorectal serrated polyps: a study of 499 serrated polyps.

Am J Cancer Res 2015 15;5(1):363-74. Epub 2014 Dec 15.

Department of Pathology, University Medical Center of Princeton Plainsboro, NJ, USA ; Department of Chemical Biology, Ernest Mario School of Pharmacy, Rutgers University Piscataway, NJ, USA ; Department of Pathology, Robert Wood Johnson Medical School, Rutgers University Piscataway, NJ, USA ; Cancer Institute of New Jersey, Rutgers University Piscataway, NJ, USA.

Sessile serrated adenomas (SSA) and traditional serrated adenomas (TSA) are considered as precursors of colorectal cancer, and are often diagnostic challenges. Their true prevalence is masked by significant inter-observer variations. To investigate the true prevalence and synchronous colorectal carcinoma (sCRC) of colorectal serrated polyps (CSP) and their associated factors, we first retrospectively identified all colorectal polyps collected at our institution between June 1995 and May 2013. After centrally reclassifying all CSP to reduce inter-observer variations, Chi-square tests and logistic regression analyses were used to analyze the potential factors. Among the included 5501 colorectal polyps, 499 CSP of 428 patients were identified and studied, including 353 hyperplastic polyps (HP, 70.7%), 80 SSA (16.0%), 61 TSA (12.2%) and 5 mixed polyp (1.0%). Diagnostic disagreements were found in 68 CSP (13.63% of CSP). SSA and TSA were more often larger than 5 mm and in proximal colon than HP. SSA were also more likely associated with older age (p=0.005), size ≥5 mm (p<0.001) and ≥3 polyps (p=0.004) than HP in distal colon, but only more likely associated with older age (p=0.006) in proximal colon. Multivariate regression analysis demonstrated that CSP with sCRC, compared with CSP without sCRC, were linked to CSP size ≥1 cm (vs <1 cm, odds ratio [OR] 4.412, 95% confidence interval [CI] 1.684-11.556, P=0.003) and a diagnosis of SSA or TSA (vs HP, OR 6.194, 95% CI 1.870-20.513, P=0.003 and OR 6.754, 95% CI 1.981-23.028, P=0.002, respectively), but not age, gender, polyp number and polyp shape. SSA and TSA are similarly often associated with sCRC (P=0.460). In conclusion, histology subtypes and polyp size may serve as markers for sCRC of CSP. SSA and TSA may warrant careful endoscopic examinations and similar follow-up intervals.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4300721PMC
January 2015

[The expressions and meanings of BMP-7 and TGF-β in idiopathic pulmonary fibrosis and idiopathic nonspecific interstitial pneumonia].

Zhonghua Jie He He Hu Xi Za Zhi 2014 Sep;37(9):664-70

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Objective: To investigate the expressions of cytokines in idiopathic pulmonary fibrosis (IPF) and in idiopathic nonspecific interstitial pneumonia (INSIP); To discuss expressions and meanings of bone morphogenetic protein 7 (BMP-7) and transforming growth factor beta (TGF-β) in IPF and IPF.

Methods: Selected 47 cases of idiopathic interstitial pneumonia (IIP), which were diagnosed by clinical-radiologic-pathologic (CRP), and classified into two groups which were group IPF (25 IPF) and group INSIP (22 INSIP, including 6 cellular pattern and 16 fibrosing pattern). The normal lung tissues were collected as the control group: The fresh tissues were made to detect more than 114 kinds of cytokines' expressions via Oligo GEArray gene microarray technology. Made a tissue microarray which applied EnVision immunohistochemistry technology to detect the expressions of BMP-7 and TGF-β in both kinds of IIPs. The two groups of patients were followed-up visited around 5 to 8 years and the survival curves were evaluated by Kaplan-Meier method.

Results: According to gene microarray results, these two groups were up-expression in TGF family,IL family and TNF family. Most of BMP members were down-expression, in comparison with the control group, except BMP-5,BMP-8B and BMP-15. As the tissue microarray results demonstrated, compared with normal lung tissues,BMP-7 expressed decreasingly in IPF and INSIP groups (t1 = 27.618, P < 0.001; t2 = -12.404, P < 0.001). The expression of IPF were lower than INSIP (t = 5.387, P < 0.05); In INSIP group, patients of cellular pattern expressed BMP-7 more than fibrosing pattern's (t = -5.341, P < 0.001). There were dramatically increasing expressions of TGF-β in IPF and INSIP, when compared with the control group (t1 = 23.393, P < 0.001; t2 = -13.445, P < 0.001) and it presented negative correlation with BMP-7(group IPF: r = -0.771, P < 0.001; group INSIP: r = -0.729, P < 0.001). (3) Clinical follow-up data showed, the stability(improvement), deterioration and death rates of the group IPF and the group INSIP were, respectively, 0(0%), 2 (8%), 23 (92%) and 15 (68.1%), 3 (13.6%), 4 (18.2%). The results were statistically significant (all P < 0.05). The median survival time of the part with higher BMP-7 expression and the part with relatively lower BMP-7 expression, in the group IPF, were 110.8 and 66.4 months (t = -2.686, P < 0.05); In the group INSIP, were 146.4 and 74.9 months (t = -3.037, P < 0.05).

Conclusions: Cellular cytokines presented different expression profiles in IPF and INSIP patients. Differently with highly activated TGF-β, BMP-7 was inhibited in IIP patients, which would remind the degree of fibrosis and prognosis of IIP. BMP-7 would be expected to be a novel target for IIP pathogenesis and prognostic research.
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September 2014

[Clinical and histopathological features of colorectal sessile serrated adenoma/polyp and its differential diagnosis].

Zhonghua Bing Li Xue Za Zhi 2014 Sep;43(9):588-92

E-mail: yixhxf

Objective: To investigate clinicopathological characteristics of colorectal sessile serrated adenoma/polyp (SSA/P) and its differential diagnosis from other serrated lesions.

Methods: Clinicopathological features of all cases of colorectal serrated lesions from 5 209 colorectal biopsy samples at Shanghai Tongji Hospital from 2008 to 2013 were reviewed. Three hundred and fifty-three cases of serrated lesions were erolled in the study. Morphological features of SSA/P were investigated with an emphasis on histologic criteria for diagnosis and a literature review was performed.

Results: Three hundred and fifty-three cases of serrated lesions were identified, including 25 SSA/P (7.1%), 278 hyperplastic polyp (HP, 78.8%), and 44 traditional serrated adenoma (TSA, 12.5%). Twenty-five patients with SSA/P consisted of 16 males and 9 females with a mean age of 62.2 years (aged 34-84 years) and the lesions involved sigmoid colon (14 cases), ascending colon (9 cases), rectum (1 case) and transverse colon (1 case). Grossly, the majority of SSA/P was sessile with an averaged size of 0.73 cm. Histologically, typical SSA/P had elongated crypts with prominent serration and distorted crypts architecture. The detection rates of crypts dilatation and branching in SSA/P and HP were 100% (25/25) and 24% (12/50, P < 0.01), 72% (18/25) and 4% (2/50, P < 0.01), respectively. Morphological features observed only in SSA/P included L-shaped crypts (48%, 12/25), pseudo infiltration of mucosa muscle (16%, 4/25), atypical nuclei (32%, 8/25), and increased mucus secretion (24%, 6/25).

Conclusions: SSA/P microscopically shows prominent serration and abnormal architectures of crypts. Complete tissue sectioning and correct embedding are helpful for the diagnosis. SSA/P without cytological dysplasia should be distinguished from HP, especially those with only a few distorted crypts.
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September 2014

Usual interstitial pneumonia coexisted with nonspecific interstitial pneumonia, What's the diagnosis?

Diagn Pathol 2012 Dec 3;7:167. Epub 2012 Dec 3.

Department of Pathology, Tongji Hospital, Tongji University School of Medicine, Shanghai 200065, China.

Unlabelled: The differential diagnosis between idiopathic nonspecific interstitial pneumonia(INSIP) and idiopathic pulmonary fibrosis(IPF)/usual interstitial pneumonia(UIP)is tough in both clinicians and pathologists. In this study, we analyzed the lesions of right lung removed from a 58-year-old patient by gross and microscopy. The results showed that the pathological appearance of nonspecific interstitial pneumonia (NSIP) and UIP coexisted in his upper lobe. Besides, because of severe fibrosis in middle and lower lobes, it was hard to distinguish the lesions of NSIP fibrotic pattern (NSIP-F) or UIP. Based on clinic-radiologic-pathological data, the diagnosis of INSIP-F was made for this patient finally. Our study suggests that UIP is not always an accurate diagnosis when the NSIP and UIP coexist, and NSIP can have regions of UIP.

Virtual Slide: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/2573531681608730.
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http://dx.doi.org/10.1186/1746-1596-7-167DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3534605PMC
December 2012

Transmission electron microscopy of sputum deposition in the diagnosis of pulmonary alveolar proteinosis.

Ultrastruct Pathol 2012 May;36(3):153-9

Tongji Hospital, Tongji University School of Medicine, Pathology, Shanghai, China.

Objective: To clarify the diagnostic value of sputum in pulmonary alveolar proteinosis (PAP) through transmission electron microscopy (TEM) of sputum deposition (SD).

Methods: Eleven SD samples and 9 bronchoalveolar lavage (BAL) sediments from a PAP group including 11 patients were observed by TEM and compared with sputum direct smear, BAL cytology, and lung biopsy histopathology. Eleven healthy adults were chosen as controls.

Results: The 11 sputum smears from the PAP group showed no diagnostic component, but TEM of SD revealed 7 of 11 samples had many myelin-like lamellar bodies with degeneration in the cytoplasm of macrophages, alveolar epithelial cells, and extracellular spaces, which suggested PAP. Especially, 2 patients on whom lung biopsy could not be performed and who failed to be diagnosed by BAL fluid were finally diagnosed by TEM of SD. TEM of BAL sediments showed 7 of 9 cases had diagnostic myelin-like lamellar bodies. No statistical significance was found between BAL fluid and SD by TEM. The control group didn't show diagnostic components by cytology or TEM of SD.

Conclusion: TEM of SD is an important noninvasive diagnostic method especially for patients against lung biopsy and BAL.
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http://dx.doi.org/10.3109/01913123.2011.639134DOI Listing
May 2012

Clinicopathologic and ultrastructural study of non-HIV-related primary pulmonary cryptococcosis in China: report of 43 cases.

Ultrastruct Pathol 2011 Feb 8;35(1):19-25. Epub 2011 Jan 8.

Tongji Hospital, Tongji, University School of Medicine, Pathology, Shanghai, China.

Objective: To clarify the clinicopathologic and ultrastructural features of primary pulmonary cryptococcosis (PC).

Methods: 43 cases of PC were observed by light microscopy and histochemical staining, including mucicarmine (MC), Alcian blue (AB), periodic acid-Schiff (PAS), and Grocott methenamine-silver (GMS). Transmission electron microscopy (TEM) was performed on 11 fresh and 8 formalin-fixed specimens.

Results: The detective rate of Cryptococcus neoformans (CN) by MC, AB, PAS, GMS staining, and TEM was 61.3% (19/31), 62.2% (23/37), 85.7% (30/35), 79.1% (34/43), and 89.5% (17/19), respectively. All CN detected by TEM had a capsule. Most of them possessed simple structure with undeveloped cellular organelles.

Conclusion: Electron microscopy has a high rate of detecting CN. A combination of histochemical staining and electron microscopy can make an accurate diagnosis of PC.
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http://dx.doi.org/10.3109/01913123.2010.521293DOI Listing
February 2011
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