OBJECTIVETo observe anti-cancer effects of Jianpi Jiedu Recipe (JJR) on liver cancer (LC) rats with Pi deficiency syndrome (PDS) and its relation with the third complementary-determining region gene spectratyping of TCRVβ-chain (TCRVβCDR3).

METHODSRats were divided into 8 groups according to random digit table, i.e., the blank control group (normal), the PDS group, the LC model group, the LC-PDS group, high, middle, and low dose JJR groups (75.00, 37.50, 18.75 g/kg, respectively by gastrogavage, once per day), the thymus pentapeptide group (5 mg/kg, intramuscular injection, twice per week), 8 in each group. Rats in the normal group were administered with physiological saline by gastrogavage once per day. PDS rat model was prepared by bitter-cold purgation. LC model was prepared by orthotopic transplantation method. Twenty gene subfamilies of TCRβCDR3 in the thymus, liver, and LC tissues were detected by Gene Scan.

RESULTSHigh and middle dose JJR could postpone the growth of LC volume (P < 0.05), with equivalent liver index and thymus index to those of the normal group (P > 0.05). In thymus and liver tissue of the normal group, the number of clones (20 and 19), gene fragment number (220 and 113), Quasi-Gaussian distribution ratio of TCRV&beta;CDR3 gene repertoire (100.0% and 42.1%), and fragment fluorescence peak area (6,539 ± 2,325 and 1,238 ± 439) were at the highest level among the 8 groups. TCRV&beta;CDR3 expressions in thymus and liver tissue of high and middle dose JJR groups were approximate to those of the normal group. They were in the middle of the thymus pentapeptide group, the PDS group, the LC model group, and poorest in the LC-PDS group. TCRV&beta;CDR3 in liver tissue expressed the best in the thymus pentapeptide group.

CONCLUSIONJJR might inhibit the growth of LC cells, and its mechanism might be related to enhancing TCRV&beta;CDR3 spectratype expression.

Animals ; Complementarity Determining Regions ; genetics ; Drugs, Chinese Herbal ; pharmacology ; Gene Expression Regulation, Neoplastic ; Genes, T-Cell Receptor beta ; Liver Neoplasms ; drug therapy ; genetics ; Random Allocation ; Rats

Genes, T-Cell Receptor gamma ; Humans ; Lymphomatoid Papulosis ; classification ; diagnosis ; Skin Neoplasms ; classification ; diagnosis

OBJECTIVE To study the morphology, immunology, cyto- and molecular genetics of a patient with lymphoplasmacytic lymphoma/Waldenström macroglobulinemia (LPL/WM), deletion of P53 gene and rearrangement of clonal T cell receptors-delta (TCR-delta) gene. METHODS The cell morphology and immunocytochemistry were analyzed by bone marrow testing and biopsy. Cellular immunology was analyzed by flow cytometry. Genetic analysis was carried out by chromosome karyotyping, fluorescent in situ hybridization (FISH) and polymerase chain reaction (PCR). Immunoglobulin M (IgM) in serum and urine was assayed by immunofixation electrophoresis. And the effect of chlorambucil therapy was evaluated. RESULTS Bone marrow biopsy suggested that the patient was of B lymphocyte type and had abnormal increase of lymphocytoid plasma cells, which were CD38 and CD138 positive. The patient had a normal male karyotype. FISH and PCR analysis of peripheral blood samples suggested deletion of P53 gene and rearrangement of TCR-delta gene. Immunofixation electrophoresis has detected IgM-kappa in both serum and urine. The patient showed partial response to chlorambucil. CONCLUSION In addition to typical clinical features, bone marrow examination, flow cytometry, histochemistry and immunophenotyping, testing for P53 gene deletion and lymphocyte gene rearrangement can facilitate the diagnosis and treatment of LPL/WM.
Aged ; Gene Rearrangement, delta-Chain T-Cell Antigen Receptor ; Genes, p53 ; Humans ; In Situ Hybridization, Fluorescence ; Male ; Polymerase Chain Reaction ; Waldenstrom Macroglobulinemia ; drug therapy ; genetics

Poikiloderma vasculare atrophicans (PVA) is a rare poikilodermatous variant of early-stage mycosis fungoides characterized by generalized poikiloderma, atrophy, mottled dyspigmentation, and telangiectasia. In 2001, a 14-year-old male presented with asymptomatic brownish-gray polymorphic macules throughout the body with flexural accentuation. A skin biopsy showed increased melanophages with focal hydropic changes. Ashy dermatosis was considered a possible diagnosis. In 2005, the lesions began to show darkening and lichenification in the lower part of the trunk. In 2011, his skin showed definite poikilodermatous changes, and a biopsy showed band-like inflammatory infiltrations of atypical lymphocytes, epidermal atrophy, and epidermotropism of predominantly CD4-CD8+ atypical T cells. In addition, results of T-cell receptor gene rearrangement analysis were positive. Based on the aforementioned findings, he was diagnosed with PVA. If a patient shows long-standing and progressive hyperpigmentary skin changes, periodic follow-up and repeated skin biopsies are recommended to determine the underlying condition.
Adolescent ; Atrophy ; Biopsy ; CD4-CD8 Ratio ; Diagnosis ; Follow-Up Studies ; Genes, T-Cell Receptor ; Humans ; Lymphocytes ; Male ; Mycosis Fungoides ; Skin ; Skin Diseases* ; T-Lymphocytes ; Telangiectasis

OBJECTIVETo investigate the cytotoxicity of normal CD8(+) T lymphocytes retrovirally transduced with WT1 peptide-specific T-cell receptor (TCR) genes against human lung cancer cells.

METHODSHLA-A*2402-restricted and WT1 peptide-specific TCR-&alpha;/&beta; genes were cloned from a cytotoxic T lymphocyte clone and inserted into a retroviral TCR expression vector. The cytotoxicity of normal peripheral CD8⁺ T cells transduced with the WT1-TCR genes against human lung cancer cells was evaluated using a standard ⁵¹Cr release assay.

RESULTSThe WT1-TCR gene-modified T cells recognized the peptide-pulsed target cells but not the non-pulsed cells. TCR-redirected CD8⁺ T cells lysed WT1-overexpressing human lung cancer cells in an HLA-A*2402-restricted manner, but did not kill normal cells positively expressing HLA-A*2402.

CONCLUSIONThese data demonstrate the feasibility of adoptive immunotherapy with TCR-redirected T cell for the treatment of lung cancer.

CD8-Positive T-Lymphocytes ; cytology ; Cell Line, Tumor ; Genes, T-Cell Receptor ; Humans ; Immunotherapy, Adoptive ; Lung Neoplasms ; pathology ; Peptides ; Receptors, Antigen, T-Cell, alpha-beta ; genetics ; Retroviridae ; T-Lymphocytes, Cytotoxic ; cytology ; Transduction, Genetic ; WT1 Proteins ; genetics

Intravascular lymphoma (IVL) is a rare disorder characterized by the presence of large neoplastic lymphoid cells restricted to the lumens of small vessels with a predilection for the skin and the central nervous system. While the vast majority of cases involving IVL are of B-cell lineage, the disease rarely affects the T-cell, the histiocytes, and the natural killer cells. We report a case of intravascular T-cell lymphoma (IVTL) associated with Epstein-Barr virus (EBV). A 23-year-old healthy woman presented with tender indurated erythematous patches with overlying telangiectasia on her right breast, abdomen, both the upper and the lower extremities and the back for 3 months. The pathology revealed an infiltration of dermal and subcutaneous vessels by large and atypical lymphoid cells with immunohistochemical features of the T-cell lineage with a cytotoxic phenotype (CD3+, CD8+, granzyme B+, TIA-1+, CD4-, CD5-, CD20-, CD56-). Interestingly, the DNA extracted from the skin biopsies demonstrated evidence of a monoclonal immunoglobulin heavy chain gene rearrangement, but no T-cell receptor gene rearrangement was found. In situ hybridization study for EBV-encoded RNA was positive. She was diagnosed with an EBV-associated IVTL. The patient's skin lesions were refractory to the combination of chemotherapy and autologous stem cell transplant, and she expired. The findings in the present case may highlight the unique clinicopathologic aspects of EBV-associated cytotoxic IVTL that occurred in a young, immunocompetent woman.
Abdomen ; B-Lymphocytes ; Biopsy ; Breast ; Central Nervous System ; DNA ; Drug Therapy ; Female ; Gene Rearrangement ; Genes, T-Cell Receptor ; Granzymes ; Herpesvirus 4, Human ; Histiocytes ; Humans ; Immunoglobulin Heavy Chains ; In Situ Hybridization ; Killer Cells, Natural ; Lower Extremity ; Lymphocytes ; Lymphoma ; Lymphoma, T-Cell* ; Pathology ; Phenotype ; RNA ; Skin ; Stem Cells ; T-Lymphocytes ; Telangiectasis ; Young Adult

T-cell acute lymphoblastic leukemia (T-ALL) accounts for approximately 10-15% of entire ALL in children. The outcome of T-ALL has been improved through the intensified therapeutic strategy, however, it is still a more aggressive disease. In T-ALL a couple of transcription factor oncogenes are known to be relocated to the juxtaposition of T-cell receptor genes, potent promoter, by chromosome translocation. However the incidence of each chimeric gene formation in T-ALL is less than 5% and their clinical significance as a prognostic marker is lacking. A decade ago it was identified that activating mutations in NOTCH1 in about 60% of T-ALL. After then, activating NOTCH1 mutations present in T-ALL have been extensively investigated with regard to understanding its molecular pathogenesis, its prognostic significance, and developing molecularly tailored novel agents. Small molecule gamma-secretase inhibitor, blocking a proteolytic step required for creation of a fragment of NOTCH intracellular domain which actually act as a controller of its target gene expression, was tried as a target therapeutic drug for T-ALL. Although outcome of this drug was not satisfactory, challenges have been launched to develop new drugs which specifically act on the aberrant behavior of mutated NOTCH1 in T-ALL.
Amyloid Precursor Protein Secretases ; Child ; Gene Expression ; Genes, T-Cell Receptor ; Humans ; Incidence ; Oncogenes ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma ; T-Lymphocytes ; Transcription Factors

The characterization of the human T-cell receptor (TCR) repertoire has made remarkable progress, with most of the work focusing on the TCRβ chains. Here, we analyzed the diversity and complexity of both the TCRα and TCRβ repertoires of three healthy donors. We found that the diversity of the TCRα repertoire is higher than that of the TCRβ repertoire, whereas the usages of the V and J genes tended to be preferential with similar TRAV and TRAJ patterns in all three donors. The V-J pairings, like the V and J gene usages, were slightly preferential. We also found that the TRDV1 gene rearranges with the majority of TRAJ genes, suggesting that TRDV1 is a shared TRAV/DV gene (TRAV42/DV1). Moreover, we uncovered the presence of tandem TRBD (TRB D gene) usage in ~2% of the productive human TCRβ CDR3 sequences.
Complementarity Determining Regions ; genetics ; DNA Primers ; chemistry ; genetics ; Female ; Gene Rearrangement, beta-Chain T-Cell Antigen Receptor ; genetics ; Gene Rearrangement, delta-Chain T-Cell Antigen Receptor ; genetics ; Genes, T-Cell Receptor beta ; genetics ; Genetic Variation ; High-Throughput Nucleotide Sequencing ; Humans ; Immunoglobulin Joining Region ; genetics ; Immunoglobulin Variable Region ; genetics ; Male ; Receptors, Antigen, T-Cell, alpha-beta ; genetics

BACKGROUND: Epstein-Barr virus (EBV)-associated hemophagocytic lymphohistiocytosis (HLH), EBV-positive systemic T-cell lymphoproliferative disease (STLPD) of childhood, and chronic active EBV (CAEBV) infection may develop after primary EBV infection. This study reviewed the clinicopathological spectrum of EBV-associated T- and natural killer (NK)-cell LPD, including STLPD and CAEBV infection, with an analysis of T-cell clonality. METHODS: Clinicopathological features of seven patients with EBV-associated HLH or STLPD and 12 patients with CAEBV infection were reviewed. Immunohistochemical staining and a T-cell receptor (TCR) gene rearrangement study were performed. RESULTS: STLPD and EBV-positive HLH showed significantly overlapping clinicopathological findings. One patient with STLPD and one patient with EBV-positive HLH demonstrated moderate to severe atypia of the infiltrating lymphocytes, whereas the remaining patients lacked significant atypia. Twelve patients had CAEBV infection, four of whom suffered mosquito-bite hypersensitivity, five showed NK lymphocytosis, and one suffered hydroa vacciniforme. Infiltrating lymphocytes were predominantly small and devoid of atypia. Hemophagocytic histiocytosis was found in seven of 11 patients. Monoclonality was detected in three (50%) of the six patients with successful TCR gene analysis. CONCLUSIONS: EBV-positive HLH and STLPD share similar clinicopathological findings and may constitute a continuous spectrum of acute EBV-associated T- or NK-cell proliferative disorders. The distinction of EBV-positive T-cell LPD from EBV-positive HLH may be difficult during routine diagnoses because of the technical limitations of clonality assessment.
Epstein-Barr Virus Infections ; Gene Rearrangement ; Genes, T-Cell Receptor ; Herpesvirus 4, Human ; Histiocytosis ; Humans ; Hydroa Vacciniforme ; Hypersensitivity ; Killer Cells, Natural ; Lymphocytes ; Lymphocytosis ; Lymphohistiocytosis, Hemophagocytic ; Lymphoma, T-Cell ; Lymphoproliferative Disorders ; Receptors, Antigen, T-Cell ; T-Lymphocytes

Nodular lymphoid hyperplasia of the stomach is a rare lymphoproliferative disorder. Here, we report a 38-year-old man who presented with multiple submucosal tumors of the stomach. Histologically, the lesions were characterized by multiple discrete submucosal nodules of lymphoid cells. The infiltrates between the lymphoid follicles were composed mainly of medium-sized lymphoid cells with abundant clear cytoplasm, as well as a few large cells with vesicular nuclei. The gastric mucosa exhibited multifocal lymphoid aggregates and some of the epithelial cells were infiltrated by small lymphocytes mimicking lymphoepithelial lesions. Histopathology was consistent with mucosa-associated lymphoid tissue lymphoma. However, the infiltrating lymphoid cells were positive for CD2, CD3, CD5, and CD7. In addition, polymerase chain reaction analysis of the immunoglobulin heavy chain and T-cell receptor gene rearrangements demonstrated polyclonality. This case was diagnosed as reactive lymphoid hyperplasia of the stomach.
Adult ; Cytoplasm ; Epithelial Cells ; Gastric Mucosa ; Genes, T-Cell Receptor ; Humans ; Hyperplasia* ; Immunoglobulin Heavy Chains ; Lymphocytes ; Lymphoma, B-Cell, Marginal Zone ; Lymphoproliferative Disorders ; Polymerase Chain Reaction ; Pseudolymphoma ; Stomach*