Re-infection (secondary) inoculation cutaneous tuberculosis.
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Adult↗
Biomedical subjects
G Srivastava
Publications and source records attributed to G Srivastava.
Detection of genetic alterations in esophageal squamous cell carcinomas and adjacent normal epithelia by comparative DNA fingerprinting using inter-simple sequence repeat PCR.
In this study, we screened 19 esophageal squamous cell carcinomas (ESCCs) for the detection of genetic alterations using inter-simple sequence repeat PCR, a DNA fingerprinting approach. Three simple repetitive unanchored primers representing tri- and tetranucleotide repeats [(GTG)(5), (GACA)(4), and (GATA)(4)] were used, and evidence of gains and losses of chromosomal sequences were detected in all tumors (19 of 19 cases) for at least one of the primers. In 13 of these cases, apparently normal marginal epithelia adjacent to the tumors were also collected and examined. Eight of the 13 (62%) patients showed matching somatic mutations in the marginal epithelia adjacent to the tumors. Five of these 8 (63%) marginal epithelial samples were histologically normal, two were dysplastic, and one had extremely rare tumor cells. In 3 of these 13 (23%) cases, the profile bands were also seen to quantitatively increase in intensity, progressing from normal epithelia to marginal epithelia to tumors. Ten profile bands showing gains and one profile band showing loss in tumors compared with the corresponding normal epithelia were cloned, and their origins were determined by sequencing. The DNA sequence of one of the profile bands showing gain in the tumor could be matched to an expressed sequence tag sequence that has been mapped to the 7q22 region, a genomic amplification novel to ESCC. The sequence of the other profile band showing gain in the tumor could be matched to a nonexonic sequence of chromosome 20, whereas the sequences of the remaining profile bands could not be matched with any known sequences after comparison with the genomic sequence data in the European Molecular Biology Laboratory and GenBank databases. The bona fide nature of the gains or losses of 11 profile bands in the original cases was confirmed by direct genomic PCR amplification. The frequencies of these specific gene alterations in tumors were then analyzed in a total of 60 ESCCs, which included 41 additional cases of ESCC. Significantly, 26 of 60 (43%) tumors showed the DNA amplification for the expressed sequence tag sequence of chromosome 7, whereas the frequency of other individual gene alterations ranged from 7% to 15%. It is concluded that the inter-simple sequence repeat PCR strategy is adequate for the detection of somatic mutations in tumors, most of which are quantitative alterations in anonymous genomic sequences. This approach is also suitable for detection of somatic mutations preceding the onset of morphologically detectable neoplasia in ESCC.
Aged↗
Identification of differentially expressed genes in esophageal squamous cell carcinoma (ESCC) by cDNA expression array: overexpression of Fra-1, Neogenin, Id-1, and CDC25B genes in ESCC.
PURPOSE: This study aims to identify differentially expressed genes in esophageal squamous cell carcinoma (ESCC) through the use of a membrane-based cDNA array. EXPERIMENTAL DESIGN: Two newly established human ESCC cell lines (HKESC-1 and HKESC-2) and one corresponding to a morphologically normal, esophageal epithelium tissue specimen, prospectively collected from the HKESC-2-related patient, were screened in parallel using a cDNA expression array containing gene-specific fragments for 588 human genes spotted onto nylon membranes. RESULTS: The results of cDNA expression array showed that 53 genes were up-regulated 2-fold or higher and 8 genes were down-regulated 2-fold or higher in both ESCC cell lines at the mRNA level. Semiquantitative RT-PCR analysis of a subset of these differentially expressed genes gave results consistent with cDNA array findings. Four of the differentially expressed genes that belong to the categories of oncogenes/tumor suppressor genes (Fra-1 and Neogenin) and cell cycle-related genes (Id-1 and CDC25B) were studied more extensively for their protein expression by immunohistochemistry. The two ESCC cell lines and their corresponding primary tissues, 61 primary ESCC resected specimens and 16 matching, morphologically normal, esophageal epithelium tissues were analyzed. The immunostaining results showed that Fra-1, Neogenin, Id-1, and CDC25B were overexpressed in both ESCC cell lines and their corresponding primary tumors at the protein level, validating the microarray findings. The results of the clinical specimens showed that the Fra-1 gene was overexpressed in ESCC compared with normal esophageal epithelium in 53 of 61 cases (87%), Neogenin in 57 of 61 cases (93%), Id-1 in 57 of 61 cases (93%), and CDC25B in 48 of 61 cases (79%). Furthermore, the expression of Fra-1, Neogenin, and Id-1 in ESCC correlated with tumor differentiation. CONCLUSIONS: Overall, this study demonstrates that multiple genes are differentially expressed in ESCC and provides the first evidence that oncogenes Fra-1 and Neogenin and cell cycle-related genes Id-1 and CDC25B are overexpressed in ESCC.
Carcinoma, Squamous Cell↗
Profiling of differentially expressed cancer-related genes in esophageal squamous cell carcinoma (ESCC) using human cancer cDNA arrays: overexpression of oncogene MET correlates with tumor differentiation in ESCC.
PURPOSE: To examine the global gene expression of cancer-related genes in esophageal squamous cell carcinoma (ESCC) through the use of Atlas Human Cancer Array membranes printed with 588 well-characterized human genes involved in cancer and tumor biology. EXPERIMENTAL DESIGN: Two human ESCC cell lines (HKESC-1 and HKESC-2) and one morphologically normal esophageal epithelium tissue specimen from the patient of which the HKESC-2 was derived were screened in parallel using cDNA expression arrays. The array results were additionally validated using semiquantitative PCR. The overexpression of oncogene MET was studied more extensively for its protein expression by immunohistochemistry in the two ESCC cell lines and their corresponding primary tissues and 61 primary ESCC resected specimens. Sixteen of these 61 ESCC cases also had available the corresponding morphologically normal esophageal epithelium tissues and were also analyzed for MET expression. The clinicopathological features associated with overexpression of the MET gene were also correlated. RESULTS: The results of cDNA arrays showed that 13 cancer-related genes were up-regulated > or =2-fold (CDC25B, cyclin D1, PCNA, MET, Jagged 2, Integrin alpha3, Integrin alpha6, Integrin beta4, Caveolin-2, Caveolin-1, MMP13, MMP14, and BIGH3) and 5 genes were down-regulated > or =2-fold (CK4, Bad, IGFBP2, CSPCP, and IL-1RA) in both ESCC cell lines at the mRNA level. Semiquantitative RT-PCR analysis of 9 of these differentially expressed genes, including the MET gene, gave results consistent with cDNA array findings. The immunostaining results of the expression of MET gene showed that MET was overexpressed in both ESCC cell lines and their corresponding primary tumors at the protein level, validating the cDNA arrays findings. The results of the clinical specimens showed that the MET gene was overexpressed in ESCC compared with normal esophageal epithelium in 56 of 61 cases (92%). Moreover, the overexpression of MET protein was more often seen in well/moderately differentiated than in poorly differentiated ESCC. CONCLUSIONS: Multiple cancer-related genes are differentially expressed in ESCC, the oncogene MET is overexpressed in ESCC compared with normal esophageal epithelium, and its protein overexpression correlates with tumor differentiation in ESCC.
Aged↗
[Detection of Immunoglobulin light chain restriction of mucosa-associated lymphoid tissue type gastric lymphoma using mRNA in situ hybridization].
OBJECTIVE: To evaluate the usefulness of in situ hybridization for Immunoglobulin kappa and lambda light chain mRNA to detect light chain restriction in the diagnosis of primary gastric lymphoma (PGL) of mucosa-associated lymphoid tissue (MALT) type. METHODS: Twenty-seven cases of PGL of MALT type and 5 cases of gastritis were analyzed using in situ hybridization with fluorescent isothiocyanate (FITC)-labeled oligonucleotide probes for kappa and lambda light chain mRNA. The kappa:lambda ratios of tumor cells, lymphocytes and plasma cells were analyzed to detect light chain restriction and clonal plasma cells. RESULTS: Light chain restriction was found in 10 of 27 (37%) cases of PGL cases (in 5/9 low grade and 5/18 in high grade). Clonal plasma cells were detected in low grade but not in high-grade cases. No light chain restriction was found in gastritis specimens, the adjacent tissue of tumors or the distant stomach mucosa in lymphoma cases. CONCLUSIONS: The detection of clonality using mRNA in situ hybridization could be a helpful diagnostic tool for gastric lymphoma. The presence of clonal plasma cells can be a marker of the early lesion of low-grade PGL.
Diagnosis, Differential↗
Establishment and characterization of HKESC-1, a new cancer cell line from human esophageal squamous cell carcinoma.
The establishment of an esophageal cancer cell line can facilitate the search for molecular mechanisms involved in esophageal carcinogenesis. A new human cancer cell line, HKESC-1, was established from a primary moderately-differentiated squamous cell carcinoma of the esophagus from a 47-year-old Hong Kong Chinese man. The pathological characteristics (morphology, immunohistochemical, and electron microscopic studies), the tumorigenecity in nude mice, the cytogenetic features, the DNA ploidy, and telomerase activity of the cell line were investigated. The HKESC-1 cells have been maintained continuously in vitro for more than 16 months and passaged over 96 times. HKESC-1 cells grow as a monolayer, with a doubling time of 46 hours. The HKESC-1 cells are of a squamous epithelial origin, as shown by their immunopositivity with the anti-cytokeratin antibodies and ultrastructural demonstration of tonofilaments and desmosomes. The HKESC-1 cells possess characteristics of malignancy because they are highly tumorigenic in nude mice and have strong telomerase activity. The HKESC-1 cells had an aneuploid DNA content, as demonstrated by flow cytometric analysis. Cytogenetic analysis revealed hyperdiploidy of greater than 50 in 80% of analyzable metaphases. Chromosome gains and losses were common, and loss of the Y chromosome was a consistent numerical aberration. Additionally, many structural chromosomal abnormalities were encountered, with frequent breakpoints at 1p32, 7p22, 7q34, and 20q13. This newly established cell line serves as a useful model for studying the molecular pathogenesis, and testing new therapeutic reagents for esophageal squamous cell carcinoma.
Animals↗
Coinfection of multiple strains of Epstein-Barr virus in immunocompetent normal individuals: reassessment of the viral carrier state.
This study reassesses the occurrence of Epstein-Barr virus (EBV) diversity and coinfection versus dominance of a single viral strain within immunocompetent normal carriers. Polymerase chain reaction analysis of several different polymorphic loci of the EBV genome was performed on collections of peripheral blood mononuclear cells and multiple lymphoid and epithelial tissues of the same individuals. Autopsy specimens from 15 individuals who died of causes unrelated to EBV infection served as normal viral carriers. Unexpectedly, coinfection of multiple distinct strains of EBV of the same type (usually type 1) and less frequently of both types 1 and 2 was found to be very high within individual viral carriers. These data indicate that coinfection with multiple EBV strains is much more prevalent in normal carriers than previously appreciated, which in turn has direct implications on EBV persistence, host-viral interaction and pathogenesis.
Carrier State↗
Identification and characterization of BCL6 translocation partner genes in primary gastric high-grade B-cell lymphoma: heat shock protein 89 alpha is a novel fusion partner gene of BCL6.
Primary gastric high-grade B-cell lymphoma (HGBL) is a special type of non-Hodgkin's lymphoma. So far, the genetic features of this tumor have not been well characterized. Recently, a high incidence of BCL6 rearrangements has been detected in HGBL. However, no previous cytogenetic studies have found translocations involving the BCL6 locus (3q27) in HGBL, and the genetic basis underlying the BCL6 rearrangements in this tumor remains unclear. We therefore characterized the partner genes of BCL6 in five primary gastric HGBLs with a rearranged BCL6 gene by analyzing BCL6 transcripts using the 5' RACE (rapid amplification of cDNA end) strategy. BCL6 translocation partner genes were identified at the 5' end of the chimeric transcripts in all five cases, including the immunoglobulin heavy-chain (IGH) gene in three cases and the immunoglobulin lambda-light-chain gene and the heat shock protein 89 alpha (HSP89A) gene in the other two cases. The chimeric transcripts in all cases contained the intact BCL6 exon 2, but lacked exon 1, which was replaced by sequences from the partner genes, suggesting that BCL6 expression was under the control of regulatory sequences of the partner genes. These results, for the first time, indicate that immunoglobulin genes, especially IGH, are the most common BCL6 translocation partner genes in primary gastric HGBL and that HSP89A is a novel partner of BCL6. Because immunoglobulin genes are also the most frequent partners of BCL6 in nodal diffuse large B-cell lymphoma (DLBCL), these data suggest that primary gastric HGBL shares a common genetic basis with nodal DLBCL. Genes Chromosomes Cancer 27:69-75, 2000.
5' Untranslated Regions↗
A study to determine the incidence and prevalence of newly discovered human immunodeficiency virus infection during the prenatal care period.
OBJECTIVES: This study asked the following questions: 1) Does HIV testing in pregnancy identify women who previously were not known to be HIV positive? 2) When in pregnancy are women identified as HIV infected? 3) Does HIV seroconversion occur during the prenatal care period? METHODS: Medical records of 97 women from two primarily indigent care hospitals in Houston, TX who were found to be HIV positive at delivery were reviewed to determine if they had tested positive during the prenatal care period. Demographics and time of gestation of the prenatal testing also were recorded. The outcome measures were: 1) number of women found positive during prenatal care; 2) week of gestation at discovery of HIV positivity; and 3) number of women seroconverting between the initiation of prenatal care and delivery. RESULTS: Thirty women were known to be HIV positive prior to pregnancy. Fifty-six women were found to be positive during prenatal care and the seropositivity of 44 was discovered before the 34th week of pregnancy. Ten women were found to be positive at their first prenatal visit, which occurred after the 34th week. Date of testing was unknown for two women. Eleven women who received no prenatal care were found to be HIV positive at delivery. There were no seroconversions while women were under prenatal care. CONCLUSIONS: HIV testing at delivery did not find any HIV-positive women who had tested negative during prenatal care. Testing is very important for women who do not receive prenatal care. Making certain that high-risk women get into prenatal care also is very important.
Adolescent↗
Incidence and pathology of primary brain lymphoma in Hong Kong Chinese patients.
Primary brain lymphoma (PBL) is an uncommon extranodal lymphoma. Its incidence is rapidly increasing in both immunocompromised and immunocompetent patients in Western countries. Eighteen cases of PBL were identified during a 16-year period among HIV negative patients in Queen Mary Hospital, Hong Kong. One case of post-transplantation lymphoproliferative disease (PTLD) was positive for Epstein Barr virus (EBV) encoded RNA (EBER) by in situ hybridization. All the remaining 17 immunocompetent cases were classified as diffuse large B-cell lymphoma, except for one case of Burkitt's lymphoma. EBER expression was negative in all 13 cases tested. Immunostaining for bcl-2 and bcl-6 was positive in 8/11 and 6/11 cases tested, with heterogeneous combination of expression and intensity. The incidence rate of PBL in immunocompetent patients was stable at 1.03 per million per year. The incidence of PBL in post transplantation (0.16%) and HIV related setting (0.29%) is also low in Chinese. PBL in Chinese patients is almost uniformly represented by EBV negative, diffuse large B-cell lymphoma, confined to the brain. However, the molecular pathogenesis may be heterogeneous.
Adult↗
Comparative analysis of Epstein-Barr virus gene polymorphisms in nasal T/NK-cell lymphomas and normal nasal tissues: implications on virus strain selection in malignancy.
Whether particular Epstein-Barr virus (EBV) strains are preferentially selected in malignant diseases remains controversial. Assessment of the importance of strain variation in the pathogenicity of EBV has been hampered principally by the lack of accurate data on the prevalence of virus variants in the normal population. To clarify this issue, a detailed comparative analysis of the EBV genomes contained in normal nasal and nasopharyngeal mucosal tissues and in nasal T/NK-cell lymphoma, which originates at these anatomic sites, was carried out by PCR amplification across the 30-bp deletion and the 33-bp repeat loci in the LMP1 gene and the type-specific polymorphic loci in the EBNA2 and EBNA3C genes and by sequence analysis of the 3' C-terminal region of the LMP1 gene. Whilst the majority of EBV strains in either normal or tumour tissues were type 1 viruses with similar numbers of LMP1 repeats, a marked predominance of LMP1 deletion (del-LMP1) over non-deleted/wild-type LMP1 (wt-LMP1) variants was observed in nasal T/NK-cell lymphoma. Although del-LMP1 variants were also prevalent in the normal carriers of our population, wt-LMP1 was detected at a significantly higher frequency in normal vs. tumour tissues (p = 0.036). More critically, wt-LMP1 variants were found frequently in mixed infection with del-LMP1 variants in the normal carriers. Sequence analysis identified 2 major del-LMP1 (and several wt-LMP1) variants containing signatory nucleotide changes in relation to the prototype B95-8 sequence in both normal and neoplastic nasal tissues. Together, our data provide strong evidence for a selection mechanism for del-LMP1 over the wt-LMP1 variants in tumours.
Antigens, Viral↗
Preferential type 1-1 cytokine gene expressions in peripheral T-cell lymphomas.
In this study, we have investigated whether a pattern of cytokine gene expression can be found in non-Hodgkin's peripheral T-cell lymphoma (PTCL). By using RNase protection assays and RT-PCR, we have systematically studied IL1alpha, IL1beta, IL1-Ra, IL2, IL4, IL5, IL6, IL9, IL10, IL12p35, IL12p40, IL13, IL14, IL15, IFNgamma, IFNbeta, TNFalpha, TNFbeta, LTbeta, and TGFbeta1, TGFbeta2 and TGFbeta3. Twenty-two cases of PTCL inclusive of three nasal NK-cell lymphomas were selected for the study; three cases of reactive lymphoproliferation were included for comparison. Results show that IFNgamma gene expression (key Type 1 cytokine) was frequently detected [18/22 (82 per cent)]. In contrast, IL4 (key Type 2 cytokine) was only detected in 4/22 (18 per cent) of cases (weaker than IFNgamma in three cases). This distinction was also found at the protein level by immunohistochemistry. In addition, TNFbeta and TNFalpha (strongly expressed by Type 1 cells) were almost complimentarily detected [4/19 (21 per cent)] and 12/19 (63 per cent), respectively). In contrast, neither IL5 nor IL13 (strongly expressed by Type 2 cells) were detected at all. However, 14/22 cases expressed IL10, another Type 2 cytokine, which suggests that the autoregulatory feedback loop is stimulated. Compared to the tumour types, the cytokine profiles in the reactive lymphoproliferative types also resembled a Type 1-like pattern but was less striking. The overall result suggested a preferential expression of certain cytokines, and these cytokines may play an important role in pathophysiologic progression in these T-cell disorders.
Cytokines↗
Impaired production of IL-12 in systemic lupus erythematosus. III: deficient IL-12 p40 gene expression and cross-regulation of IL-12, IL-10 and IFN-gamma gene expression.
Interleukin 12 (IL-12) is a heterodimer comprising p35 and p40 subunits which are encoded and regulated separately. The authors previously demonstrated deficient IL-12 production in SLE which correlates negatively with disease activity. The present study was designed to determine whether deficiency of IL-12 and excess production of IL-10 and IL-6 in systemic lupus erythematosus (SLE) are due to aberrant regulation at the gene level. Using semiquantitative RT-PCR assay, it was shown that constitutive expression of IL-12 p35 gene is somewhat impaired in SLE compared with controls and that IL-12 p40 mRNA, which was present at low levels in controls, was undetectable in unstimulated SLE peripheral blood mononuclear cells (PBMC). Gene expression of IL-12 p35 and p40 was significantly increased in response to SAC, with significantly lower SAC-induced expression of p40 in SLE patients than controls. SAC-stimulated IL-12 p35 and p40 mRNAs were significantly augmented by interferon gamma (IFN-gamma). Exogenous IL-12 or IFN-gamma significantly inhibited IL-10 gene expression, without affecting IL-6 mRNA or other proinflammatory cytokine mRNA levels. These observations were further confirmed by studies of protein production at the single cell level using ELISPOT assay. Downregulation of IL-12 p40 expression appears to be the cause of IL12 p70 deficiency in SLE. If this defect could be repaired, normalization of IL-12 and IFN-gamma production should reduce excessive IL-10 and prevent pathology.
Cells, Cultured↗
Methylation status of the Epstein-Barr virus major latent promoter C in iatrogenic B cell lymphoproliferative disease. Application of PCR-based analysis.
The Epstein-Barr virus (EBV) major latent promoter C drives the expression of viral nuclear proteins important in lymphocyte immortalization and as targets for immune surveillance by cytotoxic T cells. Hypermethylation of the C promoter silences its transcription. This promoter is methylated and silent in Burkitt's lymphoma, Hodgkin's disease, nasopharyngeal carcinoma, and nasal lymphoma. However, it is never methylated in the EBV-immortalized lymphoblastoid cell lines that serve as a model for EBV-associated lymphoproliferative disease. We have analyzed C promoter methylation in iatrogenic EBV-associated B-cell lymphoproliferative disease, mainly posttransplant lymphoma, using a sensitive polymerase chain reaction-based C promoter methylation assay. Our results showed heterogeneity in lymphoproliferative disease with methylation of viral DNA in specimens from 3 of 13 patients. In specimens from two of these patients, only methylated viral DNA was detected and viral nuclear antigen expression was correspondingly restricted. Heterogeneity in C promoter methylation and expression of associated transcripts may be an important determinant of the growth properties of lymphoproliferative lesions and may provide an explanation for the failure of some tumors to respond to withdrawal or reduction of immunosuppressive therapy.
Burkitt Lymphoma↗
Phenotypic and cytotoxic characteristics of peripheral T-cell and NK-cell lymphomas in relation to Epstein-Barr virus association.
AIMS: We investigated the phenotypic and cytotoxic characteristics of different types of peripheral T-cell and NK-cell lymphomas and correlated the findings of cytotoxic phenotype with Epstein-Barr virus (EBV) association. METHODS AND RESULTS: Eighty cases of peripheral T-cell and NK-cell lymphomas, classified according to the REAL classification, were investigated for cytotoxic phenotype (by studying T-cell intracellular antigen-1 (TIA-1) expression immunohistochemically) and EBV association (by in situ hybridization for EBV-encoded small non-polyadenylated RNAs), and the results were correlated with the specific clinicopathological types and the immunophenotype with special emphasis on CD56 expression and CD4/CD8 status. Overall, 39/80 cases (49%) expressed TIA-1. Angiocentric lymphoma (23/24 cases; 96%), aggressive NK-cell leukaemia ('large granular lymphocyte (LGL) leukaemia') (3/3 cases; 100%), intestinal T-cell lymphoma (5/6 cases; 83%) and anaplastic large cell lymphoma (4/6 cases; 67%) were the major subtypes showing a cytotoxic phenotype. Only four of the 27 cases (15%) of peripheral T-cell lymphoma, unspecified, were TIA-1+, while all the seven cases of angioimmunoblastic T-cell lymphoma, six cases of mycosis fungoides and one case of adult T-cell lymphoma/leukaemia were TIA-1-. CONCLUSIONS: Within the group of peripheral T-cell and NK-cell lymphomas, angiocentric lymphoma, aggressive NK-cell leukaemia ('LGL leukaemia'), intestinal T-cell lymphoma and anaplastic large cell lymphoma are the major subtypes displaying a cytotoxic phenotype. The relationships between the cytotoxic phenotype and EBV association, CD56 expression or CD4/CD8 status are secondary to the relationship between cytotoxic phenotype and specific lymphoma subtype.
Adult↗
Malignant lymphoma of the thyroid. A 30-year clinicopathologic experience and an evaluation of the presence of Epstein-Barr virus.
Lymphoma of thyroid is uncommon, and Epstein-Barr virus (EBV) is found in many lymphomas. We studied the clinicopathologic characteristics in Hong Kong Chinese and analyzed the presence of EBV in thyroid lymphomas by reviewing data collected during 3 decades. We studied EBV gene expression by in situ hybridization and immunohistochemistry. Primary thyroid lymphomas were found in 23 patients (diffuse large B-cell lymphoma, 18; marginal zone B-cell lymphoma, 4; plasmacytoma, 1), and secondary lymphomas were found in 9 patients (diffuse large B-cell lymphoma, 3; Burkitt lymphomas, 2; Burkitt-like lymphoma, 1; hairy cell leukemia, 1; nasal T-cell and natural killer cell lymphoma, 1; and intestinal T-cell lymphoma, 1). Primary thyroid lymphomas were large (mean, 7 cm), found commonly in older women, and often misdiagnosed as undifferentiated carcinomas. Fine-needle aspiration was not helpful for diagnosis. Fifteen patients had Hashimoto thyroiditis. A history of thyrotoxicosis was found in 3 patients, and coexistence of 3 diseases (papillary microcarcinomas, primary thyroid lymphoma, and Hashimoto thyroiditis) was found 4 patients. The 5-year survival rate for primary thyroid lymphoma was 53%. Combined surgery and radiotherapy seemed to be the best treatment. Secondary thyroid lymphomas often were asymptomatic. EBV messenger RNAs were detected in 1 primary and 1 secondary thyroid lymphoma. The EBV gene expression in primary thyroid lymphoma showed a type II latency pattern. Thyroid lymphomas in Chinese had important clinicopathologic features. EBV may have a role in a subset of cases.
Aged↗
Differential cytokine expression in EBV positive peripheral T cell lymphomas.
AIM: To investigate whether specific cytokines are secreted locally at the tumour site in Epstein-Barr virus (EBV) positive peripheral T cell lymphoma (PTCL). METHODS: An RNase protection assay system was used to study the differential expression of 21 cytokines in parallel in eight cases of EBV positive non-nasal PTCL, and compared with 11 EBV negative non-nasal PTCLs and three EBV positive nasal natural killer (NK) cell lymphomas. RESULTS: Among the eight EBV positive cases, interferon gamma (IFN-gamma), lymphotoxin beta (LT beta), interleukin 10 (IL-10), tumour necrosis factor alpha (TNF-alpha), transforming growth factor beta 1 (TGF-beta 1), and IL-1 receptor a (IL-Ra) were frequently detectable. IL-15, IL-6, IL-4, IL-1 beta, TNF-beta, and IL-9 were sporadically detectable. Of the frequently detectable cytokines, IFN-gamma and LT beta were commonly detected in the EBV negative cases. For cases with > 50% EBV encoded small non-polyadenylated RNA (EBER) positive cells, IL-10, TNF-alpha, and TGF-beta 1 were detected in three of three cases, and IL-1Ra in two of three cases. For cases with < 20% EBER positive cells, IL-10 was detected in three of five cases, TNF-alpha in two of four cases, but TGF-beta 1 and IL-1Ra were not detected. Interestingly, IL-6 was detected in two of three cases with > 50% EBER positive cells, but only in one of five cases with < 20% EBER positive cells. For comparison, in NK cell lymphomas, IL-10, TNF-alpha, IL-1Ra, and IL-6 were all detectable, but TGF-beta 1 was not detected at all. Immunohistochemical staining revealed IL-10 in many cells; in contrast, EBV latent membrane protein 1 (LMP1) was only found to be positive in isolated cells. CONCLUSIONS: Certain cytokines, such as IL-10 and TNF-alpha, might be expressed preferentially in EBV positive peripheral T cell lymphomas. It is likely that such a cytokine environment enhances EBV infection and contributes towards tumorigenesis.
Cytokines↗
Mutational analysis of the PTEN/MMAC1 gene in primary oesophageal squamous cell carcinomas.
AIM: To investigate whether PTEN/MMAC1 mutations play a role in the carcinogenesis of oesophageal squamous cell carcinoma. METHODS: A panel of 33 primary oesophageal squamous cell carcinoma tumour samples and 20 corresponding morphologically normal tissues was examined for mutations in all nine exons of the PTEN/MMAC1 gene by means of polymerase chain reaction single strand conformational polymorphism analysis (PCR-SSCP) and direct DNA sequencing methods. RESULTS: Only one of 33 oesophageal squamous cell carcinomas showed an aberrant SSCP band. Further sequencing analysis of this sample revealed an 802 -29 T-->C substitution in intron 7. PTEN/MMAC1 mutations were not found in the mutational "hot spot" in exon 5, even after direct sequencing of six oesophageal squamous cell carcinoma samples and three normal tissues. However, a deletion of one nucleotide T at position 492 +8 in intron 5 was seen in all samples. CONCLUSION: These results suggest that PTEN/MMAC1 mutations do not play a major role in the carcinogenesis of oesophageal squamous cell carcinoma.
Aged↗