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1.
J Viral Hepat ; 20(8): 575-81, 2013 Aug.
Article in English | MEDLINE | ID: mdl-23808996

ABSTRACT

There is limited information regarding follow-up and hepatitis B serological status of Asian Americans diagnosed with chronic hepatitis B (CHB) through community screening. The aims of this study were to evaluate the prevalence and characterize CHB among Asians living in Los Angeles, assess follow-up of individuals with CHB diagnosed at screening and compare with patients with CHB followed by community gastroenterologists. Between October 2007 and May 2010, 7387 Asians were tested for HBV. HBsAg positive individuals (CHB) underwent additional testing for ALT, HBeAg/anti-HBe and HBV DNA. Patients with CHB were contacted 6 months later to determine whether they received follow-up care. We compared serological patterns of these individuals with CHB to patients with CHB who were seen for the first time (treatment naïve) by community gastroenterologists during the study period. Prevalence of CHB was 5.2%. About 99% patients with CHB were foreign-born, and only 27% could read/write English. 297 (77%) patients with CHB could be reached 6 months after diagnosis; 43% did not receive follow-up care, mostly because of lack of medical insurance. Patients with CHB followed by gastroenterologists were more likely to have insurance (69% vs 26%, P < 0.0001). 90% patients with CHB at screening were HBeAg negative/anti-HBe positive with 62% having inactive disease compared to only 30% of patients seen by gastroenterologists (P < 0.0001). Among CHB participants, 13% met criteria for treatment compared to 51% of patients with CHB (P < 0.0001). Only a small number of CHB screening participants require antiviral therapy. Lack of medical insurance is the main reason for most patients with CHB not seeking follow-up care after screening.


Subject(s)
Asian , Hepatitis B, Chronic/diagnosis , Hepatitis B, Chronic/epidemiology , Mass Screening , Adult , Aged , Aged, 80 and over , Alanine Transaminase/blood , DNA, Viral/blood , Demography , Female , Follow-Up Studies , Health Services Accessibility/statistics & numerical data , Hepatitis B Antibodies/blood , Hepatitis B Surface Antigens/blood , Humans , Los Angeles/epidemiology , Los Angeles/ethnology , Male , Middle Aged , Prevalence
2.
J Biomed Mater Res A ; 101(6): 1716-25, 2013 Jun.
Article in English | MEDLINE | ID: mdl-23184852

ABSTRACT

Controlling cell organization is important in tissue engineering. Guidance by aligned features on scaffolds or stimulation by physical signals can be used to induce cell alignment. We have previously demonstrated a preferred alignment of human MSCs (hMSCs) along the compression loading axis in 3D collagen construct. In this study, we aim to investigate the collagen concentration dependence of the compression-induced hMSC organization. Results demonstrated that the compression-induced alignment and elongation of hMSCs exhibited a biphasic dose-dependent relationship with collagen concentration, and associated well with both collagen ligand density and elastic modulus of the constructs. Moreover, collagen concentration and compression loading significantly affected the expression level of integrin beta 1 and antibody neutralization against this molecule aborted the compression-induced alignment and elongation responses.


Subject(s)
Collagen/pharmacology , Mesenchymal Stem Cells/cytology , Mesenchymal Stem Cells/drug effects , Stress, Mechanical , Tissue Scaffolds/chemistry , Animals , Antibodies, Neutralizing/pharmacology , Elastic Modulus/drug effects , Humans , Image Processing, Computer-Assisted , Integrin beta1/metabolism , Protein Binding/drug effects , Rats , Staining and Labeling
3.
J R Coll Physicians Edinb ; 41(1): 67-72, 2011 Mar.
Article in English | MEDLINE | ID: mdl-21365070

ABSTRACT

At a time when the role of the laboratory in clinical medicine and in medical research was evolving rapidly, a young Chinese graduate of the Hong Kong College of Medicine and the University of Edinburgh undertook a period of intensive training at the laboratory of the Royal College of Physicians of Edinburgh that was to play a pivotal role in determining his future career as the first Professor of Pathology at the University of Hong Kong and its first professor of Chinese descent. Chung Yik Wang's subsequent achievements over a span of ten years were a testament to the solid foundation that had been laid during that early period, and was an excellent example of how the skills of medical science could be transferred across continents to best effect. Tragically, Wang's career was cut short when he succumbed to tuberculosis, the disease he had spent many years studying.


Subject(s)
Laboratories/history , Pathology/history , Schools, Medical/history , History, 20th Century , Hong Kong , Scotland
4.
Zhonghua Bing Li Xue Za Zhi ; 30(1): 31-4, 2001 Feb.
Article in Chinese | MEDLINE | ID: mdl-11866954

ABSTRACT

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.


Subject(s)
Immunoglobulin kappa-Chains/analysis , Immunoglobulin lambda-Chains/analysis , Lymphoma, B-Cell, Marginal Zone/chemistry , Diagnosis, Differential , Gastric Mucosa/chemistry , Gastritis/metabolism , Humans , Immunoglobulin kappa-Chains/genetics , Immunoglobulin lambda-Chains/genetics , In Situ Hybridization , Plasma Cells/pathology , RNA, Messenger/analysis
5.
Blood ; 95(11): 3628-30, 2000 Jun 01.
Article in English | MEDLINE | ID: mdl-10828054

ABSTRACT

Thirty-two natural killer (NK) and cytotoxic T-cell lymphomas and 14 noncytotoxic nodal T-cell lymphoma controls were immunostained with the use of monoclonal antibodies reactive against NK-cell receptor (NKR) molecules (CD94, NKG2A, p58.2, p58.1, p140, p70, p50.3). All NK-cell lymphomas (4 nasal/oral and 1 intestinal) expressed at least 1 NKR, the CD94/NKG2A complex. Two were positive for 1 or more killer immunoglobulin-like receptors. Of 15 extranodal cytotoxic T-cell lymphomas, 3 expressed CD94, including 2 intestinal and 1 hepatosplenic gammadelta T-cell lymphomas. In contrast, none of the nodal lymphomas were positive. Detection of NKRs may provide a useful tool to confirm the diagnosis of NK-cell lymphomas and to delineate a subgroup of cytotoxic T-cell lymphomas. Expression of NKRs only in extranodal cytotoxic T-cell lymphomas might reflect differences in the homing capabilities of cytotoxic T cells expressing NKRs in normal individuals and might be influenced in part by localized chronic immune reactions.


Subject(s)
Antigens, CD/analysis , Killer Cells, Natural/immunology , Lectins, C-Type , Lymphoma, T-Cell/immunology , Membrane Glycoproteins/analysis , Receptors, Immunologic/analysis , Adolescent , Adult , Aged , Child , Female , Humans , Immunophenotyping , Intestinal Neoplasms/immunology , Intestinal Neoplasms/pathology , Lymphoma, T-Cell/pathology , Lymphoma, T-Cell, Cutaneous/immunology , Lymphoma, T-Cell, Cutaneous/pathology , Lymphoma, T-Cell, Peripheral/immunology , Lymphoma, T-Cell, Peripheral/pathology , Male , Middle Aged , NK Cell Lectin-Like Receptor Subfamily C , NK Cell Lectin-Like Receptor Subfamily D , Nose Neoplasms/immunology , Nose Neoplasms/pathology , Receptors, Natural Killer Cell , Splenic Neoplasms/immunology , Splenic Neoplasms/pathology
6.
Oncogene ; 18(32): 4643-6, 1999 Aug 12.
Article in English | MEDLINE | ID: mdl-10467410

ABSTRACT

Inherited mutations in the BRCA1 gene confer increased susceptibility to breast and ovarian cancer. Its role in sporadic carcinogenesis is not well defined. Somatic mutations in breast cancers have not been reported and to date there are only three reports of somatic mutations in sporadic ovarian cancers. To investigate the contribution of BRCA1 mutations to sporadic breast and ovarian cancer in the Chinese population, we analysed 62 samples from Chinese women using the protein truncation test. There were 40 cases of breast cancer under age 50 and 22 cases of ovarian cancer, all unselected for family history. There was no age selection for the ovarian cancers. We found two somatic BRCA1 mutations in exon 11, one in a breast cancer and the other in an ovarian cancer, both of which result in truncated proteins. Our results indicate that somatic BRCA1 mutations, like somatic mutations in the BRCA2 gene, though very rare, can be found in both breast and ovarian cancers and support a tumor suppressor function for BRCA1 in sporadic tumors.


Subject(s)
Asian People/genetics , BRCA1 Protein/genetics , Breast Neoplasms/genetics , Mutation , Ovarian Neoplasms/genetics , Adult , China , Female , Humans , Middle Aged
7.
Am J Hematol ; 61(3): 159-63, 1999 Jul.
Article in English | MEDLINE | ID: mdl-10398307

ABSTRACT

We retrospectively analyzed 57 patients with advanced stage (stage III/IV) or unfavorable (presence of B symptoms or bulky disease) Hodgkin's disease from January 1977 to December 1997. There were 29 male and 28 female patients. The median age was 27 years old (range, 13-59). Lactate dehydrogenase levels ranged from 104 units/l to 2320 units/l (median, 433). Eighteen (31.6%), 13 (22.8%), and 26 (45.6%) patients had stage II bulky, stage III, and stage IV disease, respectively. Twenty-five (44%) patients had B symptoms. One (1.8%), 3 (5.3%), 36 (63.2%), and 17 (29.8%) had lymphocyte predominant, lymphocyte depleted, nodular sclerosis, and mixed cellularity histology, respectively. Chemotherapy regimens included mechlorethamine, vincristine, procarbazine, prednisone (MOPP) (n = 9), adriamycin, bleomycin, vinblastine, dacarbazine (ABVD) (n = 23), MOPP alternating with ABVD (n = 13), and COPP-ABV hybrid (n = 12). Complete remission was achieved in 47 (82.4%) patients. Eleven patients (23%) relapsed after the first complete remission and four (36%) attained a second complete remission with salvage chemotherapy. Projected overall survival was 69.0% at 10 years and 20 years. Disease-free survival rates were 71% at 10 years and 20 years. Of the potential prognostic factors analyzed (age, sex, stage, lactate dehydrogenase, serum albumin level, regimen, B symptoms and bulky disease) by using the Cox regression model, only a low albumin level was found to adversely affect overall survival (P = 0.003). In conclusion, despite the relative low incidence of Hodgkin's disease in Hong Kong Chinese, the treatment outcomes in patients with advanced stage or unfavorable Hodgkin's disease is comparable to Caucasian patients.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Hodgkin Disease/drug therapy , Hodgkin Disease/pathology , Adolescent , Adult , Bleomycin/administration & dosage , Cyclophosphamide/administration & dosage , Dacarbazine/administration & dosage , Disease-Free Survival , Doxorubicin/administration & dosage , Female , Hodgkin Disease/mortality , Hong Kong , Humans , Male , Mechlorethamine/administration & dosage , Middle Aged , Neoplasm Staging , Prednisone/administration & dosage , Procarbazine/administration & dosage , Retrospective Studies , Survival Analysis , Time Factors , Vinblastine/administration & dosage , Vincristine/administration & dosage
8.
Appl Opt ; 38(25): 5452-7, 1999 Sep 01.
Article in English | MEDLINE | ID: mdl-18324053

ABSTRACT

The influence of the TiO(2) concentration (

9.
Lab Invest ; 78(11): 1459-66, 1998 Nov.
Article in English | MEDLINE | ID: mdl-9840620

ABSTRACT

SJL mice are an inbred strain with a high incidence of spontaneous lymphomas of the B-cell type. We used molecular markers of clonality to study the process of tumor progression of SJL lymphomas in vivo. This was accomplished at time intervals ranging from 2 to 116 days by initial partial splenectomy (biopsy) followed by spleen sampling at the time of killing (autopsy). Immunoglobulin heavy chain (IgH) gene rearrangement and murine leukemia virus (MuLV) proviral integration patterns were used to study the clonal identities of the sequential tumor pairs in 11 informative mice by Southern blot hybridization. Of these 11 mice, 5 showed the same number of IgH gene rearrangement bands in the matched biopsy-autopsy samples, indicating the persistence of the original lesions. In 2 of 11 mice, a decrease in the number of IgH gene rearrangement bands was seen, consistent with a process of clonal selection in the original oligoclonal population. Another 2 of 11 mice showed an increase in the IgH gene rearrangement bands, indicating the emergence of either a new unrelated clone or, less likely, a subclone with secondary IgH gene rearrangement. The remaining two mice showed differences between the patterns in biopsy and autopsy samples, as assessed by IgH gene rearrangement and the proviral integration analysis. This finding suggests that the biopsied tumor had regressed and new clones had emerged. Tumor development was also associated with an increase in the number of clonal MuLV insertions in all mice except one, in which no non-germline integration band was detected. Of 11 mice, 5 showed an increase in the extent of tumor involvement by microscopic examination of the biopsy and autopsy samples; 3 showed a decrease, whereas 2 showed no change. A change in tumor morphology toward a more dedifferentiated appearance was found in only 1 of 11 mice. Overall, the results did not show a single paradigm that tumor progression followed, rather they indicated a complex and dynamic process of clonal evolution, which is likely to be a major feature of lymphoma progression in vivo.


Subject(s)
Lymphoma/physiopathology , Spleen/pathology , Animals , Clone Cells/pathology , Disease Progression , Gene Rearrangement , Genetic Markers , Genome, Viral , Immunoglobulin Heavy Chains/genetics , Leukemia Virus, Murine/genetics , Lymphoma/pathology , Mice , Mice, Inbred Strains
10.
J Med Virol ; 56(4): 342-50, 1998 Dec.
Article in English | MEDLINE | ID: mdl-9829640

ABSTRACT

The role of Epstein-Barr virus (EBV) in the pathogenesis of gastric lymphoma of mucosa-associated lymphoid tissue (MALT) has not been well understood. The aim of the study was to investigate EBV infection and its gene expression in this tumor in order to understand its role in the pathogenesis. EBV infection was screened by in situ hybridization for EBV-encoded non-polyadenylated RNA (EBER ISH) in 79 cases of gastric MALT lymphoma of nonimmunocompromised patients. The expression of EBV proteins [LMP1 (latent membrane protein 1), EBNA2 (EBV nuclear antigen 2), ZEBRA (switch protein encoded by BZLF1 gene)] was studied by immunohistochemistry in EBER-positive cases. EBV was detected with EBER ISH in 15 (19%) of the 79 cases. EBV was found in virtually all tumor cells in 2 cases of high-grade MALT lymphoma (2.5%) (EBV-associated), and was found only in occasional large or small lymphoid cells in 13 cases (16.5%). False positive EBER signal was detected in the mucinous glandular epithelial cells of gastric antrum with FITC-labeled oligonucleotide probe but not with digoxigenin or 35S-labeled riboprobes. Type II latency (EBER+LMP1+ EBNA2-) was detected in both EBV-associated cases. Type III latency (EBER+LMP1+EBNA2+) was also identified in one EBV-associated case besides latency II. Double labeling showed coexpression of LMP1 and EBNA2 in a small number of tumor cells, indicating the presence of type III latency in single cell level. In cases with only occasional EBER-positive large or small lymphoid cells, LMP1 and EBNA2 were not detected. ZEBRA was negative in all the cases. These findings suggest that EBV may contribute to the pathogenesis of a small proportion of high-grade MALT lymphoma, where virtually all tumor cells harbored EBV and the oncogenic viral protein LMP1 was expressed. Moreover, latency III of EBV infection may exist in nonimmunocompromised patient.


Subject(s)
Epstein-Barr Virus Infections/virology , Herpesvirus 4, Human/genetics , Herpesvirus 4, Human/pathogenicity , Lymphoma, B-Cell, Marginal Zone/virology , Stomach Neoplasms/virology , Animals , Epstein-Barr Virus Infections/complications , Epstein-Barr Virus Nuclear Antigens/genetics , Epstein-Barr Virus Nuclear Antigens/metabolism , Gene Expression , Herpesvirus 4, Human/isolation & purification , Herpesvirus 4, Human/metabolism , Humans , Immunohistochemistry , In Situ Hybridization , Lymphoma, B-Cell, Marginal Zone/pathology , RNA, Viral , Stomach Neoplasms/pathology , Trans-Activators/genetics , Trans-Activators/metabolism , Viral Matrix Proteins/genetics , Viral Matrix Proteins/metabolism , Virus Latency
11.
Am J Clin Pathol ; 110(3): 347-53, 1998 Sep.
Article in English | MEDLINE | ID: mdl-9728610

ABSTRACT

Recent studies in Western populations have shown that trisomy 3 is the most frequent chromosomal abnormality in primary gastric lymphoma (PGL). To study the incidence of trisomy 3 and its implications for the pathogenesis of PGL in Hong Kong, we have applied the technique of chromosome in situ hybridization in 13 cases of PGL by using archival paraffin-embedded tissue sections. Five cases of chronic gastritis were used as controls. Trisomy 3 was found in 9 (69%) of 13 cases, including cases of low-grade lymphoma and high-grade lymphoma with or without a low-grade component. Our findings are similar to the incidence of trisomy 3 reported in the Western literature. The persistent finding of trisomy 3 in various histologic grades of PGL suggests that it may be useful as a clonal marker in this group of neoplasms. Various molecular events involving chromosome 3 may be related to the pathogenesis of this group of lymphomas.


Subject(s)
Chromosomes, Human, Pair 16/genetics , Chromosomes, Human, Pair 3/genetics , Lymphoma, B-Cell/genetics , Stomach Neoplasms/genetics , Trisomy , Gastritis/genetics , Gastritis/pathology , Hong Kong , Humans , Immunoenzyme Techniques , In Situ Hybridization/methods , Lymphoma, B-Cell/pathology , Retrospective Studies , Stomach Neoplasms/pathology
12.
J Pathol ; 185(1): 79-85, 1998 May.
Article in English | MEDLINE | ID: mdl-9713363

ABSTRACT

Although Epstein-Barr virus (EBV) positivity has been described in peripheral T-cell lymphomas (PTCLs) in Chinese patients, the cellular lineage of EBV-harbouring cells is unknown. Forty-four cases of PTCL were therefore studied by in situ hybridization (ISH) for EBV-encoded small non-polyadenylated RNA 1 and 2 (EBER), and the lineage of the EBER+ cells was determined by double labelling. The findings were further correlated with the clonality of EBV and the genotype of these EBER+ tumours. The results for the detection of EBV by ISH show that 23 of the 44 cases were EBER+. In 5/23 of the EBER+ cases, EBER was found in around 50 per cent of atypical cells and in 18/23 cases, EBER was found in a subpopulation of atypical cells. Among the EBER+ cases, all 15 tested showed clonal T-cell receptor gene rearrangement by Southern blot hybridization. Double labelling was successfully done in 11 EBER+ cases, and by comparison, EBER+/CD20+ B cells outnumbered the EBER+/CD3+ T cells in all these cases. EBV clonality analysis revealed that EBV was monoclonal in six EBER+ cases and biclonal in three cases. With the predominance of EBV+ B cells over EBV+ neoplastic T cells being observed in most of these cases, it is possible that the EBV-infected clonal population may be of B-cell lineage. This was supported in some cases where a faint clonal band was seen over a background smear in the gene rearrangement study of immunoglobulin heavy chain gene by polymerase chain reaction (PCR), indicating a minor B-cell clone. It is concluded that in EBV+ PTCL, EBV is preferentially localized in B cells rather than neoplastic T cells. The neoplastic T cells may support the clonal proliferation of a subpopulation of EBV+ B cells in PTCLs.


Subject(s)
B-Lymphocytes/virology , Herpesvirus 4, Human/isolation & purification , Lymphoma, T-Cell, Peripheral/virology , Clone Cells , Gene Rearrangement, T-Lymphocyte , Herpesviridae Infections/complications , Humans , Immunophenotyping , In Situ Hybridization , Lymphoma, T-Cell, Peripheral/complications , Lymphoma, T-Cell, Peripheral/genetics , Polymerase Chain Reaction , RNA, Viral/analysis , Tumor Virus Infections/complications
13.
Lab Invest ; 78(2): 205-12, 1998 Feb.
Article in English | MEDLINE | ID: mdl-9484718

ABSTRACT

SJL mice are an inbred strain of mice with a high incidence of spontaneous lymphomas of B-cell type often involving multiple abdominal organs, and are therefore a useful model for studying the clonal relationship among lymphomas at multiple sites. Thirteen SJL mice with well-developed tumors were killed at a median age of 56 weeks. Autopsy samples were taken from various enlarged lymphoid organs, and the histologic appearance of lymphomas was recorded. Using rearrangements of immunoglobulin genes (heavy and kappa-light chain genes) and integration patterns of murine leukemia virus as clonal markers, 7 of the 13 informative mice showed complete clonal identity among the different sites selected from each mouse; 5 of 13 mice demonstrated at least one shared clonal band with one or more markers being different among the different sites. The histologic appearance of the lymphomas from the various sites was found to be heterogeneous, even when there was clonal identity. These findings suggest that SJL lymphomas in multiple sites within one mouse are usually derived from a single clone but may show development of subclones within a major clonal population, thus supporting the notion that clonal evolution is a common event in the course of development of lymphoid neoplasia.


Subject(s)
Lymphoma/pathology , Animals , Clone Cells/pathology , Female , Gene Rearrangement , Genome, Viral , Immunoglobulins/genetics , Leukemia Virus, Murine/genetics , Lymphoma/genetics , Lymphoma/virology , Male , Mice , Mice, Inbred Strains
14.
Zhonghua Bing Li Xue Za Zhi ; 27(4): 247-50, 1998 Aug.
Article in Chinese | MEDLINE | ID: mdl-11244989

ABSTRACT

OBJECTIVE: 27 cases of nasal NK/T cell lymphomas were studied for the expression of the cytotoxic-granule-associated protein TIA-1, its immunophenotype, genotype and Epstein-Barr virus infection status. METHODS: Immunohistochemical staining for TIA-1, CD3, CD56, CD45RO, CD8, CD20; polymerase chain reaction (PCR) for TCR gamma chain gene and immunoglobulin JH chain gene rearrangement analysis; in situ hybridization for EBER 1/2 and double staining for TIA-1, CD8 with EBER 1/2. 10 cases of lymphoid hyperplasia were used for comparison. RESULTS: (1) In the 27 cases of nasal NK/T cell lymphomas, most tumor cells expressed TIA-1, CD3, CD45RO and EBER 1/2; expression of CD56 was found in 26 cases; no CD8 or CD20 were detected in tumors cells of this series of cases. Double labelled staining showed that the TIA-1 positive tumor cells coexpress EBER 1/2. TCR gamma chain gene rearrangement was detected in only 1 of the 27 cases. (2) In the 10 cases of lymphoid hyperplasia of nasal pharynx, a small amount of TIA-1 positive cells were present in 8 cases and their distribution similar to that of CD8+ cells, in 4 of these cases a few EBER 1/2+ cells were detected, the number of CD45RO+ cells and CD20+ cells were similar in all 10 cases. Double labelled staining showed that the EBER 1/2+ cells did not coexpress TIA-1. CONCLUSION: A high percentage of these tumor cells express TIA-1 and correlate with that of CD56, CD3 epsilon, CD45RO and EBER1/2 in nasal NK/T cell lymphomas. It is suggested that expression of TIA-1 in this tumor may be related to the tumor origin and may also be responsible for its special biologic behavior.


Subject(s)
Lymphoma, T-Cell/chemistry , Membrane Proteins/analysis , Nose Neoplasms/chemistry , Proteins , RNA-Binding Proteins/analysis , Adolescent , Adult , Aged , Female , Gene Rearrangement, gamma-Chain T-Cell Antigen Receptor , Humans , Lymphoma, T-Cell/genetics , Male , Middle Aged , Nasopharyngeal Diseases/genetics , Nasopharyngeal Diseases/metabolism , Nose Neoplasms/genetics , Poly(A)-Binding Proteins , Pseudolymphoma/genetics , Pseudolymphoma/metabolism , T-Cell Intracellular Antigen-1
15.
Br J Haematol ; 99(3): 668-70, 1997 Dec.
Article in English | MEDLINE | ID: mdl-9401082

ABSTRACT

The presence of the bcl-6 gene hypermutation was studied in 40 Hong Kong Chinese patients with diffuse large B-cell lymphoma. The primary sites of involvement were nodal in 18 cases and gastric in 22. Hypermutations at the E1.11 segment of bcl-6 gene were detectable in 16/22 (73%) primary gastric and 4/18 (22%) primary nodal lymphoma (P<0.01). Three of the 22 cases of primary gastric but none of the nodal lymphoma had mutations at E1.12. The proportion of hypermutated cases in the group with bcl-6 gene rearrangement was similar to that of the germ-line group (70% v 75%). High frequency of bcl-6 gene hypermutations was found in diffuse large B-cell lymphoma of the stomach and they were independent of rearrangement of the gene as detected by Southern analysis. Unlike gene rearrangement, hypermutations of the bcl-6 gene did not appear to carry any prognostic significance clinically.


Subject(s)
DNA-Binding Proteins/genetics , Lymphoma, B-Cell/genetics , Lymphoma, Large B-Cell, Diffuse/genetics , Mutation , Proto-Oncogene Proteins/genetics , Stomach Neoplasms/genetics , Transcription Factors/genetics , Adult , Aged , Aged, 80 and over , Blotting, Southern , Female , Gene Rearrangement , Humans , Male , Middle Aged , Prognosis , Proto-Oncogene Proteins c-bcl-6
16.
Int J Cancer ; 73(3): 332-8, 1997 Nov 04.
Article in English | MEDLINE | ID: mdl-9359478

ABSTRACT

The cellular nature of nasal T/natural killer (NK)-cell lymphomas (NLs) remains controversial. It is still debatable whether these represent T-cell lymphomas with extensive loss of surface antigens or are, in fact, true NK-cell lymphomas. They are associated closely with Epstein-Barr virus (EBV), to the extent that EBV-encoded small non-polyadenylated RNAs (EBER) expression can be used as a marker for the neoplastic cells. The cell lineage of this group of lymphomas was examined further by correlating immunophenotype, genotype and EBV status with the expression of cytotoxic granule-associated proteins, perforin and T-cell intracellular antigen-1 (TIA-1) in 13 cases of NL. Combined immunophenotypic and gene rearrangement analyses demonstrated that NLs can be identified clearly as either NK-cell or T-cell tumours. Nasal NK-cell lymphomas lacked clonal rearrangement of both T-cell receptor (TCR) gamma and immunogloulin heavy chain (IgH) genes and were either CD3(Leu4)-CD56+ (8 cases) or CD3(Leu4)+CD56+ (2 cases), whereas nasal T-cell lymphomas had rearranged TCRgamma and germ-line IgH genes and were either CD3(Leu4)+CD56+ (2 cases) or CD3(Leu4)+CD56- (1 case). Immunohistochemical (IH) studies showed that both perforin and TIA-1 were expressed universally in NL, irrespective of NK- or T-cell lineage. Dual labelling of TIA-1 by IH and EBER by in situ hybridisation demonstrated that the granule proteins were expressed predominantly by the EBER+ tumour cells. Our results indicate that NLs are derived from EBV-infected cytotoxic lymphocytes of both NK- and T-cell lineage. We postulate that cytotoxic lymphocytes generated during the cellular immune response to EBV infection or re-activation at the nasal region themselves may become targets for EBV infection and subsequent transformation.


Subject(s)
Herpesvirus 4, Human , Killer Cells, Natural/pathology , Lymphoma, T-Cell/pathology , Lymphoma, T-Cell/virology , Membrane Glycoproteins/analysis , Membrane Proteins/analysis , Neoplasm Proteins/analysis , Nose Neoplasms/pathology , Nose Neoplasms/virology , Proteins , RNA-Binding Proteins/analysis , Ribosomal Proteins , T-Lymphocytes, Cytotoxic/pathology , T-Lymphocytes, Cytotoxic/virology , Gene Rearrangement, B-Lymphocyte, Heavy Chain , Gene Rearrangement, gamma-Chain T-Cell Antigen Receptor , Genotype , Humans , Killer Cells, Natural/immunology , Lymphoma, T-Cell/genetics , Lymphoma, T-Cell/immunology , Nose Neoplasms/genetics , Nose Neoplasms/immunology , Perforin , Phenotype , Poly(A)-Binding Proteins , Pore Forming Cytotoxic Proteins , T-Cell Intracellular Antigen-1 , T-Lymphocytes, Cytotoxic/immunology
17.
Cancer Genet Cytogenet ; 97(2): 114-8, 1997 Sep.
Article in English | MEDLINE | ID: mdl-9283593

ABSTRACT

The incidence of BCL-6 gene rearrangement was studied in 39 Hong Kong Chinese patients with diffuse large B-cell lymphoma. The primary site of involvement was nodal in 18 cases and gastric in 21 cases. Clonal BCL-6 gene rearrangement was found in 17% of the patients with primary nodal and 48% with primary gastric lymphoma (p = 0.05). The clinical characteristics and treatment outcome of the 21 patients with primary gastric lymphoma were analyzed according to the BCL-6 status. Significantly more patients in the germline BCL-6 gene group had advanced stage (II, III and IV) of disease. Complete remission rate following primary therapy appeared to be higher for the positive rearrangement group (70% versus 36%), but it was not statistically significant. Those with a rearranged BCL-6 gene also appeared to have better survival at 5 years (58% versus 36%) but the difference was also not statistically significant. On the other hand, patients being classified as low risk according to the International Prognostic Index had significantly better survival at 5 years (89% versus 9%, p = 0.0001). We concluded that BCL-6 gene rearrangement was more commonly found in diffuse large B-cell lymphoma of primary gastric origin than its nodal counterpart and it may be playing a more important role in the pathogenesis of gastric large B-cell lymphoma. There was a trend that the BCL-6 gene rearrangement was associated with a more favorable outcome in patients with gastric large B-cell lymphoma but the difference was not statistically significant.


Subject(s)
DNA-Binding Proteins/genetics , Lymphoma, B-Cell/genetics , Lymphoma, Large B-Cell, Diffuse/genetics , Proto-Oncogene Proteins/genetics , Stomach Neoplasms/genetics , Transcription Factors/genetics , Adult , Aged , Female , Gene Rearrangement , Humans , Male , Middle Aged , Prognosis , Proto-Oncogene Proteins c-bcl-6 , Survival Analysis
18.
Br J Haematol ; 97(4): 821-9, 1997 Jun.
Article in English | MEDLINE | ID: mdl-9217183

ABSTRACT

The surface molecule CD56 marks a category of malignant lymphoma of putative natural killer (NK) cell origin. We conducted a retrospective analysis of 24 cases of CD56+ NK lymphoma/leukaemia to define the clinicopathologic and prognostic features of this specific group of lymphomas. 56 cases of nasal lymphomas and 204 cases with an initial diagnosis of peripheral T-cell lymphoma were retrospectively analysed. To specifically examine lymphomas of putative NK origin, only those that were negative for surface expression of CD3 but positive for CD56 were analysed. 24 cases were identified. The initial predominant sites of involvement were nasal (n = 18), palate (n = 1), nodal (n = 1) and multi-organ (n = 4). Clinically, in patients with disease localized to one anatomical site (n = 20), most had symptoms confined to the nose, with a high percentage in early stage (I: 91%; IV: 9%). The marrow was not involved in any of these cases. However, patients with multi-organ involvement at presentation (n = 4) behaved differently. All presented acutely with pancytopenia, hepatosplenomegaly, and marrow infiltration with haemophagocytosis. A leukaemic phase was observed in one case. Anthracycline containing combination chemotherapy resulted in complete remission in 75% of patients with localized disease, but only in 25% with multi-organ involvement. The median survival of patients with localized disease was 12 months, compared with 2 months in the multi-organ group (P = 0.06); the disease-free survival was significantly better in the former (P < 0.01). The overall median survival of all patients was still poor at 11 months. We conclude that CD56+ NK lymphomas could be divided into two main patterns of disease presentations: localized (predominantly nasal), and multi-organ involvement. Each has different clinicopathologic and prognostic features. Conventional chemotherapy appeared ineffective for the majority of patients, and innovative treatment modalities are needed to improve outcome.


Subject(s)
Antigens, Neoplasm/metabolism , Biomarkers, Tumor/metabolism , CD56 Antigen/metabolism , Killer Cells, Natural/pathology , Lymphoma, Non-Hodgkin/diagnosis , Nose Neoplasms/diagnosis , Adolescent , Adult , Aged , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Female , Humans , Immunophenotyping , Lymphoma, Non-Hodgkin/drug therapy , Lymphoma, Non-Hodgkin/radiotherapy , Lymphoma, T-Cell, Peripheral/diagnosis , Lymphoma, T-Cell, Peripheral/drug therapy , Lymphoma, T-Cell, Peripheral/radiotherapy , Male , Middle Aged , Nose Neoplasms/drug therapy , Nose Neoplasms/radiotherapy , Retrospective Studies , Treatment Outcome
19.
Ann Oncol ; 8 Suppl 2: 41-4, 1997.
Article in English | MEDLINE | ID: mdl-9209639

ABSTRACT

BACKGROUND: Helicobacter pylori (H. pylori) infection has been postulated to be a pathogenetic factor in gastric lymphoma. However, the etiological factors for gastric lymphoma could vary in different populations. MATERIALS AND METHODS: We looked for histological evidence of H. pylori infection in 53 gastrectomy specimens from Hong Kong Chinese patients with primary gastric B-lymphoma. We also screened for Epstein-Barr virus (EBV) in these cases using in situ hybridization with oligonucleotide probes for EBV-encoded small RNA1 and 2. RESULTS: H. pylori was found in 29 of 53 (55%), including 8 of 13 (62%) cases of low-grade lymphoma of mucosa-associated lymphoid tissue (MALT) type. These infection rates in gastric lymphoma are lower than those reported in Western populations (80%-100%) and comparable to that found in healthy Chinese blood donors (55%) or in non-ulcer dyspeptic patients (52%-57%). EBV was found in tumor cells only in one case of high-grade gastric lymphoma with low-grade MALT component which was H. pylori-negative, and in occasional nontumor-lymphoid cells in 7 other cases. CONCLUSIONS: These results suggest that (1) the role of H. pylori in pathogenesis of gastric lymphoma may vary in different populations; (2) very few gastric lymphomas are associated with EBV; (3) not all low-grade gastric MALT lymphomas are H. pylori-dependent.


Subject(s)
Burkitt Lymphoma/virology , Herpesvirus 4, Human/isolation & purification , Stomach Neoplasms/virology , Tumor Virus Infections/virology , Adult , Aged , Aged, 80 and over , Burkitt Lymphoma/epidemiology , Female , Hong Kong , Humans , Male , Middle Aged , Prevalence , Retrospective Studies , Tumor Virus Infections/epidemiology
20.
Hematol Oncol ; 14(4): 173-9, 1996 Dec.
Article in English | MEDLINE | ID: mdl-9267463

ABSTRACT

Primary B cell mediastinal lymphoma has been recognized as a distinct entity recently. This is a retrospective study to define the clinical features and treatment outcome over a 10-year period. Twenty-four consecutive patients (male/female: 11/13) with B cell lymphoma primarily involving the mediastinum were studied. The median age was 34 years. Symptoms were mainly referrable to the chest, with superior vena cava syndrome (SVCO) present in one-third of the patients. Bulky disease was present in over half (58 per cent) and B symptoms were present in 38 per cent of patients. The overall CR rate was 70 per cent and the 5-year OS rates were 56 per cent and 72 per cent for all and CR patients respectively. Five (71 per cent) primary refractory patients and four (66 per cent) relapsed patients died despite salvage therapy. Six relapses occurred at a median of 6 months from treatment. This study showed that primary large B cell lymphoma of the mediastinum is a clinically distinct entity affecting young patients. A significant proportion attained CR and overall, more than half achieved prolonged remission, and most of the relapses occurred early. However, those who failed to attain CR or relapsed still had a poor outcome. An intensive therapy such as autologous bone marrow transplant has to be considered in this subgroup of patients.


Subject(s)
Lymphoma, B-Cell/pathology , Mediastinal Neoplasms/pathology , Adolescent , Adult , Aged , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Disease-Free Survival , Female , Humans , Lymphoma, B-Cell/drug therapy , Male , Mediastinal Neoplasms/drug therapy , Middle Aged , Prognosis , Retrospective Studies , Sex Characteristics
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