Biomedical subjects

Koichi Ohshima

Publications and source records attributed to Koichi Ohshima.

At least 55 records · Page 3Linked to original sources

PubMed2003

Dynamics of Epstein-Barr virus load in pyothorax-associated lymphoma.

We treated a 73-year-old man who developed a pyothorax-associated pleural lymphoma after a 52-year history of tuberculous pleuritis. The lymphoma was classified histologically as a diffuse large, B-cell type. Epstein-Barr virus (EBV) was identified in the tumor by immunocytochemical and molecular methods. Chemotherapy both without and with the addition of rituximab was only minimally effective, but adding radiotherapy to chemotherapy reduced the tumor size, resulting in a partial remission. The EBV load measured by a quantitative real-time polymerase chain reaction correlated well with the tumor size and the serum lactate dehydrogenase concentration. Monitoring the EBV load may be useful in the management of pyothorax-associated lymphoma.

Empyema, Pleural↗

PubMed2003

Expression of apoptosis-associated protein RCAS1 in macrophages of histiocytic necrotizing lymphadenitis.

Receptor-binding cancer antigen expressed on SiSo cells (RCAS1), which is recognized by the 22-1-1 monoclonal antibody (MoAb) against human uterine adenocarcinoma cell line SiSo, has been identified on various kinds of cancer cells. RCAS1 appears to be an apoptosis-associated protein that induces apoptosis in activated T-cells and erythroid progenitor cells. We previously demonstrated that monocytes/macrophages express RCAS1. In the present study, we investigated RCAS1 expression by 22-1-1 MoAb in histiocytic necrotizing lymphadenitis (HNL), which is characterized by necrotic lesions consisting of T-cells undergoing apoptosis and macrophages in proliferation. Expression of RCAS1 was analyzed by immunohistochemical staining in 9 cases of HNL and in 9 cases of reactive lymphadenitis used as a control. The ratio of RCAS1+ cells to CD68+ cells (monocytes/macrophages) was significantly higher in the patients with HNL than in the patients with reactive lymphadenitis (P = .0002; paired t test). Our findings suggest that RCAS1 expressed on macrophages may play an important role in the induction of activated T-cell apoptosis in cases of HNL.

Adolescent↗

PubMed2003

Primary colorectal T-cell lymphoma.

We report here a case of primary colorectal T-cell lymphoma in a 49-year-old man. Eighteen years previously, he was diagnosed as having ulcerative colitis based on the findings of colonoscopy and a barium enema. Since then, he had been treated with salicylazosulfapyridine until the most recent episode. He was refered to our clinic with the chief complaint of abdominal pain and excretion of mucus, and for a workup of bowel lesions. Physical examination results were not remarkable, except for the presence of low-grade fever. Total colonoscopy showed multiple shallow ulcers and aphthoid erosions through the entire colon and rectum, except for the descending colon. Endoscopic findings of the descending colon were normal, which was different from the findings of the active stage of ulcerative colitis. Biopsy specimens from the colon and rectum with ulcerations and aphthoid erosions showed a diffuse proliferation of medium-sized to large atypical lymphoid cells with irregular and indistinct nucleoli, thus revealing malignant lymphoma, diffuse pleomorphic type. The lymphoma cells were positive for CD2, CD3, CD5, CD8, and T-cell receptor (TCR) beta F1, but negative for CD4, CD19, CD20, CD103, and CD56. Southern blotting revealed rearrangement of TCR. Based on these findings, the patient was diagnosed as having high-grade T-cell lymphoma. The findings of computerized tomography of the chest and abdomen, gallium scintigraphy, and abdominal ultrasonography were all normal. There were no abdominal lesions throughout the esophagus, stomach, duodenum, and small intestine. As the patient refused total proctocolectomy, he was treated with one course of CHOP (cyclophosphamide, vincristine, adriamycin, and prednisolone) and subsequently with three courses of ProMACE-CytaBOM (consisting of cyclophosphamide, adriamycin, etoposide, cytarabine, bleomycin, vincristine, methotrexate, and prednisolone). After the therapy, improvement of the colorectal lesions was observed, though lesions clearly still remained. To our knowledge, this is the first case report of primary colorectal T-cell lymphoma with cytotoxic/suppressor T-cell phenotype.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed2003

API2-MALT1 fusion defines a distinctive clinicopathologic subtype in pulmonary extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue.

t(11;18)(q21;q21) is associated with mucosa-associated lymphoid tissue (MALT)-type lymphoma and results in API2-MALT1 fusion. However, its clinicopathologic significance remains unclarified. API2-MALT1 fusion is detected most frequently in MALT lymphomas primarily involving the lung. We therefore screened 51 cases of pulmonary MALT lymphoma for API2-MALT1 fusion, and studied its relationship with clinicopathologic factors including the immunohistochemical expression of BCL10, another MALT lymphoma-associated molecule. The API2-MALT1 fusion transcript was detected in 21 of 51 (41%) cases, and was correlated with the absence of any underlying autoimmune disease, and with a normal serum lactate dehydrogenase, a "typical" histology without marked plasmacytic differentiation or an increased number of large cells, and aberrant nuclear BCL10 expression. However, its prognostic impact was not identified in the limited follow-up (6 to 187 months, median 27). These data suggest that the API2-MALT1 fusion may be a causative gene abnormality unrelated to autoimmune disease. In addition, this alteration may define a homogeneous MALT lymphoma subtype that is clinically more indolent and histologically more "typical." Aberrant nuclear BCL10 expression may have a possible role as a tool to screen for this API2-MALT1 fusion. A large-scale study with a long follow-up is necessary to establish the prognostic significance of API2-MALT1 fusion.

Adult↗

PubMed2003

Local antigen-driven oligoclonal expansion of B cells in the liver portal areas of patients with primary biliary cirrhosis.

BACKGROUND/AIMS: The antigen-driven clonal proliferation of B cells within target tissue has been reported in some autoimmune diseases. The purpose of this study was to examine the clonal characteristics of B cells in the liver portal area of primary biliary cirrhosis (PBC). METHODS: The liver portal area was microdissected from liver biopsy sections from two PBC patients. Genomic DNA was extracted and rearranged immunoglobulin heavy chain variable region (VH) genes were amplified and sequence analyzed. RESULTS: Sixteen VH sequences from portal area 1A of patient 1 had three different rearrangements. Nineteen VH sequences from portal area 1B of this patient had three different rearrangements. In three sequences from the portal area 1B, a stepwise accumulation of somatic mutations was observed. Between the sequences from the two portal areas, no common VH sequence was observed. In patient 2, 15 VH sequences from portal area 2A had three different rearrangements. Fourteen VH sequences from portal area 2B had two different rearrangements. One rearrangement was present both in the portal area 2A and portal area 2B. CONCLUSION: The oligoclonal B cell proliferation and stepwise accumulation of somatic mutations suggested that an antigen-driven B cell response had occurred in the portal area of PBC.

Aged↗

PubMed2003

Re-entry of tumour B cells into the cycle of somatic mutation and isotype switching in follicular lymphoma.

Sequencing of the immunoglobulin (Ig) gene transcripts of the tumour B cells in lymph node (LN) and bone marrow (BM) from a follicular lymphoma (FL) patient associated with multiple myeloma identified two dominant clones. One of the clones, present in both LN and BM, had somatic mutations and extensive clonal diversity. Among the diversified clones, two dominant populations of identical sequences (group I and II) were present. Group II was a descendant population of group I and had nine more somatic mutations. Group I contained micro-, delta-, gamma- and alpha-expressing clones. Group II clones contained mainly micro- and delta-expressing clones. These findings showed that somatic mutation and isotype switching occurred repeatedly in this patient.

Aged↗

PubMed2003

Detection of human herpesvirus-8 in peripheral blood mononuclear cells from adult Japanese patients with multicentric Castleman's disease.

Human herpesvirus-8 (HHV-8) encodes viral homologues of cellular genes, including viral interleukin 6 (vIL-6), which induces endogenous human IL-6 (hIL-6) secretion. Unregulated overproduction of hIL-6 in lymph nodes (LN) is thought to be responsible for the systemic manifestations of multicentric Castleman's disease (MCD). In the present study, we assessed the presence of HHV-8 and HHV-8-encoded viral homologues in LN and peripheral blood mononuclear cells (PBMC) from adult Japanese patients with MCD. HHV-8 DNA was amplified by nested polymerase chain reaction (PCR) and was detected in LN from 13 out of 16 MCD patients (81%). HHV-8 DNA was also detected in PBMC from six out of seven patients (86%) whose LN were positive for HHV-8 DNA. Because mRNA could not be successfully extracted from LN sections that were either formalin-fixed or embedded in paraffin, we examined the expression of mRNA for HHV-8-encoded viral homologues, such as vIL-6, vBCL-2, vCyclin-D and viral G-protein-coupled receptor (vGPCR) by nested reverse transcription (RT)-PCR in PBMC from 10 MCD patients. However, mRNA of these HHV-8-encoded viral homologues was not detected in any patients tested. Although our results do not indicate a role for HHV-8-encoded viral homologues in the pathogenesis of MCD, they do suggest that HHV-8 infection may be associated with MCD in adult Japanese patients.

Adult↗

PubMed2003

HTLV-1 carriers with B-cell lymphoma of localized stage head and neck: prognosis, clinical and immunopathological features.

Human T-lymphotropic virus type I (HTLV-I) is closely associated with T-cell lymphoma/leukaemia, which always shows monoclonal HTLV-1 provirus DNA integration. HTLV-1 is not associated with B-cell lymphoma. The relationship between B-cell lymphoma and HTLV-1 was analysed retrospectively in early stage B-cell non-Hodgkin's lymphoma (NHL) according to HTLV-1 infection and pathological features. We analysed 198 cases of head and neck B-cell NHL treated with radiotherapy and/or chemotherapy; 21 were seropositive and 177 were seronegative for HTLV-1. We also immunostained 26 cases of diffuse large B-cell lymphoma (DLBL), including 12 seropositive and 14 seronegative for HTLV-1 respectively, for CD20, CD3, CD4, CD8, CD56, MIB-1 and T-cell-restricted intracellular antigen (TIA-1) to examine the phenotype, immunity and proliferation activity. The 5-year overall survival rates were 78% and 49% (P = 0.007, log rank test) for HTLV-1 seronegative and seropositive cases respectively. Infection with HTLV-1 was significantly associated with poor survival in patients with B-cell lymphoma by multivariate analysis. For DLBL, HTLV-1 infection was not a significant factor, but the overall survival curve was similar to that of the 21 seropositive B-cell lymphoma cases. Lymphoma cells were negative for TIA-1, but the background lymphocytes were positive for this marker. The number of TIA-1-positive cells was higher in HTLV-1-negative cases than in-positive cases. In conclusion, patients with B-cell-NHL (B-NHL) who are also HTLV-1 carriers have a poorer prognosis than non-carriers. HTLV-1 does not seem to be associated with lymphomagenesis of the B phenotype itself, but correlates with host immunity by reducing the number of cytotoxic T-cells.

Adult↗

PubMed2003

Phenotypic analysis of peripheral T/NK cell lymphoma: study of 408 Japanese cases with special reference to their anatomical sites.

The World Health Organization (WHO) classification of malignant lymphoma presented a list of disease entities well defined by clinical, immunological and genetic features. Therefore, the current diagnosis of peripheral T/NK-cell lymphomas (PTNKLs) essentially requires the inclusion of anatomical sites of disease and phenotypical features. We analyzed 408 Japanese cases of PTNKLs in order to clarify the relationship between anatomical sites of disease and phenotypical features and to translate the functional subsets of T and NK cells into their diagnoses for further understanding lymphomatic biology. The T/NK-cell lymphoma entities were allocated into three categories: (i) cytotoxic memory T-cell and/or NK-cell lymphoma (n = 151) consisting of extranodal NK/T-cell tumors other than mycosis fungoides (MF); (ii) non-cytotoxic memory T-cell lymphoma (n = 142) consisting of nodal and cutaneous tumors such as angioimmunoblastic T-cell lymphoma, adult T-cell lymphoma/leukemia and MF; and (iii) anaplastic lymphoma kinase positive anaplastic large cell lymphoma (n = 110) that has unique features and might be regarded as cytotoxic 'naive' T-cell lymphoma. Overall, these three categories were significantly correlated with age of onset, anatomical sites, the level of expression of cytotoxic molecules and CD45RO, and association with Epstein-Barr virus. This concept might provide a new insight enabling further understanding of the interrelationships among WHO T/NK-cell disease entities.

Adolescent↗

PubMed2003

Primary esophageal small cell carcinoma with concomitant invasive squamous cell carcinoma or carcinoma in situ.

Esophageal small cell carcinoma (SmCC) is a rarer, more highly aggressive, and more rapidly growing neoplasm than esophageal squamous cell carcinoma (SqCC). SmCC and SqCC also differ in terms of chemotherapy of choice, response to therapy, and prognosis. Accordingly, it is important to differentiate the 2 carcinomas. We studied the histology and immunohistochemical profiles of 6 cases of esophageal SmCC to elucidate the correct diagnosis of this tumor. We performed immunohistochemical analysis antibodies against cytokeratins (CKAE1/AE3, CKCAM5.2, CK34betaE12, CK7, CK8, CK10/13, and CK19), epithelial membrane antigen (EMA), neural cell adhesion molecule (NCAM; CD56), neuron-specific enolase (NSE), chromogranin-A, S-100 protein, carcinoembryonic antigen (CEA), E-cadherin, thyroid transcription factor-1 (TTF-1), and p53. In 3 of the 6 SmCCs, heterogeneous components of in situ or invasive SqCC were observed. SqCC was found in the mucosa adjacent to the main SmCC, and the boundary between SmCC and SqCC was distinct, with no transitional features. Staining for NCAM, NSE, and chromogranin-A was positive in SmCCs, but negative in SqCCs. Both SmCCs and SqCCs were positive for CKAE1/AE3, CKCAM5.2, CK8, and EMA, but only SqCCs were positive for CK34betaE12 and CK19. Moreover, SmCCs containing SqCC components were positive for CEA and E-cadherin, whereas SmCCs without SqCC were negative. Our study suggests that NCAM and NSE are useful markers in diagnosing esophageal SmCC, and CK34betaE12 and CK19 are useful for differentiating SqCC components from SmCC.

Aged↗

PubMed2003

Expression of chemokine receptor CXCR3 and its ligand, mig, in gastric and thyroid marginal zone lymphomas. Possible migration and autocrine mechanism.

Chemokine receptors mediate the migration of lymphocytes through the binding of ligands, and the expression is differentially regulated in lymphocyte subsets. CXCR3 is usually expressed in Th1 T cells, however, recently is reported to be expressed in B cell chronic lymphocytic leukemia, mucosa-associated lymphoid tissue type lymphoma (MALT) (extranodal marginal zone lymphoma), and other B cell non-Hodgkin lymphomas. Our study was designed to investigate the expression of CXCR3 and its ligand Mig, and their relationships in MALT using immunohistochemistry. In addition, CCR4, which is characteristic Th2 helper phenotype, and its ligand thymus and activation-regulated chemokine (TARC), were compared with CXCR3, as Th1 phenotype. We studied 14 cases of gastric B cell lymphoma [low-grade MALT, 5 cases; high-grade MALT, 5 cases; and diffuse large (DL), 4 cases] and 16 cases of thyroid B cell lymphoma [low-grade MALT, 4 cases; high-grade MALT, 5 cases; and DL, 7 cases]. CXCR3-expressing lymphoid cells were detected in all cases. In double immunostaining (CXCR3-CD20), gastric and thyroid low/high MALT showed CXCR3-positive neoplastic B cells, but DL, except two cases, did not. In DL, CXCR3-positive lymphoid cells were mainly reactive T-cells (CD3-positive cells). Mig was expressed mainly in stromal cells (histiocytes, macrophages, fibroblasts, and endothelial cells). In gastric lymphoma, low-grade MALT contained abundant Mig-strongly expressing cells, while staining in high-grade MALT and DL was mild. In thyroid lymphoma, staining was strong in low- and high-grade MALT, but moderate in DL. In double-staining, CXCR3-Mig-coexpressing lymphoma cells were abundant in high MALT of the stomach and thyroid, but rare in other subtypes. TARC-positive cells and CCR4-positive cells were rarely encountered in all cases. Our results indicate a tendency for low-grade MALT to contain CXCR3(+)Mig- lymphoma cells, high-grade to contain CXCR3(+)Mig+ and DL to contain CRCR3(-)Mig- lymphoma cells. We speculate that CXCR3 is associated with migration of lymphoma cells in low-grade MALT, and autocrine function in high-grade MALT, and not associated with any function in DL.

Aged↗

PubMed2003

Differential chemokine, chemokine receptor and cytokine expression in Epstein-Barr virus-associated lymphoproliferative diseases.

T cell immunity plays an important role in the clinicopathology of Epstein-Barr virus (EBV)-associated diseases. Acute EBV-induced infectious mononucleosis (IM) is a common self-limiting disease, however, other EBV-associated diseases, including chronic active EBV infection (CAEBV), NK cell lymphoma (NKL), and Hodgkin's lymphoma (HL), exhibit distinct clinical features. Chemokines are members of a family of small-secreted proteins. The relationships between chemokines and the chemokine receptor (R) are thought to be important for selectivity of local immunity. Some chemokines, chemokine R and cytokines closely associate with the T cell subtypes, Th1 and Th2 T cells and cytotoxic cells. To clarify the role of T cell immunity in EBV-associated diseases, we conducted gene expression profiling, using chemokine, chemokine R and cytokine DNA chips. Compared to EBV negative non-specific lymphadenitis, CAEBV and NKL exhibited diffuse down- and up-regulation, respectively, of these gene profiles. IM had a predominantly Th1-type profile, whereas HL had a mixed Th1/Th2-type profile. Reduction of the Th1-type cytokine interferon gamma (IFN-gamma) in CAEBV was confirmed by Reverse transcriptase-polymerase chain reaction, whereas IFN-gamma expression was markedly enhanced in NKL, and moderately enhanced in IM. Compared to IM, CAEBV showed slight elevation of "regulated upon activation, normal T expressed and secreted" (RANTES), but almost all other genes assayed were down-regulated. NKL exhibited elevated expression of numerous genes, particularly IFN-gamma-inducible-10 (IP-10) and monokine induced by IFN-gamma (MIG). HL showed variable elevated and reduced expression of various genes, with increased expression of IL-13 receptor and MIG. Our study demonstrated the enormous potential of gene expression profiling for clarifying the pathogenesis of EBV-associated diseases.

Adolescent↗

PubMed2003

Senile EBV+ B-cell lymphoproliferative disorders: a clinicopathologic study of 22 patients.

Twenty-two Epstein-Barr virus-associated B-cell lymphoproliferative disorders (LPDs) without predisposing immunodeficiencies were evaluated clinically and pathologically. All patients were Japanese and negative for anti-human immunodeficiency virus antibody. They were all more than 60 years old with a median age of 75.5 years. Eighteen (82%) patients showed extranodal involvement. Biopsied specimens contained variable numbers of centroblasts, immunoblasts, and Reed-Sternberg-like giant cells often with necrosis and an angiocentric pattern. The 13 cases showing polymorphous composition and inflammatory background were categorized as polymorphic LPD subtype. The other nine cases contained diffuse proliferative lesions of large lymphoid cells and were categorized as large cell lymphoma subtype. Tumor cells expressed CD20 and/or CD79a, and in situ hybridization showed them to be associated with Epstein-Barr virus. LMP1 was detected in all cases and EBNA2 in seven. Eighteen patients initially received combination chemotherapy, and 12 achieved complete remission. However, six patients were refractory to chemotherapy and four patients with complete remission later relapsed. Eight of the 18 patients who received chemotherapy showed an aggressive disease course within a year after the diagnosis. There was a significant difference in prognosis between the group with polymorphic LPDs and the one with large cell lymphomas (p = 0.003). Although the disease profile of the 22 cases was analogous to that of immunodeficiency-associated B-cell LPDs, none of the patients showed evidence of underlying immunodeficiency-related diseases. These findings suggest that Epstein-Barr virus-associated LPD without immunodeficiency mainly occurs in elderly patients. Further investigations are needed to clarify the pathogenesis of this disease and to determine the optimal treatment strategy.

Aged↗

PubMed2003

Non-B, non-T neoplasms with lymphoblast morphology: further clarification and classification.

We studied the morphologic, immunohistochemical, and clinical characteristics of 158 cases of lymphoblastic lymphoma. Based on immunophenotyping and cell lineage, cases were classified into B-cell type (CD20,CD19 or CD79a+, n = 53), T-cell type (surface CD3+, n = 84), and non-B, non-T type (B cell marker- and surface CD3-, n = 21). The latter group was further divided based on immunohistochemistry into: 1) CD7+ stem cell lymphoma (CD7+SCL) [CD4-, CD7+, CD33+/-, CD56-], 2) blastic natural killer cell lymphoma (B-NKL) [CD4-, CD7+/-, CD33-, CD56+, CD123-], 3) myeloid/NK precursor cell leukemia (M/NKL) [CD4-, CD7+, CD33+, CD56+], and 4) CD4+CD56+ hematodermic malignancy (CD4+CD56+) type [CD4+, CD7+/-, CD33-, CD56+, CD123+]. The CD7+SCL and M/NKL types frequently exhibited bone marrow invasion and mediastinal masses. All CD4+CD56+ types were associated with skin lesions. B-NKL type is included into Blastic NK lymphoma in new World Health Organization classification with CD4+CD56+ type. But the cases of B-NKL were more reminiscent of CD7+SCL or M/NKL type than the CD4+CD56+ type, both clinically and histologically. We propose that blastic NK lymphoma, a disease entity in the new WHO classification, should be divided into two types based on phenotypes and clinical features. The non-B, non-T lymphomas exhibited poorer prognoses, similar to that of B-cell lymphomas, than T-cell type tumors (P = 0.009). Among the 21 tumors, the prognosis of the four subtypes did not differ significantly; however, cases receiving aggressive chemotherapy and stem cell transplantation had a more favorable prognosis than those receiving only traditional chemotherapy and radiation therapy (P = 0.0089).

Adolescent↗

PubMed2003

Reduced expression of heterogeneous nuclear ribonucleoprotein B1 in adult T-cell lymphoma/leukemia.

It is considered that hnRNP B1 expresses similarly in the various types of tumor cells. Recently, we demonstrated high B1 expression in B-cell lymphoma and carcinoma. To evaluate the difference of B1 expression between B and T-cell lymphoma, we immunologically studied the B1 expression in 22 cases with nodal T-cell lymphoma, comprising adult T-cell leukemia/lymphoma (ATLL; n=15) and angioimmunoblastic T-cell lymphoma (AILD; n=7), using an anti-hnRNP B1 monoclonal antibody, 2B2. In ATLL cases, scattered large transformed lymphoma cells demonstrated strong B1 expression, while the medium-sized lymphoma cells were negative. On the one hand, lymphoma cells in AILD diffusely expressed B1. The mean B1 expression rate in ATLL was 22%, which was significantly lower than that in AILDs (45%), B-cell lymphomas (44%), and metastatic carcinomas (53%) (p<0.01). Our result might suggest that process of hnRNP B1 expression in ATLL differs from those in other lymphoid neoplasms and carcinoma.

Adolescent↗

PubMed2003

Follicular lymphoma of the stomach: immunohistochemical and molecular genetic studies.

The gastrointestinal (GI) tract is the most common site for the development of extranodal non-Hodgkin's lymphomas, with most cases having a diffuse architectural pattern. Follicular lymphoma (FL) of the stomach is a very rare disease, and little is known about the immuno-histochemical and molecular genetic characteristics of this type of lymphoma. Despite their rarity, FLs are an important consideration in the differential diagnosis of follicular hyperplasia of mucosa-associated lymphoid tissue (MALT), a relatively frequently encountered lesion with the potential to cause significant diagnostic difficulty, especially when assessment is based on scanty biopsy material. We report a 57-year-old woman with gastric FL, and describe the results of immunohistochemical and molecular genetic studies.

Biomarkers, Tumor↗

PubMed2003

[Successful treatment of refractory peripheral T-cell lymphoma by allogeneic peripheral blood stem cell transplantation].

A 40-year-old man was admitted to our hospital suffering from abdominal pain. He revealed marked splenomegaly, lymphadenopathy and pancytopenia. Lymph node biopsy showed diffuse proliferation of medium to large atypical lymphoid cells. Immunohistochemically the cells were positive for T-cell markers. He was diagnosed as having peripheral T cell lymphoma (PTCL) with involvement of the spleen and bone marrow. Because of refractoriness to combination chemotherapies and splenic irradiation, we performed allogeneic peripheral blood stem cell transplantation from an HLA-identical sister. Conditioning was consisted of conventional doses of total body irradiation and cyclophosphamide, and GVHD prophylaxis was performed with cyclosporine and methotrexate. After the patient developed grade III graft-versus-host disease, his splenomegaly improved dramatically. Although the effectiveness of allogeneic hematopoietic cell transplantation in the treatment of malignant lymphoma is controversial, we should consider this as a second-line therapy to refractory subsets of PTCL.

Adult↗

PubMed2003

Differential chemokine, chemokine receptor, cytokine and cytokine receptor expression in pulmonary adenocarcinoma: diffuse down-regulation is associated with immune evasion and brain metastasis.

Pulmonary adenocarcinoma is frequently associated with brain metastasis at some stage during the disease course. Host immunity, particularly T cell immunity, plays an important role in the clinicopathological features of carcinoma proliferation and metastasis. Cytokines and chemokines are members of a family of small secreted proteins. The relationships between the cytokines and cytokine receptor (R), and between chemokines and chemokine R are important determinants of selectivity in local immunity. RCAS1 (receptor-binding cancer antigen expressed on SiSo cells) and Fas ligand (FasL) are present in neoplastic cells, induce apoptosis of NK/T cells, and play a role in immune evasion. To investigate differences in host immunity between pulmonary adenocarcinoma with and without brain metastasis, we performed gene expression profiling, using chemokine, chemokine R, cytokine and cytokine R DNA chips. In addition, to assess the extent of immune evasion, we examined the expression of RCAS and FasL. We studied five cases of pulmonary adenocarcinoma with brain metastasis (meta) and five cases without brain metastasis (non-meta). The brain meta cases exhibited diffuse down-regulated profiles, in comparison with normal non-carcinomatous lungs, which were used as controls. Non-meta cases also displayed diffuse down-regulation, however the degree was variable. Expression of RCAS and FasL was detected in almost all cases, but was stronger in meta than non-meta cases. Our findings suggested that tumor cells evaded host immunity. In the gene tree analysis, brain meta cases and non-meta cases exhibited distinct clustering. Brain meta cases exhibited significantly lower expression of interleukin 13 receptor alpha2 (IL-13Ralpha2) than non-meta cases. The reduction of IL-13Ralpha2 expression was confirmed by RT-PCR. Immunohistochemically, non-meta adenocarcinoma cells frequently expressed IL-13Ralpha2, however, IL-13Ralpha2 expression was rare or weak in adenocarcinomas with meta. Our results suggested that, in addition to immune evasion, the characteristics of the adenocarcinoma tumors themselves were important for brain metastasis. However, our study demonstrated the enormous potential of gene expression profiling in clarifying the pathogenesis of brain metastasis in pulmonary adenocarcinoma.

Adenocarcinoma↗