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N Niitsu

Publications and source records attributed to N Niitsu.

At least 19 recordsLinked to original sources
PubMed2003

Primary gastric T-cell lymphoma not associated with human T-lymphotropic virus type I: a case report and review of the literature.

Primary gastric T-cell lymphoma (PGTL) not associated with human T-lymphotropic virus type I (HTLV-I) is extremely rare and such a case is reported herein. The patient was a 58-year-old Japanese male presenting with submucosal tumor of the stomach identified on endoscopic examination. The lesion was diagnosed as non-Hodgkin's lymphoma by endoscopic biopsy and classified as peripheral T-cell lymphoma, unspecified, due to clonal rearrangement of the T-cell receptor beta (TCR) gene and expression of TCR beta protein in the absence of B-cell genotypes and phenotypes. Unlike previously reported cases of HTLV-I-unassociated PGTL, lymphoma in the current case was characterized histologically as "low grade" and phenotypically as CD4+, TIA-1+, granzyme B+, and CD103-. The lymphoma responded well to chemotherapy and radiation, and the patient was well with no detectable disease 10 months after initiation of therapy. A review of patients with PGTL in the literature revealed a few long-term survivors, and the investigation of therapeutic strategies for PGTL is, therefore, necessary.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2003

Clinical significance of nm23-H1 proteins expressed on cell surface in non-Hodgkin's lymphoma.

The nm23 gene was isolated as a metastasis suppressor gene that exhibits low expression in high-level metastatic cancer cells. Its gene is related to the prognosis of acute myelogenous leukemia (AML) and non-Hodgkin's lymphoma (NHL). In this study, we examined the expression of nm23-H1 protein on the lymphoma cell surface of NHL. In 28 of 108 cases (25.9%), we observed > or = 20% of cell surface nm23-H1 protein expression and expression was especially high in peripheral T cell lymphomas and extranodal NK/T cell lymphomas. We also observed a significant correlation between serum nm23-H1 level and cell surface nm23-H1 expression levels. In patients with high levels of cell surface nm23-H1 expression, overall and progression-free survival rates were significantly lower than those in patients with low surface nm23-H1 expression levels. When surface nm23-H1 and serum nm23-H1 were combined, patients with high levels of both exhibited a poorer prognosis than patients with a high level of one or the other. These results indicate that in addition to serum nm23-H1, cell surface nm23-H1 may be used as a prognostic factor in planning a treatment strategy. The nm23-H1 protein appears to be intimately related to biological aggressiveness of lymphoma and, therefore, might be a molecular target of NHL treatment.

Adult↗
PubMed2001

Serum nm23-H1 protein as a prognostic factor in aggressive non-Hodgkin lymphoma.

Advances in chemotherapy have led to a favorable long-term prognosis in approximately 50% of patients with aggressive non-Hodgkin lymphoma (NHL). However, the remaining patients do not enjoy such prolonged survival after standard treatment. New prognostic factors are needed to define this poor-prognosis group and to plan an appropriate treatment strategy. It has been reported that serum nm23-H1 protein may be a new prognostic factor for aggressive NHL. In the present study involving multiple institutions and a large number of patients, the level of nm23-H1 protein was compared among different types of lymphoma; it was lowest for indolent lymphoma, followed by aggressive lymphoma and then highly aggressive lymphoma. In addition, patients with aggressive NHL and higher nm23-H1 levels had worse overall and progression-free survival rates than those with lower nm23-H1 levels. The nm23-H1 level was also compared between patients with diffuse large B-cell lymphoma and patients with peripheral T-cell lymphoma. The results suggest that the level of nm23-H1 could serve as a prognostic factor in both groups. Moreover, the prognosis of lymphoma patients could be ascertained even more precisely by combining soluble interleukin-2 receptor or soluble CD44 and nm23-H1 levels. A multivariate analysis confirmed that the nm23-H1 level is an independent and important prognostic factor in aggressive NHL. Therefore, it may provide useful information for clinicians to determine the appropriate therapy for each type of lymphoma.

Actuarial Analysis↗
PubMed2001

Downregulation of MLL-CBP fusion gene expression is associated with differentiation of SN-1 cells with t(11;16)(q23;p13).

The translocation t(11;16)(q23;p13) has only been documented in patients with acute leukemia or myelodysplasia secondary to therapy with drugs targeting DNA topoisomerase II. We have established a myeloid cell line (SN-1) with the MLL-CBP fusion gene from an acute leukemia patient with t(11;16)(q23;p13). Although SN-1 cells were not induced to differentiate by all-trans retinoic acid (ATRA) and 1alpha,25-dihydroxyvitamin D(3) (VD3), retinoid X receptor (RXR) agonists, such as 9-cis retinoic acid and Ro48-2250, effectively induced differentiation of the cells. Downregulation of the expression of the MLL-CBP fusion gene occurred during the differentiation of SN-1 cells. When SN-1 cells were treated with MLL-CBP antisense oligonucleotide, the cells were induced to differentiate by ATRA or VD3, suggesting that the MLL-CBP fusion gene dominant-negatively suppresses ATRA- or VD3-induced differentiation. Moreover, suboptimal concentrations of sodium butyrate, a histone deacetylase inhibitor, had a cooperative effect with ATRA or VD3 in inducing the differentiation of SN-1 cells. The downregulation of the expression of MLL-CBP mRNA was accompanied by the induction of differentiation. These findings suggest that RXR agonists or a clinically applicable combination of ATRA and butyrate derivatives might be useful for differentiation therapy in leukemia patients with the MLL-CBP fusion gene.

Alitretinoin↗
PubMed2001

Induction of differentiation of acute promyelocytic leukemia cells by a cytidine deaminase-resistant analogue of 1-beta-D-arabinofuranosylcytosine, 1-(2-deoxy-2-methylene-beta-D-erythro-pentofuranosyl)cytidine.

Since the establishment of all-trans retinoic acid (ATRA) differentiation therapy, the prognosis of acute promyelocytic leukemia (APL) has improved, and APL has become a curable subtype of acute myelocytic leukemia. Complete remission can be achieved with ATRA alone, but disease-free survival is still too short because of relapse. To overcome this drawback, ATRA has been used in combination with chemotherapeutic agents such as 1-beta-D-arabinofuranosylcytosine (araC) and daunorubicin. However, growth of the APL cell lines NB4 and HT93 is less sensitive to araC than to that of other myeloid leukemia cell lines such as HL-60 and U937. ATRA effectively induced granulocytic differentiation of NB4 and HT93 cells, whereas araC did not, even in a high concentration. A cytidine deaminase-resistant analogue of araC, 1-(2-deoxy-2-methylene-beta-D-erythro-pentofuranosyl)cytidine (DMDC), inhibited the growth of NB4 and HT-93 cells and was also effective on HL-60 and U937 cells. The promyelocytic cell lines were induced to differentiate by DMDC and other cytidine deaminase-resistant analogues. Among them, DMDC was the most potent in inducing differentiation and inhibiting the growth of NB4 cells. The ATRA-induced differentiation of NB4 cells was not augmented by araC, whereas combined treatment with ATRA and DMDC had more than additive effects in inducing the differentiation of NB4 cells. Similar results were observed in a primary culture of leukemia cells that had been freshly isolated from APL patients. These results suggest that DMDC may play a role in the treatment of APL.

Antimetabolites, Antineoplastic↗
PubMed2001

Combination therapy with irinotecan (CPT-11), mitoxantrone, and dexamethasone in relapsed or refractory non-Hodgkin's lymphoma: a pilot study.

Irinotecan hydrochloride (CPT-11) is a topoisomerase I inhibitor with a broad antitumor spectrum. In the present study, we combined CPT-1 and mitoxantrone (MIT) with dexamethasone because the effect elicited by this combination was additive or better in a preclinical study. This study was performed to determine the efficacy and toxicities of this combination. Thirty-two patients were evaluable. CPT-11 combined with MIT achieved a complete remission in 11 patients (34.4%) and a partial remission in 9 patients (28.1%). The median follow-up period was 20 months. The 4-year survival rate was 31.8% (95% confidence intervals: 11.2-64.6%), and the 3-year event-free survival rate was 16.1% (95% confidence intervals: 8.2-24.6%). Grade 3 or higher hematological toxicity included neutropenia in 96.9%, anemia in 3.1%, and thrombocytopenia in 15.6%. Grades 1, 2, and 3 nonhematological toxicity included diarrhea in one patient, nausea/vomiting in five patients, and hematuria in one patient, respectively. CPT-11 combined with MIT was safe even for elderly patients and was effective even in patients who had received pretreatment with doxorubicin. In addition, this regimen can be used on an outpatient basis. This combination should be tested further to determine the optimum doses and administration schedule.

Adult↗
PubMed2001

Full-dose CHOP chemotherapy combined with granulocyte colony-stimulating factor for aggressive non-Hodgkin's lymphoma in elderly patients: a prospective study.

We assessed the efficacy and safety of full-dose CHOP regimen plus granulocyte colony-stimulating factor to treat aggressive non-Hodgkin's lymphoma in elderly patients. Forty-two patients with untreated disease were included in this study, aged 70-79 years, with stage II or higher disease and a performance status of 0-3, without severe organ dysfunction. Of the 40 patients who could be evaluated 87.5% achieved complete remission, with a 4-year survival rate of 69% and a 3-year progression-free survival rate of 49%. When stratified by the International prognostic Index, the 4-year survival rate was 90.9% for the low and low-intermediate risk group and 41.3% for the high-intermediate and high risk group, whereas the 3-year progression survival rate was 87.7% and 11.3%, respectively. Grade 3 or 4 hematological toxicity was found in 31 instances of granulocytopenia (77.5%) and 7 of anemia (17.5%). Nonhematological toxicity of grade 3 or 4 included pneumonia in two patients, heart failure in one, and gastrointestinal bleeding in one. Full-dose CHOP regimen with granulocyte colony-stimulating factor support could achieve a high-dose intensity in elderly patients whose general physical condition was good and hence achieved a high complete remission rate, but the disease often recurred within 2 years. Consequently, a new therapeutic strategy needs to be established, particularly for patients with high-intermediate or high risk.

Aged↗
PubMed2001

A high serum-soluble interleukin-2 receptor level is associated with a poor outcome of aggressive non-Hodgkin's lymphoma.

Soluble interleukin-2 receptor (sIL-2R) is produced by activated T and B cells, and the level of this receptor is elevated in patients with non-Hodgkin's lymphoma (NHL). The present study demonstrated that the sIL-2R level was high in the following groups of patients with aggressive NHL; those aged > or = 60 yr, those with a poor PS, those in Ann Arbor stage III or IV, and those in the high intermediate or high risk group according to the International Prognostic Index (IPI). Overall survival was significantly poorer when the sIL-2R level was 2000 U/ml or more. In addition, the overall survival of patients in the low (L) and low-intermediate (L-I) risk groups with an sIL-2R level of 3000 U/ml or more was significantly poorer, suggesting that the sIL-2R level could be particularly useful for identifying patients with a poor prognosis among the L and L-I risk groups. Univariate analysis identified some significant prognostic factors, and multivariate analysis of these factors plus the five IPI prognostic factors showed that the sIL-2R level was an independent prognostic indicator. In conclusion, the present findings established that the sIL-2R level is a significant independent prognostic factor in patients with aggressive NHL.

Adolescent↗
PubMed2001

Serum nm23-H1 protein as a prognostic factor for indolent non-Hodgkin's lymphoma.

Standard chemotherapy has been ineffective for improving the poor 10-year survival rate of patients with indolent lymphoma. However, a wider choice of therapeutic modalities has become recently available, including immunotherapy with monoclonal antibodies and allogeneic peripheral blood stem cell transplantation. Accordingly, a sensitive prognostic indicator is required to identify high-risk patients and to help design new therapeutic approaches for them. We previously reported that the serum nm23-H1 protein level was an independent prognostic factor for aggressive lymphoma. The present study was performed to assess the clinical implications of this protein on indolent lymphoma and whether it can be used to classify the aggressiveness of the disease in order to assist in the individualization of therapy. A total of 130 patients with indolent lymphoma were enrolled in this multicenter study. The serum nm23-H1 protein level was significantly higher in patients with indolent lymphoma than in a normal control group. In addition, indolent lymphoma patients with higher nm23-H1 levels had worse overall and progression-free survival rate than those with lower nm23-H1 levels. Therefore, nm23-H1 in serum may be useful for identifying a distinct group of patients at high risk.

Adolescent↗
PubMed2001

Sensitization by 5-aza-2'-deoxycytidine of leukaemia cells with MLL abnormalities to induction of differentiation by all-trans retinoic acid and 1alpha,25-dihydroxyvitamin D3.

Most chromosomal abnormalities associated with breakage at 11q23 in acute leukaemia involve the MLL gene, and the presence of this breakage strongly predicts a poor clinical outcome. We assessed the possibility of differentiation-inducing therapy for acute leukaemias with chromosomal translocations involving 11q23. Among the cell lines with MLL translocations that we examined, KOCL48 and KOPN-1 cells were induced to differentiate into granulocytes by all-trans retinoic acid (ATRA) or into monocytes by 1alpha,25-dihydroxyvitamin D3 (VD3). These cells expressed p16 mRNA before treatment with 5-aza-2'-deoxycytidine (5-AZA), an inhibitor of DNA methylation. On the other hand, differentiation was not induced in SN-1, KOCL33, KOCL51 or KOCL44 cells by ATRA or VD3, and these cells did not express mRNA of this gene. However, these cells were effectively induced to differentiate by ATRA or VD3 in the presence of 5-AZA, and concomitantly exhibited p16 gene expression, suggesting an association between DNA demethylation and restoration of sensitivity to differentiation-inducing activity of ATRA or VD3 in leukaemia cells with MLL abnormalities. Based on these findings, combined treatment with ATRA or VD3 plus 5-AZA may be clinically useful in therapy for acute leukaemia with MLL abnormalities.

Antimetabolites, Antineoplastic↗
PubMed2001

Reduced-dose chop therapy for elderly patients with non-Hodgkin's lymphoma.

While CHOP therapy is effective for malignant lymphoma, the optimum schedule for elderly patients remains controversial. The present study investigated the usefulness of reduced-dose CHOP therapy for elderly patients. Previously untreated patients aged 65 years or older with intermediate to high-grade non-Hodgkin's lymphoma were given up to 6 courses of reduced-dose CHOP therapy at 3-week intervals. Group A patients were given (5/6) of the standard dose and Group B received 7/12 of the standard dose. Filgrastim was administered when the white blood cell count fell below 2,000/microL. Fifty-seven patients were evaluable and the scheduled therapy was completed in 37. For patients aged from 65 to 79 years and for patients older than 80 years, the complete response rate was 79.5% and 46.2%, overall 3-year survival was 58.2% and 30.4%, and event-free 3-year survival was 49.3% and 44.4%, respectively. Major toxicities (> or = grade 3) included leukopenia in 42 patients and documented infection in 7 patients. Grade 3 cardiac plus renal failure, grade 3 peritonitis due to small bowel perforation, and grade 3 liver dysfunction occurred in 1 patient each. One patient died of toxicity (grade 4 hematological toxicity and pneumonia). In conclusion, it seems that in the elderly patients with non-Hodgkin's lymphoma, response to reduced-dose ((5/6) dose) CHOP therapy is comparable to that for standard CHOP in younger adults, mainly because of improved dose-intensity.

Actuarial Analysis↗
PubMed2001

[Primary lymphoma of the vagina].

Primary vaginal non-Hodgkin's lymphomas (NHL) are rare, and are clinically difficult to differentiate from inflammatory diseases or vaginal cancer. Here, we present such a case in a 74-year-old woman complaining of fever and difficulty with urination. Pelvic examination revealed a tumor involving most of the vaginal wall, and pelvic MRI demonstrated vaginal wall thickening. A biopsy of this lesion confirmed NHL (diffuse large B-cell lymphoma), and the patient was admitted. Abdominal CT and MRI detected a vaginal tumor, and Ga scintigraphy confirmed accumulation in the pelvis, but no abnormalities were seen in other areas. Therefore, the patient was diagnosed as having NHL at clinical stage IB with low-intermediate risk (international prognosis index) (LDH 1,309 IU/L). The patient underwent three courses of CHOP therapy followed by radiotherapy, and complete remission was achieved. Primary vaginal NHL often affects women younger than 50 years of age, and abnormal hemorrhage is the initial symptom in many cases. There have been a number of reports of long-term survival following appropriate early chemotherapy and radiation therapy, suggesting that early diagnosis and treatment based on vaginal biopsy findings greatly influence the prognosis.

Aged↗
PubMed2000

Antileukemic efficacy of 2-deoxycoformycin in monocytic leukemia cells.

2'-Deoxycoformycin (dCF) as a single agent has been reported to be less effective against myeloid than against lymphoid malignancies in clinical trials. However, previous studies have shown that in the presence of 2'-deoxyadenosine (dAd), human monocytoid leukemia cell lines are much more sensitive to dCF with regard to the inhibition of cell proliferation. Thus, dCF might be useful for treating monocytoid leukemia with the aid of dAd analogs. The antiproliferative effects of dCF in combination with dAd or its derivatives were examined on normal and malignant blood and bone marrow cells. In the presence of 10 micromol/L dAd, the concentration of dCF required to inhibit the viability of primary monocytoid leukemia cells was much lower than that required to inhibit normal or non-monocytoid leukemic cells. Among the dAd analogs, 9-beta-D-arabinofuranosyladenine (AraA) was also effective in combination with dCF. Athymic nude mice were inoculated with human monocytoid leukemia U937 cells and treated with dCF or a dAd analog or both. Although dCF alone slightly but significantly prolonged the survival of mice inoculated with U937 cells, combined treatment with dCF and AraA markedly prolonged their survival. These data suggest that the combination of dCF and AraA may be useful for the clinical treatment of acute monocytic leukemia. (Blood. 2000;96:1512-1516)

Animals↗
PubMed2000

Plasma levels of the differentiation inhibitory factor nm23-H1 protein and their clinical implications in acute myelogenous leukemia.

A previous study reported that a nondifferentiating myeloid leukemia cell line produced differentiation-inhibiting factors. One of the factors was purified as a homologue of the nm23 genes. The nm23 genes were overexpressed in acute myelogenous leukemia (AML) cells, and a higher level of nm23 gene expression was correlated with a poor prognosis in AML. The present study determined the plasma levels of nm23-H1 protein by enzyme-linked immunosorbent assay and assessed the association between this level and the clinical outcome in 102 patients with AML. The plasma concentration of nm23-H1 was higher in patients with AML than in normal controls (P =.0001). Plasma nm23-H1 levels were correlated with the product of the intracellular nm23 messenger RNA (mRNA) level and the white blood cell count, but not with the mRNA level alone. Therefore, nm23-H1 plasma levels probably depend on the total mass of leukemic cells overexpressing the nm23-H1 gene. Overall survival was lower in patients with higher plasma nm23-H1 levels than in those with lower levels. Multivariate analysis using the Cox proportional hazard model showed that elevated plasma nm23-H1 levels significantly contributed to the prognosis of AML patients. Furthermore, the plasma nm23-H1 levels were investigated in 70 patients with other hematologic neoplasms, including 6 with acute lymphoblastic leukemia, 13 with chronic myelogenous leukemia, and 12 with myelodysplastic syndrome. Plasma nm23-H1 levels were significantly higher in all of these hematologic neoplasms than in normal controls. Increased plasma levels of nm23-H1 may have prognostic value in these hematologic malignancies as well as in AML.

Adult↗
PubMed2000

SN-1, a novel leukemic cell line with t(11;16)(q23;p13): myeloid characteristics and resistance to retinoids and vitamin D3.

The MLL gene is fused with the cAMP-responsive element binding protein-binding protein (CBP) gene in t(11;16)(q23;p13), which has been reported to be associated with therapy-related acute leukemia. We established a novel myeloid cell line, SN-1, from a patient with T-cell acute lymphoblastic leukemia with t(11;16)(q23;p13) having in-frame MLL-CBP fusion transcripts. The majority of the SN-1 cells were positive for myeloperoxidase when examined using an electron microscope and expressed CD13, CD33, CD56, and HLA-DR antigens, but not CD7, CD10, CD19, CD34, or CD41 antigens, suggesting that these cells are of myeloid origin. SN-1 cells underwent functional and morphological differentiation when treated with actinomycin D or sodium butyrate, but not with all-trans-retinoic acid (ATRA) or 1alpha,25-dihydroxyvitamin D3 (VD3). Exposure of SN-1 cells to ATRA hardly affected cell growth and differentiation, whereas the growth of HL-60 and NB4 cells treated with ATRA was effectively inhibited, and differentiation into mature granulocytes was induced. SN-1 cells were relatively insensitive to VD3 with respect to inhibiting the cell growth and inducing the ability to reduce nitroblue tetrazolium, lysozyme activity, and morphological differentiation, although the expression of CD11b was slightly induced by VD3. These results suggest that the cell line was impaired in the signal transduction systems of ATRA and VD3. This cell line should be useful for the study of the role of CBP as a transcriptional regulator in leukemia differentiation and for the functional analysis of the MLL-CBP fusion gene, which will provide new insights into leukemogenesis caused by 11q23 translocations.

Amino Acid Sequence↗
PubMed2000

Human herpes virus-8 associated with two cases of primary-effusion lymphoma.

Primary-effusion lymphoma (PEL) is a rare form of non-Hodgkin's lymphoma which predominantly occurs in patients with acquired immunodeficiency syndrome and is characterized by the presence of a malignant effusion in one or more of the body cavities, generally in the absence of a primary tumor mass. Recently, we encountered two cases of PEL presenting as cardiac tamponade. In both cases, a diagnosis of diffuse large B-cell lymphoma was made by examination of the pericardial fluid. Because human herpes virus-8 (HHV-8) antibodies were positive and human immunodeficiency virus antibodies were negative, HHV-8 seemed likely to be an etiologic agent for the PEL. One of the two patients (case 1) was not treated for religion reasons and died. The other (case 2) achieved complete remission after treatment using the CHOP regimen and is alive at present. The prognosis of this disease is believed to be poor, therefore more cases should be collected to establish reliable therapy for PEL.

Adult↗