Somatic hypermutations in the VH segment of immunoglobulin genes of CD5-positive diffuse large B-cell lymphomas.

De novo CD5-positive (CD5+) diffuse large B-cell lymphoma (DLBL) has recently been identified as constituting a homogeneous subgroup with distinct clinicopathologic and genotypic characteristics, but its origin remains to be elucidated. Previous studies by sequence analysis of the variable region of the immunoglobulin heavy chain (VH) have shown that CD5+ B-cell malignancies such as mantle cell lymphoma (MCL) and B-cell chronic lymphocytic leukemia (B-CLL) cells represent pre-germinal center (pre-GC) stage B cells in contrast with the post-GC stage of most DLBLs, which show somatic hypermutations in VH genes. In the present study, we investigated the VH sequence of de novo CD5+ DLBL to clarify whether CD5+ DLBL represents the pre-GC stage, as do other CD5+ B-cell malignancies, or the post-GC stage, as is typical of DLBL.

Anaplastic large cell lymphoma: a distinct molecular pathologic entity: a reappraisal with special reference to p80(NPM/ALK) expression.

The p80(NPM/ALK) expression activated by the t(2;5) (p23;q35) translocation recently has been shown to play an important role in the pathogenesis of anaplastic large cell lymphoma (ALCL). However, the clinicopathologic significance of identification of p80 among ALCL cases has not been completely resolved. Difficulties also exist in the histologic and immunophenotypic identification of ALCL and Hodgkin's disease (HD) as separate processes, often complicating the clinicopathologic evaluation of and therapeutic approach to these entities.

Complete cytogenetic response with host-derived hematopoiesis induced by cyclosporin A discontinuation in a patient with relapsed chronic myelogenous leukemia after bone marrow transplantation.

A 46-year-old woman with Ph-positive CML received an unmanipulated BMT from an HLA-identical brother, conditioned with busulfan-cyclophosphamide. Five months after BMT, cytogenetic relapse occurred, and CsA was decreased and then discontinued. Mild acute GVHD occurred, but gradually improved with no immunosuppression.

CD7+ and CD56+ myeloid/natural killer cell precursor acute leukemia: a distinct hematolymphoid disease entity.

The disease spectrum of natural killer (NK) cell leukemias and lymphomas has recently been expanding with the continuing evolution in diagnostic concepts. We describe here seven cases of acute leukemia of conceivable myeloid and NK cell precursor phenotype in six men and one woman varying from 19 to 59 years of age (median, 46 years). Striking extramedullary involvement was evident at initial presentation, with peripheral lymphadenopathy and/or mediastinal masses.

Complementarity determining region-III is a useful molecular marker for the evaluation of minimal residual disease in mantle cell lymphoma.

Bone marrow (BM) and peripheral blood (PB) involvement in 10 patients with mantle cell lymphoma (MCL) was analysed by a polymerase chain reaction (PCR)-mediated RNase protection assay. The complementarity determining regions (CDR)-III of all 10 MCLs examined was amplified efficiently with consensus V(H) and J(H) primers by PCR. and BM and/or PB involvement was evaluated by RNase protection assay in all 10 patients examined.

Technical considerations for fractionated stereotactic radiotherapy of hepatocellular carcinoma.

Technical aspects of fractionated stereotactic radiotherapy for solitary hepatocellular carcinoma have been investigated. Precise positioning of the patient and substantial reduction of the liver movement due to respiration were achieved by placing the patient ventrally on the treatment couch without a body cast. Repeated CT examinations were required for verification of tumor targeting.

A nodal gamma/delta T-cell lymphoma with an association of Epstein-Barr virus.

The postthymic gamma/delta T-cell lymphoma is rare, and most occur as extranodal tumors, e.g., in hepatosplenic or cutaneous forms.

Thoracic esophageal carcinoma above the carina: a more formidable adversary?

Background: Prognosis with esophageal carcinoma above the carina is generally thought to be the worst without any conclusive demonstration.

Methods: Clinicopathologic features of 101 patients with thoracic esophageal carcinoma above the carina (AC group) were compared with those of 665 patients with a tumor below this level (BC group).

Results: The number of T4 tumor was significantly larger in the AC group (P < 0.

Protracted 5-fluorouracil infusion with concurrent radiotherapy as a treatment for locally advanced pancreatic carcinoma.

Background: Radiotherapy plus bolus 5-fluorouracil (5-FU) is generally accepted as the standard treatment for locally advanced pancreatic carcinoma. To intensify the antitumor effect of chemotherapy, the authors administered protracted 5-FU infusion with concurrent radiotherapy. The aim of this study was to determine the feasibility and effectiveness of this combined therapy.

Fractionated stereotactic radiotherapy for choroidal melanoma.

Stereotactic radiotherapy used for the treatment of choroidal melanoma made use of a 6-MeV linac with built-in multileaf collimators and a simple plastic head mold. The latter provided excellent head and ocular immobilization. The system resulted in highly localized dose distributions with a maximum 2-mm targeting error during fractionated treatments.

[Improvement in function-preservation in radiotherapy for pediatric malignancies].

In radiotherapeutic management for pediatric tumors, we have to pay more attention to confinement of higher dose to the target volume than for adult tumors, in order that the risk of untoward normal tissue complications dose not increase, such as growth retardation. Two current approaches performing in our department to match this purpose are presented, namely, perioperative brachytherapy and fractionated stereotactic radiotherapy (F-SRT). In perioperative brachytherapy for bone and soft tissue sarcoma, plastic guide tubes for introducing radioactive sources are placed in the residual tumor bed or at the margins during the surgery, and patients are treated by high-dose-rate brachytherapy after surgery.

Treatment of squamous cell carcinoma of the esophagus with alternating radiotherapy and chemotherapy (cisplatin, methotrexate, and peplomycin).

Between 1985 and 1990, 20 patients with stage 2 and 3 esophageal cancer without esophagopulmonary fistulas were treated with alternating radiotherapy and chemotherapy (cisplatin, methotrexate, and peplomycin). Patients given the combined therapy received courses of chemotherapy during weeks 1 and 6 and radiotherapy during weeks 2-5 and 7-9. Chemotherapy consisted of i.

Phase I/II trial of cure-oriented high-dose chemoradiotherapy with transplantation of CD34+ peripheral blood stem cells purified by the immunomagnetic bead method for refractory hematological malignancies. Nagoya CD34+ PBSCT Study Group.

A multicenter phase I/II clinical trial was conducted to evaluate the safety of a device (Isolex System; Baxter Health Corporation, Irvine, Calif., USA) using the immunomagnetic bead method to purify CD34+ stem cells from peripheral blood and to assess the efficacy and toxicity of high-dose chemoradiotherapy with peripheral blood stem-cell transplantation (PBSCT) using purified CD34+ stem cells in patients with refractory hematological malignancies. Patients eligible for the study included those who had T-cell acute lymphoblastic leukemia (T-ALL), lymphoblastic lymphoma (LBL), mantle-cell lymphoma (MCL), high-risk aggressive non-Hodgkin's lymphoma (NHL), and adult T-cell leukemia/lymphoma (ATLL) in first complete remission (CR) and those who had standard-risk aggressive NHL, indolent lymphoma, Hodgkin's disease, or acute promyelocytic leukemia (APL) in second CR or first partial remission (PR) after the completion of first-line chemotherapy and were chemosensitive to salvage chemotherapy, in whom tumor contamination of harvested peripheral blood stem cells (PBSCs) was possible due to bone marrow or peripheral blood involvement.

Clinicopathologic study of nasal T/NK-cell lymphoma among the Japanese.

A high prevalence of nasal lymphoma expressing a T- or natural killer (NK)-cell phenotype (NTCL) with frequent association of Epstein-Barr virus (EBV) has been indicated in Asians. To characterize NTCL among the Japanese, the clinicopathologic features of 32 cases were evaluated and the cases were also analyzed for EBV-RNA using an ISH method. Morphologically, 31 cases were identified by atypical pleomorphic lymphoid infiltrates with polymorphous, angicentric, and necrotic features.

Identification of MLL and chimeric MLL gene products involved in 11q23 translocation and possible mechanisms of leukemogenesis by MLL truncation.

11q23 chromosome aberrations are frequently observed in infantile as well as therapy-related leukemias. The target gene at 11q23, MLL, is disrupted by the translocation and becomes fused to various translocation partner genes such as AF4/FEL, LTG9/AF9 and LTG19/ENL. The resulting chimeric mRNAs are fused in frame and have been predicted to encode leukemia-specific chimeric proteins.

Feasibility of salvage chemotherapy for refractory or relapsed non-Hodgkin's lymphoma with two topoisomerase II inhibitors, MST-16 and VP-16. MST-16 Study Group.

A feasibility study was carried out on the treatment for refractory and relapsed non-Hodgkin's lymphomas with a combination of two oral topoisomerase II inhibitors, MST-16 and VP-16. On the basis of the synergistic activity in preclinical studies and the schedule dependency in these drugs, low-dose and long-term administration was planned. For the anticipated myelosuppression, two different regimens were designed as an open label trial in this study.

Clinicopathologic study of PRAD1/cyclin D1 overexpressing lymphoma with special reference to mantle cell lymphoma. A distinct molecular pathologic entity.

Mantle cell lymphomas (MCLs) are frequently associated with the overexpression of PRAD1/cyclin D1, activated by 11q13 translocation and its molecular counterpart BCL-1 gene rearrangement. We recently described the correlation of positive nuclear staining using monoclonal antibody against a PRAD1/cyclin D1 product with mRNA overexpression in MCLs. In the present study, we immunohistochemically investigated the PRAD1/cyclin D1 protein in a large series of 334 lymphoproliferative disorders, including 39 cases of MCLs on paraffin sections.

Tumor bed implant brachytherapy for residual carcinoma after palliative esophagectomy.

Twenty-six patients with esophageal carcinoma at stage pT4 underwent esophagectomy with lymph node dissection leaving part of the tumor in adjacent organs. Several plastic catheters were fixed to the tumor bed and led to the outside of the thorax for postoperative brachytherapy. Using these catheters, the patients underwent brachytherapy followed by external beam irradiation.

Clinicopathologic study of CD56 (NCAM)-positive angiocentric lymphoma occurring in sites other than the upper and lower respiratory tract.

The expression of the neural cell adhesion molecule (NCAM) (CD56, NKH-1) is a rare phenomenon in malignant lymphoma. Recently, several authors, including our group, described the clinicopathologic, phenotypic, and genotypic features of NCAM-positive tumors as a unique subgroup within a larger category of hematolymphoid malignancies. Ten cases of CD56+ angiocentric lymphoma occurring in sites other than the upper aerodigestive tract were studied for evaluating their characteristics.

Immunohistochemical analysis of cyclin D1 protein in hematopoietic neoplasms with special reference to mantle cell lymphoma.

Immunohistochemical expression of PRAD1/cyclin D1 protein has been investigated in 106 tissue specimens of 104 cases of lymphoma, non-neoplastic lymphoid disorders and other hematologic malignancies by employing the monoclonal antibody 5D4 with formalin-fixed paraffin-embedded sections, using the microwave oven heating method. Positive neoplastic cells were found in 60 (74%) of 81 cases of non-Hodgkin's lymphoma. The positivity pattern was nuclear in 17 (85%) of 20 cases of mantle cell lymphoma in which cytoplasmic staining was also seen.

Column-switching high-performance liquid chromatographic analysis of BO-2727, a new carbapenem antibiotic, in human plasma and urine by direct injection.

A column-switching high-performance liquid chromatographic method has been developed for the simple and sensitive analysis of BO-2727 (I) in human plasma and urine. Plasma samples were diluted with an equal volume of a stabilizer, and the mixture was directly injected onto the HPLC system. The analyte was enriched in a pre-treatment column, while endogenous components were eluted to waste.

Recovery of polyclonal hematopoiesis in patients with myelodysplastic syndromes following successful chemotherapy.

We performed X-linked restriction fragment length polymorphism (RFLP)-methylation analysis to study the clonality of hematopoiesis in five patients with myelodysplastic syndromes (MDS), who had responded to chemotherapy. Two patients had MDS in blast crisis, two had refractory anemia with an excess of blasts in transformation (RAEB-T), and one had acute myelogenous leukemia with trilineage myelodysplasia (AML-TMDS). Following the administration of low-dose cytarabine therapy or of conventional intensive chemotherapy, we observed a reversion to polyclonal hematopoiesis in three patients who achieved a complete remission (CR).

Novel interleukin-2 dependent T-cell line derived from adult T-cell leukemia not associated with human T-cell leukemia virus type I.

A novel interleukin-2 (IL-2)-dependent T-cell line, WHN2, was established from a patient with adult T-cell leukemia (ATL) not associated with human T-cell leukemia virus type I (HTLV-I). Neither the original leukemic cells nor the WHN2 cells showed proviral integration in their cellular DNAs by Southern blot analysis. The surface phenotype showed that both the original leukemic cells and the WHN2 cells had a common phenotype of ATL, i.

Erythroid potentiating activity of tissue inhibitor of metalloproteinases on the differentiation of erythropoietin-responsive mouse erythroleukemia cell line, ELM-I-1-3, is closely related to its cell growth potentiating activity.

The erythroid-potentiating activity (EPA) of the tissue inhibitor of metalloproteinase-1 (TIMP-1) was re-examined using ELM-I-1-3, a mouse erythroleukemia cell line, which responded well to erythropoietin. Depletion of pre-existing TIMP-1 from fetal calf serum in culture medium using monoclonal antibody suppressed erythropoietin-induced differentiation as measured by the induction of hemoglobin, commitment assay and globin mRNAs. The removal of TIMP-1 also suppressed the proliferation of ELM-I-1-3 as measured by cell number and de novo DNA synthesis.

Results of cesium needle interstitial implantation for carcinoma of the oral tongue.

One hundred thirty previously untreated patients with invasive squamous cell carcinoma of the oral tongue received interstitial radiotherapy with curative intent using cesium needles. Ninety-nine patients were treated with interstitial radiotherapy alone and 31 patients received interstitial radiotherapy combined with external beam irradiation. The recurrence-free rates in the primary lesions were 94.