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Toyotaka Iguchi

Publications and source records attributed to Toyotaka Iguchi.

10 recordsLinked to original sources
PubMed2005

Tubulin-polymerization inhibitors derived from thalidomide.

2-(2,6-Diisopropylphenyl)-5-hydroxy-1H-isoindole-1,3-dione (5HPP-33), which was obtained during our previous structural development studies on thalidomide, was revealed to possess potent tubulin-polymerization-inhibiting activity, comparable to that of the known tubulin-polymerization inhibitors, rhizoxin and colchicine. A major metabolite of thalidomide, 5-hydroxythalidomide, which possesses a hydroxyl group at the position corresponding to that of 5HPP-33, also showed moderate inhibitory activity.

Colchicine↗
PubMed2005

Multilineage involvement of light microscopic myeloperoxidase-negative acute leukemia.

The classification of acute leukemia has traditionally been based on a combination of morphology and cytochemical staining data, including myeloperoxidase (MPO) reaction; however, a recent World Health Organization (WHO) classification entails use of cytogenetic and molecular findings in addition to the classic morphological and immunophenotypic analyses. Nevertheless, there have been rare cases in which blastic cells show multilineage phenotypes. These cases may be classified as acute leukemia of ambiguous lineage in the recent WHO classification. We report the case of a 49-year-old man with acute leukemia with multilineage phenotypes. Morphological findings led to a diagnosis of acute myeloid leukemia M2 by the French-American-British classification, but at light microscopy the results of MPO staining were negative for blast cells. In contrast, results of reverse transcription polymerase chain reaction and fluorescence-activated cell sorter analyses were positive for expression of MPO messenger RNA and protein. The blast cells expressed CD4, CD19, CD22, CD33, CD38, CD79a, and HLA-DR and showed rearrangement of the immunoglobulin heavy chain and TCR-3 genes. Results of immunoelectron microscopic analysis of the blast cells were positive for MPO, CD19, CD33, CD34, CD38 and glycophorin A but not for platelet peroxidase. According to these results, the blast cells had at least 4 lineage phenotypes. We concluded that the multiparameter analyses conducted in this case, including immunological and ultrastructural assays, were important in arriving at the appropriate diagnosis of acute leukemia of ambiguous lineage in the new WHO classification.

Acute Disease↗
PubMed2005

[Soft tissue amyloidoma].

A 59-year-old man was referred to our hospital for the evaluation of pain on exertion of the right arm. X-ray examination showed a humeral tumor, and a tumorectomy was subsequently performed. The histological analysis showed necrotic tissue with no malignant cells. Serum protein electrophoresis yielded a small amount of M proteins without monoclonality of immunoglobulins. The bone survey in the whole body showed lucency of the right humerus, vertebra, ribs, left femur, skull, and right scapla. During outpatient clinic observation, a computed tomography scan of the pelvis showed a painless large tumor in the gluteus, appearing as an amyloidoma. Soft tissue amyloidoma occur very rarely, and so we here report a case of a soft tissue amyloidoma in the gluteus with review of the literatures.

Amyloidosis↗
PubMed2005

[Pulmonary tuberculosis and adenovirus-hemorrhagic cystitis after autologous peripheral blood stem cell transplantation for follicular lymphoma].

A 58-year-old man had a relapsed follicular lymphoma (Grade 2) and was treated with mitoxantrone, fludarabine and dexamethasone followed by rituximab, and achieved partial remission. The patient then underwent high-dose chemotherapy followed by autologous peripheral blood stem cell transplantation (auto-PBSCT). Three days after starting high-dose therapy, he developed a fever, and a chest X-ray revealed pneumonia in the right lower lung. Despite of the administration of antibiotics and the recovery of neutrophils to normal levels, the pneumonia got worse. Bronchoalveolar lavage (BAL) was performed on day 32, the Ziehl-Neelsen staining of the BAL fluid showed acid-fast bacilli, and the culture grew Mycobacterium tuberculosis. The patient was diagnosed as having pulmonary tuberculosis and placed on an antituberculosis regimen (isoniazid, rifampicin, ethambutol, pyrazinamide). On day 43 he also developed hemorrhagic cystitis due to adenovirus type 11, and on day 49 positive CMV antigenemia was detected, which were treated supportively. On day 75 he developed pneumonia probably due to Pneumocystis jirovecii, which was treated with sulfamethoxazole/trimethoprim. The pulmonary tuberculosis resolved completely 4 months after starting the treatment, and the hemorrhagic cystitis and pneumocystis pneumonia resolved 1 month after the diagnosis. He remains in complete remission 2 years after transplantation.

Adenoviridae Infections↗
PubMed2004

Thalidomide for the treatment of multiple myeloma.

Although thalidomide was withdrawn in the 1960s after its teratogenic property was recognized, it was subsequently found that this drug possesses immunomodulatory and anti-inflammatory effects. Recent studies have also demonstrated that thalidomide has antineoplastic activity via an antiangiogenic mechanism. Observations in the late 1990s that the microenvironment in the bone marrow plays a role in tumor progression in multiple myeloma provided an impetus to use thalidomide for the treatment of this disease. It is known that thalidomide monotherapy is effective in one-third of refractory cases, and in combination with glucocorticoids and/or antineoplastic drugs, thalidomide provides a response rate of more than 50%. Thus, thalidomide therapy is considered a standard approach for the treatment of relapsed and refractory myeloma. The exact mechanism of the antimyeloma effect of thalidomide is not yet clearly understood. Anti-angiogenic effects, direct activity in tumor cells such as the induction of apoptosis or G1 arrest of the cell cycle, the inhibition of growth factor production, the regulation of interactions between tumor and stromal cells, and the modulation of tumor immunity have been considered as possible mechanisms. In addition to its teratogenicity, the adverse effects of thalidomide have been general symptoms such as somnolence and headache, peripheral neuropathy, constipation, skin rash, and other symptoms. Although these adverse effects are generally reversible and mild, grade 3 and 4 toxicities such as peripheral neuropathy, deep venous thrombosis, neutropenia, and toxic dermal necrosis have occasionally been reported. The application of thalidomide therapy in patients with multiple myeloma is being broadened to include not only cases of refractory myeloma, but also previously untreated cases, as well as for maintenance therapy after hematopoietic stem cell transplantation and for the treatment of other hematological diseases. The safe use of this drug will depend on the establishment of diagnostic and treatment guidelines. In addition, the establishment of a nation-wide regulation system is urgently needed in Japan.

Angiogenesis Inhibitors↗
PubMed2004

[Successful bone marrow transplantation with a matched unrelated donor in an acute promyelocytic leukemia patient after reinduction therapy with arsenic trioxide].

A 44-year-old man with relapsed acute promyelocytic leukemia (APL), refractory to all-trans-retinoic acid (ATRA), daunorubicin, and cytosine arabinoside, was treated with arsenic trioxide (ATO). ATO was given intravenously at a dose of 0.15 mg/kg/day for 20 days, and the patient achieved complete remission. No serious adverse events related to ATO infusion were observed. He received ATO for 10 days as consolidation therapy and subsequently underwent HLA-matched unrelated donor stem cell transplantation. He remains in molecular remission 10 months after transplant. This case suggests that ATO could be a useful therapy prior to allogeneic stem cell transplantation in relapsed APL.

Adult↗
PubMed2004

[Interstitial pneumonia during treatment with thalidomide in a patient with multiple myeloma].

A 66-year-old man was referred to our hospital for the treatment of refractory multiple myeloma with thalidomide. He had a history of an interstitial pneumonia of unknown etiology two months before admission. Eight days after starting 200 mg/ day of thalidomide, he developed dyspnea and fever, followed by a macropapular rash in the trunk. The dyspnea got worse and a CT scan revealed interstitial pneumonia 16 days after the treatment. He required mechanical ventilatory support. Bronchoalveolar lavage fluid revealed eosinophilia, suggesting a thalidomide-induced interstitial pneumonia. Thalidomide was discontinued and methylprednisolone (1000 mg/d x 3 days) was started, and the pneumonia and rash markedly improved within six days. After that the patient contracted MRSA pneumonia and died of MRSA septicemia.

Aged↗
PubMed2003

Nitrogen-containing bisphosphonates induce S-phase cell cycle arrest and apoptosis of myeloma cells by activating MAPK pathway and inhibiting mevalonate pathway.

Bisphosphonates have been used for the treatment of hypercalcemia associated with malignancies and osteoporosis. It was previously reported that the mevalonate pathway is involved in nitrogen-containing bisphosphonate-induced apoptosis in osteoclasts and myeloma cells. The aim of this study was to determine the effects of two bisphosphonates, incadronate, and newly developed bisphosphonate YM529 on human myeloma cells, U266, RPMI-8226, and HS-Sultan. Both incadronate and YM529 induced S-phase cell cycle arrest and apoptosis in these myeloma cells. Treatment of the myeloma cells with cell-permeable substrates for mevalonate pathways, geranylgeraniol, and farnesol prevented bisphosphonate-mediated growth suppression. Checkpoint kinases, Chk1/2, and MAPK became phosphorylated after stimulation with bisphosphonates in the myeloma cells. Bisphosphonate-induced apoptosis was partially prevented by the pretreatment with MAPK inhibitor. These results demonstrate that incadronate and YM529 suppress the proliferation of myeloma cells through mevalonate pathway and MAPK pathway.

Apoptosis↗
PubMed2003

[Chronic myelogenous leukemia in a lymphoblastic crisis complicated with deep venous thrombosis successfully treated by thromboembolectomy].

A 20-year-old man was referred to our hospital because of leukocytosis and was diagnosed as having chronic myelogenous leukemia in lymphoblastic crisis. His left leg began to swell soon after the beginning of induction chemotherapy and deep vein thrombosis (DVT) was confirmed by doppler echography, which progressed to compartment syndrome next day. After placing a venous filter in the inferior vena cava, the patient successfully underwent thromboembolectomy. Venous congestion due to massive lymphadenopathy enlarged kidneys, and a hypercoagulable condition due to the rapid destruction of leukemic cells may have contributed to the formation of the thrombus. This case demonstrates the importance of aggressive surgical intervention for severe DVT in patients with leukemia.

Adult↗