Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0019829 (Hodgkin's disease)
 30,247 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Since 1970, we have carried out cancer chemotherapy and immunotherapy in cooperation with Japanese scientists, particularly Prof. H. Umezawa, who has generously supplied bleomycin, peplomycin, acalcinomycin A (ACM), THP-adriamycin (THP), neothramycin and bestatin. Malignant tumors curable by pharmacotherapy are polycythemia vera (CR 100%), acute lymphoid leukemia (ALL) (CR 80%), Burkitt tumor (CR 80 or 50%), Hodgkin disease (CR 80%), chorioepithelioma (CR 80%), testicular cancer (CR 80%), ovary cancer of children (CR 80%), Wilms renal cancer (CR 60%), rhabdomyosarcoma (CR 75%), osteosarcoma (CR 60%), Ewing tumor (CR 60%), brain tumor of children (CR greater than 50%), testicular embryonal cancer of children (CR greater than 50%), acute myeloid leukemia (AML) (CR 50%), non-Hodgkin lymphoma (NHL) (CR 50%), ovary cancer of adults (CR 40%), small cell lung cancer (CR 20%) and breast cancer. Our experimental and/or clinical experience with ACM, THP, methoxy-9-ellipticine lactate, navelbine, 4-demethyl-epipodophyllotoxin-beta-d-ethyledene glucoside, bestatin and interferon is presented. ACM is effective against AML, ALL, NHL, Burkitt tumor, breast cancer. We have comparatively investigated cardiac and dermal toxicity of 12 kinds of anthracycline antibiotics and mitoxantrone, using golden hamsters. Of the drugs examined, ACM, THP, AD-32 and AD-143 cause much less cardiomyopathy and alopecia than the other agents. The results have been confirmed by electron microscopic studies. Bestatin is an immunorestorator, which recovers immunological functions decreased in aged animals. We hope that cancer chemotherapy and immunotherapy will progress in future and contribute to cure of neoplasms. Japanese scientists have been making a great contribution in the field of cancer pharmacotherapy, and we are eager to cooperate with Japanese scientists in cancer treatment studies.
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PMID:[Japanese-French cooperation in tumor pharmacotherapy: 1970-1990]. 619 71

Bestatin (ubenimex), an inhibitor of aminopeptidase, is an oral immunomodulator that binds to CD13 (aminopeptidase N) on macrophages/monocytes. To examine its immunomodulatory effect after high-dose therapy and autologous bone marrow transplantation (BMT), a dose-finding phase Ib trial was conducted with 30 Hodgkin's disease and non-Hodgkin's lymphoma patients who received no drug (control), 10 and 30 mg (low dose), or 90 and 180 mg (high dose) of bestatin daily for 60 days following autologous BMT. Bestatin administration was initiated when the absolute neutrophil count was greater than 250/mm3 on 2 consecutive days. The serum neopterin levels, an indicator of monocyte/macrophage activation, increased in the high-dose group compared to the control group (not significantly) and the low-dose group (significantly). Similarly, the colony-stimulating activity in the sera was significantly increased in the high-dose group compared to the control and low-dose groups. We also examined the expression of cell-surface markers on monocytes in these patients by fluorescent cytometry analysis. There was no significant difference either in the frequency or absolute number of monocytes (CD14+) among the three groups at any time. However, a significant increase in the frequency of CD16(FcgRIII)-positive monocytes (a marker of activation) was observed in the high-dose group compared to controls from day 14 to day 60 after the start of bestatin administration. Further, the frequency of HLA-DR+ monocytes (another marker of activation) was significantly increased in the high-dose group. These results indicate that bestatin at higher doses (90 and 180 mg daily), but not lower doses, activates macrophages/monocytes, as demonstrated by phenotypic marker (HLA-DR and CD16) up-regulation, and this provides augmentation of neopterin and colony-stimulating activity in the serum of patients following autologous BMT.
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PMID:Monocyte activation by an oral immunomodulator (bestatin) in lymphoma patients following autologous bone marrow transplantation. 900 65

In two separate lymphoma populations, we examined immune reconstitution following high dose chemotherapy (HDT) and bone marrow transplantation (BMT). In the first study we followed immune reconstitution for one year after HDT and BMT. In the second study we examined the ability of the orally active immunomodulator, Bestatin to augment immune reconstitution following HDT and BMT. The studies on immune reconstitution following HDT and BMT were undertaken in a cohort of non-Hodgkin's lymphoma (NHL) patients (n = 35) and examined the peripheral blood (PB) leukocyte subsets and their in vitro functions. Our results demonstrate that monocyte and natural killer (NK) cell engraftment occurred more rapidly then did T cell reconstitution. We also observed a significant decrease in the CD4:CD8 ratio post-transplantation as compared to normal PB donors due to a decrease in CD4+ cells. In addition, following HDT and BMT, measures of T cell function (phytohemagglutinin [PHA] mitogenesis) and T helper cell activity (pokeweed mitogen [PWM] mitogenesis) were consistently depressed as compared to cells from normal PB. Further, we demonstrate a correlation between the loss of T cell function and the frequency of circulating monocytes, suggesting a cause-effect relationship. Despite the dysfunction in T cells following HDT and BMT, immune-modulating agents can still augment the immune function. One such drug is Bestatin (ubenimex), an inhibitor of aminopeptidase (AP) that binds to CD13 on macrophage/monocytes. To examine its immune modulatory activity after HDT and BMT, a dose finding (10, 30, 90 and 180 mg/day) phase Ib trial was conducted with 30 Hodgkin's disease (HD) and NHL patients who received no drug (control), or Bestatin daily for 60 days following BMT. In these studies, Bestatin administration was initiated when the absolute neutrophil count was greater than 250/mm3 on two consecutive days. These studies revealed that Bestatin significantly increased the PHA and PWM responses in a dose-dependent manner. Flow cytometric analysis revealed a significant increase in NK cells (CD56+), B cells (CD19+), as well as the CD4:CD8 cell ratio. The latter observation was associated largely with a depression in the percent of CD8+ T cells as opposed to an increase in CD4+ T cells. We conclude that despite the peripheral tolerance observed following HDT and BMT, Bestatin could significantly increase some, but not all, immune surrogates.
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PMID:Partial review of immunotherapeutic pharmacology in stem cell transplantation. 1075 81