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Biomedical subjects

K Sampi

Publications and source records attributed to K Sampi.

At least 37 records · Page 2Linked to original sources

Induction of differentiation of human myeloid leukemia HL-60 cells by novel pyrimidine nucleoside analogs.

New pyrimidine nucleoside analogs (18 compounds) were synthesized and their growth-inhibiting and differentiation-inducing activities on human myeloid leukemia HL-60 cells were examined. Some of the analogs were found to induce nitroblue tetrazolium (NBT) reducing activity in the HL-60 cells. The inducing activities of these compounds were compared at their concentrations for 50% inhibition of cell growth. TI-79 (3-benzyl-5-methyl-3-(beta-D-ribofuranosyl)pyrido[2,3-d]pyrimidine- 2,4(1H,3H)-dione) was a very effective inducer of NBT-reduction and of differentiation of the cells into mature granulocytes. The induction of NBT-reducing activity by TI-79 was inhibited by high concentrations of the natural nucleoside, adenosine. Other differentiation inducers, such as retinoic acid, 1 alpha,25-dihydroxyvitamin D-3 and staurosporin markedly enhanced the induction of differentiation of HL-60 cells by TI-79. Nucleoside analogs such as TI-79 should be useful for differentiation therapy of some types of myelogenous leukemia.

Adenosine↗

Induction of differentiation of human leukemia cells by inhibitors of myosin light chain kinase.

Inhibitors of myosin light chain kinase, 1-(5-chloronaphthalene-1-sulfonyl)-1H-hexahydro-1,4-diazepine hydrochloride (ML-9) and 1-(5-iodonaphthalene-1-sulfonyl)-1H-hexahydro-1,4-diazepine hydrochloride (ML-7), induced Nitroblue tetrazolium reducing activity, lysozyme activity and morphological maturation of human monoblastic U937, THP-1 and promyelocytic HL-60 cells, but not of erythroblastic K562 cells. However, three analogs of ML-9, which are an inhibitor and an activator of protein kinase C, and a calmodulin antagonist, respectively, did not induce differentiation of the cells.

Azepines↗

Effects of inhibitors of protein tyrosine kinase activity and/or phosphatidylinositol turnover on differentiation of some human myelomonocytic leukemia cells.

The activities of protein tyrosine kinase and phosphatidylinositol turnover have been found to be associated with cell growth and differentiation. We examined the effects of some inhibitors for these biochemical activities in human myelogenous leukemia cells. Genistein, which is known to inhibit the activities of protein tyrosine kinase, phosphatidylinositol turnover and topoisomerase II, induced nitroblue tetrazolium (NBT) reduction and lysozyme activity in ML-1, HL-60 and U937 cells. Morphological studies showed that genistein-induced differentiation of myeloblastic ML-1 cells into promyelocytes and of promyelocytic HL-60 cells into mature granulocytes. The differentiation-inducing effect of genistein was augmented by addition of 1 alpha,25-dihydroxyvitamin D3 (VD3) or retinoic acid, VD3 being more effective than retinoic acid. Methyl 2,5-dihydroxycinamate, a protein tyrosine kinase inhibitor, had only a weak effect in inducing differentiation of ML-1 cells. On the other hand, psi-tectorigenin was more effective than genistein in inducing the differentiations of ML-1 and HL-60 cells. Psi-tectorigenin is reported to inhibit phosphatidylinositol turnover without inhibiting protein tyrosine kinase. Thus modulation of phosphatidylinositol turnover might be more important than that of protein tyrosine kinase activity for differentiation of some myelogenous leukemia cells.

Cell Differentiation↗

[An 8; 21 chromosome translocation associated leukemia presenting with large intestinal granulocytic sarcoma: a report of two cases].

Two patients of acute myelogenous leukemia (AML) presented with a large intestinal tumor and related symptoms. They had a tumor in the rectum or the ascending colon. Bone marrow cells obtained from both patients showed a karyotype with t(8;21). Chromosomal findings in the former patient has already been reported in detail (Am J Hematol 4, 273, 1978). These findings and reports in the literature indicate that large intestinal tumor may not be rare in AML with an 8;21 translocation. Complete remission was achieved after chemotherapy, when their intestinal tumors disappeared.

Adult↗

[Clinical application of thymidine kinase activity in patients with acute non-lymphocytic leukemia].

An improved method for the detection of thymidine kinase (TK) activity with the use of 125I-iododeoxyuridine as the substrate. Radioimmunoassay of prolifigen TK "Daiichi", was used for this assay. Eighty-seven serum samples were collected from 40 patients with acute nonlymphocytic leukemia in four institutions. The levels of TK were measured in the time of pretreatment, remission, and recurrence, and the relationship between the levels of TK and either LDH, marrow blasts, or circulating blasts was also examined. The levels of TK were significantly lower in the state of remission than in the pretreatment. However, the level of TK in remission was much elevated in the majority of cases than normal range (less than or equal to 5 units/l). On the contrary, LDH in remission was within normal limits in the majority of cases. The level of TK in the state of relapse was significantly higher than in the remission. The level of TK correlated in some extent with the percentage of marrow blasts (r = 0.508), and the level of TK in more than 5% of marrow blast was most beyond normal range. Correlation coefficient between the percentage of circulating blasts and TK (r = 0.577) was slightly higher than that between the percentage of marrow blasts and TK. Correlation coefficient between the level of TK and the number of marrow blasts was higher than that between LDH and number of marrow blasts. The levels of TK correlated well with serum LDH (r = 0.778), and was more sensitive than LDH. In conclusion, it was suggested that TK could be used as one of an useful and supplemental tumor marker in the follow-up of treatment of acute nonlymphocytic leukemia and to monitor the effect of therapy.

Biomarkers, Tumor↗

[Similar efficacy of less than 6 and 7-10 courses of therapy with anthracycline-based combination chemotherapy for localized non-Hodgkin's lymphoma of extranodal type].

We studied retrospectively the influence on the prognosis of patients with localized non-Hodgkin's lymphoma of extranodal type with regard to the duration of an anthracycline-based combination chemotherapy-modified CHOP regimen. The patients who were given at least 2 courses of chemotherapy and attained complete remission were selected. These were subdivided into two groups; one for patients who were given 2-6 courses, the other for patients given 7-10 courses. The relapse-free survival curve for patients treated with 7-10 courses was slightly better than that of the patients treated with less than 6 courses. However, the difference between them was not significant. From the results, it was considered possible to reduce the chemotherapy from 10 to 6 courses in patients with localized non-Hodgkin's lymphoma of extranodal type. A prospective randomized study is now in progress at Saitama Cancer Center.

Adult↗

[Gastrointestinal toxicity induced by anticancer drugs--including new antiemetic drugs].

In a cross-over design of a study of prevention of emesis induced by cancer chemotherapy done in Saitama Cancer Center, the efficacy of oral lorazepam was superior to that of i.v. domperidone. And then, we proceeded a parallel study with use of oral lorazepam and oral domperidone. However, in this situation lorazepam was not superior to domperidone despite accrual of more than 60 patients. Recently, a multi-institutional study has been started in October of 1988 in an evaluation of the efficacy and safety of the new anti-emetic drug of a 5HT3 receptor antagonist, ondansetron. Two methods of its administration were designed. In one study ondansetron was given 2 hr prior to non-platinum chemotherapy as an 2 or 8 mg dose by oral administration, followed by receiving it 6 hr and 12 hr after chemotherapy. In another study, it was given 15 min prior to cisplatin including chemotherapy as an 2 or 8 mg loading dose by i.v. injection over 5 min, followed by continuous infusion at a rate of 0.25 mg/h or 1 mg/h for 24 h, respectively. Efficacy was assessed by measurement of the number of episodes of retching and vomiting occurring in the 24h after administration of chemotherapy and by an assessment of nausea during the same period. This time the major efficacy category was adopted, which is made up of the complete responder and major responder categories of both vomiting and nausea. 19 patients were evaluable for efficacy in the non-platinum group; the major efficacy rates showed 45% in 2 mg-given group and 88% in 8 mg-given group, respectively. 108 patients were evaluable for efficacy in the cisplatin group: the major efficacy rates showed more than 70% in both 2 mg and 8 mg-given group. However, in the patients given more than 75 mg/mg2 of cisplatin, the major efficacy rates were 55% in the 2 mg-given group, compared to 73% in the 8 mg-given group. Ondansetron was well tolerated, with no significant drug-related adverse events.

Adult↗

[Epirubicin-based combination chemotherapy in the treatment of non-Hodgkin's lymphoma: with emphasis of elderly patients].

Twenty-four patients with non-Hodgkin's lymphoma aged 60 years and older were treated with epirubicin-based combination chemotherapy. Complete remission was obtained in nineteen (83%) of 23 patients with measurable disease. Of these complete responders seventeen patients with localized disease attained complete remission. No patients received radiation therapy after chemotherapy. The survival rate was 78% at 50 months in patients with the localized disease. The median follow-up time is 40 months, ranging from 13 to 65 months. All of the localized disease were treated in the out-patient clinic and no patients died of chemotherapy-related infectious complications. No severe infection such as either bacteremia or pneumonia occurred. It was concluded that epirubicin-based combination chemotherapy was highly effective in patients with localized non-Hodgkin's lymphoma.

Administration, Oral↗

Combination of pipemidic acid, colistin sodium methanesulfonate and nystatin may be less effective than nystatin alone for prevention of infection during chemotherapy-induced granulocytopenia in acute leukemia.

Pipemidic acid (PPA) and colistin sodium methanesulfonate (CLM) may selectively suppress aerobic gram-negative bacilli. Twenty-nine patients with acute leukemia were randomized after each course of consolidation chemotherapy to receive a single agent of nystatin (NYS) (34 courses) versus a combination of NYS, PPA and CLM (36 courses). The duration of fever over 39 degrees C was longer with the three drug combination (4.6 +/- 5.1 days) than with NYS alone (1.8 +/- 1.8 days) (P less than 0.01). Four cases of pneumonia occurred and four patients including one having pneumonia died of infection with the three drug combination, while no pneumonia or death occurred with NYS alone (P = 0.06 and P = 0.06, respectively). The combination of NYS, PPA and CLM may be less effective than NYS alone for the prevention of infection in acute leukemia patients with chemotherapy-associated granulocytopenia.

Acute Disease↗

[Malignant lymphoma NHL].

The long-term survivors of malignant lymphoma who had been treated in Saitama Cancer Center since September 1976 were evaluated. The primary treatment was scheduled as follows; radiotherapy alone was to be delivered to the involved field only in stage I lymphoma with less than 5 cm in diameter, the remaining lymphoma was mainly treated with anthracycline-based combination chemotherapy. 25 patients were treated with primary radiotherapy, and the actuarial 5-yr relapse-free survival rate was 83%. Primary adriamycin-based chemotherapy was given to 20 patients with nodal localized lymphoma. 10 patients died with this treatment and actuarial survival rate at 5 years was 41%. 36 patients with stage II lymphoma involving Waldeyer's ring were treated with primary chemotherapy. Complete response was obtained in 92% with 83% of 5-yr actuarial survival rate. 5-yr actuarial survival rate of 50 patients with advanced stage of lymphoma was 36%, but 69% of responders who obtained complete response had long-term survive. 20 patients aged 70 or older had a 31% actuarial 5-yr survival rate, however, the older patients with localized lymphoma who received primary chemotherapy had a 77% actuarial 5-yr survival rate. 10 older patients of the localized lymphoma arising from Waldeyer's ring are all surviving.

Actuarial Analysis↗

[Aclarubicin-combined combination chemotherapy in patients with refractory or relapsed non-Hodgkin's lymphoma].

Patients with lymphoma who became refractory or resistant to standard chemotherapy including anthracyclines were treated with aclarubicin-combined chemotherapy including VP-16, ifosfamide, and carboquone in a multicenter study. Twenty-one patients were entered in this study, and 18 of them were evaluable. The median age was 52 years old (range 27-74), and there were 17 male and 3 female patients. The vast majority of patients were diagnosed as having diffuse lymphoma, of which 10 cases had large cell type. Surface markers were measured in 8 patients, of whom 4 had T-cell lymphoma. Remission was attained in 3 of 18 patients (17%) with one complete and lasting remission with T-cell lymphoma. In conclusion, the response rate in this study was poor, but this type of combination chemotherapy might be considered in patients with T-cell lymphoma.

Aclarubicin↗

[Chemotherapy of stage III-IV Hodgkin's disease. A retrospective analysis of the 53 cases collected from 9 institutions in Japan].

The clinical data of 53 patients with Stage III-IV Hodgkin's disease collected from 9 institutions in Japan were analyzed for the efficacy of chemotherapy. CR rate (78%) and five-year relapse-free survival (RFS) rate (61%) were higher in the patients treated with VEPA/CHOP regimen than those in patients with VEMP/BONP or MOPP/C-MOPP regimen, although the difference was not statistically significant because of the small number of the patients. As to 14 patients treated with CHOP regimen, CR rate was 87% and RFS curve trend toward plateau at 67% after 2 years and 3 months from the initiation of chemotherapy. Salvage therapy with adriamycin-based combination chemotherapy achieved CRs in 9 of 14 (64%) patients who had been treated with VEMP, BONP, modified MOPP or C-MOPP regimen. The CHOP regimen was effective in the treatment of III-IV Hodgkin's disease but an alternative multidrug chemotherapy with ADM, CPM, VCR, BLM, etoposide and procarbazine is recommended for achieving a higher CR rate and a better RFS. Prospective study is needed to establish the standard chemotherapy for Hodgkin's disease in Japan.

Adolescent↗

[Follicular lymphoma in Japan: retrospective study on natural history and therapeutic results in 50 cases collected from 4 institutions].

Clinical data of the 50 patients with nodal follicular lymphoma were collected from 4 institutions in Japan and were analysed retrospectively. A frequency of follicular lymphoma was 9.3% in the 364 patients with nodal lymphoma registered between 1981-1986. Twenty-one patients (42%) were classified as follicular medium-sized cell type (F-medium; identical with follicular small cleaved cell type by Working Formulation criteria), 12 (24%) as follicular mixed (F-mixed), and 17 (34%) as follicular large (F-large). There were 31 (62%) patients with Stage III-IV disease involving bone marrow in 6 patients, liver in 2, bone marrow and liver in 2, stomach in 1. Overall five- and ten-year survival rates were 65% and 32%, respectively, in the 49 patients whose median follow-up period was 3 years, ranging from 2 to 11 years. Adriamycin-based combination chemotherapy [ADM(+) therapy] produced 10 (100%) complete response (CR) of 10 patients with F-large lymphoma and 8 (80%) of them were free from relapse. But, in the patients with F-medium lymphoma, ADM(+) therapy produced one (17%) CR of 6 patients and their survivals were not superior to those treated with ADM(-) therapy, single agents or radiotherapy alone. There was no difference in the natural history or therapeutic results between the patients in Japan and United States, although the frequency of follicular lymphoma was extremely lower in Japan. ADM(+) therapy can be accepted as the first-line chemotherapy for the patients with F-large lymphoma, but the best modality of treatment should be investigated for the patients with F-medium lymphoma.

Adult↗

[High-dose cytosine arabinoside treatment of leukemia with special reference to the optimal number of doses].

A high dose of cytosine arabinoside (ara-C) was given to 51 patients during consolidation therapy or with refractory or relapsed acute leukemia. Ara-C was administered as a 3-hour infusion at a dose ranging from 2 to 3 g/m2 every 12 hours, diluted in 500 ml of 5% dextrose in water for 2 to 6 days. Complete remission was attained in 3 (25%) of 12 evaluable patients. Two with blast crisis of chronic myelogenous leukemia of these did not obtain complete remission. Death due to marrow aplasia occurred in five patients, and two of these had relatively good performance status and were given a dose of 3.0 g/m2 x 8 or 12 of ara-C. At a dose of 3.0 g/m2 x 6, the mean duration of granulocytes of less than 100/mm3 was 6.7 days. This duration seemed to be manageable myelosuppression. Therefore, 3.0 g/m2 x 6 was thought to be an adequate dose. Seizure occurred in one patient, and conjunctivitis was seen in another. In conclusion, from the manageable myelosuppression observed, administration of 3.0 g/m2 x 6 of ara-C seemed to be an adequate dose.

Adolescent↗

Induction of differentiation of mouse myeloid leukemia M1 cells by serum of patients with chronic myeloid leukemia.

We examined the capacities of sera from patients with myeloid leukemia to induce differentiation in mouse myeloid leukemic M1 cells. Higher differentiation-inducing activity (D-activity) was detected in sera of patients with chronic myelomonocytic leukemia or chronic myeloid leukemia (CML) than in sera of patients with acute myeloid leukemia and normal volunteers. The D-activity in the sera was lost on heating the sera at 56 degrees for 30 min. The major peak of D-activity on Sephadex G-200 gel filtration had an apparent molecular weight of 160,000. The origin of the D-activity in sera of patients with CML was studied by culturing fractions of peripheral blood cells of patients with D-activity for 3 days and then measuring the ability of the conditioned medium (CM) to induce differentiation of M1 cells. The cells in the myeloblast and promyelocyte fraction differentiated spontaneously into macrophage-like cells during culture for 3 days and the cells in the late granulopoietic cell fraction differentiated into neutrophil-like cells. Higher D-activity was present in CM of cells in the myeloblast and promyelocyte fraction than in CMs of late granulopoietic cell fractions. These results suggest that human leukemic cells produce D-activity for M1 cells during their differentiation into macrophage-like cells.

Animals↗

[Phase II study of carboplatin in malignant lymphoma].

A phase II study of carboplatin for malignant lymphoma was conducted. Thirty-nine patients with malignant lymphoma were entered into this study, and 6 of them were excluded from evaluation due to violation of selection criteria. The remaining 33 cases were studied to assess the effectiveness and safety of this drug. Two CR and 11 PR were obtained with this medication (effective rate 39%). The significant affecting factors were previous treatment, disease stage and P.S. score. Many cases suffered from gastrointestinal symptoms and reduced hematopoiesis. The former complication was self-limited without any fatal episodes. However, the latter included severe cases, especially thrombocytopenia, which is suggested to be a dose limiting factor (DLF) of this drug.

Adolescent↗