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J Yopp

Publications and source records attributed to J Yopp.

7 recordsLinked to original sources
PubMed1995

Gamma chain-associated cytokine receptors signal through distinct transducing factors.

The IL-2, IL-4, and IL-7 signaling pathways have been shown to utilize shared components. The receptors for these cytokines are composed of ligand-specific binding chains that associate with a shared signaling subunit, the common gamma (gamma c) chain. In addition, IL-2, IL-4, and IL-7 induce activation of a common set of nonreceptor tyrosine kinases, Jak-1 and Jak-3. We have further investigated the signaling events induced by these cytokines and find that the gamma c-associated receptors activate distinct signal transducing factors (STFs). In addition, we show that a 94-kDa STAT-related protein (p94) is activated in response to IL-2 and IL-7, but not IL-4. These data indicate that IL-2, IL-4, and IL-7 activate distinct signaling molecules which might be differentially recruited to the receptor complex by the ligand-specific units of the IL-2, IL-4, and IL-7 receptors.

Amino Acid Sequence↗
PubMed1988

Comparative regimens for the ex vivo chemopurification of B cell lymphoma-contaminated marrow.

The success of autologous bone marrow transplantation for B cell lymphoma may depend on the efficacy of in vitro purification of patients' tumor cell-contaminated marrow. In this study, we tested the toxicity of seven different chemotherapeutic agents against two B cell lymphoma lines (LY-16 and SK-DHL-2) as compared to normal human bone marrow granulocyte-macrophage progenitor cells (CFU-GM). 4-Hydroperoxycyclophosphamide (4-HC), VP-16-213 (VP-16), nitrogen mustard, and vincristine showed a highly selective toxicity against cultured lymphoma cells; i.e., at doses sufficient to induce a 4-log clonogenic tumor cell reduction (4-HC 21 micrograms/ml, VP-16 50 micrograms/ml, nitrogen mustard and vincristine 5 micrograms/ml), 10.0 +/- 6.7, 3.0 +/- 3.2, 23.2 +/- 22.7 and 24.0 +/- 17.0% (mean +/- 1 SD), respectively, of normal bone marrow CFU-GM were preserved. The differential sensitivity of tumor cells and normal hematopoietic precursors was less prominent after exposure of cells to cis-diamminechloroplatinum II (cis-platinum); thus, at a drug dose of 100 micrograms/ml, all detectable lymphoma cells could be eradicated (i.e., greater than or equal to 4 log reduction) while a CFU-GM recovery of only 0.2 +/- 0.2% was observed. In contrast, adriamycin and bleomycin, at the highest tumoricidal concentrations tested (5 and 100 micrograms/ml, respectively) did not exhibit a selective toxicity toward lymphoma cell lines. In summary, our results suggest that nitrogen mustard and vincristine, as well as 4-HC and VP-16, may be useful agents for the ex vivo treatment of bone marrow grafts form B cell lymphoma patients.

Antineoplastic Agents↗
PubMed1988

Autologous bone marrow transplantation for patients with poor-prognosis lymphoma.

Review of prognostic factors at Memorial Hospital in New York City has shown that adult patients with large-cell lymphoma (diffuse histiocytic lymphoma by Rappaport classification) who have high lactic dehydrogenase (LDH) and/or bulky mediastinal or abdominal disease are destined to do poorly with conventional combination chemotherapy, with a 2-year disease-free survival of about 20%. Patients who relapse after conventional combination chemotherapy have a similar poor prognosis. Thirty-one such patients with lymphoma were studied to evaluate the efficacy of intensive radiotherapy (hyperfractionated total body irradiation [TBI] [1,320 rad]), and cyclophosphamide (60 mg/kg/d for two days) followed by autologous bone marrow transplantation (ABMT). Our results show a disease-free survival advantage (P = .002) for 14 patients who underwent ABMT immediately after induction of remission with 79% surviving at a median follow-up 49.2+ months, compared with a median survival of 5.2 months for 17 patients administered ABMT while in relapse and/or after failing conventional treatment. Our results support the use of aggressive therapy as early treatment for patients with poor prognostic features.

Adolescent↗
PubMed1985

Synergistic effect of 4-hydroperoxycyclophosphamide and etoposide on a human promyelocytic leukemia cell line (HL-60) demonstrated by computer analysis.

Autologous stem cell transplantation using cryopreserved bone marrow offers the opportunity to rescue patients from hematopoietic toxicity caused by intensive chemotherapy. This approach is potentially useful for high-risk leukemias as well as for other cancers. The development of suitable methods for purging malignant cells from the bone marrow will offer a better chance of success for autologous stem cell transplantation. In this paper, we describe our efforts at purging myeloid cells. HL-60, a promyelocytic leukemia cell line, was used as a model. 4-Hydroperoxycyclophosphamide (4-HC) and VP-16-213 (VP-16) (either alone or in combination) were used to treat HL-60 cells and normal bone marrow. The cytotoxic effect of 4-HC (29.2 micrograms/ml; 100 microM) upon the HL-60 cell line was 99.8 +/- 0.12% (SE), and the colony-forming units-granulocyte, macrophage (CFU-cs) of normal bone marrow was inhibited by 82.5%. VP-16, at a concentration of 25 micrograms/ml (42.5 microM), can kill 99% of HL-60 cells and inhibit 72.7% of the CFU-cs. A drug mixture containing 4-HC (29.2 micrograms/ml) and VP-16 (10 micrograms/ml) (combination ratio, 1:0.342) reduces HL-60 cells to an undetectable number, and the CFU-cs were inhibited by 87.2%. The laboratory data were further analyzed for the synergistic effect of these two drugs by quantitative determination of the median effect plot and the multiple drug equation recently described by Chou and Talalay (Adv. Enz. Regul., 22: 27-55, 1984). Interactions of two drugs at different effect levels and at different combination ratios were then determined by computer simulation. At high effect levels, 4-HC and VP-16 in combination gave a synergistic cytocidal effect on HL-60 leukemic cells and gave an antagonistic inhibitory effect on normal bone marrow CFU-cs. This combination greatly increases the safety margin. Computer simulation of a dose effect relationship has also shown that the 4-HC:VP-16 combination ratio of 1:0.342 yields a better selective effect than a ratio of 1:0.856. This quantitative analysis suggests that the combination of these two drugs at the selected dose level offers a good method for purging nonlymphoblastic leukemia cells.

Antineoplastic Combined Chemotherapy Protocols↗
PubMedDate not supplied

Neuroblastoma.

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Adolescent↗
PubMedDate not supplied

Non-Hodgkin's lymphoma.

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Antineoplastic Combined Chemotherapy Protocols↗