scholarly journals Opposite effects of recombinant interferon-alpha A and deoxycoformycin on adenosine deaminase activity in the Daudi B lymphoblastoid cell line

Blood ◽  
1988 ◽  
Vol 71 (1) ◽  
pp. 59-64 ◽  
Author(s):  
CR Faltynek
Keyword(s):  
Growth Inhibition ◽  
Cell Line ◽  
Adenosine Deaminase ◽  
Interferon Alpha ◽  
Lymphoblastoid Cell Line ◽  
Recombinant Interferon ◽  
Growth Inhibitory ◽  
Adenosine Deaminase Activity ◽  
Recombinant Interferon Alpha

Abstract Interferon-alpha and the adenosine deaminase (ADA) inhibitor deoxycoformycin (dCF) have each been shown to be efficacious in the treatment of some lymphoid malignancies and to have potent antiproliferative activities in vitro. This study examined whether dCF and recombinant interferon-alpha A (rIFN-alpha A) were additive, synergistic, or antagonistic in their effects on the cultured B lymphoblastoid cell line Daudi. Treatment of Daudi cells for three to four days with doses of rIFN-alpha A that were growth inhibitory was unexpectedly found to increase the level of ADA activity per cell two- to threefold and therefore to prevent the inhibition of ADA by limiting concentrations of dCF. However, the opposite effects of dCF and rIFN- alpha A on ADA activity did not lead to antagonistic effects on growth inhibition. The higher concentrations of dCF (with deoxyadenosine) necessary for appreciable growth inhibition could inhibit the increased ADA activity in rIFN-alpha A-treated cells, thus resulting in additive antiproliferative effects.

scholarly journals Opposite effects of recombinant interferon-alpha A and deoxycoformycin on adenosine deaminase activity in the Daudi B lymphoblastoid cell line

Blood ◽  
1988 ◽  
Vol 71 (1) ◽  
pp. 59-64
Author(s):  
CR Faltynek
Keyword(s):  
Growth Inhibition ◽  
Cell Line ◽  
Adenosine Deaminase ◽  
Interferon Alpha ◽  
Lymphoblastoid Cell Line ◽  
Recombinant Interferon ◽  
Growth Inhibitory ◽  
Adenosine Deaminase Activity ◽  
Recombinant Interferon Alpha

Interferon-alpha and the adenosine deaminase (ADA) inhibitor deoxycoformycin (dCF) have each been shown to be efficacious in the treatment of some lymphoid malignancies and to have potent antiproliferative activities in vitro. This study examined whether dCF and recombinant interferon-alpha A (rIFN-alpha A) were additive, synergistic, or antagonistic in their effects on the cultured B lymphoblastoid cell line Daudi. Treatment of Daudi cells for three to four days with doses of rIFN-alpha A that were growth inhibitory was unexpectedly found to increase the level of ADA activity per cell two- to threefold and therefore to prevent the inhibition of ADA by limiting concentrations of dCF. However, the opposite effects of dCF and rIFN- alpha A on ADA activity did not lead to antagonistic effects on growth inhibition. The higher concentrations of dCF (with deoxyadenosine) necessary for appreciable growth inhibition could inhibit the increased ADA activity in rIFN-alpha A-treated cells, thus resulting in additive antiproliferative effects.

Enforced CD19 Expression Leads to Growth Inhibition and Reduced Tumorigenicity

Blood ◽  
1999 ◽  
Vol 94 (10) ◽  
pp. 3551-3558 ◽  
Author(s):  
Maged S. Mahmoud ◽  
Ryuichi Fujii ◽  
Hideaki Ishikawa ◽  
Michio M. Kawano
Keyword(s):  
Growth Inhibition ◽  
Cell Line ◽  
Myeloma Cell ◽  
Inhibitory Effect ◽  
Myeloma Cell Line ◽  
Growth Inhibitory Effect ◽  
Myeloma Cells ◽  
Growth Inhibitory ◽  
Human Myeloma Cell Line

In multiple myeloma (MM), the cell surface protein, CD19, is specifically lost while it continues to be expressed on normal plasma cells. To examine the biological significance of loss of CD19 in human myeloma, we have generated CD19 transfectants of a tumorigenic human myeloma cell line (KMS-5). The CD19 transfectants showed slower growth rate in vitro than that of control transfectants. They also showed a lower capability for colony formation as evaluated by anchorage-independent growth in soft agar assay. The CD19 transfectants also had reduced tumorigenicity in vivo when subcutaneously implanted into severe combined immunodeficiency (SCID)-human interleukin-6 (hIL-6) transgenic mice. The growth-inhibitory effect was CD19-specific and probably due to CD19 signaling because this effect was not observed in cells transfected with a truncated form of CD19 that lacks the cytoplasmic signaling domain. The in vitro growth-inhibitory effect was confirmed in a nontumorigenic human myeloma cell line (U-266). However, introduction of the CD19 gene into a human erythroleukemia cell line (K-562) also induced growth inhibition, suggesting that this effect is CD19-specific, but not restricted to myeloma cells. These data suggest that the specific and generalized loss of CD19 in human myeloma cells could be an important factor contributing to the proliferation of the malignant plasma cell clones in this disease.

Phase I study of a combination of recombinant interferon-alpha and recombinant interferon-gamma in cancer patients.

1986 ◽  
Vol 4 (11) ◽  
pp. 1677-1683 ◽  
Author(s):  
R Kurzrock ◽  
M G Rosenblum ◽  
J R Quesada ◽  
S A Sherwin ◽  
L M Itri ◽  
...  
Keyword(s):  
Interferon Gamma ◽  
Interferon Alpha ◽  
Maximum Tolerated Dose ◽  
Blood Levels ◽  
Recombinant Interferon ◽  
Starting Dose ◽  
The Individual ◽  
Dose Levels ◽  
Recombinant Interferon Alpha

Combinations of interferon-alpha and interferon-gamma demonstrate synergistic antiviral and anti-proliferative activity in vitro. Therefore, we initiated a clinical study of combination interferon therapy in humans. Eighteen patients with metastatic solid tumors received daily intramuscular (IM) injections of recombinant interferon-alpha-A (IFN alfa-2a, Roferon-A; Hoffman-LaRoche, Nutley, NJ) and recombinant IFN-gamma (rIFN-gamma) for 6 weeks. The dose levels were 0.5, 1.0, 2.0, and 5.0 X 10(6) U/m2/d of each interferon. A minimum of two patients were entered sequentially at each dose level. Fever, chills, fatigue, and a greater than or equal to 50% drop in granulocyte counts were observed at all doses. Severity of symptoms corresponded to increasing dose levels. In contrast to the tachyphylaxis to these symptoms that usually develops in patients treated with the individual interferons, many patients on this study experienced persistent fever and worsening fatigue over 6 weeks. The maximum tolerated dose was 1 X 10(6) U/m2/d of each interferon. One patient with renal-cell carcinoma achieved a partial remission (duration, 3 months). Enzyme-linked immunoassay analysis in all four patients for whom complete data were available revealed that peak blood levels of IFN alfa-2a on day 22 were about tenfold higher than on day 1. Because of the possibility of cumulative toxicity, the recommended starting dose for further studies is 0.5 X 10(6) U/m2/d of each interferon, with escalation to 1.0 X 10(6) U/m2/d after 1 month if tolerance is acceptable. Phase II investigations to explore the antitumor efficacy of this regimen are planned.

In vitro phase II trial of recombinant interferon alpha-2 in gastrointestinal cancer

1985 ◽  
Vol 3 (4) ◽  
pp. 188-198 ◽  
Author(s):  
W. Scheithauer ◽  
E. M. Temsch ◽  
K. Schieder ◽  
H. Funovics ◽  
R. Schiessel ◽  
...  
Keyword(s):  
Interferon Alpha ◽  
Phase Ii ◽  
Gastrointestinal Cancer ◽  
Phase Ii Trial ◽  
Recombinant Interferon ◽  
Recombinant Interferon Alpha

Phase II evaluation of recombinant interferon alpha and BCNU in recurrent glioma

1995 ◽  
Vol 82 (3) ◽  
pp. 430-435 ◽  
Author(s):  
Jan C. Buckner ◽  
Loren D. Brown ◽  
John W. Kugler ◽  
Terrence L. Cascino ◽  
James E. Krook ◽  
...  
Keyword(s):  
Radiation Therapy ◽  
Antitumor Activity ◽  
Interferon Alpha ◽  
Tumor Regression ◽  
Recurrent Glioma ◽  
Chemotherapy Response ◽  
Recombinant Interferon ◽  
Content Type ◽  
Recombinant Interferon Alpha

✓ The goal of this study was to determine the antitumor activity and toxicity of 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) plus recombinant interferon-alpha (IFN-a) in patients with recurrent glioma. As single agents, both BCNU and IFN-α can cause tumor regression in patients with recurrent glioma. In vitro studies suggest synergy between the two agents. Thirty-five patients in whom computerized tomography (CT) or magnetic resonance (MR) evidence was obtained of progressive astrocytoma, oligoastrocytoma, or oligodendroglioma received recombinant IFN-α2a (12 × 106 U/m2 intramuscularly) on Days 1 through 3 and BCNU (150 mg/m2 intravenously) on Day 3 of each 6-week cycle. All patients had tumor progression despite radiation therapy and had received no prior chemotherapy. Response was assessed by CT or MR evidence and by neurological examination while the patients were on a regimen of stable or decreasing doses of corticosteroids. All patients could be evaluated for response and toxicity. Twenty-nine percent of the patients demonstrated objective tumor regression; 37% remained stable for more than 6 months and 25% were stable for less than 6 months. The median duration of response to IFN-α and BCNU was 9.9 months and the median survival for all patients was 13.3 months. Toxicity consisted primarily of moderate myelosuppression, venous irritation, vomiting, flulike symptoms, and transient reversible exacerbation of underlying neurological symptoms. The use of BCNU plus IFN-α is a safe, active regimen in the treatment of patients with recurrent glioma who have failed to respond to prior radiation therapy. The contribution of IFN to the antitumor activity observed in this study compared with that previously described with BCNU alone cannot be assessed from this trial.

scholarly journals SYNERGISTIC GROWTH INHIBITORY EFFECT OF FLAVONOL–KAEMPFEROL AND CONVENTIONAL CHEMOTHERAPEUTIC DRUGS ON CANCER CELLS

2017 ◽  
Vol 9 (2) ◽  
pp. 123 ◽  
Author(s):  
Chepuri Kalyani ◽  
Mangamoori Lakshmi Narasu ◽  
Yumnum Priyadarshini Devi
Keyword(s):  
Growth Inhibition ◽  
Cancer Cells ◽  
Cell Line ◽  
Cell Lines ◽  
Apoptotic Cell ◽  
Inhibitory Effect ◽  
Chemotherapeutic Drugs ◽  
Growth Inhibitory Effect ◽  
Growth Inhibitory

<p><strong>Objective: </strong>The objective of the present study was to evaluate synergistic growth inhibitory effect of a flavonol, kaempferol in combination with chemotherapeutic drugs doxorubicin or cisplatin.</p><p><strong>Methods: </strong>The anti-proliferative activities of kaempferol, doxorubicin and cisplatin on human colorectal cancer cells (HCT-15) and human breast cancer (MDA MB 231) were analyzed by 3-(4,5-dimehylthiaol-2-yl)-2,5-diphenyltetraolium bromide (MTT) assay. Further, combinational studies were performed in both the cell lines to evaluate the interaction of drugs with kaempferol. The combination index (CI) method was used to assess the synergism of kaempferol with doxorubicin or cisplatin. Finally, morphological alterations associated with apoptosis were examined under fluorescent microscope.</p><h1>Results: All compounds showed dose-dependent growth inhibition in both HCT-15 and MDA MB 231 cells. The phytochemical kaempferol showed fifty percent inhibitory concentrations (IC<sub>50</sub>) at 120±3.2 µg/ml and 64±1.2 µg/ml on HCT-15 and MDA MB 231 respectively. IC<sub>50 </sub>concentrations of doxorubicin and cisplatin on both the cell lines were achieved at 49.6±0.5 µg/ml, 25.4±2.9 µg/ml and 44±1.8 µg/ml, 40.6±0.8 µg/ml respectively. Further, <em>in vitro </em>therapeutic effect (IC<sub>50</sub>) of doxorubicin and cisplatin in terms of cell growth inhibition on HCT-15 cells were achieved at their one-fifth (10±0.83 µg/ml) and half (10±1.34 µg/ml) concentrations respectively when they were combined with 30 µg/ml of kaempferol individually. Simultaneously, on MDA-MB 231 cell line, the IC<sub>50</sub> concentrations were reduced to 18±1.22 µg/ml and 15±1.87 µg/ml respectively in combination with 32 µg/ml of kaempferol. The combinational index studies revealed the synergistic association of kaempferol with doxorubicin and cisplatin individually in each cell line. The fluorescence imaging studies strongly supported the synergistic association between kaempferol and doxorubicin or cisplatin by confirming significant apoptotic cell death in both the cell lines which was ~3 fold higher than each agent alone.</h1><p><strong>Conclusion: </strong>The study reveals<strong> </strong>the prominent synergism between the phytochemical, kaempferol and chemotherapeutic drugs doxorubicin or cisplatin which helps in elevating the therapeutic efficacy of drugs.</p>

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