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Biomedical subjects

T Robak

Publications and source records attributed to T Robak.

At least 19 recordsLinked to original sources
PubMed1996

[Treatment of multiple myeloma--present status and perspectives].

Multiple myeloma (MM) remains incurable. Despite many chemotherapy programs for large numbers of patients, there has been little improvement in outcome during the past 25 years. For many years, intermittent courses of melphalan and prednisone have represented the standard chemotherapy for newly diagnosed symptomatic MM. Many other drug combinations have been assessed, including regimens using multiple alkylating agents, and programs with vincristine, or an anthracycline, and have failed to show any superiority to melphalan-prednisone. Interferon alpha (IFN alpha) inhibits plasma cell growth and has induced responses in approximately 15% of previously untreated patients. This cytokine may have a role when used in those patients who have reached a good "plateau phase" with low tumor burden at the end of a chemotherapeutic program or after a transplantation procedure. The results of myeloablative therapy with allogenic or autologous marrow transplantation are promising and suggest possibility of a cure in some patients. Important problem in the management of MM patients is the treatment of complications, especially bone destruction, hypercalcemia, anemia and infections. Experimental modalities, especially immunotherapy, hold promise for use in humans and may also provide further insights into the pathogenesis of MM.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1995

Effect of granulocyte-macrophage colony stimulating factor and granulocyte colony stimulating factor on melatonin secretion in rats in vivo and in vitro studies.

The study was performed in order to clarify whether granulocyte-macrophage colony stimulating factor (GM-CSF) and granulocyte colony stimulating factor (G-CSF) affect melatonin production and release. We have found that both factors (GM-CSF at doses of 10.0 and 100.0 micrograms/kg, and G-CSF at doses of 1.0, 10.0, and 100.0 micrograms/kg) stimulate melatonin secretion in rats in vivo. Positive correlations between tested doses of GM-CSF and G-CSF and plasma melatonin levels were observed (P < 0.01). Moreover, GM-CSF at doses of 2.0 and 20.0 ng/ml activated in vitro the pineal gland to melatonin release (P < 0.05) in a dose-dependent manner.

Animals↗
PubMed1995

[Cytokines in the treatment of blood diseases].

Cytokines are a class of signal peptides which represent a major communication network in living organism. Over the last decade, the discovery, cloning and purification of hematopoietic cytokines (interleukins, hematopoietic growth factors) has increased our understanding of the regulation, proliferation, differentiation and function of hematopoietic cells. More recently, the large scale production of the recombinant forms of these molecules has enabled to treat the patients with pharmacologic doses of cytokines. The therapeutic activity of interferon-alpha (IFN-alpha) has been demonstrated in patients with chronic myeloid leukaemia and other chronic myeloproliferative syndromes. IFN-gamma is useful in the prevention of infections in patients with chronic granulomatous disease. Erythropoietin (EPO) was the first hematopoietic growth factor available for clinical use, initially to treat anaemia in renal failure patients. The next cytokines introduced into the clinic were granulocyte colony-stimulating factor (G-CSF) and granulocyte-macrophage CSF (GM-CSF). They are used successfully in haematological malignant disorders to stimulate granulopoiesis after chemotherapy or bone marrow transplantation and to help mobilise marrow stem cells for peripheral blood stem cell transplantation. Interleukin (IL)-1, -2, -3, -4, -6 and -11 have been tested in clinical trials. However, the value of these agents remains to be established.

Cytokines↗
PubMed1995

[Hematologic problems in systemic lupus erythematosus].

Systemic lupus erythematosus (SLE) remains a disease of unknown origin, characterized by major alterations of both the cellular and the humoral arms of immunity. Hematological changes, including anaemia, leucopenia and thrombocytopenia, occur in more than one half of patients with this disease. Anaemia is the most common hematological abnormality seen in SLE. Its possible causes are anaemia of chronic disease (ACD), auto-immune haemolytic anaemia and hypoplastic anaemia. Leucopenia affects both granulocytic and lymphocytic lines and may be caused by autoantibodies. The influence of drugs, hypersplenism and marrow suppression are also possible. Thrombocytopenia occurs frequently and is almost invariably autoimmune. Patients with SLE are at increased risk of thrombosis. Haematological abnormalities in patients with this disease require careful long-term monitoring and prompt therapeutic intervention.

Autoimmune Diseases↗
PubMed1995

[Clinical pharmacology of hydroxyurea].

Hydroxyurea, an antineoplastic drug evaluated clinically more than 30 years ago, is still the principal drug in patients with myeloproliferative syndromes. It is suggested now that it should be used as initial therapy for chronic myelogenous leukemia. Recently hydroxyurea is used in the treatment of patients with sickle cell disease. It has been shown to augment production of fetal hemoglobin and decrease the propensity of abnormal hemoglobin to polymerize and from the sickle cells in this way.

Anemia, Sickle Cell↗
PubMed1995

[Clinical pharmacology of all-trans retinoic acid (ATRA)].

All-trans-retinoic acid (ATRA, tretinoin) is a natural metabolite of retinol and is normally found in plasma, at concentrations of approximately 0.5-1.5 ng/ml. The in vivo and in vitro studies has demonstrated that in pharmacological doses it can differentiate leukemic cells in acute promyelocytic leukemia (APL). ATRA has been shown to induce complete remission (CR) rates of approximately 90% in newly diagnosed and first relapsing APL. However, CR induced by ATRA alone are usually not sustained and intensive antileukemic consolidation therapy is required to prolong remission. ATRA followed by intensive chemotherapy has improved the outcome of newly diagnosed APL, by increasing the CR rate and by reducing the risk of relapse. The presence of the PML/retinoic acid receptor-alpha (PML/RAR-alpha) fusion gene is a marker for sensitivity to this agent. ATRA therapy is associated with the risk of rapidly rising leukocyte counts, leading to the retinoid acid syndrome which may be fatal if the increase in leukocytes is not reversed. A side effects from these complications ATRA therapy is generally well tolerated.

Animals↗
PubMed1995

[Progress and controversy in treatment of Hodgkin's disease].

Hodgkin's disease (HD) is a malignant disease originating from hematopoietic tissue which is characterized by the presence of Hodgkin and Reed-Sternberg cells. The vast majority of HD patients are cured with current standard therapy. Both megavoltage radiotherapy and combination chemotherapy are effective treatment modalities. Radiotherapy is curative for localized Hodgkin's disease, and it is now generally agreed that advanced Hodgkin's disease can be cured by combination chemotherapy. Data from uncontrolled trials suggest that in patients with advanced disease the addition of low-dose radiation to sites of previous disease involvement is associated with better long term and relapse free survival. Patients who relapse after initial treatment with chemotherapy are considered suitable candidates for systemic salvage programs. These programs may include treatment with the same drugs, the use of non-cross resistant chemotherapy programs or investigational programs such as high dose chemotherapy with autologous or allogenic bone marrow rescue. An appropriate management decision depends upon assessment of the disease and also on the impact of treatment side effects on the individual patients.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1994

The interaction of 2-chlorodeoxyadenosine (2-CDA) and interferon alpha (IFN-alpha) on normal and myeloid leukemia hematopoiesis in vitro.

The influence of 2-CDA and interferon alpha (IFN-alpha) on the CFU-GM cells from ten normal individuals as well as on the CFU-GM from ten patients with chronic myeloid leukemia (CML) and on clonogenic leukemic blasts (CFU-L) from ten patients with acute myeloid leukemia (AML) in semi-solid cultures in vitro was investigated. The agents were added to the cultures alone and in combinations at concentrations of 20, 40 and 80 nM/l of 2-CDA and 10(2), 10(3) and 10(4) U/ml of IFN-alpha. A dose-dependent growth inhibition of CFU-GM as well as of CFU-L was observed. The inhibitory effect of both drugs used alone was significantly greater on the CFU-GM cells from patients with CML than on cells from normal donors. However, 2-CDA and IFN-alpha used together showed greater additive effect on the CFU-L than on the CFU-GM from normal donors and from CML patients.

Adult↗
PubMed1994

Treatment of patients with hairy cell leukemia with 2-chloro-2'-deoxyadenosine (2-CdA).

Six patients with hairy cell leukemia have been treated with 2-chloro-2'-deoxyadenosine in a dose 0.05 mg/kg/daily in 2 h intravenous infusions during 7 consecutive days. Two patients underwent splenectomy with no clinical or hematologic improvement. Complete remission has been achieved in 4 patients and partial remission in one. 2-CdA was not effective in a patient with HCL-variant. The longest unmaintained CR lasted 11 months. The drug was well tolerated. Only slight side effects were observed. The drug exerted, however, myelosuppressive action resulting in cytopenias in the peripheral blood. Clinical consequences of this activity require further investigation. 2-CdA seems to be a drug of choice in the management of HCL.

Aged↗
PubMed1994

Influence of 2-chloro-2'-deoxyadenosine alone and in combination with cyclophosphamide or methotrexate on murine leukemia L1210.

The influence of 2-CdA administrated alone and in combination with CY or MTX on the survival time of mice bearing L1210 leukemia was investigated. 2-CdA treated mice lived longer than control animals. Survival times of mice receiving combined therapy of 2-CdA and CY were significantly prolonged as compared with mice treated with these agents separately. Survival times of mice treated with 2-CdA and MTX were not significantly prolonged, compared with animals receiving 2-CdA alone.

Animals↗
PubMed1994

[Stem cell factor].

Stem cell factor (CSF), also called c-kit ligand (KL) or mast cell growth factor (MGF) is a peptide growth factor/cytokine with broad activities, especially on hematopoiesis. Its physiological role is best understood through the naturally occurring steel and W mutations in the mouse. This cytokine has recently been made available because of molecular cloning and its expression in recombinant form SCF is produced by a variety of cells, especially fibroblast, and interacts with target cells in each of the hematopoietic lineages to stimulate proliferation and differentiation. It has been found that SCF is important for the survival, proliferation and differentiation of mast cells and that it influences all stages of their development. SCF activity is not restricted to hematopoiesis, as it plays an important role in the development of germ cells and melanocytes as well. Preclinical studies show that SCF can protect against lethal irradiation, elicit multilineage responses in peripheral blood and bone marrow cellularity and increase circulating peripheral blood progenitor cells in a dose-dependent manner. Recombinant human SCF has major clinical potential through its synergy with other factors, especially G-CSF, to enhance mobilization of stem cells in peripheral blood.

Animals↗
PubMed1994

[Biology of interleukin 6 (IL-6) and its significance in the pathogenesis of some diseases].

In the paper numerous activities of IL-6 toward various normal and neoplastic cells are reviewed. The role of this cytokine in pathophysiology of a various disease including infections and inflammatory and autoimmune diseases as well as in leukaemias, lymphomas and other neoplastic diseases is presented. Potential clinical value of the IL-6 levels in the serum and the role of its recombinant form in the treatment of thrombocytopenia and some neoplastic diseases is also discussed.

Acquired Immunodeficiency Syndrome↗
PubMed1994

[Anagrelide--new antiplatelet drug].

Anagrelide is a quinazoline compound developed as a potent inhibitor of platelet aggregation. During studies in human it has produced rapid and selective thrombocytopenia and has therefore been evaluated for use in conditions associated with thrombocythaemia. Anagrelide significantly inhibits human megakaryocyte colony development in vitro by preventing full megakaryocyte maturation, and inhibits platelet aggregation as a result of potent inhibition of cyclic adenosine monophosphate (cAMP) phosphodiesterase activity. In 60 to 93% of patients with essential or myeloproliferative thrombocythaemia anagrelide produces sustain reductions in platelet counts and also reduces the incidence of disease-related symptoms. Most adverse effects are related to its vasodilatory or positive inotropic properties. This new agent appears promising in the treatment of thrombocytosis in patients with chronic myeloproliferative diseases, especially in younger persons in whom the risk of leukaemogenic transformation with some alternative drugs is of particular concern.

Animals↗
PubMed1994

[Acute basophilic leukemia].

Acute basophilic leukemia is a relatively uncommon variant of acute nonlymphocytic leukemia accounting for 4-5 percent of cases of acute nonlymphocytic leukemia and less than 2 percent of all hematopoietic malignancies. It is usually characterized by a very rapid clinical course, symptoms of hyperhistaminemia, peptic ulceration, gastrointestinal cerebrovascular bleeding and resistance to therapy. This leukemia is somewhat heterogeneous in term of morphology, immunology and chromosome alterations. No specific marker chromosome has been described but trisomy 8 and monosomy 7 are the most frequent chromosomal abnormalities. The cytochemical reactions in basophilic leukemia are positive results with toluidine blue and Astra blue stains. Peroxidase stain is reported to show positive reactions. Ultrastructural analysis usually reveals immature basophil granules and provides evidence of basophilic differentiation of the blasts.

Humans↗