Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0002871 (anemia)
 52,094 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Retinoids affect the growth and differentiation of haemopoietic cells. Individuals deficient in retinoids become anaemic; replacement therapy with retinoids corrects the anaemia. Retinoids enhance the clonal proliferation of erythroid and myeloid precursors in soft-gel culture; all-trans-retinoic acid and 13-cis-retinoic acid are the most potent. Retinoids also induce the differentiation of HL-60 promyelocytes to functional granulocytes and can induce cells from other relatively mature, myeloid cell lines to undergo partial differentiation. Cells from less mature myeloid leukaemic lines are often resistant to induction of differentiation by retinoids. Like cells from established lines, relatively mature leukaemic cells (promyelocytes, myelomonoblasts) harvested from patients can undergo differentiation in vitro in the presence of retinoids. A few reports suggests that a minority of patients with myeloid leukaemia or preleukaemia who receive 13-cis-retinoic acid will have improvement in their haemopoiesis. Further studies are required to understand the mechanism of action of retinoids on the growth and differentiation of haemopoietic cells and to explore more fully the therapeutic potential of retinoids.
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PMID:The effect of retinoids on haemopoiesis--clinical and laboratory studies. 386 8

The major limitation for continuous administration of natural retinoids for chemoprevention of cancer is their high toxicity; however, synthetic retinamides have the desirable quality of reduced toxicity while retaining most of the biological activity. We have presently evaluated the comparative toxicity of all-trans- and 13-cis-isomers of N-ethyl retinamide (ER), N-2-hydroxyethyl retinamide (HER), and N-4-hydroxyphenyl retinamide (HPR) in mice and rats after po and ip administration. The computed LD90, DL50, and LD10 values for combined sexes of mice following 21 daily doses of the above retinoids were determined. Identical doses of the same retinoid by ip administration produced more toxicity and deaths than by the po route. The 13-cis-isomers exhibited comparatively less toxicity than the corresponding all-trans-isomer. Based on the lethality data, all-trans-retinoic acid was most toxic followed by all-trans-HER greater than all-trans-HPR greater than all-trans-ER. Changes in clinical chemistry and hematological parameters associated with administration of the retinamides include a dose-dependent peripheral anemia evidenced by erythrocytopenia and decreased hemoglobin concentration and packed cell volume. Retinoid treatment also caused increased plasma alkaline phosphatase activity and decreased serum albumin levels. Histopathological changes associated with retinoid administration primarily included liver lesions as characterized by degeneration and enlargement of hepatocytes. The present studies indicate that synthetic retinoids are less toxic than the natural ones.
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PMID:Subacute toxicity of all-trans- and 13-cis-isomers of N-ethyl retinamide, N-2-hydroxyethyl retinamide, and N-4-hydroxyphenyl retinamide. 622 23

Sprague-Dawley rats received daily oral gavage doses of either 2-retinylidene-5,5-dimethyl-1,3-cyclohexanedione (retinylidene dimedone; 14, 50, 150, or 330 mg/kg) or all-trans-retinoic acid (1, 4, 14, or 50 mg/kg) for 13 weeks. Rats given 50 mg/kg of all-trans-retinoic acid developed numerous long-bone fractures and became moribund during the third week of the study. Those receiving lower dosages survived until scheduled termination, but the 14 mg/kg group showed clear signs of retinoid intoxication including growth depression, anemia, serum alkaline phosphatase elevation, bone fracture, and testicular degeneration. Exposure to retinylidene dimedone did not result in any treatment-related deaths, growth depression, or histopathologic lesions, even at the highest dose, 300 mg/kg. Animals given this dosage exhibited mild anemia, equivocal evidence of bone fracture, but no increase in alkaline phosphatase activity. Retinylidene dimedone appears to be considerably less toxic than all-trans-retinoic acid.
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PMID:Subchronic toxicity of all-trans-retinoic acid and retinylidene dimedone in Sprague-Dawley rats. 671 May 36

It has been shown that all-trans-methylretinoate, 13-cis-methyl retinoate and retinoid C15 administered intraperitoneally in the form of 0.05% solutions in excess doses reduce the red cell count, hemoglobin content, and osmotic resistance of red cells in C57Bl/6 mice. Administration of 13-cis-methylretinoate and retinoid C15 resulted in the increase of the number of cells uncapable to stain with paraldehyde fuchsin. Anemia induced by all-trans-methylretinoate in AKR mice was accompanied by erythropoiesis enhancement in the bone marrow.
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PMID:[Erythrocyte changes from the administration of excess doses of retinoids]. 715 Jul 58

Retinoids have anti-tumor activity in several malignant and premalignant conditions. Since Kaposi's sarcoma is regulated by steroid hormones both in vivo and in vitro, we hypothesized that retinoids may have anti-tumor effects in AIDS-related Kaposi's sarcoma. Thus, 27 patients with mucocutaneous, non-visceral AIDS-related Kaposi's sarcoma were treated with all-trans retinoic acid (tRA). Poor tolerance was observed at the initial starting dose of 150 mg/m2, and thus subsequent patients were treated using a weekly dose escalation, starting with 45 mg/m2 (given daily, in subdivided doses), to the target dose of 150 mg/m2 (given daily in three subdivided doses). Nearly half (46%) of the patients had extensive mucocutaneous disease with over 25 lesions. No patient had received prior cytotoxic chemotherapy. Ten patients had CD4 lymphocytes of 200/mm3 or greater (strata I); and 17 had under 200/mm3 CD4 lymphocytes (strata II). The median of the average daily tRA dose administered was 150 mg (90 mg/m2; there was no significant difference in the dose tolerance between the two strata). Adverse effects consisted of transient mild to moderate headaches in 65% of patients, mild to moderate skin dryness and cheilitis in 61%, and nausea and vomiting in 31%. Hematologic toxicities included hypertriglyceridemia in 62%, anemia in 23%, and neutropenia in 23%. Partial response to therapy was observed in 4/24 (17%) evaluable patients, occurring after 12, 20, 24, and 28 weeks of therapy, and lasting 4-24 weeks. Three responders had baseline CD4 lymphocyte counts < 200/mm3. Three additional patients experienced reduction in measured indicator lesions of greater than 25% but less than 50%, and seven patients experienced disease stabilization of 16 weeks or greater. In evaluable patients, the median time to disease progression was 22 weeks and the overall median survival in all patients was 27.3 months. No significant changes in CD4 lymphocyte counts, p24 antigen, and beta 2 microglobulin were observed over time. However, a statistically significant increase was observed in soluble IL-2 receptor levels while on tRA (p = 0.037). We conclude that tRA has activity in patients with mucocutaneous AIDS-related Kaposi's sarcoma with acceptable toxicity. tRA has immunological effects without upregulation of HIV parameters. Additional studies in combinations or with more active retinoids are warranted.
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PMID:All-trans retinoic acid for the treatment of AIDS-related Kaposi's sarcoma: results of a pilot phase II study. 780 21

Acute hypergranular promyelocytic leukemia (AML M3) belongs to malignant diseases leading very rapidly to death. Immediate treatment based on early diagnosis may cure one third of patients. The typical finding in peripheral blood of patients is pancytopenia with or without atypical promyelocytes. In published studies only 15-25% patients exhibit leukocyte counts above 10 x 10(9)/l. Five of our ten patients studied had leukocyte count above 10 x 10(9)/l. The difference might be in connection with late and slow diagnosis of AML M3. AML is not taken into consideration during medical examination even if the disease occurs in medical family. Thus we describe clinical signs of AML M3 that could be divided into three main groups: bleeding, infections and anemia. In patients with bleeding or anemia or with infections repeating within a short period or with an infection and concurrent signs of bleeding or anemia the complete blood cell count should be examined immediately. If blood cell count abnormalities are found the patient should be sent immediately to hematology unit for further examination and treatment. Early diagnosis enables to start "differentiation therapy" with all-trans retinoic acid that could be administered as monotherapy only in patients with leukocytes below 5 x 10(9)/l. Early diagnosis of AML M3 might ameliorate the fate of patients, since four of our five patients referred to us with elevated leukocyte counts expired in the first five days.
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PMID:[Late and slow diagnosis of acute promyelocytic leukemias--the main cause of early death]. 781 84

Considering the beneficial effect of all-trans retinoic acid (ATRA) in acute promyelocytic leukemia (APL), it has been speculated that ATRA might also be useful for treating other hematologic malignancies. To test this hypothesis, we performed a dose-escalating 3-month-trial of ATRA in 15 patients with primary or secondary myelodysplastic syndromes (MDS). Morphologic diagnoses were refractory anemia (RA) in 4, RA with ring sideroblasts (RARS) in 2, RA with excess blasts (RAEB) in 7, and RAEB in transformation (RAEB/T) in 2 cases. Patients included were required to have one or more of the following criteria: transfusion-dependent anemia, pronounced neutropenia (< or = 0.5 x 10(9)/L) or thrombocytopenia (< or = 20 x 10(9)/L), or increasing blast cells in the peripheral blood or bone marrow. Therapy was started at an ATRA dose of 30 mg/m2/d, administered orally as two doses of 15 mg/m2 every 12 hours. The retinoid dose was increased to 60 mg/m2/d after 4 weeks and to 90 mg/m2/d after 8 weeks. Among 14 patients assessable for response, none obtained a complete or partial remission. Three patients had a minor response, manifested by either reduction in transfusion requirements (2 patients) or increase in neutrophil and platelet counts (1 patient). During the study period, 5 patients progressed to more advanced stages of MDS or overt leukemia. Three patients with chromosomal abnormalities receiving ATRA for a period of 10 to 12 weeks retained their cytogenetic marker after completion of treatment. Side effects of ATRA primarily affected the skin and mucous membranes, with 13 of 15 patients having at least low-grade dermatologic toxicity. In 2 cases, treatment had to be prematurely stopped because of intolerable conjunctivitis or progressive neurologic symptoms. These data suggest that ATRA has little effect on MDS. The lack of response of MDS patients, as compared with those with APL, may be attributed to the absence of the t(15;17) translocation that seems to be a prerequisite for clinical efficacy of ATRA.
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PMID:All-trans retinoic acid in patients with myelodysplastic syndromes: results of a pilot study. 821 88

The membrane expression of CD45RA and CD45RO on fresh leukaemic cells taken from 529 cases of acute haemopoietic malignancies, including 117 B-origin acute lymphoblastic leukaemia (B-origin ALL), 37 T-origin acute lymphoblastic leukaemia (T-origin ALL0, 297 de novo acute myeloid leukaemia (AML), 42 refractory anaemia with excess of blasts in transformation (RAEB-T) and 36 myeloid blastic phase of chronic myelogenous leukaemia (CML-BP-my), was analysed. B-origin ALLs were characterized by the lack of the RO isoform along with the consistent presence of RA. Conversely, a differential expression of the two isoforms was detected in different subsets of T-origin ALL, in that T-stem cell leukaemias (T-SCL: CD7+, CD4-, CD8-, CD1-) preferentially expressed CD45RA whereas conventional T-acute lymphoblastic leukaemias (T-ALL: CD7+, CD4+ and/or CD8+ and/or CD1+) were consistently marked by CD45RO. Within myeloid malignancies, most of AMLs displayed CD45RA, while a substantial group of CML-BP-my preferentially exhibited CD45RO. As a general rule, a reciprocal exclusion of the two isoforms was observed in AML as well as in ALL. Nevertheless, a frequent coexpression of CD45RA and CD45RO was observed in CD14+ AML. In vitro treatment with all-trans retinoic acid (ATRA) was able to promote a switch from CD45RA to CD45RO expression in 27 de novo AML, independently from morphological subtyping. To our knowledge, this is the first report on CD45 isoform expression in a large series of patients with acute leukaemia. The knowledge of the differential expression of CD45RA and CD45RO can ameliorate our classificative approach to haematological malignancies, as well as disclose new multiple overlap points between normal and leukaemic cell differentiation.
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PMID:Expression of the leucocyte common antigen (LCA, CD45) isoforms RA and RO in acute haematological malignancies: possible relevance in the definition of new overlap points between normal and leukaemic haemopoiesis. 854 36

Investigating 208 patients with acute haematological malignancies, we found that stem cell factor receptor (SCFR) was expressed on high numbers of blast cells from the vast majority of patients (93%) with refractory anaemia with excess of blasts in transformation. SCFR was also detected in 62% of AMLs, in which it was directly associated to the expression of CD7, interleukin 6 receptor and CD34, and inversely to that of CD11b and CD14. SCFR-positive cases were preferentially represented in AML-M1 (70%) and in AML-M2 (83%) subsets, whereas only 45% of the remaining samples (M3-M4-M5) exhibited SCFR positively. Interestingly, 50% of cases with acute promyelocytic leukaemia expressed SCFR and this molecule was heterogenously regulated by in vitro treatment with all-trans retinoic acid.
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PMID:Stem cell factor receptor (c-kit, CD117) is expressed on blast cells from most immature types of acute myeloid mallignancies but is also a characteristic of a subset of acute promyelocytic leukaemia. 861 17

A 21-year-old Japanese woman was referred to our hospital because of severe anemia and thrombocytopenia. Bone marrow aspiration showed a hypercellular marrow with 91.5% promyelocytes. Cytochemical study and surface marker a diagnosis of acute promyelocytic leukemia. Because leukocyte count elevated, she was treated with all-trans retinoic acid (ATRA) after conventional chemotherapy. After 11 days of ATRA therapy, the patient started to develop severe headache, nausea and diplopia. Ophthalmologic examination revealed bilateral papilledema. Computed tomography and magnetic resonance imaging of the head showed no intracranial lesion. ATRA was discontinued because it was suspected to cause intracranial hypertension. Her symptoms were relieved and patilledema improved gradually. ATRA is safe and well-tolerated, if the retinoic acid syndrome can be prevented or managed. As the tolerable dose of ATRA in adults is higher than that in children, the side effects tend to occur in children. In Japan, only two childhood cases of intracranial hypertension during ATRA therapy have been reported. We must remember the possibility of intracranial hypertension during ATRA therapy, even in adults.
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PMID:[Intracranial hypertension in a patient with acute promyelocytic leukemia treated with all-trans retinoic acid]. 902 61


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