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)

Renal cell cancer is resistant to most forms of therapy. Cytokine therapy with either interleukin-2 or interferon-alpha yields the best results, with response rates from 10% to 20%. Therapy is not without toxicity, which means that the majority of patients treated with cytokines suffer toxicity without any therapeutic benefit. Recent endeavors have tried to find new ways to identify responders to cytokine therapy. Prognostic factors, such as good performance status, lack of anemia, normal calcium, normal lactate dehydrogenase, and prior nephrectomy, correlate with an increased likelihood of responding to cytokine therapy. Recent studies have examined whether altered subpopulations of lymphocytes, the presence of eosinophils, or altered levels of cytokines can predict response to cytokine therapy. Although prior nephrectomy does correlate with improved survival while the patient is receiving cytokine therapy, it is unclear if this is due to a significant alteration in the tumor's response to cytokine or some unrelated benefit from surgery. Further studies are needed to confirm the current immune parameters and disease characteristics that suggest a better response to cytokine therapy.
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PMID:Prognostic factors for biologic therapy in kidney cancer. 1208 17

Interleukin-2 (IL-2) therapy is associated with serious toxic effects on the cardiopulmonary system. Less frequent toxicity is described in liver and the gastrointestinal system. A case of severe liver toxicity is described in a patient who underwent long-term immunotherapy with IL-2 (4.5 MU/m(2) s.c. daily, 5 days per week for 6 weeks, with 4 weeks of interval) plus interferon-alpha (IFN-alpha) (3 MU s.c. t.i.w., also covering the intervals between IL-2 cycles) for a metastatic renal carcinoma. A review of the literature is provided. The patient tolerated well the immunotherapy scheduled with apparently only a World Health Organization (WHO) G3 anemia and a G2 asthenia and is still alive, with a disease-free survival of 28 months. Notwithstanding a complete absence of liver function test abnormality during all scheduled clinical controls, the patient developed portal hypertension due to liver cirrhosis, which was histologically demonstrated. All common etiologic viral and toxic agents were ruled out. Long-term IL-2 therapy can induce liver cirrhosis. The appearance of liver and spleen enlargement during IL-2 therapy can be considered an indicator of liver damage. Thus, in this setting, closer monitoring is warranted despite normal liver function tests.
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PMID:Liver cirrhosis after prolonged therapy with IFN-alpha plus interleukin-2 in a metastatic renal cancer long-term survivor. 1216 79

The effects of interleukin-2 (IL-2) deficiency on hematopoiesis were tested by measuring cellular compositions in peripheral blood, spleen, thymus, and bone marrow of 3- to 5-month-old gene-targeted Il2 null (Il2(-/-)) mice using the Advia 120 Hematology system and fluorescence-activated cell staining (FACS). Il2(-/-) mice developed hematological failure and autoimmune responses, showing variable but significant degrees of anemia, lymphocytopenia, thrombocytopenia, splenomegaly, thymus involution, and weight loss. Surprisingly, Il2(-/-) mice had normal numbers of bone marrow cells (BMCs) with increased numbers of Lin(-)Kit(+)Sca1(+)CD34(-) and Lin(-)Kit(+)Sca1(+)CD34(+) cells that are normally associated with hematopoietic stem cells (HSCs) and progenitor cells. Day-12 colony-forming units-spleen cells were slightly reduced in Il2(-/-) mice. When Il2(-/-) and Il2(+/+) mice were compared for long-term HSC function in vivo in the competitive repopulation assay, BMCs from Il2(-/-) donors had 10- to 20-fold less HSC repopulating ability, which affected both myeloid and lymphoid cell lineages. Thus, HSCs from Il2(-/-) mice can proliferate normally but are functionally defective for reconstituting lethally irradiated recipients.
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PMID:Hematopoietic stem cell functional failure in interleukin-2-deficient mice. 1259 Jul 5

Patients with refractory advanced or metastatic urothelial carcinoma derive only minor benefit from chemotherapy. Based on evidence that urothelial carcinoma may be associated with impaired immunological reactivity, we conducted a phase II trial of interleukin-2 (IL-2), a biologic response modifier, to assess its efficacy and toxicity in treating refractory advanced or metastatic urothelial carcinoma. Seventeen patients with urothelial carcinoma who had undergone no more than 1 cisplatin-containing chemotherapy regimen were treated with IL-2 at a dose of 3 x 10(6) IU/m(2)/day by continuous intravenous infusion for 4 consecutive days each week for 4 weeks. Cycles were to be repeated every 6 weeks until disease progression. Toxic effects could be assessed in all 17 patients and response in 13. The most common grade III and IV toxic effects included hypotension (13/17); anemia (6/17); thrombocytopenia (4/17); granulocytopenia (3/17); and, in 1 patient each, cardiac ischemia, bowel perforation, and an increase in creatinine level. One sudden death was assumed to be treatment related. Although we found no objective antitumor activity for IL-2, median patient survival was 10.5 months (95% confidence interval, 5.8 to 17.1 months), with a 15.9-month median survival for 3 patients with poor performance status and visceral metastases. Further clinical investigation of the biological effect of IL-2 in urothelial carcinoma may be warranted.
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PMID:Treating refractory advanced or metastatic urothelial carcinoma with interleukin-2: a phase II study. 1268 23

In this phase 2 study, the authors assessed the hematologic and clinical toxicities of a melanoma peptide vaccine administered in conjunction with low-dose interleukin-2 (IL-2) therapy. Forty patients were randomized to receive a weekly vaccine paired with a regimen of subcutaneous IL-2 (3 x 10(6) IU/m2/day) administered daily for 6 weeks beginning either at week 1 or at week 4 of vaccine therapy. The differences in the time course of the IL-2 between the two groups permitted assessment of the cause of the toxicities, due either to IL-2 or to vaccine components. Both treatment regimens were well tolerated in the outpatient setting. Toxicities attributable to the vaccine components were principally limited to grade 1 injection site reactions. Systemic clinical toxicities correlated with the initiation of IL-2 therapy. These toxicities coincided temporally and in magnitude with changes in circulating eosinophil counts, suggesting that systemic clinical toxicities and eosinophilia may have common etiologic pathways. Other minor toxicities attributable to this low-dose IL-2 regimen were clinically insignificant hepatic toxicity, mild anemia, and mild thrombocytosis. The hematologic effects of this therapy were delayed in time between the two treatment groups, without dramatic differences in magnitude, which suggests minimal modulation of the IL-2 toxicity by components of the vaccine.
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PMID:Assessment of the toxicities of systemic low-dose interleukin-2 administered in conjunction with a melanoma peptide vaccine. 1531 46

Various toxicities have been observed during the treatment of advanced renal cell carcinoma with interferon-alpha (IFN-alpha) and/or interleukin-2 (IL-2). We report a case of severe anemia, which responded well to steroid therapy, in a patient receiving IL-2 plus IFN-alpha for metastatic renal cell carcinoma.
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PMID:Progressive anemia following combination therapy with interferon-alpha and interleukin-2 in a patient with metastatic renal cell carcinoma. 1547 99

Basiliximab is a chimeric anti-intcrleukin-2 receptor monoclonal antibody. Basiliximab is a glycoprotein produced by recombinant technology. It is used to prevent white blood cells from acute renal transplantation rejection. It specifically binds to and blocks the alpha chain of interleukin-2 receptors (IL-2R alpha), also known as CD25 antigen, on the surface of activated T-lymphocytes. Due to its monoclonal nature it provides safer and more predictable therapeutic, that is, immunosuppressive response of the polyclonal antibodies. The most common adverse effects in adult patients are constipation, infections, pain, nausea, peripheral oedema, hypertension, anaemia, headache, hyperkalacmia, hypercholesterolemia, increase in serum creatinine, and hypophosphataemia.
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PMID:Basiliximab, mechanism of action and pharmacological properties. 1564 37

Ulcerative colitis (UC) patients frequently require iron supplementation to remedy anemia. The impact of systemic iron supplementation (intraperitoneal injection) on UC-associated carcinogenesis was assessed in mice subjected to cyclic dextran sulfate sodium (DSS) treatment and compared with dietary iron enrichment. Systemic iron supplementation, but not a twofold iron diet, remedied iron deficiency as indicated by the histochemical detection of splenic iron stores. A twofold iron diet, but not systemic iron, increased iron accumulation in colonic luminal contents, at the colonic mucosal surface, and in superficial epithelial cells. Colitis-associated colorectal tumor incidence after 15 DSS cycles was not affected by systemic iron (2/28; 7.1%) compared to nonsupplemented controls (4/28; 14.1%) but was significantly increased by the twofold iron diet (24/33; 72.7%) (P < 0.001). Mechanistic study revealed that systemic iron had no effect on DSS-induced inflammation, or colonic iNOS and COX-2 protein levels, compared to controls. Systemic iron supplementation for 16 weeks replenished splenic iron in a spontaneous colitis model (interleukin-2-deficient mice) and significantly reduced colonic inflammation compared to interleukin-2 (-/-) controls without increasing hyperplastic lesions. These results suggest that iron supplemented systemically could be used to remedy anemia in UC patients without exacerbating inflammation or enhancing colon cancer risk. These findings need to be verified in clinical studies.
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PMID:Systemic iron supplementation replenishes iron stores without enhancing colon carcinogenesis in murine models of ulcerative colitis: comparison with iron-enriched diet. 1584 5

Immunochemotherapy consisting of interferon-alpha (IFN-alpha), interleukin-2 (IL-2), and gemcitabine (GEM) for metastatic renal cell carcinoma. A partial response maintained for 15 months, was obtained in one case resistant to IFN-alpha and IL-2 of para-aortic lymph node metastases (case 1). A minor response with 30% reduction of lung metastasis was obtained in one IFN-alpha resistant case, and the duration was 6 months (case 2). In one case, in contra-lateral renal metastasis, no disease progression was obtained for 6 months (case 3). One case with resistance to IFN-alpha and IL-2, and who had preoperative abnormalities of corrected serum calcium, serum c-reactive protein and hemoglobin, had progressive disease and died of cancer after 6 months (case 4). Grade 3 toxicity was noted in leucopenia (4/4), anemia (1/4), and nausea/ vomiting (1/4). Although the response duration was short, the combination immunochemotherapy consisting of IFN-alpha, IL-2 and GEM may be a promising salvage regimen for the patients with metastatic renal cell carcinoma.
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PMID:[Active combination immunochemotherapy with interferon-alpha, interleukin-2 and gemcitabine for four patients with metastatic renal cell carcinoma]. 1585 69

Juzen-taiho-to (TJ-48), a mixture of extracts from 10 medicinal herbs, has been used traditionally to treat patients with anemia, anorexia or fatigue. It is well known that the treatment of TJ-48 result in the decrease of patient's complaints, as well as the increase of NK cytolytic activity (NK activity) although its augmentation is not clear in the other kampo formula from the clinical viewpoint. To investigate its biological activities, such as the augmentation of NK activity, we analyzed the effects of TJ-48 on the expression of killer-cell immunoglobulin-like receptors (KIRs) in vitro experiment. The peripheral lymphocytes were incubated in medium alone, or medium containing TJ-48 or interleukin-2 (IL-2) plus TJ-48 at several concentrations for 48 h. After each incubation, cells were collected and their KIRs were detected by flow cytometry using monoclonal antibodies CD158a and CD158b. TJ-48 increased the populations of CD16+CD158a+ and CD16+CD158b+ cells in a dose-dependent manner. In contrast, CD16-CD158a/b+ cells did not increase. Additionally, the extract of TJ-48 enhanced the increase of KIRs expression induced by IL-2. These actions contribute to the augmentation of NK cytolytic activity by TJ-48, and might explain, in part, its antitumor effects which has been observed in vivo.
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PMID:The effect of Juzen-taiho-to/TJ-48 on the expression of killer-cell immunoglobulin-like receptors (CD158a/b) on peripheral lymphocytes in vitro experiment. 1595 65


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