Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0019829 (Hodgkin's disease)
 30,247 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

It has been reported that patients with Hodgkin's disease (HD) show altered porphyrin metabolism, and suggested that the cause is the neoplastic process itself. If this is true, disease progression should be associated with higher levels of porphyrin excretion. The aim of this study was to evaluate urinary coproporphyrin levels in patients with Hodgkin's disease at different stages. As many of the patients received chemotherapy, another aim was to verify experimentally whether chemotherapeutic agents might increase porphyrin levels in rabbits. All of the patients had above-normal urinary coproporphyrin levels. On the other hand, rabbits receiving the porphyrin precursor 5-aminolevulinic acid (5-ALA), and also treated with doxorubicin, showed very high plasma porphyrin levels. The increased levels of urinary coproporphyrins seem to be due to the disease itself, since the patients in stages III and IV had higher excretion values, presumably due to biochemical heme synthesis lesions that lead to the availability of the porphyrin precursor, as well as coproporphyrin accumulation and excretion. The altered porphyrin synthesis may be attributable to the cytotoxic oxygen species generated in the presence of NADH and iron. As the patients also received extensive chemotherapy regimes, the altered porphyrin metabolism may be affected by antineoplastic treatment generating oxygen reactive radicals. The alterations in porphyrin metabolism induced by chemotherapeutic agents appear to be demonstrated in rabbits in which doxorubicin increases porphyrin synthesis after porphyrin precursor treatment.
 ...
PMID:Increased urinary coproporphyrin excretion observed in patients with differently staged Hodgkin's disease treated with chemotherapy. 1566 80

The hereditary hemochromatosis (HHC) gene, HFE on chromosome 6p21.3, encodes a protein involved in iron homeostasis. HFE mutations have low penetrance with a mild effect on serum iron levels. Animal, twin, and population studies have shown that carrier state for C282Y can increase iron levels. A proportion of heterozygotes show slightly elevated serum iron levels. Increased serum iron has been suggested to increase the risk for oxidative damage to DNA. Epidemiologic studies established a correlation between iron levels and cancer risk. Case-control studies have reported associations between HFE mutations C282Y/H63D and several cancers, some of which in interaction with the transferrin receptor gene TFRC or dietary iron intake. Increased cancer risk in C282Y carriers is likely due to higher iron levels in a multifactorial setting. In childhood acute lymphoblastic leukemia (ALL), there is an association of C282Y with a gender effect in two British populations. No association has been found in acute myeloblastic leukemia and Hodgkin disease in adults. The childhood leukemia association possibly results from elevated intracellular iron in lymphoid cells increasing the vulnerability to DNA damage at a critical time window during lymphoid cell development. Interactions of HFE with environmental and genetic factors, most of which are recognized, may play a role in modification of susceptibility to leukemia conferred by C282Y. Given the population frequency of C282Y and the connection between iron and cancer, clarification of the mechanism of HFE associations in leukemia and cancer will have strong implications in public health.
 ...
PMID:HFE gene mutations in susceptibility to childhood leukemia: HuGE review. 1577 51

Rheumatoid arthritis is the commonest form of inflammatory arthritis and affects about 1-3% of the population in the West and even more in the developing world due to the compounded factors of late detection and inadequate treatment in the overall background of poverty, deprivation, and improper macro and micronutrients in the diet in a sizeable segment of the population. Nearly 90% of patients with aggressive disease will become clinically disabled within 20 years. Furthermore, in patients with severe disease or extra-articular symptoms, mortality is equal to that for patients with triple artery coronary artery disease or Stage IV Hodgkin's lymphoma. Anemia is a very common comorbidity of rheumatoid arthritis. Anemia in rheumatoid arthritis is caused by various factors, for instance, cytokine impact of the advanced arthritic process on the host, or lack of proper nutrition and essential micronutrients in the diet, or coexistent helminthiasis, and/or impact of antiarthritic drugs on the host system, i.e., high steroid induced gastritis or ulcerations in gastric mucosa or subclinical or clinical hepatitis due to methotrexate or salazopyrin effects on bone marrow, only to name a few. Other pre-existing or compounding gastrointestinal problems, which alter the available iron stores or cause bone marrow dysfunction, may also help in adding to an anemic condition. If the anemia is 8 g/dl or less, blood transfusion or erythropoietin injection with adequate hematinic reserve is effective in normal situations, but is not that effective in anemia with a chronic disease background like rheumatoid arthritis. Cord blood, because of its rich mix of fetal and adult hemoglobin, high platelet and white blood cell (WBC) counts, and a plasma filled with cytokine and growth factors, as well as its hypo antigenic nature and altered metabolic profile, has all the potential of a real and safe alternative to adult blood transfusion. Seventy-eight units (42 ml -136 ml mean 80.6 ml +/- 3.6 ml SD, median 82.4 ml, mean packed cell volume 48.2 +/- 2.1 SD, mean percent hemoglobin concentration 16.4 g/dl +/- 1.5 g/dl SD) of placental umbilical cord whole blood was transfused (from 1 April 1999 to April 2005) after lower uterine cesarean section (LUCS) from consenting mothers to 28 informed consenting patients with advanced rheumatoid arthritis who had plasma hemoglobin of 8 g/dl or less. After collection, the blood was immediately transfused following the standard adult blood transfusion protocol. Each case was passed through the institutional ethical committee. The patients received two to six units of freshly collected placental umbilical cord blood without encountering any clinical, immunological or non-immunological reactions. Three days after completion of the transfusion of placental umbilical cord blood, the peripheral blood hematopoietic stem cell (CD34) estimation revealed a rise from the pretransfusion base level (.09%), varying from 2.03 to 23%, which returned to base level in most of the cases at the three-month CD34 re-estimation, without provoking any clinical graft vs host reaction in any of the patients.
 ...
PMID:Placental umbilical cord whole blood transfusion to combat anemia in the background of advanced rheumatoid arthritis and emaciation and its potential role as immunoadjuvant therapy. 1676 35

The optimal treatment of primary central nervous system lymphoma (PCNSL), a rare form of extranodal non-Hodgkin lymphoma, has yet to be defined. Whole-brain radiation therapy (WBRT) has limited efficacy as a single therapeutic modality and is associated with a high risk of delayed neurotoxicity. Methotrexate-based chemotherapy regimens yield poor drug penetration across the blood-brain barrier (BBB), thus necessitating administration of high doses with the concomitant risk of increased systemic and neurological toxicity. Combined-modality therapy (WBRT plus chemotherapy) can improve response and survival rates, yet it is associated with a high risk of neurotoxicity. The aim of chemotherapy in conjunction with BBB disruption is to maximize drug delivery to the brain and improve the agent's efficacy, while preserving neurocognitive function and minimizing systemic toxicity. Methotrexate-based chemotherapy regimens administered in conjunction with BBB disruption have shown promising results in PCNSL. Animal models of central nervous system lymphoma and drug neurotoxicity offer new possibilities to study the effects of various treatments on PCNSL and normal brain and can also help understand biological and pathophysiological aspects of this disease. Because the intact BBB is even less permeable to antibodies than it is to drugs, preclinical and clinical studies of monoclonal antibody delivery (for example, rituximab and 90Y ibritumomab tiuxetan) to the brain in conjunction with BBB disruption offer a new possibility to make these novel treatments more efficient against PCNSL. Regarding the evaluation of more sensitive and specific diagnostic imaging tools, iron oxide-based contrast agents for magnetic resonance imaging have shown promise for better differentiation of PCNSL from other white matter diseases.
 ...
PMID:Implications of the blood-brain barrier in primary central nervous system lymphoma. 1713 13

The young age at onset of many cancers in childhood has led to investigations on maternal exposures during pregnancy. Data from a population-based case-control study in Germany (1992-1997) that included 1,867 cases and 2,057 controls was used to investigate this question. Maternal use of vitamin, folate or iron supplementation was associated with a reduced risk of non-Hodgkin lymphoma and tumors and, less clearly, with leukemia, but not with CNS tumors. An increased risk of neuroblastoma was associated most markedly with diuretics and other antihypertensives, but also with vitamin, folate or iron supplementation. No associations were seen with pain relievers, antinauseants or cold medications, nor with delivery by Caesarian section. The strengths of this study are its population base, the large number of cases and the inclusion of different case groups to identify disease specificity of associations. The limitation of this study is an exposure assessment relying on maternal self-reports. In conclusion, these data indicate a potential influence of some maternal medication during pregnancy on the risk of childhood cancer in the offspring; however, no clear picture is seen.
 ...
PMID:Medication use during pregnancy and the risk of childhood cancer in the offspring. 1734 98

The hematologic, histologic and morphologic bone marrow findings of 18 patients with human immunodeficiency virus (HIV) infection were reviewed. The mean age of the patients studied was 27 years; age range was six to 63 years. The main bone marrow morphologic finding was hypercellularity (72%), which was mainly due to megakaryocytic hyperplasia with or without granulocytic or erythrocytic hyperplasia. Naked (denuded) megakaryocytic nuclei, which are considered an indicator of HIV infection, were present in 72% of the bone marrows examined. Reticuloendothelial iron blockade was identified in 78% of cases. Other less frequent findings included erythrocytic dysplasia (44%), plasmacytosis (28%), nonspecific granulomas (17%), Hodgkin's and non-Hodgkin's lymphoma (17%), lymphocytic aggregates (11%) and histiocytosis (6%) . The bone marrow findings in this series of HIV patients appear to be similar to what has been previously reported from other countries.
 ...
PMID:Bone marrow morphologic findings in patients with human immunodeficiency virus (HIV) infection. 1737 95

Transferrin, the major iron binding protein in human plasma transports iron to various tissues. The first step in cellular iron uptake is binding of transferrin complex to the cell surface membrane by specific molecule known as transferrin receptors. Transferrin receptors are found in limited sites in normal tissues, in contrast, the receptors are widely distributed in majority of carcinomas and sarcomas. Presence of increased transferrin receptors implies a stage of moderate or less differentiation corresponding to elevated proliferative activity and therefore, has a prognostic value. Demonstration of transferrin receptors and its distribution pattern within a tumour as well as its quantitative determination can provide data helpful for, both, an additional understanding of tumour biology and as an approach for planning therapy. In present study, we analysed 60 cases, 30 each of reactive lymphadenitis and lymphomas for transferrin receptors using immunohistochemical technique (DAKO, Code-K0673). Grade II and Grade III intensity was recorded in the germinal centers and the histiocytes in sinus histocytosis indicating the proliferating cells and activated histocytes. Most of the low grade non-Hodgkin lymphomas (83.66%) showed weak (Grade I) positivity for transferrin receptors. Intermediate grade lymphomas showed moderate (Grade II) to high intensity (Grade III) for transferrin receptors (57.14% and 42.85%) respectively. Seventy five percent of high grade lymphomas showed strong (Grade III) positivity. All the 9 cases of Hodgkin lymphoma (100%) showed grade III positivity. Proportion of the cells within a tumour expressing transferrin receptors in high density are therefore likely to represent the growth fraction of the tumour.
 ...
PMID:Transferrin receptor expression in reactive and neoplastic lesions of lymphnodes. 1788 2

Alveolar rhabdomyosarcoma (RMS) accounts for 20% to 30% of childhood RMS and is associated with a prognosis worse than embryonal RMS. Disseminated RMS can present with extensive bone marrow involvement. Assessing the extent of the tumor is critical, because therapy and prognosis depend on the degree to which the mass has spread beyond the primary site. The value of F-18 FDG PET in patients with RMS has been reported in some series but none specifically involving bone marrow. Children have a highly cellular hematopoietic bone marrow and differentiation of a highly cellular marrow from neoplastic infiltration may be difficult. Various other conditions associated with diffuse FDG uptake in the bone marrow include marrow hyperplasia resulting from hemolytic/iron-deficiency/blood-loss anemia, after chemotherapy with granulocyte/macrophage colony-stimulating factor and recombinant erythropoietin treatment, leukemia, non-Hodgkin lymphoma, and myelodysplasia. It is therefore important to consider the above differential diagnoses in mind when evaluating cases of unexpected marrow uptake in F-18 FDG PET studies. We report here a case of RMS with diffuse bone marrow involvement detected on F-18 FDG PET wherein FDG PET was useful in determining the true extent (primary and metastases) of RMS before definitive therapy and the valuable adjunct role it has with structural imaging in management.
 ...
PMID:Rhabdomyosarcoma with widespread bone marrow infiltration: beneficial management role of F-18 FDG PET. 1788 59

Bendamustine was first synthesized in the early 1960s at the Institute for Microbiology and Experimental Therapy in Jena, East Germany by Ozegowski and Krebs. The molecule, originally termed IMET 3393 (4-[5-(bis[2-chloroethyl]amino)-1-methyl-2-benzimidazolyl] butyric acid), was intended to be a "bi-functional" molecule with alkylator and antimetabolite properties. Extensive studies were conducted using this compound over a 20-year period in East Germany, and it became a highly used chemotherapeutic agent in the eastern block before the fall of the Iron Curtain. After its licensing in Europe in the mid 1990s, more than 18,000 patients were studied using this compound, principally in Germany. Over the past decade, significant interest has been generated as a result of ongoing studies that have demonstrated the unique antitumor properties of this compound as a single agent and in different combinations. This article provides a review of studies using bendamustine in the treatment of non-Hodgkin lymphomas.
 ...
PMID:Bendamustine in non-Hodgkin lymphoma: the double-agent that came from the Cold War. 1828 61

Predicting transfusion requirements relies both on epidemiology and therapeutic changes in hematology. The incidence rate of B-cell neoplasias especially non-Hodgkin lymphoma and myelodysplasia is increasing. Chemotherapy related myelodysplasia will reflect the improvement of solid tumor prognostic in the future. For myelodysplasias, therapeutic changes including oral iron chelators and more intensive transfusion policies will likely result in an increase of PRC requirements, a situation shared by sickle-cell disease.
 ...
PMID:[Evolution of transfusionnal requirements in hematology]. 1895 20


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>