Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Osiris Therapeutics is developing the donor-derived mesenchymal stem cell (MSC) therapy OTI-010, which repopulates the bone marrow stroma and thus supports engraftment of hematopoietic stem cells from the same donor. This stem cell therapy, which has been awarded Orphan Drug status, is currently in development for the potential enhancement of bone marrow transplants in cancer patients, for the prevention of graft versus host disease (GVHD), and for the treatment of Crohn's disease. Japanese licensee JCR Pharmaceuticals is investigating the therapy for the potential treatment of GVHD in patients undergoing bone marrow transplantation to treat leukemia. Phase II clinical trials in acute gastrointestinal GVHD and in adult and pediatric patients with treatment-refractory severe GVHD are currently underway.
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PMID:OTI-010 Osiris Therapeutics/JCR Pharmaceuticals. 1672 25

A small number of cases of Crohn disease associated with myelodysplastic syndromes or leukemia have been reported in adults in the last 25 years in the English-language medical literature. The authors report a case of a 9-year-old boy who developed Crohn disease and myelodysplastic syndrome concurrently. Analysis of his bone marrow showed a chromosome 20 abnormality. Although chromosome 20 abnormalities have been reported in a minority of these patients, the significance of this association remains unclear at the present time.
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PMID:Concurrent development of Crohn disease and myelodysplastic syndrome in a child: case report and literature review. 1684 78

Several forms of primary and secondary hematological malignancies were rarely observed during the clinical course of inflammatory bowel diseases (IBD). Patients needing a prolonged treatment with immunosuppressants, such as azathioprine or methotrexate, with familiarity and genetic predisposition seem to be at a higher risk of leukemia. On the other hand, asthenia, thickness, and fever may be the symptoms of the onset of each kind of hematological malignancy. The finding of anemia, alteration of leukocyte count and large undetermined cells may suggest increased probability of abnormal proliferation of a single white blood cell line. In this report, the occurrence of hematological malignancies is described in five patients affected by IBD (three with ulcerative colitis and two with Crohn's disease) attending our Gastroenterology Unit.
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PMID:Hematological malignancies in chronic inflammatory bowel diseases: report of five cases and review of the literature. 1702 96

The term PEGylation describes the modification of biological molecules by covalent conjugation with polyethylene glycol (PEG), a non-toxic, non-immunogenic polymer, and is used as a strategy to overcome disadvantages associated with some biopharmaceuticals. PEGylation changes the physical and chemical properties of the biomedical molecule, such as its conformation, electrostatic binding, and hydrophobicity, and results in an improvement in the pharmacokinetic behavior of the drug. In general, PEGylation improves drug solubility and decreases immunogenicity. PEGylation also increases drug stability and the retention time of the conjugates in blood, and reduces proteolysis and renal excretion, thereby allowing a reduced dosing frequency. In order to benefit from these favorable pharmacokinetic consequences, a variety of therapeutic proteins, peptides, and antibody fragments, as well as small molecule drugs, have been PEGylated. This paper reviews the chemical procedures and the conditions that have been used thus far to achieve PEGylation of biomedical molecules. It also discusses the importance of structure and size of PEGs, as well as the behavior of linear and branched PEGs. A number of properties of the PEG polymer--e.g. mass, number of linking chains, the molecular site of PEG attachment--have been shown to affect the biological activity and bioavailability of the PEGylated product. Releasable PEGs have been designed to slowly release the native protein from the conjugates into the blood, aiming at avoiding any loss of efficacy that may occur with stable covalent PEGylation. Since the first PEGylated drug was developed in the 1970s, PEGylation of therapeutic proteins has significantly improved the treatment of several chronic diseases, including hepatitis C, leukemia, severe combined immunodeficiency disease, rheumatoid arthritis, and Crohn disease. The most important PEGylated drugs, including pegademase bovine, pegaspargase, pegfilgrastim, interferons, pegvisomant, pegaptanib, certolizumab pegol, and some of the PEGylated products presently in an advanced stage of development, such as PEG-uricase and PEGylated hemoglobin, are reviewed. The adaptations and applications of PEGylation will undoubtedly prove useful for the treatment of many previously difficult-to-treat conditions.
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PMID:The impact of PEGylation on biological therapies. 1877 13

Acute tumour lysis syndrome (TLS) is a catastrophic complication of the treatment of certain neoplastic disorders. It most commonly occurs in association with hematologic malignancies and appears a few hours to a few days after initiation of specific chemotherapy, as the result from the release of intracellular components into the bloodstream due to abrupt malignant cell death. Acute spontaneous TLS is rare, and it has been described in leukemia and lymphoma and in some patients with solid tumors prior to institution of therapy. The syndrome is characterized by hyperuricemia, hyperphosphatemia, hypocalcemia, hyperkalemia, and acute oliguric or anuric renal failure due to uric acid precipitation within the tubules (acute uric acid nephropathy) and to calcium phosphate deposition in the renal parenchyma and vessels.We report a case of acute spontaneous TLS in a patient with Crohn s disease treated with immunosuppressive drugs, who developed a plasmocytoma, in which serum uric acid concentration attained exceptionally high levels (44 mg/dL). The patient underwent acute oliguric renal failure, which required treatment with hyperhydration, urine alkalinization, urate oxidase and hemodialysis, with a fatal evolution.In conclusion, the present case report has several peculiarities: that of being one of the rare examples of spontaneous TLS, that of showing an exceptionally severe hyperuricemia, probably the highest ever reported in the literature, and that of the possible increased risk of tumours in patients with Crohn s disease taking inmunosuppressives and/or TNF antagonists.
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PMID:Acute spontaneous tumor lysis syndrome in a patient with Crohn's disease taking immunosuppressants. 1949 6

Crystalline keratopathy can be successfully treated by the Nd:YAG laser. We present two cases of crystalline keratopathy managed this way. A 36-year-old female contact lens wearer presented with crystalline keratopathy following recent treatment with topical steroids and antibiotics for a corneal abscess. In this case crystalline keratopathy developed despite the intensive topical antibiotic treatment. A 55-year-old man with a history of acne rosacea, chronic myelomonocytic leukaemia, asthma and Crohn's disease presented with crystalline keratopathy following an episode of infectious keratitis. Treatment with the Nd:YAG laser to the area of involvement was instituted in both cases. Noticeable resolution occurred within days, with subsequent full recovery. No side-effects from the use of the Nd:YAG laser were noted. There have been only two cases previously reported using this treatment modality.
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PMID:Laser corneal biofilm disruption for infectious crystalline keratopathy. 1972 25

The human body is made of some 250 different cell types. From them, only a small subset of cell types is able to produce histamine. They include some neurons, enterochromaffin-like cells, gastrin-containing cells, mast cells, basophils, and monocytes/macrophages, among others. In spite of the reduced number of these histamine-producing cell types, they are involved in very different physiological processes. Their deregulation is related with many highly prevalent, as well as emergent and rare diseases, mainly those described as inflammation-dependent pathologies, including mastocytosis, basophilic leukemia, gastric ulcer, Crohn disease, and other inflammatory bowel diseases. Furthermore, oncogenic transformation switches some non-histamine-producing cells to a histamine producing phenotype. This is the case of melanoma, small cell lung carcinoma, and several types of neuroendocrine tumors. The bioactive compound epigallocatechin-3-gallate (EGCG), a major component of green tea, has been shown to target histamine-producing cells producing great alterations in their behavior, with relevant effects on their proliferative potential, as well as their adhesion, migration, and invasion potentials. In fact, EGCG has been shown to have potent anti-inflammatory, anti-tumoral, and anti-angiogenic effects and to be a potent inhibitor of the histamine-producing enzyme, histidine decarboxylase. Herein, we review the many specific effects of EGCG on concrete molecular targets of histamine-producing cells and discuss the relevance of these data to support the potential therapeutic interest of this compound to treat inflammation-dependent diseases.
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PMID:Targeting of histamine producing cells by EGCG: a green dart against inflammation? 2065 70

The term 'autoimmune diseases' encompasses a spectrum of diseases whose clinical manifestations and, possibly, biological features vary widely. The results of conventional treatment are considered unsatisfactory in aggressive forms, with subsets of patients having short life expectancies. Relying on wide experimental evidence and more feeble clinical data, some research groups have used autologous hematopoietic stem cell transplantation (HSCT) in the most disabling autoimmune diseases with the aim of resetting the patient's immune system. Immunoablative conditioning regimens are preferred over their myeloablative counterparts, and some form of in vivo and/or ex vivo T-cell depletion is generally adopted. Despite 15 years' experience, published controlled clinical trials are still lacking, with the evidence so far available coming from pilot studies and registry surveys. In multiple sclerosis, clinical improvement, or at least lasting disease stabilization, can be achieved in the majority of the patients; nevertheless, the worst results are observed in patients with progressive disease, where no benefit can be expected from conventional therapy. Concerning rheumatologic diseases, wide experience has been acquired in systemic sclerosis, with long-term improvements in cutaneous disease being frequently reported, although visceral involvement remains unchanged at best. Autografting has proved to be barely effective in rheumatoid arthritis and quite toxic in juvenile idiopathic arthritis, whereas it leads to clinical remission and the reversal of visceral impairment in the majority of patients with systemic lupus erythematosus. A promising indication is Crohn's disease, in which long-term endoscopic remission is frequently observed. Growing experience with autologous HCST in autoimmune diseases has progressively reduced concerns about transplant-related mortality and secondary myelodysplasia/leukemia. Therefore, a sustained complete remission seems to be within the reach of autografting in some autoimmune diseases; in others, the indications, risks and benefits of autografting need to be better defined. Consequently, the search for new drugs should also be encouraged.
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PMID:Autologous hematopoietic stem cell transplantation in autoimmune diseases. 2108 59

Careful examination of the oral cavity may reveal findings indicative of an underlying systemic condition, and allow for early diagnosis and treatment. Examination should include evaluation for mucosal changes, periodontal inflammation and bleeding, and general condition of the teeth. Oral findings of anemia may include mucosal pallor, atrophic glossitis, and candidiasis. Oral ulceration may be found in patients with lupus erythematosus, pemphigus vulgaris, or Crohn disease. Additional oral manifestations of lupus erythematosus may include honeycomb plaques (silvery white, scarred plaques); raised keratotic plaques (verrucous lupus erythematosus); and nonspecific erythema, purpura, petechiae, and cheilitis. Additional oral findings in patients with Crohn disease may include diffuse mucosal swelling, cobblestone mucosa, and localized mucogingivitis. Diffuse melanin pigmentation may be an early manifestation of Addison disease. Severe periodontal inflammation or bleeding should prompt investigation of conditions such as diabetes mellitus, human immunodeficiency virus infection, thrombocytopenia, and leukemia. In patients with gastroesophageal reflux disease, bulimia, or anorexia, exposure of tooth enamel to acidic gastric contents may cause irreversible dental erosion. Severe erosion may require dental restorative treatment. In patients with pemphigus vulgaris, thrombocytopenia, or Crohn disease, oral changes may be the first sign of disease.
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PMID:Oral manifestations of systemic disease. 2112 23

Acute leukaemia (AL) has been observed in association with Crohn's disease (CD) notably in patients treated with azathioprine (AZA), which is an immunosuppressant known for its carcinogenicity and in particular known to induce therapy-related acute myeloid leukaemia according to the 2008 WHO classification. Whereas the link between inflammatory bowel disease and AL has been well established, the exact role of AZA remains controversial. In this paper, we report the case of a 71-year-old white Caucasian male with CD treated for 7 years with AZA who developed an acute leukaemia. Chemotherapy was administered unsuccessfully and the patient died from this haematological disorder 9 months after diagnosis. We reviewed the current evidence on the interactions between CD, AL and AZA as well as the potential underlying mechanisms of leukaemia in AZA-treated patients. From this review, we concluded that AL should be questioned when facing cytopenia in a patient with CD. The nature of the association between AZA and AL in CD patients warrants further investigation.
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PMID:A case of therapy-related myeloid neoplasm in a patient with Crohn's disease treated with azathioprine. 2300 30


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