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

Dacarbazine (DTIC) is a prodrug that is clinically effective in the treatment of Hodgkin's disease, melanoma and soft tissue sarcoma. To better characterize the clinical pharmacology of parent drug and reactive metabolites, a reversed-phase HPLC method with UV detection was developed for simultaneous determination of dacarbazine and the metabolites 5-(3-hydroxymethyl-3-methyl-1-triazeno)imidazole-4-carboxamide (HMMTIC) and 5-(3-methyl-1-triazeno)imidazole-4-carboxamide (MTIC). Chromatographic separation was achieved with a Zorbax SB-CN column and with a mobile phase of 80% 50 mM ammonium phosphate, pH 6.5, 20% methanol and 0.1% triethylamine. HMMTIC, MTIC and DTIC were extracted from plasma with methanol precipitation of the proteins. Recovery of DTIC and the metabolites from whole blood was greater than 92%. Rapid processing of whole blood, methanol extraction and storage at -70 degrees C substantially increased the stability of HMMTIC and MTIC from less than 15 min to 3 days. Precision for HMMTIC, MTIC and DTIC ranged from 3.7 to 16.3% relative standard deviation. The accuracy ranged from 101 to 114% for all three analytes. The validated assay was used to determine the pharmacokinetic data for dacarbazine and its active metabolites for human patients with recurrent glioma receiving DTIC intravenously.
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PMID:Validated high-performance liquid chromatographic assay for simultaneous determination of dacarbazine and the plasma metabolites 5-(3-hydroxymethyl-3-methyl-1-triazeno)imidazole-4-carboxamide and 5-(3-methyl-1-triazeno)imidazole-4-carboxamide. 1131 31

The pharmacokinetics of two etoposide (E) formulations were evaluated in patients with refractory hematologic malignancies receiving high-dose conditioning with autologous stem cell transplantation. Patients were randomized to either E at 800 mg/m(2) (containing polysorbate 80 and polyethylene glycol) or etoposide phosphate (EP) at 910 mg/m(2) on days -7 and -5, prior to melphalan, 80 mg/m(2) on day -5. On day -3, EP was repeated. Plasma E was analyzed after each formulation on days -7 and -5 to compare intrapatient pharmacokinetics. In total, 10 patients were treated: four each with multiple myeloma or Hodgkin's disease and two with non-Hodgkin's lymphoma. Mucositis was the major toxicity with seven patients. EP first produced grade 3 mucositis. There was no procedure-related mortality and eight patients remained alive 1 year post-transplant. Cumulative etoposide exposure (AUC) was slightly greater with EP (P=0.056). Conversely, the volume of distribution was slightly, 33%, larger (P=0.052) and clearance was increased with the E infusion (P=0.14). As none of the differences reached statistical significance, both E formulations appear to be pharmacokinetically equivalent in the high-dose transplant setting. The combination of high-dose EP with melphalan is an active preparative regimen prior to ABMT for hematologic malignancies.
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PMID:Comparative pharmacokinetic study of high-dose etoposide and etoposide phosphate in patients with lymphoid malignancy receiving autologous stem cell transplantation. 1269 3

Long-term survival of children with end-stage renal disease (ESRD) has increased in the last 20 years, but the mortality rate remains high. Cardiovascular disease accounts for 40 to 50% of all deaths, infectious disease for about 20%. A prolonged period of dialysis versus having a renal graft and persistent hypertension are mortality risk factors. The prevalence of the various morbidities is high among those who have reached adulthood. Nearly 50% of all these patients suffer from left ventricular hypertrophy and life-threatening vascular changes; nearly one third has clinical signs of metabolic bone disease. This accounts for both dialysis and transplant recipients. The chance of getting cancer is increased ten times compared to the general population; skin cancer and non-Hodgkin lymphomas are most commonly reported. A long period of dialysis at childhood is associated with impairment of both cognitive and educational attainment. However, despite all these negative outcomes, the health perception of young adults with childhood onset ESRD is positive. Research and therapy in children with ESRD should focus not only on prevention of graft failure, but also on prevention of co-morbidity, especially cardiovascular disease, life-threatening infections and malignancies. Early transplantation, more extended forms of frequent hemodialysis in those who can not be transplanted, a more rigorous treatment of hypertension, avoidance or at least dosage reduction of calcium-containing phosphate binders, reduction of the chronic inflammatory state, and tailor made anti-rejection therapy after transplantation may all be targets to improve the outcome in future patients.
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PMID:Long-term outcomes of children with end-stage renal disease. 1583 18

In an effort to improve the outcome of poor-risk lymphoma patients, we evaluated a novel regimen of tandem high-dose chemotherapy (THDC) with autologous stem cell transplantation. A total of 41 patients (median age 40 years, range 15-68 years) with poor-risk non-Hodgkin's lymphoma and Hodgkin's disease were enrolled. THDC consisted of melphalan (180 mg/m2) and escalating dose mitoxantrone (30-50 mg/m2) (MMt) for the first conditioning regimen, and thiotepa (500 mg/m2), carboplatin (800 mg/m2), and escalating dose etoposide phosphate (400-850 mg/m2), (ETCb) as the second regimen. In all, 31 patients (76%) completed both transplants, with a median time between transplants of 55 days (range 26-120). The maximum tolerated dose was determined as 40 mg/m2 for mitoxantrone and 550 mg/m2 for etoposide phosphate. The overall toxic death rate was 12%. Following high-dose chemotherapy, 10 of 24 evaluable patients (42%) were in CR. The two-year overall survival and event-free survival is 67% (95% CI, 52-81%) and 45%, (95% CI, 29-61%) for the 41 patients enrolled; and 69% (95% CI, 525-586%) and 48% (95% CI, 30-67%) for the 31 patients completing both transplants. This THDC regimen is feasible but with notable toxicity in heavily pretreated patients; its role in the current treatment of high-risk lymphoma remains to be determined.
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PMID:Pilot study of tandem high-dose chemotherapy and autologous stem cell transplantation with a novel combination of regimens in patients with poor risk lymphoma. 1604 39

Tumor lysis syndrome (TLS) is an important complication associated with hematological malignancies leading to increased morbidity and mortality. Metastatic calcification due to calcium phosphate crystals precipitated in soft tissues is rarely encountered in TLS. We describe a child with non-Hodgkin lymphoma who had gastric mucosal calcification related to severe hyperphosphatemia due to TLS. Upper-gastrointestinal endoscopic examination performed because of abdominal complaints revealed diffuse mucosal white lesions in mucosa of the gastric antrum and corpus. Pathological examination of the mucosa of the gastric corpus showed marked calcification in the lamina propria. We suggest that calcification in mucosa of the gastric corpus may be seen in patients with TLS. We also suggest that gastric mucosal calcifications should be considered in patients with hematological malignancies from TLS.
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PMID:Calcification of the gastric mucosa associated with tumor lysis syndrome in a child with non-Hodgkin lymphoma. 1677 82

Hypercalcemia is a frequent complication in chronic hemodialysis (CHD) patients. A rare cause of this condition is sarcoidosis, and has only been reported 6 times in CHD. Herein, we report on 3 cases of sarcoidosis-related hypercalcemia in CHD patients: an overt case, a probable case, and a recurrence of pre-dialysis sarcoidosis. Hypercalcemia is a frequent complication in chronic hemodialysis patients: it is often related to uncontrollable secondary hyperparathyroidism or to the inappropriate use of calcium phosphate binders, 1alpha-hydroxylated vitamin D metabolites, high dialysate calcium concentrations, or to aluminium-related bone disease [Uach and Bover 1996]. However, other rare causes should also be considered, such as multiple myeloma, non-Hodgkin lymphoma [Uach and Bover 1996], vitamin A intoxication [Fishbane et al. 1995], or granulomatous diseases such as sarcoidosis. The latter has only been described in a total of 6 hemodialysis patient reports [Barbour et al. 1981, Barnard et al. 2002, Herrero et al. 1998, Kalantar-Zadeh et al. 1994, Kuwae et al. 2003, Naito et al. 1999]. In the present paper, we report on 3 cases of sarcoidosis-related hypercalcemia in chronic hemodialysis patients with 3 different patterns, i.e. overt sarcoidosis, probable sarcoidosis, and recurrence of pre-dialysis sarcoidosis.
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PMID:Sarcoidosis-related hypercalcemia in 3 chronic hemodialysis patients. 1679 43

The possibilities to preserve fertility in women exposed to chemotherapy are: in vitro fertilization plus embryo cryopreservation, ovarian cryopreservation, unfertilized ova cryopreservation, and the administration of a gonadotropin-releasing hormone (GnRH) agonist. Because none of these methods is ideal, combination of several methods should be considered. Because the chances of preserving gonadal function following combined-modality treatment are significantly better for girls than for boys, simulation of a prepubertal milieu was applied only to women of reproductive age. The administration of GnRH agonists to women with Hodgkin's disease, breast cancer, and other malignancies, or to patients with lupus nephropathy, in parallel with chemotherapy, by others and by us, has demonstrated a significantly lower rate of premature ovarian failure in survivors than in nonrandomized controls. Several prospective, randomized studies are ongoing. A recent meta-analysis found that the administration of a GnRH agonist, in addition to chemotherapy, to patients with breast cancer was associated with less recurrence and superior survival. Several possibilities to explain the beneficial effect of GnRH agonists to minimize chemotherapy-associated gonadotoxicity are suggested: (a) The hypogonadotropic milieu decreases the number of primordial follicles entering the differentiation stage, which is more vulnerable to chemotherapy; (b) The hypoestrogenic state decreases ovarian perfusion and delivery of chemotherapy to the ovaries; (c) A direct effect of the GnRH agonist on the ovary occurs independently of the gonadotropin level; (d) GnRH agonists may upregulate an intragonadal antiapoptotic molecule such as sphingosine-1-phosphate; (e) The GnRH agonist may protect ovarian germline stem cells.
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PMID:How to preserve fertility in young women exposed to chemotherapy? The role of GnRH agonist cotreatment in addition to cryopreservation of embrya, oocytes, or ovaries. 1791 76

Sphingolipids serve an important role as effector molecules in signaling pathways bearing on apoptosis and cell survival. The balance between proapoptotic ceramide and prosurvival sphingosine-1-phosphate, sometimes termed the "sphingolipid rheostat," has received particular attention. Less well studied is the role of the follicular lymphoma variant translocation 1 (FVT1) gene, which was identified through its involvement in an atypical follicular lymphoma translocation and which encodes an enzyme in the synthetic pathway of ceramide. We investigated the expression of FVT1 in a variety of B-cell non-Hodgkin lymphomas and found that FVT1 is significantly underexpressed by germinal center-type diffuse large B-cell lymphoma (DLBCL) when compared with non-germinal center-type DLBCL, follicular lymphoma, and normal tonsil control samples. Increased expression of FVT1 correlated with decreased survival, suggesting that changes in the expression of FVT1 and in the concentrations of bioactive sphingolipids may be important in the pathogenesis and treatment of some types of DLBCL.
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PMID:Expression of the follicular lymphoma variant translocation 1 gene in diffuse large B-cell lymphoma correlates with subtype and clinical outcome. 1901 74

Calcinosis of the cutis and the subcutis is a rare complication of calcium-containing heparin cutaneous injections, mostly occurring in a context of severe renal failure. We report 2 cases. The first patient developed firm erythematous nodules on his thighs and right arm, in a context of disseminated tuberculosis and acute severe renal failure related to human immunodeficiency virus nephropathy. Cutaneous location of tuberculosis was suspected. Histological features allowed to establish the diagnosis of calcinosis of the cutis and the subcutis, showing violaceous and crackled von Kossa-positive calcium deposits in the whole reticular dermis and in thin collagenous septa of subcutaneous tissue. A retrospective inquiry confirmed that subcutaneous injections of calcium-containing heparin had been performed on the sites where lesions occurred. The second patient developed similar lesions at injection sites of calcium-containing heparin, in a context of non-Hodgkin lymphoma and end-stage renal failure. Similar histological features were observed. Calcinosis of the cutis and the subcutis after subcutaneous injections of calcium-containing heparin is rare. It always occurs in a context of elevated calcium-phosphate product, a situation mostly encountered in severe renal failure. Early cutaneous lesions do not bear specific clinical features.
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PMID:Calcinosis cutis: a rare reaction to subcutaneous injections of calcium-containing heparin in patients with renal failure. 1985 Oct 86

The expression of beclin-1, an oncosuppressor monoallelically deleted in >60% epithelial cancers, has been shown to be developmentally regulated in T and B lymphocytes. By interacting with either bcl-2 or class III phosphatidyl-inositol-3-phosphate kinase, beclin-1 regulates apoptosis and autophagy, two processes crucial for lymphatic tissue homeostasis. We analyzed the potential link between beclin-1-mediated autophagy and the malignant behaviour of lymphomas. The tissue expression of beclin-1 was analyzed in a large series of non-Hodgkin lymphomas and correlated with patient's clinical outcome. By immunofluorescence, beclin-1 staining showed faintly detectable and diffusely distributed in the cytoplasm (regarded as negative) or confined to the perinuclear region as large and brilliant puncta suggestive of macro-aggregate reactivity (regarded as positive). The positive expression of beclin-1 well correlated with the presence of LC3-positive autophagic vacuoles and was inversely correlated with the expression of bcl-2. Non-Hodgkin lymphomas in which > or =20% of tumour cells expressed high level of beclin-1 aggregates were associated with a complete (57%) or partial (35%) remission. The 5-year overall survival probability, calculated by the Kaplan-Meier method, was 92% and 42% in beclin-1-expressing non-Hodgkin lymphomas with > or =20% and <20% positive cells, respectively (log-rank test, P<0.000.1). In Cox multivariate analysis, the level of beclin-1 expression, adjusted for patient's age and pathologic stage, revealed to be significantly correlated with patient's survival (P<0.0001). This is the first demonstration of the involvement of beclin-1 and autophagy in the clinical behaviour of non-Hodgkin lymphomas. The present data are compatible with the hypothesis that non-Hodgkin lymphomas with upregulated autophagy are more responsive to chemotherapy and indicate that beclin-1 could be a valuable independent prognostic factor in this heterogeneous group of tumours.
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PMID:Autophagy-active beclin-1 correlates with favourable clinical outcome in non-Hodgkin lymphomas. 2047 82


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