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)

A 60-year-old woman presented to her primary care physician with fatigue and anemia. Laboratory evaluation revealed a hemoglobin level of 9.8 g/dL and an erythrocyte sedimentation rate (ESR) of 64 mm/hour. She subsequently developed nocturnal episodes of diaphoresis, confusion, and hypothermia. Capillary glucose measurements during the spells revealed hypoglycemia. During two supervised fasts, the patient's plasma glucose levels fell to 35 mg/dL and 32 mg/dL, respectively. Plasma insulin and C-peptide levels were appropriately suppressed, but a low concentration of beta-hydroxy-butyrate and normal increase of plasma glucose concentration after a glucagon injection suggested the presence of an insulin-like substance. Computed tomographic (CT) scan of the abdomen and subsequent positron emission tomographic (PET) scan revealed extensive lymphadenopathy. Biopsy of periaortic lymph nodes revealed Hodgkin's disease of the mixed cellularity type. Following chemotherapy, a complete remission ensued, the spells abated, and hypoglycemia was not induced by a 23-hour fast. We believe that the patient's Hodgkin's disease was producing an insulin-like substance. The observations of others suggest that this substance may be an autoantibody to the insulin receptor.
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PMID:Recurrent hypoglycemia and hypothermia in a patient with Hodgkin's disease. 1719 56

Cancer is a life-threatening condition. We describe the case of a 22-yr-old world-class endurance athlete who presented with mild local lymphadenopathy but without any systemic complaints or impaired performance. He was subsequently diagnosed with stage III A (S) Hodgkin's lymphoma. A complete physiological workup before the diagnosis revealed high aerobic capacity. Immediately after six courses of escalated BEACOPP chemotherapy in an identical test setting, aerobic capacity was markedly reduced (-42%), mainly because of a decrease in total hemoglobin mass (-37%), despite maintaining a certain amount of endurance training. Other potentially performance-limiting systems such as heart, lung, or aerobic metabolism did not show any signs of impairment. Two months after chemotherapy, the athlete had recovered his hemoglobin mass, and his aerobic performance was almost back to pretherapy levels. This case illustrates that advanced malignancies can be present in elite athletes without affecting performance, and that aerobic capacity can be regained within a short time after systemic chemotherapy.
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PMID:Hodgkin's Lymphoma in an elite endurance athlete. 1837 99

The aim of this study was to assess the efficacy of a gemcitabine-containing regimen in pretreated Hodgkin's lymphoma (HL) patients. Relapsed or refractory HL patients treated with gemcitabine, used alone or in combination with other cytotoxic agents, were retrospectively reviewed. Fifty-five patients were included in the study. Initial characteristics before gemcitabine administration were: Ann Arbor stage III-IV: 84%; International Prognostic Score less than 3 in 18/39 cases (46%); 31 primary refractory patients at the end of first-line therapy (56%); median number of previous chemotherapy regimens of 3. Twenty-nine patients received gemcitabine alone with a median maximal dose of 900 mg/m2 per injection (range: 300-1500 mg/m2). Gemcitabine was administered at a maximal dose of 1000 mg/m2 per injection (range: 650-1250) in combination with vinorelbine in 10 patients, oxaliplatin in 13 patients, and other drugs in three patients, with a median of six injections (range: 1-18). Reported toxicity was mainly hematologic. Overall response rate was 20% with 11% of complete remission. On univariate analysis, two adverse factors at progression were significant for response to gemcitabine-based regimen: stage III-IV disease and hemoglobin level was less than 10.5 g/dl. This study demonstrated the limited efficacy of gemcitabine-containing regimen in heavily pretreated HL patients.
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PMID:A multicenter study of gemcitabine-containing regimen in relapsed or refractory Hodgkin's lymphoma patients. 1851 Jan 78

Nitric oxide ((.)NO) induces apoptosis at high concentrations by S-nitrosating proteins such as glyceraldehyde-3-phosphate dehydrogenase. This literature analysis revealed that failure to sustain high (.)NO concentrations is common to all cancers. In cervical, gastric, colorectal, breast, and lung cancer, the cause of this failure is the inadequate expression of inducible nitric oxide synthase (iNOS), resulting from the inhibition of iNOS expression by TGF-beta1 at the mRNA level. In bladder, renal, and prostate cancer, the reason for the insufficient (.)NO levels is the depletion of arginine, resulting from arginase overexpression. Arginase competes with iNOS for arginine, catalyzing its hydrolysis to ornithine and urea. In gliomas and ovarian sarcomas, low (.)NO levels are caused by inhibition of iNOS by N-chlorotaurine, produced by infiltrating neutrophils. Stimulated neutrophils express myeloperoxidase, catalyzing H2O2 oxidation of Cl- to HOCl, which N-chlorinates taurine at its concentration of 19 mM in neutrophils. In squamous cell carcinomas of the skin, ovarian cancers, lymphomas, Hodgkin's disease, and breast cancers, low (.)NO concentrations arise from the inhibition of iNOS by N-bromotaurine, produced by eosinophil-peroxidase-expressing infiltrating eosinophils. Eosinophil peroxidase catalyzes the H2O2 oxidation of Br- to HOBr, which N-brominates taurine to N-bromotaurine at its concentration of 15 mM in eosinophils. In microvascularized tumors, the (.)NO concentration is further depleted; (.)NO is rapidly consumed by red blood cells (RBCs) through S-nitrosation of RBC glutathione and hemoglobin, and by oxidation to nitrate by RBC oxyhemoglobin. Angiogenesis-inhibiting antibodies are currently used to treat cancers; their mode of action is not, as previously thought, reduction of the tumor O2 or nutrient supply. They actually decrease the loss of (.)NO to RBCs.
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PMID:Apoptosis-inducing high (.)NO concentrations are not sustained either in nascent or in developed cancers. 1875 45

The treatment of B-cell non-Hodgkin lymphoma, the most common posttransplant lymphoproliferative disorder, is not well defined. Herein we have reported a case of gastric mucosa-associated lymphoid tissue (MALT) lymphoma with rapid, persistent, and complete remission after conversion of the immunosuppression from cyclosporine (CsA) to sirolimus (SRL). A 42-year-old woman underwent renal transplantation in 1992 with no major abnormalities until 2006 when a gastroscopy performed to investigate dyspeptic symptoms showed a mixed MALT gastric lymphoma (with low- and high-grade components) associated with the presence of Helicobacter pylori infection. Two therapeutic interventions in a 1-week interval were performed: treatment of the H. pylori infection (omeprazole, amoxicillin, and clarithromycin for 14 days) and modification of the immunosuppression by substitution of CsA and azathioprine (AZA) with SRL. Control endoscopy performed 1 month later showed persistence of H. pylori infection and absence of the gastric tumor. New endoscopies performed at 2 and 7 months after therapy confirmed the absence of neoplasia and H. pylori eradication. Currently, the patient has no complaints, displaying a creatinine value of 1.8 mg/dL and a hemoglobin of 9.4 mg/dL using SRL and ibersatan. SRL has been studied extensively as an anticancer drug, acting as a mammalian target for rapamycin (mTOR) inhibitor. Accumulating data support the role of mTOR in lymphomagenesis. In conclusion, our case of gastric MALT lymphoma in a renal transplant patient displayed a complete remission after alteration of the immunosuppressive scheme with the introduction of SRL.
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PMID:Mucosa-associated lymphoid tissue gastric lymphoma regression in a renal transplant patient after conversion of the immunosuppression to sirolimus: a case report. 1937 98

Therapy-related myelodysplastic syndrome/acute myeloid leukemia (t-MDS/AML) is a long-term complication of pediatric cancer. We retrospectively studied pediatric t-MDS/AML patients treated at MD Anderson from 1975 to 2007. We also compared those patients to pediatric patients with de novo MDS/AML during this time interval. Among 2589 children with cancer treated at MD Anderson, we identified 22 patients with t-MDS/AML. Patients with t-MDS/AML had a median age of 14 years. There was a male and Hispanic predominance. The most common primary malignancies were osteosarcoma and Hodgkin lymphoma. The median latency period was 4.1 years. Three patients received supportive care only. Group 1 (n=5) underwent stem cell transplantation without induction chemotherapy. Group 2 (n=5) patients received AML-type chemotherapy and a stem cell transplant postremission (n=5). Group 3 (n=4) received a stem cell transplant as salvage therapy. The respective 2-year survival rates for groups 1, 2, and 3 were 20%, 40%, and 25% (P=0.85). Patients with de novo AML were younger (P=0.001) and higher rates of complete remission (P=0.03), and survival (P<0.0001). Independent factors predicting shorter survival were poor/intermediate-risk cytogenetics (P=0.01), lower hemoglobin level (P=0.0001), and t-MDS/AML (vs. de novo) (P=0.003). Childhood t-MDS/AML has a poor prognosis. Although patients benefited from AML-type induction chemotherapy followed by stem cell transplantation as postremission therapy, effective therapies, and prevention are needed.
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PMID:Pediatric therapy-related myelodysplastic syndrome/acute myeloid leukemia: the MD Anderson Cancer Center experience. 1980 47

Although anemia is widely considered an early sign of malignant disease, little is known about the pattern of hemoglobin decline before diagnosis. As an approach to understanding the duration of the preclinical phase of different types of malignant diseases, we investigated prediagnostic hemoglobin concentration changes in a large cohort of blood donors. Using a nested case-control design, we analyzed a population-based cohort comprising 1.1 million Scandinavian blood donors with complete follow-up through record linkage to population and cancer registers. A total of 16,375 cancer cases were identified, for whom we selected 161,995 controls. We used conditional logistic regression to estimate the risk of cancer in relation to hemoglobin concentration during the 5 years preceding the cancer diagnosis. Hemoglobin concentration decline began already 3 years before diagnosis of stomach cancer, multiple myeloma, and lymphatic leukemia; 2 years before diagnosis of small intestinal and colon cancer as well as of Hodgkin lymphoma. A decline was evident during the last year for non-Hodgkin lymphoma and myeloid/monocytic leukemia, whereas no change was found for cancer of the esophagus, breast or prostate. In conclusion, in this study, we have demonstrated that the pattern of declining hemoglobin concentration before cancer diagnosis varies considerably between malignancies without being a suitable screening tool for any of them. For some malignancies, however, the long duration of hemoglobin decline before clinical diagnosis suggests a substantial lead-time with systemic effects, during which earlier diagnosis should be achievable by emerging diagnostic tools.
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PMID:Pattern of declining hemoglobin concentration before cancer diagnosis. 2002 Apr 93

Posttransplant lymphoproliferative disorders are classified as monomorphic, polymorphic, early lesions, or Hodgkin lymphoma type. Staging bone marrow examination is recommended in posttransplant lymphoproliferative disorder patients; however, information regarding bone marrow involvement in these disorders, especially as related to the posttransplant lymphoproliferative disorder subtype, is scarce. We reviewed the clinicopathologic features of 72 posttransplant lymphoproliferative disorder cases to determine the frequency of bone marrow involvement by various subtypes of posttransplant lymphoproliferative disorder, the clinical features of patients with and without bone marrow involvement, and their outcome. We also compared the incidence of bone marrow involvement of monomorphic posttransplant lymphoproliferative disorder (diffuse large B-cell lymphoma) with de novo diffuse large B-cell lymphoma (in both immunocompetent and HIV+ patients), and assessed the utility of various hematologic and serologic parameters as predictors of bone marrow involvement. Bone marrow involvement was seen in 23.5% of monomorphic posttransplant lymphoproliferative disorders and 15.7% of polymorphic posttransplant lymphoproliferative disorders, and the detection of bone marrow involvement on staging bone marrow biopsy upstaged 42% of monomorphic posttransplant lymphoproliferative disorders and 100% of polymorphic posttransplant lymphoproliferative disorders. Although bone marrow involvement appeared independent of patient age, organ transplanted, Epstein-Barr virus status, interval from transplantation to posttransplant lymphoproliferative disorder, or involvement of the grafted organ, it was significantly more frequent in cases without extranodal involvement; and it was associated with a significantly shorter survival. The incidence of bone marrow involvement in monomorphic posttransplant lymphoproliferative disorder (diffuse large B-cell lymphoma) was similar to that in HIV-associated diffuse large B-cell lymphoma, but higher than that in immunocompetent diffuse large B-cell lymphoma cases. No individual hematologic and serologic parameter was predictive of bone marrow involvement; however, the combination of elevated lactate dehydrogenase (>225 U/L) and decreased hemoglobin (<10 g/DL) can be used as a sensitive screening tool in determining which patients should proceed to bone marrow staging biopsy.
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PMID:Bone marrow involvement in patients with posttransplant lymphoproliferative disorders: incidence and prognostic factors. 2038 Nov 13

Anemia is a widely prevalent complication among cancer patients. At the time of diagnosis, 30% to 40% of patients with non-Hodgkin lymphoma or Hodgkin lymphoma and up to 70% of patients with multiple myeloma are anemic; rates are higher among persons with myelodysplastic syndromes. Among patients with solid cancers or lymphomas, up to half develop anemia following chemotherapy. For almost 2 decades, erythropoiesis-stimulating agents (ESAs) were the primary treatment for cancer-related anemia. However, reassessments of benefits and risks of ESAs for cancer-associated anemia have occurred internationally. We reviewed guidelines and notifications from regulatory agencies and manufacturers, reimbursement policies, and utilization for ESAs in the cancer and chronic kidney disease settings within the United States, Europe, and Canada. In 2008 the US Food and Drug Administration (FDA) restricted ESAs from cancer patients seeking cure. Reimbursement is limited to hemoglobin levels < 10 g/dL. In the United States, ESA usage increased 340% between 2001 and 2006, and decreased 60% since 2007. The European Medicines Agency (EMEA) recommended that ESA benefits do not outweigh risks. In Europe between 2001 and 2006, ESA use increased 51%; since 2006, use decreased by 10%. In 2009, Canadian manufacturers recommended usage based on patient preferences. In Canada in 2007, approximately 20% of anemic cancer patients received ESAs, a 20% increase since 2004. In contrast to Europe, where ESA use has increased over time, reassessments of ESA-associated safety concerns in the United States have resulted in marked decrements in ESA use among cancer patients.
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PMID:Reassessments of ESAs for cancer treatment in the US and Europe. 2039 40

Primary gastro-intestinal lymphoma (PGIL) is the most common type of extra-nodal non Hodgkin's lymphoma. Their clinical and histological presentations are heterogeneous depending on the site of the lesion. There is no consensus regarding the role of surgery and chemotherapy in the therapeutic approach. In our country epidemiology of the disease is unknown with IPSID being the most frequent type. We report anatomo-clinical features and prognostic factors of PGIL and compare intestinal to gastric forms in our region. This is a retrospective study of 153 cases of PGIL in adults diagnosed and treated in the department of medical oncology in Farhat Hached Hospital between 1994 and 2006. The median age was 52 years and the sex-ratio 2.1. Tumor sites were gastric (67%), intestinal (26%) and gastrointestinal (7%). Abdominal pain (87%) followed by vomiting and diarrhoea (37 and 15%) were the most common symptoms. Performance status (PS) < 2 was seen in 80% of patients, high grade lymphoma in 70.5% of cases and B phenotype was noted in 85%. MALT lymphoma accounts for 50% of cases, and IPSID for only 5% of PGIL. About 47.5% of cases were stage IE, 138 patients had chemotherapy with an objective response rate of 77%. Only 46% of patients had surgery (14 for surgical complication, 6 for residual tumor after chemotherapy and 22 to have histological diagnosis). The five-year overall survival (OS) was 62%. In high grade lymphoma patients favorable prognostic factors for OS included young age < or = 60 years, PS < 2, normal serum LDH, hemoglobin > 12 g/dL, B phenotype, localised stage (IE-IIE1), anthracycline-based chemotherapy regimen, achieving complete or partial response to induction chemotherapy and no relapse. In multivariate study only relapse and PS were significant prognostic factors for OS. In low-grade lymphoma patients, none of these factors had a significant correlation with OS: age < or = 60 years, PS < 2, stage (IE-IIE1), response to induction chemotherapy, relapse. Compared to gastric lymphomas, intestinal cases occurred at a younger age, frequently with diarrhoea, weight loss, and occlusion. They are more often high-grade, T phenotype and have locally advanced stage (IIE); surgery is more common in this group. We conclude that stomach is the main site of PGIL in our region, intestinal lymphoma is less frequent and IPSID has become rare. Recent progress in chemotherapy has allowed good therapeutic results with a conservative approach. Surgery may be performed in case of emergency or for residual lesions after medical treatment.
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PMID:[Primary digestive tract lymphoma in central region of Tunisia: anatomoclinical study and therapeutic results about 153 cases]. 2039 89


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