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)

Monoclonal antibodies to the glycoprotein product of the MIC2 gene strongly and reliably stain primitive neuroectodermal tumors and Ewing's sarcomas, and are negative in neuroblastomas and most rhabdomyosarcomas. Therefore, these antibodies are helpful in the diagnosis of small round cell tumors of childhood (SRCT). Lymphomas also are in the differential diagnosis of SRCT, but few have been studied with respect to MIC2 protein expression. In the present study we used the 12E7 antibody to assess MIC2 expression in 82 pediatric non-Hodgkin's lymphomas. Forty lymphoblastic, 22 small noncleaved, and 20 large cell lymphomas were studied. Strong immunoreactivity was found in 37 of the 40 (93%) lymphoblastic lymphomas, whereas only one of the 22 (5%) small noncleaved lymphomas was 12E7 positive. Four of the 20 (20%) large cell lymphomas also were immunoreactive. Three 12E7+ lymphoblastic lymphomas were primary in bone and were of B-progenitor lineage; Ewing's sarcoma was included in the initial differential diagnosis of these cases. Evaluation of 125 pediatric acute lymphocytic leukemia (ALL) cases for MIC2 expression showed similar results, with all 36 T-cell ALLs showing strong expression, one of eight B-cell (Burkitt-like) ALLs showing 12E7 expression, and 62 of 81 B-progenitor ALLs showing 12E7 positivity. We conclude that among the SRCTs, MIC2 expression is not limited to Ewing's sarcoma and primitive neuroectodermal tumors, but also shows strong and reliable expression in lymphoblastic lymphomas and related leukemias. MIC2 analysis continues to be helpful in the diagnosis of SRCT, provided that a panel of antibodies is used. In addition, the possibility that MIC2 analysis may aid in the distinction of lymphoblastic lymphomas from small noncleaved lymphomas needs to be further addressed.
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PMID:MIC2 analysis in pediatric lymphomas and leukemias. 816 72

The serum levels of soluble interleukin 2 receptor (SIL-2R) and tumor necrosis factor (TNF) were assessed in 69 children from 6 months to 14 years old who suffered from acute lymphoblastic leukemia (39), Hodgkin's disease (15), non-Hodgkin's lymphoma (15) and in 54 normal age-matched controls prior to any therapy and at remission. Both SIL-2R and TNF levels were significantly higher at diagnosis compared with normal controls (P < 0.001), but decreased significantly at remission. The SIL-2R and TNF levels were significantly higher in an advanced stage of lymphoma than in an early stage. In the patients with acute lymphoblastic leukemia (ALL) and lymphoma, higher levels of SIL-2R (> 1030 units/ml) and TNF (> 30 pg/ml) were associated with a poorer treatment outcome (P < 0.01). Our findings indicate that elevated TNF serum secretion together with SIL-2R are useful markers in childhood ALL and lymphoma and can be used to assess both disease activity and prognosis in this group of malignancies.
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PMID:Serum levels of tumor necrosis factor and soluble interleukin 2 receptor as markers of disease activity and prognosis in childhood leukemia and lymphoma. 849 93

Seasonal trends in month of diagnosis have been reported for childhood acute lymphoblastic leukaemia (ALL) and non-Hodgkin's lymphoma (NHL). This seasonal variation has been suggested to represent an underlying viral aetiology for these malignancies. Some studies have shown the highest frequency of diagnoses in the summer months, although this has been inconsistent. Data from the Children's Cancer Group and the Pediatric Oncology Group were analysed for seasonal incidence patterns. A total of 20,949 incident cancer cases diagnosed in the USA from 1 January 1989 through 31 December 1991 were available for analyses. Diagnosis-specific malignancies available for evaluation included ALL, acute myeloid leukaemia (AML), Hodgkin's disease, NHL, rhabdomyosarcoma, neuroblastoma, retinoblastoma, osteosarcoma, Wilms' tumour, retinoblastoma, Ewings' sarcoma, central nervous system (CNS) tumours and hepatoblastoma. Overall, there was no statistically significant seasonal variation in the month of diagnosis for all childhood cancers combined. For diagnosis-specific malignancies, there was a statistically significant seasonal variation for ALL (P = 0.01; peak in summer), rhabdomyosarcoma (P = 0.03; spring/summer) and hepatoblastoma (P = 0.01; summer); there was no seasonal variation in the diagnosis of NHL. When cases were restricted to latitudes greater than 40 degrees ('north'), seasonal patterns were apparent only for ALL and hepatoblastoma. Notably, 33% of hepatoblastoma cases were diagnosed in the summer months. In contrast, for latitudes less than 40 degrees ('south'), only CNS tumours demonstrated a seasonal pattern (P = 0.002; winter). Although these data provide modest support for a summer peak in the diagnosis of childhood ALL, any underlying biological mechanisms that account for these seasonal patterns are likely complex and in need of more definitive studies.
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PMID:Seasonal variations in the diagnosis of childhood cancer in the United States. 1094 15

The interval between courses of chemotherapy have classically been kept to a minimum in order to maximize dose intensity. Certain clinical observations suggest that longer intervals, particularly in the high-dose setting, may be more effective. This is based in part on the evidence that resistance is reversible over time and that the interval should be sufficient to allow for such a reversal. Clinical evidence for such reversibility include the following. In metastatic breast cancer, double or double high-dose stem cell rescue (HD-SCR) studies involving a minimal interval, have not, at least as yet, been shown to be superior to single HD-SCR. In Hodgkin's disease, response after relapse correlates directly with duration of time to relapse. In a comparative study of metastatic breast cancer, early HD-SCR preceded by daunorubicin induction was inferior to delayed HD-SCR. The latter was not preceded by induction chemotherapy. In a comparative study of childhood ALL, patients randomized to delayed (4 month interval) intensification had a significantly superior survival as compared to patients randomized to immediate (1 month interval) intensification. Taken together, these clinical observations indicate that resistance is reversible and that optimization of the interval must take this into account. Cytokinetic modeling of those clinical studies also found that delayed HD-SCR could result in a superior effect. Cytokinetic models of minimal residual tumor which were also examined included the Skipper exponential model, the Norton-Simon model which emphasizes the Gompertzian effect, the clonal evolution model, and the Retsky-Demisheli model which derives from a bimodal relapse pattern above. Biological and clinical data have resulted in a clinical protocol in the CALGB wherein patients with metastatic breast cancer are randomly allocated to (1) a single HD-SCR arm; (2) a double HD-SCR with a 5-week interval; and (3) a double HD-SCR arm with a 16 week interval.
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PMID:The interval between courses of high-dose chemotherapy with stem cell rescue: therapeutic hypotheses. 1055 51

The CHK2 gene encodes a protein kinase that is important for the regulation of cell cycle arrest after DNA damage. CHK2 acts downstream of ataxia teleangiecstasia mutated (ATM), modulates the function of p53 and may help mediate cell cycle arrest at G2/M by phosphorylation of Cdc25C. Recently, the human homolog of the checkpoint kinase Cds1 (CHK2) has been suggested to be a tumor suppressor gene. Heterozygous germline mutations have been reported in Li-Fraumeni syndrome (LFS), a highly penetrant familial cancer phenotype, and in sporadic colon cancer. LFS is associated with the development of lymphoid malignancies, especially childhood ALL. Therefore, we analyzed the DNA from 143 lymphoid malignancies to determine whether they had mutations of the CHK2 gene. The 14 exons of CHK2 were studied by polymerase chain reaction-single strand conformational polymorphism (PCR-SSCP) and sequencing of aberrantly migrating bands. One missense mutation changing serine to phenylalanine (codon 428) in an evolutionarily highly conserved domain was found in a non-Hodgkin's aggressive lymphoma. Another point mutation in the non-coding region was identified in one of adult T-cell leukemias (ATL) samples. This result suggests that mutation of the CHK2 gene may rarely be involved in the development of selected lymphomas.
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PMID:Analysis of the CHK2 gene in lymphoid malignancies. 1169 18

The gene causing hereditary hemochromatosis (HH), HFE is an HLA class I-like gene with no known immunological function but indirectly related to the immune functions because of its role in iron transport. It is located 6.5 Mb telomeric to HLA-A. The most common mutation of HFE, C282Y, has a Celtic origin and most patients with HH are homozygous for it in Northern European populations. While there is an enormously increased risk for hepatocellular cancer in hemochromatosis that is attributed to the toxic effects of iron, the risk for extra-hepatic cancers is also increased slightly. Recent studies have found genetic associations between several cancers and C282Y but only in the presence of a particular allele of the transferrin receptor gene. This suggests that the increased cancer risk is more likely due to the effects of iron. In childhood acute lymphoblastic leukemia (ALL), however, there is a strong association of C282Y with a gender effect in two different Celtic populations. This association does not require homozygosity for C282Y or an interaction with the transferrin receptor gene, and is male-specific. The other HFE mutation H63D does not confer increased risk to childhood ALL. Acute myeloblastic leukemia and Hodgkin's disease in adults do not have an association with HFE. Its male-specificity, occurrence in childhood and the lack of a gene-dosage effect suggest that the C282Y association in childhood ALL may reflect the involvement of another HLA-linked gene in leukemia susceptibility.
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PMID:Hemochromatosis gene in leukemia and lymphoma. 1200 48

Second malignant neoplasms are a serious complication after successful treatment of childhood acute lymphoblastic leukemia (ALL). With improvement in survival, it is important to assess the impact of contemporary risk-based therapies on second neoplasms in ALL survivors. A cohort of 8831 children diagnosed with ALL and enrolled on Children's Cancer Group therapeutic protocols between 1983 and 1995 were observed to determine the incidence of second neoplasms and associated risk factors. The median age at diagnosis of ALL was 4.7 years. The cohort had accrued 54 883 person-years of follow-up. Sixty-three patients developed second neoplasms, including solid, nonhematopoietic tumors (n = 39: brain tumors n = 19, other solid tumors n = 20), myeloid leukemia or myelodysplasia (n = 16), and lymphoma (n = 8). The cumulative incidence of any second neoplasm was 1.18% at 10 years (95% confidence interval, 0.8%-1.5%), representing a 7.2-fold increased risk compared with the general population. The risk was increased significantly for acute myeloid leukemia (standardized incidence ratio [SIR] 52.3), non-Hodgkin lymphoma (SIR 8.3), parotid gland tumors (SIR 33.4), thyroid cancer (SIR 13.3), brain tumors (SIR 10.1), and soft tissue sarcoma (SIR 9.1). Multivariate analysis revealed female sex (relative risk [RR] 1.8), radiation to the craniospinal axis (RR 1.6), and relapse of primary disease (RR 3.5) to be independently associated with increased risk of all second neoplasms. Risk of second neoplasms increased with radiation dose (1800 cGy RR 1.5; 2400 cGy RR 3.9). Actuarial survival at 10 years from diagnosis of second neoplasms was 39%. Follow-up of this large cohort that was treated with contemporary risk-based therapy showed that the incidence of second neoplasms remains low after diagnosis of childhood ALL.
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PMID:Low incidence of second neoplasms among children diagnosed with acute lymphoblastic leukemia after 1983. 1203 51

Infection has long been suspected as a possible factor in the aetiology of leukemia and lymphoma, one of the most common malignancies in children. Since most viral infections have seasonal variations of onset, if seasonal trends in 1 month of diagnosis of leukemia and lymphoma could be proved, this would be supportive evidence for an infectious aetiology. A total of 367 cases in the Hospitals of Shiraz University of Medical Sciences, from April 1996 through March 2000, who were diagnosed as having acute lymphocytic leukemia (ALL), acute myeloblastic leukemia (AML), Burkitt's lymphoma (BL) chronic myeloblastic lymphoma (CML), Hodgkin's disease (HD) or non-Burkitt's type non-Hodgkin's lymphoma (NBNHL) were analysed. The month of appearance of the first symptom and the date of diagnosis were recorded. ALL demonstrated statistically significant monthly variation in the date of appearance of the first symptom (p < 0.05; peak in October) and the date of diagnosis (p < 0.05; peak in November). Seasonal variation was demonstrated in the date of the first appearance of symptoms in BL (p < 0.042), and in the date of diagnosis in AML (p < 0.049). There was no statistically significant seasonal variation in the month of diagnosis for other groups. Analysis based on the date of the first symptoms and the date of diagnosis for ALL patients, using summer-winter ratios, also showed a significant winter excess (p < 0.001). Our data provide modest support for an autumn-winter peak in the diagnosis of childhood ALL, underlying mechanisms that account for these patterns are likely to be complex and need more definitive studies.
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PMID:Seasonal variations in the onset of childhood leukemia/lymphoma: April 1996 to March 2000, Shiraz, Iran. 1280 9

Among pediatric non-Hodgkin lymphomas, the most frequent type is small noncleaved-cell lymphoma (including Burkitt and Burkitt-like). Specific chromosome abnormalities are associated with prognosis in childhood acute lymphoblastic leukemia (ALL); however, chromosome abnormalities have not been evaluated for prognostic value in pediatric Burkitt and Burkitt-like lymphomas. For Children's Cancer Group protocol CCG-E-08 Etiologic Study of Non-Hodgkin Lymphoma in Childhood, 19 patients were enrolled with cytogenetic analysis of Burkitt or Burkitt-like lymphoma and simultaneously enrolled on treatment protocols CCG-503 or CCG-552. Pathology material and karyotypes at initial diagnosis underwent central review. Demographics included an age range of 2 to 14 years (median 8 years) and a male:female ratio of 14:5. All patients had advanced disease (stages III and IV, or ALL). Disease relapsed in five patients (event-free survival 74%, median follow-up 10.4 years). Chromosome abnormalities were identified in 18 patients (95%) including t(8;14)(q24.1;q32) in 12 (63%); t(8;22)(q24.1;q11.2) in 1 (5%); partial duplication of 1q in 7 (37%); and 13q32 abnormalities in 2 (11%). In patients who had relapses, in addition to the t(8;14)(q24. ;q32), two had abnormalities of 13q32 and two had partial duplication of 1q. CMYC translocations were absent in Burkitt-like lymphomas from all three patients. Burkitt and Burkitt-like lymphomas in children have a high frequency of chromosome abnormalities. Burkitt lymphoma abnormalities often involve CMYC translocations, usually a t(8;14)(q24.1;q32). Additional chromosome abnormalities that involved 13q32 and partial duplication of 1q were associated with poor prognosis. Burkitt-like lymphomas were not associated with CMYC translocations. Further studies are warranted in larger cohorts of children and adolescents with Burkitt and Burkitt-like lymphomas.
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PMID:Chromosome abnormalities may correlate with prognosis in Burkitt/Burkitt-like lymphomas of children and adolescents: a report from Children's Cancer Group Study CCG-E08. 1512 9

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.
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PMID:HFE gene mutations in susceptibility to childhood leukemia: HuGE review. 1577 51


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