Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:Q06643 (non-Hodgkin's lymphoma)
 11,307 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Methotrexate (MTX) is a clinically important antifolate that has been used in combination with other chemotherapeutic agents in the treatment of malignancies including acute lymphocytic leukemia, osteosarcoma, carcinomas of the breast, head and neck, choriocarcinoma and non-Hodgkin's lymphoma. The primary target of MTX is the enzyme dihydrofolate reductase (DHFR) which catalyzes the reduction of folate and 7,8-dihydrofolate to 5,6,7,8-tetrahydrofolate. Understanding of MTX action has revealed how cells acquire resistance to this drug. The four known mechanisms of MTX resistance are a decrease in the uptake of the drug, a decrease in the retention of the drug due to defective polyglutamylation or an increase in polyglutamate breakdown, an increase in the enzyme activity and a decrease in the binding of MTX to DHFR. The molecular basis for some of these mechanisms has been elucidated in MTX resistant cell lines; in particular the occurrence of gene amplification resulting in increased DHFR and point mutations resulting in altered DHFR with reduced affinity for MTX. Cloning of the human folylpolyglutamate synthase gene and the reduced folate transport gene have been reported recently and should facilitate the identification of the molecular basis of these resistant phenotypes. DHFR protein has been shown to regulate its synthesis by exerting an inhibitory influence on its own translation. Addition of MTX relieves this inhibition thus providing a possible molecular explanation for the rapid rise in DHFR activity noted in some cells after MTX administration. Alterations in genes involved in regulating the cell cycle such as cyclin D1 and the retinoblastoma (Rb) gene have also been shown to influence cellular response to MTX. Overexpression of cyclin D1 in HT1080, a human fibrosarcoma cell line, results in decreased MTX sensitivity. The molecular basis of this observation is under investigation. Abnormalities in the Rb gene may also have profound effects on MTX sensitivity. Rb interacts with the family of transcription factors called E2F reducing transcription of genes that contain E2F binding sites in the promoter regions e.g. DHFR. When Rb is deleted or rendered nonfunctional levels of "free" or unbound E2F are high resulting in enhanced transcription of genes such as DHFR. This results in increased DHFR protein and may lead to MTX resistance. As the knowledge regarding mechanisms of resistance increases newer approaches to circumvent such resistance or to target resistant cells can be undertaken.
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PMID:Molecular mechanisms of resistance to antifolates, a review. 885 36

Small round cell tumors (SRCTs) of the bone make up a family of primary bone sarcomas with morphologically, biologically, and clinically specific features. Among them, Ewing's sarcoma (ES) is the most common entity, but several varieties such as atypical ES, large cell ES, and ES with neuroectodermal differentiation (peripheral primitive neuroectodermal tumor of the bone or neuroepithelioma of the bone) have been identified recently. Histology and electron microscopy together with the variable expression of several epitopes (as shown by immunohistochemistry, mainly HBA/71 [Mic2 antigen]) provide the basis for characterizing the group within the context of neuroectodermal-derived neoplasms. A number of other ES-like tumors with small round cells, mimicking those previously described, have been characterized; Askin's tumor of the thoracopulmonary region will be considered as an ES similar to those already described, but within a particularly anatomic location. On the other hand, the presence of an endothelial appearance within a poorly differentiated neoplasm may be present in some ES-like SRCTs (atypical ES with endothelial features). The differential diagnosis with other sarcomas defined by small round to spindle cell contours might prove difficult. Particular attention must be paid to small cell osteosarcoma and mesenchymal chondrosarcoma. Likewise, "primitive sarcoma of bone" is considered in this study because it is a very rare neoplasm differing from the formerly discussed types; its pluripotentiality provides this tumor a blastemic character and a multiphenotypic expression. Malignant non-Hodgkin's lymphoma is an unusual presentation when primary to the bone, previous to any other anatomic location. Several subtypes have been considered within a histology that encompasses that seen in lymph nodes.
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PMID:Histology, immunohistochemistry, and electron microscopy of small round cell tumors of bone. 887 7

The patient was initially diagnosed as having non-Hodgkin's lymphoma and was cured following treatment with prednisolone, vincristine, daunorubicin, 1-asparaginase, and cyclophosphamide. Seven years and two months later, he developed osteosarcoma in his right femur. He received chemotherapy consisting of methotrexate, carboplatin, etoposide, and ifosfamide and again obtained remission. After 2 years and 7 months, however, he was found to have pancytopenia with morphological abnormalities in the erythroid and myeloid series. Diagnosis of myelodysplastic syndrome (MDS) was made. Cytogenetic analysis of bone marrow cells revealed -5 and -7, which is typical for secondary MDS. This is a rare case of third malignancy presumably caused by alkylating agents.
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PMID:Myelodysplastic syndrome presenting as third malignancy after non-Hodgkin's lymphoma and osteosarcoma. 906 80

In the framework of the ITACARE project, a cooperative investigation conducted on the data from the Italian population-based cancer registries, survival of patients with childhood malignant neoplasms was studied. The study included 1,768 cases diagnosed at age 0-14 plus 29 osteosarcoma cases diagnosed at age 15-19. Cases were collected over the period 1978-1989, or more limited periods for some participating registries. A total of 1,138 cases were from the Childhood Cancer Registry of Piedmont and 659 from the registries operating in the provinces of Varese, Parma, Modena, Forli and Ravenna, Florence, Latina, Ragusa and in the cities of Genova and Torino (the last contributed only for bone neoplasm diagnosed at age 15-19). Overall 5-year survival was 54% for malignancies diagnosed in 1978-1981, 60% for the period 1982-1985; and 69% for the period 1986-1989. The range among registries of 5-year survival for cases diagnosed in 1986-1989 was 55-78%. Most diagnostic categories presented an improved prognosis for the cases diagnosed more recently. For cases diagnosed in 1986-1989, 5-year survival was: 74% for acute lymphatic leukaemia, 40% for acute non-lymphatic leukaemia, 65% for central nervous system neoplasms (76% for astrocytoma, 75% for ependymoma and 85% for medulloblastoma), 66% for osteosarcoma, 55% for Ewing's sarcoma, 87% for Hodgkin's disease, 64% for non-Hodgkin's lymphoma, 74% for rhabdomyosarcoma, 64% for neuroblastoma, 78% for nephroblastoma and 100% for retinoblastoma. Italian survival was similar to that observed in other population-based surveys in the UK and USA.
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PMID:Survival of childhood cancer patients in Italy, 1978-1989. ITACARE Working Group. 915 68

A retrospective analysis of 515 pediatric cancer cases diagnosed over 18 years, 1973-1990, showed an annual incidence of pediatric solid tumors in northern Israel of 77.1 per million, somewhat lower than previously reported. Lymphomas predominated over central nervous system (CNS) neoplasms, suggesting an Afro-Asian rather than a Western pattern. Jewish and non-Jewish children were at approximately equal risk (1:07:1.0) for the nonleukemic cancer. However, there was a notably higher frequency in males than females (1:42:1.0) and in Ashkenasi Jews as compared to either Sephardi Jews (1.25:1.00) or non-Jews (1.23:1.0). Ethnic, age, and sex predispositions for particular types of malignancy were also noted. Non-Jews tended to have lymphomas or retinoblastomas and Sephardi Jews were predisposed to soft tissue sarcomas. Ashkenasi Jews tended to manifest CNS tumors, retinoblastoma, and osteosarcoma. Children under 5 years showed Burkitt's lymphoma and neuroblastoma, whereas the older group tended to have Hodgkin's lymphoma. Boys were more vulnerable to non-Hodgkin's lymphoma, medulloblastoma, neuroblastoma, and rhabdomyosarcoma, and girls were subject to higher incidences of bone, gonadal, germ cell, and epithelial tumors, as well as to astrocytoma. The implications for genetic or environmental contributions to several cancers are considered in conjunction with ethnic or gender predisposition to those cancers.
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PMID:Patterns of childhood solid tumor incidence in northern Israel, 1973-1990. 938 5

Second malignancy after childhood neoplasms is a well-known complication. However, frequency differs considerably according to the types of primary neoplasm and the specifics of therapy. Ten patients with a second malignancy after being cured of the primary tumor are described. There were 2 patients with acute lymphoblastic leukemia, one with non-Hodgkin's lymphoma, and one with breast cancer after Hodgkin's disease. Two patients with heritable retinoblastoma developed osteosarcomas in the irradiation field after a latent period of 7 and 14 years respectively. There was another osteosarcoma in a Wilms' tumor survivor. One patient with acute lymphoblastic leukemia developed a secondary AML 10 years after achieving initial remission, and a meningioma was diagnosed in another patient with cured acute lymphoblastic leukemia. One patient died of peritoneal sarcomatosis of unknown origin 20 years after the diagnosis of acute myeloid leukemia. All patients received radiotherapy for the primary neoplasms. Secondary neoplasms in other patients were probably missed because they occurred in adulthood when the patients were transferred to other medical centres. It is impossible to trace these patients because central registration of patients with neoplasms is lacking. It is therefore important to establish a central cancer registry for the whole of Switzerland. Second malignancy after childhood cancer is not a rare event and requires long-term follow-up of patients with neoplasms.
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PMID:[Insufficient understanding of second tumors after childhood neoplasms in Switzerland]. 958 99

The incidence of documented infections after autologous peripheral blood progenitor cells transplantation (PBPCT) was retrospectively evaluated in 86 consecutive patients (47 males 39 females; median age 36 years, range, 18-63) treated in our institution; 83 patients had refractory hematological malignancies (40 non-Hodgkin's lymphoma, 19 Hodgkin's disease, 17 multiple myeloma, 7 acute myeloblastic leukemia) and 3 had solid tumors (1 rabdomyosarcoma, 1 neuroblastoma, 1 osteosarcoma). All patients developed fever after transplantation lasting a median of 2 days (range 1-17); 20 instances of documented sepsis developed in 17 patients (19.7%). Gram positive microorganisms were implicated in all but 4 cases. There were no fatalities directly due to infections and no correlation was found between the risk of infection and reaching PMN > 0, 1 x 10(9)/L, PMN > 0.5 x 10(9)/L. In addition no specific risk factors related to age, disease, conditioning regimen, use of central venous catheter (CVC), type of transplant, and isolation measures were identified.
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PMID:Incidence of sepsis after peripheral blood progenitor cells transplantation: analysis of 86 consecutive hemato oncological patients. 966 90

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

Telomerase activity can be detected in most human cancers. This is consistent with the telomere hypothesis, which predicts upregulation of telomerase expression after a number of mitotic divisions to prevent the progressive and catastrophic loss of telomeres. However, telomerase has not been fully analyzed in oral cancers. In this report, telomerase activity was analyzed in 31 human oral malignant tumors, 11 leukoplakias, three pleomorphic adenomas, and 40 samples taken from normal tissues of the oral cavity, using a polymerase chain reaction (PCR)-based telomeric repeat amplification protocol assay. Telomerase activity was detected in most oral cancers [squamous cell carcinoma (SCC), non-Hodgkin's lymphoma, adenoid cystic carcinomas, mucoepidermoid carcinoma, osteosarcoma, acinic cell carcinoma, rhabdomyosarcoma]. None of the normal tissues or pleomorphic adenomas displayed telomerase activity. In leukoplakia, telomerase activity was seen in moderate or severe dysplastic tissue and carcinoma in situ. Mild dysplasia did not reveal telomerase activity. In SCC, there was no clear association between relative telomerase activity and grade or stage. These results suggest that detection of telomerase activity in oral tissues could be used to differentiate malignant from benign or normal tissues.
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PMID:Telomerase activity in oral cancer. 1062 49

Survival following cancer was analysed in relation to ethnic group among children diagnosed in Britain during 1981-1996 and treated at paediatric oncology centres by members of the UK Children's Cancer Study Group. Survival was analysed for 11 diagnostic groups: acute lymphoblastic leukaemia (ALL), acute non-lymphocytic leukaemia, Hodgkin's disease, non-Hodgkin's lymphoma, astrocytoma, primitive neuroectodermal tumour, neuroblastoma, Wilms' tumour, osteosarcoma, Ewing's sarcoma and rhabdomyosarcoma. There were no significant differences in survival between White and non-White children over the study period as a whole. Among children with ALL, however, the relative risk of death allowing for period of diagnosis, age and white blood count was 1.25 for those of South Asian ethnic origin compared with Whites (P = 0.057).
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PMID:Ethnic group and survival from childhood cancer: report from the UK Children's Cancer Study Group. 1075 11


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