UMLS:C0023418 - FACTA Search

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Query: UMLS:C0023418 (leukemia)
93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The outcome of 31 patients with malignant ovarian germ cell tumors treated by surgery and a medium dose etoposide containing short chemotherapy regimen between 1988 and 1997 is reported. Of the 31 patients, 16 (51.6%) had malignant teratomas, 8 (25.8%) had dysgerminomas, 6 (19%) endodermal sinus tumors and one (3.2%) mixed germ cell tumor. Twenty-four (77.4%) patients were at FIGO stage I (of which 18 were stage IA), 2 (6.5%) at stage II, 4 (12.9%) at stage III and 1 (3.2%) at stage IV. Twenty-five (80.6%) patients underwent conservative surgery, 1 (3.2%) underwent bilateral salpingo-oophorectomy and 4 (12.9%) had total hysterectomy with bilateral salpingo-oophorectomy and omentectomy. One (3.2%) patient refused definitive treatment. Three patients with stage IA grade 1 immature teratomas were not treated with adjuvant chemotherapy and one patient with a stage IA dysgerminoma refused chemotherapy. Two patients with endodermal sinus tumor returned to their countries of origin after surgery. Twenty-five patients received bleomycin, etoposide, and cisplatin (BEP) regimen with etoposide dosage fixed at 120 mg/m2 on day 1 and day 2, bleomycin 15 mg intravenous bolus on days 1 and 2 and cisplatin 100 mg/m2 on day 1. Chemotherapy was administered at four weekly intervals for 4 cycles or until complete response was achieved. The median number of cycles of chemotherapy was four (range 3-6) for stage I, 6 (range 4-7) for stage II and 5 (range 5-6) for stage III tumors. Of the entire cohort of 29 patients analyzed, the median follow up period was 5 years. One patient died from stage IIIC endodermal sinus tumor and one patient had persistent teratoma in the lungs. The overall disease free survival control rate was 93.1%. There were three cases of the growing teratoma syndrome involving the liver, abdominal peritoneum, and the pelvis, respectively. No mortality resulted from the growing teratomas. No pulmonary complications, secondary primary tumor or leukemia was detected. Menstrual function returned in all patients with fertility-preserving surgery and one pregnancy occurred. This interesting data suggest that a medium dose 2-day BEP postsurgical adjuvant chemotherapy regimen is effective and superior to expectant treatment of malignant ovarian germ cell tumors. This report, however, should be viewed as a pilot study. The result indicates that a prospective randomised controlled trial to demonstrate equivalence of this regimen with the standard BEP regimen is warranted.
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PMID:Experience of a 2-day BEP regimen in postsurgical adjuvant chemotherapy of ovarian germ cell tumors. 1124 Jun 46

The author reviewed 1,517 human malignant mesothelioma cases from 1975 through August 2000. These mesothelioma cases were definite or probable in diagnostic certainty. Sources of these cases varied including asbestos insulation workers, UNARCO workers, Cancer and Leukemia B mesothelioma panel cases and random cases. Pathology materials consisted of autopsy, biopsy and rare cytology specimens. 92.3% of these patients were male, and 85.8% were between 50 and 79 years in age. The major primary site of the tumor was the pleura (73.1%). However, in a group of the asbestos insulation workers, the peritoneum was the more common primary site of malignant mesothelioma, compared to the pleura. Histologically, epithelial cell type was the majority (61.1%), followed by biphasic (22.1%) and fibrosarcomatous (16.4%). A double primary tumor (malignant mesothelioma associated with other cancer) was present in 32 of the 1,517 cases. These 32 cancers included lung cancers, renal cell carcinomas, colorectal cancers, pancreatic cancers and a cancer of the larynx, which are known to be at higher risk among asbestos insulation workers. The latency period of the vast majority (98.1%) of these mesothelioma cases were longer than 20 years. It is well accepted that cigarette smoking does not contribute to the induction of malignant mesothelioma. Indeed, the present study confirmed that 19.9% of these mesothelioma patients had never smoked cigarettes.
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PMID:Pathology of human malignant mesothelioma--preliminary analysis of 1,517 mesothelioma cases. 1134 49

There is a known association between lymphoid malignancy and Hodgkin's disease (HD), but the development of HD in children who have been treated for leukemia or lymphoma is very uncommon. Hodgkin's disease is, after retinoblastoma, the most common primary tumor that is associated with development of second malignant neoplasm. For reasons that remain to be determined, HD is very rare as a second malignancy [1, 2, 3]. We report the case of a eight-year-old girl who developed HD 6 years after treatment for common acute lymphoblastic leukemia (ALL). This case prompted us to review the published literature for cases of secondary HD in childhood. Our experience suggests that we should follow strictly our patients with ALL and be ready to intervene with invasive diagnostic procedures at the least suspicion of a second or recurrent neoplasm. The most frequent causes of second tumors are radiotherapy, genetic susceptibility and prior treatment with certain chemotherapeutic agents, such as nitrogen mustards. It is likely that any type of immunodeficiency, even without symptoms, might play a role in the development of second tumors in childhood.
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PMID:Hodgkin's disease as a second malignant neoplasm in childhood: report of a case and review of the literature. 1155 36

Thymic lymphomas induced by Moloney murine leukemia virus (MMLV) have provided many examples of oncogene activation, but the role of tumor suppressor pathways in these tumors is less clear. These tumors display little evidence of loss of heterozygosity, and MMLV is only weakly synergistic with the Trp53 null genotype, suggesting that viral lymphomagenesis involves mechanisms which do not require mutational loss of Trp53 function. To explore this relationship in greater depth, we infected CD2-myc transgenic mice with MMLV and examined the role of Trp53 in the genesis of these tumors. Most (19 of 27) of the tumors from MMLV-infected, CD2-myc Trp53(+/-) mice retained the wild-type Trp53 allele in vivo while tumors of uninfected CD2-myc Trp53(+/-) mice invariably showed allele loss from a significant fraction of primary tumor cells. The functional integrity of the Trp53 gene in these tumors was indicated by ongoing allele loss or selection for mutational stabilization during in vitro propagation and by the radiosensitivity of selected Trp53(+/-) tumor cell lines. An inverse correlation was noted between retention of the wild-type Trp53 allele and expression of p19(ARF), providing further evidence of negative-feedback control of the latter by p53. However, expression of p19(ARF) does not appear to be counterselected in the absence of p53, and its integrity in Trp53(+/-) tumors was indicated by its transcriptional upregulation on Trp53 wild-type allele loss in vitro in selected tumor cell lines. The role of MMLV was investigated further by analysis of proviral insertion sites in tumors of CD2-myc transgenic mice sorted for Trp53 genotype. A proportion of tumors showed insertions at Runx2, an oncogene which has been shown to collaborate independently with CD2-myc and with the Trp53 null genotype, and at a novel common integration site (ptl-1) on chromosome 8. Genotypic analysis of the panel of tumors suggested that neither of these integrations is functionally redundant with loss of p53, but it appears that the combination of the MMLV oncogenic program with the CD2-myc oncogene relegates p53 loss to a late step in tumor progression or in vitro culture. While the means by which these tumors preempt the p53 tumor suppressor response remains to be established, this study provides further evidence that irreversible inactivation of this pathway is not a prerequisite for tumor development in vivo.
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PMID:Selection for loss of p53 function in T-cell lymphomagenesis is alleviated by Moloney murine leukemia virus infection in myc transgenic mice. 1155 12

To investigate the clinicopathological features of patients with secondary tumors of the pancreas, we reviewed autopsy records and pathological features of 103 cases with pancreatic secondary tumors from 690 cases of malignant tumors (excluding cases of primary pancreatic cancer) over a 10-year period. There were 67 men and 36 women in the study, ranging in age from 2 to 94 years (mean: 61 years). The incidence of pancreatic secondary tumors was 15% in the autopsy cases of malignant tumors, and the majority of the secondary tumors were carcinomas. The stomach was the most common primary tumor site (20%), followed by the lung (18%) and extrahepatic bile duct (13%). Because the total number of each primary carcinoma differed, we paid specific attention to the incidence of pancreatic metastasis in each primary carcinoma. We found that carcinoma of the papilla of Vater showed the highest rate of incidence (75%) of pancreatic metastasis in each type of primary carcinoma. Approximately half of the metastatic lesions were solitary, but the metastatic lesions in the pancreas could not be identified macroscopically in 34 cases (33%). Histologically, the most common carcinoma was adenocarcinoma, followed by large cell carcinoma, small cell carcinoma and neuroendocrine carcinoma. The most common non-epithelial tumor was leukemia, followed by malignant lymphoma. Undifferentiated carcinoma and neuroendocrine carcinoma were often found in cases of extrahepatic bile duct or urinary bladder carcinoma with pancreatic metastasis. As for the microscopic infiltration patterns of tumor cells, 73% of cases showed an interlobular and intralobular infiltration. Fat necrosis was most frequently seen as an associated pathological finding (19%). Our study indicates that secondary tumors of the pancreas can be found in approximately one out of six to seven autopsy cases of malignant tumors, and in Japan, the most common of these is adenocarcinoma of the stomach.
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PMID:Secondary tumors of the pancreas: clinicopathological study of 103 autopsy cases of Japanese patients. 1169 71

We investigated the potential role of defective DNA-mismatch repair (MMR) as a mediator of leukemogenic susceptibility in patients with therapy-related myelodysplasia (t-MDS) and leukemia (t-leuk). Thirty-seven individuals with t-MDS/t-leuk were analyzed for microsatellite instability (MSI), the hallmark of defective DNA-MMR. Using standardized international criteria, 5/37 (14%) patients displayed high MSI, whereas 3 other patients had low MSI (8%). To determine the stage at which MSI had developed, we analyzed the primary tumors of 12 patients. Three of 4 patients with high MSI t-MDS/t-leuk also had microsatellite unstable primary tumors. Conversely, MSI was not detected in any primary malignancy of patients with low MSI or microsatellite stable t-MDS/t-leuk (P = 0.0182). In the high MSI group, we further investigated genes targeted by defective DNA-MMR (BAX, TGFBRII, IGFIIR, Caspase-5, APC, PTEN, E2F4, MBD4, MSH6, and MSH3) in both primary tumor and t-MDS/t-leuk. However, no mutation was found in any gene. The significant association of MSI in t-MDS/t-leuk and corresponding primary tumors suggests that defective DNA-MMR confers leukemogenic susceptibility to this cohort of patients.
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PMID:Defective DNA-mismatch repair: a potential mediator of leukemogenic susceptibility in therapy-related myelodysplasia and leukemia. 1197 58

A frequent outcome of allogeneic stem cell transplantation (alloSCT) in the treatment of leukemia is the destruction of the host hematolymphoid compartment and, thus, the malignancy, through the combined action of high-dose chemoradiotherapy and a T-cell-mediated graft-versus-host effect. Unfortunately, alloSCT is frequently limited by toxicity, including graft-versus-host disease (GVHD), and has not been successful in the treatment of tumors derived from solid organs. Here we report a novel cooperation between host and donor T cells in the response to a tumor cell vaccine given after a nonmyeloablative allogeneic stem cell transplantation (NST) protocol that achieves stable mixed bone marrow chimerism. Treatment of animals with NST, posttransplantation donor lymphocyte infusions (DLIs), and a vaccine, comprising irradiated autologous tumor cells mixed with a granulocyte-macrophage colony-stimulating factor (GM-CSF)-producing bystander line, results in potent and specific antitumor immunity. This combined modality immunotherapy, administered after surgical removal of the primary tumor, cured metastatic mammary cancer in most animals without inducing GVHD. Cured animals contained tumor-specific T cells of both host and donor origin, but immunodeficient hosts could not be cured by NST, DLI, and vaccine administration. Thus, transfer of allogeneic donor T cells may help break functional tolerance of a host immune system to a solid tumor, thereby providing a rationale for the generation of mixed hematopoietic chimerism by NST prior to tumor cell vaccination.
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PMID:Successful therapy of metastatic cancer using tumor vaccines in mixed allogeneic bone marrow chimeras. 1240 77

The activation of the NF-kappaB family of transcription factors plays a crucial role in oncogenesis. The IkappaB family has the ability to retain the NF-kappaB in an inactive complex in the cytoplasm. Recently, mutations of the IkappaBalpha gene were found in Hodgkin's lymphoma, which allows NF-kappaB proteins to translocate into the nucleus in an active form. In this report, we describe a mutational analysis of IkappaBalpha for primary tumor cells obtained from patients with a variety of hematologic malignancies (acute myelogenous leukemia, chronic myelogenous leukemia, myelodysplastic syndrome, hairy cell leukemia, adult T-cell leukemia, and mantle cell lymphoma) as well as 15 leukemia, lymphoma, and myeloma cell lines (HL60, U937, HEL, K562, NALM1, Jurkat, JM, MOLT4, Raji, KS1, OKM2T, OKM3T, F6T, Su9T01, and C2-2). RT-PCR, followed by direct sequencing, was performed and all samples expressed IkappaBalpha. One missense mutation was identified in a primary effusion lymphoma cell line, KS1. However, NF-kappaB (p65) protein was absent from the nucleus of KS1 immunohistochemically, suggesting that the mutation did not alter the function of IkappaBalpha in this case. Taken together, although it is not clear whether normal IkappaBalpha protein was expressed in hematologic malignancies, mutations of IkappaBalpha could be rare events in these diseases, except for Hodgkin's lymphoma. Alterations of other members of NF-kappaB/ IkappaB family proteins might act on the development of hematologic malignancies.
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PMID:Mutational analysis of IkappaBalpha in hematologic malignancies. 1252 85

Coagulation disorders are common in cancer patients. In patients with solid tumors, a low-grade activated coagulation can result in systemic and cerebral arterial or venous thrombosis. Cancer treatments may also contribute to this coagulopathy, which usually, but not exclusively, occurs in the setting of advanced malignant disease. There may be TIAs or cerebral infarctions. Because of the widespread distribution of cerebral thromboses, there may be a superimposed encephalopathy; sometimes this is the only sign. Concurrent systemic thrombosis is present in many patients and is a useful clue to the diagnosis. In cerebral venous occlusion, the initial symptom is usually a headache. Except for cerebral intravascular coagulation that is unassociated with NBTE, neuriomaging studies usually demonstrate one or more parenchymal infarctions. MRI or MRV may demonstrate venous thrombosis. The laboratory evidence of coagulopathy is difficult to distinguish from the asymptomatic coagulopathy that often accompanies advanced cancer, and the test results must be interpreted cautiously. NBTE can be diagnosed by transesophageal echocardiography. There is no established treatment for the thrombotic coagulopathy associated with cancer, but anticoagulation should be considered. In leukemia and lymphoma, the coagulopathy is typically acute DIC that can lead to systemic and brain hemorrhages. It is especially common in acute myelogenous leukemias. The clinical signs of cerebral hemorrhage are fulminant and may be fatal. The bleeding usually occurs in the brain or subdural compartment, and rarely in the subarachnoid space. The diagnosis can be suspected by the clinical setting and by systemic thrombosis or hemorrhage. It can be established by examination of the peripheral smear, the platelet count, and tests of coagulation function. Therapy of acute DIC is controversial and should be individualized for the clinical setting. Cerebrovascular disorders can complicate metastatic or primary tumor in the brain, skull, dura, or leptomeninges. The clinical signs of infarction are indistinguishable from other causes of stroke, except that tumor-related venous occlusion will usually first produce signs of increased intracranial pressure. The diagnosis of tumor-related infarction can usually be established by neuroimaging studies that show infarction and may show extracerebral sites of tumor. CSF examination is useful in diagnosing leptomeningeal metastasis. A search for lung or cardiac tumor should be performed when embolic tumor infarction is suspected. Primary or metastatic tumors in the brain or dura may hemorrhage, producing the initial clinical signs of the brain tumor or a change in chronic signs induced by the tumor. There are helpful clues to a neoplastic hemorrhage on brain CT or MRI scans. The brain hemorrhage may require evacuation and the underlying tumor will usually require additional antineoplastic treatment. Hyperleukocytosis (extreme elevation of the cell count) in acute myelogenous leukemia is a less common cause of brain hemorrhage in recent years because of improved methods to lower the cell count. Cerebral arterial or venous thrombosis is sometimes the result of cancer therapy. The attribution of thrombosis to chemotherapy in many published cases is only speculative, because carefully conducted prospective studies that include investigation for other thrombotic causes are not available. The best-known associations with thrombosis are L-asparaginase, which is typically used in the induction therapy of acute lymphocytic leukemia, and combination hormonal therapy and chemotherapy for breast cancer. Radiation to the head and neck, typically administered for head and neck epithelial cancers or lymphoma, may result in delayed carotid atherosclerosis. The distribution of stenosis or occlusion is within the radiation portal and is typically more extensive than is atherosclerosis that develops in the absence of radiation. Small clinical series suggest that surgical treatment is equally effective as in nonirradiated carotid atherosclerosis. In children, the cerebral vessels can be affected by brain radiation resulting in stenosis or occlusion. Brain hemorrhages can result from chemotherapy effects on the hemostatic system or a microangiopathic anemia. Hemorrhages from radiation-induced vascular abnormalities are rare. Opportunistic infections, especially fungal infections, can complicate cancer or its treatment. Septic cerebral emboli may result in focal cerebral signs, seizures, or encephalopathy. Sometimes there is an associated hemorrhagic vasculitis or cerebritis. Rarely, mycotic aneurysms may bleed. A high index of suspicion is needed to diagnose fungal infection because of the difficulty in culturing the organism from the blood or CSF. A clinician can usually establish the cause of stroke in the cancer patient by performing a careful review of the clinical setting--including the type and extent of cancer and the type of antineoplastic therapy--in which the stroke occurred. Systemic thrombosis, embolism, or hemorrhage can be a clue to the cause, and appropriate neuroimaging and coagulation studies to aid in the diagnosis are available. Therapy may ameliorate symptoms or prevent further episodes. The identification of one of these unusual stroke syndromes that leads to the diagnosis of an occult and treatable cancer can be particularly rewarding.
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PMID:Cerebrovascular complications in cancer patients. 1269 Jun 49

Methylation profile was analyzed in eleven cases of therapy-related leukemia (t-leukemia) for p14, p15, p16, Rb, hMLH1, hMSH2, MGMT, APC, RAR beta, DAPK, RIZ1, FHIT, and SOCS-1 genes by using methylation specific polymerase chain reaction (MSP) analysis. Six (55%) of eleven cases showed methylation of at least one gene. The average time to the development of t-leukemia after the treatment of the primary tumor was significantly shorter in patients with methylation than those without methylation (49.3 months vs. 133.2 months, P=0.044). These results suggest that hypermethylation might be involved in the development of t-leukemia.
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PMID:Aberrant methylation in promoter-associated CpG islands of multiple genes in therapy-related leukemia. 1288 5

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