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)

We report the results of PBPC collection by large-volume leukaphereses and the hematologic recovery after high-dose chemotherapy supported by autologous PBPC reinfusion in a series of cancer patients treated at the Hematological Intensive Care Unit (UCHI) (Portuguese Institute of Oncology, Lisbon). Large volume leukaphereses were used to increase the efficacy of the PBPC collection. This modification of the standard apheresis technique allowed the harvesting, in only one session, of enough progenitors to proceed to transplantation in nearly 2/3 of patients and without significant toxicity. From December 1993 until September 1997, 95 autologous PBSC transplants were performed at the UCHI; 45% were performed in solid tumor patients and 55% in patients with hematologic malignancies. Hematologic recovery was similar to that published in the literature and related to the number of CD34+ cells infused. Patients supported with bone marrow in addition to PBPC showed delayed hematopoietic recovery, probably because the bone marrow harvest was only performed when an insufficient number of PBPC had been collected (2 x 10(6) CD34+ cells/Kg). The speed of hematological recovery differed per diagnosis, being higher in multiple myeloma and solid tumor patients and lower in Hodgkin's disease patients.
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PMID:[The use of peripheral blood progenitor cells as an autologous hematopoietic support in high-dose chemotherapy. II. The experience of the Hematological Intensive Care Unit of the IPOFG. Franciso Gentil Portuguese Institute of Oncology]. 1070 65

We have studied the frequency of p53 mutations in genomic DNA extracted from peripheral blood or the spleen of 61 patients with hairy cell leukemia using PCR-SSCP and automated cycle sequencing. We identified exon 5-8 mutations in 17 cases, corresponding to a frequency of 28%. In four cases, mutations were localized in exon 5; one patient with atypical HCL had a mutation in exon 6 at the 3' boundary; five cases showed mutations in exon 7, while exon 8 was found to be mutated in seven cases. The mutations found could be divided into three major categories: structural (n=9), inactivating (n= 6), and neutral (n= 2) mutations. None of the three transitions found occurred at CpG dinucleotides. The rate of p53 mutations found in this large cohort of HCL patients is unexpectedly high as in other non-Hodgkin lymphomas p53 mutations predict for poor treatment outcome. The character of the mutations we have found is entirely different from that described in other hematologic malignancies.
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PMID:p53 mutations in hairy cell leukemia. 1076 58

Over the past decade, splenic preservation has become a well-reported and accepted principle in trauma management. The reasons for splenic preservation may have influenced nontraumatic surgical management as well. To investigate the changing incidence and indications for splenectomy, we conducted a 10-year review of all splenectomies at our institution. During this time, between January 1, 1986, and December 31, 1995, 896 patients underwent splenectomy. Hospital charts and records were examined to determine the etiology and incidence of splenectomy. Indications were classified as: 1) trauma, i.e., performed for blunt or penetrating injury; 2) hematologic malignancy, i.e., therapy or staging of underlying leukemia, Hodgkin's lymphoma, or non-Hodgkin's lymphoma; 3) cytopenia, i.e., treatment of thrombocytopenia, anemia, or leukopenia; 4) iatrogenic, i.e., injury during another procedure; 5) incidental, i.e., required for adjacent organ resection; 6) portal hypertension, i.e., left-sided portal hypertension or during shunting procedure; 7) diagnostic, i.e., uncertainty excluding hematologic malignancy; or 8) other, i.e., miscellaneous indications. Trauma accounted for 41.5 per cent of all splenectomies during this time period, hematologic malignancy 15.4 per cent, cytopenia 15.6 per cent, incidental 12.3 per cent, iatrogenic 8.1 per cent, portal hypertension 2.3 per cent, diagnostic 2.0 per cent, and other 2.7 per cent. Comparing the first and second 5-year time periods, the following increases/decreases in average annual incidence were noted: splenectomy for all indications, -36.9 per cent; trauma, -32.9 per cent; hematologic malignancy, -51.4 per cent; cytopenia, 35.1 per cent; incidental, -35.9 per cent; iatrogenic, -30.2 per cent; diagnostic, +4.9 per cent, and other, -57 per cent. Traumatic injury to the spleen remains the most common indication for splenectomy, but the incidence has decreased dramatically over the past 10 years. Splenectomies for treatment of hematologic malignancies and cytopenia, as well as incidental and iatrogenic splenectomies, have also decreased significantly. Only the incidence of diagnostic splenectomy has remained stable. Although initiated within the field of trauma, the advantages of splenic preservation now appear to be well recognized beyond that field.
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PMID:The incidence of splenectomy is decreasing: lessons learned from trauma experience. 1082 50

The Bcl10 gene was identified through characterization of the t(1;14)(p22;q32) associated with mucosa-associated lymphoid tissue (MALT) lymphoma. Bcl10 is implicated in the regulation of apoptosis and has been reported to be mutated in other subtypes of non-Hodgkin's B-cell lymphoma (B-NHL) and leukaemic cell lines, raising the possibility that its deregulation could be implicated in other forms of haematological malignancy. We screened 226 cases, including 123 acute myeloid leukaemia (AML), 50 acute lymphoblastic leukaemia (ALL), 20 chronic myeloid leukaemia (CML), 10 chronic lymphocytic leukaemia-prolymphocytic leukaemia (CLL/PLL) and 23 cases with 1p abnormalities, for Bcl10 mutations by reverse transcription polymerase chain reaction-single-stranded conformation polymorphism (RT-PCR/SSCP). Three known polymorphisms and two common splice variants were identified; however, no mutations were detected. One splice variant led to a 33-bp in frame deletion, whereas the other caused a 16-bp deletion predicting C-terminal truncation of Bcl10. However, both splice variants were also detected in normal bone marrow, suggesting that they are unlikely to be of pathogenetic significance. Furthermore, Southern blot analysis revealed no rearrangements of Bcl10 among 16 ALL and 11 cases of haematological malignancy with 1p abnormalities. Our results suggest that mutation of the Bcl10 gene as a mechanism of tumorigenesis is not associated with leukaemia.
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PMID:Screening for mutations of Bcl10 in leukaemia. 1088 11

Interleukin-2 (IL-2) has proven to be able to generate an effective anticancer immunity against both solid and hematologic malignancies. Moreover, recent advances in the knowledge of psychoneuroimmunology have demonstrated that anticancer immunity is under neuroendocrine control and that the pineal hormone melatonin (MLT) may stimulate the IL-2-dependent anticancer reaction. Finally, preliminary clinical studies have already shown that the concommitant administration of MLT may amplify the efficacy of IL-2 in the treatment of advanced solid neoplasms, whereas there are no data about MLT influence on IL-2 activity in hematologic malignancies. The aim of the present study was to evaluate the efficacy and tolerability of a neuroimmunotherapeutic combination of low-dose IL-2 plus MLT in advanced hematologic malignancies which did not respond to previous standard therapies. The study included 12 evaluable patients. Tumor histotypes were as follows: non-Hodgkin's lymphoma (NHL) 6; Hodgkin's disease (HD), 2; multiple myeloma, 2; acute myelogenous leukemia (ALM), 1 and chronic myelomonocytic leukemia (CMML), 1. IL-2 was injected subcutaneously at a dose of 3 million IU/day for 6 days per week for 4 weeks, corresponding to one cycle. MLT was given orally at 20 mg/day in the evening, without interruption. In non-progressing patients, a second IL-2 cycle was planned after a 3 week-rest period. A partial response was achieved in one patient with multiple myeloma. Stable disease occurred in 7 other patients (NHL, 3; HD, 1; AML, 1; CLLM, 1; multiple myeloma, 1), whereas the other 4 patients progressed. Therefore, lack of progression was obtained in 8 out of 12 (67%) patients, with a median duration of 21+ months (14-30+ months). The treatment was well tolerated in all patients. These preliminary results would suggest that the concomitant administration of low-dose IL-2 plus the pineal hormone MLT may prolong the survival time in untreatable advanced hematologic malignancies, with results comparable to those previously reported using a more toxic immunotherapy, consisting of high-dose IL-2 alone.
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PMID:A phase II study of neuroimmunotherapy with subcutaneous low-dose IL-2 plus the pineal hormone melatonin in untreatable advanced hematologic malignancies. 1092 60

A 57-year-old female in complete remission of grade IV non-Hodgkin lymphoma whilst on intensive chemotherapy, suddenly developed unilateral hemispheric stroke with a fatal outcome in 3 days. She was apyrexial and had received antifungal prophylaxis during her treatment. Post-mortem examination showed complete thrombosis of the internal carotid artery leading to infarction in the territory of the middle and anterior cerebral arteries. Microscopic examination of the brain showed involvement of intra-cranial vessel walls and brain parenchyma by mucormyces, with no evidence of systemic mucormycosis. Isolated cerebral mucormycosis is a rare occurrence, more commonly found in intravenous drug abusers, but can occur in patients with haematological malignancy.
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PMID:Acute isolated cerebral mucormycosis in a patient with high grade non-Hodgkins lymphoma. 1097 6

Monoclonal antibodies are receiving ever-increasing utilization in the treatment of hematologic malignancies. Campath-1 antibodies are directed against the surface antigen CD52 that is expressed on virtually all lymphocytes and monocytes. Murine forms, Campath-1G and Campath-1M, have been utilized extensively in allogeneic bone marrow transplants in order to purge the allograft of lymphocytes. The humanized form, Campath-1H, is currently the focus of many clinical trials in hematologic malignancies and autoimmune diseases. The genetically engineered Campath-1H has been utilized in the treatment of lymphomas and lymphoid leukemias with impressive results. T-cell prolymphocytic leukemia, chronic lymphocytic leukemia, and non-Hodgkin lymphomas appear to be particularly good targets for this agent. Campath-1H may be administered intravenously or subcutaneously. Infectious complications are the most significant side effect associated with its usage, with fevers, chills, nausea, and vomiting most common. Antibiotic prophylaxis has made the infectious morbidity associated with Campath-1H more manageable. The efficacy demonstrated in clinical trials and manageable toxicities make Campath-1H an appealing agent in the treatment of hematologic malignancies.
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PMID:Campath-1H monoclonal antibody therapy. 1108 57

Hodgkin's disease (HD) is the most common haematological malignancy after chronic lymphocytic leukaemia, but very little is known about its pathogenesis or the genetic events that contribute to the malignant phenotype of the tumour cells. p53 is assumed to play an important role in the pathogenesis of HD, based on the observation that p53 protein is frequently accumulated in Hodgkin and Reed-Sternberg (H & RS) cells. We investigated single H & RS cells from five different HD patients for point mutations at the genomic level using multiplex polymerase chain reaction amplification and subsequent sequencing. No point mutations were detected in 50 single H & RS cells analysed. Hence, accumulation of p53 protein cannot be explained by mutations within the gene. A genome-wide screening for genomic imbalances using comparative genomic hybridization revealed gain on chromosome 12q14, i.e. the mapping position of the MDM2 gene in several HD cases. Therefore, we assessed the copy number of the MDM2 gene using fluorescence in situ hybridization. In four out of six HD cases analysed, the copy number of the MDM2 gene was found to be increased. As gene amplification is frequently associated with protein overexpression, the observed accumulation of p53 in the nuclei of H & RS cells could be as a result of elevated MDM2 protein levels resulting in stabilization of p53 protein.
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PMID:MDM2 gene amplification and lack of p53 point mutations in Hodgkin and Reed-Sternberg cells: results from single-cell polymerase chain reaction and molecular cytogenetic studies. 1126 82

Arsenic trioxide inhibits growth and promotes apoptosis in many different cancer cell lines. The National Cancer Institute is working cooperatively with research centers across the U.S. to evaluate its clinical activity in hematologic malignancies, such as acute promyelocytic leukemia, acute myeloid leukemia, acute lymphocytic leukemia, chronic myelogenous leukemia, non-Hodgkin's lymphoma, Hodgkin's disease, chronic lymphocytic leukemia, myelodysplastic syndrome, and multiple myeloma. It is also supporting research in solid tumors, such as advanced hormone-refractory prostate cancer and renal cell cancer and in cervical cancer and refractory transitional cell carcinoma of the bladder. The safety and pharmacokinetics of arsenic trioxide are also being evaluated in pediatric patients with refractory leukemia and lymphoma. The results of these ongoing studies should provide important insights into the clinical utility of arsenic trioxide in these diseases.
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PMID:Clinical trials of arsenic trioxide in hematologic and solid tumors: overview of the National Cancer Institute Cooperative Research and Development Studies. 1133 37

To target CD30 on Hodgkin's disease and anaplastic large-cell lymphoma, anti-CD30 single-chain antibodies were obtained by DNA immunization of mice with the complete human CD30 cDNA. Spleens were isolated from mice with high anti-CD30 titer, and the RNA was used for the production of an scFv-displaying phage library. Specific phages were enriched by 3 rounds of panning on soluble CD30 or CD30+ K562 cells. Recombinant immunotoxins (rITs) were made from 3 ELISA-positive scFv phages by fusion to a 38 kDa truncated mutant of Pseudomonas exotoxin (PE38) with or without a KDEL mutant sequence at the C terminus. In vitro cytotoxicity of purified anti-CD30 rITs was measured on CD30-transfected A431 cells. IC50 values ranged from 3 to 7 ng/ml (50-110 pM) for PE38 rITs and 0.1 ng/ml (2 pM) for the PE38-KDEL IT on A431-CD30 cells. The parental A431 cells were resistant, indicating that the cytotoxicity was specific and CD30-mediated. rITs were tested for anti-tumor activity in a nude mouse model. A431-CD30 cells were injected s.c. on day 0; then, mice bearing measurable tumors were treated beginning on day 4 with 3 alternate daily doses i.v. Anti-tumor activity was dose-dependent and not found when irrelevant ITs were administered or when CD30- tumors were treated. Our data show that DNA immunization and antibody phage display may be useful in producing new rITs against hematologic malignancies. Published 2001 Wiley-Liss, Inc.
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PMID:Isolation of new anti-CD30 scFvs from DNA-immunized mice by phage display and biologic activity of recombinant immunotoxins produced by fusion with truncated pseudomonas exotoxin. 1135 8


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