Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0027651 (tumor)
 685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The goals of study NHL-BFM 90 for the therapy group Non-B NHL are to prospectively evaluate the dynamic of tumor regression and the persistence of a residual mass after induction therapy for its prognostic impact. Patients (pts) of stages I and II receive induction composed of prednisone, vincristine (VCR), daunorubicin, L-asparaginase (L-ASP), cyclophosphamide (CP), cytarabine (ARA-C), 6-mercaptopurine (6-MP) and intrathecally (i.th.) methotrexate (MTX), followed by consolidation (6-MP,MTX 5 g/m2 x 4, MTX i.th.), and maintenance up to 24 months. Pts of stages III and IV receive additionally reinduction (Dexamethasone, VCR, doxorubicin, L-ASP, CP, ARA-C, 6-thioguanine, MTX i.th.) and cranial irradiation. Pts with < 70% tumor regression at day 33 of induction receive an intensified chemotherapy. Pts with > 70% tumor regression at day 33 but a persistent mass at the end of induction have a surgical resection. Pts with a completely necrotic residual mass continue with consolidation therapy. Pts with active residual lymphoma receive an intensified chemotherapy. No local radiotherapy is given. From 4/1990 to 12/1992, 80 pts were registered; 71 pts are evaluable for response. The distribution of stages is as follows: 6, 1, 47, 17 pts of stage I, II, III, IV, respectively. The probability of event free survival at 3 years is 87 +/- 4% for the whole group (median observation time 21 months). 66 pts are evaluable for the dynamic of response.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:[NHL-BFM 90 therapy study in treatment of malignant non-Hodgkin's lymphomas in children and adolescents. Part 2: An intermediate term analysis of the non-B-NHL therapy group. BFM Study group]. 796 19

The resistance of certain tumor cells to the chemotherapeutic agent L-asparaginase has often been found to be associated with the presence of asparagine synthetase activity. In an attempt to study the translational regulation of the asparagine synthetase gene, the 5'-untranslated region of human asparagine synthetase cDNA was mapped by antisense oligonucleotide-mediated hybrid arrest translation in reticulocyte lysate. Three consecutive cis-acting regulatory elements, spanning from -60 to -120 bases from the initiation codon, in the 5'-untranslated region of the asparagine synthetase gene, were identified. T1 RNase footprinting analysis showed that those regulatory elements can be protected from T1 digestion when incubated with reticulocyte lysate. A 46-kDa trans-acting protein factor that interacts with the cis-acting regulatory element of asparagine synthetase mRNA was detected. This 46-kDa protein factor is most likely to be the eucaryotic peptide chain initiation factor eIF-4A as determined by immunoprecipitation experiments using a monoclonal antibody raised against reticulocyte eIF-4A.
 ...
PMID:Interaction of the eucaryotic peptide chain initiation factor eIF-4A with the specific elements at the 5'-untranslated sequence of human asparagine synthetase mRNA. 809 51

Amino acid-degrading enzymes are known to inhibit the growth of tumor cells in culture by depleting amino acids in the medium. Here we demonstrate that arginine deiminase (EC 3.5.3.6) from Mycoplasma arginini had stronger growth-inhibitory activity against all 4 kinds of tumor cell lines tested than L-asparaginase and arginase, which are well-known anti-tumor enzymes. Next, chemical modification of the arginine deiminase molecule with polyethylene glycol was shown to enhance its potency as an anti-tumor enzyme. The percentage of modified amino groups per molecule was estimated to be 51% of the total amino groups, and the average molecular weight was estimated to be about 400,000 by gel-filtration HPLC. The enzymic activity of the modified enzyme was 25.5 units/mg protein, which was equivalent to 57% of that of the native enzyme. The modified enzyme strongly inhibited growth of a mouse hepatoma cell line, MH134, at a concentration of more than 10 ng/ml, showing almost the same dose-response curve as the native enzyme. When a bolus of 5 units of the modified enzyme was intravenously injected into male BDF1 mice, L-arginine in the blood completely disappeared within 5 min, and remained undetectable for more than 8 days. On the other hand, in the case of bolus injection of the same number of units of native enzyme, the plasma L-arginine level recovered up to 66% of the control level at 8 days. These results suggest that this modified enzyme has a longer plasma clearance time and may be more effective as a new anti-tumor agent than the native enzyme.
 ...
PMID:Chemical modification by polyethylene glycol of the anti-tumor enzyme arginine deiminase from Mycoplasma arginini. 827 24

We reported a case of ALL complicated with acute pancreatitis caused by L-asparaginase (L-Asp). The patient was a 42-year-old man, who showed eosinophilia in peripheral blood and an increase of lymphoblast in bone marrow. He was diagnosed as ALL (L2) and treated by JALSG '87 protocol. Remission induction chemotherapy including L-Asp was administered by 5,000 IU i.v. for 10 days. The day after giving all dose of L-Asp, slight epigastralgia developed and then became severe. After two days, s-amylase was markedly elevated, and the patient was diagnosed as acute pancreatitis caused by L-Asp. He was treated conservatively, but hyperglycemia occurred. The epigastrial tumor was palpable and gradually grew in size. CT-scan and abdominal ultrasonography revealed pancreatic pseudocyst, so he was treated by percutaneous cyst drainage. The patient died of a relapse of ALL. The prophylaxis and early diagnosis of the pancreatitis and hyperglycemia caused by L-Asp are very difficult. We have to examine more cases and pay greater attention to the chemotherapy, including L-Asp.
 ...
PMID:[A case of ALL complicated with acute pancreatitis and pancreatic pseudocyst caused by L-asparaginase ]. 842 80

Dural sinus thrombosis (DST) has been reported in association with cancer in both adults and children. We describe the seven patients seen with this complication in our centre between 1981 and 1995. Diagnosis was confirmed by either cerebral CT scanning, MRI or angiography. Median age was 13 years (range 8-15). Six patients were boys. Six children were being treated for non-Hodgkin lymphoma and one for neuroblastoma. Presenting symptoms were seizures and transient neurologic deficit, often preceded by headaches. The probable cause of DST was found in two cases. Tumour localisation in the central nervous system (CNS) probably caused DST in one patient who was treated for ki 1 lymphoma. Dehydration in combination with a poor general condition seemed to be the cause of DST in the patient with neuroblastoma. In five children with stage III or IV non-Hodgkin lymphoma (three lymphoblastic lymphoma; two Burkitt's lymphoma), etiology remained unknown. In these children, DST occurred early in the course of therapy. The median interval between start of chemotherapy and onset of symptoms was 19 days (range 8-40). No child had received L-asparaginase. Prognosis was favourable, with symptoms completely disappearing without therapy within 1 to 5 days. The incidence of DST in patients with advanced stage non-Hodgkin lymphoma during induction and consolidation was calculated to be below 3%. We conclude that DST is rarely diagnosed in children with cancer. Occurrence during the initial phase of therapy for non-Hodgkin lymphoma is associated with a benign prognosis.
 ...
PMID:Dural sinus thrombosis in children with cancer. 1211 89

We describe the clinical and laboratory features of an unusual case with Sezary cell-like leukemia. Clinical manifestations were: anemia (Hb 9.4 g/dl), severe thrombocytopenia (5 x 10(9)/l), lymphocytosis (43 x 10(9)/l) and splenomegaly. There was no lymphadenopathy, hepatomegaly or skin lesions. Bone marrow trephine showed diffuse infiltration by atypical lymphoid cells. By ultrastructural analysis the cells were small to medium-size lymphocytes with nuclear features identical to Sezary cells. Immunophenotyping showed that most peripheral blood mononuclear cells were negative with B lymphoid, myeloid, and stem cell-associated markers and were also negative with most T lymphoid markers (CD2, CD4, membrane/cytoplasmic CD3, CD5 and CD8). However, they were positive with CD38 (70%), CD7 (25%) and TIA-2 (25%). Molecular analysis showed a clonal rearrangement of the TCR beta and gamma chain genes. The patient was initially treated with vincristine, doxorubicin and asparaginase and then with six cycles of CHOP, achieving a complete remission and remaining free of disease 22 months from diagnosis. Aberrant immunophenotypes are not frequent in primary T cell leukemias. This is the first case of a rare type of T cell neoplasm, Sezary cell-like leukemia, in which cells lacked most of the T cell-associated antigens.
 ...
PMID:Sezary cell-like leukemia with atypical immunophenotype. 926 98

Involvement of the temporal bone in patients with malignant lymphomas is very rare. Most of the reported cases have been clinically asymptomatic and were diagnosed only by post-mortem examinations. We present a nasal, paranasal, nasopharyngeal lymphoma that occurred in a 12-year-old child and also involved the temporal bone. Clinical presentation began with bilateral chronic otitis media. Histopathologically, tumor was found to be an angiocentric lymphoma of B-cell origin. Association with Epstein-Barr virus could not be demonstrated. Despite combination chemotherapy (with cyclophosphamide, vincristine, doksorubicine, prednisolone, L-asparaginase, cytosine arabinoside, metotraxate) and radiotherapy (to 40 Gy), disease progressed locally as well as to cervical lymph nodes and the lungs.
 ...
PMID:Angiocentric lymphoma involving the temporal bone in a child. 1039 3

A 30-year-old man was admitted to our hospital with subcutaneous tumors and a high fever. Based on biomicroscopic findings of the tumor, the patient was diagnosed as having diffuse, medium, well-differentiated malignant lymphoma. Immunochemical analysis showed that CD3, CD4, CD25, and TCR beta were positive, and in situ hybridization revealed Epstein-Barr virus-encoded small RNAs in the nuclei of the lymphoma cells. Despite the patient's resistance to multidrug therapy, complete remission was achieved using L-asparaginase. This case is unique because of its peculiar clinical course and a possible association with the Epstein-Barr virus. L-asparaginase may be an important treatment in other patients who exhibit some of these characteristics.
 ...
PMID:L-asparaginase induced complete remission in Epstein-Barr virus positive, multidrug resistant, cutaneous T-cell lymphoma. 1040 84

The aim of this study was to investigate the prognostic importance of different clinical, immunohistologic and tumor proliferation characteristics in dogs with malignant lymphoma treated with chemotherapy. From 74 dogs with malignant lymphoma at least one enlarged peripheral lymph node was taken for biopsy before chemotherapy following a standardized protocol (vincristine, cyclophosphamide, prednisolone, doxorubicin, and L-asparaginase). The variables evaluated as prognostic factors were age, sex, and tumor stage, as well as histomorphologic grade (Kiel classification, Working Formulation), immunophenotype (using markers for CD3 and CD79a), and cell proliferation (Ki-67, proliferation cell nuclear antigen, mitotic index, and argyrophil nucleolar organizer regions [AgNORs]) in extirpated lymph nodes. All markers were used on routinely formalin-fixed, paraffin-embedded tissues. The AgNORs were assessed qualitatively, based on the AgNOR pattern distribution, and quantitatively using image analysis and routine counting. In both univariate and multivariate survival analyses, AgNORs were a valuable prognostic marker for the treatment of canine malignant lymphomas. Based on the results of the multivariate analysis longer survival time correlated with a B-cell type, a larger mean AgNOR area, a larger total AgNOR area, a shorter distance between two AgNORs, and a smaller AgNOR area to nucleus ratio. Longer disease-free survival time correlated with a smaller number of AgNORs per nucleus, a larger mean AgNOR area, a larger maximal AgNOR area, and a larger total AgNOR area. This study clearly demonstrates the additional benefit of the use of AgNORs in predicting treatment outcome in dogs with malignant lymphoma.
 ...
PMID:Prognostic factors for treated canine malignant lymphoma. 1042 Oct 95

Polymer conjugation is of increasing interest in pharmaceutical chemistry for delivering drugs of simple structure or complex compounds such peptides, enzymes and oligonucleotides. For long time drugs, mainly with antitumoral activity, have been coupled to natural or synthetic polymers with the purpose of increasing their blood permanence time, taking advantage of the increased mass that reduces kidney ultrafiltration. However only recently complex constructs were devised that exploit the 'enhanced permeability and retention' (EPR) effect for an efficient tumor targeting, the high molecular weight for adsorption or receptor mediated endocytosis and finally a lysosomotropic targeting, taking advantage of acid labile bonds or cathepsin susceptible polypeptide spacers between polymer and drug. New original, very active conjugates of this type, as those based on poly(hydroxyacrylate) polymers, are already in advanced state of development. Labile oligonucleotides, including antisense drugs, were also successfully coupled to polymers in view of an increased cell penetration and stabilization towards nucleases. However, the most active research activity resides in the field of polypeptides and proteins delivery, mainly for the two following reasons: first of all because a great number of therapeutically interesting compounds are now being produced by genetic engineering in large quantity and, secondly, because these products are difficult to administer to patients for several inherent drawbacks. Proteins are in fact easily digested by many endo- and exo-peptidases present in blood or in other body districts; most of them are immunogenic to some extent and, finally, they are rapidly excreted by kidney ultrafiltration. Covalent polymer conjugation at protein surface was demonstrated to reduce or eliminate these problems, since the bound polymer behaves like a shield hindering the approach of proteolytic enzymes, antibodies, or antigen processing cell. Furthermore, the increase of the molecular weight of the conjugate allows to overcome the kidney elimination threshold. Many successful results were already obtained in peptides and proteins, conjugated mainly to water soluble or amphiphilic polymers like poly(ethylene glycol) (PEG), dextrans, or styrenemaleic acid anhydride. Among the most successful are the conjugates of asparaginase, interleukin-2 or -6 and neocarcinostatin, to remind some antitumor agents, adenosine deaminase employed in a genetic desease treatment, superoxide dismutase as scavenger of toxic radicals, hemoglobin as oxygen carrier and urokinase and streptokinase as proteins with antithrombotic activity. In pharmaceutical chemistry the conjugation with polymers is also of great importance for synthetic applications since many enzymes without loss of catalytic activity become soluble in organic solvents where many drug precursors are. The various and often difficult chemical problems encountered in conjugation of so many different products prompted the development of many synthetic procedures, all characterized by high specificity and mild condition of reaction, now known as 'bioconjugation chemistry'. Bioconjugation developed also the design of new tailor-made polymers with the wanted molecular weight, shape, structure and with the functional groups needed for coupling at the wanted positions in the chain.
 ...
PMID:Bioconjugation in pharmaceutical chemistry. 1051 Aug 47


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>