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

In the present study we investigated the frequency of p16 gene exon 2 mutations in 35 malignant gliomas, using either direct sequencing of the PCR products or cloning into the pCRII vector and sequencing of the cloned PCR products. No mutations were detected during direct sequencing of the PCR products. However, after sequencing of individual clones, we found multiple mutations in 5 tumors involving codons 73(GCC to ACC, Ala to Thr), 76 (GCC to GTC, Ala to Val), 85(GCT to ACT, Ala to Thr), 98(CAC to TAC, His to Tyr), 102 (GCG to GTG, Ala to Val), 106 (GTG to ATG, Val to Met), 107 (CGC to TGC, Arg to Cys), 127 (GCA to GTA, Ala to Val), 128 (CGG to TGG, Arg to Trp) and 136 (GGC to GAC, Gly to Asp). Mutations were found only in glioblastomas and were either C to T or G to A transitions. Each mutation was detected in a small percentage of tumor cells (1.3-22%) using individual colony sequencing and southern hybridization with mutant oligonucleotides, consistent with the heterogenous cell population of glioblastomas. The presence of p16 gene mutations only in glioblastomas suggests that they are late events in glioma development.
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PMID:Mutations of the p16 gene in gliomas. 855

Allogeneic bone marrow transplantation (BMT) is the only effective treatment for hematologic malignancies resistant to conventional chemotherapy. Until recently, no cure existed for patients who relapsed post-BMT. We present our long-term observations on remission induction, after relapse post-BMT, by allogeneic cell therapy (allo-CT) and the feasibility of remission induction in allo-CT-resistant patients by activation of antileukemia effector cells with recombinant human interleukin-2 (rhIL-2) in vitro and in vivo. The longest observation of successful allo-CT (event-free survival, greater than 8 years) was made in a patient with resistant pre-B lymphoblastic leukemia who received infusions with graded increments of donor (female) peripheral blood lymphocytes (PBL) as soon as bulky hematologic and extramedullary relapse was noticed early post-BMT. The patient is currently without evidence of residual host (male) cells as determined by polymerase chain reaction (PCR). Of 17 patients with acute and chronic leukemia in relapse after BMT, 10 were reinduced into complete remission. Four patients with cytogenetic relapse responded to allo-CT alone, while five of six patients with overt hematologic relapse responded only after additional activation of donor with rhIL-2. Allo-CT can, therefore, successfully reverse chemoradiotherapy-resistant relapse of both acute and chronic leukemia. Moreover, in patients resistant to donor lymphocyte infusion, remission can be accomplished by additionally activating donor PBL in vitro and/or in vivo with rhIL-2. Based on our observations, after BMT, allo-CT should be considered the treatment of choice for patients with hematologic malignancies resistant to conventional anticancer modalities. Allogeneic activated cell therapy (allo ACT) should be considered for patients with tumor cells resistant to allo-CT. Although allo-CT, followed if indicated by allo-ACT, can be effective for patients with overt hematologic relapse, reversal of persistent minimal residual disease or documented molecular/cytogenetic relapse early after BMT may also be considered as a possible indication for allo-CT.
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PMID:Allogeneic cell therapy with donor peripheral blood cells and recombinant human interleukin-2 to treat leukemia relapse after allogeneic bone marrow transplantation. 863 Mar 79

Several advantages become immediately apparent when the prostate specific antigen (PSA, or tPSA) assay is replaced by the assay specific for the serum PSA-alpha 1-antichymotrypsin (PSA-ACT) complex. For instance, random contributions to the tPSA value by various serum minor PSA isoforms can be avoided, making possible the determination of a more accurate relation of the PSA-ACT concentration to the tumor activity. Discrepancies in percent free PSA (% fPSA) values from the same specimens due to the use of different commercial kits also can be eliminated, mainly because the PSA-ACT assay does not have the problems in antibody selection and calibrator preparation usually associated with the tPSA assay. We found that at the present time different cutoffs of % fPSA for the differentiation of BPH from prostate cancer must be established for each individual tPSA assay. Cutoffs established using values from one tPSA assay should not be used for making clinical decisions when their tPSA values are determined by a different kit. Moreover, when we monitored the patients during treatment with serum tPSA, specific fPSA, and specific PSA-ACT complex assays simultaneously, it was clear that any interpretation of the patient's clinical status based on tPSA values alone could be misleading. Because there is less PSA-ACT complex in BPH specimens relative to that found in cancer serum samples, expressing fPSA as "fPSA/PSA-ACT x 100" and measuring PSA-ACT complex concentrations instead of tPSA during screening improve the measurable contrast between BPH and prostate cancer. Although individually modest, collectively these advantages can add up to considerable improvements.
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PMID:Advantages of replacing the total PSA assay with the assay for PSA-alpha 1-antichymotrypsin complex for the screening and management of prostate cancer. 948 67

Based on the recent findings that show how recombinant human tumor necrosis factor (rh-TNF)-alpha has potent antitumor activity on human cancer patients when it locally administrated, we have tested the cytotoxicity of rh-TNF-alpha on 3 canine cultured cells: (1) canine kidney carcinoma (CKCa-1), (2) mastocytoma and (3) Mardin Darby canine kidney cells (MDCK). The cell surface expression of TNF-alpha receptors on these canine cells was also determined with anti-human TNF RI and RII polyclonal antibodies. Our data shows that on CKCa-1 which has TNF RI receptors rh-TNF-alpha induced cytotoxicity. By contrast, it exhibited no toxicity on canine mastocytoma which has mainly RII receptors. The data also suggest actinomycin D (ACT-D), an anticancer antibiotic, enhanced the cytotoxicity of rh-TNF-alpha. Combined with ACT-D, rh-TNF-alpha showed the cytotoxicity on MDCK which possessed both TNF RI and RII receptors. The results indicate that the cytotoxicity of rh-TNF-alpha depends on the presence of TNF RI receptors on canine tumor cells.
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PMID:Cytotoxicity induced by recombinant human tumor necrosis factor-alpha dependent on the types of its receptors on canine cells. 976

The in vitro cytotoxicity of recombinant human tumor necrosis factor-alpha (rh-TNF-alpha) and actinomycin D (ACT-D) on canine normal and tumor cells was investigated. rh-TNF-alpha showed dose-dependent cytotoxic and cell-growth inhibitory effects on cultured canine kidney carcinoma cells (CKCa-1). rh-TNF-alpha alone produced little cytotoxic effect on canine normal cells. However, combined with ACT-D, it showed moderate cytotoxicity on normal canine cells from the kidney medulla, spleen, heart muscle and lung. When the effects on the spontaneous tumor cells were examined, the combination of rh-TNF-alpha and ACT-D produced substantial cytotoxic effect on 60% of the tumor cells. All mammary mixed tumors and perianal gland tumors tested were susceptible to this combination. The data indicated the combination of rh-TNF-alpha and ACT-D have in vitro cytotoxicity on certain canine tumor cells.
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PMID:In vitro cytotoxicity of recombinant human-TNF-alpha and actinomycin D on canine normal and tumor cells. 981 61

Deletions and rearrangements involving the long arm of chromosome 11 are not infrequent occurrences in the non-Hodgkin's lymphomas. Recently, a tumor suppressor gene, the multiple endocrine neoplasia type 1 gene (MEN1) was cloned and mapped to chromosome 11q13. To assess the potential involvement of this gene in lymphomagenesis, we examined 94 primary cases of lymphoma and 12 cell lines by a combination of fluorescent in situ hybridization and PCR-SSCP analysis. In our initial analysis of 41 primary B or T lymphomas, MEN1 FISH analysis revealed allelic deletions in 15 cases (three of four B cell chronic lymphocytic leukemias, six of 15 follicular lymphomas, three of nine diffuse large B cell lymphomas, two of five mantle cell lymphomas, one of four Burkitt's lymphoma). To discern whether the MEN1 gene was in fact the target of the deletions, we assessed 20 of these 41 cases and an additional 74 primary lymphomas and 12 cell lines for MEN1 gene mutations using PCR-SSCP analysis. Abnormal SSCP patterns were found in exon 2 in two of the primary lymphoma cases and in one of the cell lines, but not in any of the original cases that showed MEN1 deletions by FISH. Furthermore, sequencing analysis revealed that the abnormal SSCP patterns in exon 2 were the result of a previously described genetic polymorphism (S145S: AGC --> ACT), and in one sample, the result of this S145S polymorphism associated with a second nucleotide substitution at position 498 which left the encoded amino acid unchanged. Our study indicates that the 11q13 locus is a frequent target of deletion in lymphoid neoplasms, but that there are no associated mutations of the MEN1 gene. This suggests that the 11q deletions either target another gene in lymphomas, or that the MEN1 gene is inactivated through means other than mutation.
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PMID:Allelic loss of 11q13 as detected by MEN1-FISH is not associated with mutation of the MEN1 gene in lymphoid neoplasms. 1004 65

Fourteen cases (13 pleural and one intrapulmonary) of solitary fibrous tumors (SFTs) (the so-called fibrous mesothelioma) were studied. The lesions occurred more in females (nine cases) than males (five cases). The age of patients ranged from 44 to 73 years old (median 60 years). The tumors presented as cough with or without blood-tinged sputum, exertional dyspnea, chest pain, nausea, body weight loss, fever, or as asymptomatic masses detected by routine chest radiograph. Two patients with huge (tumor larger than 20 cm) malignant tumors had accompanying pleural effusion and one associated with hypoglycemia. Ten benign tumors measured 2-11 cm (median size 7 cm) while the remaining four histologically malignant ones measured 20-30 cm in size. All of them were well circumscribed and thinly encapsulated. Hemorrhage and necrosis were more frequently seen in the malignant tumors. Histologically, these lesions were characterized by 'patternless pattern' with occasional hemangiopericytic features (three cases). The tumor cells were all immunoreactive for vimentin, CD 34, and focally actin-positive in one case, but not for keratin, desmin, S-100 protein, carcinoembryonic antigen, alpha 1-ACT and F VIII-related antigen, supported a primitive mesenchymal origin. p53 protein was expressed in two of the malignant cases. Proliferating cell nuclear antigen stain was positive with 50 and 80% of the labeling index in the benign and malignant tumors, respectively, but retinoblastoma gene protein was negative in all tumors. This analysis confirmed the relationship between histological malignant SFTs and tumor size, cellularity, mitotic activity, necrosis and tumor suppressor gene expression. However, the clinical behavior was unpredictable. Complete respectability seemed to be the most important indicator of clinical outcome in the less aggressive tumors.
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PMID:Thoracic solitary fibrous tumor: clinical and pathological diversity. 1010 Jan 46

Gallium-67-citrate and 99mTc-diphosphate bone imaging agents are localized in myositis ossificans, a tumor-like benign soft-tissue mass that makes it impossible to differentiate between malignant tumor and the infection/inflammatory process. We present such a myositis ossificans patient whose bone and 67Ga-citrate imagings showed increased uptake in the left thigh and two foci of the right gluteal region leading to inconclusive results. Technetium-99m-MIBI imaging showed the absence of substantial uptake in these regions. ACT scan confirmed myositis ossificans. The lack of 99mTc-MIBI uptake in myositis ossificans means that 99mTc-MIBI imaging may be useful in the differential diagnosis.
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PMID:Myositis ossificans demonstrated by positive gallium-67 and technetium-99m-HMDP bone imaging but negative technetium-99m-MIBI imaging. 1032 77

For over four decades, 5-fluorouracil (5-FU) has been the mainstay of therapy for colorectal cancer and a major cytotoxic agent for treating gastrointestinal tumors and a variety of others, including breast and head and neck cancers. Xeloda (capecitabine) is a new drug that is administered orally and has been rationally designed to generate 5-FU selectively within solid tumors. Theoretically, it has two major advantages, which should translate into an improved therapeutic index: firstly, enhanced drug concentration at the cancer site and therefore greater anti-tumor activity and secondly, reduced drug levels in non-tumor tissues, with a consequent reduction in systemic toxicity. After promising preclinical studies, phase I clinical trials of Xeloda have been performed with a variety of schedules, both with and without the oral biomodulator leucovorin. Anti-tumor activity has been observed with all regimens tested. In the setting of colorectal cancer, a randomized phase II study substantiated the phase I reports of activity and established the most promising regimen for phase III clinical trials. Patients in the phase II trial were randomly selected to receive either continuous Xeloda, intermittent Xeloda or intermittent Xeloda plus leucovorin. There were complete or partial responses in 21% of patients in the continuous arm, 24% in the intermittent arm, and 23% in the arm with intermittent Xeloda plus leucovorin. In addition, 51-63% of patients in each arm achieved stable disease. Therapy was well tolerated in all three arms. The intermittent regimen of Xeloda alone was associated with a longer time to disease progression and offered a one-week rest period to the patient. It was therefore selected for subsequent studies. Two randomized phase III trials of Xeloda versus the 'Mayo' regimen in patients with advanced colorectal cancer have completed recruitment. They are designed to demonstrate at least equivalent efficacy, with important secondary endpoints of comparisons of toxicity, medical care utilization, and quality of life. No formal results are yet available from these studies. The same regimen of Xeloda is now being evaluated in a large scale adjuvant study, which is expected to recruit approximately 1,700 Dukes' C colonic cancer patients (X-ACT study). The modest toxicity of Xeloda (particularly its low incidence of neutropenia) makes it a suitable candidate for novel combination therapies involving other agents that are active in colorectal cancer, including camptothecin and its analogues, oxaliplatin and radiotherapy. Further studies of Xeloda can be expected with other diseases known to be responsive to fluoropyrimidines, together with diseases traditionally thought to be resistant.
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PMID:Potential of Xeloda in colorectal cancer and other solid tumors. 1043 14

We have investigated the role of 23 candidate genes in the control of bone mineral density (BMD) by linkage studies in families of probands with osteoporosis (lumbar spine [LS] or femoral neck [FN] BMD T score < -2.5) and low BMD relative to an age- and gender-matched cohort (Z score < -2.0). One hundred and fifteen probands (35 male, 80 female) and 499 of their first- or second-degree relatives (223 males and 276 females) were recruited for the study. BMD was measured at the LS and FN using dual-energy X-ray absorptiometry and expressed as age- and gender-matched Z scores corrected for body mass index. The candidate genes studied were the androgen receptor, type I collagen A1 (COLIA1), COLIA2, COLIIA1, vitamin D receptor (VDR), colony-stimulating factor 1, calcium-sensing receptor, epidermal growth factor (EGF), estrogen receptor 1 (ESR1), fibrillin type 1, insulin-like growth factor 1, interleukin-1 alpha (IL-1alpha), interleukin-4 (IL-4), interleukin-6 (IL-6), interleukin-11 (IL-11), osteopontin, parathyroid hormone (PTH), PTH-related peptide, PTH receptor type 1 (PTHR1), transforming growth factor-beta 1, and tumor necrosis factors alpha and beta. Sixty-four microsatellites lying close to or within these genes were investigated for linkage with BMD. Using the program MapMaker/Sibs there was suggestive evidence of linkage between BMD and PTHR1 (maximum LOD score obtained [MLS] 2.7-3.5). Moderate evidence of linkage was also observed with EGF (MLS 1.8), COLIA1 (MLS 1.7), COLIIA1/VDR (MLS 1.7), ESR1 (MLS 1.4), IL-1alpha (MLS 1.4), IL-4 (MLS 1.2), and IL-6 (MLS 1.2). Variance components analysis using the program ACT, correcting for proband-wise ascertainment, also showed evidence of linkage (p </= 0.05) at markers close to or within the candidate genes IL-1alpha, PTHR1, IL-6, and COLIIA1/VDR. Further studies will be required to confirm these findings, to refine the location of gene responsible for the observed linkage, and to screen the candidate genes targeted at these loci for mutations.
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PMID:Suggestive linkage of the parathyroid receptor type 1 to osteoporosis. 1062 57


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