Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0178874 (tumor progression)
 40,807 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The presence of RAS gene mutations in precancerous lesions suggests that they participate in the early stages of neoplastic development. Furthermore, neoplastic progression from monoclonal gammopathy of undetermined significance (MGUS) to overt multiple myeloma (MM) have been frequently observed. These observations prompted us to study the pathogenetic role of RAS genes in MM and related monoclonal gammopathies. DNA from 18 patients with monoclonal gamma-globulinemia including 12 MM were investigated for the presence of N- and K-RAS gene mutations by polymerase chain reaction (PCR)/oligonucleotide hybridization. Mutations involving codons 12, 13 or 61 of N-RAS gene were identified in 3 of the 12 MM patients, 1 of the solitary plasmacytoma patients and none of the 3 of the MGUS patients. In the case of plasmacytoma, RAS mutations were detected in his bone marrow specimens.
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PMID:RAS gene mutations in multiple myeloma and related monoclonal gammopathies. 192 Dec 61

Criteria were defined for recognizing 29 patients with a localized plasmacytoma of bone and 20 patients with an indolent variety of multiple myeloma in order to justify long-term follow-up without chemotherapy. All patients with indolent myeloma were asymptomatic from their low tumor mass disease, had a hemoglobin greater than 10 g/dl, and showed no more than 3 lytic bone lesions. The presence of more than 200 mg/day of Bence Jones protein was usually followed by disease progression within 2 yr. Serial assessments of myeloma protein level provided a useful index of changing tumor load and the need for chemotherapy. In patients with localized disease, radiotherapy usually reduced myeloma proteins markedly with subsequent disease control for many years, even though small serum peaks persisted. Chemotherapy for multiple myeloma was not required for a median of 8 yr in patients presenting with localized disease and of 3 yr in those with indolent myeloma. The additional survival from the start of drug treatment was similar to that of comparable patients treated promptly for overt multiple myeloma. The delay of chemotherapy until evidence of tumor progression did not affect the long-term outcome of patients with localized or indolent myeloma.
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PMID:Localized and indolent myeloma. 740 16

N- and K-ras oncogene mutations represent the most frequent molecular lesions in plasma cell dyscrasias. They are not randomly distributed since they are detectable in multiple myeloma (MM) (9-31%) and plasma cell leukemia (PCL) (30%), and not in monoclonal gammopathy of undetermined significance (MGUS) and solitary plasmacytoma (SP). Codons 12, 13 and 61 of N- and K-ras genes have been found mutated. Mutations affecting codon 61 of N-ras gene are the most frequent finding. A heterogeneous pattern of mutations is described with a prevalence of purine-pyrimidine transversions. Ras gene mutations have been predominantly detected in myelomas characterized by an advanced stage disease, and adverse prognostic parameters. These findings suggest that ras mutations represent a late molecular lesion and may be implicated in tumor progression rather than tumor initiation.
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PMID:N- and K-ras oncogenes in plasma cell dyscrasias. 785 96

BALB/cAn mice are highly susceptible to the induction of plasmacytomas (PCTs) by the i.p. injection of paraffin oils, whereas DBA/2 mice are solidly resistant. To search for genes that control the dominant resistant phenotype of DBA/2, BALB/c.DBA/2 (C.D2) congenic strains were constructed, and the susceptibility and resistance to PCT development were determined. PCT formation takes place over an extended period of 365 days but begins morphologically in focal proliferations of atypical plasma cells (foci) in the reactive oil granuloma that forms on mesenteric surfaces. Cells from some of these foci spread to other locations in oil granuloma tissue, forming new foci. Mice that develop six or more foci appear to be progressing towards eventual overgrowth and replacement of all peritoneal tissues with PCT cells. From Days 100 to 250, between 28 and 56% of PCT-susceptible BALB/cAn mice had 6 or more foci, whereas less than 5% of resistant DBA/2, BALB/c x DBA/2 F1 (hereafter called CD2F1), C57BL/6, and BALB/cJ mice had 6 or more foci. Four CD2 congenic strains carrying D2 alleles of genes on chromosomes other than chromosome 4 were highly susceptible. Between 0 and 20% of the mice in C.D2-Chr 4 congenic strains C.D2-MIA, C.D2-TF3, C.D2-Fv-1n/n, C.D2-Pnd7, C.D2-Lgm-1A, C.D2-Lgm-1B, C.D2-Lgm-1C, and C.D2-Lgm-1H developed 6 or more foci from 125 to 260 days, indicating resistance. The segments of DBA/2 chromosome 4 chromatin in C.D2-Fv-1n/n and C.D2-Pnd7 were discontinuous with those in C.D2-TF3, C.D2-Lgm-1A, C.D2-Lgm-1B, C.D2-Lgm-1C, and C.D2-Lgm-1H, indicating there are at least two genes (Pctr1 and Pctr2) in the distal half of this chromosome that confer resistance. Pctr1 is located between Ifa and D4Rck41, and Pctr2 is between Tnfr-1 and Pkcz. Each locus acting alone distinctly conferred a partial resistant phenotype. Pctr1 and Pctr2 did not appear to prevent the formation of clonal foci but did appear to limit the ability of the plasma cells in foci to acquire greater autonomy; thus, these genes affect tumor progression.
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PMID:Identification of two genes on chromosome 4 that determine resistance to plasmacytoma induction in mice. 831 88

The majority of inflammation-induced peritoneal BALB/c plasmacytomas (approximately 90%) harbor a balanced T(12;15) chromosomal translocation that deregulates the expression of the proto-oncogene c-myc. Recent evidence suggests that the T(12;15) is an initiating tumorigenic mutation that occurs in early plasmacytoma precursor cells. However, plasmacytomas take a long time to develop (average tumor latency approximately 220 days), which suggests that additional tumor progression events may be required to complete oncogenesis. We hypothesized that such tumor progression events may take the form of secondary chromosomal aberrations that can be detected by spectral karyotyping (SKY). We screened the entire chromosome complement of 18 primary BALB/c plasmacytomas carrying the T(12;15) and found in nine tumors (50% recurrence) secondary cytogenetic aberrations that involved bands D, E and F chromosome (Chr) 5. The Chr 5D-F rearrangements were manifested predominantly as unbalanced translocations with various partner chromosomes. This finding led us to propose the existence of an important plasmacytoma progression locus in the central region of Chr 5, which presumably becomes involved in peritoneal plasmacytoma development by promiscuous chromosomal translocations.
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PMID:Recurrent non-reciprocal translocations of chromosome 5 in primary T(12;15)-positive BALB/c plasmacytomas. 1039 54

Myc-activating chromosomal 12;15 translocations, the hallmark mutations of inflammation-induced BALB/c plasmacytomas, have recently been shown to undergo remodeling by isotype switch-like genetic recombinations that remove approximately 180 kb of immunoglobulin heavy-chain sequence in the vicinity of the rearranged, expressed Myc gene. Here we combine cytogenetic data on the 12;15 translocation (SKY and FISH) with the molecular analysis of key junction sites (long-range PCR followed by DNA sequencing) to demonstrate that translocation remodeling occurred as an infrequent, stepwise, and disomic tumor progression event in the tetraploid, fully transformed, and transplantable plasmacytoma TEPC 3610. This result was used, in conjunction with previously obtained molecular data on five other primary plasmacytomas, to devise a hypothesis that predicts that the selective pressure to undergo translocation remodeling may be predetermined by the location of the break site in Myc. The pressure may be low if the break occurs 5' of the normal promoter region of Myc, but it may be considerably stronger if the break occurs 3' of the Myc promoter. Published 2001 Wiley-Liss, Inc.
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PMID:Translocation remodeling in the primary BALB/c plasmacytoma TEPC 3610. 1117 Feb 86

IL-10 is assumed to be a major immunosuppressive factor produced by most B-cell tumors. The immunosuppressive role of tumor-derived IL-10 was analyzed using the MHC class II-negative BALB/c plasmacytoma ADJ-PC-5 as a model tumor. Immune monitoring of tumor-bearing mice was based on the measurement of tumor burden, tumor-specific CTL cytotoxicity and intracellular cytokine staining using FACS. ADJ-PC-5 tumor progression in syngeneic recipients is associated with strong, concomitant, tumor-specific CTL responses during early stages of tumor progression which are sufficient to cause rejection of small s.c. autologous test tumors. These initial CTL responses gradually decline during later tumor stages. Blocking of IL-10 in vivo did not abolish CTL suppression or retard tumor growth. More strikingly, application of anti-IL-10 antibodies during early tumor stages abrogated CTL induction and markedly accelerated tumor growth. In contrast to anti-IL-10 treatment, application of cyclo-oxygenase inhibitors to ADJ-PC-5 tumor-bearing mice led to enhanced tumor-specific CTL responses throughout all stages of tumor progression, paralleled by retarded tumor growth and a significantly delayed onset of suppression. Both findings contradict a dominant immunosuppressive role of IL-10 during B-cell tumor progression. Tumor-derived IL-10 must therefore be considered an immunostimulating factor, which accounts for the high immunogenicity of B-cell tumors, whereas prostaglandins, which are not produced by the tumor cells themselves, are the dominant immunosuppressors in this system.
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PMID:Prostaglandins, but not tumor-derived IL-10, shut down concomitant tumor-specific CTL responses during murine plasmacytoma progression. 1126 84

Anti-4-1BB monoclonal antibody (mAb) has been shown to induce antitumor immunity by a CD4/CD8-dependent mechanism, but its direct effect on tumor-specific CD8+ T cells in tumor rejection is unclear. Here we used transgenic CD8+ T cells against the unmutated tumor rejection antigen P1A to analyze whether this mAb can promote CD8+ T-cell function against large tumors in the absence of CD4+ T-helper cells. RAG-2(-/-) mice were challenged with P1A-expressing plasmacytoma J558. Once tumor size reached a diameter of 0.85-1.75 cm, mice were treated with P1A-specific CD8+ CTL (P1CTL) in conjunction with anti-4-1BB mAb or control IgG. All of the mice showed a partial regression of tumor, but mice treated with anti-4-1BB mAb exhibited markedly enhanced tumor rejection, delayed tumor progression, and prolonged survival. Correspondingly, we observed a substantial increase in the number of P1CTL in anti-4-1BB mAb-treated mice. Surprisingly, anti-4-1BB mAb did not accelerate division of the tumor-specific CD8+ T cells, and the increase in tumor-specific T-cell number was due to reduced activation-induced cell death. These results indicate that anti-4-1BB mAb can promote CD8+ T cell-mediated protection against large tumors in the absence of CD4+ T-cell help by promoting P1CTL survival without increasing initial clonal expansion.
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PMID:Anti-4-1BB monoclonal antibody enhances rejection of large tumor burden by promoting survival but not clonal expansion of tumor-specific CD8+ T cells. 1206 89

BACKGROUND: Solitary extramedullary plasmacytoma of the parotid gland is a rare condition. Intracytoplasmic Crystalline inclusions in the tumor are even rarer and have been reported only once in the parotid gland. CASE PRESENTATION: We report here, a case of plasmacytoma of the parotid gland with intracellular crystalline inclusions in a 73-year-old woman CONCLUSION: Solitary extramedullary plasmacytoma of the parotid gland and crystalline inclusions in the tumor is of rare occurrence. The importance of such a finding with relation to tumor progression, clinical course of the disease or prognosis in general remains to be understood.
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PMID:Solitary Plasmacytoma of the Parotid Gland with Crystalline Inclusions: A Case Report. 1292 38

A 69-year-old woman visited a hospital with a complaint of left abdominal dull pain. A computed tomographic scan demonstrated a large tumor with central necrosis in the left retroperitoneum, and an angiography revealed hypervascular tumor which was fed from splenic, left renal, left gastric and left colic arteries. Renal cell carcinoma with extrarenal progression was pre-operatively suspected, and a resection was attempted. However, since the celiac artery was involved in the tumor, only a biopsy was performed. The histopathological finding of the biopsy specimen was a plasmacytoma. A combination of chemotherapy and radiation therapy resulted in a marked reduction of the tumor. There was no evidence of tumor progression one year after the chemotherapy.
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PMID:[A case of retroperitoneal extramedullary plasmacytoma]. 1497 56


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