Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0006142 (breast cancer)
 160,383 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Neoplastic meningitis is a diffuse dissemination of tumor cells into the cerebrospinal fluid (CSF) and/or leptomeninges. It occurs in approximately 5-10% of malignant diseases, most often in breast cancer, lung cancer, melanoma or B-cell lymphoma. Symptoms of neoplastic meningitis are head or back pain, cranial nerve palsies, diffuse radicular symptoms or psychiatric disturbances. MRI shows nodular contrast enhancement lining CSF spaces. Positive CSF cytology requires optimal sampling and processing. Treatment must be individually shaped: the CSF dissemination may be treated with intrathecal chemotherapy with methotrexate or cytarabinoside (Ara-C). Liposomal Ara-C is distributed over the entire CSF space even after lumbar application and maintains cytotoxic levels for at least 2 weeks. Radiotherapy should be applied only to symptomatic solid spinal manifestations or fast progressing cranial nerve palsies. Systemic chemotherapy is needed to control solid manifestations or, in the case of substances entering the CSF, to support intrathecal chemotherapy.
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PMID:Diagnosis and individualized therapy of neoplastic meningitis. 2064 2

B-cell lymphoma 3 (Bcl3) is a proto-oncogene upregulated in a wide range of cancers, including breast cancer. Although Bcl3 is known to promote cell proliferation and inhibit apoptosis, the molecular mechanisms underlying the proto-oncogenic function of Bcl3 have not been completely elucidated. To gain insight into the oncogenic role of Bcl3, we applied a proteomic approach, which led to the identification of C-terminal binding protein 1 (CtBP1) as a binding partner of Bcl3. A PXDLS/R motif embedded in Bcl3 was found to mediate the interaction between Bcl3 and CtBP1, which caused the stabilization of CtBP1 by blocking proteasome-dependent degradation. Apoptotic stimuli-induced degradation of CtBP1 was significantly abolished by the upregulation of Bcl3, leading to the sustained repression of pro-apoptotic gene expression and subsequent inhibition of apoptosis. Intriguingly, a strong positive correlation between the protein levels of Bcl3 and CtBP1 was detected in breast cancer patient samples. Our study reveals a novel combinatorial role for Bcl3 and CtBP1, providing an explanation for the acquisition of resistance to apoptosis in cancer cells, which is a major requirement for cancer development.
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PMID:Bcl3-dependent stabilization of CtBP1 is crucial for the inhibition of apoptosis and tumor progression in breast cancer. 2080 May 78

The diagnosis, prognostic factors, and optimal management of primary breast lymphomas (PBL) is difficult. Seven patients recorded at the Geneva Cancer Registry between 1973-1998 were reviewed. Five patient had diffuse large B-cell lymphoma, one a follicular lymphoma and one a MALT-lymphoma. All patients had clinical and radiological findings consistent with breast cancer and underwent mastectomy, which is not indicated in PBL. Diagnosis should be established prior to operative interventions, as fine needle aspiration missed the diagnosis for one patient and intra-operative frozen sections for 3 patients in our study. Five-year and 10-year overall survivals were 57% and 15%, respectively. Of the 3 patients who died from PBL, 2 had tumors that were Bcl-2 positive but Bcl-6 negative. All 3 surviving patients have positive Bcl-2 and Bcl-6 immunostaining, which could be important prognostic factors if confirmed by a larger study.
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PMID:Primary breast lymphomas. 2113 85

The novel protein p33MONOX (p33Monooxygenase) was over-expressed in neuroblastoma cells demonstrating its inhibitory effect on the phosphorylation of the App (amyloid precursor protein) and Bcl2 (B-cell lymphoma 2) proteins but mediating higher activation of Mapk1/3 (mitogen-activated protein kinase 1/3). We employed a variety of cell biology techniques to show the localization of p33MONOX to the cytoplasm of pyramidal neurons in the mouse brain hippocampus. We also carried out a yeast-two-hybrid screening plus co-immunoprecipitation and bio-informatics to determine COBRA1 (cofactor of BRCA1 (breast cancer type 1)), NOL12 (nucleolar protein 12), and PRNP (prion protein) as p33MONOX-interacting proteins. Bio-computational analyses revealed a flavine-containing monooxygenase (FMO)-1 motif, thus linking p33MONOX to a group of previously characterized proteins, the MICALs (molecule interacting with CasL). Concluding, p33MONOX might regulate pre- and post-transcriptional control of dynamic processes related to growth cone guidance.
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PMID:Characterizing the novel protein p33MONOX. 2115 84

Vaccines based on peptide mimics (mimotopes) of conformational tumor antigen epitopes have been investigated for a variety of human tumors including breast cancer, tumors expressing the carcinoembryonic antigen, B cell lymphoma, neuroblastoma, and melanoma. In our previous work, we designed a vaccine based on a mimotope of the high molecular weight-melanoma associated antigen (HMW-MAA) that elicited HMW-MAA-specific antibodies (Abs) with anti-tumor activity in vitro and in vivo. In this study, we aimed to identify mimotopes of additional distinct HMW-MAA epitopes, since they could be used to construct a polymimotope melanoma vaccine. For this purpose, random peptide phage libraries were screened with the anti-HMW-MAA monoclonal antibodies (mAbs) VT80.12 and VF1-TP43 yielding one peptide ligand for each mAb. Both peptides inhibited the binding of the corresponding mAb to the HMW-MAA. Furthermore, when coupled to the carrier protein keyhole limpet hemocyanin (KLH), both HMW-MAA mimotopes elicited peptide-specific Abs in rabbits or BALB/c mice, but only the mimotope isolated with the mAb VT80.12 elicited HMW-MAA-specific Abs and only in mice. However, the latter Abs had no detectable effect on HMW-MAA expressing human melanoma cells in vitro. These results describe limitations related to the phage display technique and emphasize the need to characterize the functional properties of the mAb utilized to isolate mimotopes of the corresponding epitopes.
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PMID:Specificity of mimotope-induced anti-high molecular weight-melanoma associated antigen (HMW-MAA) antibodies does not ensure biological activity. 2157 18

A 193 base pair repeat polymorphism in the human poly(ADP-ribose) polymerase (PADPRP) pseudogene found on chromosome 13 has been associated with lung cancer, endemic Burkitt lymphoma, B-cell lymphoma, breast cancer and colorectal carcinoma. We investigated the frequency of the PADPRP genetic polymorphism in a hospital-based case-control study of lung cancer for 54 cases and 47 controls. There was a statistically significant difference in allelic frequency between Caucasians and African Americans (p<0.001). For African Americans, the odds ratio for lung cancer and the 'B' allele was 2.38 (95% C.I.=0.73, 7.69) and for Caucasians 0.44 (95% C.I.=0.11, 1.77). The results for the African Americans, however, were not in Hardy-Weinberg equilibrium, although the Caucasians were. Thus, this study, albeit small, does not find that the PADPRP pseudogene duplicated region located on chromosome 13 is a risk factor for lung cancer.
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PMID:Chromosome 13 poly(ADP-ribose) polymerase polymorphisms and lung cancer risk. 2159 40

Polymorphisms of the H2A histone family member X (H2AFX) gene have been associated with decreased non-Hodgkin lymphoma (NHL, -417AA) risk and increased breast cancer (1654AG/GG, and -1420GA/AA) risk. We investigated whether H2AFX polymorphisms are associated with the risk of NHL and its subtypes in 573 NHL Korean patients and 721 cancer-free control subjects, using high resolution melting polymerase chain reaction and an automatic sequencer. There was no association between polymorphisms and the risk of overall NHL, all B cell lymphoma, or all T cell lymphoma. However, the -1420 AA genotype was associated with decreased diffuse large B cell lymphoma (DLBCL) risk (OR, 0.65; 95% CI, 0.43-0.97), and there was a trend for allele dose-effect (p-trend=0.03). The -1187 CC genotype was associated with decreased DLBCL risk with borderline significance (OR, 0.70; 95% CI, 0.48-1.02). There was a trend for an allele dose-effect with borderline significance (p-trend=0.06). These results suggest that the -1420 AA genotype of H2AFX may be associated with reduced DLBCL risks in the Korean population.
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PMID:H2AFX polymorphisms are associated with decreased risk of diffuse large B cell lymphoma in Koreans. 2163 Dec 83

A biomarker is defined as "a characteristic that is objectively measured and evaluated as an indicator of normal biologic processes, pathogenic processes, or pharmacologic/pharmacodynamic responses to a therapeutic intervention". Various assays, including immunohistochemistry, gene constitution such as amplification, mutation, and rearrangement, gene and protein expression analysis such as single gene or protein expression, exhaustive analysis and gene or protein signature and single nucleotide polymorphism have been used to identify biomarkers in recent years. No therapeutic effects have yet been predicted based on the results of such exhaustive gene analysis because of low reproducibility although some correlate with the prognosis of patients. Biomarkers such as HER2 for breast cancer or EGFR mutation for lung cancer and KRAS mutation in colon cancer have contributed to identify a patient population that might show a good and bad treatment response, respectively. On the other hand, other biomarkers such as bcr-abl, c-kit gene mutation and CD20 expression, which are positive for CML, GIST and B cell lymphoma, respectively, have crucial biological significance but have not necessarily been used for practical clinical screening since pathological diagnosis coincide with finding of biomarkers. Hence, much work remains to be done in many areas of biomarker research.
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PMID:Critical comments for roles of biomarkers in the diagnosis and treatment of cancer. 2165 49

Vaccines to large B cell lymphoma were made by the covalent attachment of an epitope from the gp70 glycoprotein (SSWDFITV) to the N-termini of the conformationally biased, response-selective C5a agonists EP54 (YSFKPMPLaR) and EP67 (YSFKDMP(MeL)aR). Syngeneic Balb/c mice were immunized with these EP54/EP67-containing vaccines and challenged with a lethal dose of the highly liver metastatic and gp70-expressing lymphoma cell line RAW117-H10 to evaluate the ability of these vaccines to induce protective immune outcomes. All mice immunized with SSWDFITVRRYSFKPMPLaR (Vaccine 2) and SSWDFITVRRYSFKDMP(MeL)aR (Vaccine 3) were protected to a lethal challenge of RAW117-H10 lymphoma (>170 days survival) and exhibited no lymphoma infiltration or solid tumor nodules in the liver relative to unvaccinated controls (<18 days survival). Vaccines 2 and 3 contained the protease-sensitive double-Arg (RR) linker sequence between the epitope and the EP54/EP67 moieties in order to provide a site for intracellular proteases to separate the epitope from the EP54/EP67 moieties once internalized by the APC and, consequently, enhance epitope presentation in the context of MHC I/II. These protected mice exhibited an immune outcome consistent with increased involvement of CD8(+) and/or CD4(+) T lymphocytes relative to controls and mice that did not survive or showed low survival rates as with Vaccines 1 and 4, which lacked the RR linker sequence. CD8(+) T lymphocytes activated in response to Vaccines 2 and 3 express cytotoxic specificity for gp70-expressing RAW117-H10 lymphoma cells, but not antigen-irrelevant MDA-MB231A human breast cancer cells. Results are discussed against the backdrop of the ability of EP54/EP67 to selectively target antigens to and activate C5a receptor-bearing antigen presenting cells and the prospects of using such vaccines therapeutically against lymphoma and other cancers.
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PMID:Tumor-specific peptide-based vaccines containing the conformationally biased, response-selective C5a agonists EP54 and EP67 protect against aggressive large B cell lymphoma in a syngeneic murine model. 2172 1

Clinical cancer dormancy is defined as an unusually long time between removal of the primary tumor and subsequent relapse in a patient who has been clinically disease-free. The condition is frequently observed in certain carcinomas (e.g., breast cancer), B-cell lymphoma, and melanoma, with relapse occurring 5-25 y later. Clinical data suggest that a majority of breast cancer survivors have cancer cells for decades but can remain clinically cancer-free for their lifetime. Thus, there is a major effort to characterize the molecular mechanisms responsible for inducing tumor cell dormancy using experimental models or studying the early phases of cancer growth in humans. Many molecules and signaling pathways have been characterized and have led to concepts that dominate the field, such as the possible role of innate and adaptive immunity in immune surveillance and initiation and maintenance of dormancy. However, recent clinical data do not support many of these concepts. Several areas need further study to determine their relevance to clinical cancer dormancy. We suggest hypotheses that may contribute to elucidation of the mechanisms underlying the dormant state.
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PMID:Controversies in clinical cancer dormancy. 2174 94


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