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)

Corticotropin-releasing hormone (CRH) is a 41-amino acid peptide which mediates behavioural and physiological responses to stress. A major target of CRH is the proopiomelanocortin (POMC) gene. Three transcription factors have been identified that affect transcription of the POMC gene by binding to two different sites within the CRH-responsive element of that promoter. We searched Genbank and found that nucleotide sequences in the POMC promoter which bind POMC-transcription factors are also contained in the genome of HIV-1 and cytomegalovirus, in c-fes and human MAT-1 breast cancer oncogenes, and in proinflammatory molecules, such as the interleukin-1 beta converting enzyme. We hypothesise a mechanism of hormone action by which a peptide hormone, such as CRH, might affect disease susceptibility by eliciting the production of transcription factors which may bind to unexpected intracellular targets, such as viruses, oncogenes, or the genes encoding for inflammatory mediators. Infection, inflammation, and possibly neoplastic transformation would thus be facilitated. This hypothesis can be tested. If confirmed, CRH antagonists may prove useful in the treatment of disorders whose pathophysiology involves molecules that respond to CRH-regulated POMC transcription factors.
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PMID:A molecular mechanism for stress-induced alterations in susceptibility to disease. 762 47

To detect shared human melanoma Ag that are recognized by HLA-A2 restricted, melanoma-specific CTL derived from tumor infiltrating lymphocytes, we have developed a convenient method to insert and express foreign HLA genes capable of presenting Ag on target cell lines. Seventeen melanoma cell lines and 11 nonmelanoma cell lines were infected with recombinant vaccinia virus containing the HLA-A2.1 gene. Infection by the vaccinia virus resulted in expression of functional HLA-A2 molecules on the cell surface of virtually 100% of infected cells within a 3.5-h period. The results showed that 11 of 17 (65%) naturally HLA-A2- melanoma cell lines were specifically lysed by the HLA-A2-restricted, melanoma-specific TIL after infection with the vaccinia-HLA-A2.1 virus. None of the nine human nonmelanoma cell lines tested (three colon cancer, four breast cancer, or two immortalized non-tumor cell lines) or two murine melanoma cell lines were lysed by the HLA-A2-restricted TIL after vaccinia-HLA-A2.1 infection. Coinfection of the vaccinia virus containing the beta 2-microglobulin gene with the vaccinia-HLA-A2.1 virus increased the surface expression of HLA-A2 and subsequent lysis by melanoma-specific tumor infiltrating lymphocytes. With this new method we could extend previous findings demonstrating that shared melanoma Ag recognized by HLA-A2-restricted tumor infiltrating lymphocytes exist among melanoma cells from different patients regardless of HLA type. These Ag represent excellent candidates for the development of vaccines to induce T cell responses for the immunotherapy of patients with melanoma.
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PMID:Detection of shared MHC-restricted human melanoma antigens after vaccinia virus-mediated transduction of genes coding for HLA. 833 37

Hippocrates, in his days, was already aware of 'karkinos' or 'karkinoma' for tumors, above all the breast. The etiology of the carcinoma of the breast was seen in the fluids of the body. The humoralistic theory persisted till the second half of the 19th century, although considerable progress in the ability of diagnoses and operating techniques had meanwhile been made. In the 19th century a classification of breast cancer was developed and the first statistical analysis presented. Although anesthesia was introduced in 1846 and antisepsis somewhat later, surgical techniques could not be improved until the 20th century, when radiotherapy and hormonal treatment were discovered. Despite all efforts made since antiquity to cure breast cancer, the medical community today is not much further than were the doctors facing the dangers of infectious disease prior to the discovery of antibiotics.
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PMID:[Breast cancer in medical history]. 837 92

Data was compiled from a wide variety sources in order to construct a demographic profile of elderly women in Latin America. Data was organized into a cross-classification matrix based on three age groups (midlife, young old, and old old) and three country types (highly rural, mixed, and highly urban). The macro-level overview takes into account such factors as education, family structure, and employment. Smaller reports and research project reports of micro conditions are used to help explain the macro trends. Women older than 40 represented 9-20% of the population of the region (of 21 Latin American and Caribbean countries). 6-14% of midlife women were widowed, with the highest concentrations in urban countries. Widows and single women comprised about 20-35% of midlife women and 50-65% of older women. Female household headship increased with age from 9-23% in midlife to 24-41% among women 60 years and older. In all countries with the exception of Uruguay, women had less primary schooling than men. Women's salaried employment in the formal sector decreased rapidly with increasing age. For example, in highly urban countries the range of employment was from 34% of women in midlife to only 4% among women 65 years and older. Women were working, but often in the informal sector or as prostitutes or beggars. Women's health conditions included 12-37% with chronic anemia and many with signs of premature aging (early onset of diabetes, hypertension, and osteoarthritic joint changes). Depression among older women may have been as high as 40%. The strain of maintaining a double work load of child care and housekeeping and employment is unmeasured. Regardless of the level of development, older women suffered primarily from heart disease. Breast cancer was more common in urban countries. Highly rural or mixed countries had greater incidence of cervical cancer. Chronic liver disease was appearing in some countries. In highly rural countries infectious diseases and malnutrition still contributed significantly to causes of death. Most women did not have social security coverage. Evidence points to women's remarkable responses (creativity, initiative, and persistence) to fulfilling survival needs.
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PMID:Older women in Latin America: the health and socioeconomic situation of this important subgroup. 857 13

Bcl-xs is a dominant negative repressor of Bcl-2 and Bcl-xL, both of which inhibit apoptosis. We used a replication-deficient adenoviral vector to transiently overexpress Bcl-xs in MCF-7 human breast cancer cells, which overexpress Bcl-xL. Infection with this vector induced apoptosis in vitro. We then determined the effects of intratumoral injection of bcl-xs adenovirus on solid MCF-7 tumors in nude mice. Tumors injected four times with the bcl-xs adenovirus showed a 50% reduction in size. Using terminal transferase-mediated dUTP-digoxigenin nick end labeling, we observed apoptotic cells at sites of bcl-xs adenoviral injection. These experiments demonstrate the feasibility of using bcl-xs gene therapy to induce apoptosis in human breast tumors.
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PMID:bcl-xs gene therapy induces apoptosis of human mammary tumors in nude mice. 861 32

To examine the potential use of adenovirus vectors in cancer gene therapy as a mechanism for purging bone marrow cells of possible breast cancer contaminants, we compared the infection efficiency of adenovirus and the transfection efficiency of plasmid DNA in the presence of adenovirus in human breast cancer and bone marrow cells. Following infection of breast cancer cells with an adenovirus expressing beta-galactosidase gene, high levels of beta-galactoside activity were observed. No beta-galactosidase activity was observed in low-density human bone marrow cells. A replication-deficient adenovirus mutant dl312 enhanced the transfection efficiency of a plasmid DNA-expressing beta-galactosidase gene into breast cancer cells, and addition of a liposome, lipofectamine, further enhanced the transfection efficiency. In contrast, human bone marrow cells treated under the same conditions expressed very low levels of transfected beta-galactosidase DNA. Transfection of cells with plasmid DNA expressing a truncated but fully active Pseudomonas exotoxin gene in the presence of dl312 and lipofectamine resulted in marked breast cancer cell killing, whereas colony-forming unit granulocyte-macrophage (CFU-GM) were relatively resistant to these treatments. A recombinant adenovirus expressing human wild-type p53 protein (AdWTp53) was also highly cytotoxic to breast tumor cells. Infection of breast cancer cells with AdWTp53 (100 plaque-forming units/cell) resulted in 100% loss of the clonogenicity of breast tumor cells. However, colony formation from CFU-GM was relatively resistant to the cytotoxic effects of AdWTp53 alone or in the presence of pULI100 plasmid and lipofectamine. On the basis of these results, it is proposed that human adenoviruses are potentially useful for cancer gene therapy and bone marrow purging.
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PMID:Adenovirus-mediated gene transfer to human breast tumor cells: an approach for cancer gene therapy and bone marrow purging. 864 Aug 24

A recombinant adenovirus expressing Escherichia coli cytosine deaminase (AdCD) was constructed with the purpose of exploring its utility for the treatment of breast cancer. Infection of the human breast cancer cell line, MDA-MB-231, with AdCD resulted in high levels of cytosine deaminase enzyme activity. MDA-MB-231 cells infected with AdCD were 1000-fold more sensitive to 5-fluorocytosine (5-FC) than cells infected with a control adenovirus. Cell mixing experiments indicated that only 10% of AdCD-infected cells in a population were needed to induce complete cytotoxicity of noninfectious cells exposed to 5-FC. This suggests that bystander effects play an important role in AdCD-mediated cytotoxicities. Direct injection of AdCD into human breast MDA-MB-231-derived tumors grown as xenografts in nude mice, followed by daily intraperitoneal injection 5-FC was sufficient to inhibit tumor growth. These results suggest that in vivo gene therapy for breast cancer using AdCD is feasible.
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PMID:Enzyme/prodrug gene therapy approach for breast cancer using a recombinant adenovirus expressing Escherichia coli cytosine deaminase. 908 Jan 20

A patient with end stage breast cancer was admitted to hospital due to fever, chills, multiply eroded discharging wounds, and sudden onset of left hemiparesis. Clostridium septicum bacteremia and brain abscess were diagnosed. The patient was treated successfully with intravenous penicillin and clindamycin and stereotactic aspiration of the abscess. Eleven cases of C. septicum central nervous system infection are reviewed. They showed an extremely fulminant course and high fatality. Nevertheless, some relationship seems to exist between outcome and type of brain lesion. Hemolytic-uremic syndrome associated with central nervous system infection is also discussed, because all these cases in the literature were due to this organism. Early diagnosis and aggressive treatment, including surgical drainage and appropriate antibiotics, are the key to improving the prognosis. A long-term prophylactic oral antimicrobial agent is suggested for patients who survive this infection.
Infection
PMID:Central nervous system infection due to Clostridium septicum: a case report and review of the literature. 918 86

Promising results from clinical trials with unconjugated antibodies stimulated renewed interest in immune effector mechanisms of monoclonal antibodies (MoAbs). We investigated the potential of IgA as antibody isotype for cell- or complement-mediated tumor cell lysis and assessed the potential of its myeloid Fc receptor, FcalphaRI (CD89), as trigger molecule for bispecific antibody (BsAb)-mediated immunotherapy. Comparing hapten-directed antibodies of human IgA2 with IgG1 or IgG3 isotypes, we found all three to mediate effective killing of sensitized tumor target cells in whole blood assays. Analysis of effector mechanisms showed IgG-mediated lysis to be predominantly complement-dependent, whereas IgA-dependent killing was primarily effector cell-mediated. A comparison of effector cell populations in antibody-dependent cell-mediated cytotoxicity (ADCC) showed neutrophils to be most important for IgA-dependent tumor cell killing, involving FcalphaRI as shown with Fc receptor blocking antibodies. Reverse ADCC experiments against target cells sensitized with Fc receptor antibodies, or assays with FcalphaRI-directed bispecific antibodies confirmed FcalphaRI as effective trigger molecule in polymorphonuclear neutrophil (PMN)-mediated lysis. During granulocyte colony-stimulating factor (G-CSF ) therapy, (FcalphaRI x HER-2/neu) bispecific antibodies induced enhanced killing of HER-2/neu positive SK-BR-3 breast cancer cells in whole blood assays. This enhanced cytotoxicity was paralleled by increased PMN counts, which lead to higher effector to target cell ratios in G-CSF-primed blood. Furthermore, bispecific antibodies, directed to FcalphaRI and Candida albicans, enhanced neutrophils' phagocytosis of fungi. In summary, these results identify IgA as an effective antibody isotype for immunotherapy, working primarily via FcalphaRI on neutrophils. They suggest FcalphaRI-directed bispecific antibodies and G-CSF to be an attractive combination for malignant or infectious diseases.
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PMID:FcalphaRI (CD89) as a novel trigger molecule for bispecific antibody therapy. 937 59

A better understanding of immune recognition of cells has led to identification of potential new targets on tumor cells. Noticeable successes in melanoma have been immunization with the GM2 ganglioside vaccine, and the identification of novel antigens such as MAGE, BAGE and GAGE recognized by T cells cloned from cancer patients with regressing disease. However, the unexpected finding that other antigens recognized by these T cells were overexpressed normal differentiation antigens such as tyrosinase. Pmel 17 and Melan A have led to vaccines developed against differentiation antigens expressed in other solid tumors. Monoclonal antibody, anti-idiotype and antigen based vaccines for colorectal target antigens 17-1A, CEA and 791Tgp72 are all in clinical development. Similarly HER2/neu and mucin overexpression in breast cancer represent promising targets. Mutations in tumor oncogenes or suppressor genes which lead to malignant transformation can also present tumor-specific antigens. The most effective vaccines against infectious disease are live viruses. The development of DNA vaccines which act like viruses in entering cells and show continuous production of antigens offers great potential for the future.
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PMID:Cancer vaccines. 939 16


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