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PubMedDate not supplied

Nuclear receptor conformation, coregulators, and tamoxifen-resistant breast cancer.

The development of tamoxifen resistance and consequent disease progression are common occurrences in breast cancers, often despite the continuing expression of estrogen receptors (ER). Tamoxifen is a mixed antagonist, having both agonist and antagonist properties. We have suggested that the development of tamoxifen resistance is associated with an increase in its agonist-like properties, resulting in loss of antagonist effects or even inappropriate tumor stimulation. Nuclear receptor function is influenced by a family of transcriptional coregulators, that either enhance or suppress transcriptional activity. Using a mixed antagonist-biased two-hybrid screening strategy, we identified two such proteins: the human homolog of the nuclear receptor corepressor, N-CoR, and a novel coactivator, L7/SPA (Switch Protein for Antagonists). In transcriptional studies, N-CoR suppressed the agonist properties of tamoxifen and RU486, and L7/SPA increased agonist effects. We speculated that the relative levels of these coactivators and corepressors may determine the balance of agonist and antagonist properties of mixed antagonists, such as tamoxifen. Using quantitative RT-PCR, we, therefore, measured the levels of transcripts encoding these coregulators, as well as the corepressor SMRT, and the coactivator SRC-1, in a small cohort of tamoxifen-resistant and sensitive breast tumors. The results suggest that tumor sensitivity to mixed antagonists may be governed by a complex set of transcription factors, which we are only now beginning to understand.

Breast Neoplasms↗
PubMed1975

Renal pathologic findings associated with monoclonal gammopathies.

The myeloma kidney is characterized by casts in the distal and collecting tubules. The glomeruli are hardly affected unless amyloidosis is present. When the glomeruli are involved, the proteinuria is nonselective and, in some cases, the whole paraprotein is excreted in the urine. Nephrocalcinosis may be present and focal myeloma cell infiltration in the interstitium is a characteristic, but inconstant, finding. The nephrotic syndrome is extremely rare; if it exists, amyloidosis should be suspected. In contrast to multiple myeloma, the glomeruli are frequently involved in macroglobulinemia of Waldenstrom. Hyaline intracapillary deposits consisting of pure IgM are a characteristic finding as is infiltration of the kidney with lymphoid cells. No characteristic lesion of the kidney has been described in the heavy-chain diseases. Mixed cryoglobulinemia associated with an IgM paraprotein can produce glomerulonephritis that is due to the deposition in the glomeruli of an immune complex consisting of IgG, IgM, and complement.

Animals↗
PubMed1990

Cloning and characterization of two alternatively spliced rat alpha-amidating enzyme cDNAs from rat medullary thyroid carcinoma.

The alpha-amidating enzyme activity in rat medullary thyroid carcinoma (MTC) consists of multiple, active enzymes that can be resolved by ion-exchange chromatography. Amino acid sequences from one form of purified rat MTC alpha-amidating enzyme have been utilized to design oligonucleotide probes for isolating cDNAs encoding this protein. Sequence analysis of multiple cDNA clones indicates that there are at least two types of cDNA in rat tissues. These cDNAs differ primarily by the absence (type A) or the presence (type B) of a 315-base internal sequence. Additional heterogeneity in the 3' coding regions of the different mRNAs has also been found. Both types of cDNA predict primary translation products that are preproenzymes which must be post-translationally processed at both their amino and carboxyl termini. Sequence analysis of the purified peak III protein from rat MTC demonstrates that the type A mRNA encodes this 75-kDa protein. This analysis also provides support for the assignment of the C-terminal processing site. In addition, data are presented which demonstrate that type B mRNA is also functional. The implications of the internal and carboxyl-end heterogeneity are discussed.

Amino Acid Sequence↗
PubMed1984

Progressive immune failure in dyskeratosis congenita. Report of an adult in whom Pneumocystis carinii and fatal disseminated candidiasis developed.

Community-acquired Pneumocystis carinii pneumonia developed in a young adult patient with dyskeratosis congenita. His hospitalization ended fatally with disseminated candidiasis. Evaluation during the admission showed evidence of cellular immune dysfunction as indicated by skin test anergy and absent lymphocyte proliferation in an in vitro mixed lymphocyte culture. Treatment with transfer factor failed to reverse the cutaneous anergy or affect the clinical course. Dyskeratosis congenita is a rare multisystem disorder with prominent dermatologic manifestations; bone marrow failure or malignant neoplasm are common fatal outcomes. Immune system abnormalities are not classically considered a part of the disease complex. Serial evaluation of our patient's condition over several years suggests that depressed immune function, especially of the cellular limb, may evolve as a feature of clinical importance in these patients.

Acquired Immunodeficiency Syndrome↗
PubMed1988

Genetic analysis of human breast cancer: implications for family study designs.

Genetic analysis of human breast cancer, as with many common diseases, raises several problems including sampling strategies, genetic heterogeneity, and gene-environment interactions. A reanalysis of 200 Danish breast cancer pedigrees, under the unified mixed model, was conducted to investigate more specifically these three points. We found that use of different sampling schemes leads to similar conclusions: familial transmission of breast cancer in this whole Danish sample cannot be accounted for by the Mendelian segregation of a dominant gene. Homogeneity tests, based on an a priori subdivision of the sample, were all nonsignificant under a given genetic model. However, it was possible to isolate a particular subgroup of pedigrees displaying only breast cancer, which was compatible with the segregation of a dominant gene. We have also shown that correct specification of a liability indicator according to epidemiological factors is of major importance to detect a major effect under the mixed model. Our results emphasize the need to design family studies including various types of information in the probands and family members to permit some progress in the understanding of complex diseases.

Breast Neoplasms↗
PubMed2000

Thoughts on tamoxifen resistant breast cancer. Are coregulators the answer or just a red herring?

The antiestrogen tamoxifen is an effective treatment for estrogen receptor positive breast cancers, slowing tumor growth and preventing disease recurrence, with relatively few side effects. However, many patients who initially respond to treatment, later become resistant to treatment. Tamoxifen has both agonist and antagonist activities, which are manifested in a tissue-specific pattern. Development of tamoxifen resistance can be characterized by an increase in the partial agonist properties of the antiestrogen in the breast, resulting in loss of growth inhibition and even inappropriate tumor stimulation. Nuclear receptor function is modulated by transcriptional coregulators, which either enhance or repress receptor activity. Using a mixed antagonist-biased two-hybrid screening strategy, we identified two such proteins: the human homolog of the nuclear receptor corepressor, N-CoR, and a novel coactivator, L7/SPA (Switch Protein for Antagonists). In transcriptional studies N-CoR suppressed the agonist properties of tamoxifen and RU486, while L7/SPA increased agonist effects. We speculated that the relative level of these coactivators and corepressors might determine the balance of agonist and antagonist properties of mixed antagonists such as tamoxifen. Using quantitative RT-PCR we therefore measured the levels of transcripts encoding these coregulators, as well as the corepressor SMRT, and the coactivator SRC-1, in a small cohort of tamoxifen resistant and sensitive breast tumors. The results suggest that tumor sensitivity to mixed antagonists may be governed by a complex set of transcription factors, which we are only now beginning to understand.

Animals↗
PubMed1990

[Diagnosis of postoperative coagulopathic hemorrhage in oncology patients].

The condition of the hemostatic system during operation and in the early postoperative period was studied in 288 oncological patients in blood loss of different volumes. A relation of changes in hemostasis to the amount of blood lost was found. The increase in the volume of blood loss was caused first of all by the traumatic character of the operation itself, i.e. surgical hemorrhages, while the coagulopathic hemorrhages were of a secondary character. They evolve as acute and subacute syndrome with generalized, hypercompensated or moderate fibrinolysis in the form of hemodilution coagulopathy with predominant reduction of the number of platelets and their dysfunctions, or are mixed in character. A complex of rapid methods for the diagnosis of coagulopathic hemorrhages is recommended.

Adult↗
PubMedDate not supplied

[Mixed carcinoid-adenocarcinoma tumor of the appendix: a case report and diagnostic and therapeutic considerations].

The layout of the work has stayed motivated from the recent observation of mixed carcinoid, located to the appendix and wide to the peritoneal cable, joint to our observation in an elderly patient with aspecific demonstration clinical-symptomatologic. The study of the endocrine tumors is in continuous evolution also if, to the actual state, there is a better comprehension of this neoplasm, variegated and complex and, under some appearances, still not known well. Jejunoileal carcinoid tumors differ, under many appearances, from those occurring in other sites of the gut. They have relatively high rate of transmural invasion and aggressive clinical behavior, contrasted by a scarce objectivity; the demonstration of symptoms generally implicates the presence of an illness in advanced stage. Also pharmacological therapy made important progress, with the possibility of administer composed able to interfere with the development and the neoplastic growth.

Adenocarcinoma↗
PubMed1985

Immunocytochemical localization of the surfactant apoprotein and Clara cell antigen in chemically induced and naturally occurring pulmonary neoplasms of mice.

The localization of surfactant apoprotein (SAP) and the Clara cell antigen(s) (CCA) was studied in naturally occurring and experimentally induced pulmonary hyperplasias and neoplasms by avidin-biotin peroxidase complex (ABC) immunocytochemistry. Lungs of B6C3F1 and A strain mice with naturally occurring lesions, B6C3F1 mice given injections of N-nitrosodiethylamine (DEN), BALB/c nu/nu or nu/+ mice exposed transplacentally on Day 16 of gestation to ethylnitrosourea (ENU), or BALB/c nu/+ mice exposed to ENU at 8-12 weeks of age were preserved in formalin or Bouin's fixative. After ABC immunocytochemistry, SAP was found in the cytoplasm of normal alveolar Type II cells; in the majority of cells in focal alveolar and solid hyperplasias originating in peribronchiolar or peripheral locations; and in solid, tubular, papillary, and mixed adenomas and carcinomas. The larger mixed-pattern neoplasms and small or large tubular neoplasms usually had the least number of cells with SAP. The majority of large papillary adenomas and carcinomas in BALB/c mice exposed to ENU and in untreated A strain mice contained SAP in the nuclei of many neoplastic cells but only in the cytoplasm of a few neoplastic cells. CCA was found in normal Clara cells of bronchi and bronchioles but not in any hyperplastic or neoplastic lesion of any mouse studied. This study provided immunocytochemical evidence that the vast majority of naturally occurring and experimentally induced pulmonary neoplasms of mice are alveolar Type II cell adenomas and carcinomas.

Adenoma↗
PubMed2006

Managing breathlessness: providing comfort at the end of life.

Dyspnea is a common symptom at the end of life. It occurs as the result of a complex mix of physical, biochemical, and perceptual components. When patients and their healthcare providers focus on the "numbers" related to oxygenation, rather than comfort, the individual's quality of life can suffer.

Analgesics, Opioid↗
PubMed1990

[Tumor cells and extracellular matrix with special reference to mamma tumors in dogs and cats].

The essence of the cell-matrix interaction in tissues is that cells influence the composition of the extracellular matrix but that, on the other hand, components of the matrix are also involved in the regulation of growth and differentiation of the cells. Interaction is also found to occur in tumours though in a different way, so that infiltration and metastasis and the occurrence of scirrhous carcinomas are the result. Canine and feline mammary tumours are interesting objects for the study of this interaction since fibroadenomatous changes, in which connective tissue is the predominating tissue, is a common finding in cats only, whereas mixed and complex mammary tumours, producing matrix components of varying type, are common tumours in dogs.

Animals↗
PubMed2004

Molecular cytogenetic characterization of a case of Müllerian adenosarcoma.

Müllerian adenosarcoma is a distinctive type of mixed Müllerian tumor of the female genital tract. To our knowledge, no cytogenetic data have been documented on Müllerian adenosarcoma in the literature so far. We report here the chromosomal findings of a Müllerian adenosarcoma in a 15-year-old female. Cytogenetic and molecular cytogenetic analysis revealed a complex karyotype involving chromosomes 2, 8, 10, 13, 19, and 21. These numerical and structural abnormalities may be of etiologic significance. This report may highlight the potential value of molecular cytogenetic analysis in differential diagnosis of Müllerian tumors. More cases are warranted to further genetically characterize this type of neoplasm.

Abdominal Neoplasms↗
PubMed2005

Androgen metabolic genes in prostate cancer predisposition and progression.

Significant evidence implicates androgens in prostate cancer etiology. We review recent data with regard to the association between several allelic variants of specific androgen-metabolic genes and the predisposition to prostate cancer. We also review the emerging evidence regarding the role of genetic variants of these genes as well as the androgen receptor in prostate cancer progression. Based on the prostate cancer paradigm, we propose that a multidisciplinary attack on the problem--involving biochemistry, genetics, pharmacogenetics, endocrinology and molecular epidemiology--may be important for the understanding and successful treatment of complex (in terms of etiology) human diseases.

Androgens↗
PubMed1994

[Tumor cells on the inside and tumor cells on the outside. A contribution to the diagnosis and elucidation of the pathogenesis of mammary tumors in dogs].

This review discusses some recent experience with intra- and extracellular components of tumours as markers for tumour diagnosis. Intermediate filaments are cytoskeletal proteins of either epithelial or mesenchymal cells. Antibodies raised against human intermediate filament proteins cross-react with their canine counterparts. A study of the presence and distribution of intermediate filaments in normal mamma and mammary tumours of dogs showed that they do not contribute to a more adequate classification of the tumours. However, the presence of vimentin in epithelial tumour cells may be a marker of malignancy. Proteoglycans are extracellular matrix proteins, containing long chains of glycosaminoglycans (GAGs). Analysis of the presence of GAGs in canine mammary tumours showed that accumulation of chondroitin sulfate, frequently of an abnormal type, was a predominant finding in all tumour types, but not in normal mamma, and was not related to biological behaviour. Although demonstration of the before-mentioned tumour components does not help tumour diagnosis, it may contribute to the elucidation of the development of such tumours as the complex and mixed adenomas of the mamma of which cartilage and bone are important constituents of unknown origin.

Animals↗