Subject(s)
Membrane Glycoproteins/analysis , Mesothelioma/pathology , Pleura/pathology , Pleural Neoplasms/pathology , Adenocarcinoma/diagnosis , Adenocarcinoma/metabolism , Adenocarcinoma/secondary , Antibodies, Monoclonal/immunology , Biopsy , Breast Neoplasms/diagnosis , Breast Neoplasms/metabolism , Breast Neoplasms/secondary , Colonic Neoplasms/diagnosis , Colonic Neoplasms/metabolism , Colonic Neoplasms/secondary , Diagnosis, Differential , GPI-Linked Proteins , Humans , Immunohistochemistry , Lung Neoplasms/diagnosis , Lung Neoplasms/metabolism , Lung Neoplasms/secondary , Membrane Glycoproteins/immunology , Mesothelin , Mesothelioma/diagnosis , Mesothelioma/metabolism , Pleura/chemistry , Pleural Neoplasms/diagnosis , Pleural Neoplasms/metabolism , Sensitivity and SpecificityABSTRACT
We have developed a series of 4-thiophenoxy-N-(3,4,5-trialkoxyphenyl) pyrimidine-2-amines as potent and selective inhibitors of p56lck tyrosine kinase activity. In particular, the most potent inhibitor shows cellular activity in T-cell receptor (TCR) stimulated models of cytokine release, which suggests an immunomodulatory role for this class of inhibitor.
Subject(s)
Adjuvants, Immunologic/pharmacology , Amines/pharmacology , Enzyme Inhibitors/pharmacology , Lymphocyte Specific Protein Tyrosine Kinase p56(lck)/antagonists & inhibitors , Pyrimidines/pharmacology , T-Lymphocytes/drug effects , Adjuvants, Immunologic/chemistry , Amines/chemistry , Binding, Competitive , Cells, Cultured , Enzyme Inhibitors/chemistry , Humans , Interleukin-2/immunology , Models, Molecular , Molecular Structure , Pyrimidines/chemistry , Structure-Activity Relationship , T-Lymphocytes/enzymology , T-Lymphocytes/immunology , Tumor Necrosis Factor-alpha/immunologyABSTRACT
We describe a case of hepatocellular carcinoma (HCC) after long term tamoxifen therapy in a 71-year-old woman. The patient was prescribed tamoxifen for 12 years following right mastectomy and axillary node clearance for breast carcinoma in 1985. In 1997, she complained of abdominal pain and fullness. An abdominal ultrasound scan showed lesions in the right lobe of liver which were thought to be metastases. However, a biopsy showed primary HCC. Studies in rats suggest that tamoxifen is involved in hepatic carcinogenesis but studies in humans have failed to show any increased risk. However, these studies followed up patients for less than five years. An increased risk of HCC may not become apparent until after a decade or more of tamoxifen therapy. In addition, HCC in tamoxifen treated patients may be under-reported since there may be reluctance to biopsy liver tumours which are assumed to be secondary carcinoma of the breast.
Subject(s)
Antineoplastic Agents, Hormonal/adverse effects , Carcinoma, Hepatocellular/chemically induced , Liver Neoplasms/chemically induced , Tamoxifen/adverse effects , Aged , Axilla , Breast Neoplasms/drug therapy , Carcinoma, Hepatocellular/diagnosis , Female , Humans , Liver Function Tests , Liver Neoplasms/diagnosis , Lymph Node Excision , Lymph Nodes , Lymphatic Metastasis , Mastectomy , Time FactorsABSTRACT
We present a case of anaemia and intestinal obstruction in a 78-year-old woman taking nonsteroidal anti-inflammatory drugs who was found to have diaphragm disease at laparotomy.
Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/adverse effects , Ileal Diseases/chemically induced , Intestinal Obstruction/chemically induced , Aged , Anemia, Iron-Deficiency/chemically induced , Female , Humans , Ileal Diseases/pathology , Intestinal Obstruction/pathologyABSTRACT
AIMS: To reconstruct the arrangement in space of all major ducts and their branches from nipple to periphery of a human breast obtained at necropsy. METHODS: Duct tracing through cleared haematoxylin stained 2 mm sub-gross coronal slices of a complete necropsy breast and computer modelling of duct territories. RESULTS: All branches were traced for 10 complete duct systems of a single breast from a 19 year old girl. Their complexity prevented comprehensive modelling of individual ducts and rami using available computer software, but the territories (catchments) drained by individual duct systems did not overlap and could be reconstructed. Catchment volume and length of the central unbranched duct draining each catchment varied greatly. Duct spacing showed non-random uniformity which is also seen in rodent mammary glands. CONCLUSIONS: These spatial relations are consistent with mutual growth inhibition between duct systems during mammary development. Although there is no clear morphological distinction between mammary duct end buds and lateral buds in women, the present study does suggest that processes of branching morphogenesis occurring during development of the breasts in women do show some analogies with the growth of end buds/lateral branches/alveoli during rodent mammary gland development. Rodent models of mammary development may usefully suggest hypotheses about human breast biology. Less laborious methods of three dimensional reconstruction of mammary ducts and their branches from sub-gross slices, allowing more specimens to be studied, would be valuable for the study of normal human breast development and mammary intraepithelial neoplasia. Increasing power and decreasing costs of high definition image processing hardware and software may make such endeavours practicable.
