ABSTRACT
A 26-year-old female presented with abdominal pain and distension in 2003. Clinical evaluation and imaging were suggestive of bilateral benign renal solid masses. Fine needle aspiration showed tubular cells only. Patient was kept under periodic follow up. She reported 4 years later with increase in pain and size of masses, and underwent bilateral staged nephron sparing surgery. The histopathology was reported as bilateral oncocytoma. Two years after surgery, she developed epidural spinal cord compression and liver metastasis. A decompression laminectomy and biopsy revealed conventional renal cell carcinoma (RCC). To our knowledge this is the first case report of sporadic bilateral synchronous hybrid RCC and oncocytoma in a young woman, with spinal epidural metastasis.
Subject(s)
Adenoma, Oxyphilic/pathology , Carcinoma, Renal Cell/secondary , Epidural Neoplasms/secondary , Kidney Neoplasms/pathology , Liver Neoplasms/secondary , Neoplasms, Multiple Primary/pathology , Adenoma, Oxyphilic/surgery , Adult , Carcinoma, Renal Cell/therapy , Combined Modality Therapy , Epidural Neoplasms/diagnostic imaging , Epidural Neoplasms/therapy , Female , Humans , Kidney Neoplasms/surgery , Liver Neoplasms/diagnostic imaging , Liver Neoplasms/drug therapy , Neoplasms, Multiple Primary/surgery , Palliative Care , RadiographyABSTRACT
Steroid and thyroid hormone receptors are members of the superfamily of nuclear receptors (NR) that participate in developmental and homeostatic mechanisms by changes in the transcription of specific genes. These activities are governed by the receptors' cognate ligands and through interaction with the components of the transcriptional machinery. A number of coactivator molecules of the steroid receptor coactivator (SRC)/nuclear receptor coactivator (NCoA) family interact with activation functions within NRs through a conserved region containing helical domains of a core LXXLL sequence and, thereby, participate in transcriptional regulation. Using a mammalian-two-hybrid assay, we show that the thyroid hormone receptor beta (TRbeta) and estrogen receptor beta (ERbeta) have different LXXLL motif preferences for interactions with SRC-1. Using large random and focused (centered on the LXXLL motif) recombinant peptide diversity libraries, we have obtained novel peptide sequences that interact specifically with ERbeta or with TRbeta in a ligand-dependent manner. Random sequence libraries yielded LXXLL-containing peptides, and sequence analysis of selected clones revealed that the preferred residues within and around the LXXLL motif vary significantly between these two receptors. We compared the receptor binding of library-selected peptides to that of peptides derived from natural coactivators. The affinities of selected peptides for the ligand binding domains of ERbeta and TRbeta were similar to the best natural LXXLL motifs tested, but showed a higher degree of receptor selectivity. These selected peptides also display receptor-selective dominant inhibitory activities when introduced into mammalian cells. Finally, by directed mutations in specific residues, we were able to alter the receptor binding preference of these peptides.
Subject(s)
Peptides/pharmacology , Receptors, Estrogen/agonists , Receptors, Thyroid Hormone/agonists , Transcription Factors/metabolism , Transcription, Genetic/drug effects , Amino Acid Motifs , Amino Acid Sequence , Drug Synergism , Estradiol/pharmacology , Estrogen Receptor beta , Histone Acetyltransferases , Humans , Ligands , Molecular Sequence Data , Mutagenesis, Site-Directed , Nuclear Receptor Coactivator 1 , Peptide Library , Peptides/chemistry , Peptides/isolation & purification , Protein Binding , Protein Structure, Tertiary , Receptors, Estrogen/chemistry , Receptors, Thyroid Hormone/chemistry , Recombinant Fusion Proteins/pharmacology , Sequence Alignment , Sequence Homology, Amino Acid , Structure-Activity Relationship , Two-Hybrid System TechniquesABSTRACT
Clinical and hematological features of nine cases of Hemoglobin E variant were studied prospectively over three years. There were three cases of HbE-beta thalassemia and six cases of homozygous HbE disease. Two cases were asymptomatic. The commonest symptom was jaundice (unconjugated 2). Other symptoms were left hypochondrial pain, tiredness, syncope and failure to thrive. Splenomegaly and microcytosis was detected in all. Mild anaemia was present in majority (6/9), and the mean hemoglobin was 11.3 gm/dl. Reticulocyte count was normal in all and cholelithiasis was seen in one patient only. Clinical and hematological features were evaluated and compared to reported series. Splenomegaly was found to be more common.
