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1.
Diagn Cytopathol ; 51(2): 140-145, 2023 Feb.
Article in English | MEDLINE | ID: mdl-36334039

ABSTRACT

INTRODUCTION: Scalp masses are often the initial presentation of a widely disseminated malignancy. Fine-needle aspiration (FNA) is an optimal method for obtaining an accurate tissue diagnosis, in these patients with initial presentation and those with a known malignancy. MATERIALS AND METHODS: We reviewed all FNAs of skin and soft tissue lesions from the scalp at our institution over a period of 31 years (1990-2021). Relevant clinical information was obtained from the review of computerized patient record. The histologic type, presentation, previous diagnoses, and survival after the diagnosis were correlated. RESULTS: Thirty patients with scalp masses were identified. All the patients were males with a median age of 61 years (27-81 years). The scalp masses ranged from 0.4 to 6 cm in size. Ten cases (33%) were benign, but the majority of cases (n = 20, 67%) were malignant. Of the malignant lesions sampled, 1 case was a primary squamous-cell carcinoma (SCC), and the remaining 19 cases were metastatic tumors. Of these, 13 cases (68.4%) had a previously diagnosed malignancy. Most of the 19 metastatic lesions were adenocarcinomas or poorly differentiated carcinomas (n = 12, 63.2%), followed by melanoma (n = 4), SCC (n = 1), alveolar soft part sarcoma (n = 1) and large cell lymphoma (n = 1). The most common site of primary was the gastrointestinal tract (6/19, 31.5%) and lung (6/19, 31.5%). The average survival after the diagnosis of these scalp metastases was around 6.3 months, signifying a poor prognosis. CONCLUSION: In our patient population, most scalp masses were metastatic tumors. Metastasis to the scalp signals advanced disease and is associated with a very poor prognosis. FNA is an easy, safe, rapid, cost effective and precise modality for diagnosing these masses. It can also yield material for molecular testing for newer directed therapies, if needed.


Subject(s)
Adenocarcinoma , Carcinoma, Squamous Cell , Male , Humans , Middle Aged , Female , Biopsy, Fine-Needle/methods , Scalp
2.
J Pathol ; 224(4): 540-52, 2011 Aug.
Article in English | MEDLINE | ID: mdl-21674502

ABSTRACT

Ribosomal stress is an important, yet poorly understood, mechanism that results in activation of the p53 tumour suppressor. We present a mutation in the ribosomal protein Rpl27a gene (sooty foot ataxia mice), isolated through a sensitized N-ethyl-N-nitrosourea (ENU) mutagenesis screen for p53 pathway defects, that shares striking phenotypic similarities with high p53 mouse models, including cerebellar ataxia, pancytopenia and epidermal hyperpigmentation. This phenocopy is rescued in a haploinsufficient p53 background. A detailed examination of the bone marrow in these mice identified reduced numbers of haematopoietic stem cells and a p53-dependent c-Kit down-regulation. These studies suggest that reduced Rpl27a increases p53 activity in vivo, further evident with a delay in tumorigenesis in mutant mice. Taken together, these data demonstrate that Rpl27a plays a crucial role in multiple tissues and that disruption of this ribosomal protein affects both development and transformation.


Subject(s)
Cerebellar Ataxia/genetics , Ribosomal Proteins/genetics , Tumor Suppressor Protein p53/metabolism , Anemia/genetics , Anemia/metabolism , Animals , Body Weight/genetics , Cell Transformation, Neoplastic/genetics , Cell Transformation, Neoplastic/metabolism , Cerebellar Ataxia/metabolism , Cerebellar Ataxia/pathology , Disease Models, Animal , Growth Disorders/genetics , Growth Disorders/metabolism , Haploinsufficiency/genetics , Hematopoietic Stem Cells/pathology , Hyperpigmentation/genetics , Hyperpigmentation/metabolism , Mice , Mice, Inbred C57BL , Mice, Mutant Strains , Mutagenicity Tests , Phenotype , Ribosomal Proteins/metabolism , Ribosomal Proteins/physiology , Signal Transduction/physiology
3.
Hum Reprod ; 19(12): 2907-12, 2004 Dec.
Article in English | MEDLINE | ID: mdl-15492023

ABSTRACT

BACKGROUND: Recently we discovered that human oviducts produce a significant amount of prostacyclin (prostaglandin I2, PGI2) and that PGI2 enhances the potentials of live birth of mouse embryos. However, the eicosanoid profile of mouse oviducts remains unknown. METHODS: The metabolites of [14C]arachidonic acid by mouse oviducts were analysed by high-performance liquid chromatography. The expression of cyclooxygenase (COX)-1, COX-2 and PGI2 synthase (PGIS) was analysed by western blot analysis and immunohistochemistry. The PGI2 synthetic capacities and the COX transcripts during the preimplantation period were compared. The effects of COX-2 inhibitor on PGI2 production were ascertained. RESULTS: Mouse oviducts produced, in order of abundance, PGI2, PGD2 and PGE2. Western blot analysis confirmed the expression of COX-1, -2 and PGIS which were expressed by luminal epithelia and smooth muscle cells. Day 2-3 post-coitus (p.c.) oviducts produced PGI2 10-fold higher than day 4 p.c. oviducts (P = 0.0087); day 1 p.c. oviducts expressed COX-2 transcript 5-fold higher than day 3 p.c. oviducts (P = 0.0004). The PGI2 production was markedly reduced by a selective COX-2 inhibitor. CONCLUSIONS: Mouse oviducts synthesized maximal PGI2 during day 2-3 p.c., coinciding with the transformation of 2-cell embryos to morulae. The results suggest that oviduct-derived PGI2 may enhance embryo development in a paracrine fashion.


Subject(s)
Embryonic Development/physiology , Epoprostenol/metabolism , Fallopian Tubes/metabolism , Animals , Blastocyst , Cyclooxygenase 1 , Cyclooxygenase 2 , Cyclooxygenase 2 Inhibitors , Cyclooxygenase Inhibitors/pharmacology , Cytochrome P-450 Enzyme System/genetics , Cytochrome P-450 Enzyme System/metabolism , Eicosanoids/metabolism , Fallopian Tubes/drug effects , Female , Intramolecular Oxidoreductases/genetics , Intramolecular Oxidoreductases/metabolism , Membrane Proteins , Mice , Mice, Inbred Strains , Nitrobenzenes/pharmacology , Pregnancy , Prostaglandin-Endoperoxide Synthases/genetics , Prostaglandin-Endoperoxide Synthases/metabolism , Sulfonamides/pharmacology
5.
Hum Reprod ; 17(12): 3053-9, 2002 Dec.
Article in English | MEDLINE | ID: mdl-12456602

ABSTRACT

BACKGROUND: It was recently discovered that prostacyclin constituted 40-50% of prostaglandins (PG) produced by minced human oviduct. It is well established that prostacyclin relaxes vascular smooth muscle, but whether oviductal smooth muscle synthesizes prostacyclin and whether its contraction is affected by prostacyclin remain unclear. METHODS: Smooth muscle microdissected from human oviducts was used for the study. The expression of prostacyclin synthase (PGIS) and prostacyclin receptor (IP) was confirmed by Western blot analysis. Metabolites of [(3)H]PGH(2) were analysed for prostacyclin. Functional coupling of IP to adenyl cyclase was assessed by the accumulation of intracellular cAMP upon prostacyclin challenge. The presence of saturable, specific binding sites for prostacyclin was confirmed by binding assay. The identity of IP was further confirmed by RT-PCR and nucleotide sequence analysis. Finally, the effects of prostacyclin on muscle contraction were studied. RESULTS: Human oviductal smooth muscle expresses functionally active PGIS and IP. The IP expressed is the same as that cloned from human lung tissue. The ED(50) of prostacyclin to increase intracellular cAMP was 16 nmol/l. Prostacyclin dose-dependently decreased the amplitude of muscle contraction. CONCLUSIONS: Human oviductal smooth muscle produces prostacyclin, which, in turn, decreases its contractility. Prostacyclin may regulate embryo transport.


Subject(s)
Epoprostenol/physiology , Fallopian Tubes/physiology , Muscle Contraction/physiology , Muscle, Smooth/physiology , Adenylyl Cyclases/metabolism , Binding Sites , Blotting, Western , Cells, Cultured , Cyclic AMP/metabolism , Cytochrome P-450 Enzyme System/analysis , Epoprostenol/metabolism , Epoprostenol/pharmacology , Female , Humans , Iloprost/metabolism , Intramolecular Oxidoreductases/analysis , Muscle Contraction/drug effects , Prostaglandin H2 , Prostaglandins H/metabolism , Receptors, Epoprostenol , Receptors, Prostaglandin/analysis , Reverse Transcriptase Polymerase Chain Reaction , Tritium
6.
J Clin Endocrinol Metab ; 87(9): 4361-8, 2002 Sep.
Article in English | MEDLINE | ID: mdl-12213900

ABSTRACT

Animal studies unequivocally support the indispensable role of prostaglandin (PG) and cyclooxygenase (COX) in ovulation and implantation. Available data also suggest that PG and COX may be important in the transport of embryos. The effects of PGE(2) and PGF(2alpha) on the contractility of human tubal muscle have been studied extensively; the expression of COX in human fallopian tubes was also reported. Despite all these, two fundamentally important questions remained to be answered: 1) which PGs are produced by human fallopian tubes; and 2) which COX isoform(s) is expressed by the fallopian tubes. We used reverse-phase HPLC to study the metabolism of [1-(14)C] arachidonic acid by the fallopian tubes. We found that 6 keto-PGF(1alpha), a stable metabolite of prostacyclin (PGI), and PGE(2) constituted 56% +/- 10% and 35% +/- 10% (mean +/- SEM, four samples), respectively, of total eicosanoids synthesized. Western blot analysis revealed the expression of both COX isoforms. Immunohistochemistry study showed that both COX-1 and -2 were localized to nonciliated epithelia and tubal smooth muscle. In addition, COX-2 was also expressed in ciliated epithelial cells. Western blot analysis revealed the expression of PGI synthase (PGIS) and PGI receptor by fallopian tubes. Immunohistochemistry confirmed the expression of PGIS by luminal epithelia, tubal smooth muscle, vascular endothelial cells, and vascular smooth muscle cells. Iloprost, a PGI analog, inhibited the activities of circular and longitudinal muscles of the fallopian tube. Thus, the fallopian tube expresses both COX isoforms and PGIS. Furthermore, it is a source and a target of PGI. PGI and COX may be important to gamete function, embryo transport, and embryo development.


Subject(s)
Cytochrome P-450 Enzyme System/metabolism , Epoprostenol/biosynthesis , Fallopian Tubes/enzymology , Intramolecular Oxidoreductases/metabolism , Isoenzymes/metabolism , Muscle Contraction/physiology , Prostaglandin-Endoperoxide Synthases/metabolism , Cyclooxygenase 1 , Cyclooxygenase 2 , Cyclooxygenase 2 Inhibitors , Cyclooxygenase Inhibitors/pharmacology , Dinoprostone/metabolism , Epithelial Cells/enzymology , Female , Humans , Immunohistochemistry , Membrane Proteins , Microsomes/enzymology , Muscle, Smooth/physiology , Nitrobenzenes/pharmacology , Sulfonamides/pharmacology
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