Expression of cyclins A and E and cyclin-dependent kinase 2 (CDK2) was examined immunohistochemically in 190 cases of human lung carcinoma. Cyclin A and CDK2 were expressed in the majority of squamous cell carcinomas , small cell carcinomas, and large cell carcinomas , but in significantly fewer cases of adenocarcinomas. Cyclin E was expressed in a minority of all subtypes. In particular , well differentiated cells in squamous cell carcinoma stained positively for cyclin E; in contrast , cyclin A was expressed in the nonkeratinized proliferating areas of the tumor nests. Immunoblotting revealed that all these proteins were expressed at higher levels in tumor tissues than in adjacent normal tissues. Immunoprecipitation also revealed higher levels of cyclin A and cyclin E associated with CDK2 in tumor tissues. Furthermore , tumor tissues which exhibited higher cyclin A and CDK2 expression also had higher CDK2 kinase activity. However , cyclin E-associated kinase activity was barely detectable even in tumor samples exhibiting higher cyclin E expression. Consistent with these data , elevated expression of cyclin A correlated to shorter survival periods in contrast to expression of cyclin E , which correlated to longer survival periods. These results suggest that in human lung carcinomas, elevated expression of active cyclin A-CDK2 complexes with associated higher CDK2 kinase activity is critical for promoting cell cycle progression and unrestrained proliferation of tumor cells and can be a predictive marker for patients' prognosis. Cell proliferation is ultimately dependent on cell cycle control and the decision to continue to proliferate is made mainly during G 1 phase as a result of the activities of G 1 cyclins and CDK complexes. 1-8 Cyclin D is expressed initially in the G 1 phase and associated kinase activity, manifested mainly by CDK4, oscillates from mid-G 1 . Cyclin E is expressed periodically, assembling with CDK2 and inducing maximum kinase activity at the G 1 /S transition. 7,8 Subsequently cyclin A is expressed and is thought to be required, in association with CDK2 and CDC2 (cell-cycle division 2), for progression through the S phase and the G 2 /M transition, respectively. 9 Among these cyclins only cyclin D1 has been identified as a proto-oncogene, designated PRAD1. It is overexpressed in lung, breast, gastric, and esophageal carcinomas at a frequency ranging from 13 to 60% with or without amplification of the 11q13 region. 10 -15 Amplification and/or overexpression of cyclin E has also been reported in colorectal and breast carcinomas. 16 -21 Overexpression of cyclin A has been reported in several cases of cultured cell lines from alveolar epithelial cells of the lung. 22 In addition, the cyclin A gene was found to be the unique insertion site of hepatitis B virus (HBV) in one clonal hepatoma. Cyclin A may thus play a role in the continuous proliferation of liver cells and ultimately in the pathogenesis of hepatocellular carcinoma. 23,24 Based on these observations cyclins and CDKs are simply belie...
The human homolog 1 of the Drosophila neurogenic achaete-scute genes, hASH1, is specifically expressed in fetal pulmonary neuroendocrine cells and in some neuroendocrine tumor cell lines. However, no data have been gathered regarding its in vivo expression in tumors. hASH1 mRNA expression was investigated by in situ hybridization in 238 surgically resected lung carcinomas, and the correlations between hASH1 expression status and immunostaining results of neuroendocrine markers chromogranin A, neural cell adhesion molecule, gastrin-releasing peptide and calcitonin, and clinical outcome were analyzed. hASH1 expression was detected in 2/20 (10%) adenocarcinomas, 4/30 (13.3%) typical carcinoids, 11/13 (84.6%) atypical carcinoids, 38/67 (56.7%) large-cell neuroendocrine carcinomas and 56/78 (71.8%) small-cell carcinomas, respectively, but not in any squamous cell carcinoma (0/21) or large-cell carcinoma (0/9). The 2 hASH1 þ adenocarcinomas also expressed multiple neuroendocrine markers. Thus, hASH1 expression was restricted to lung cancers with neuroendocrine phenotypes. However, not all neuroendocrine tumors expressed hASH1. Within the entities of large-cell neuroendocrine carcinoma and small-cell carcinoma, hASH1 expression correlated very closely with chromogranin A, gastrin-releasing peptide and calcitonin expression (Po0.0001, r ¼ 0.852), but was not related to neural cell adhesion molecule expression (P ¼ 0.8892), suggesting that hASH1 expression, at least in lung cancer, is associated with endocrine phenotype expression other than 'neuroendocrine differentiation' in a broad sense. The fact that hASH1 was virtually absent in almost fully differentiated typical carcinoids, but was expressed in most, if not all, less differentiated atypical carcinoids as well as large-cell neuroendocrine carcinomas and small-cell carcinomas, suggests that hASH1 expression in lung cancer imitates its early and transient expression in fetal development, and that hASH1 is instrumental in the establishment, but not in the maintenance, of a cellular endocrine phenotype. Finally, hASH1 expression correlated with a significantly shortened survival in small-cell carcinoma patients (P ¼ 0.041).
The human homolog 1 of the Drosophila neurogenic achaete-scute genes, hASH1, is specifically expressed in fetal pulmonary neuroendocrine cells and in some neuroendocrine tumor cell lines. However, no data have been gathered regarding its in vivo expression in tumors. hASH1 mRNA expression was investigated by in situ hybridization in 238 surgically resected lung carcinomas, and the correlations between hASH1 expression status and immunostaining results of neuroendocrine markers chromogranin A, neural cell adhesion molecule, gastrin-releasing peptide and calcitonin, and clinical outcome were analyzed. hASH1 expression was detected in 2/20 (10%) adenocarcinomas, 4/30 (13.3%) typical carcinoids, 11/13 (84.6%) atypical carcinoids, 38/67 (56.7%) large-cell neuroendocrine carcinomas and 56/78 (71.8%) small-cell carcinomas, respectively, but not in any squamous cell carcinoma (0/21) or large-cell carcinoma (0/9). The 2 hASH1 þ adenocarcinomas also expressed multiple neuroendocrine markers. Thus, hASH1 expression was restricted to lung cancers with neuroendocrine phenotypes. However, not all neuroendocrine tumors expressed hASH1. Within the entities of large-cell neuroendocrine carcinoma and small-cell carcinoma, hASH1 expression correlated very closely with chromogranin A, gastrin-releasing peptide and calcitonin expression (Po0.0001, r ¼ 0.852), but was not related to neural cell adhesion molecule expression (P ¼ 0.8892), suggesting that hASH1 expression, at least in lung cancer, is associated with endocrine phenotype expression other than 'neuroendocrine differentiation' in a broad sense. The fact that hASH1 was virtually absent in almost fully differentiated typical carcinoids, but was expressed in most, if not all, less differentiated atypical carcinoids as well as large-cell neuroendocrine carcinomas and small-cell carcinomas, suggests that hASH1 expression in lung cancer imitates its early and transient expression in fetal development, and that hASH1 is instrumental in the establishment, but not in the maintenance, of a cellular endocrine phenotype. Finally, hASH1 expression correlated with a significantly shortened survival in small-cell carcinoma patients (P ¼ 0.041).
The p53 and c-myc expression patterns indicate that EBV-infected gastric carcinomas are less likely to have a natural regression via apoptosis at an early stage and explain, in part, the resistance to treatment of late stage of gastric cancers.
Langerhans cell histiocytosis (LCH) has been thought to be a disorder of immune regulation, and increasingly, evidence showing that the tissue damage in LCH involves lymphokines and pro-inflammatory cytokines is reported. We detected human cytomegalovirus (HCMV)-DNA in LCH cells in the foci of LCH lesions by immunohistochemistry, in situ hybridization and PCR. HCMV was detected in the nuclei and/or cytoplasm of LCH cells in 9 of 27 LCH cases by immunostaining. HCMV was probably an early antigen. In situ hybridization revealed signals for HCMV-DNA only in the nuclei of LCH cells in 10 of the 27 LCH cases. PCR analysis was performed in 20 of the LCH cases, and HCMV-DNA was detected in 7 of these. All 7 positive cases were also positive for HCMV by ISH and IHC. These findings suggested that early phase infection or reactivation of HCMV occurred in the LCH lesions. HCMV infection may be accompanied by impaired cytokine production. Our study also suggested a relationship between HCMV infection and expression of TNFalpha. In tissues affected by LCH, dermatopathic lymphadenopathy or malignant fibrous histiocytoma and in normal tissues no signals for Epstein-Barr virus-RNA were detected. These findings suggest that in some cases LCH is associated with HCMV infection.
We treated a 14-year-old boy with Henoch -Schönlein purpura nephritis (HSPN) who died of an intracranial hemorrhage (ICH). Although ICH is a rare complication of HSPN, the consequence of this complication is sometimes very serious. 1 But there are no reports on the pathology and pathogenesis of ICH occurring in the course of HSPN. We examined the autopsied brain tissue and renal biopsy specimen using in situ hybridization (ISH) and polymerase chain reaction (PCR) of human cytomegalovirus (HCMV). The results indicated that he had had latent HCMV infection on admission to hospital. This suggests that reactivation of latent HCMV infection superimposed on HSPN worsened his vasculitis and resulted in fatal ICH. This is the fi rst report investigating the brain pathology of ICH as a result of severe vasculitis of HSPN. Case reportFive years prior to coming to Surugadai Nihon University Hospital , a 9-year-old boy was admitted to a local hospital for abdominal pain and vomiting. He was diagnosed as having HSPN because purpura had appeared on his legs. He was followed as an outpatient by the hospital and was admitted fi ve times after his fi rst admission due to abdominal colic. The patient had proteinuria and hematuria and was given only dipyridamole during these periods. Two months prior to admission to Surugadai Nihon University Hospital he had pretibial edema, hypertension and abdominal distention with heavy proteinuria. He was referred to Surugadai Nihon University Hospital because of his severe nephritis.On admission he was 6 kg heavier than 1 month previously, and he had hypertension (140/92 mmHg) and anasarca. The laboratory fi ndings on admission were as follows: blood urea nitrogen 25.6 mg/dL, creatinine (Cr) 2.29 mg/dL, total protein (TP) 4.1 g/dL, albumin (Alb) 2.3 g/dL, total cholesterol (T-cho) 272 mg/dL, urine red blood cells >100 per high-power fi eld, and urinary protein 819 mg/dL (3.62 g/day), and creatinine clearance (Ccr) 39.6 mL/min, IgG 338 mg/dL, IgA 233 mg/dL, third component of complement (C3) 97.7 mg/dL, fourth component of complement (C4) 19.2 mg/dL, anti-nucleic antibody, anti ds-DNA antibody, proteinase 3 antineutrophil cytoplasmic antibody (PR3-ANCA) and myeloperoxidase antineutrophil cytoplasmic antibody (MPO-ANCA) were negative.Based on these fi ndings a clinical diagnosis of nephronephritic HSPN was made, and treatment with oral prednisolone (2 mg/kg) was started. A renal biopsy showed diffuse mesangial proliferative glomerulonephritis, which was compatible with the International Study of Kidney Disease in Children (ISKDC) grade Vb. Intravenous methylprednisolone pulse therapy in combination with urokinase (3 days/week) was administered for 3 weeks. 2 After this therapy his serum creatinine decreased to 1.5 mg/dL. We then conducted double fi ltration plasmapheresis for 3 days to remove the IgA immune complex (IgA-IC), 3,4 which reduced IgA-IC from 3 mg/dL to 1 mg/dL. But on day 26 he had a fever and complained of a severe headache and delirium. Brain computed tomography (CT) showed a smal...
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.