ABSTRACT
Potential prognostic biomarkers in acute myeloid leukemia (AML) can be identified by understanding the cellular pathway and molecular changes underlying leukemogenesis. Deregulation of apoptosis is one of the important features of AML and to understand the molecular mechanism underlying apoptosis and its contribution to tumor progression, this study aimed to evaluate anti-apoptotic Bcl2 protein expression in AML and correlate with FLT3 parameters for their role in prognosis of disease.Bcl2 and FLT3 protein expression was quantified by flow cytometry on leukemic blasts in total 174 de novo AML, myelodysplastic syndrome (MDS) and aplastic anemia patients. FLT3 internal tandem duplication (ITD), Tyrosine kinase domain (TKD) point mutations and quantification of mRNA level was carried out using PCR and RT-PCR methods. The incidence of Bcl2 positivity was 71% in AML patients. Bcl2 positivity was significantly associated with CD34+ and CD117+ AML. Bcl2 positivity tended to be associated with reduced DFS while Bcl2 positivity with FLT3 protein positivity was significantly associated with reduced DFS. In multivariate analysis, Bcl2+ and combined Bcl2+/FLT3 protein+ along with high WBC count emerged as poor prognostic factors for reduced DFS and high blast count for predicting reduced OS. In MDS patients, the incidence of Bcl2 expression was high while in aplastic anemia patients, incidence of Bcl2 expression was low.Patients with Bcl2 and FLT3 protein positivity showed significantly reduced DFS suggesting parallel role of these proteins in imparting chemoresistance to the leukemic cells.
Subject(s)
Anemia, Aplastic/metabolism , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Drug Resistance, Neoplasm , Leukemia, Myeloid, Acute/metabolism , Myelodysplastic Syndromes/metabolism , Proto-Oncogene Proteins c-bcl-2/metabolism , fms-Like Tyrosine Kinase 3/metabolism , Adolescent , Adult , Anemia, Aplastic/drug therapy , Anemia, Aplastic/mortality , Arsenic Trioxide , Arsenicals/administration & dosage , Female , Flow Cytometry , Humans , Immunophenotyping , Leukemia, Myeloid, Acute/drug therapy , Leukemia, Myeloid, Acute/mortality , Male , Middle Aged , Mutation/genetics , Myelodysplastic Syndromes/drug therapy , Myelodysplastic Syndromes/mortality , Oxides/administration & dosage , Prognosis , Proto-Oncogene Proteins c-bcl-2/genetics , RNA, Messenger/genetics , Real-Time Polymerase Chain Reaction , Reverse Transcriptase Polymerase Chain Reaction , Survival Rate , Tandem Repeat Sequences/genetics , Tretinoin/administration & dosage , Young Adult , fms-Like Tyrosine Kinase 3/geneticsABSTRACT
BACKGROUND: The present study evaluated the clinical significance of BAG-1, an antiapoptotic protein, in leukoplakia and carcinoma of the tongue. METHODS: BAG-1 expression was evaluated by immunohistochemistry in paraffin-embedded tissues of leukoplakia (n=25) and carcinoma of the tongue (n=61). RESULTS: Cytoplasmic expression was predominantly seen in 80% and 70% of patients with leukoplakia and carcinoma, respectively. BAG-1 expression was found to be significantly lower in tobacco users than in non-tobacco users. BAG-1 expression in tobacco-using leukoplakia and carcinoma patients was compared by grouping the carcinoma patients according to lymph node status and disease stage. Carcinoma patients with tumor-positive lymph nodes had significantly lower BAG-1 expression than patients with negative lymph nodes and leukoplakia. Further, a trend towards an inverse correlation was observed with p53 and c-erbB2. In univariate and multivariate survival analysis, patient subgroups with 2+ or 3+ marker positivity (BAG-1 negativity, p53 and c-erbB2 positivity) had a reduced overall survival compared with patient subgroups with 1+ marker positivity or negativity. CONCLUSION: BAG-1 negativity in association with p53 and c-erbB2 positivity identified a subgroup of tongue cancer patients with an aggressive phenotype. Hence, an antiapoptotic protein, BAG-1, was found to be down-regulated in chewing-tobacco-mediated tongue carcinogenesis.
Subject(s)
DNA-Binding Proteins/genetics , Leukoplakia, Oral/pathology , Neoplasm Proteins/genetics , Receptor, ErbB-2/metabolism , Tongue Neoplasms/pathology , Transcription Factors/genetics , Tumor Suppressor Protein p53/metabolism , Cytoplasm/pathology , DNA-Binding Proteins/metabolism , Humans , Immunohistochemistry , Lymphatic Metastasis , Neoplasm Proteins/metabolism , Neoplasm Staging , Smoking/blood , Survival Analysis , Tobacco, Smokeless , Tongue Neoplasms/mortality , Transcription Factors/metabolismABSTRACT
Freyer prostatectomy is infrequently indicated today. One of the blind steps in this procedure is when the urethra is disconnected at the prostatic apex. There is risk of stress urinary incontinence and damage to the sphincter. We describe a safe and a simple endoscopic technique to overcome this difficulty.
Subject(s)
Endoscopy/methods , Prostatectomy/methods , Urinary Incontinence, Stress/prevention & control , Endoscopy/adverse effects , Humans , Male , Postoperative Complications/prevention & control , Prognosis , Prostatectomy/adverse effects , Prostatic Diseases/surgery , Sensitivity and SpecificityABSTRACT
A simple and safe technique for the replacement of a dislodged nephrostomy tube using a ureteroscope is presented.
Subject(s)
Nephrostomy, Percutaneous/instrumentation , Ureteroscopes , Ureteroscopy/methods , Equipment Failure , Humans , Nephrostomy, Percutaneous/adverse effects , Sensitivity and Specificity , Treatment OutcomeABSTRACT
We present a simple technique to reposition an open-ended ureteric catheter in the pelvicalyceal system during percutaneous nephrolithotomy. A through-and-through glidewire is straightened using a stone-grasping forceps. The open-ended catheter is advanced in the pelvicalyceal system over this taut glidewire.
Subject(s)
Kidney Calculi/surgery , Nephrostomy, Percutaneous/methods , Urinary Catheterization , Humans , Treatment Outcome , UreterABSTRACT
A wild-type strain, Sp972 h-, of Schizosaccharomyces pombe was mutagenized with ethylmethanesulfonate (EMS), and 2-deoxyglucose (2-DOG)-resistant mutants were isolated. Out of 300 independent 2-DOG-resistant mutants, 2 failed to grow on glucose and fructose (mutants 3/8 and 3/23); however, their hexokinase activity was normal. They have been characterized as defective in their sugar transport properties, and the mutations have been designated as std1-8 and std1-23 (sugar transport defective). The mutations are allelic and segregate as part of a single gene when the mutants carrying them are crossed to a wild-type strain. We confirmed the transport deficiency of these mutants by [14C]glucose uptake. They also fail to grow on other monosaccharides, such as fructose, mannose, and xylulose, as well as disaccharides, such as sucrose and maltose, unlike the wild-type strain. Lack of growth of the glucose transport-deficient mutants on maltose revealed the extracellular breakdown of maltose in S. pombe, unlike in Saccharomyces cerevisiae. Both of the mutants are unable to grow on low concentrations of glucose (10 to 20 mM), while one of them, 3/23, grows on high concentrations (50 to 100 mM) as if altered in its affinity for glucose. This mutant (3/23) shows a lag period of 12 to 18 h when grown on high concentrations of glucose. The lag disappears when the culture is transferred from the log phase of its growth on high concentrations. These mutants complement phenotypically similar sugar transport mutants (YGS4 and YGS5) reported earlier by Milbradt and Hoefer (Microbiology 140:2617-2623, 1994), and the clone complementing YGS4 and YGS5 was identified as the only glucose transporter in fission yeast having 12 transmembrane domains. These mutants also demonstrate two other defects: lack of induction and repression of shunt pathway enzymes and defective mating.
