Gene/Protein Disease Symptom Drug Enzyme Compound
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Quantification of residual disease by real-time polymerase chain reaction (PCR) will become a pivotal tool in the development of patient-directed therapy. In recent years, various protocols to quantify minimal residual disease in leukemia or lymphoma patients have been developed. These assays assume that PCR efficiencies are equal for all samples. Determining t(14;18) and albumin reaction efficiencies for sixteen follicular lymphoma patient samples revealed higher efficiencies for blood samples than for lymph node samples in general. However, within one sample both reactions had equivalent efficiencies. Differences in amplification efficiencies between patient samples (low efficiencies) and the calibrator in quantitative analyses result in the underestimation of residual disease in patient samples whereby the weakest positive patient samples are at highest error. Based on these findings for patient samples, the efficiency compensation control was developed. This control includes two reference reactions in a multiplex setting, specific for the beta-actin and albumin housekeeping genes that are present in a constant ratio within DNA templates. The difference in threshold cycle values for both reference reactions, ie, the Ct(2) value, is dependent on the amplification efficiency, and is used to compensate for efficiency differences between patient samples and the calibrator. The beta-actin reference reaction is also used to normalize for DNA input. Furthermore, the efficiency compensation control facilitates identification of patient samples that are so contaminated with PCR inhibitory compounds that different amplification reactions are affected to a different extent. Accurate quantitation of residual disease in these samples is therefore impossible with the current quantitative real-time PCR protocols. Identification and exclusion of these inadequate samples will be of utmost importance in quantitative retrospective studies, but even more so, in future molecular diagnostic analyses.
J Mol Diagn 2001 May
PMID:A novel method to compensate for different amplification efficiencies between patient DNA samples in quantitative real-time PCR. 1168 3

The t(14;18) translocation is a useful marker to characterize follicular lymphoma and to monitor residual disease. The polymerase chain reaction (PCR) is a powerful technique to detect this translocation. Located on chromosome 18, within the Bcl-2 gene, breakpoints occur mainly in the 3; untranslated region, in the third exon of Bcl-2 (MBR region). In this study, the authors amplified MBR breakpoints by PCR and found an unexpectedly large fragment of 1 Kb that corresponds to a recently described new breakpoint in the Bcl-2 gene. With a new primer set, a further previously considered t(14;18)-unrelated tumor was in fact positive for this new breakpoint.
Diagn Mol Pathol 2001 Jun
PMID:A 1-kb Bcl-2-PCR fragment detection in a patient with follicular lymphoma and development of a new diagnostic PCR method. 1138 16

About 20 years ago, gallium-67 planar scintigraphy was introduced for the evaluation of advanced esophageal squamous cell carcinoma (AESCC). Although single-photon emission tomography (SPET) is now available in many institutions, there have been no reports regarding the evaluation of AESCC using (67)Ga SPET. The aims of this preliminary study were to assess the potential of (67)Ga SPET for the detection of AESCC and to further evaluate whether (67)Ga SPET can predict the effect of preoperative chemoradiotherapy on AESCC. Thirty-eight patients with histologically proven AESCC (35 men and 3 women, mean age 62+/-6.9 years) underwent (67)Ga SPET before and after preoperative chemoradiotherapy. The histological response to the chemoradiotherapy was determined from a surgical specimen of the esophagus: grade 0, 100% viable tumor cells; grade 1a, 99%-67%; grade 1b, 66%-34%; grade 2, 33%-1%; grade 3, no viable cells. Thirty-seven out of 38 AESCCs (97.4%) were detected on pre-chemoradiotherapy SPET. In these 37 cancers, the tumor-to-lung ratio (TLRpre) was 3.5+/-2 (range 1.5-9.6). Post-chemoradiotherapy SPET exhibited positive results in 22 cancers, with a TLRpost of 1.8+/-0.4 (range 1.1-2.6). No patient exhibiting a pathologically complete response had a positive post-chemoradiotherapy SPET result, whereas 80% of patients with negative post-chemoradiotherapy SPET (12/15) results had residual tumor. The percent reduction rate was defined as (TLRpre-TLRpost)/TLRpre x100 and did not correlate with histological response grade ( P=0.5169 for Kruskal-Wallis test). These results suggest that (67)Ga SPET is a powerful tool for the detection of AESCC. However, (67)Ga SPET seems to be of little use in predicting the effects of preoperative chemoradiotherapy on AESCC. Further studies are warranted in order to further clarify the clinical usefulness of (67)Ga SPET in patients with AESCC.
Eur J Nucl Med Mol Imaging 2002 Aug
PMID:Detection and chemoradiotherapeutic evaluation of advanced esophageal squamous cell carcinoma using gallium-67 SPET: a preliminary study. 1217 22

The aim of post-surgical follow-up for differentiated thyroid carcinoma is the early identification of the small proportion of patients who have residual disease or develop a recurrence. When total thyroidectomy and radioiodine ablation have been the initial treatment, three powerful tools are available for the follow-up: basal and TSH-stimulated serum thyroglobulin (Tg) measurement, iodine-131 whole body scan (WBS) and neck ultrasound. Serum Tg measurement is the most sensitive and specific marker of differentiated thyroid cancer. Undetectable serum Tg levels are found in the large majority of disease-free patients, while elevated concentrations of serum Tg are associated with the presence of residual or metastatic thyroid tissue. In the last case, WBS under TSH stimulation (either after withdrawal of L-thyroxine therapy or after recombinant human TSH stimulation) and neck ultrasound are the most informative tests for the detection of distant or local metastases, respectively, that require more appropriate treatment (surgery and/or radioiodine therapy). Using this strategy, most patients will achieve definitive cure and will have a normal quality of life.
Eur J Nucl Med Mol Imaging 2002 Aug
PMID:Follow-up of differentiated thyroid cancer. 1219 51

Diagnosis of a second HIV-associated non-Hodgkin lymphoma (HIV-NHL) is rare, but additional cases may occur as aggressive therapy for both HIV and NHL improves. An 11-year-old presented with a second primary HIV-NHL following remission for 9 years. Analysis of the tumor demonstrated presence of EBV and HIV with absence of CMV, HHV-8, and HHV-6. Although microscopic disease was present only in CSF, analysis of peripheral blood and bone marrow by PCR was positive. The patient underwent a stem cell transplant, but within 3 months, his disease recurred. Analysis for residual disease and viruses in similar cases may provide information in understanding pediatric HIV-NHL.
Pediatr Pathol Mol Med
PMID:Molecular analysis and pathology of a second pediatric HIV-associated Burkitt lymphoma. 1253 69

Recent advances in molecular genetics impact the health care and outcome of patients with acute lymphoblastic leukemia (ALL). BCR-ABL, a common molecular defect in adult ALL, is a valuable tumor marker whose detection influences prognosis and clinical management decisions. Molecular methods such as fluorescence in situ hybridization (FISH), reverse-transcriptase polymerase chain reaction (rtPCR), and real-time quantitative rtPCR can be used to detect the chimeric BCR-ABL gene or its transcripts. These molecular assays improve our ability to measure residual disease and to estimate risk of relapse. On the horizon are gene expression profiles that will likely provide additional information beyond what is obtainable with current clinical and laboratory approaches.
J Mol Diagn 2003 May
PMID:Clinical applications of BCR-ABL molecular testing in acute leukemia. 1270 70

Positron emission tomography (PET) and single-photon emission tomography (SPET) are cross-sectional, quantitative functional imaging modalities in routine use in oncology for the initial staging of cancer, the assessment of patients with recurrent or residual disease and, more recently, for monitoring tumour response to therapy. Both PET and SPET can track tumour biological and metabolic changes caused by therapy or by disease progression, which usually precede the anatomical alterations conventionally detected by anatomical imaging methods. These highly sensitive functional imaging modalities have been used for the early assessment of subclinical tumour response, the evaluation of therapy after its completion and the detection of viable recurrent or relapsing tumour. Timely assessment of response to treatment using PET and SPET may result in modifications in treatment planning and individualisation of therapy and may have prognostic value for the long-term outcome. This review attempts to summarise the current data available on the expanding role of SPET and PET, using a variety of tracers, in monitoring tumour response to therapy in a wide range of malignancies, with emphasis on their clinical impact.
Eur J Nucl Med Mol Imaging 2003 Aug
PMID:The role of SPET and PET in monitoring tumour response to therapy. 1281 21

In regions with a high prevalence of granulomatous diseases, benign inflammatory fluorine-18 fluorodeoxyglucose (FDG) uptake in the mediastinum is frequently observed even in healthy subjects. We examined parameters of mediastinal FDG uptake to determine whether they can differentiate malignancy from benign lesions. Seventy patients with non-thoracic tumours who had mediastinal uptake on FDG positron emission tomography (PET) were included (33 males, 37 females; age 57.5 +/- 16.9 years; 168 lymph nodes). Determination of metastasis was confirmed by biopsy or computed tomography (CT) follow-up over 12 months (metastasis, 29; benign lesions, 41). No significant difference between the metastasis group and the benign group was found in terms of residual disease in the primary site (48% vs 46%), lung invasion (29% vs 20%), number of sites of uptake (2.3 vs 2.4), smoking history (30.3% vs 46.3%) or bilateral uptake (52% vs 54%). Maximal standardised uptake values (SUVs) in the mediastinal metastasis group were higher (4.9 +/- 1.8) than those in the benign group (2.5 +/- 0.9) (P < 0.05). Using 3.4 as a cut-off value for maximal SUV, a sensitivity of 86% and a specificity of 85% were achieved (AUC = 0.917). Maximal SUV showed better predictive value than lymph node size measured on chest CT (P < 0.05). In 8 of 51 normal subjects who underwent FDG PET as a routine check-up, mediastinal FDG uptake was observed. Maximal SUV in normal subjects was 2.5 +/- 0.8, which was similar to that in the benign group. In conclusion, maximal SUV was identified as a significant parameter for determining whether mediastinal FDG uptake represents malignant metastasis. When maximal SUV exceeded 3.4, the metastasis rate was high regardless of lymph node size.
Eur J Nucl Med Mol Imaging 2004 Feb
PMID:Differentiation of mediastinal FDG uptake observed in patients with non-thoracic tumours. 1512 2

Cardiovascular disease is the major cause of premature death in modern society, and its impact is increasing due to rising rates of obesity and type 2 diabetes. Clinical studies based on targeting metabolic abnormalities and biomarkers demonstrate significant benefits, but always an element of disease remains which is resistant to treatment. Recent evidence has strongly implicated an early interaction of atherogenic lipoproteins with vascular matrix proteoglycans as the initiating step in atherogenesis. Expert commentary has pointed to the need for vascular directed therapies to provide reductions in the residual disease component. We propose that the regulation of synthesis and thus structure of glycosaminoglycans on proteoglycans provides a potential pathway to this reduction. We review existing evidence that the vascular synthesis of glycosaminoglycan chains can be regulated in a manner which reduces lipoprotein binding and the potential application of this strategy to attenuation of the current cardiovascular disease pandemic.
Cell Mol Life Sci 2004 Jun
PMID:Regulation of glycosaminoglycan structure and atherogenesis. 1517 May 8

Positron emission tomography (PET) using the positron emitting glucose analogue 18F-fluorodeoxyglucose (FDG) has emerged as a useful metabolism-based wholebody imaging tool for gastro-esophageal cancer diagnosis and follow up. Most large cancer centers worldwide are now equipped for PET (or even PET-CT). Therefore, there is a growing need for a clear definition of the relative position of PET within the currently available diagnostic modalities. Significant scientific data indicate that FDG-PET adds clinically useful information to the information obtained by standard means (mainly CT and endoscopic ultrasound) throughout the different phases of clinical patient management: 1) at initial diagnosis: PET detects more frequently distant lymph node involvement and organ metastases compared to conventional diagnostics, allowing a more accurate selection of the most appropriate treatment; 2) during chemotherapy: semi-quantitative FDG-PET allows early identification of non-responding patients. Indeed, the metabolic response as measured by serial FDG-PET can be used to predict the clinical and histopathological response. Moreover, the PET-response seems to be related to overall and disease free survival; 3) after a treatment: FDG-PET allows accurate assessment of the residual tumor load; 4) in the follow up: FDG-PET allows accurate detection and restaging of recurrent disease.
Q J Nucl Med Mol Imaging 2004 Jun
PMID:Position of positron emission tomography and other imaging diagnostic modalities in esophageal cancer. 1524 7


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