ABSTRACT
MicroRNA-mediated gene silencing is a fundamental mechanism in the regulation of gene expression. It remains unclear how the efficiency of RNA silencing could be influenced by RNA-binding proteins associated with the microRNA-induced silencing complex (miRISC). Here we report that fused in sarcoma (FUS), an RNA-binding protein linked to neurodegenerative diseases including amyotrophic lateral sclerosis (ALS), interacts with the core miRISC component AGO2 and is required for optimal microRNA-mediated gene silencing. FUS promotes gene silencing by binding to microRNA and mRNA targets, as illustrated by its action on miR-200c and its target ZEB1. A truncated mutant form of FUS that leads its carriers to an aggressive form of ALS, R495X, impairs microRNA-mediated gene silencing. The C. elegans homolog fust-1 also shares a conserved role in regulating the microRNA pathway. Collectively, our results suggest a role for FUS in regulating the activity of microRNA-mediated silencing.
Subject(s)
Caenorhabditis elegans Proteins/metabolism , Caenorhabditis elegans/metabolism , Gene Silencing , MicroRNAs/metabolism , RNA, Helminth/metabolism , RNA-Binding Protein FUS/metabolism , Amyotrophic Lateral Sclerosis/genetics , Amyotrophic Lateral Sclerosis/metabolism , Amyotrophic Lateral Sclerosis/pathology , Animals , Caenorhabditis elegans/genetics , Caenorhabditis elegans Proteins/genetics , HEK293 Cells , Humans , Mice , MicroRNAs/genetics , RNA, Helminth/genetics , RNA-Binding Protein FUS/geneticsABSTRACT
BACKGROUND: Accumulating evidence has demonstrated a pathogenic role of advanced glycation end products (AGEs) and receptors for AGEs (RAGE) in inflammation. Soluble RAGE (sRAGE), with the same ligands-binding capacity as full-length RAGE, acts as a "decoy" receptor. However, there has been scanty data regarding AGEs and sRAGE in adult-onset Still's disease (AOSD). This study aimed to investigate AGEs and sRAGE levels in AOSD patients and examine their association with clinical characteristics. METHODS: Using ELISA, plasma levels of AGEs and sRAGE were determined in 52 AOSD patients, 36 systemic lupus erythematosus(SLE) patients and 16 healthy controls(HC). Their associations with activity parameters and disease courses were evaluated. RESULTS: Significantly higher median levels of AGEs were observed in active AOSD patients (16.75 pg/ml) and active SLE patients (14.80 pg/ml) than those in HC (9.80 pg/ml, both p < 0.001). AGEs levels were positively correlated with activity scores (r = 0.836, p < 0.001), ferritin levels (r = 0.372, p < 0.05) and CRP levels (r = 0.396, p < 0.005) in AOSD patients. Conversely, significantly lower median levels of sRAGE were observed in active AOSD patients (632.2 pg/ml) and active SLE patients (771.6 pg/ml) compared with HC (1051.7 pg/ml, both p < 0.001). Plasma sRAGE levels were negatively correlated with AOSD activity scores (r = -0.320, p < 0.05). In comparison to AOSD patients with monocyclic pattern, significantly higher AGEs levels were observed in those with polycyclic or chronic articular pattern. With treatment, AGEs levels declined while sRAGE levels increased in parallel with the decrease in disease activity. CONCLUSION: The elevation of AGEs levels with concomitant decreased sRAGE levels in active AOSD patients, suggests their pathogenic role in AOSD.
Subject(s)
Glycation End Products, Advanced/blood , Receptor for Advanced Glycation End Products/blood , Still's Disease, Adult-Onset/blood , Adult , Biomarkers/blood , Case-Control Studies , Enzyme-Linked Immunosorbent Assay , Female , Humans , Logistic Models , Lupus Erythematosus, Systemic/blood , Lupus Erythematosus, Systemic/diagnosis , Male , Middle Aged , Predictive Value of Tests , Prognosis , Prospective Studies , Severity of Illness Index , Still's Disease, Adult-Onset/diagnosis , Still's Disease, Adult-Onset/drug therapy , Young AdultABSTRACT
Frameworks have been developed to standardize the assessment of carcinogenic potential in the pharmaceutical and agrochemical industries, building upon decades of research. Carcinogenicity is also evaluated during the safety evaluation of food substances, using a comprehensive approach unique to each substance. To better understand these approaches, a retrospective assessment was conducted on the publicly available database of substances notified to the United States Food and Drug Administration (US FDA) as being Generally Recognized As Safe (GRAS). The data contained within these GRAS notifications (GRNs) were reviewed for the methods used to evaluate carcinogenic potential (genotoxicity studies, 2-year bioassays, other pre-clinical animal studies) to identify patterns that could provide an understanding of how this assessment has been conducted for different categories of food substances. While different approaches to the safety evaluation were required to adapt to the unique food substances, the data in all notifications supported the conclusion of safety. The evaluation of food substances for carcinogenic potential must consider all available data, including identifying the need for when more data must be generated to support an evaluation. Due to the complexity of substances used in food, ranging from defined chemical entities to minimally processed agricultural commodities to live microorganisms, the approach to conducting the safety evaluation of food substances must be able to adapt to the most relevant scientifically supported approach. This paper illustrates the data commonly used to support the safety of different types of food substances and proposes an approach familiar to other product sectors.
Subject(s)
Carcinogenicity Tests , Carcinogens , United States Food and Drug Administration , United States , Animals , Carcinogens/toxicity , Humans , Retrospective Studies , Risk Assessment/methods , Food Safety , Databases, FactualABSTRACT
Introduction: Atypical anti-neutrophil cytoplasmic antibody (a-ANCA) is characterized by a positive fluorescence staining other than typical cytoplasmic or perinuclear ANCA. ANCA is associated with increased risk of dialysis and mortality in patients with ANCA vasculitis. However, comorbidities related to a-ANCA and whether a-ANCA exhibits an increased risk for renal failure and mortality remain unclear. This study aimed to explore the comorbidities and outcome associated with a-ANCA. Materials and methods: This retrospective study enrolled 164 and 170 patients with typical ANCA and a-ANCA positivity, respectively, who visited Taichung Veterans General Hospital, Taiwan from January 2016 to March 2021. Logistic regression analysis was used to determine risk factors and the rheumatological diagnosis associated with a-ANCA. Cox proportional hazard regression and Kaplan-Meier curves were employed to identify variables associated with 5-year renal survival and mortality. Results: Patients with a-ANCA had lower chance of ANCA-associated vasculitis (OR: 0.02, 95 % CI: 0.01-0.07 p < 0.001), and systemic lupus erythematosus (OR: 0.23, 95 % CI: 0.11-0.48, p < 0.001), but a higher risk of rheumatoid arthritis (OR: 2.99, 95 % CI: 1.15-7.83, p = 0.025) and ulcerative colitis (OR: 5.50, 95 % CI: 1.20-25.29, p = 0.028). Patients with a-ANCA had a better renal survival (OR: 0.14, 95 % CI: 0.08-0.24, p < 0.001) and lower mortality (OR: 0.31, 95 % CI: 0.16-0.60, p = 0.001) than patents in the typical ANCA group. The 5-year renal survival and mortality was 89.3 % and 8.8 %, respectively, in patients with a-ANCA. Conclusion: Patients with a-ANCA had better renal survival and lower mortality rates compared to patients with typical ANCA. These real-world data provide evidence of the long-term outcome and shed light on avenues for the strategic management of patients with a-ANCA.
ABSTRACT
Background: Aspergillus diseases are frequently encountered in patients who are immunocompromised. Without a prompt diagnosis, the clinical consequences may be lethal. Aspergillus-specific antibodies have been widely used to facilitate the diagnosis of Aspergillus diseases. To date, universally standardized cut-off values have not been established. This study aimed to investigate the cut-off values of Aspergillus-specific antibodies and perform a narrative review to depict the geographic differences in the Taiwanese population. Methods: We analyzed enrolled 118 healthy controls, 29 patients with invasive aspergillosis (IA), chronic pulmonary aspergillosis (CPA), and allergic bronchopulmonary aspergillosis (ABPA) and 99 with disease control, who were tested for Aspergillus fumigatus and Aspergillus niger-specific IgG and IgE using ImmunoCAP. 99 participants not fulfilling the diagnosis of IA, CPA, and ABPA were enrolled in the disease control group. The duration of retrieval of medical records from June 2018 to September 2021. Optimal cut-offs and association were determined using receiver operating characteristic curve (ROC) analysis. Results: We found that patients with CPA had the highest A. fumigatus-specific IgG levels while patients with ABPA had the highest A. fumigatus-specific IgE, and A. niger-specific IgG and IgE levels. In patients with CPA and ABPA, the optimal cut-offs of A. fumigatus-specific IgG and A. niger-specific IgG levels were 41.6, 40.8, 38.1, and 69.9 mgA/l, respectively. Geographic differences in the cut-off values of A. fumigatus-specific IgG were also noted. Specifically, the levels were different in eco-climatic zones. Conclusion: We identified the optimal cut-offs of Aspergillus-specific antibodies to facilitate a precise diagnosis of aspergillosis. The observed geographic differences of the antibody levels suggest that an eco-climatic-specific reference is needed to facilitate a prompt and accurate diagnosis of aspergillosis.
ABSTRACT
Dendritic trafficking and translation of brain-derived neurotrophic factor (BDNF) transcripts play a key role in mediating synaptic plasticity. Recently, we demonstrated that siRNA-mediated knockdown of translin, an RNA-binding protein, impairs KCl-induced dendritic trafficking of BDNF mRNA in cultured hippocampal neurons. We have now assessed whether translin deletion impairs dendritic trafficking of BDNF mRNA in hippocampal neurons in vivo. We have found that translin and its partner protein, trax, undergo dendritic translocation in response to treatment with pilocarpine, a pro-convulsant muscarinic agonist that increases dendritic trafficking of BDNF mRNA in hippocampal neurons. In translin knockout mice, the basal level of dendritic BDNF mRNA is decreased in CA1 pyramidal neurons. However, translin deletion does not block pilocarpine's ability to increase dendritic trafficking of BDNF mRNA indicating that the requirement for translin in this process varies with the stimulus employed to drive it. Consistent with this inference, we found that dendritic trafficking of BDNF mRNA induced by bath application of recombinant BDNF in cultured hippocampal neurons, is not blocked by siRNA-mediated knockdown of translin. Taken together, these in vivo and in vitro findings indicate that dendritic trafficking of BDNF mRNA can be mediated by both translin-dependent and -independent mechanisms.
Subject(s)
Brain-Derived Neurotrophic Factor/genetics , Dendrites/metabolism , Matrix Metalloproteinase 3/physiology , RNA, Messenger/metabolism , Analysis of Variance , Animals , DNA-Binding Proteins/metabolism , Dendrites/drug effects , Electrophoretic Mobility Shift Assay/methods , Hippocampus/cytology , Immunoprecipitation/methods , In Vitro Techniques , Matrix Metalloproteinase 3/deficiency , Mice , Mice, Inbred C57BL , Mice, Knockout , Muscarinic Agonists/pharmacology , Neurons/cytology , Pilocarpine/pharmacology , RNA, Small Interfering/pharmacologyABSTRACT
This study aimed to compare the test results of anti-double-stranded DNA (anti-dsDNA) antibodies obtained using chemiluminescent immunoassay (CIA) and enzyme-linked immunosorbent assay (ELISA), and investigate predictors of inconsistent results. This retrospective study included 502 patients who underwent CIA and ELISA to determine their anti-dsDNA antibody values within a year. We compared the diagnostic power for SLE, disease activity, and predictive power for lupus nephritis (LN). A multivariate analysis was performed to determine the predictors of inconsistencies. CIA and ELISA were moderately correlated in terms of their consistency (Cronbach's α = 0.571), and yielded comparably favorable results in terms of SLE diagnostic power and SLE disease activity. However, if the patient had LN, CIA displayed higher predictive power than ELISA (0.620 vs. 0.555, p = 0.026). Compared with the CIA/ELISA double-positive group, the inconsistent group had lower anti-C1q circulating immune complexes (CIC) antibody values (OR: 0.42, 95% CI: 0.18-0.94, p = 0.036), and lower SLEDAI scores (≥4) (OR: 0.33, 95% CI: 0.14-0.79, p = 0.013). Anti-dsDNA antibody detection with CIA exhibited higher predictability for diagnosing LN than did ELISA. In the event of inconsistencies between anti-dsDNA methods, SLE disease activity and CIC test values should be considered simultaneously.
ABSTRACT
BACKGROUND: Antinuclear antibody pattern recognition is vital for autoimmune disease diagnosis but labor-intensive for manual interpretation. To develop an automated pattern recognition system, we established machine learning models based on the International Consensus on Antinuclear Antibody Patterns (ICAP) at a competent level, mixed patterns recognition, and evaluated their consistency with human reading. METHODS: 51,694 human epithelial cells (HEp-2) cell images with patterns assigned by experienced medical technologists collected in a medical center were used to train six machine learning algorithms and were compared by their performance. Next, we choose the best performing model to test the consistency with five experienced readers and two beginners. RESULTS: The mean F1 score in each classification of the best performing model was 0.86 evaluated by Testing Data 1. For the inter-observer agreement test on Testing Data 2, the average agreement was 0.849 (κ) among five experienced readers, 0.844 between the best performing model and experienced readers, 0.528 between experienced readers and beginners. The results indicate that the proposed model outperformed beginners and achieved an excellent agreement with experienced readers. CONCLUSIONS: This study demonstrated that the developed model could reach an excellent agreement with experienced human readers using machine learning methods.
ABSTRACT
Prader-Willi syndrome (PWS) is a rare, multifaceted genetic disorder resulting from the absence of normally active paternally expressed genes from the 15q11-q13 chromosome region. Due to a lack of anthropometric and intellectual data in Taiwan, we attempted these evaluations. Twenty patients (14 males/6 females) aged 7-23 years with molecularly confirmed PWS were enrolled with parental consent. Their mean height standard deviation score (SDS) was -1.26 +/- 1.89 (from -4.3 to +2.16); mean weight SDS was +1.77 +/- 2.00 (from -0.44 to +5.89); mean body mass index SDS was +3.84 +/- 10.54 (from -0.08 to +10.48); and mean body fat tissue SDS was 39.4 +/- 10.54% (14.7-57.8%) by an InBody 3.0 analyzer. All were hypogonadal. Nine of them had once been given growth hormone therapy, and were taller and slimmer than the rest. Their intelligence tests showed full intelligence quotient = 52.0 +/- 7.6; verbal intelligence quotient = 55.9 +/- 8.77; performance intelligence quotient = 53.2 +/- 9.0. Chronic health status revealed that diabetes was prevalent among the older population. Their IQ was in the range of those with moderate retardation.
Subject(s)
Body Size , Intelligence , Prader-Willi Syndrome/psychology , Adolescent , Adult , Child , Female , Humans , Male , Prader-Willi Syndrome/pathologyABSTRACT
Long-lasting forms of synaptic plasticity and memory require de novo protein synthesis. Yet, how learning triggers this process to form memory is unclear. Translin/trax is a candidate to drive this learning-induced memory mechanism by suppressing microRNA-mediated translational silencing at activated synapses. We find that mice lacking translin/trax display defects in synaptic tagging, which requires protein synthesis at activated synapses, and long-term memory. Hippocampal samples harvested from these mice following learning show increases in several disease-related microRNAs targeting the activin A receptor type 1C (ACVR1C), a component of the transforming growth factor-ß receptor superfamily. Furthermore, the absence of translin/trax abolishes synaptic upregulation of ACVR1C protein after learning. Finally, synaptic tagging and long-term memory deficits in mice lacking translin/trax are mimicked by ACVR1C inhibition. Thus, we define a new memory mechanism by which learning reverses microRNA-mediated silencing of the novel plasticity protein ACVR1C via translin/trax.
Subject(s)
Activin Receptors, Type I/metabolism , DNA-Binding Proteins/metabolism , Gene Expression , Learning , Memory , RNA-Binding Proteins/metabolism , Ribonucleases/metabolism , Animals , Hippocampus/physiology , Mice , Neuronal PlasticityABSTRACT
BACKGROUND: Studies comparing the growth of children between Tibetan and Han ethnic groups have not been reported. OBJECTIVE: To increase the understanding regarding the growth status of children and the growth difference between the Tibetan and Han ethnic groups. METHODS: Body weight, body height, and BMI of 894 Tibetan monks aged from 8-17 years old, residing in South India were collected, while growth information for boys in Taiwan was obtained from the Taiwan growth chart developed in 1997. RESULTS: In the 50th percentile, the median height difference between those boys 8 and 17 years of age was 46.8 cm, with a 5-6 cm increase each year. The median weight difference between 8- and 17-year-old groups was 33 kg, with a 0-6.5 kg increase each year. Each year, the BMIs of monks in the 5th, 50th, and 95th percentiles had 3.0-5.4%, 1.6-10%, and 3.1-8.8% increased rates, respectively. The differences of height and weight between the two groups increased between the ages of 9 and 14 years of age, but Taiwan boys and Tibetan monks had nearly the same height and weight at 17 years old. Based on the BMI-for-age curve, there were more Taiwanese boys overweight or obese than Tibetan monks. CONCLUSIONS: Even after using the data of ten years ago in Taiwan, Taiwanese boys had superior nutrition and growth status compared with Tibetan monks between the ages of eight and seventeen years, inclusive. In addition, racial differences might also play a significant factor in growth.
Subject(s)
Body Height/physiology , Body Mass Index , Body Weight/physiology , Child Development , Adolescent , Altitude , Child , Growth , Humans , India , Male , Obesity/epidemiology , Overweight , Taiwan/epidemiology , Tibet/epidemiologyABSTRACT
BACKGROUND: Extrapelvic endometriosis may occur at unusual sites. We report a rare case of an endometrioma presenting as a suburethral mass in a woman without a previous surgical history. CASE: A 27-year-old, nulliparous woman presented with a painful suburethral mass, dyspareunia and voiding difficulty. Ultrasonographic examination showed an echolucent mass over the suburethral area measuring 3.7 cm in diameter. Double-balloon cystourethrography showed that the mass did not communicate with the urethral lumen. Complete excision was performed later. The final pathologic examination revealed endometriosis. CONCLUSION: Extrapelvic endometriosis should be considered as a possible diagnosis for a suburethral mass even if no pelvic endometriosis is detected from a detailed history and vaginal examination. Ultrasonography and double-balloon cystourethrography may be helpful for clinical evaluation. Complete excision is advisable for management of a suburethral endometrioma.
Subject(s)
Endometriosis/diagnostic imaging , Endometriosis/surgery , Urethral Diseases/diagnostic imaging , Urethral Diseases/surgery , Adult , Endometriosis/pathology , Female , Humans , Ultrasonography , Urethral Diseases/pathologyABSTRACT
Genetic defects in the microRNA (miRNA) generating enzyme, dicer, are increasingly linked to disease. Loss of miRNA in dicer deficiency is thought to be due to loss of miRNA-generating activity. Here, we demonstrate a catabolic mechanism driving miRNA depletion in dicer deficiency. We developed a Dicer-antagonist assay revealing a pre-miRNA degrading enzyme that competes with pre-miRNA processing. We purified this pre-miRNA degrading activity using an unbiased chromatographic procedure and identified the ribonuclease complex Translin/Trax (TN/TX). In wild-type dicer backgrounds, pre-miRNA processing was dominant. However, in dicer-deficient contexts, TN/TX broadly suppressed miRNA. These findings indicate that miRNA depletion in dicer deficiency is due to the combined loss of miRNA-generating activity and catabolic function of TN/TX. Importantly, inhibition of TN/TX mitigated loss of both miRNA and tumor suppression with dicer haploinsufficiency. These studies reveal a potentially druggable target for restoring miRNA function in cancers and emerging dicer deficiencies.
Subject(s)
DNA-Binding Proteins/antagonists & inhibitors , RNA-Binding Proteins/antagonists & inhibitors , Ribonuclease III/metabolism , Animals , Base Sequence , Cell Fractionation , Chromatography , DNA-Binding Proteins/metabolism , HCT116 Cells , Haploinsufficiency , HeLa Cells , Humans , Mice, Inbred C57BL , MicroRNAs/metabolism , Molecular Sequence Data , RNA Precursors/metabolism , RNA Processing, Post-Transcriptional , RNA Stability , RNA-Binding Proteins/metabolismABSTRACT
Parkinson's disease (PD) is a progressive neurodegenerative movement disorder characterized by selective loss of dopaminergic neurons and the presence of Lewy bodies. Alpha-synuclein is a major component of Lewy bodies in sporadic PD, and genetic alterations in alpha-synuclein cause autosomal-dominant hereditary PD. The pathogenesis of PD remains incompletely understood, but it appears to involve both genetic susceptibility and environmental factors. Here we investigated the effect of alpha-synuclein expression on cell susceptibility to proteasome inhibition, oxidative and nitrative stresses by using a PC 12-Tet-off regulatory system. We found that inducible expression of A30P or A53T mutant alpha-synuclein decreased the proteasome activity, increased intracellular ROS levels, and enhanced lactacystin- and H2O2-induced cell death. Furthermore, 3-nitrotyrosine levels increased in cells expressing alpha-synuclein, and further increased after Sin-1 (a NO donor) treatment compared with untreated or treated non-induced cells. Expression of alpha-synuclein (mutant more than wild type) significantly enhances Sin-1 toxicity. These results indicate that genetic mutations in alpha-synuclein may increase neuronal vulnerability to cellular stress in aging and PD pathogenesis.
Subject(s)
Genetic Predisposition to Disease , Hydrogen Peroxide/toxicity , Molsidomine/analogs & derivatives , Mutation , Parkinson Disease/genetics , Parkinson Disease/pathology , alpha-Synuclein/genetics , Animals , Cell Death/drug effects , Cell Death/physiology , Dose-Response Relationship, Drug , Molsidomine/toxicity , PC12 Cells , Parkinson Disease/metabolism , Rats , Reactive Oxygen Species/metabolism , alpha-Synuclein/biosynthesis , alpha-Synuclein/physiologyABSTRACT
PURPOSE: We conducted a pilot trial to evaluate the value of 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) in gestational trophoblastic tumours (GTTs). METHODS: Patients with placental site trophoblastic tumour (PSTT), high-risk GTT (World Health Organisation score > or =8, disease onset at postpartum or greater than 6 months after antecedent pregnancy), metastatic GTT, recurrent/resistant GTT after chemotherapy, or post-molar GTT with unexplained abnormal beta-hCG regression and patients undergoing re-evaluation after salvage treatment were enrolled. PET was undertaken within 1 week after computed tomography (CT). Clinical impacts of additional PET were determined on a scan basis. RESULTS: A total of 14 patients were recruited. Sixteen PET scans were performed, with one patient having three serial studies. Benefits of additional PET were seen in 7 of 16 (43.8%) scans; these benefits included disclosure of chemotherapy-resistant lesions (n = 2), exclusion of false-positive CT lesions (n = 1), detection of an additional lesion not found by conventional imaging (n = 1) in high-risk GTT at the start of primary chemotherapy, and confirmation of complete response to treatment for PSTT or to salvage therapy for recurrent/resistant GTT (n = 3). On the other hand, in two instances there were false-negative PET findings, six scans yielded no benefit, and one showed an indeterminate lesion. CONCLUSION: Our preliminary results suggest that 18F-FDG PET is potentially useful in selected patients with GTT by providing precise mapping of metastases and tumour extent upfront, by monitoring treatment response and by localising viable tumours after chemotherapy. A larger study is necessary to further define the role of 18F-FDG PET in GTT.
Subject(s)
Fluorodeoxyglucose F18 , Gestational Trophoblastic Disease/diagnosis , Positron-Emission Tomography/methods , Adult , Antineoplastic Agents/pharmacology , Chorionic Gonadotropin, beta Subunit, Human/blood , Female , Gestational Trophoblastic Disease/pathology , Humans , Image Processing, Computer-Assisted , Middle Aged , Neoplasm Metastasis , Pilot Projects , Pregnancy , Tomography, X-Ray ComputedABSTRACT
PURPOSE: The role of positron emission tomography (PET) with [18F]-fluoro-2-deoxy-D-glucose (FDG) in early-stage cervical cancer is unclear. We aimed to investigate the clinical benefit of FDG-PET in primary staging before radical hysterectomy and pelvic lymphadenectomy (RH-PLND). PATIENTS AND METHODS: Patients with untreated stage IA2 to IIA adenocarcinoma (AD) or adenosquamous carcinoma (ASC) or nonbulky (< or = 4 cm) squamous cell carcinoma cervical cancer with magnetic resonance imaging (MRI) -defined negative nodal metastasis were enrolled onto a prospective study with a two-stage design. All patients had a preoperative dual-phase FDG-PET, technetium-99m-sulfur colloid lymphoscintigraphy, and intraoperative sentinel lymph node (LN) detection at RH-PLND. The gold standard of LN metastasis is histologic. A sample size of 120 patients was calculated to fit study aims (diagnostic efficacy of PET and sentinel LN sampling). An interim analysis was performed when 60 patients were accrued, which led to the current report. RESULTS: There were 36 SCCs, 20 ADs, and four ASCs. Of the 60 patients, 10 (16.7%) had pelvic LN metastases, and one (1.7%) had para-aortic LN (PALN) metastasis histologically. FDG-PET detected the single PALN metastasis (one of one patient) but detected only one (10%) of the 10 pelvic LN metastases. The PET false-negative pelvic LN micrometastases measured a median of 4.0 x 3.0 mm (range, 0.5 x 0.5 to 7 x 6 mm). The second stage of this trial will be continued without PET. CONCLUSION: This study shows that dual-phase FDG-PET has little value in primary, nonbulky, stage IA2 to IIA and MRI-defined, LN-negative cervical cancer.