Sulfonylurea (SU) herbicides are widely used and often detected in environmental matrices and have toxic effects on ecosystems and plant development. However, the interaction between SU and soil-plant metabolism during the whole wheat growth cycle remains poorly investigated. Field trials demonstrated that bensulfuron methyl exposure reduced wheat height and a thousand grains' weight, disrupting the critical metabolic pathways, including linoleic acid and amino acid metabolism in the maturity stage. During different growth processes, bensulfuron methyl exposure decreases wheat soil and plants' defense-related indole alkaloid compounds, such as benzoxazinoids and melatonin. Microbial sequencing results showed that bensulfuron methyl treated decreased the abundance of beneficial microorganisms (Gammaproteobacteria, Bacteroidia, and Blastocatella) in the rhizosphere soil, which positively correlated with the inhibition of soil enzyme activity and the secretion of allelopathic substances (benzoxazinoids and melatonin). Molecular docking further confirmed that bensulfuron methyl affects protein molecular structure by establishing hydrogen bonds, which disequilibrate wheat benzoxazinoids and melatonin metabolism. Therefore, bensulfuron methyl exposure disrupted the interaction between soil microorganisms and indole alkaloid metabolism, hindering plant development. This study provides constructive insights into the environmental risks of herbicides and agricultural product safety throughout wheat development.
Purpose: With China's rapidly aging population and the rising proportion of obese people, an increase in the number of women suffering from urinary incontinence (UI) is to be expected. In order to identify high-risk groups before leakage occurs, we aimed to develop and validate a model to predict the risk of stress UI (SUI) in rural women. Patients and methods: This study included women aged 20-70 years in rural Fujian who participated in an epidemiologic survey of female UI conducted between June and October 2022. Subsequently the data was randomly divided into training and validation sets in a ratio of 7:3. Univariate and multivariate logistic regression analyses were used to identify independent risk factors as well as to further construct a nomogram for risk prediction. Finally, concordance index (C-index), calibration curve and decision curve analysis were applied to evaluate the performance of the predictive models. Results: A total of 5290 rural females were enrolled, of whom 771 (14.6%) had SUI. Age, body mass index (BMI), postmenopausal status, number of vaginal deliveries, vaginal delivery of large infant, constipation and family history of pelvic organ prolapse (POP) and SUI were included in the nomogram. C-index of this prediction model for the training and validation sets was 0.835 (95% confidence interval [CI] = 0.818-0.851) and 0.829 (95% CI = 0.796-0.858), respectively, and the calibration curves and decision analysis curves for both the training and validation sets showed that the model was well-calibrated and had a positive net benefit. Conclusion: This model accurately estimated the SUI risk of rural women in Fujian, which may serve as an effective primary screening tool for the early identification of SUI risk and provide a basis for further implementation of individualized early intervention. Moreover, the model is concise and intuitive, which makes it more operational for rural women with scarce medical resources.
BACKGROUND: m6A modification has close connection with the occurrence, development, and prognosis of tumors. This study aimed to explore the roles of m6A modification and its related mechanisms in non-small cell lung cancer (NSCLC). METHODS: NSCLC tissues and their corresponding para-cancerous tissues were collected to determine the m6A levels of total RNA/lncRNAs and the expression of m6A modification-related genes/lncRNAs. Then, A549 cells were transfected with si-METTL14 or oe-METTL14, and the cell transfection efficiency was assessed. Subsequently, the viability, apoptosis, cell colony formation, migration and invasion of the different cells were determined. Finally, the nude mouse tumorigenicity experiments were performed to observe the effects of METTL14 in vivo. RESULTS: Compared to the para-NSCLC tissues, the m6A level and METTL14 expression were both significantly increased in the NSCLC tissues (P < 0.05). Based on the expression of METTL14 in the different cell lines, A549 cells were chosen for further experiments. Then, the A549 cells with METTL14 knockdown and overexpression were successfully established, as well as it was found that METTL14 knockdown could inhibit the viability, colony formation, migration, and invasion of A549 cells, while facilitate their apoptosis. In vivo experiments also showed that METTL14 knockdown could inhibit tumor formation and growth. Additionally, the m6A level of MSTRG.292666.16 was higher in the NSCLC tissues; and after METTL14 knockdown, the expression and m6A level of MSTRG.292666.16 were both significantly reduced in A549 cells, and vice versa. CONCLUSION: METTL14 may promote the progression of NSCLC through up-regulating MSTRG.292666.16 and enhance its m6A modification level.
Patients with non-small cell lung cancer (NSCLC) treated with tyrosine kinase inhibitors (TKIs) inevitably exhibit drug resistance, which diminishes therapeutic effects. Nonetheless, the molecular mechanisms of TKI resistance in NSCLC remain obscure. In this study, data from clinical and TCGA databases revealed an increase in DNMT3A expression, which was correlated with a poor prognosis. Using NSCLC organoid models, we observed that high DNMT3A levels reduced TKI susceptibility of NSCLC cells via upregulating inhibitor of apoptosis proteins (IAPs). Simultaneously, the DNMT3Ahigh subset, which escaped apoptosis, underwent an early senescent-like state in a CDKN1A-dependent manner. Furthermore, the cellular senescence induced by TKIs was observed to be reversible, whereas DNMT3Ahigh cells reacquired their proliferative characteristics in the absence of TKIs, resulting in subsequent tumour recurrence and growth. Notably, the blockade of DNMT3A/IAPs signals enhanced the efficacy of TKIs in DNMT3Ahigh tumour-bearing mice, which represented a promising strategy for the effective treatment of NSCLC.
Purpose: To investigate the prevalence, risk factors, and impact on quality of life (QOL) of female urinary incontinence (UI) in a region of southeastern China. Patients and Methods: This cross-sectional study, conducted between June 2022 and March 2023, included 9584 women aged 20-70 years who completed a standardized questionnaire through face-to-face interviews. This sample size represents almost 10% of the population in the target area. Results: The prevalence of female UI was found to be 24.8%, with stress UI being the most common subtype (12.7%), followed by mixed UI (8.0%) and urgency UI (4.1%). Notably, the prevalence of UI increased progressively with age and body mass index (BMI). The study also revealed several risk factors for UI, including urban residence, postmenopausal status, multiple vaginal deliveries, instrumental vaginal deliveries, previous delivery of macrosomia, and prior history of pelvic floor surgery as determined by multivariate analysis. Furthermore, the study showed that 89.5% of women who reported UI experienced varying degrees of negative impact on their QOL. The incontinence quality of life (I-QOL) scale had an average score of 79.70±19.03, which decreased with increasing severity of UI. Despite the adverse effects on QOL, only 20.6% of women with UI had sought medical help. Conclusion: UI is common among women in the survey area. UI has been observed to have varying degrees of adverse effects on the QOL of those affected, but most of them do not seek treatment for several reasons, highlighting the urgent need for health authorities to develop effective UI intervention strategies.
Introduction: Despite the benefit of adjuvant systemic therapy for patients with resected non-small cell lung cancer (NSCLC), the risk of postoperative recurrence remains high. Our objective was to characterize temporal genetic heterogeneity between primary resected and recurrent tumors, and its impact on treatment outcomes. Methods: In this study, next-generation sequencing (NGS) testing was performed on tissue specimens and circulating tumor DNA (ctDNA) collected at postoperative recurrence, and results were compared to the genotypes of initial surgical specimens. Results: Of forty-five patients with matched primary and post-operative recurrent tumors, EGFR status switched in 17 patients (37.8%) at post-operative recurrence and 28 patients (62.2%) had no genotype change (17 mutant, 11 wild-type). Based on the changes of EGFR status, patients were divided into 4 groups. Following subsequent treatment with EGFR TKI o chemotherapy: In group A, with sustained sensitive mutation, the percentage achieving partial response (PR) was the highest, at 72.2%, the median progression-free survival (PFS) was 17 months, and the median overall survival (OS) was 44.0 months respectively; In group B, with genotype changed from wild-type to mutant, 50% achieved PR, PFS was 10 months, and OS was 35 months; In group C, in which mutant status shifted to wild-type or new co-mutation emerged, the percentage achieving PR was 30%, PFS was 9 months, and OS was 35 months. In group D, with sustained wild type, the percentage achieving PR was 27.3%, PFS was 8 months, and OS was 22 months. Discussion: Genotypic shift between paired primary and post-operative recurrent tumors was not infrequent, and this temporal genomic heterogeneity substantially impacted subsequent treatment outcomes.
The integration of halide perovskites with other functional materials provides a new platform for applications beyond photovoltaics, which has been realized in experiments. Here, through first-principles methods, we explore the possibility of constructing halide perovskite/antiperovskite oxide van der Waals heterostructures (vdWHs) for the first time with monolayers Rb2CdCl4 and Ba4OSb2 as representative compounds. Our calculation results reveal that the Rb2CdCl4/Ba4OSb2 vdWHs have negative binding energies and their most stable stacking possesses a rare type-III band alignment with a broken gap, which is highly promising for tunnel field-effect transistor (TFET) applications. Moreover, their electronic features can be further tuned by applying strain or an external electric field. Specifically, compressive strain can enlarge the tunneling window, while tensile strain can realize a type-III to type-II band alignment transformation. Therefore, our work provides fundamental insights into the electronic properties of Rb2CdCl4/Ba4OSb2 vdWHs and paves the way for the design and fabrication of future halide perovskite/antiperovskite-based TFETs.
To evaluate the relationships among exercise identity, exercise behavior and mobile phone addiction in 516 left-behind children in rural China (48.06% boys; Mage = 12.13 ± 1.95, range 8-16). Specifically, cross-sectional design was carried out to test the hypothesis that the association between rural left-behind children' exercise identity and mobile phone addition would be fully mediated by their exercise behavior. The participants filled in self-reported instruments. The data was analyzed using structural equation modeling and decomposition of direct and indirect effects. Exercise identity and exercise behavior were significantly negatively correlated with left-behind children's mobile phone addiction (r = -0.486, -0.278, P < 0.01), and exercise identity was positively correlated with their exercise behavior (r = 0.229, P < 0.01); the direct effect of exercise identity on mobile phone addiction was -0.226 (95% CI: -0.363 â¼ -0.108), accounting for 68.9% of the total effect of -0.328, and its indirect effect was 0.102 (95% CI: -0.161â¼-0.005), accounting for 31.1% of the total effect. These findings suggest that exercise identity may be an effective measure to reduce left-behind children's mobile phone addiction. It is suggested that school administrators and guardians should pay attention to improving left-behind children's exercise identity level in the education process.
INTRODUCTION AND HYPOTHESIS: To determine the prevalence, severity, risk factors and self-perception of female urinary incontinence (UI) in rural Fujian, China. METHODS: This population-based cross-sectional study was conducted between June and October 2022. Women aged 20 to 70 years from rural communities in Fujian Province were selected by multistage random sampling. Data from respondents were collected by completing standardised questionnaires through face-to-face interviews. The main outcome was prevalence and self-perception of UI. RESULTS: A total of 5659 valid questionnaires were collected. The overall prevalence of female UI was 23.6% (95% CI 22.5-24.7). The most common type was stress UI with a prevalence of 14.0% (95% CI 13.1-14.9), followed by mixed UI with a prevalence of 6.1% (95% CI 5.5-6.7), and finally urgency UI with a prevalence of 3.5% (95% CI 3.0-3.9). Multivariate regression analysis suggested that older age, obesity, postmenopausal status, multiple vaginal deliveries, macrosomia, instrumental vaginal delivery and previous pelvic floor surgeries were independently associated with UI (P < 0.05). The overall awareness rate of UI was 24.7%, and older age, lower level of education, and income were significantly associated with a decrease in awareness (P < 0.05). Only 33.3% of respondents believed they should seek medical help for UI. CONCLUSION: UI affects more than one-fifth of women in rural Fujian, and several factors are thought to be associated with its development. Rural women have a poor self-perception of UI, which is exacerbated by older age, lower levels of education, and lower income.
Urinary Incontinence, Stress , Urinary Incontinence , Female , Humans , Male , Cross-Sectional Studies , Rural Population , Prevalence , Urinary Incontinence/epidemiology , Urinary Incontinence/etiology , Risk Factors , Urinary Incontinence, Stress/epidemiology , Urinary Incontinence, Stress/complications , Surveys and Questionnaires , China/epidemiology , Self Concept
BACKGROUND: Boswellic acids in Olibanum (known as frankincense) are potent anti-inflammatory properties in treating ulcerative colitis (UC), but its low bioavailability limited drug development. Evidence accumulated that vinegar processing of frankincense exerts positive effects on improving absorption of compositions. The underlying mechanism is unknown. In recent decades, spectacular growth and multidisciplinary integration of metabolic application were witnessed. The relationship between drug absorption and curative effect has been more or less established. However, it remains a knowledge gap in the field between drug absorption and endocrine metabolism. PURPOSE: To investigate the enhancement mechanism of vinegar processing in the absorption of boswellic acids via the aspect of bile acid metabolism. METHODS: The effects of raw frankincense (RF) and processed frankincense (PF) were compared by the UC model of rats. The plasma concentration of boswellic acids and the hepatic and colonic bile acids contents were quantified by UPLC-TQ-MS. The levels of mRNA and protein associated with bile acid metabolism were also compared. RESULTS: The results showed that PF exhibited re-markable mitigating effects on UC with the elevated plasma level of boswellic acid and upregulated expression of the absorption-related protein multidrug resistance-associated protein 2 (MRP2) and organic anion transporting polypeptide 1B3 (OATP1B3) in the liver and colon. It improved colonic lithocholic acid (LCA), which promoted the expression of bile acid nuclear receptors constitutive androstane receptor (CAR) and pregnane X receptor (PXR), resulting in the upregulation of MRP2 and OATP1B3. CONCLUSION: This paper revealed the mechanisms behind the absorption promotion effects of processing. Bile acids metabolism exhibits potential status in pharmaceutical development. The results shed light on the interdisciplinary collaboration between the metabolism and drug absorption fields.
BACKGROUND: Osimertinib resistance limits the treatment of epidermal growth factor receptor-(EGFR)-mutated non-small-cell lung carcinoma (NSCLC). The mechanisms of osimertinib resistance need to be elucidated to determine alternative treatment strategies. This study explores the role of M2 type tumor-associated macrophage (TAM)-derived exosomal MSTRG.292666.16 in osimertinib resistance, and its related competing endogenous RNA (ceRNA) mechanism. METHODS: M2 type TAMs were induced with 200 ng/mL phorbol 12-myristate 13-acetate, 20 ng/mL IL-4 and IL-13, and M2 type macrophage markers were measured by RT-qPCR. Next, the exosomes were isolated and characterized. Tumor formation in nude mice was conducted using H1975 cells under different treatment conditions. Small RNA sequencing was performed on exosomes derived from sensitive and resistant plasma, and ceRNA networks were constructed. Fluorescence in situ hybridization was used to observe the localization of MSTRG.292666.16, and a ceRNA network (MSTRG.292666.16-miR-6836-5p-MAPK8IP3) was selected for further validation. RESULTS: M2 type TAMs, and M2 type TAM-derived exosomes were successfully induced and isolated. Nude mice results showed that M2 type TAM-derived exosomes and MSTRG.292666.16 overexpression significantly increased tumor volume after administration of osimertinib for 4 weeks. M2 type TAMs were found in the resistant plasma, and MSTRG.292666.16 localized in the cytoplasm of H1975 cells. In addition, the genes in the ceRNA networks were significantly enriched in eight GO terms and seven KEGG pathways, including the MAPK signaling pathway. Subsequently, the levels of MSTRG.292666.16 and MAPK8IP3 significantly increased in both resistant plasma-derived exosomes and M2 type TAM-derived exosomes, while miR-6836-5p levels were significantly reduced. Finally, MSTRG.292666.16, miR-6836-5p, and MAPK8IP3 were part of the same network. CONCLUSIONS: M2 type TAM-derived exosomes promoted osimertinib resistance in NSCLC by regulating the MSTRG.292666.16/miR-6386-5p/MAPK8IP3 axis.
The presence of hypertension (HTN) in type 2 diabetes mellitus (DM) is a common phenomenon in more than half of the diabetic patients. Since HTN constitutes a predictor of vascular complications and cardiovascular disease in type 2 DM patients, it is of significance to understand the molecular and cellular mechanisms of type 2 DM binding to HTN. This review attempts to understand the mechanism via the perspective of the metabolites. It reviewed the metabolic perturbations, the biological function of perturbated metabolites in two diseases, and the mechanism underlying metabolic perturbation that contributed to the connection of type 2 DM and HTN. DM-associated metabolic perturbations may be involved in the pathogenesis of HTN potentially in insulin, angiotensin II, sympathetic nervous system, and the energy reprogramming to address how perturbated metabolites in type 2 DM affect the pathogenesis of HTN. The recent integration of the metabolism field with microbiology and immunology may provide a wider perspective. Metabolism affects immune function and supports immune cell differentiation by the switch of energy. The diverse metabolites produced by bacteria modified the biological process in the inflammatory response of chronic metabolic diseases either. The rapidly evolving metabolomics has enabled to have a better understanding of the process of diseases, which is an important tool for providing some insight into the investigation of diseases mechanism. Metabolites served as direct modulators of biological processes were believed to assess the pathological mechanisms involved in diseases.
Isobavachalcone, a naturally occurring chalcone in Psoralea corylifolia, posses many biological properties including anticancer, antiplatelet, and antifungal. However, its glucuronidation, glucuronides excretion, and drug-drug interaction (DDI) involving in human cytochrome P450 (CYP), UDP-glucuronosyltransferase (UGT) enzymes, and efflux transporters (BCRP and MRPs) remains unclear so far. After incubation, three glucuronides were produced by HLM and HIM with total intrinsic clearance (CLint) of 236.71 and 323.40 µL/min/mg, respectively. Reaction phenotyping proved UGT1A1, 1A3, 1A7, 1A8, and 1A9 played important roles in glucuronidation with total CLint values of 62.69-143.00 µL/min/mg. Activity correlation analysis indicated UGT1A1 and UGT1A3 participated more in the glucuronidation. In addition, the glucuronidation showed marked species differences, and rabbits and dogs were probably appropriate model animals to investigate the in vivo glucuronidation. Furthermore, BCRP, MRP1, and MRP4 transporters were identified as the most important contributors to glucuronides excretion in HeLa1A1 cells based on gene silencing method. Moreover, isobavachalcone demonstrated broad-spectrum inhibitory effects against CYP2B6, CYP2C9, CYP2C19, CYP2D6, CYP2E1, UGT1A1, UGT1A9, UGT2B7 with IC50 values of 1.08-9.78 µM. Except CYP2B6 and CYP2D6, the calculated [I]/Ki values for other enzymes were all greater than 0.1, indicating the inhibition of systemic metabolism or elimination for these enzyme substrates seems likely. Taken together, we summarized metabolic fates of isobavachalcone including glucuronidation and efflux transport as well as inhibitory effects involving in human CYP and UGT enzymes.
Chalcones , ATP Binding Cassette Transporter, Subfamily G, Member 2/metabolism , Animals , Chalcones/pharmacology , Cytochrome P-450 Enzyme System/metabolism , Dogs , Glucuronides , Glucuronosyltransferase/metabolism , Humans , Kinetics , Microsomes, Liver/metabolism , Neoplasm Proteins/metabolism , Rabbits
Boswellic acids (BAs), as the main components of frankincense, exhibit notable anti-inflammatory properties. However, their pharmaceutical development has been severely limited by their poor oral bioavailability. Traditional Chinese medicinal processing, called Pao Zhi, is believed to improve bioavailability, yet the mechanism is still completely unclear. Previous research suggested that the bioavailability of a drug can be influenced by physical properties. This paper was designed to investigate the physical properties of frankincense and processed frankincense, including the surface morphology, particle size, polydispersity index (PDI), zeta potential (ZP), specific surface area, porosity, and viscosity. The differences in the intestinal absorption characteristics and equilibrium solubilities between frankincense and processed frankincense were determined by an ultra-high-performance liquid chromatography coupled with a triple quadrupole electrospray tandem mass spectrometry (UHPLC-TQ-MS) analysis method. The results showed that vinegar processing can alter the surface morphology, decrease the particle size and PDI, raise the absolute values of the ZP, specific surface area and porosity, and drop the viscosity of frankincense. Meanwhile, the rates of absorption and dissolution of the main BAs were increased after the processing of frankincense. The present study proves that the physical properties were changed after processing, in which case the bioavailability of frankincense was enhanced.
Drugs, Chinese Herbal/chemistry , Frankincense/chemistry , Plant Extracts/chemistry , Triterpenes/chemistry , Chromatography, High Pressure Liquid , Intestinal Absorption , Tandem Mass Spectrometry , Viscosity
Interleukin-10 (IL-10) has been recently identified as a multifunctional cytokine, because of its close link with immunoregulation and anti-inflammatory responses. This study investigated the association of IL-10 genetic polymorphisms with the immune traits of New Zealand white rabbits (N-W), Fujian yellow rabbits (F-Y) and their reciprocal crosses (N-Y and Y-N, respectively). SNPs on five exons of the IL-10 gene were genotyped in 204 healthy rabbits via PCR-SSCP and DNA sequencing. Two SNPs (A1435G and G1519A, both were synonymous mutations) and six genotypes (AA, BB, CC, AB, AC and BC) were found on exon 3 and one SNP (T base insertion between loci 2532 and 2533, which caused a frameshift mutation), and three genotypes (OO, TT and TO) were present on exon 4. Allele A was the most frequent allele on exon 3 (from 0.548 to 0.771), whereas O was the most frequent on exon 4 (from 0.808 to 0.968). These four populations were all in Hardy-Weinberg equilibrium on both exon3 and exon4. Association analysis between polymorphisms and immune parameters showed that SNPs on exon 3 were significantly associated with immune traits, while SNP on exon 4 may not significantly affect immune traits, but the mechanism is yet to be further studied.
Immunity/genetics , Interleukin-10/genetics , Polymorphism, Single Nucleotide/genetics , Rabbits/genetics , Animals , Base Sequence , Crosses, Genetic , DNA Primers/genetics , Genotype , Molecular Sequence Data , Polymorphism, Single-Stranded Conformational/genetics , Rabbits/immunology , Sequence Analysis, DNA/veterinary
B5 clearing is a step used before immunoperoxidase staining to remove the precipitated mercuric chloride deposits caused by B5 fixation of tissue. In the B5 clearing procedure, the slides are treated with Lugol's iodine and 5% sodium thiosulfate before antigen retrieval and the application of the primary antibody. The goal of this project was to study the effect of the B5 clearing protocol on immunoperoxidase staining on paraffin-embedded tissue, which has not been previously reported in a series of antibodies. We evaluated 75 antibodies using the 2-step clearing protocol and performed paired immunoperoxidase staining on the Ventana ES instrument, with and without the clearing protocol. We found that among 75 antibodies studied, 3 (CD5, CD30, and synaptophysin) showed total obliteration of reactivity, and 3 (ALK, Ulex, and GFAP) showed partial reduction of the staining compared with the controls. Pathologists must be aware of the possible false-negative staining effect caused by the routinely used B5 clearing protocol. Control tissues must receive the same clearing protocol (i.e., placed on case slides) to ensure detection of this effect.
Antibodies/metabolism , Immunoenzyme Techniques , Mercuric Chloride/chemistry , Peroxidases/metabolism , Tissue Fixation , Humans
In this investigation, we selected PAX3/FKHR and PAX7/FKHR fusion transcript-positive and -negative alveolar rhabdomyosarcomas (ARMSs) and embryonal rhabdomyosarcomas (ERMSs) with and without anaplastic features, to ascertain genomic imbalance differences and/or similarities within these histopathologic and genetic rhabdomyosarcoma (RMS) variants. Comparative genomic hybridization (CGH) and fluorescence in situ hybridization (FISH) studies were performed on 45 rhabdomyosarcoma specimens consisting of 23 ARMSs and 22 ERMSs (12 ERMS cases were included from an earlier study). The anaplastic variant of RMS has not previously been subjected to CGH analysis. Overall, the most prominent imbalances were gain of chromosomes or chromosomal regions 2/2q (40%), 7/7q (31%), 8/8p (53%), 11/11q (31%), 12q13-15 (49%), 13q14 (22%), and 20/20p (31%), and loss of 1p36 (27%), 3p14-21 (22%), 9q21-22 (33%), 10q22-qter (18%), 16q (27%), 17p (22%), and 22 (22%). These gains and losses were distributed equally between ARMS and ERMS histologic subtypes (excluding 7/7q and 11/11q gain that were observed chiefly in ERMS), demonstrating that these entities are similar with respect to recurrent genomic imbalances. Moreover, genomic imbalances were also evenly distributed among the ARMS fusion transcript subtypes, providing evidence for a genetic kinship despite the absence of a fusion transcript in some cases. Genomic amplification was detected in 26% and 23% of the ARMS and ERMS cases, respectively (with nearly all of the latter subset exhibiting anaplastic features). One amplicon, involving 15q25-26, corresponds to the locus of the insulin-like growth factor type I receptor (IGF1R) gene. Amplification of IGF1R was confirmed molecularly in the cases exhibiting a 15q25-26 amplicon. In summary, these results indicate that genomic gains and losses involve alike chromosomes with similar frequencies within the histopathologic and genetic subtypes of rhabdomyosarcoma, that genomic amplification is frequent not only in the alveolar histologic subtype of rhabdomyosarcoma but also in ERMS with anaplasia, and that amplification of IGF1R possibly plays a role in the development or progression of a subset of rhabdomyosarcomas.
Anaplasia/genetics , Chromosome Deletion , Gene Amplification/genetics , Rhabdomyosarcoma, Alveolar/genetics , Rhabdomyosarcoma, Embryonal/genetics , Adolescent , Adult , Anaplasia/pathology , Child , Child, Preschool , Cytogenetic Analysis , Female , Head and Neck Neoplasms/genetics , Head and Neck Neoplasms/pathology , Humans , Immunohistochemistry , In Situ Hybridization, Fluorescence , Infant , Male , Nucleic Acid Hybridization , Polymerase Chain Reaction , Reverse Transcriptase Polymerase Chain Reaction , Rhabdomyosarcoma, Alveolar/pathology , Rhabdomyosarcoma, Embryonal/pathology
