The lung metagene model provides a potential mechanism to refine the estimation of a patient's risk of disease recurrence and, in principle, to alter decisions regarding the use of adjuvant chemotherapy in early-stage NSCLC.
Endometrial stromal tumors are divided into three types: benign stromal nodules, endometrial stromal sarcomas, and undifferentiated endometrial sarcomas. A variety of cytogenetic abnormalities involving chromosome 7 have been reported in endometrial stromal sarcomas, including a recurrent t(7;17)(p15;q21). We have identified two zinc finger genes, which we have termed JAZF1 and JJAZ1, at the sites of the 7p15 and 17q21 breakpoints. Analyses of tumor RNA indicate that a JAZF1͞JJAZ1 fusion is present in all types of endometrial stromal tumors; however, the fusion appears to be rarer among endometrial stromal sarcomas that would be considered high-grade according to certain classification schemes. These findings suggest that the less malignant endometrial stromal tumors may evolve toward more malignant types, but that some endometrial stromal sarcomas with relatively abundant mitotic activity may compose a biologically distinct group.
We have explored the application of the bacteriophage resolvases T4 endonuclease VII and T7 endonuclease I for detecting mutations in genomic DNA. Heteroduplex DNA fragments prepared by amplification from DNA containing known mutations were cleaved by one or both enzymes at nucleotide mismatches created by 3 of 3 short deletions and 13 of 14 point mutations in fragments as large as 940 basepairs. Heteroduplexes representing all four classes of possible single nucleotide mismatches were cleaved, and the sizes of the cleavage products generated correlated with the location of the mutation. We conclude that bacteriophage resolvases may be useful reagents for the rapid screening of DNA for mutations.
Nonrandom cytogenetic abnormalities of chromosomes 6, 7, and 17 have been reported within low-grade endometrial stromal sarcomas (LGESSs), and among these abnormalities, the t(7;17)(p15;q21) is the most common aberration described. Previously we had shown that this translocation joins 2 genes, JAZF1 and JJAZ1, located on chromosomes 7 and 17, respectively. To determine the frequency of the t(7;17), we analyzed 4 stromal nodules and 24 LGESS by both reverse transcriptase-polymerase chain reaction and fluorescence in situ hybridization (FISH). In addition, we examined 4 cases of highly cellular leiomyoma, a benign morphologic mimic of LGESS. Overall, evidence for the JAZF1-JJAZ1 fusion was found in 60% of endometrial stromal neoplasms analyzed (8/16 ESS and 4/4 stromal nodules). One LGESS demonstrated only rearrangement of 7p15 by FISH analysis and karyotypic analysis of this case showed t(6;7)(p21;p15). The fusion was not detected in any highly cellular leiomyomas. Our data suggest that the JAZF1-JJAZ1 fusion is a frequent, although nonuniform, feature of endometrial stromal neoplasia, irrespective of benign versus malignant classification and smooth muscle differentiation. In addition, the detection of the fusion by reverse transcriptase-polymerase chain reaction or FISH for JJAZ1 at 7p15 may be diagnostically useful.
A series of 7-azabicyclo[2.2.l]hept-5-ene complexes are prepared from [0s(NH3)5(q2-L)l2+ (L = pyrrole, 1-methylpyrrole, 2,5-dimethylpyrrole, 1,2,5-trimethylpyrrole, or 1-(trimethylsily1)pyrrole) and various dipolarophiles (e.g., acrylonitrile, methyl acrylate, a-methylene-y-butyrolactone, dimethyl maleate, dimethyl fumarate, N-phenyl maleimide, cyclopentene-1,2-dicarboxylic acid anhydride, and (E>-and (a-methyl 3-(3'-pyridyl)acrylate). The cycloaddition is promoted by coordination of the pyrrole with [Os(NH&]*+ across C3 and C4, transforming the uncoordinated portion of the pyrrole nucleus into an azomethine ylide capable of undergoing 1,3-dipolar cycloadditions.The metal serves not only to activate the pyrrole ring but also to stabilize the resulting 7-azabicyclo[2.2.l]heptene ligands. A number of organic 7-azabicyclo[2.2. llheptanes, including analogs of the alkaloid epibatidine, have been synthesized by this methodology. For the cases examined, the cycloaddition favors ex0 stereochemistry of the electronwithdrawing substituent when the pyrrole nitrogen is unsubstituted. Crystal structures have been determined for the complexes obtained from the reactions of pyrrole with N-phenylmaleimide @a), 2,5dimethylpyrrole with dimethyl maleate (13a), and 2,5-dimethylpyrrole with a-methylene-y-butyrolactone (22a).
Polycomb group genes (PcGs) have been implicated in cancer based on altered levels of expression observed in certain tumors and the behavior of cultured cells containing inserted PcG transgenes. Endometrial stromal tumors provide evidence for a direct causal relationship because they contain several chromosomal translocations and resultant gene fusions involving PcGs, the most common of which joins portions of the JAZF1 gene to the PcG JJAZ1/SUZ12. We show here that both benign and malignant forms of this tumor have the JAZF1-JJAZ1 fusion but only the malignant form also exhibits exclusion of the unrearranged JJAZ1 allele. To evaluate the effects of both the JJAZ1/SUZ12 fusion and allelic exclusion on functions related to cell growth, we studied HEK293 cells that were modified with respect to JJAZ1 expression. We found that the JAZF1-JJAZ1 fusion restored levels of the polycomb protein EZH2 and histone 3 lysine 27 trimethylation, which were reduced by knockdown of endogenous JJAZ1. At the same time, the presence of JAZF1-JJAZ1 markedly inhibited apoptosis and induced above normal proliferation rates, although the latter effect occurred only when normal JJAZ1 was suppressed. Our findings suggest a genetic pathway for progression of a benign precursor to a sarcoma involving increased cell survival associated with acquisition of a PcG rearrangement, followed by accelerated cellular proliferation upon allelic exclusion of the unrearranged copy of that gene. Furthermore, these results indicate the likely functional importance of allelic exclusion of genes disrupted by chromosomal translocations, as seen in a variety of other cancers.chromosomal translocation ͉ endometrial stromal tumor ͉ polycomb group gene ͉ chromatin remodeling ͉ apoptosis
Background
Arrhythmia recurrence after cardiac radiofrequency ablation (RFA) for atrial fibrillation (AF) has been linked to conduction through discontinuous lesion lines. Intraprocedural visualization and corrective ablation of lesion line discontinuities could decrease post-procedure AF recurrence. Intracardiac acoustic radiation force impulse (ARFI) imaging is a new imaging technique that visualizes RFA lesions by mapping the relative elasticity contrast between compliant-unablated and stiff-RFA treated myocardium.
Objective
To determine if intraprocedure ARFI images can identify RFA treated myocardium in vivo.
Methods
In eight canines, an electroanatomical mapping (EAM) guided intracardiac echo catheter (ICE) was used to acquire 2D ARFI images along right atrial ablation lines before and after RFA. ARFI images were acquired during diastole with the myocardium positioned at the ARFI focus (1.5 cm) and parallel to the ICE transducer for maximal and uniform energy delivery to the tissue. Three reviewers categorized each ARFI image as depicting no lesion, non-contiguous, or contiguous lesion. For comparison, three separate reviewers confirmed RFA lesion presence and contiguity based on functional conduction block at the imaging plane location on EAM activation maps.
Results
Ten percent of ARFI images were discarded due to motion artifacts. Reviewers of the ARFI images detected RFA-treated sites with high sensitivity (95.7%) and specificity (91.5%). Reviewer identification of contiguous lesion had 75.3% specificity and 47.1% sensitivity.
Conclusions
Intracardiac ARFI imaging was successful in identifying endocardial RFA treatment when specific imaging conditions were maintained. Further advances in ARFI imaging technology would facilitate a wider range of imaging opportunities for clinical lesion evaluation.
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.