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Dysregulated crosstalk between different signaling pathways contributes to tumor development, including resistance to cancer therapy. In the present study, we found that the mitogen-activated extracellular signal-regulated kinase (MEK) inhibitor trametinib failed to suppress the proliferation of PANC-1 and MGC803 cells by activating the Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) signaling pathway, while the JAK2 inhibitor fedratinib failed to inhibit the growth of the PANC-1 cells upon stimulation of extracellular signal-regulated kinase (ERK) signaling. In particular, the most prominent enhancement of the anti-proliferative effect resulted from the concurrent blockage of the JAK2/STAT3 and ERK signaling pathways. Furthermore, the combination of the two inhibitors resulted in a reduced tumor burden in mice. Our evidence suggests novel crosstalk between JAK2/STAT3 and ERK signaling in gastric cancer (GC) and pancreatic ductal adenocarcinoma (PDAC) cells and provides a therapeutic strategy to overcome potential resistance in gastrointestinal cancer.
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Objective To evaluate a new prenatal diagnosis model of chromosomal abnormalities and nine microdeletion syndromes by using both traditional karyotyping and a newly-developed rapid prenatal diagnosis technology, BACs-on-Beads (BoBs) technique. Methods From June 2012 to December 2014, 807 pregnant women with high risk after screening or with other indicators, were performed amniocentesis. Traditional karyotyping and BoBs were employed simultaneously for prenatal diagnosis. Results Thirty-two cases with chromosome aneupoidies were successfully detected both by BoBs and karyotyping, including 18 cases of trisomy 21, 6 cases of trisomy 18, 1 case of trisomy 13, and 7 cases with sex chromosome abnormality. All 8 fetuses with chromosome structural abnormalities detected by karyotyping were missed by BoBs;while BoBs contributed more in detection of five microdeletion syndrome cases, including 3 cases of DiGeorge syndromes (two with microduplication and one with microdeletion), one case of Miller-Dieker syndrome, and one case of Wolf-Hirschhorn syndrome. Conclusion Combined use of traditional karyotyping and BoBs, is a rapid and effective prenatal diagnosis model that may enlarge our horizon on chromosomal diseases and should be widely used in future clinical service.
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<p><b>OBJECTIVE</b>To establish a strategy for screening and diagnosing common microdeletion and microduplication syndromes among children with idiopathic mental retardation and development abnormalities.</p><p><b>METHODS</b>Potential chromosomal variations among patients with unexplained mental retardation, cardiac anomalies, particular facial features, learning disabilities and other clinical characteristics were detected with bacterial artificial chromosome BACs-on-Beads (BoBs) technique and karyotyping. Positive results were verified with array-based comparative genomic hybridization (Array-CGH).</p><p><b>RESULTS</b>Fifty eight of the 60 patients had a normal chromosome karyotype. Ten patients with microdeletion and microduplication syndromes were detected by BoBs, which included two positive cases identified through chromosome karyotyping. Two patients were respectively diagnosed as Smith-Magenis syndrome and Prader-Willi/Angelman syndrome by BoBs and the results were confirmed by Array-CGH.</p><p><b>CONCLUSION</b>BoBs is capable of detecting chromosome microdeletion and microduplication with high specificity and throughput, which can compensate the shortcomings of conventional cytogenetic technology and will be widely applied for clinical diagnosis.</p>
Subject(s)
Adolescent , Child , Child, Preschool , Female , Humans , Infant , Infant, Newborn , Male , Chromosome Deletion , Chromosome Duplication , Chromosomes, Artificial, Bacterial , Genetics , Comparative Genomic Hybridization , Cytogenetic Analysis , Methods , Karyotyping , Oligonucleotide Array Sequence AnalysisABSTRACT
Objective To compare the prognosis of sentinel node-positive breast cancer patients forgoing axillary lymph node dissection.Methods A systematic literature search (Medline,Embase,Cochrane Library)ended in April 2014 was performed to identify all eligible articles.Two reviewers independently screened and extracted data.RevMan5 was used for statistical analysis.Results A total of 1026 abstracts were retrieved and 18 clinical controlled studies finally included,the total number of patients were 47 894,7389 had micrometastases in sentinel lymph node,35 217 had macrometastases in sentinel lymph node and 5288 had positive sentinel lymph node regardless of micrometastases or macrometastases.For patients with MIC,the 5-year axillary recurrence rate,5-year disease free survival and 5-year overall survival had no significant difference between patients who only received sentinel lymph node biopsy and patients who received further axillary lymph node dissection,(OR =1.78;95％ CI:0.72-4.39,P=0.21),(OR =0.76,95％CI:0.56-1.04,P=0.08),(OR=0.77,95％CI:0.43-1.40,P=0.39).For patients with MAC,the 5-year axillary recurrence rate had no significant difference between patients who only received sentinel lymph node biopsy and patients who received further axillary lymph node dissection,(OR =1.21;95％ CI:O.76-1.91,P =0.42).For patients with positive sentinel lymph node regardless of micrometastases or macrometastases,the 5-year axillary recurrence rate and 5-year overall survival had no significant difference between patients who only received sentinel lymph node biopsy and patients who received further axillary lymph node dissection,(OR =1.29;95％ CI:0.92-1.80,P =0.14),(OR =0.96,95％ CI:0.64-1.45,P =0.84).Conclusions Among patients with limited positive SLN of breast cancer,patients forgoing ALND compared with ALND did not have obvious affect on long-term survival.