31 research outputs found
Evaluation of Trastuzumab Anti-Tumor Efficacy and its Correlation with HER-2 Status in Patient-Derived Gastric Adenocarcinoma Xenograft Models
Similar Morphologies but Different Origins: Hybrid Status of Two More Semi-creeping Taxa of Melastoma
Inferring the origins of hybrid taxa based on morphology alone is difficult because morphologically similar hybrids can arise from hybridization between different populations of the same parental species or be produced by hybridization of different parental species. In this study, we investigated the origins of two semi-creeping taxa in Melastoma, which are morphologically similar to a natural hybrid, M. intermedium, by sequencing a chloroplast intergenic spacer, nuclear ribosomal internal transcribed spacer and two low-copy nuclear genes (tpi and cam) in these taxa and their putative parental species. Our sequence analysis provides compelling evidence for the hybrid status of the two semi-creeping taxa: one originating from hybridization between M. dodecandrum and M. malabathricum, and the other between M. dodecandrum and M. normale. The origins of these hybrids are therefore clearly different from M. intermedium, and morphological similarity for the three hybrids is most likely due to their origins from hybridization between the same creeping species M. dodecandrum and a different erect species in each of the three cases. We also observed low rate of introgression from M. normale to M. dodecandrum, and genetic exchange between them may transfer adaptive traits to M. dodecandrum. Rare occurrence of these two hybrids may be due to small range overlaps between parental species in one case, and different flowering periods between parental species in the other
Intra-Tumoral Heterogeneity of HER2, FGFR2, cMET and ATM in Gastric Cancer: Optimizing Personalized Healthcare through Innovative Pathological and Statistical Analysis.
Current drug development efforts on gastric cancer are directed against several molecular targets driving the growth of this neoplasm. Intra-tumoral biomarker heterogeneity however, commonly observed in gastric cancer, could lead to biased selection of patients. MET, ATM, FGFR2, and HER2 were profiled on gastric cancer biopsy samples. An innovative pathological assessment was performed through scoring of individual biopsies against whole biopsies from a single patient to enable heterogeneity evaluation. Following this, false negative risks for each biomarker were estimated in silico. 166 gastric cancer cases with multiple biopsies from single patients were collected from Shanghai Renji Hospital. Following pre-set criteria, 56 ~ 78% cases showed low, 15 ~ 35% showed medium and 0 ~ 11% showed high heterogeneity within the biomarkers profiled. If 3 biopsies were collected from a single patient, the false negative risk for detection of the biomarkers was close to 5% (exception for FGFR2: 12.2%). When 6 biopsies were collected, the false negative risk approached 0%. Our study demonstrates the benefit of multiple biopsy sampling when considering personalized healthcare biomarker strategy, and provides an example to address the challenge of intra-tumoral biomarker heterogeneity using alternative pathological assessment and statistical methods
Extensive Hybridization and Introgression between <i>Melastoma candidum</i> and <i>M. sanguineum</i>
<div><p>Natural hybridization can lead to various evolutionary outcomes in plants, including hybrid speciation and interspecific gene transfer. It can also cause taxonomic problems, especially in plant genera containing multiple species. In this study, the hybrid status of <i>Melastoma affine</i>, the most widespread taxon in this genus, and introgression between its putative parental species, <i>M. candidum</i> and <i>M. sanguineum</i>, were assessed on two sites, Hainan and Guangdong, using 13 SSR markers and sequences of a chloroplast intergenic spacer. Bayesian-based STRUCTURE analysis detected two most likely distinct clusters for the three taxa, and 76.0% and 73.9% of the morphologically identified individuals of <i>M. candidum</i> and <i>M. sanguineum</i> were correctly assigned, respectively. 74.5% of the <i>M. affine</i> individuals had a membership coefficient to either parental species between 0.1 and 0.9, suggesting admixture between <i>M. candidum</i> and <i>M. sanguineum</i>. Furthermore, NewHybrids analysis suggested that most individuals of <i>M. affine</i> were F2 hybrids or backcross hybrids to <i>M. candidum</i>, and that there was extensive introgression between <i>M. candidum</i> and <i>M. sanguineum</i>. These SSR data thus provides convincing evidence for hybrid origin of <i>M. affine</i> and extensive introgression between <i>M. candidum</i> and <i>M. sanguineum.</i> Chloroplast DNA results were consistent with this conclusion. Much higher hybrid frequency on the more disturbed Guangdong site suggests that human disturbance might offer suitable habitats for the survival of hybrids, a hypothesis that is in need of further testing.</p></div
Variable sites in the chloroplast <i>trn</i>S-<i>trn</i>G region in <i>M. candidum</i>, <i>M. sanguineum</i> and <i>M. affine</i>.
<p>Variable sites in the chloroplast <i>trn</i>S-<i>trn</i>G region in <i>M. candidum</i>, <i>M. sanguineum</i> and <i>M. affine</i>.</p
Overview of biopsy number in clinical samples.
<p><b>(A) Distribution of total and positive biopsy number.</b> In this Chinese GC cohort, total biopsy numbers range from 1 to 9, with a median of 4. Positive biopsy (biopsy with tumor) is slightly lower than total biopsy number. <b>(B) Distribution of positive biopsy number.</b> Majority of biopsy numbers fall into 3~4 (47%) and 5~6 (25%).</p
An illustration of heterogeneity distribution of each biomarker.
<p>Heterogeneity distribution of MET protein expression <b>(A)</b>, <i>MET</i> average gene copy number <b>(B)</b>, ATM protein expression <b>(C)</b>, <i>FGFR2</i> amplification <b>(D)</b>, and HER2 positivity <b>(E)</b>. AMP: amplification. AVG: average copy number.</p
Morphological illustrations for <i>M. sanguineum</i>, <i>M. affine</i> and <i>M. candidum</i>.
<p>(a) <i>M. sanguineum</i>; (b) <i>M. affine</i>; (c) <i>M. candidum</i>;(d) Leaves of <i>M. sanguineum</i>, <i>M. affine</i> and <i>M. candidum</i> (from left to right), (e) Branchlets of <i>M. sanguineum</i>, <i>M. affine</i> and <i>M. candidum</i> (from left to right) (f) Fruits of <i>M. sanguineum</i>, <i>M. affine</i> and <i>M. candidum</i> (from left to right).</p
Posterior probability distribution by using the NewHybrids program.
<p>All the samples (a, Hainan; b, Guangdong) are represented as a vertical bar partitioned into segments whose length is proportional to the likelihood of belonging to a certain class. Ms, Ma and Mc represent morphologically identified <i>M. sanguineum</i>, <i>M. affine</i> and <i>M. candidum</i>, respectively. HN and GD represent the sampling sites, Hainan and Guangdong, respectively.</p