Quantitative Clinical Imaging Methods for Monitoring Intratumoral Evolution.

PubMed

Kim, Joo Yeun; Gatenby, Robert A

2017-01-01

Solid tumors are multiscale, open, complex, dynamic systems: complex because they have many interacting components, dynamic because both the components and their interactions can change with time, and open because the tumor freely communicates with surrounding and even distant host tissue. Thus, it is not surprising that striking intratumoral variations are commonly observed in clinical imaging such as MRI and CT and that several recent studies found striking regional variations in the molecular properties of cancer cells from the same tumor. Interestingly, this spatial heterogeneity in molecular properties of tumor cells is typically ascribed to branching clonal evolution due to accumulating mutations while macroscopic variations observed in, for example, clinical MRI scans are usually viewed as functions of blood flow. The clinical significance of spatial heterogeneity has not been fully determined but there is a general consensus that the varying intratumoral landscape along with patient factors such as age, morbidity and lifestyle, contributes significantly to the often unpredictable response of individual patients within a disease cohort treated with the same standard-of-care therapy.Here we investigate the potential link between macroscopic tumor heterogeneity observed by clinical imaging and spatial variations in the observed molecular properties of cancer cells. We build on techniques developed in landscape ecology to link regional variations in the distribution of species with local environmental conditions that define their habitat. That is, we view each region of the tumor as a local ecosystem consisting of environmental conditions such as access to nutrients, oxygen, and means of waste clearance related to blood flow and the local population of tumor cells that both adapt to these conditions and, to some extent, change them through, for example, production of angiogenic factors. Furthermore, interactions among neighboring habitats can produce broader regional dynamics so that the internal diversity of tumors is the net result of complex multiscale somatic Darwinian interactions.Methods in landscape ecology harness Darwinian dynamics to link the environmental properties of a given region to the local populations which are assumed to represent maximally fit phenotypes within those conditions. Consider a common task of a landscape ecologist: defining the spatial distribution of species in a large region, e.g., in a satellite image. Clearly the most accurate approach requires a meter by meter survey of the multiple square kilometers in the region of interest. However, this is both impractical and potentially destructive. Instead, landscape ecology breaks the task into component parts relying on the Darwinian interdependence of environmental properties and fitness of specific species' phenotypic and genotypic properties. First, the satellite map is carefully analyzed to define the number and distribution of habitats. Then the species distribution in a representative sampling of each habitat is empirically determined. Ultimately, this permits sufficient bridging of spatial scales to accurately predict spatial distribution of plant and animal species within large regions.Currently, identifying intratumoral subpopulations requires detailed histological and molecular studies that are expensive and time consuming. Furthermore, this method is subject to sampling bias, is invasive for vital organs such as the brain, and inherently destructive precluding repeated assessments for monitoring post-treatment response and proteogenomic evolution. In contrast, modern cross-sectional imaging can interrogate the entire tumor noninvasively, allowing repeated analysis without disrupting the region of interest. In particular, magnetic resonance imaging (MRI) provides exceptional spatial resolution and generates signals that are unique to the molecular constituents of tissue. Here we propose that MRI scans may be the equivalent of satellite images in landscape ecology and, with appropriate application of Darwinian first principles and sophisticated image analytic methods, can be used to estimate regional variations in the molecular properties of cancer cells.We have initially examined this technique in glioblastoma, a malignant brain neoplasm which is morphologically complex and notorious for a fast progression from diagnosis to recurrence and death, making a suitable subject of noninvasive, rapidly repeated assessment of intratumoral evolution. Quantitative imaging analysis of routine clinical MRIs from glioblastoma has identified macroscopic morphologic characteristics which correlate with proteogenomics and prognosis. The key to the accurate detection and forecasting of intratumoral evolution using quantitative imaging analysis is likely to be in the understanding of the synergistic interactions between observable intratumoral subregions and the resulting tumor behavior.

Clonal Heterogeneity and Tumor Evolution: Past, Present, and the Future.

PubMed

McGranahan, Nicholas; Swanton, Charles

2017-02-09

Intratumor heterogeneity, which fosters tumor evolution, is a key challenge in cancer medicine. Here, we review data and technologies that have revealed intra-tumor heterogeneity across cancer types and the dynamics, constraints, and contingencies inherent to tumor evolution. We emphasize the importance of macro-evolutionary leaps, often involving large-scale chromosomal alterations, in driving tumor evolution and metastasis and consider the role of the tumor microenvironment in engendering heterogeneity and drug resistance. We suggest that bold approaches to drug development, harnessing the adaptive properties of the immune-microenvironment while limiting those of the tumor, combined with advances in clinical trial-design, will improve patient outcome. Crown Copyright © 2017. Published by Elsevier Inc. All rights reserved.

Myeloid transformation of plasma cell myeloma: molecular evidence of clonal evolution revealed by next generation sequencing.

PubMed

Gralewski, Jonathon H; Post, Ginell R; van Rhee, Frits; Yuan, Youzhong

2018-02-20

Plasma cell myeloma (PCM) is a neoplasm of terminally differentiated B lymphocytes with molecular heterogeneity. Although therapy-related myeloid neoplasms are common in plasma cell myeloma patients after chemotherapy, transdifferentiation of plasma cell myeloma into myeloid neoplasms has not been reported in literature. Here we report a very rare case of myeloid neoplasm transformed from plasma cell myeloma. A 60-year-old man with a history of plasma cell myeloma with IGH-MAF gene rearrangement and RAS/RAF mutations developed multiple soft tissue lesions one year following melphalan-based chemotherapy and autologous stem cell transplant. Morphological and immunohistochemical characterization of the extramedullary disease demonstrated that the tumor cells were derived from the monocyte-macrophage lineage. Next generation sequencing (NGS) studies detected similar clonal aberrations in the diagnostic plasma cell population and post-therapy neoplastic cells, including IGH-MAF rearrangement, multiple genetic mutations in RAS signaling pathway proteins, and loss of tumor suppressor genes. Molecular genetic analysis also revealed unique genomic alterations in the transformed tumor cells, including gain of NF1 and loss of TRAF3. To our knowledge, this is the first case of myeloid sarcoma transdifferentiated from plasma cell neoplasm. Our findings in this unique case suggest clonal evolution of plasma cell myeloma to myeloma neoplasm and the potential roles of abnormal RAS/RAF signaling pathway in lineage switch or transdifferentiation.

The spectrum of metanephric adenofibroma and related lesions: clinicopathologic study of 25 cases from the National Wilms Tumor Study Group Pathology Center.

PubMed

Arroyo, M R; Green, D M; Perlman, E J; Beckwith, J B; Argani, P

2001-04-01

The authors report nine new metanephric adenofibroma (MAFs; previously termed nephrogenic adenofibroma) and 16 related tumors from the files of the National Wilms Tumor Study Group Pathology Center (NWTSGPC). All tumors contained a variable amount of a bland spindle cell stroma, which is essentially identical to the recently described metanephric stromal tumor (MST). Features that distinguish this stroma from congenital mesoblastic nephroma (CMN) include intratumoral angiodysplasia, concentric cuffing of entrapped tubules ("onion skinning"), and heterologous differentiation. The epithelial components of these lesions spanned a wide range of appearances. All tumors contained at least focally an inactive embryonal epithelium identical morphologically to metanephric adenoma (MA), and hence each case could be classified as containing MAF. The epithelium of nine tumors had this appearance throughout, and hence these were considered usual MAFs. The epithelium of four tumors demonstrated increased mitotic activity but was otherwise similar to MA. The epithelial component of seven tumors spanned a morphologic spectrum from inactive MA to malignant epithelial predominant Wilms tumor (WT), with gradual transitions noted in several cases. Five other tumors contained a carcinomatous component distinct from these lesions but identical morphologically to papillary renal cell carcinoma (PRCC). In one of these cases, this component had metastasized to the regional lymph nodes at the time of diagnosis. No tumor recurred during follow-up, although almost all patients received adjuvant therapy for WT regardless of their tumor's histology and NWTSGPC diagnosis. In conclusion, MAF is a biphasic tumor that spans the morphologic spectrum between benign pure stromal (MST) and pure epithelial (MA) lesions, and can merge with the morphology of WT, supporting the concept that these are all related lesions. A relationship to PRCC is also evident.

Detailed longitudinal sampling of glioma stem cells in situ reveals Chr7 gain and Chr10 loss as repeated events in primary tumor formation and recurrence.

PubMed

Baysan, Mehmet; Woolard, Kevin; Cam, Margaret C; Zhang, Wei; Song, Hua; Kotliarova, Svetlana; Balamatsias, Demosthenes; Linkous, Amanda; Ahn, Susie; Walling, Jennifer; Belova, Galina I; Fine, Howard A

2017-11-15

Intratumoral heterogeneity at the genetic, epigenetic, transcriptomic, and morphologic levels is a commonly observed phenomenon in many aggressive cancer types. Clonal evolution during tumor formation and in response to therapeutic intervention can be predicted utilizing reverse engineering approaches on detailed genomic snapshots of heterogeneous patient tumor samples. In this study, we developed an extensive dataset for a GBM case via the generation of polyclonal and monoclonal glioma stem cell lines from initial diagnosis, and from multiple sections of distant tumor locations of the deceased patient's brain following tumor recurrence. Our analyses revealed the tissue-wide expansion of a new clone in the recurrent tumor and chromosome 7 gain and chromosome 10 loss as repeated genomic events in primary and recurrent disease. Moreover, chromosome 7 gain and chromosome 10 loss produced similar alterations in mRNA expression profiles in primary and recurrent tumors despite possessing other highly heterogeneous and divergent genomic alterations between the tumors. We identified ETV1 and CDK6 as putative candidate genes, and NFKB (complex), IL1B, IL6, Akt and VEGF as potential signaling regulators, as potentially central downstream effectors of chr7 gain and chr10 loss. Finally, the differences caused by the transcriptomic shift following gain of chromosome 7 and loss of chromosome 10 were consistent with those generally seen in GBM samples compared to normal brain in large-scale patient-tumor data sets. © 2017 UICC.

The Genomic Evolution of Prostate Cancer

DTIC Science & Technology

2017-06-01

management and grant writing skills. 15. SUBJECT TERMS Cancer genetics , tumor evolution, tumor heterogeneity, prostate cancer, exome sequencing 16...aggressive disease, it is unclear if the genetic alterations more common in late disease are present early on, but at low frequency, or if they only...from localized to metastatic prostate cancer. 2. KEYWORDS: Cancer genetics , tumor evolution, tumor heterogeneity, prostate cancer, exome sequencing

Breast tumor angiogenesis analysis using 3D power Doppler ultrasound

NASA Astrophysics Data System (ADS)

Chang, Ruey-Feng; Huang, Sheng-Fang; Lee, Yu-Hau; Chen, Dar-Ren; Moon, Woo Kyung

2006-03-01

Angiogenesis is the process that correlates to tumor growth, invasion, and metastasis. Breast cancer angiogenesis has been the most extensively studied and now serves as a paradigm for understanding the biology of angiogenesis and its effects on tumor outcome and patient prognosis. Most studies on characterization of angiogenesis focus on pixel/voxel counts more than morphological analysis. Nevertheless, in cancer, the blood flow is greatly affected by the morphological changes, such as the number of vessels, branching pattern, length, and diameter. This paper presents a computer-aided diagnostic (CAD) system that can quantify vascular morphology using 3-D power Doppler ultrasound (US) on breast tumors. We propose a scheme to extract the morphological information from angiography and to relate them to tumor diagnosis outcome. At first, a 3-D thinning algorithm helps narrow down the vessels into their skeletons. The measurements of vascular morphology significantly rely on the traversing of the vascular trees produced from skeletons. Our study of 3-D assessment of vascular morphological features regards vessel count, length, bifurcation, and diameter of vessels. Investigations into 221 solid breast tumors including 110 benign and 111 malignant cases, the p values using the Student's t-test for all features are less than 0.05 indicating that the proposed features are deemed statistically significant. Our scheme focuses on the vascular architecture without involving the technique of tumor segmentation. The results show that the proposed method is feasible, and have a good agreement with the diagnosis of the pathologists.

Quantitative morphological magnetic resonance imaging follow-up of low-grade glioma: a plea for systematic measurement of growth rates.

PubMed

Pallud, Johan; Taillandier, Luc; Capelle, Laurent; Fontaine, Denys; Peyre, Matthieu; Ducray, François; Duffau, Hugues; Mandonnet, Emmanuel

2012-09-01

Supratentorial hemispheric diffuse low-grade gliomas (LGGs), i.e., World Health Organization grade II gliomas, are a heterogeneous group of tumors. During their natural course, LGGs tend to progress to a higher grade of malignancy, leading to neurological disability and ultimately to death. In this review, we will show, that during their low-grade period, these tumors exhibit systematically a spontaneous and continuous radiological growth, whatever their histological subtypes. The radiological tumor growth is easily quantified by measuring the evolution of the equivalent tumor diameter (calculated from the tumor volume), obtaining the velocity of diametric expansion (VDE). The spontaneous VDE of LGGs varies markedly with an average VDE of about 4 mm/year. It depends on intrinsic factors (1p19q codeletion status, P53 overexpression status) and can be modified by extrinsic factors (pregnancy). The spontaneous VDE carries a strong prognostic significance regarding progression-free and overall survivals. As a consequence, VDE should be integrated along with the other "static" parameters (multimodal imaging, histological and molecular analyses) in the initial investigations. In addition, the assessment of VDE obtained before, during, and after a particular oncological treatment helps in analyzing their effects on LGGs on an individual basis, helping to guide the decision making.

Questing for an optimal, universal viral agent for oncolytic virotherapy

NASA Astrophysics Data System (ADS)

Paiva, L. R.; Martins, M. L.; Ferreira, S. C.

2011-10-01

One of the most promising strategies to treat cancer is attacking it with viruses designed to exploit specific altered pathways. Here, the effects of oncolytic virotherapy on tumors having compact, papillary, and disconnected morphologies are investigated through computer simulations of a multiscale model coupling macroscopic reaction-diffusion equations for the nutrients with microscopic stochastic rules for the actions of individual cells and viruses. The interaction among viruses and tumor cells involves cell infection, intracellular virus replication, and the release of new viruses in the tissue after cell lysis. The evolution over time of both the viral load and cancer cell population, as well as the probabilities for tumor eradication, were evaluated for a range of multiplicities of infection, viral entries, and burst sizes. It was found that in immunosuppressed hosts, the antitumor efficacy of a virus is primarily determined by its entry efficiency, its replicative capacity within the tumor, and its ability to spread over the tissue. However, the optimal traits for oncolytic viruses depend critically on the tumor growth dynamics and do not necessarily include rapid replication, cytolysis, or spreading, currently assumed as necessary conditions for a successful therapeutic outcome. Our findings have potential implications on the design of new vectors for the viral therapy of cancer.

[Imaging of gliomas].

PubMed

Martin-Duverneuil, N; Guillevin, R; Chiras, J

2008-11-01

The imaging of gliomas, as well as diffuse infiltrative gliomas or as more recently individualized entities, has been profoundly modified these last years. Correlated with the classic morphological MRI, numerous new sequences have appeared that allowed a more metabolic approach of the tumors, such as diffusion, perfusion--related to angiogenesis--and spectroscopy--reflecting metabolic data. Their development in daily practice allows to precise the diagnostic, to definite the more active areas (correlated with the hyperperfused or more metabolic active areas in relation with the Ki67 index) and so optimize the biopsy and/or evaluate the evolution of the lesion. When associated, they allow also and perhaps especially to precise the diagnostic, particularly with other tumoral masses such as lymphomas or metastases that can present misleading patterns, but also with other more benign lesions such as abcesses. Always critically analysed, and reevaluated along the time if necessary, they can sometimes help the histological diagnosis, but never can be used in place of it.

Big Bang Tumor Growth and Clonal Evolution.

PubMed

Sun, Ruping; Hu, Zheng; Curtis, Christina

2018-05-01

The advent and application of next-generation sequencing (NGS) technologies to tumor genomes has reinvigorated efforts to understand clonal evolution. Although tumor progression has traditionally been viewed as a gradual stepwise process, recent studies suggest that evolutionary rates in tumors can be variable with periods of punctuated mutational bursts and relative stasis. For example, Big Bang dynamics have been reported, wherein after transformation, growth occurs in the absence of stringent selection, consistent with effectively neutral evolution. Although first noted in colorectal tumors, effective neutrality may be relatively common. Additionally, punctuated evolution resulting from mutational bursts and cataclysmic genomic alterations have been described. In this review, we contrast these findings with the conventional gradualist view of clonal evolution and describe potential clinical and therapeutic implications of different evolutionary modes and tempos. Copyright © 2018 Cold Spring Harbor Laboratory Press; all rights reserved.

RASSF1A promoter methylation in high-grade serous ovarian cancer: A direct comparison study in primary tumors, adjacent morphologically tumor cell-free tissues and paired circulating tumor DNA.

PubMed

Giannopoulou, Lydia; Chebouti, Issam; Pavlakis, Kitty; Kasimir-Bauer, Sabine; Lianidou, Evi S

2017-03-28

The RASSF1A promoter is frequently methylated in high-grade serous ovarian cancer (HGSC). We examined RASSF1A promoter methylation in primary tumors, adjacent morphologically tumor cell-free tissues and corresponding circulating tumor DNA (ctDNA) samples of patients with HGSC, using a real-time methylation specific PCR (real-time MSP) and a methylation-sensitive high-resolution melting analysis (MS-HRMA) assay for the detection and semi-quantitative estimation of methylation, respectively. Two groups of primary HGSC tumor FFPE samples were recruited (Group A n=67 and Group B n=61), along with matched adjacent morphologically tumor cell-free tissues (n=58) and corresponding plasma samples (n=59) for group B. Using both assays, RASSF1A promoter was found highly methylated in primary tumors of both groups, and at lower percentages in the adjacent morphologically tumor cell-free tissues. Interestingly, RASSF1A promoter methylation was also observed in ctDNA by real-time MSP. Overall survival (OS) was significantly associated with RASSF1A promoter methylation in primary tumor samples using MS-HRMA (P=0.023). Our results clearly indicate that RASSF1A promoter is methylated in adjacent tissue surrounding the tumor in HGSC patients. We report for the first time that RASSF1A promoter methylation provides significant prognostic information in HGSC patients.

RASSF1A promoter methylation in high-grade serous ovarian cancer: A direct comparison study in primary tumors, adjacent morphologically tumor cell-free tissues and paired circulating tumor DNA

PubMed Central

Giannopoulou, Lydia; Chebouti, Issam; Pavlakis, Kitty; Kasimir-Bauer, Sabine; Lianidou, Evi S.

2017-01-01

The RASSF1A promoter is frequently methylated in high-grade serous ovarian cancer (HGSC). We examined RASSF1A promoter methylation in primary tumors, adjacent morphologically tumor cell-free tissues and corresponding circulating tumor DNA (ctDNA) samples of patients with HGSC, using a real-time methylation specific PCR (real-time MSP) and a methylation-sensitive high-resolution melting analysis (MS-HRMA) assay for the detection and semi-quantitative estimation of methylation, respectively. Two groups of primary HGSC tumor FFPE samples were recruited (Group A n=67 and Group B n=61), along with matched adjacent morphologically tumor cell-free tissues (n=58) and corresponding plasma samples (n=59) for group B. Using both assays, RASSF1A promoter was found highly methylated in primary tumors of both groups, and at lower percentages in the adjacent morphologically tumor cell-free tissues. Interestingly, RASSF1A promoter methylation was also observed in ctDNA by real-time MSP. Overall survival (OS) was significantly associated with RASSF1A promoter methylation in primary tumor samples using MS-HRMA (P=0.023). Our results clearly indicate that RASSF1A promoter is methylated in adjacent tissue surrounding the tumor in HGSC patients. We report for the first time that RASSF1A promoter methylation provides significant prognostic information in HGSC patients. PMID:28206954

Malagasy cichlids differentially limit impacts of body shape evolution on oral jaw functional morphology.

PubMed

Martinez, Christopher M; Sparks, John S

2017-09-01

Patterns of trait covariation, such as integration and modularity, are vital factors that influence the evolution of vertebrate body plans. In functional systems, decoupling of morphological modules buffers functional change in one trait by reducing correlated variation with another. However, for complex morphologies with many-to-one mapping of form to function (MTOM), resistance to functional change may also be achieved by constraining morphological variation within a functionally stable region of morphospace. For this research, we used geometric morphometrics to evaluate the evolution of body shape and its relationship with jaw functional morphology in two independent radiations of endemic Malagasy cichlid (Teleostei: Cichlidae). Our results suggested that the two subfamilies used different strategies to mitigate impacts of body shape variation on a metric of jaw function, maxillary kinematic transmission (MKT): (1) modularity between cranial and postcranial morphologies, and (2) integration of body and jaw evolution, with jaw morphologies varying in a manner that limits change in MKT. This research shows that, unlike modularity, MTOM allows traits to retain strong evolutionary covariation while still reducing impacts on functionality. These results suggest that MTOM, and its influence on the evolution of correlated traits, is likely much more widespread than is currently understood. © 2017 The Author(s). Evolution © 2017 The Society for the Study of Evolution.

Dynamic evolutionary change in post-Paleozoic echinoids and the importance of scale when interpreting changes in rates of evolution.

PubMed

Hopkins, Melanie J; Smith, Andrew B

2015-03-24

How ecological and morphological diversity accrues over geological time has been much debated by paleobiologists. Evidence from the fossil record suggests that many clades reach maximal diversity early in their evolutionary history, followed by a decline in evolutionary rates as ecological space fills or due to internal constraints. Here, we apply recently developed methods for estimating rates of morphological evolution during the post-Paleozoic history of a major invertebrate clade, the Echinoidea. Contrary to expectation, rates of evolution were lowest during the initial phase of diversification following the Permo-Triassic mass extinction and increased over time. Furthermore, although several subclades show high initial rates and net decreases in rates of evolution, consistent with "early bursts" of morphological diversification, at more inclusive taxonomic levels, these bursts appear as episodic peaks. Peak rates coincided with major shifts in ecological morphology, primarily associated with innovations in feeding strategies. Despite having similar numbers of species in today's oceans, regular echinoids have accrued far less morphological diversity than irregular echinoids due to lower intrinsic rates of morphological evolution and less morphological innovation, the latter indicative of constrained or bounded evolution. These results indicate that rates of evolution are extremely heterogenous through time and their interpretation depends on the temporal and taxonomic scale of analysis.

Front Instabilities and Invasiveness of Simulated Avascular Tumors

PubMed Central

Popławski, Nikodem J.; Agero, Ubirajara; Gens, J. Scott; Swat, Maciej; Glazier, James A.; Anderson, Alexander R. A.

2009-01-01

We study the interface morphology of a 2D simulation of an avascular tumor composed of identical cells growing in an homogeneous healthy tissue matrix (TM), in order to understand the origin of the morphological changes often observed during real tumor growth. We use the GlazierGraner-Hogeweg model, which treats tumor cells as extended, deformable objects, to study the effects of two parameters: a dimensionless diffusion-limitation parameter defined as the ratio of the tumor consumption rate to the substrate transport rate, and the tumor-TM surface tension. We model TM as a nondiffusing field, neglecting the TM pressure and haptotactic repulsion acting on a real growing tumor; thus our model is appropriate for studying tumors with highly motile cells, e.g., gliomas. We show that the diffusion-limitation parameter determines whether the growing tumor develops a smooth (noninvasive) or fingered (invasive) interface, and that the sensitivity of tumor morphology to tumor-TM surface tension increases with the size of the dimensionless diffusion-limitation parameter. For large diffusion-limitation parameters we find a transition (missed in previous work) between dendritic structures, produced when tumor-TM surface tension is high, and seaweed-like structures, produced when tumor-TM surface tension is low. This observation leads to a direct analogy between the mathematics and dynamics of tumors and those observed in nonbiological directional solidification. Our results are also consistent with biological observation that hypoxia promotes invasive growth of tumor cells by inducing higher levels of receptors for scatter factors that weaken cell-cell adhesion and increase cell motility. These findings suggest that tumor morphology may have value in predicting the efficiency of antiangiogenic therapy in individual patients. PMID:19234746

Predictive oncology: multidisciplinary, multi-scale in-silico modeling linking phenotype, morphology and growth

PubMed Central

Sanga, Sandeep; Frieboes, Hermann B.; Zheng, Xiaoming; Gatenby, Robert; Bearer, Elaine L.; Cristini, Vittorio

2007-01-01

Empirical evidence and theoretical studies suggest that the phenotype, i.e., cellular- and molecular-scale dynamics, including proliferation rate and adhesiveness due to microenvironmental factors and gene expression that govern tumor growth and invasiveness, also determine gross tumor-scale morphology. It has been difficult to quantify the relative effect of these links on disease progression and prognosis using conventional clinical and experimental methods and observables. As a result, successful individualized treatment of highly malignant and invasive cancers, such as glioblastoma, via surgical resection and chemotherapy cannot be offered and outcomes are generally poor. What is needed is a deterministic, quantifiable method to enable understanding of the connections between phenotype and tumor morphology. Here, we critically review advantages and disadvantages of recent computational modeling efforts (e.g., continuum, discrete, and cellular automata models) that have pursued this understanding. Based on this assessment, we propose and discuss a multi-scale, i.e., from the molecular to the gross tumor scale, mathematical and computational “first-principle” approach based on mass conservation and other physical laws, such as employed in reaction-diffusion systems. Model variables describe known characteristics of tumor behavior, and parameters and functional relationships across scales are informed from in vitro, in vivo and ex vivo biology. We demonstrate that this methodology, once coupled to tumor imaging and tumor biopsy or cell culture data, should enable prediction of tumor growth and therapy outcome through quantification of the relation between the underlying dynamics and morphological characteristics. In particular, morphologic stability analysis of this mathematical model reveals that tumor cell patterning at the tumor-host interface is regulated by cell proliferation, adhesion and other phenotypic characteristics: histopathology information of tumor boundary can be inputted to the mathematical model and used as phenotype-diagnostic tool and thus to predict collective and individual tumor cell invasion of surrounding host. This approach further provides a means to deterministically test effects of novel and hypothetical therapy strategies on tumor behavior. PMID:17629503

Primitive Neuroectodermal Tumors of the Female Genital Tract: A Morphologic, Immunohistochemical, and Molecular Study of 19 Cases.

PubMed

Chiang, Sarah; Snuderl, Matija; Kojiro-Sanada, Sakiko; Quer Pi-Sunyer, Ariadna; Daya, Dean; Hayashi, Tohru; Bosincu, Luisanna; Ogawa, Fumihiro; Rosenberg, Andrew E; Horn, Lars-Christian; Wang, Lu; Iafrate, A John; Oliva, Esther

2017-06-01

Primary primitive neuroectodermal tumor (PNET) of the female genital tract is rare, and its proper classification remains unclear. The clinical, histologic, and immunophenotypic features as well as EWSR1 rearrangement status of 19 gynecologic PNETs, including 10 ovarian, 8 uterine, and 1 vulvar tumors, are herein reported. Patient age ranged from 12 to 68 years, with a median age of 20 and 51 years among those with ovarian and uterine PNETs, respectively. Morphologic features of central nervous system (CNS) tumors were seen in 15 PNETs, including 9 medulloblastomas, 3 ependymomas, 2 medulloepitheliomas, and 1 glioblastoma, consistent with central PNET. The remaining 4 PNETs were composed entirely of undifferentiated small round blue cells and were classified as Ewing sarcoma/peripheral PNET. Eight PNETs were associated with another tumor type, including 5 ovarian mature cystic teratomas, 2 endometrial low-grade endometrioid carcinomas, and a uterine carcinosarcoma. By immunohistochemistry, 17 PNETs expressed at least 1 marker of neuronal differentiation, including synaptophysin, NSE, CD56, S100, and chromogranin in 10, 8, 14, 8, and 1 tumors, respectively. GFAP was positive in 4 PNETs, all of which were of central type. Membranous CD99 and nuclear Fli-1 staining was seen in 10 and 16 tumors, respectively, and concurrent expression of both markers was seen in both central and Ewing sarcoma/peripheral PNETs. All tumors expressed vimentin, whereas keratin cocktail (CAM5.2, AE1/AE3) staining was only focally present in 4 PNETs. Fluorescence in situ hybridization was successful in all cases and confirmed EWSR1 rearrangement in 2 of 4 tumors demonstrating morphologic features of Ewing sarcoma/peripheral PNET and concurrent CD99 and Fli-1 expression. In conclusion, central and Ewing sarcoma/peripheral PNETs may be encountered in the female genital tract with central PNETs being more common. Central PNETs show a spectrum of morphologic features that overlaps with CNS tumors but lack EWSR1 rearrangements. GFAP expression supports a morphologic impression of central PNET and is absent in Ewing sarcoma/peripheral PNET. Ewing sarcoma/peripheral PNETs lack morphologic features of CNS tumors.

Dynamic evolutionary change in post-Paleozoic echinoids and the importance of scale when interpreting changes in rates of evolution

PubMed Central

Hopkins, Melanie J.; Smith, Andrew B.

2015-01-01

How ecological and morphological diversity accrues over geological time has been much debated by paleobiologists. Evidence from the fossil record suggests that many clades reach maximal diversity early in their evolutionary history, followed by a decline in evolutionary rates as ecological space fills or due to internal constraints. Here, we apply recently developed methods for estimating rates of morphological evolution during the post-Paleozoic history of a major invertebrate clade, the Echinoidea. Contrary to expectation, rates of evolution were lowest during the initial phase of diversification following the Permo-Triassic mass extinction and increased over time. Furthermore, although several subclades show high initial rates and net decreases in rates of evolution, consistent with “early bursts” of morphological diversification, at more inclusive taxonomic levels, these bursts appear as episodic peaks. Peak rates coincided with major shifts in ecological morphology, primarily associated with innovations in feeding strategies. Despite having similar numbers of species in today’s oceans, regular echinoids have accrued far less morphological diversity than irregular echinoids due to lower intrinsic rates of morphological evolution and less morphological innovation, the latter indicative of constrained or bounded evolution. These results indicate that rates of evolution are extremely heterogenous through time and their interpretation depends on the temporal and taxonomic scale of analysis. PMID:25713369

Between-Region Genetic Divergence Reflects the Mode and Tempo of Tumor Evolution

PubMed Central

Sun, Ruping; Hu, Zheng; Sottoriva, Andrea; Graham, Trevor A.; Harpak, Arbel; Ma, Zhicheng; Fischer, Jared M.; Shibata, Darryl; Curtis, Christina

2017-01-01

Given the implications of tumor dynamics for precision medicine, there is a need to systematically characterize the mode of evolution across diverse solid tumor types. In particular, methods to infer the role of natural selection within established human tumors are lacking. By simulating spatial tumor growth under different evolutionary modes and examining patterns of between-region subclonal genetic divergence from multi-region sequencing (MRS) data, we demonstrate that it is feasible to distinguish tumors driven by strong positive subclonal selection from those evolving neutrally or under weak selection, as the latter fail to dramatically alter subclonal composition. We developed a classifier based on measures of between-region subclonal genetic divergence and projected patient data into model space, revealing different modes of evolution both within and between solid tumor types. Our findings have broad implications for how human tumors progress, accumulate intra-tumor heterogeneity, and ultimately how they may be more effectively treated. PMID:28581503

An Improved Binary Differential Evolution Algorithm to Infer Tumor Phylogenetic Trees.

PubMed

Liang, Ying; Liao, Bo; Zhu, Wen

2017-01-01

Tumourigenesis is a mutation accumulation process, which is likely to start with a mutated founder cell. The evolutionary nature of tumor development makes phylogenetic models suitable for inferring tumor evolution through genetic variation data. Copy number variation (CNV) is the major genetic marker of the genome with more genes, disease loci, and functional elements involved. Fluorescence in situ hybridization (FISH) accurately measures multiple gene copy number of hundreds of single cells. We propose an improved binary differential evolution algorithm, BDEP, to infer tumor phylogenetic tree based on FISH platform. The topology analysis of tumor progression tree shows that the pathway of tumor subcell expansion varies greatly during different stages of tumor formation. And the classification experiment shows that tree-based features are better than data-based features in distinguishing tumor. The constructed phylogenetic trees have great performance in characterizing tumor development process, which outperforms other similar algorithms.

Intra-Tumor Genetic Heterogeneity in Wilms Tumor: Clonal Evolution and Clinical Implications.

PubMed

Cresswell, George D; Apps, John R; Chagtai, Tasnim; Mifsud, Borbala; Bentley, Christopher C; Maschietto, Mariana; Popov, Sergey D; Weeks, Mark E; Olsen, Øystein E; Sebire, Neil J; Pritchard-Jones, Kathy; Luscombe, Nicholas M; Williams, Richard D; Mifsud, William

2016-07-01

The evolution of pediatric solid tumors is poorly understood. There is conflicting evidence of intra-tumor genetic homogeneity vs. heterogeneity (ITGH) in a small number of studies in pediatric solid tumors. A number of copy number aberrations (CNA) are proposed as prognostic biomarkers to stratify patients, for example 1q+ in Wilms tumor (WT); current clinical trials use only one sample per tumor to profile this genetic biomarker. We multisampled 20 WT cases and assessed genome-wide allele-specific CNA and loss of heterozygosity, and inferred tumor evolution, using Illumina CytoSNP12v2.1 arrays, a custom analysis pipeline, and the MEDICC algorithm. We found remarkable diversity of ITGH and evolutionary trajectories in WT. 1q+ is heterogeneous in the majority of tumors with this change, with variable evolutionary timing. We estimate that at least three samples per tumor are needed to detect >95% of cases with 1q+. In contrast, somatic 11p15 LOH is uniformly an early event in WT development. We find evidence of two separate tumor origins in unilateral disease with divergent histology, and in bilateral WT. We also show subclonal changes related to differential response to chemotherapy. Rational trial design to include biomarkers in risk stratification requires tumor multisampling and reliable delineation of ITGH and tumor evolution. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

Fluorine-18-fluorodeoxyglucose positron emission tomography as an objective substitute for CT morphologic response criteria in patients undergoing chemotherapy for colorectal liver metastases.

PubMed

Nishioka, Yujiro; Yoshioka, Ryuji; Gonoi, Wataru; Sugawara, Toshitaka; Yoshida, Shuntaro; Hashimoto, Masaji; Shindoh, Junichi

2018-05-01

The computed tomography (CT) morphologic response of colorectal liver metastases (CLM) after chemotherapy is reportedly correlated with pathologic response and survival outcomes of patients undergoing surgery. However, they are rather subjective criteria and not evaluable without adequate quality of contrast-enhanced CT images. This study sought the potential use of fluorine-18-fluorodeoxyglucose (FDG) positron emission tomography (PET) as an objective substitute for predicting pathological viability of CLM after chemotherapy. Predictive ability of tumor viability of ≤10% was compared between FDG-PET/CT and contrast-enhanced CT in 34 patients who underwent curative surgical resection for CLM after chemotherapy. The CT morphology and response were defined according to the reported criteria (Chun YS, JAMA 2009). The mean standard uptake value (SUV-mean) in CLM was significantly lower in patients with group 1 and group 2 CT morphology (median, 2.53 and 3.00, respectively) than in group 3 (median, 3.32). The tumor SUV-mean showed moderate correlation with the tumor pathologic viability (r = 0.660, P < 0.0001). A receiver operating characteristic curve analysis revealed that both the tumor SUV-mean (area under the curve [AUC], 0.916; the cut-off value, 3.00) and the CT morphology (AUC, 0.882) have excellent predictive power for ≤10% of tumor viability, while degree of tumor shrinkage showed lower predictive power (AUC, 0.692). FDG-PET shows significant correlation with pathologic viability of CLM after chemotherapy and may offer additional objective information for estimating tumor viability when the CT morphologic response is not evaluable.

Development of a Prognostic Marker for Lung Cancer Using Analysis of Tumor Evolution

DTIC Science & Technology

2017-08-01

SUPPLEMENTARY NOTES 14. ABSTRACT The goal of this project is to sequence the exomes of single tumor cells from tumors in order to construct evolutionary trees...dissociation, tumor cell isolation, whole genome amplification, and exome sequencing. We have begun to sequence the exomes of single cells and to...of populations, the evolution of tumor cells within a tumor can be diagrammed on a phylogenetic tree. The more diverse a tumor’s phylogenetic tree

Comprehensive Computational Pathological Image Analysis Predicts Lung Cancer Prognosis.

PubMed

Luo, Xin; Zang, Xiao; Yang, Lin; Huang, Junzhou; Liang, Faming; Rodriguez-Canales, Jaime; Wistuba, Ignacio I; Gazdar, Adi; Xie, Yang; Xiao, Guanghua

2017-03-01

Pathological examination of histopathological slides is a routine clinical procedure for lung cancer diagnosis and prognosis. Although the classification of lung cancer has been updated to become more specific, only a small subset of the total morphological features are taken into consideration. The vast majority of the detailed morphological features of tumor tissues, particularly tumor cells' surrounding microenvironment, are not fully analyzed. The heterogeneity of tumor cells and close interactions between tumor cells and their microenvironments are closely related to tumor development and progression. The goal of this study is to develop morphological feature-based prediction models for the prognosis of patients with lung cancer. We developed objective and quantitative computational approaches to analyze the morphological features of pathological images for patients with NSCLC. Tissue pathological images were analyzed for 523 patients with adenocarcinoma (ADC) and 511 patients with squamous cell carcinoma (SCC) from The Cancer Genome Atlas lung cancer cohorts. The features extracted from the pathological images were used to develop statistical models that predict patients' survival outcomes in ADC and SCC, respectively. We extracted 943 morphological features from pathological images of hematoxylin and eosin-stained tissue and identified morphological features that are significantly associated with prognosis in ADC and SCC, respectively. Statistical models based on these extracted features stratified NSCLC patients into high-risk and low-risk groups. The models were developed from training sets and validated in independent testing sets: a predicted high-risk group versus a predicted low-risk group (for patients with ADC: hazard ratio = 2.34, 95% confidence interval: 1.12-4.91, p = 0.024; for patients with SCC: hazard ratio = 2.22, 95% confidence interval: 1.15-4.27, p = 0.017) after adjustment for age, sex, smoking status, and pathologic tumor stage. The results suggest that the quantitative morphological features of tumor pathological images predict prognosis in patients with lung cancer. Copyright © 2016 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.

Concepts in solid tumor evolution.

PubMed

Sidow, Arend; Spies, Noah

2015-04-01

Evolutionary mechanisms in cancer progression give tumors their individuality. Cancer evolution is different from organismal evolution, however, and we discuss where concepts from evolutionary genetics are useful or limited in facilitating an understanding of cancer. Based on these concepts we construct and apply the simplest plausible model of tumor growth and progression. Simulations using this simple model illustrate the importance of stochastic events early in tumorigenesis, highlight the dominance of exponential growth over linear growth and differentiation, and explain the clonal substructure of tumors. Copyright © 2015 Elsevier Ltd. All rights reserved.

Long-term follow-up of nutritional status, pancreatic function, and morphological changes of the pancreatic remnant after pancreatic tumor resection in children.

PubMed

Sugito, Kiminobu; Furuya, Takeshi; Kaneda, Hide; Masuko, Takayuki; Ohashi, Kensuke; Inoue, Mikiya; Ikeda, Taro; Koshinaga, Tsugumichi; Tomita, Ryouichi; Maebayashi, Toshiya

2012-05-01

The objectives of the present study were to determine nutritional status, pancreatic function, and morphological changes of the pancreatic remnant after pancreatic tumor resection in children. The nutritional status was evaluated by the patterns of growth. Pancreatic function was evaluated by using a questionnaire, the Bristol stool form chart, the serum levels of fasting blood glucose, and hemoglobin A1c (HbA1c). Morphological changes of the pancreatic remnant were evaluated by computed tomography, magnetic resonance image, or magnetic resonance cholangiopancreatography. The present study consisted of 6 patients with pancreatic tumor (5 solid pseudopapillary tumors of the pancreas and 1 pancreatoblastoma) who underwent the following operations: tumor enucleation (3), distal pancreatectomy with splenectomy (1), and pylorus-preserving pancreatoduodenectomy (PPPD [2]). The serum levels of HbA1c have been gradually elevated in 2 patients with PPPD. A significant decrease in pancreatic parenchymal thickness and dilatation of the main pancreatic duct were observed in 2 patients with PPPD. Endocrine pancreatic insufficiency after PPPD may be explainable by obstructive pancreatitis after operation. Taking together the results of pancreatic endocrine function and morphological changes of pancreatic remnant after PPPD, tumor enucleation should be considered as surgical approach in children with pancreas head tumor whenever possible.

Malignant Perivascular Epithelioid Cell Tumor (PEComa) of the Adrenal Gland: Report of a Rare Case Posing Diagnostic Challenge with the Role of Immunohistochemistry in the Diagnosis.

PubMed

Pant, Leela; Kalita, Dipti; Chopra, Ratna; Das, Abhijit; Jain, Gaurav

2015-05-01

Histological diagnosis of adrenal tumors is often challenging as diverse groups of tumors, both primaries and metastatic, may be seen in the adrenal gland with overlapping morphological features. Immunohistochemistry (IHC) plays the most important role in their diagnosis. Perivascular epithelioid cell tumor (PEComa), a rarely reported tumor in the adrenal gland, shares many features with another rare tumor sarcomatoid adrenocortical carcinoma (ACC). Extensive immunohistochemical study is required to distinguish this tumor from adrenocortical carcinoma and from other morphologically similar tumors. The unique combination of immunoreactivity for melanocytic markers, such as HMB-45 and Melan A, and myogenic markers, such as smooth muscle actin, is the hallmark of PEComas biological behavior, and prognosis of malignant PEComas is yet to be fully understood. Few cases of malignant PEComa have been reported in the adrenal gland. We report a case of malignant PEComa of the adrenal gland posing diagnostic challenge and compare its morphological and immunohistochemical features with those of sarcomatoid ACC.

[Risk factors for malignant evolution of gastrointestinal stromal tumors].

PubMed

Andrei, S; Andrei, Adriana; Tonea, A; Andronesi, D; Becheanu, G; Dumbravă, Mona; Pechianu, C; Herlea, V; Popescu, I

2007-01-01

Gastrointestinal stromal tumors are the most frequent non-epithelial digestive tumors, being classified in the group of primitive mesenchymal tumors of the digestive tract. These tumors have a non predictable evolution and where stratified regarding the risk for malignant behavior in 4 categories: very low risk, low risk, intermediate risk and high risk. We performed a retrospective non randomised study including the patients with gastrointestinal stromal tumors treated in the Department of General Surgery and Liver Transplantation of Fundeni Clinical Institute in the period January 2002 - June 2007, to define the epidemiological, clinico-paraclinical, histological and especially evolutive features of the gastrointestinal stromal tumors from this group, with a special regard to the risk factors for their malignant behavior. The most important risk factors in gastrointestinal stromal tumors are the tumor size and the mitotic index, based on them being realised the classification of Fletcher in the 4 risk categories mentioned above. In our group all the local advanced or metastatic gastrointestinal stromal tumors, regardless of their location, were classified in the group of high risk for the malignant behavior. The gastric location and the epithelioid type were positive prognostic factors, and the complete resection of the tumor, an other important positive prognostic feature, was possible in about 80% of the cases, probably because the gastrointestinal stromal tumors in our study were diagnosed in less advanced evolutive situations, only about one third being metastatic and about 14% being locally advanced at the time of diagnose. The association with other neoplasias was in our cases insignificant, only 5% of the patients presenting concomitant malignant digestive tumors and 7.6% intraabdominal benign tumors. Gastrointestinal stromal tumors remain a challenge for the medical staff, regarding their diagnose and therapeutical management, the stratification of the risk for their malignant behavior being essential for the evolution of these patients.

Character trees from transcriptome data: Origin and individuation of morphological characters and the so-called "species signal".

PubMed

Musser, Jacob M; Wagner, Günter P

2015-11-01

We elaborate a framework for investigating the evolutionary history of morphological characters. We argue that morphological character trees generated by phylogenetic analysis of transcriptomes provide a useful tool for identifying causal gene expression differences underlying the development and evolution of morphological characters. They also enable rigorous testing of different models of morphological character evolution and origination, including the hypothesis that characters originate via divergence of repeated ancestral characters. Finally, morphological character trees provide evidence that character transcriptomes undergo concerted evolution. We argue that concerted evolution of transcriptomes can explain the so-called "species signal" found in several recent comparative transcriptome studies. The species signal is the phenomenon that transcriptomes cluster by species rather than character type, even though the characters are older than the respective species. We suggest the species signal is a natural consequence of concerted gene expression evolution resulting from mutations that alter gene regulatory network interactions shared by the characters under comparison. Thus, character trees generated from transcriptomes allow us to investigate the variational independence, or individuation, of morphological characters at the level of genetic programs. © 2015 Wiley Periodicals, Inc.

Evaluation of nuclear unrest and p53 immunostaining in Wilms' tumor.

PubMed

Salama, Asmaa; Kamel, Ahmad

2011-03-01

Nuclear unrest is a term applied to Wilms' tumors (WT) that show nuclear abnormalities close to anaplasia but without abnormal mitoses. p53 is claimed to be associated with anaplasia and poor prognosis. This study was undertaken to evaluate the clinical significance of nuclear unrest and p53 immunostaining in Wilms' tumor. This is a retrospective study of 63 patients who presented at NCI with Wilms' tumors, and underwent preoperative chemotherapy followed by nephrectomy. Histopathologic assessment and p53 immunohistochemistry were done. WT with nuclear unrest grade III closely resembled anaplastic tumors and both of them (group 1) constituted 19% of cases. Group 1 constituted 29% of cases showing blastema dominant morphology compared to 9.4% of cases without blastema dominant morphology with significant statistical difference (p=0.047). Almost 83% of cases that achieved 1st complete remission were stages I, II and III, while 17% were stages IV and V with significant statistical difference (p<0.001). Stage affected the 3-year relapse-free-survival (RFS) significantly (p=0.014) as it was more in stages I, II and III than in stages IV and V (75.4% versus 50%). Blastema dominant morphology and high risk state significantly lowered the 3-year overall survival (OS) into 54.8% in comparison to 80.9% for cases with non-blastema dominant morphology (p=0.042). Regarding p53 immunohistochemistry, group 1 tumors showed positive p53 more than group 2 with significant statistical difference (p=0.014). p53 Positive immunostaining was significantly associated with high risk nephroblastoma (p=0.004). Tumor stage and blastema dominant morphology are potent prognostic factors. p53 is linked to blastema dominant morphology. WT with nuclear unrest grade III closely resembles anaplastic WT. It may be appropriate to group tumors with nuclear unrest grade III with anaplastic histology regarding treatment stratification. Copyright © 2011. Published by Elsevier B.V.

A New Ghost Cell/Level Set Method for Moving Boundary Problems: Application to Tumor Growth

PubMed Central

Macklin, Paul

2011-01-01

In this paper, we present a ghost cell/level set method for the evolution of interfaces whose normal velocity depend upon the solutions of linear and nonlinear quasi-steady reaction-diffusion equations with curvature-dependent boundary conditions. Our technique includes a ghost cell method that accurately discretizes normal derivative jump boundary conditions without smearing jumps in the tangential derivative; a new iterative method for solving linear and nonlinear quasi-steady reaction-diffusion equations; an adaptive discretization to compute the curvature and normal vectors; and a new discrete approximation to the Heaviside function. We present numerical examples that demonstrate better than 1.5-order convergence for problems where traditional ghost cell methods either fail to converge or attain at best sub-linear accuracy. We apply our techniques to a model of tumor growth in complex, heterogeneous tissues that consists of a nonlinear nutrient equation and a pressure equation with geometry-dependent jump boundary conditions. We simulate the growth of glioblastoma (an aggressive brain tumor) into a large, 1 cm square of brain tissue that includes heterogeneous nutrient delivery and varied biomechanical characteristics (white matter, gray matter, cerebrospinal fluid, and bone), and we observe growth morphologies that are highly dependent upon the variations of the tissue characteristics—an effect observed in real tumor growth. PMID:21331304

The molecular aspects of personalized anticancer treatment

NASA Astrophysics Data System (ADS)

Cherdyntseva, N.; Litviakov, N.; Ivanova, F.; Denisov, E.; Gervas, P.; Cherdyntsev, E.

2016-08-01

Only 25% of cancer patients, on average, benefit from therapy. Even in the cases of complete clinical response the tumor progression is an event of high level expectation. The main reasons for tumor progression are: intratumor heterogeneity resulted from clonal evolution, drug resistance, and tumor-promoting microenvironment. The reprogramming of microenvironmental stromal-inflammatory components is expected to allow tumor phenotype reversion. So, to find the new effective markers of tumor progression, drug response and targets for therapy, it could be promising to take into account the tumor-microenvironment heterogeneity and tumor clonal evolution.

Development of a Prognostic Marker for Lung Cancer Using Analysis of Tumor Evolution

DTIC Science & Technology

2016-08-01

construct evolutionary trees , the characteristics of which will be used to predict whether a tumor will metastasize or not. We established a procedure for...of populations, the evolution of tumor cells within a tumor can be diagrammed on a phylogenetic tree . The more diverse a tumor’s phylogenetic tree ...individual tumor cells from the tumors of a training set of patients (half early stage, half late stage). We will reconstruct each tumor’s phylogenetic tree

Clonal evolution of acute myeloid leukemia highlighted by latest genome sequencing studies.

PubMed

Zhang, Xuehong; Lv, Dekang; Zhang, Yu; Liu, Quentin; Li, Zhiguang

2016-09-06

Decades of years might be required for an initiated cell to become a fully-pledged, metastasized tumor. DNA mutations are accumulated during this process including background mutations that emerge scholastically, as well as driver mutations that selectively occur in a handful of cancer genes and confer the cell a growth advantage over its neighbors. A clone of tumor cells could be superseded by another clone that acquires new mutations and grows more aggressively. Tumor evolutional patterns have been studied for years using conventional approaches that focus on the investigation of a single or a couple of genes. Latest deep sequencing technology enables a global view of tumor evolution by deciphering almost all genome aberrations in a tumor. Tumor clones and the fate of each clone during tumor evolution can be depicted with the help of the concept of variant allele frequency. Here, we summarize the new insights of cancer evolutional progression in acute myeloid leukemia. Cancer evolution is currently thought to start from a clone that has accumulated the requisite somatically-acquired genetic aberrations through a series of increasingly disordered clinical and pathological phases, eventually leading to malignant transformation [1-3]. The observations in invasive colorectal cancer that usually emerges from an antecedent benign adenomatous polyp and in cervical cancer that proceeds through intraepithelial neoplasia support the idea of stepwise or linear cancerous progression [3-5]. Genetically, such progression is achieved by successive waves of clonal expansion during which cells acquire novel genomic alterations including single nucleotide variants (SNVs), small insertions and deletions (indels), and/or copy number variations (CNVs) [6]. The latest improvement in sequencing technology has allowed the deciphering of the whole exome or genome in different types of tumor and normal tissue pairs, providing detailed catalogue about genome aberrations during tumor initiation and progression, which have been reviewed in several papers [7-10]. Here, we focus on demonstrating the cancer clonal evolution pattern revealed by recent deep sequencing studies of samples from acute myeloid leukemia (AML) patients.

Tumor evolution: Linear, branching, neutral or punctuated?☆

PubMed Central

Davis, Alexander; Gao, Ruli; Navin, Nicholas

2017-01-01

Intratumor heterogeneity has been widely reported in human cancers, but our knowledge of how this genetic diversity emerges over time remains limited. A central challenge in studying tumor evolution is the difficulty in collecting longitudinal samples from cancer patients. Consequently, most studies have inferred tumor evolution from single time-point samples, providing very indirect information. These data have led to several competing models of tumor evolution: linear, branching, neutral and punctuated. Each model makes different assumptions regarding the timing of mutations and selection of clones, and therefore has different implications for the diagnosis and therapeutic treatment of cancer patients. Furthermore, emerging evidence suggests that models may change during tumor progression or operate concurrently for different classes of mutations. Finally, we discuss data that supports the theory that most human tumors evolve from a single cell in the normal tissue. This article is part of a Special Issue entitled: Evolutionary principles - heterogeneity in cancer?, edited by Dr. Robert A. Gatenby. PMID:28110020

Genetic evolution of nevus of Ota reveals clonal heterogeneity acquiring BAP1 and TP53 mutations.

PubMed

Vivancos, Ana; Caratú, Ginevra; Matito, Judit; Muñoz, Eva; Ferrer, Berta; Hernández-Losa, Javier; Bodet, Domingo; Pérez-Alea, Mileidys; Cortés, Javier; Garcia-Patos, Vicente; Recio, Juan A

2016-03-01

Melanoma presents molecular alterations based on its anatomical location and exposure to environmental factors. Due to its intrinsic genetic heterogeneity, a simple snapshot of a tumor's genetic alterations does not reflect the tumor clonal complexity or specific gene-gene cooperation. Here, we studied the genetic alterations and clonal evolution of a unique patient with a Nevus of Ota that developed into a recurring uveal-like dermal melanoma. The Nevus of Ota and ulterior lesions contained GNAQ mutations were c-KIT positive, and tumors showed an increased RAS pathway activity during progression. Whole-exome sequencing of these lesions revealed the acquisition of BAP1 and TP53 mutations during tumor evolution, thereby unmasking clonal heterogeneity and allowing the identification of cooperating genes within the same tumor. Our results highlight the importance of studying tumor genetic evolution to identify cooperating mechanisms and delineate effective therapies. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

[Multifocal tubulopapillary tumors of the kidney. Morphologic features and prognosis. Three cases].

PubMed

Abdelmoula, N B; Boudawara, T; Bahloul, A; Hmida, M B; Hachicha, J; Rebai, T; Mhiri, N; Jlidi, R

1999-01-01

Tubulopapillary tumors of the kidney represent a particular group of renal tumors characterized by their less aggressive behavior. These tumors are distinguished from non papillary tumors by their morphologic, cytochemical and genotypic features. They correspond to a continuous spectrum of tumors ranging from papillary renal cell adenoma to papillary renal cell carcinoma. These TTPR show multifocal, bilateral development and chronic lesions of the kidney parenchyma in nearly all cases. The authors report three cases of multifocal TTPR, including one bilateral case. Based on analysis of these cases and a review of the literature, they discuss the histogenetic features and prognosis of TTPR.

APC/β-catenin-rich complexes at membrane protrusions regulate mammary tumor cell migration and mesenchymal morphology

PubMed Central

2013-01-01

Background The APC tumor suppressor is mutated or downregulated in many tumor types, and is prominently localized to punctate clusters at protrusion tips in migratory cells, such as in astrocytes where it has been implicated in directed cell motility. Although APC loss is considered an initiating event in colorectal cancer, for example, it is less clear what role APC plays in tumor cell motility and whether loss of APC might be an important promoter of tumor progression in addition to initiation. Methods The localization of APC and β-catenin was analyzed in multiple cell lines, including non-transformed epithelial lines treated with a proteasome inhibitor or TGFβ to induce an epithelial-to-mesenchymal transition (EMT), as well as several breast cancer lines, by immunofluorescence. APC expression was knocked down in 4T07 mammary tumor cells using lentiviral-mediated delivery of APC-specific short-hairpin (sh) RNAs, and assessed using quantitative (q) reverse-transcriptase (RT)-PCR and western blotting. Tumor cell motility was analyzed by performing wound-filling assays, and morphology via immunofluorescence (IF) and phase-contrast microscopy. Additionally, proliferation was measured using BrdU incorporation, and TCF reporter assays were performed to determine β-catenin/TCF-mediated transcriptional activity. Results APC/β-catenin-rich complexes were observed at protrusion ends of migratory epithelial cells treated with a proteasome inhibitor or when EMT has been induced and in tumor cells with a mesenchymal, spindle-like morphology. 4T07 tumor cells with reduced APC levels were significantly less motile and had a more rounded morphology; yet, they did not differ significantly in proliferation or β-catenin/TCF transcriptional activity. Furthermore, we found that APC/β-catenin-rich complexes at protrusion ends were dependent upon an intact microtubule cytoskeleton. Conclusions These findings indicate that membrane protrusions with APC/β-catenin-containing puncta control the migratory potential and mesenchymal morphology of mammary tumor cells and suggest that APC loss during later stages of tumor progression might impact tumor cell dissemination or colonization. PMID:23302090

Systemic estimation of the effect of photodynamic therapy of cancer

NASA Astrophysics Data System (ADS)

Kogan, Eugenia A.; Meerovich, Gennadii A.; Torshina, Nadezgda L.; Loschenov, Victor B.; Volkova, Anna I.; Posypanova, Anna M.

1997-12-01

The effects of photodynamic therapy (PDT) of cancer needs objective estimation and its unification in experimental as well as in clinical studies. They must include not only macroscopical changes but also the complex of following morphological criteria: (1) the level of direct tumor damage (direct necrosis and apoptosis); (2) the level of indirect tumor damage (ischemic necrosis); (3) the signs of vascular alterations; (4) the local and systemic antiblastome resistance; (5) the proliferative activity and malignant potential of survival tumor tissue. We have performed different regimes PDT using phthalocyanine derivatives. The complex of morphological methods (Ki-67, p53, c-myc, bcl-2) was used. Obtained results showed the connection of the tilted morphological criteria with tumor regression.

Morphological and immunohistochemical diversity of endometrial stromal sarcoma in rats.

PubMed

Kumabe, Shino; Sato, Junko; Tomonari, Yuki; Takahashi, Miwa; Inoue, Kaoru; Yoshida, Midori; Doi, Takuya; Wako, Yumi; Tsuchitani, Minoru

2018-04-01

To clarify the histopathological characteristics of rat endometrial stromal sarcoma (ESS), we morphologically reviewed 12 malignant uterine tumors protruding into the lumen in previous rat carcinogenicity studies. The 12 cases were classified into the following 6 types based on their morphological features: spindle cell and collagen rich type, pleomorphic/spindle cell and compact type, decidual alteration type, histiocytic and multinucleated giant cell mixture type, Antoni A-type schwannoma type, and Antoni B-type schwannoma type. Immunohistochemically, tumor cells in all cases exhibited focal or diffuse positive reactions for vimentin, and 11 of the 12 cases were positive for S-100. Interestingly, 9 cases were positive for desmin or αSMA, indicating tumor cells expressing smooth muscle properties. Both Antoni A- and B-type schwannoma types showed low reactions for both muscle markers. Positive results for estrogen receptor α in the 11 cases suggested that they were derived from endometrial stromal cells. On the basis of their immunohistochemical profiles, they were considered to be derived from endometrial stromal cells while they showed morphological variation. The detection of a basement membrane surrounding tumor cells might not be a definitive indicator for differential diagnosis of ESS from malignant schwannoma. In conclusion, ESS could exhibit wide morphological and immunohistochemical variation including features of schwannoma or smooth muscle tumor.

Morphological change in machines accelerates the evolution of robust behavior

PubMed Central

Bongard, Josh

2011-01-01

Most animals exhibit significant neurological and morphological change throughout their lifetime. No robots to date, however, grow new morphological structure while behaving. This is due to technological limitations but also because it is unclear that morphological change provides a benefit to the acquisition of robust behavior in machines. Here I show that in evolving populations of simulated robots, if robots grow from anguilliform into legged robots during their lifetime in the early stages of evolution, and the anguilliform body plan is gradually lost during later stages of evolution, gaits are evolved for the final, legged form of the robot more rapidly—and the evolved gaits are more robust—compared to evolving populations of legged robots that do not transition through the anguilliform body plan. This suggests that morphological change, as well as the evolution of development, are two important processes that improve the automatic generation of robust behaviors for machines. It also provides an experimental platform for investigating the relationship between the evolution of development and robust behavior in biological organisms. PMID:21220304

Character evolution and missing (morphological) data across the core asterids (Gentianidae)

USDA-ARS?s Scientific Manuscript database

Character evolution and missing (morphological) data across Asteridae. Premise of the study: Our current understanding of flowering plant phylogeny provides an excellent framework for exploring various aspects of character evolution through comparative analyses. However, attempts to synthesize this ...

Elevated rates of morphological and functional diversification in reef-dwelling haemulid fishes.

PubMed

Price, Samantha A; Tavera, Jose J; Near, Thomas J; Wainwright, Peter C

2013-02-01

The relationship between habitat complexity and species richness is well established but comparatively little is known about the evolution of morphological diversity in complex habitats. Reefs are structurally complex, highly productive shallow-water marine ecosystems found in tropical (coral reefs) and temperate zones (rocky reefs) that harbor exceptional levels of biodiversity. We investigated whether reef habitats promote the evolution of morphological diversity in the feeding and locomotion systems of grunts (Haemulidae), a group of predominantly nocturnal fishes that live on both temperate and tropical reefs. Using phylogenetic comparative methods and statistical analyses that take into account uncertainty in phylogeny and the evolutionary history of reef living, we demonstrate that rates of morphological evolution are faster in reef-dwelling haemulids. The magnitude of this effect depends on the type of trait; on average, traits involved in the functional systems for prey capture and processing evolve twice as fast on reefs as locomotor traits. This result, along with the observation that haemulids do not exploit unique feeding niches on reefs, suggests that fine-scale trophic niche partitioning and character displacement may be driving higher rates of morphological evolution. Whatever the cause, there is growing evidence that reef habitats stimulate morphological and functional diversification in teleost fishes. © 2012 The Author(s). Evolution© 2012 The Society for the Study of Evolution.

Dynamics of morphological evolution in experimental Escherichia coli populations.

PubMed

Cui, F; Yuan, B

2016-08-30

Here, we applied a two-stage clonal expansion model of morphological (cell-size) evolution to a long-term evolution experiment with Escherichia coli. Using this model, we derived the incidence function of the appearance of cell-size stability, the waiting time until this morphological stability, and the conditional and unconditional probabilities of morphological stability. After assessing the parameter values, we verified that the calculated waiting time was consistent with the experimental results, demonstrating the effectiveness of the two-stage model. According to the relative contributions of parameters to the incidence function and the waiting time, cell-size evolution is largely determined by the promotion rate, i.e., the clonal expansion rate of selectively advantageous organisms. This rate plays a prominent role in the evolution of cell size in experimental populations, whereas all other evolutionary forces were found to be less influential.

Asynchronous evolution of physiology and morphology in Anolis lizards.

PubMed

Hertz, Paul E; Arima, Yuzo; Harrison, Alexis; Huey, Raymond B; Losos, Jonathan B; Glor, Richard E

2013-07-01

Species-rich adaptive radiations typically diversify along several distinct ecological axes, each characterized by morphological, physiological, and behavioral adaptations. We test here whether different types of adaptive traits share similar patterns of evolution within a radiation by investigating patterns of evolution of morphological traits associated with microhabitat specialization and of physiological traits associated with thermal biology in Anolis lizards. Previous studies of anoles suggest that close relatives share the same "structural niche" (i.e., use the same types of perches) and are similar in body size and shape, but live in different "climatic niches" (i.e., use habitats with different insolation and temperature profiles). Because morphology is closely tied to structural niche and field active body temperatures are tied to climatic niches in Anolis, we expected phylogenetic analyses to show that morphology is more evolutionarily conservative than thermal physiology. In support of this hypothesis, we find (1) that thermal biology exhibits more divergence among recently diverged Anolis taxa than does morphology; and (2) diversification of thermal biology among all species often follows diversification in morphology. These conclusions are remarkably consistent with predictions made by anole biologists in the 1960s and 1970s. © 2013 The Author(s). Evolution © 2013 The Society for the Study of Evolution.

MO-DE-207B-10: Impact of Morphologic Characteristics On Radiomics Features From Contast-Enhanced CT for Primary Lung Tumors

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fried, D; Zhang, L; Fave, X

Purpose: Determine the impact of morphologic characteristics (e.g. necrosis, vascular enhancement, and cavitation) on radiomic features from contrast enhanced CT (CE-CT) in primary lung tumors. Methods: We developed an auto-segmentation algorithm to separate lung tumors on contrast-enhanced CT into cavitation (air), necrosis, tissue, and enhancing vessels using a combination of thresholding and region-growing. An auto-segmentation algorithm was also designed to identify necrosis on FDG-PET scans. Wilcoxon rank-sum tests were used to determine if significant differences existed in radiomics features (histogram-uniformity and Laplacian-of-Gaussian average) from 249 patients, found to prognostic in previous work, based on the presence/absence of morphologic features. Featuremore » values were also compared between the original tumor contours and contours excluding a specific morphologic feature. Comparison of necrosis segmentation on CE-CT versus FDG-PET was performed in 78 patients to assess for agreement using the concordance correlation coefficient (CCC). Results: Tumors with cavitation and enhancing vasculature had lower uniformity values (p = 0.001 and p = 0.03, respectively). Tumors with enhancing vasculature and necrosis had higher Laplacian-of-Gaussian average values (measure of “edges” within the tumor) (p < 0.001). Removing these tissue types from regions-of-interest did not drastically alter either radiomic feature value (all scenarios had R{sup 2} > 0.8). This suggests there may be interactions between morphologic characteristics and the radiomic feature value of tumor tissue. Comparison of necrosis volume and percent necrosis volume of tumor were found to have CCC values of 0.85 and 0.76, respectively between CE-CT and FDG-PET segmentation methods. Conclusions: Tumors with enhancing vasculature, necrosis, and cavitation have higher radiomic feature values that are associated with poor prognosis than tumors without these features. Removing these tissue types from quantitative assessment did not drastically impact radiomic feature values. High reproducibility of CE-CT segmented necrosis compared to FDG-PET segmented necrosis provides a reasonable validation of segmentation accuracy on CE-CT.« less

Serine, Glycine and One-carbon Metabolism in Colorectal Cancer Cell in Heterogeneous Microenvironment

NASA Astrophysics Data System (ADS)

Lin, Ke-Chih; Austin, Robert; Ducker, Greg; Sturm, James; Sturm, James

The up-regulation of serine metabolism associated with one-carbon metabolism has been identified to support cellular biosynthesis and redox maintenance of tumors. The consistently over-expressed one-carbon genes have been targeted for potential drug development. To investigate the biological function of specific enzymes, we had genetic engineered HCT116 cell lines, methylenetetrahydrofolate dehydrogenase (MTHFD) and phosphoglycerate dehydrogenase (PHGDH) deleted cell lines, growing in the artificial microhabitats array with serine and glycine gradient across. The impact of depletion of serine and the blocking of biosynthesis pathway will be shown in terms of cell morphology, proliferation rate, and cell motility. The evolution dynamic and migration rate can also be tracked throughout the experiments.

Coastal Foredune Evolution, Part 2: Modeling Approaches for Meso-Scale Morphologic Evolution

DTIC Science & Technology

2017-03-01

ERDC/CHL CHETN-II-57 March 2017 Approved for public release; distribution is unlimited. Coastal Foredune Evolution, Part 2: Modeling Approaches...for Meso-Scale Morphologic Evolution by Margaret L. Palmsten1, Katherine L. Brodie2, and Nicholas J. Spore2 PURPOSE: This Coastal and Hydraulics...Engineering Technical Note (CHETN) is the second of two CHETNs focused on improving technologies to forecast coastal foredune evolution. Part 1

Inference of tumor evolution during chemotherapy by computational modeling and in situ analysis of genetic and phenotypic cellular diversity.

PubMed

Almendro, Vanessa; Cheng, Yu-Kang; Randles, Amanda; Itzkovitz, Shalev; Marusyk, Andriy; Ametller, Elisabet; Gonzalez-Farre, Xavier; Muñoz, Montse; Russnes, Hege G; Helland, Aslaug; Rye, Inga H; Borresen-Dale, Anne-Lise; Maruyama, Reo; van Oudenaarden, Alexander; Dowsett, Mitchell; Jones, Robin L; Reis-Filho, Jorge; Gascon, Pere; Gönen, Mithat; Michor, Franziska; Polyak, Kornelia

2014-02-13

Cancer therapy exerts a strong selection pressure that shapes tumor evolution, yet our knowledge of how tumors change during treatment is limited. Here, we report the analysis of cellular heterogeneity for genetic and phenotypic features and their spatial distribution in breast tumors pre- and post-neoadjuvant chemotherapy. We found that intratumor genetic diversity was tumor-subtype specific, and it did not change during treatment in tumors with partial or no response. However, lower pretreatment genetic diversity was significantly associated with pathologic complete response. In contrast, phenotypic diversity was different between pre- and posttreatment samples. We also observed significant changes in the spatial distribution of cells with distinct genetic and phenotypic features. We used these experimental data to develop a stochastic computational model to infer tumor growth patterns and evolutionary dynamics. Our results highlight the importance of integrated analysis of genotypes and phenotypes of single cells in intact tissues to predict tumor evolution. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

Inference of tumor evolution during chemotherapy by computational modeling and in situ analysis of cellular diversity for genetic and phenotypic features

PubMed Central

Almendro, Vanessa; Cheng, Yu-Kang; Randles, Amanda; Itzkovitz, Shalev; Marusyk, Andriy; Ametller, Elisabet; Gonzalez-Farre, Xavier; Muñoz, Montse; Russnes, Hege G.; Helland, Åslaug; Rye, Inga H.; Borresen-Dale, Anne-Lise; Maruyama, Reo; van Oudenaarden, Alexander; Dowsett, Mitchell; Jones, Robin L.; Reis-Filho, Jorge; Gascon, Pere; Gönen, Mithat; Michor, Franziska; Polyak, Kornelia

2014-01-01

SUMMARY Cancer therapy exerts a strong selection pressure that shapes tumor evolution, yet our knowledge of how tumors change during treatment is limited. Here we report the analysis of cellular heterogeneity for genetic and phenotypic features and their spatial distribution in breast tumors pre- and post-neoadjuvant chemotherapy. We found that intratumor genetic diversity was tumor subtype-specific and it did not change during treatment in tumors with partial or no response. However, lower pre-treatment genetic diversity was significantly associated with complete pathologic response. In contrast, phenotypic diversity was different between pre- and post-treatment samples. We also observed significant changes in the spatial distribution of cells with distinct genetic and phenotypic features. We used these experimental data to develop a stochastic computational model to infer tumor growth patterns and evolutionary dynamics. Our results highlight the importance of integrated analysis of genotypes and phenotypes of single cells in intact tissues to predict tumor evolution. PMID:24462293

Inference of tumor evolution during chemotherapy by computational modeling and in situ analysis of genetic and phenotypic cellular diversity

DOE PAGES

Almendro, Vanessa; Cheng, Yu -Kang; Randles, Amanda; ...

2014-02-01

Cancer therapy exerts a strong selection pressure that shapes tumor evolution, yet our knowledge of how tumors change during treatment is limited. Here, we report the analysis of cellular heterogeneity for genetic and phenotypic features and their spatial distribution in breast tumors pre- and post-neoadjuvant chemotherapy. We found that intratumor genetic diversity was tumor-subtype specific, and it did not change during treatment in tumors with partial or no response. However, lower pretreatment genetic diversity was significantly associated with pathologic complete response. In contrast, phenotypic diversity was different between pre- and post-treatment samples. We also observed significant changes in the spatialmore » distribution of cells with distinct genetic and phenotypic features. We used these experimental data to develop a stochastic computational model to infer tumor growth patterns and evolutionary dynamics. Our results highlight the importance of integrated analysis of genotypes and phenotypes of single cells in intact tissues to predict tumor evolution.« less

Modelling rate distributions using character compatibility: implications for morphological evolution among fossil invertebrates.

PubMed

Wagner, Peter J

2012-02-23

Rate distributions are important considerations when testing hypotheses about morphological evolution or phylogeny. They also have implications about general processes underlying character evolution. Molecular systematists often assume that rates are Poisson processes with gamma distributions. However, morphological change is the product of multiple probabilistic processes and should theoretically be affected by hierarchical integration of characters. Both factors predict lognormal rate distributions. Here, a simple inverse modelling approach assesses the best single-rate, gamma and lognormal models given observed character compatibility for 115 invertebrate groups. Tests reject the single-rate model for nearly all cases. Moreover, the lognormal outperforms the gamma for character change rates and (especially) state derivation rates. The latter in particular is consistent with integration affecting morphological character evolution.

Morphological diversity and evolution of egg and clutch structure in amphibians

USGS Publications Warehouse

Altig, Ronald; McDiarmid, Roy W.

2007-01-01

The first part of this synthesis summarizes the morphology of the jelly layers surrounding an amphibian ovum. We propose a standard terminology and discuss the evolution of jelly layers. The second part reviews the morphological diversity and arrangement of deposited eggs?the ovipositional mode; we recognize 5 morphological classes including 14 modes. We discuss some of the oviductal, ovipositional, and postovipositional events that contribute to these morphologies. We have incorporated data from taxa from throughout the world but recognize that other types will be discovered that may modify understanding of these modes. Finally, we discuss the evolutionary context of the diversity of clutch structure and present a first estimate of its evolution.

Temporal morphologic changes in human colorectal carcinomas following xenografting.

PubMed

Barkla, D H; Tutton, P J

1983-03-01

The temporal morphologic changes of human colorectal carcinomas following xenografting into immunosuppressed mice were investigated by the use of light and transmission electron microscopy. The results show that colorectal carcinomas undergo a series of morphologic changes during the initial 30-day period following transplantation. During the initial 1-5-day period the majority of tumor cells die, and during the following 5-10-day period the necrotic debris created during the 1-5-day period is removed by host-supplied inflammatory cells. Only small groups of peripherally placed tumor cells survived at the end of the first 10 days. During the 10-20-day period the tumor cell populations of xenografts were reestablished by a morphologically heterogeneous population of tumor cells, and during the 20-30 day period consolidation of this process continued and some xenografts showed macroscopic evidence of growth. The authors hypothesize that human colorectal carcinomas, like the antecedent epithelium, contain subpopulations of undifferentiated cells that give rise to populations of more-differentiated cells.

High-grade endometrial stromal sarcomas: a clinicopathologic study of a group of tumors with heterogenous morphologic and genetic features.

PubMed

Sciallis, Andrew P; Bedroske, Patrick P; Schoolmeester, John K; Sukov, William R; Keeney, Gary L; Hodge, Jennelle C; Bell, Debra A

2014-09-01

The existence of a "high-grade endometrial stromal sarcoma" category of tumors has been a controversial subject owing to, among other things, the difficulty in establishing consistent diagnostic criteria. Currently, the recommended classification for such tumors is undifferentiated uterine/endometrial sarcoma. Interest in this subject has recently increased markedly with the identification of recurrent molecular genetic abnormalities. At Mayo Clinic, a group of neoplasms has been observed that morphologically resemble, either cytologically or architecturally, classic "low-grade" endometrial stromal sarcoma but feature obvious deviations, specifically, 17 tumors with unequivocally high-grade morphology. These high-grade tumors displayed 3 morphologic themes: (1) tumors with a component that is identical to low-grade ESS that transitions abruptly into an obviously higher-grade component; (2) tumors composed exclusively of high-grade cells with uniform nuclear features but with a permeative pattern of infiltration; (3) tumors similar to the second group but with a different, yet characteristic, cytomorphology featuring enlarged round to ovoid cells (larger than those found in low-grade ESS) with smooth nuclear membranes and distinct chromatin clearing but lacking prominent nucleoli. We collected clinicopathologic data, applied immunohistochemical studies, and also tested tumors by fluorescence in situ hybridization for abnormalities in JAZF1, PHF1, YWHAE, and CCND1. Tumors from these 3 groups were found to be immunohistochemically and genetically distinct from one another. Most notable was the fact that category 3 contained all the cases that tested positive for YWHAE rearrangement, did not show any classic translocations for JAZF1, PHF1, or CCND1, often presented at a high stage, and behaved aggressively. This study demonstrates the morphologic, immunophenotypic, and molecular genetic heterogeneity that exists within "undifferentiated endometrial sarcomas" as currently defined and lends credence to the effort of subclassifying some tumors as truly "high-grade endometrial stromal sarcomas." Our study also shows that, in the context of undifferentiated endometrial sarcomas, recognition of cytomorphologic features on routine hematoxylin and eosin-stained sections may be used to select tumors with specific molecular genetic changes-that is, translocations involving YWHAE. Our conclusions will help further efforts towards proper sub-classification of these tumors which will aid in diagnosis and potentially affect clinical management.

Imaging, morphologic, and immunohistochemical correlation in gastrointestinal stromal tumors.

PubMed

Logrono, Roberto; Bhanot, Punam; Chaya, Charles; Cao, Li; Waxman, Irving; Bhutani, Manoop S

2006-08-25

Gastrointestinal stromal tumors (GISTs) recently have been distinguished morphologically, immunohistochemically, and genetically from other gastrointestinal-tract spindle cell neoplasms. The objective of this study was to correlate clinical and imaging findings with morphology and immunohistochemistry to diagnose GISTs and to differentiate them from other spindle cell lesions in the gastrointestinal tract. The authors reviewed 9 patients who had tumors that were diagnosed as GIST by image-guided and endosonographic-guided fine-needle aspiration (FNA) with or without core biopsy (7 stomach tumors and 2 intraabdominal tumors). The male:female ratio was 3:6, and the patients ranged in age from 38 years to 80 years. Onsite evaluation, preliminary cytologic evaluation, and immunohistochemistry were provided for 6 patients. Immunostains were performed, depending on sample size, on aspirates and/or core biopsies. On imaging studies, most tumors were smooth and homogenous, consistent with GIST. Tumors ranged in size from 1.8 cm to 22 cm. The largest neoplasm showed solid/cystic and necrotic components. Aspirates consisted of spindle cell, neoplastic proliferation arranged in fascicles that exhibited focal, nuclear palisading; indistinct, cytoplasmic borders; and no significant atypia or mitosis. Focal epithelioid changes or cytologic atypia and mitoses were observed in 2 tumors. Immunostains revealed tumor expression of CD117 and/or CD34 in 5 of 6 tumors, expression of actin in 3 of 6 tumors, and expression of desmin in 1 of 6 tumors. All tumors were diagnosed as GIST (or consistent with GIST for tumors that lacked immunochemical analysis). Five patients underwent surgical excision, and the GIST diagnosis was confirmed in 3 patients, whereas 1 tumor proved to be neurofibroma, and another tumor was leiomyoma. No surgical follow-up was available for the remaining 4 patients, who had imaging and morphologic findings consistent with GIST. In the setting of consistent clinical and radiologic findings, the combined use of cytomorphology and immunohistochemistry on FNA and/or core biopsy in most instances provides a reliable pathologic diagnosis of GIST. The need of sufficient material for performing ancillary studies and the usual impossibility of excluding malignancy are limitations of FNA cytology of GIST. Copyright 2006 American Cancer Society.

Capturing tumor heterogeneity and clonal evolution in solid cancers using circulating tumor DNA analysis.

PubMed

Perdigones, Nieves; Murtaza, Muhammed

2017-06-01

Circulating tumor DNA analysis has emerged as a potential noninvasive alternative to tissue biopsies for tumor genotyping in patients with metastatic cancer. This is particularly attractive in cases where tissue biopsies are contraindicated or repeat genotyping after progression on treatment is required. However, tissue and plasma analysis results are not always concordant and clinical interpretation of discordant results is not completely understood. Discordant results could arise due to analytical limits of assays used for tumor and plasma DNA analysis or due to low overall contribution of tumor-specific DNA in plasma. Once these factors are ruled out, tissue-plasma concordance and quantitative levels of somatic mutations in plasma can capture tumor heterogeneity. During longitudinal follow-up of patients, this feature can be leveraged to track subclonal evolution and to guide combination or sequential adaptive treatment. Here, we summarize recent results evaluating the opportunities and limitations of circulating tumor DNA analysis in the context of tumor heterogeneity and subclonal evolution in patients with advanced cancers. Copyright © 2017 Elsevier Inc. All rights reserved.

Evolution of Body Elongation in Gymnophthalmid Lizards: Relationships with Climate

PubMed Central

Grizante, Mariana B.; Brandt, Renata; Kohlsdorf, Tiana

2012-01-01

The evolution of elongated body shapes in vertebrates has intrigued biologists for decades and is particularly recurrent among squamates. Several aspects might explain how the environment influences the evolution of body elongation, but climate needs to be incorporated in this scenario to evaluate how it contributes to morphological evolution. Climatic parameters include temperature and precipitation, two variables that likely influence environmental characteristics, including soil texture and substrate coverage, which may define the selective pressures acting during the evolution of morphology. Due to development of geographic information system (GIS) techniques, these variables can now be included in evolutionary biology studies and were used in the present study to test for associations between variation in body shape and climate in the tropical lizard family Gymnophthalmidae. We first investigated how the morphological traits that define body shape are correlated in these lizards and then tested for associations between a descriptor of body elongation and climate. Our analyses revealed that the evolution of body elongation in Gymnophthalmidae involved concomitant changes in different morphological traits: trunk elongation was coupled with limb shortening and a reduction in body diameter, and the gradual variation along this axis was illustrated by less-elongated morphologies exhibiting shorter trunks and longer limbs. The variation identified in Gymnophthalmidae body shape was associated with climate, with the species from more arid environments usually being more elongated. Aridity is associated with high temperatures and low precipitation, which affect additional environmental features, including the habitat structure. This feature may influence the evolution of body shape because contrasting environments likely impose distinct demands for organismal performance in several activities, such as locomotion and thermoregulation. The present study establishes a connection between morphology and a broader natural component, climate, and introduces new questions about the spatial distribution of morphological variation among squamates. PMID:23166767

Nuclear markers reveal that inter-lake cichlids' similar morphologies do not reflect similar genealogy.

PubMed

Kassam, Daud; Seki, Shingo; Horic, Michio; Yamaoka, Kosaku

2006-08-01

The apparent inter-lake morphological similarity among East African Great Lakes' cichlid species/genera has left evolutionary biologists asking whether such similarity is due to sharing of common ancestor or mere convergent evolution. In order to answer such question, we first used Geometric Morphometrics, GM, to quantify morphological similarity and then subsequently used Amplified Fragment Length Polymorphism, AFLP, to determine if similar morphologies imply shared ancestry or convergent evolution. GM revealed that not all presumed morphological similar pairs were indeed similar, and the dendrogram generated from AFLP data indicated distinct clusters corresponding to each lake and not inter-lake morphological similar pairs. Such results imply that the morphological similarity is due to convergent evolution and not shared ancestry. The congruency of GM and AFLP generated dendrograms imply that GM is capable of picking up phylogenetic signal, and thus GM can be potential tool in phylogenetic systematics.

The effect of parity on morphological evolution among phrynosomatid lizards.

PubMed

Oufiero, C E; Gartner, G E A

2014-11-01

The shift from egg laying to live-bearing is one of the most well-studied transitions in evolutionary biology. Few studies, however, have assessed the effect of this transition on morphological evolution. Here, we evaluated the effect of reproductive mode on the morphological evolution of 10 traits, among 108 species of phrynosomatid lizards. We assess whether the requirement for passing shelled eggs through the pelvic girdle has led to morphological constraints in oviparous species and whether long gestation times in viviparous species have led to constraints in locomotor morphology. We fit models to the data that vary both in their tempo (strength and rate of selection) and mode of evolution (Brownian or Ornstein-Uhlenbeck) and estimates of trait optima. We found that most traits are best fit by a generalized multipeak OU model, suggesting differing trait optima for viviparous vs. oviparous species. Additionally, rates (σ(2) ) of both pelvic girdle and forelimb trait evolution varied with parity; viviparous species had higher rates. Hindlimb traits, however, exhibited no difference in σ(2) between parity modes. In a functional context, our results suggest that the passage of shelled eggs constrains the morphology of the pelvic girdle, but we found no evidence of morphological constraint of the locomotor apparatus in viviparous species. Our results are consistent with recent lineage diversification analyses, leading to the conclusion that transitions to viviparity increase both lineage and morphological diversification. © 2014 European Society For Evolutionary Biology. Journal of Evolutionary Biology © 2014 European Society For Evolutionary Biology.

Malignant perivascular epithelioid cell tumor in children: description of a case and review of the literature.

PubMed

Alaggio, Rita; Cecchetto, Giovanni; Martignoni, Guido; Bisogno, Gianni; Cheng, Liang; Sperlì, Domenico; d'Amore, Emauele S G; Dall'Igna, Patrizia

2012-06-01

Perivascular epithelioid cell tumors (PEComas) include different morphological entities originating from perivascular epithelioid cells. Their clinical behavior is not predictable, and there are no strict histologic criteria for malignancy, although larger tumors with infiltrative growth, hypercellularity, cellular atypia, atypical mitoses, and necrosis generally have a malignant course. Pediatric PEComas are rare, with less than 40 cases reported, mostly in children older than 5 years. We describe a case of malignant PEComa of the ligamentum teres in a 2-year-old girl, characterized by the occurrence of local relapse after primary treatment with chemotherapy and surgery and poor response to imatinib mesilate and temsirolimus used after further analyses confirmed p70S6K expression involved in the mTOR pathway. The girl was eventually treated with a debulking surgical procedure and is now alive with disease 6 years after diagnosis. Literature data of children affected by PEComas were also analyzed, trying to identify pathologic characteristics that could predict their course and therapeutic options. Histologically, they may be differentiated in 3 prognostic categories: (1) benign, lacking unfavorable morphological markers; (2) with uncertain malignant potential, carrying 1 unfavorable marker; and (3) malignant, with at least 2 unfavorable markers. In the literature, 9% of cases occurred as a second malignancy probably because of genomic instability related to treatment. Their different biology and the potential value of targeted therapies remain to be explored. The indolent evolution in our patient was similar to that reported in some other cases in the literature. In terms of treatment, the present case suggests a minor response to temsirolimus compared with the adult population. Copyright © 2012 Elsevier Inc. All rights reserved.

Modelling rate distributions using character compatibility: implications for morphological evolution among fossil invertebrates

PubMed Central

Wagner, Peter J.

2012-01-01

Rate distributions are important considerations when testing hypotheses about morphological evolution or phylogeny. They also have implications about general processes underlying character evolution. Molecular systematists often assume that rates are Poisson processes with gamma distributions. However, morphological change is the product of multiple probabilistic processes and should theoretically be affected by hierarchical integration of characters. Both factors predict lognormal rate distributions. Here, a simple inverse modelling approach assesses the best single-rate, gamma and lognormal models given observed character compatibility for 115 invertebrate groups. Tests reject the single-rate model for nearly all cases. Moreover, the lognormal outperforms the gamma for character change rates and (especially) state derivation rates. The latter in particular is consistent with integration affecting morphological character evolution. PMID:21795266

Extremely high genetic diversity in a single tumor points to prevalence of non-Darwinian cell evolution.

PubMed

Ling, Shaoping; Hu, Zheng; Yang, Zuyu; Yang, Fang; Li, Yawei; Lin, Pei; Chen, Ke; Dong, Lili; Cao, Lihua; Tao, Yong; Hao, Lingtong; Chen, Qingjian; Gong, Qiang; Wu, Dafei; Li, Wenjie; Zhao, Wenming; Tian, Xiuyun; Hao, Chunyi; Hungate, Eric A; Catenacci, Daniel V T; Hudson, Richard R; Li, Wen-Hsiung; Lu, Xuemei; Wu, Chung-I

2015-11-24

The prevailing view that the evolution of cells in a tumor is driven by Darwinian selection has never been rigorously tested. Because selection greatly affects the level of intratumor genetic diversity, it is important to assess whether intratumor evolution follows the Darwinian or the non-Darwinian mode of evolution. To provide the statistical power, many regions in a single tumor need to be sampled and analyzed much more extensively than has been attempted in previous intratumor studies. Here, from a hepatocellular carcinoma (HCC) tumor, we evaluated multiregional samples from the tumor, using either whole-exome sequencing (WES) (n = 23 samples) or genotyping (n = 286) under both the infinite-site and infinite-allele models of population genetics. In addition to the many single-nucleotide variations (SNVs) present in all samples, there were 35 "polymorphic" SNVs among samples. High genetic diversity was evident as the 23 WES samples defined 20 unique cell clones. With all 286 samples genotyped, clonal diversity agreed well with the non-Darwinian model with no evidence of positive Darwinian selection. Under the non-Darwinian model, MALL (the number of coding region mutations in the entire tumor) was estimated to be greater than 100 million in this tumor. DNA sequences reveal local diversities in small patches of cells and validate the estimation. In contrast, the genetic diversity under a Darwinian model would generally be orders of magnitude smaller. Because the level of genetic diversity will have implications on therapeutic resistance, non-Darwinian evolution should be heeded in cancer treatments even for microscopic tumors.

Extremely high genetic diversity in a single tumor points to prevalence of non-Darwinian cell evolution

PubMed Central

Ling, Shaoping; Hu, Zheng; Yang, Zuyu; Yang, Fang; Li, Yawei; Lin, Pei; Chen, Ke; Dong, Lili; Cao, Lihua; Tao, Yong; Hao, Lingtong; Chen, Qingjian; Gong, Qiang; Wu, Dafei; Li, Wenjie; Zhao, Wenming; Tian, Xiuyun; Hao, Chunyi; Hungate, Eric A.; Catenacci, Daniel V. T.; Hudson, Richard R.; Li, Wen-Hsiung; Lu, Xuemei; Wu, Chung-I

2015-01-01

The prevailing view that the evolution of cells in a tumor is driven by Darwinian selection has never been rigorously tested. Because selection greatly affects the level of intratumor genetic diversity, it is important to assess whether intratumor evolution follows the Darwinian or the non-Darwinian mode of evolution. To provide the statistical power, many regions in a single tumor need to be sampled and analyzed much more extensively than has been attempted in previous intratumor studies. Here, from a hepatocellular carcinoma (HCC) tumor, we evaluated multiregional samples from the tumor, using either whole-exome sequencing (WES) (n = 23 samples) or genotyping (n = 286) under both the infinite-site and infinite-allele models of population genetics. In addition to the many single-nucleotide variations (SNVs) present in all samples, there were 35 “polymorphic” SNVs among samples. High genetic diversity was evident as the 23 WES samples defined 20 unique cell clones. With all 286 samples genotyped, clonal diversity agreed well with the non-Darwinian model with no evidence of positive Darwinian selection. Under the non-Darwinian model, MALL (the number of coding region mutations in the entire tumor) was estimated to be greater than 100 million in this tumor. DNA sequences reveal local diversities in small patches of cells and validate the estimation. In contrast, the genetic diversity under a Darwinian model would generally be orders of magnitude smaller. Because the level of genetic diversity will have implications on therapeutic resistance, non-Darwinian evolution should be heeded in cancer treatments even for microscopic tumors. PMID:26561581

Diagnostic Value of Multidetector CT and Its Multiplanar Reformation, Volume Rendering and Virtual Bronchoscopy Postprocessing Techniques for Primary Trachea and Main Bronchus Tumors.

PubMed

Luo, Mingyue; Duan, Chaijie; Qiu, Jianping; Li, Wenru; Zhu, Dongyun; Cai, Wenli

2015-01-01

To evaluate the diagnostic value of multidetector CT (MDCT) and its multiplanar reformation (MPR), volume rendering (VR) and virtual bronchoscopy (VB) postprocessing techniques for primary trachea and main bronchus tumors. Detection results of 31 primary trachea and main bronchus tumors with MDCT and its MPR, VR and VB postprocessing techniques, were analyzed retrospectively with regard to tumor locations, tumor morphologies, extramural invasions of tumors, longitudinal involvements of tumors, morphologies and extents of luminal stenoses, distances between main bronchus tumors and trachea carinae, and internal features of tumors. The detection results were compared with that of surgery and pathology. Detection results with MDCT and its MPR, VR and VB were consistent with that of surgery and pathology, included tumor locations (tracheae, n = 19; right main bronchi, n = 6; left main bronchi, n = 6), tumor morphologies (endoluminal nodes with narrow bases, n = 2; endoluminal nodes with wide bases, n = 13; both intraluminal and extraluminal masses, n = 16), extramural invasions of tumors (brokethrough only serous membrane, n = 1; 4.0 mm-56.0 mm, n = 14; no clear border with right atelectasis, n = 1), longitudinal involvements of tumors (3.0 mm, n = 1; 5.0 mm-68.0 mm, n = 29; whole right main bronchus wall and trachea carina, n = 1), morphologies of luminal stenoses (irregular, n = 26; circular, n = 3; eccentric, n = 1; conical, n = 1) and extents (mild, n = 5; moderate, n = 7; severe, n = 19), distances between main bronchus tumors and trachea carinae (16.0 mm, n = 1; invaded trachea carina, n = 1; >20.0 mm, n = 10), and internal features of tumors (fairly homogeneous densities with rather obvious enhancements, n = 26; homogeneous density with obvious enhancement, n = 1; homogeneous density without obvious enhancement, n = 1; not enough homogeneous density with obvious enhancement, n = 1; punctate calcification with obvious enhancement, n = 1; low density without obvious enhancement, n = 1). MDCT and its MPR, VR and VB images have respective advantages and disadvantages. Their combination could complement to each other to accurately detect locations, natures (benignancy, malignancy or low malignancy), and quantities (extramural invasions, longitudinal involvements, extents of luminal stenoses, distances between main bronchus tumors and trachea carinae) of primary trachea and main bronchus tumors with crucial information for surgical treatment, are highly useful diagnostic methods for primary trachea and main bronchus tumors.

ACCELERATED EVOLUTION OF LAND SNAILS MANDARINA IN THE OCEANIC BONIN ISLANDS: EVIDENCE FROM MITOCHONDRIAL DNA SEQUENCES.

PubMed

Chiba, Satoshi

1999-04-01

An endemic land snail genus Mandarina of the oceanic Bonin (Ogasawara) Islands shows exceptionally rapid evolution not only of morphological and ecological traits, but of DNA sequence. A phylogenetic relationship based on mitochondrial DNA (mtDNA) sequences suggests that morphological differences equivalent to the differences between families were produced between Mandarina and its ancestor during the Pleistocene. The inferred phylogeny shows that species with similar morphologies and life habitats appeared repeatedly and independently in different lineages and islands at different times. Sequential adaptive radiations occurred in different islands of the Bonin Islands and species occupying arboreal, semiarboreal, and terrestrial habitat arose independently in each island. Because of a close relationship between shell morphology and life habitat, independent evolution of the same life habitat in different islands created species possesing the same shell morphology in different islands and lineages. This rapid evolution produced some incongruences between phylogenetic relationship and species taxonomy. Levels of sequence divergence of mtDNA among the species of Mandarina is extremely high. The maximum level of sequence divergence at 16S and 12S ribosomal RNA sequence within Mandarina are 18.7% and 17.7%, respectively, and this suggests that evolution of mtDNA of Mandarina is extremely rapid, more than 20 times faster than the standard rate in other animals. The present examination reveals that evolution of morphological and ecological traits occurs at extremely high rates in the time of adaptive radiation, especially in fragmented environments. © 1999 The Society for the Study of Evolution.

Different evolutionary pathways underlie the morphology of wrist bones in hominoids

PubMed Central

2013-01-01

Background The hominoid wrist has been a focus of numerous morphological analyses that aim to better understand long-standing questions about the evolution of human and hominoid hand use. However, these same analyses also suggest various scenarios of complex and mosaic patterns of morphological evolution within the wrist and potentially multiple instances of homoplasy that would benefit from require formal analysis within a phylogenetic context. We identify morphological features that principally characterize primate – and, in particular, hominoid (apes, including humans) - wrist evolution and reveal the rate, process and evolutionary timing of patterns of morphological change on individual branches of the primate tree of life. Linear morphological variables of five wrist bones – the scaphoid, lunate, triquetrum, capitate and hamate – are analyzed in a diverse sample of extant hominoids (12 species, 332 specimens), Old World (8 species, 43 specimens) and New World (4 species, 26 specimens) monkeys, fossil Miocene apes (8 species, 20 specimens) and Plio-Pleistocene hominins (8 species, 18 specimens). Result Results reveal a combination of parallel and synapomorphic morphology within haplorrhines, and especially within hominoids, across individual wrist bones. Similar morphology of some wrist bones reflects locomotor behaviour shared between clades (scaphoid, triquetrum and capitate) while others (lunate and hamate) indicate clade-specific synapomorphic morphology. Overall, hominoids show increased variation in wrist bone morphology compared with other primate clades, supporting previous analyses, and demonstrate several occurrences of parallel evolution, particularly between orangutans and hylobatids, and among hominines (extant African apes, humans and fossil hominins). Conclusions Our analyses indicate that different evolutionary processes can underlie the evolution of a single anatomical unit (the wrist) to produce diversity in functional and morphological adaptations across individual wrist bones. These results exemplify a degree of evolutionary and functional independence across different wrist bones, the potential evolvability of skeletal morphology, and help to contextualize the postcranial mosaicism observed in the hominin fossil record. PMID:24148262

The tumor-stromal ratio as a strong prognosticator for advanced gastric cancer patients: proposal of a new TSNM staging system.

PubMed

Peng, Chunwei; Liu, Jiuyang; Yang, Guifang; Li, Yan

2018-05-01

Insufficient attention is paid to the underlying tumor microenvironment (TME) evolution, that resulting in tumor heterogeneity and driving differences in cancer aggressiveness and treatment outcomes. The morphological evaluation of the proportion of the stroma at the most invasive part of primary tumor (tumor-stromal ratio, TSR) in cancer is gaining momentum as evidence strengthens for the clinical relevance. Tissue samples from the most invasive part of the primary gastric cancer (GC) of 494 patients were analyzed for their TSR, and a new TSNM (tumor-stromal node metastasis) staging system based on patho-biological behaviors was established and assessed. TSR is a new and strong independent prognostic factor for GC patients. The likelihood of tumor invasion is increased significantly for patients in the stromal-high subgroup compared to those in the stromal-low subgroup (P = 0.011). The discrimination ability of TSR was not less than the TNM staging system and was better in patients with stages I and II GC. We integrated the TSR parameter into the TNM staging system and proposed a new TSNM staging system creatively. There were three new subgroups (IC, IIC, IIID). There were four major groups and 10 subgroups in the TSNM system. The difference in overall survival (OS) was statistically significant among all TSNM system (P < 0.005 for all). Deep analyses revealed well predictive performance of the TSNM (P < 0.001). This study confirms the TSR as a TME prognostic factor for GC. TSR is a candidate TME parameter that could easily be implemented in routine pathology diagnostics, and the TSNM staging system has been established to optimize risk stratification for GC. The value of the TSNM staging system should be validated in further prospective study.

Acinic Cell Carcinoma of the Parotid Gland with Four Morphological Features

PubMed Central

Rosero, David S; Alvarez, Ramiro; Gambó, Paula; Alastuey, María; Valero, Alberto; Torrecilla, Nerea; Roche, A. Belén; Simón, Sara

2016-01-01

Acinic cell carcinoma arising in salivary glands is a rare tumor, accounting for 2% to 5% of the primary neoplasms of the parotid gland. When these tumors are well-differentiated, the neoplasia has innocuous aspect, due to the similarity to normal parotid tissue. This makes the diagnosis difficult. Initially the malignancy of this tumor was uncertain; however, recent studies have declared it as malignant. The female / male ratio is 3:2. The nodule usually presents as solitary and well defined shape. Several authors have used different terms to describe histomorphological patterns of these tumors. Four descriptive categories (solid, microcystic, papillary-cystic and follicular) are useful for pathologists. Here we report a case of a 49 yr old man with a left parotid nodule of 5 cm. Parotidectomy was performed at the Hospital Universitario Miguel Servet, in Zaragoza (Spain). The microscopy showed a tumor with acinic semblance, having the four morphologic patterns previously described. The morphological and immunohistochemical study was consistent with the diagnosis of acinic cell carcinoma. PMID:27499783

Acinic Cell Carcinoma of the Parotid Gland with Four Morphological Features.

PubMed

Rosero, David S; Alvarez, Ramiro; Gambó, Paula; Alastuey, María; Valero, Alberto; Torrecilla, Nerea; Roche, A Belén; Simón, Sara

2016-01-01

Acinic cell carcinoma arising in salivary glands is a rare tumor, accounting for 2% to 5% of the primary neoplasms of the parotid gland. When these tumors are well-differentiated, the neoplasia has innocuous aspect, due to the similarity to normal parotid tissue. This makes the diagnosis difficult. Initially the malignancy of this tumor was uncertain; however, recent studies have declared it as malignant. The female / male ratio is 3:2. The nodule usually presents as solitary and well defined shape. Several authors have used different terms to describe histomorphological patterns of these tumors. Four descriptive categories (solid, microcystic, papillary-cystic and follicular) are useful for pathologists. Here we report a case of a 49 yr old man with a left parotid nodule of 5 cm. Parotidectomy was performed at the Hospital Universitario Miguel Servet, in Zaragoza (Spain). The microscopy showed a tumor with acinic semblance, having the four morphologic patterns previously described. The morphological and immunohistochemical study was consistent with the diagnosis of acinic cell carcinoma.

Rates of morphological evolution, asymmetry and morphological integration of shell shape in scallops.

PubMed

Sherratt, Emma; Serb, Jeanne M; Adams, Dean C

2017-12-08

Rates of morphological evolution vary across different taxonomic groups, and this has been proposed as one of the main drivers for the great diversity of organisms on Earth. Of the extrinsic factors pertaining to this variation, ecological hypotheses feature prominently in observed differences in phenotypic evolutionary rates across lineages. But complex organisms are inherently modular, comprising distinct body parts that can be differentially affected by external selective pressures. Thus, the evolution of trait covariation and integration in modular systems may also play a prominent role in shaping patterns of phenotypic diversity. Here we investigate the role ecological diversity plays in morphological integration, and the tempo of shell shape evolution and of directional asymmetry in bivalved scallops. Overall, the shape of both valves and the magnitude of asymmetry of the whole shell (difference in shape between valves) are traits that are evolving fast in ecomorphs under strong selective pressures (gliders, recessers and nestling), compared to low rates observed in other ecomorphs (byssal-attaching, free-living and cementing). Given that different parts of an organism can be under different selective pressures from the environment, we also examined the degree of evolutionary integration between the valves as it relates to ecological shifts. We find that evolutionary morphological integration is consistent and surprisingly high across species, indicating that while the left and right valves of a scallop shell are diversifying in accordance with ecomorphology, they are doing so in a concerted fashion. Our study on scallops adds another strong piece of evidence that ecological shifts play an important role in the tempo and mode of morphological evolution. Strong selective pressures from the environment, inferred from the repeated evolution of distinct ecomorphs, have influenced the rate of morphological evolution in valve shape and the magnitude of asymmetry between valves. Our observation that morphological integration of the valves making up the shell is consistently strong suggests tight developmental pathways are responsible for the concerted evolution of these structures while environmental pressures are driving whole shell shape. Finally, our study shows that directional asymmetry in shell shape among species is an important aspect of scallop macroevolution.

Morphological rates of angiosperm seed size evolution.

PubMed

Sims, Hallie J

2013-05-01

The evolution of seed size among angiosperms reflects their ecological diversification in a complex fitness landscape of life-history strategies. The lineages that have evolved seeds beyond the upper and lower boundaries that defined nonflowering seed plants since the Paleozoic are more dispersed across the angiosperm phylogeny than would be expected under a neutral model of phenotypic evolution. Morphological rates of seed size evolution estimated for 40 clades based on 17,375 species ranged from 0.001 (Garryales) to 0.207 (Malvales). Comparative phylogenetic analysis indicated that morphological rates are not associated with the clade's seed size but are negatively correlated with the clade's position in the overall distribution of angiosperm seed sizes; clades with seed sizes closer to the angiosperm mean had significantly higher morphological rates than clades with extremely small or extremely large seeds. Likewise, per-clade taxonomic diversification rates are not associated with the seed size of the clade but with where the clade falls within the angiosperm seed size distribution. These results suggest that evolutionary rates (morphological and taxonomic) are elevated in densely occupied regions of the seed morphospace relative to lineages whose ecophenotypic innovations have moved them toward the edges. © 2013 The Author(s). Evolution © 2013 The Society for the Study of Evolution.

Mixed cortical adenoma and composite pheochromocytoma-ganglioneuroma: an unusual corticomedullary tumor of the adrenal gland.

PubMed

Lau, Sean K; Chu, Peiguo G; Weiss, Lawrence M

2011-06-01

Adrenal neoplasms composed of more than one cell type and demonstrating a mixed histologic appearance are exceedingly rare. We report the clinical and pathologic features of a morphologically distinctive tumor of the adrenal gland composed of cortical, chromaffin, and neural cells. Histologically, the tumor consisted of intermixed areas of proliferating cortical cells resembling adrenal cortical adenoma, neoplastic chromaffin cells consistent with pheochromocytoma, and a ganglioneuromatous stroma. The presence of the cortical, medullary, and neural components within the tumor was confirmed by immunohistochemical studies. The present case serves to broaden the morphologic spectrum of mixed tumors that may be encountered in the adrenal gland. Copyright © 2011 Elsevier Inc. All rights reserved.

Emerging principles of regulatory evolution.

PubMed

Prud'homme, Benjamin; Gompel, Nicolas; Carroll, Sean B

2007-05-15

Understanding the genetic and molecular mechanisms governing the evolution of morphology is a major challenge in biology. Because most animals share a conserved repertoire of body-building and -patterning genes, morphological diversity appears to evolve primarily through changes in the deployment of these genes during development. The complex expression patterns of developmentally regulated genes are typically controlled by numerous independent cis-regulatory elements (CREs). It has been proposed that morphological evolution relies predominantly on changes in the architecture of gene regulatory networks and in particular on functional changes within CREs. Here, we discuss recent experimental studies that support this hypothesis and reveal some unanticipated features of how regulatory evolution occurs. From this growing body of evidence, we identify three key operating principles underlying regulatory evolution, that is, how regulatory evolution: (i) uses available genetic components in the form of preexisting and active transcription factors and CREs to generate novelty; (ii) minimizes the penalty to overall fitness by introducing discrete changes in gene expression; and (iii) allows interactions to arise among any transcription factor and downstream CRE. These principles endow regulatory evolution with a vast creative potential that accounts for both relatively modest morphological differences among closely related species and more profound anatomical divergences among groups at higher taxonomical levels.

Transcriptomic and macroevolutionary evidence for phenotypic uncoupling between frog life history phases

PubMed Central

Wollenberg Valero, Katharina C.; Garcia-Porta, Joan; Rodríguez, Ariel; Arias, Mónica; Shah, Abhijeet; Randrianiaina, Roger Daniel; Brown, Jason L.; Glaw, Frank; Amat, Felix; Künzel, Sven; Metzler, Dirk; Isokpehi, Raphael D.; Vences, Miguel

2017-01-01

Anuran amphibians undergo major morphological transitions during development, but the contribution of their markedly different life-history phases to macroevolution has rarely been analysed. Here we generate testable predictions for coupling versus uncoupling of phenotypic evolution of tadpole and adult life-history phases, and for the underlying expression of genes related to morphological feature formation. We test these predictions by combining evidence from gene expression in two distantly related frogs, Xenopus laevis and Mantidactylus betsileanus, with patterns of morphological evolution in the entire radiation of Madagascan mantellid frogs. Genes linked to morphological structure formation are expressed in a highly phase-specific pattern, suggesting uncoupling of phenotypic evolution across life-history phases. This gene expression pattern agrees with uncoupled rates of trait evolution among life-history phases in the mantellids, which we show to have undergone an adaptive radiation. Our results validate a prevalence of uncoupling in the evolution of tadpole and adult phenotypes of frogs. PMID:28504275

[Effect of depsides salts from Salvia miltiorrhiza on human hepatoma cell line SMMC-7721 subcutaneous xenografts in nude mice].

PubMed

Li, Xiangping; Song, Zhouye; Zhong, Haiying; Gong, Zhicheng; Yin, Tao; Zhang, Zanling; Zhou, Boting

2015-02-01

To exlpore the eff ect of depsides salts from Salvia miltiorrhiza on human hepatoma cell line SMMC-7721 xenograft tumors and the possible mechanisms. A total of 36 nude mice were divided into 6 groups: A model group, a negative control group, a positive control group, and 3 treatment groups at low, middle or high dose (n=6). The tumor model of nude mice was given depsides salts at a dose of 10, 20 or 50 mg/kg every 3 day for 16 days. Then samples of subcutaneous tumors in nude mice were collected. The morphological changes of tumor samples were observed by HE staining and the expression of vascular endothelial growth factor (VEGF) and the tumor antigen Ki67 was detected by immunohistochemical method. The tumor growth was inhibited by all doses of depsides salts. The morphology of tumors was shrinkage, broken and irregularly arranged compared with the tumors in the model group and the negative control group. Morphological changes were more obvious in tumors with treatment at high dose. Expression of VEGF and Ki67 in treatment groups and the positive control group were lower than that in the model group and the negative control group, with a significant difference (P<0.05). Depsides salts from Salvia miltiorrhiza can inhibit the growth of human hepatoma cell line SMMC-7721 tumor in nude mice, which is related to the inhibition of Ki67 and VEGF.

Quantitative morphometric analysis of hepatocellular carcinoma: development of a programmed algorithm and preliminary application.

PubMed

Yap, Felix Y; Bui, James T; Knuttinen, M Grace; Walzer, Natasha M; Cotler, Scott J; Owens, Charles A; Berkes, Jamie L; Gaba, Ron C

2013-01-01

The quantitative relationship between tumor morphology and malignant potential has not been explored in liver tumors. We designed a computer algorithm to analyze shape features of hepatocellular carcinoma (HCC) and tested feasibility of morphologic analysis. Cross-sectional images from 118 patients diagnosed with HCC between 2007 and 2010 were extracted at the widest index tumor diameter. The tumor margins were outlined, and point coordinates were input into a MATLAB (MathWorks Inc., Natick, Massachusetts, USA) algorithm. Twelve shape descriptors were calculated per tumor: the compactness, the mean radial distance (MRD), the RD standard deviation (RDSD), the RD area ratio (RDAR), the zero crossings, entropy, the mean Feret diameter (MFD), the Feret ratio, the convex hull area (CHA) and perimeter (CHP) ratios, the elliptic compactness (EC), and the elliptic irregularity (EI). The parameters were correlated with the levels of alpha-fetoprotein (AFP) as an indicator of tumor aggressiveness. The quantitative morphometric analysis was technically successful in all cases. The mean parameters were as follows: compactness 0.88±0.086, MRD 0.83±0.056, RDSD 0.087±0.037, RDAR 0.045±0.023, zero crossings 6±2.2, entropy 1.43±0.16, MFD 4.40±3.14 cm, Feret ratio 0.78±0.089, CHA 0.98±0.027, CHP 0.98±0.030, EC 0.95±0.043, and EI 0.95±0.023. MFD and RDAR provided the widest value range for the best shape discrimination. The larger tumors were less compact, more concave, and less ellipsoid than the smaller tumors (P < 0.0001). AFP-producing tumors displayed greater morphologic irregularity based on several parameters, including compactness, MRD, RDSD, RDAR, entropy, and EI (P < 0.05 for all). Computerized HCC image analysis using shape descriptors is technically feasible. Aggressively growing tumors have wider diameters and more irregular margins. Future studies will determine further clinical applications for this morphologic analysis.

Evidence for determinism in species diversification and contingency in phenotypic evolution during adaptive radiation.

PubMed

Burbrink, Frank T; Chen, Xin; Myers, Edward A; Brandley, Matthew C; Pyron, R Alexander

2012-12-07

Adaptive radiation (AR) theory predicts that groups sharing the same source of ecological opportunity (EO) will experience deterministic species diversification and morphological evolution. Thus, deterministic ecological and morphological evolution should be correlated with deterministic patterns in the tempo and mode of speciation for groups in similar habitats and time periods. We test this hypothesis using well-sampled phylogenies of four squamate groups that colonized the New World (NW) in the Late Oligocene. We use both standard and coalescent models to assess species diversification, as well as likelihood models to examine morphological evolution. All squamate groups show similar early pulses of speciation, as well as diversity-dependent ecological limits on clade size at a continental scale. In contrast, processes of morphological evolution are not easily predictable and do not show similar pulses of early and rapid change. Patterns of morphological and species diversification thus appear uncoupled across these groups. This indicates that the processes that drive diversification and disparification are not mechanistically linked, even among similar groups of taxa experiencing the same sources of EO. It also suggests that processes of phenotypic diversification cannot be predicted solely from the existence of an AR or knowledge of the process of diversification.

Tipping the scales: Evolution of the allometric slope independent of average trait size.

PubMed

Stillwell, R Craig; Shingleton, Alexander W; Dworkin, Ian; Frankino, W Anthony

2016-02-01

The scaling of body parts is central to the expression of morphology across body sizes and to the generation of morphological diversity within and among species. Although patterns of scaling-relationship evolution have been well documented for over one hundred years, little is known regarding how selection acts to generate these patterns. In part, this is because it is unclear the extent to which the elements of log-linear scaling relationships-the intercept or mean trait size and the slope-can evolve independently. Here, using the wing-body size scaling relationship in Drosophila melanogaster as an empirical model, we use artificial selection to demonstrate that the slope of a morphological scaling relationship between an organ (the wing) and body size can evolve independently of mean organ or body size. We discuss our findings in the context of how selection likely operates on morphological scaling relationships in nature, the developmental basis for evolved changes in scaling, and the general approach of using individual-based selection experiments to study the expression and evolution of morphological scaling. © 2016 The Author(s). Evolution © 2016 The Society for the Study of Evolution.

Evidence for determinism in species diversification and contingency in phenotypic evolution during adaptive radiation

PubMed Central

Burbrink, Frank T.; Chen, Xin; Myers, Edward A.; Brandley, Matthew C.; Pyron, R. Alexander

2012-01-01

Adaptive radiation (AR) theory predicts that groups sharing the same source of ecological opportunity (EO) will experience deterministic species diversification and morphological evolution. Thus, deterministic ecological and morphological evolution should be correlated with deterministic patterns in the tempo and mode of speciation for groups in similar habitats and time periods. We test this hypothesis using well-sampled phylogenies of four squamate groups that colonized the New World (NW) in the Late Oligocene. We use both standard and coalescent models to assess species diversification, as well as likelihood models to examine morphological evolution. All squamate groups show similar early pulses of speciation, as well as diversity-dependent ecological limits on clade size at a continental scale. In contrast, processes of morphological evolution are not easily predictable and do not show similar pulses of early and rapid change. Patterns of morphological and species diversification thus appear uncoupled across these groups. This indicates that the processes that drive diversification and disparification are not mechanistically linked, even among similar groups of taxa experiencing the same sources of EO. It also suggests that processes of phenotypic diversification cannot be predicted solely from the existence of an AR or knowledge of the process of diversification. PMID:23034709

Kidins220/ARMS depletion is associated with the neural-to Schwann-like transition in a human neuroblastoma cell line model.

PubMed

Rogers, Danny A; Schor, Nina F

2013-03-10

Peripheral neuroblastic tumors exist as a heterogeneous mixture of neuroblastic (N-type) cells and Schwannian stromal (S-type) cells. These stromal cells not only represent a differentiated and less aggressive fraction of the tumor, but also have properties that can influence the further differentiation of nearby malignant cells. In vitro neuroblastoma cultures exhibit similar heterogeneity with N-type and S-type cells representing the neuroblastic and stromal portions of the tumor, respectively, in behavior, morphology, and molecular expression patterns. In this study, we deplete kinase D-interacting substrate of 220kD (Kidins220) with an shRNA construct and thereby cause morphologic transition of the human SH-SY5Y neuroblastoma cell line from N-type to S-type. The resulting cells have similar morphology and expression profile to SH-EP1 cells, a native S-type cell line from the same parent cell line, and to SH-SY5Y cells treated with BrdU, a treatment that induces S-type morphology. Specifically, both Kidins220-deficient SH-SY5Y cells and native SH-EP1 cells demonstrate down-regulation of the genes DCX and STMN2, markers for the neuronal lineage. We further show that Kidins220, DCX and STMN2 are co-down-regulated in cells of S-type morphology generated by methods other than Kidins220 depletion. Finally, we report that the association of low Kidins220 expression with S-type morphology and low DCX and STMN2 expression is demonstrated in spontaneously occurring human peripheral neuroblastic tumors. We propose that Kidins220 is critical in N- to S-type transition of neural crest tumor cells. Copyright © 2013 Elsevier Inc. All rights reserved.

Subsets of salivary duct carcinoma defined by morphologic evidence of pleomorphic adenoma, PLAG1 or HMGA2 rearrangements, and common genetic alterations.

PubMed

Chiosea, Simion I; Thompson, Lester D R; Weinreb, Ilan; Bauman, Julie E; Mahaffey, Alyssa M; Miller, Caitlyn; Ferris, Robert L; Gooding, William E

2016-10-15

The authors hypothesized that histogenetic classification of salivary duct carcinoma (SDC) could account for de novo tumors and those with morphologic or molecular evidence (pleomorphic adenoma gene 1 [PLAG1], high-mobility group AT hook 2 [HMGA2] rearrangement, amplification) of pleomorphic adenoma (PA). SDCs (n = 66) were reviewed for morphologic evidence of PA. PLAG1 and HMGA2 alterations were detected by fluorescence in situ hybridization (FISH). PLAG1-positive tumors were tested by FISH for fibroblast growth factor receptor 1 (FGFR1) rearrangement. Thirty-nine tumors were analyzed using a commercial panel for mutations and copy number variations in 50 cancer-related genes. On the basis of combined morphologic and molecular evidence of PA, 4 subsets of SDC emerged: 1) carcinomas with morphologic evidence of PA but intact PLAG1 and HMGA2 (n = 22); 2) carcinomas with PLAG1 alteration (n = 18) or 3) HMGA2 alteration (n = 12); and 4) de novo carcinomas, without morphologic or molecular evidence of PA (n = 14). The median disease-free survival was 37 months (95% confidence interval, 28.4-45.6 months). Disease-free survival and other clinicopathologic parameters did not differ for the subsets defined above. Combined Harvey rat sarcoma viral oncogene homolog/phosphatidylinositol-4,5-biphosphate 3-kinase, catalytic subunit α (HRAS/PIK3CA) mutations were observed predominantly in de novo carcinomas (5 of 8 vs 2 of 31 tumors; P = .035). Erb-B2 receptor tyrosine kinase 2 (ERBB2) copy number gain was not observed in de novo carcinomas (0 of 8 vs 12 of 31 tumors; P = .08). Tumor protein 53 (TP53) mutations were more common in SDC ex pleomorphic adenomas than in de novo carcinomas (17 of 31 vs 1 of 8 tumors; P = .033). The genetic profile of SDC varies with the absence or presence of pre-existing PA and its cytogenetic signature. Most de novo SDCs harbor combined HRAS/PIK3CA mutations and no ERBB2 amplification. Cancer 2016;122:3136-44. © 2016 American Cancer Society. © 2016 American Cancer Society.

Morphological evolution of Jinshan Trough in Hangzhou Bay (China) from 1960 to 2011

NASA Astrophysics Data System (ADS)

Liu, Yifei; Xia, Xiaoming; Chen, Shenliang; Jia, Jianjun; Cai, Tinglu

2017-11-01

An extensive system of tidal channels, starting with Jinshan Trough in the east, is located along the north shore of Hangzhou Bay, China. This contribution investigates the morphological evolution of Jinshan Trough by using 17 bathymetric charts from a series covering a period of 51 years from 1960 to 2011. Three stages of evolution during this period are distinguishable based on the morphology and annual mean volume data. The first stage (1960-1987) is characterized by extension of the trough; the second stage (1987-1996) is a relatively stable period with some adjustments in the trough morphology; the third stage (1996-2011) is marked by the processes of erosion and deposition in the beginning of the period and a subsequent slow erosion process. Spatio-temporal variability of the trough was evaluated by using empirical orthogonal function (EOF) analysis. The first eigenfunction indicates that erosion is the main evolution process and there exists three stages similar to those distinguished from volume variations. The second eigenfunction mainly reflects erosion and deposition in the northwest part of the trough located in the flood tidal current shadow area of the artificial headland in Jinshan. The third eigenfunction mainly reflects annual fluctuations of erosion and deposition in the side slope at the artificial headland in Jinshan. A particularly intense erosion process occurred between 1996 and 1998. The major effects on morphological evolution in Jinshan Trough from 1960 to 2011 were investigated and tentative conclusions were presented. Continuous coastal reclamations in Jinshan had the most pronounced effect on the morphological evolution during the first and the second stages. The storm surge had a pronounced effect on the evolution at the beginning of the third stage.

Evolutionary developmental genetics of fruit morphological variation within the Solanaceae

PubMed Central

Wang, Li; Li, Jing; Zhao, Jing; He, Chaoying

2015-01-01

Morphological variations of fruits such as shape and size, and color are a result of adaptive evolution. The evolution of morphological novelties is particularly intriguing. An understanding of these evolutionary processes calls for the elucidation of the developmental and genetic mechanisms that result in particular fruit morphological characteristics, which determine seed dispersal. The genetic and developmental basis for fruit morphological variation was established at a microevolutionary time scale. Here, we summarize the progress on the evolutionary developmental genetics of fruit size, shape and color in the Solanaceae. Studies suggest that the recruitment of a pre-existing gene and subsequent modification of its interaction and regulatory networks are frequently involved in the evolution of morphological diversity. The basic mechanisms underlying changes in plant morphology are alterations in gene expression and/or gene function. We also deliberate on the future direction in evolutionary developmental genetics of fruit morphological variation such as fruit type. These studies will provide insights into plant developmental processes and will help to improve the productivity and fruit quality of crops. PMID:25918515

New insights in non-small-cell lung cancer: circulating tumor cells and cell-free DNA

PubMed Central

Duréndez-Sáez, Elena; Azkárate, Aitor; Meri, Marina; Calabuig-Fariñas, Silvia; Aguilar-Gallardo, Cristóbal; Blasco, Ana

2017-01-01

Lung cancer is the second most frequent tumor and the leading cause of death by cancer in both men and women. Increasing knowledge about the cancer genome and tumor environment has led to a new setting in which morphological and molecular characterization is needed to treat patients in the most personalized way in order to achieve better outcomes. Since tumor products can be detected in body fluids, the liquid biopsy, particularly, peripheral blood, has emerged as a new source for lung cancer biomarker’s analysis. A variety of tumor components can be used for this purpose. Among them, circulating tumor cells (CTCs) and circulating tumor DNA (ctDNA) should be especially considered. Different detection methods for both CTCs and ctDNA have been and are being developed to improve the sensitivity and specificity of these tests. This would lead to better characterization and would solve some clinical doubts at different disease evolution times, e.g., intratumoral or temporal heterogeneity, difficulty in the obtaining a tumor sample, etc., and would also avoid the side effects of very expensive and complicated tumor obtaining interventions. CTCs and ctDNA are useful in different lung cancer settings. Their value has been shown for the early diagnosis, prognosis, prediction of treatment efficacy, monitoring responses and early detection of lung cancer relapse. CTCs have still not been validated for use in clinical settings in non-small-cell lung cancer (NSCLC), while ctDNA has been approved by the Food and Drug Administration (FDA) and European Medical Association (EMA), and the main clinical guidelines used for detect different epidermal growth factor receptor (EGFR) mutations and the monitoring and treatment choice of mutated patients with tyrosine kinase inhibitors (TKIs). This review, describes how ctDNA seem to be winning the race against CTCs from the laboratory bench to clinical practice due to easier obtaining methods, manipulation and its implementation into clinical practice. PMID:29184672

SciClone: inferring clonal architecture and tracking the spatial and temporal patterns of tumor evolution.

PubMed

Miller, Christopher A; White, Brian S; Dees, Nathan D; Griffith, Malachi; Welch, John S; Griffith, Obi L; Vij, Ravi; Tomasson, Michael H; Graubert, Timothy A; Walter, Matthew J; Ellis, Matthew J; Schierding, William; DiPersio, John F; Ley, Timothy J; Mardis, Elaine R; Wilson, Richard K; Ding, Li

2014-08-01

The sensitivity of massively-parallel sequencing has confirmed that most cancers are oligoclonal, with subpopulations of neoplastic cells harboring distinct mutations. A fine resolution view of this clonal architecture provides insight into tumor heterogeneity, evolution, and treatment response, all of which may have clinical implications. Single tumor analysis already contributes to understanding these phenomena. However, cryptic subclones are frequently revealed by additional patient samples (e.g., collected at relapse or following treatment), indicating that accurately characterizing a tumor requires analyzing multiple samples from the same patient. To address this need, we present SciClone, a computational method that identifies the number and genetic composition of subclones by analyzing the variant allele frequencies of somatic mutations. We use it to detect subclones in acute myeloid leukemia and breast cancer samples that, though present at disease onset, are not evident from a single primary tumor sample. By doing so, we can track tumor evolution and identify the spatial origins of cells resisting therapy.

SciClone: Inferring Clonal Architecture and Tracking the Spatial and Temporal Patterns of Tumor Evolution

PubMed Central

Dees, Nathan D.; Griffith, Malachi; Welch, John S.; Griffith, Obi L.; Vij, Ravi; Tomasson, Michael H.; Graubert, Timothy A.; Walter, Matthew J.; Ellis, Matthew J.; Schierding, William; DiPersio, John F.; Ley, Timothy J.; Mardis, Elaine R.; Wilson, Richard K.; Ding, Li

2014-01-01

The sensitivity of massively-parallel sequencing has confirmed that most cancers are oligoclonal, with subpopulations of neoplastic cells harboring distinct mutations. A fine resolution view of this clonal architecture provides insight into tumor heterogeneity, evolution, and treatment response, all of which may have clinical implications. Single tumor analysis already contributes to understanding these phenomena. However, cryptic subclones are frequently revealed by additional patient samples (e.g., collected at relapse or following treatment), indicating that accurately characterizing a tumor requires analyzing multiple samples from the same patient. To address this need, we present SciClone, a computational method that identifies the number and genetic composition of subclones by analyzing the variant allele frequencies of somatic mutations. We use it to detect subclones in acute myeloid leukemia and breast cancer samples that, though present at disease onset, are not evident from a single primary tumor sample. By doing so, we can track tumor evolution and identify the spatial origins of cells resisting therapy. PMID:25102416

Morphological and immunohistochemical characterization of isolated tumor cells by p53 status in gastrointestinal tumors.

PubMed

Milsmann, C; Füzesi, L; Heinmöller, E; Krause, P; Werner, C; Becker, H; Horstmann, O

2008-01-01

Isolated tumor cells (ITCs) in cancer patients are retrieved mostly using immunohistochemistry with antibodies directed against antiepithelial antigens (for example Ber-EP4), which are supposed not to be present in metastatic-free tissue. To date, there has been ongoing controversy whether those cells have biologic significance and are linked with tumor progression and impaired patient's prognosis. Therefore, the aim of this study was to further characterize Ber-EP4-positive cells in various tissues, with special emphasis on their tumorigenic origin. The frequency and prognostic impact of ITCs in lymph nodes displayed by means of monoclonal antibody Ber-EP4 were evaluated in retrospective (n = 292) and prospective (n = 100) collectives of various gastrointestinal carcinomas free of metastatic disease in conventional histopathology (pN0). Furthermore, the frequency of ITCs in the peritoneal cavity and bone marrow was analyzed in case of absence of overt distant metastasis (pM0) in the prospective collective. Ber-EP4-immunoreactive cells were further characterized for tumorigenic origin using morphological criteria and immunohistochemical double staining for Ber-EP4 and p53. Ber-EP4-positive cells could be revealed in lymph nodes in 44.3% of pN0-gastrointestinal carcinomas, in the peritoneal cavity in 19%, and in the bone marrow in 10%. In lymph nodes, BerEP4-immunoreactive cells exhibited a metastatic-atypical morphology in 59%; however, it was always typical for true tumor cells in the peritoneal cavity or bone marrow. The cumulative 5-year survival rate was adversely affected by Ber-EP4-immunoreactive cells in uni- and multivariate analysis, irrespective of the underlying cell morphology (68% for Ber-EP4 negative, 41% for Ber-EP4 positive with atypical and typical morphology each). In the case of a p53-positive primary tumor, 70% of the corresponding ITCs also overexpressed p53, while the remainder was deemed p53 negative (p = 0.002). ITCs detected by the antiepithelial antibody Ber-EP4 are present in a substantial proportion of apparently tumor-free lymph nodes. These cells impair patients' prognoses, irrespective of the underlying cell morphology. As approximately one third of Ber-EP4-positive cells in p53-positive primary tumors do not overexpress p53; their true tumorigenic origin needs to be further investigated.

[Primary perivascular epitheloid cell tumour (PEComa) of the liver - is a new entity of the liver tumors?].

PubMed

Panahova, S; Rempp, H; Sipos, B; Malek, N P; Boozari, B

2015-05-01

Perivascular epitheloid cell tumor (PEComa) is a rare tumor, characterized by dual Expression of smooth muscle and melanocytic markers. Due to the development of diagnostic procedures, we now diagnose PEComa more often. We report about a case of PEComa of the liver as an accidental finding. We analyze the clinical and morphological characteristics of this tumor and compare it with the data of the literature. Management of patients with PEComa is not yet standardized; therefore biopsy with immunhistochemical staining is necessary for the diagnosis. In case of liver tumors which cannot be classified by their morphology on imaging modalities, it is important to think about this rare entity. © Georg Thieme Verlag KG Stuttgart · New York.

Forecasting longitudinal changes in oropharyngeal tumor morphology throughout the course of head and neck radiation therapy

PubMed Central

Yock, Adam D.; Rao, Arvind; Dong, Lei; Beadle, Beth M.; Garden, Adam S.; Kudchadker, Rajat J.; Court, Laurence E.

2014-01-01

Purpose: To create models that forecast longitudinal trends in changing tumor morphology and to evaluate and compare their predictive potential throughout the course of radiation therapy. Methods: Two morphology feature vectors were used to describe 35 gross tumor volumes (GTVs) throughout the course of intensity-modulated radiation therapy for oropharyngeal tumors. The feature vectors comprised the coordinates of the GTV centroids and a description of GTV shape using either interlandmark distances or a spherical harmonic decomposition of these distances. The change in the morphology feature vector observed at 33 time points throughout the course of treatment was described using static, linear, and mean models. Models were adjusted at 0, 1, 2, 3, or 5 different time points (adjustment points) to improve prediction accuracy. The potential of these models to forecast GTV morphology was evaluated using leave-one-out cross-validation, and the accuracy of the models was compared using Wilcoxon signed-rank tests. Results: Adding a single adjustment point to the static model without any adjustment points decreased the median error in forecasting the position of GTV surface landmarks by the largest amount (1.2 mm). Additional adjustment points further decreased the forecast error by about 0.4 mm each. Selection of the linear model decreased the forecast error for both the distance-based and spherical harmonic morphology descriptors (0.2 mm), while the mean model decreased the forecast error for the distance-based descriptor only (0.2 mm). The magnitude and statistical significance of these improvements decreased with each additional adjustment point, and the effect from model selection was not as large as that from adding the initial points. Conclusions: The authors present models that anticipate longitudinal changes in tumor morphology using various models and model adjustment schemes. The accuracy of these models depended on their form, and the utility of these models includes the characterization of patient-specific response with implications for treatment management and research study design. PMID:25086518

Forecasting longitudinal changes in oropharyngeal tumor morphology throughout the course of head and neck radiation therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yock, Adam D.; Kudchadker, Rajat J.; Rao, Arvind

2014-08-15

Purpose: To create models that forecast longitudinal trends in changing tumor morphology and to evaluate and compare their predictive potential throughout the course of radiation therapy. Methods: Two morphology feature vectors were used to describe 35 gross tumor volumes (GTVs) throughout the course of intensity-modulated radiation therapy for oropharyngeal tumors. The feature vectors comprised the coordinates of the GTV centroids and a description of GTV shape using either interlandmark distances or a spherical harmonic decomposition of these distances. The change in the morphology feature vector observed at 33 time points throughout the course of treatment was described using static, linear,more » and mean models. Models were adjusted at 0, 1, 2, 3, or 5 different time points (adjustment points) to improve prediction accuracy. The potential of these models to forecast GTV morphology was evaluated using leave-one-out cross-validation, and the accuracy of the models was compared using Wilcoxon signed-rank tests. Results: Adding a single adjustment point to the static model without any adjustment points decreased the median error in forecasting the position of GTV surface landmarks by the largest amount (1.2 mm). Additional adjustment points further decreased the forecast error by about 0.4 mm each. Selection of the linear model decreased the forecast error for both the distance-based and spherical harmonic morphology descriptors (0.2 mm), while the mean model decreased the forecast error for the distance-based descriptor only (0.2 mm). The magnitude and statistical significance of these improvements decreased with each additional adjustment point, and the effect from model selection was not as large as that from adding the initial points. Conclusions: The authors present models that anticipate longitudinal changes in tumor morphology using various models and model adjustment schemes. The accuracy of these models depended on their form, and the utility of these models includes the characterization of patient-specific response with implications for treatment management and research study design.« less

The origin and early evolution of vascular plant shoots and leaves.

PubMed

Harrison, C Jill; Morris, Jennifer L

2018-02-05

The morphology of plant fossils from the Rhynie chert has generated longstanding questions about vascular plant shoot and leaf evolution, for instance, which morphologies were ancestral within land plants, when did vascular plants first arise and did leaves have multiple evolutionary origins? Recent advances combining insights from molecular phylogeny, palaeobotany and evo-devo research address these questions and suggest the sequence of morphological innovation during vascular plant shoot and leaf evolution. The evidence pinpoints testable developmental and genetic hypotheses relating to the origin of branching and indeterminate shoot architectures prior to the evolution of leaves, and demonstrates underestimation of polyphyly in the evolution of leaves from branching forms in 'telome theory' hypotheses of leaf evolution. This review discusses fossil, developmental and genetic evidence relating to the evolution of vascular plant shoots and leaves in a phylogenetic framework.This article is part of a discussion meeting issue 'The Rhynie cherts: our earliest terrestrial ecosystem revisited'. © 2017 The Authors.

The origin and early evolution of vascular plant shoots and leaves

PubMed Central

2018-01-01

The morphology of plant fossils from the Rhynie chert has generated longstanding questions about vascular plant shoot and leaf evolution, for instance, which morphologies were ancestral within land plants, when did vascular plants first arise and did leaves have multiple evolutionary origins? Recent advances combining insights from molecular phylogeny, palaeobotany and evo–devo research address these questions and suggest the sequence of morphological innovation during vascular plant shoot and leaf evolution. The evidence pinpoints testable developmental and genetic hypotheses relating to the origin of branching and indeterminate shoot architectures prior to the evolution of leaves, and demonstrates underestimation of polyphyly in the evolution of leaves from branching forms in ‘telome theory’ hypotheses of leaf evolution. This review discusses fossil, developmental and genetic evidence relating to the evolution of vascular plant shoots and leaves in a phylogenetic framework. This article is part of a discussion meeting issue ‘The Rhynie cherts: our earliest terrestrial ecosystem revisited’. PMID:29254961

Identification of neutral tumor evolution across cancer types

PubMed Central

Barnes, Chris P; Graham, Trevor A; Sottoriva, Andrea

2016-01-01

Despite extraordinary efforts to profile cancer genomes, interpreting the vast amount of genomic data in the light of cancer evolution remains challenging. Here we demonstrate that neutral tumor evolution results in a power-law distribution of the mutant allele frequencies reported by next-generation sequencing of tumor bulk samples. We find that the neutral power-law fits with high precision 323 of 904 cancers from 14 types, selected from different cohorts. In malignancies identified as neutral, all clonal selection occurred prior to the onset of cancer growth and not in later-arising subclones, resulting in numerous passenger mutations that are responsible for intra-tumor heterogeneity. Reanalyzing cancer sequencing data within the neutral framework allowed the measurement, in each patient, of both the in vivo mutation rate and the order and timing of mutations. This result provides a new way to interpret existing cancer genomic data and to discriminate between functional and non-functional intra-tumor heterogeneity. PMID:26780609

Application of morphological synthesis for understanding electrode microstructure evolution as a function of applied charge/discharge cycles

DOE PAGES

Glazoff, Michael V.; Dufek, Eric J.; Shalashnikov, Egor V.

2016-09-15

Morphological analysis and synthesis operations were employed for analysis of electrode microstructure transformations and evolution accompanying the application of charge/discharge cycles to electrochemical storage systems (batteries). Using state-of-the-art morphological algorithms, it was possible to predict microstructure evolution in porous Si electrodes for Li-ion batteries with sufficient accuracy. Algorithms for image analyses (segmentation, feature extraction, and 3D-reconstructions using 2D-images) were also developed. Altogether, these techniques could be considered supplementary to phase-field mesoscopic approach to microstructure evolution that is based upon clear and definitive changes in the appearance of microstructure. However, unlike in phase-field, the governing equations for morphological approach are geometry-,more » not physics-based. Similar non-physics based approach to understanding different phenomena was attempted with the introduction of cellular automata. It is anticipated that morphological synthesis and analysis will represent a useful supplementary tool to phase-field and will render assistance to unraveling the underlying microstructure-property relationships. The paper contains data on electrochemical characterization of different electrode materials that was conducted in parallel to morphological study.« less

Diagnostic Value of Multidetector CT and Its Multiplanar Reformation, Volume Rendering and Virtual Bronchoscopy Postprocessing Techniques for Primary Trachea and Main Bronchus Tumors

PubMed Central

Luo, Mingyue; Duan, Chaijie; Qiu, Jianping; Li, Wenru; Zhu, Dongyun; Cai, Wenli

2015-01-01

Purpose To evaluate the diagnostic value of multidetector CT (MDCT) and its multiplanar reformation (MPR), volume rendering (VR) and virtual bronchoscopy (VB) postprocessing techniques for primary trachea and main bronchus tumors. Methods Detection results of 31 primary trachea and main bronchus tumors with MDCT and its MPR, VR and VB postprocessing techniques, were analyzed retrospectively with regard to tumor locations, tumor morphologies, extramural invasions of tumors, longitudinal involvements of tumors, morphologies and extents of luminal stenoses, distances between main bronchus tumors and trachea carinae, and internal features of tumors. The detection results were compared with that of surgery and pathology. Results Detection results with MDCT and its MPR, VR and VB were consistent with that of surgery and pathology, included tumor locations (tracheae, n = 19; right main bronchi, n = 6; left main bronchi, n = 6), tumor morphologies (endoluminal nodes with narrow bases, n = 2; endoluminal nodes with wide bases, n = 13; both intraluminal and extraluminal masses, n = 16), extramural invasions of tumors (brokethrough only serous membrane, n = 1; 4.0 mm—56.0 mm, n = 14; no clear border with right atelectasis, n = 1), longitudinal involvements of tumors (3.0 mm, n = 1; 5.0 mm—68.0 mm, n = 29; whole right main bronchus wall and trachea carina, n = 1), morphologies of luminal stenoses (irregular, n = 26; circular, n = 3; eccentric, n = 1; conical, n = 1) and extents (mild, n = 5; moderate, n = 7; severe, n = 19), distances between main bronchus tumors and trachea carinae (16.0 mm, n = 1; invaded trachea carina, n = 1; >20.0 mm, n = 10), and internal features of tumors (fairly homogeneous densities with rather obvious enhancements, n = 26; homogeneous density with obvious enhancement, n = 1; homogeneous density without obvious enhancement, n = 1; not enough homogeneous density with obvious enhancement, n = 1; punctate calcification with obvious enhancement, n = 1; low density without obvious enhancement, n = 1). Conclusion MDCT and its MPR, VR and VB images have respective advantages and disadvantages. Their combination could complement to each other to accurately detect locations, natures (benignancy, malignancy or low malignancy), and quantities (extramural invasions, longitudinal involvements, extents of luminal stenoses, distances between main bronchus tumors and trachea carinae) of primary trachea and main bronchus tumors with crucial information for surgical treatment, are highly useful diagnostic methods for primary trachea and main bronchus tumors. PMID:26332466

Testing Phylogenetic Hypotheses of the Subgenera of the Freshwater Crayfish Genus Cambarus (Decapoda: Cambaridae)

PubMed Central

Breinholt, Jesse W.; Porter, Megan L.; Crandall, Keith A.

2012-01-01

Background The genus Cambarus is one of three most species rich crayfish genera in the Northern Hemisphere. The genus has its center of diversity in the Southern Appalachians of the United States and has been divided into 12 subgenera. Using Cambarus we test the correspondence of subgeneric designations based on morphology used in traditional crayfish taxonomy to the underlying evolutionary history for these crayfish. We further test for significant correlation and explanatory power of geographic distance, taxonomic model, and a habitat model to estimated phylogenetic distance with multiple variable regression. Methodology/Principal Findings We use three mitochondrial and one nuclear gene regions to estimate the phylogenetic relationships for species within the genus Cambarus and test evolutionary hypotheses of relationships and associated morphological and biogeographical hypotheses. Our resulting phylogeny indicates that the genus Cambarus is polyphyletic, however we fail to reject the monophyly of Cambarus with a topology test. The majority of the Cambarus subgenera are rejected as monophyletic, suggesting the morphological characters used to define those taxa are subject to convergent evolution. While we found incongruence between taxonomy and estimated phylogenetic relationships, a multiple model regression analysis indicates that taxonomy had more explanatory power of genetic relationships than either habitat or geographic distance. Conclusions We find convergent evolution has impacted the morphological features used to delimit Cambarus subgenera. Studies of the crayfish genus Orconectes have shown gonopod morphology used to delimit subgenera is also affected by convergent evolution. This suggests that morphological diagnoses based on traditional crayfish taxonomy might be confounded by convergent evolution across the cambarids and has little utility in diagnosing relationships or defining natural groups. We further suggest that convergent morphological evolution appears to be a common occurrence in invertebrates suggesting the need for careful phylogenetically based interpretations of morphological evolution in invertebrate systematics. PMID:23049950

Evaluating Cancer of the Central Nervous System Through Next-Generation Sequencing of Cerebrospinal Fluid

PubMed Central

Pentsova, Elena I.; Shah, Ronak H.; Tang, Jiabin; Boire, Adrienne; You, Daoqi; Briggs, Samuel; Omuro, Antonio; Lin, Xuling; Fleisher, Martin; Grommes, Christian; Panageas, Katherine S.; Meng, Fanli; Selcuklu, S. Duygu; Ogilvie, Shahiba; Distefano, Natalie; Shagabayeva, Larisa; Rosenblum, Marc; DeAngelis, Lisa M.; Viale, Agnes; Berger, Michael F.

2016-01-01

Purpose Cancer spread to the central nervous system (CNS) often is diagnosed late and is unresponsive to therapy. Mechanisms of tumor dissemination and evolution within the CNS are largely unknown because of limited access to tumor tissue. Materials and Methods We sequenced 341 cancer-associated genes in cell-free DNA from cerebrospinal fluid (CSF) obtained through routine lumbar puncture in 53 patients with suspected or known CNS involvement by cancer. Results We detected high-confidence somatic alterations in 63% (20 of 32) of patients with CNS metastases of solid tumors, 50% (six of 12) of patients with primary brain tumors, and 0% (zero of nine) of patients without CNS involvement by cancer. Several patients with tumor progression in the CNS during therapy with inhibitors of oncogenic kinases harbored mutations in the kinase target or kinase bypass pathways. In patients with glioma, the most common malignant primary brain tumor in adults, examination of cell-free DNA uncovered patterns of tumor evolution, including temozolomide-associated mutations. Conclusion The study shows that CSF harbors clinically relevant genomic alterations in patients with CNS cancers and should be considered for liquid biopsies to monitor tumor evolution in the CNS. PMID:27161972

Intra-tumor heterogeneity: lessons from microbial evolution and clinical implications

PubMed Central

2013-01-01

Multiple subclonal populations of tumor cells can coexist within the same tumor. This intra-tumor heterogeneity will have clinical implications and it is therefore important to identify factors that drive or suppress such heterogeneous tumor progression. Evolutionary biology can provide important insights into this process. In particular, experimental evolution studies of microbial populations, which exist as clonal populations that can diversify into multiple subclones, have revealed important evolutionary processes driving heterogeneity within a population. There are transferrable lessons that can be learnt from these studies that will help us to understand the process of intra-tumor heterogeneity in the clinical setting. In this review, we summarize drivers of microbial diversity that have been identified, such as mutation rate and environmental influences, and discuss how knowledge gained from microbial experimental evolution studies may guide us to identify and understand important selective factors that promote intra-tumor heterogeneity. Furthermore, we discuss how these factors could be used to direct and optimize research efforts to improve patient care, focusing on therapeutic resistance. Finally, we emphasize the need for longitudinal studies to address the impact of these potential tumor heterogeneity-promoting factors on drug resistance, metastatic potential and clinical outcome. PMID:24267946

Loss of YABBY2-Like Gene Expression May Underlie the Evolution of the Laminar Style in Canna and Contribute to Floral Morphological Diversity in the Zingiberales.

PubMed

Morioka, Kelsie; Yockteng, Roxana; Almeida, Ana M R; Specht, Chelsea D

2015-01-01

The Zingiberales is an order of tropical monocots that exhibits diverse floral morphologies. The evolution of petaloid, laminar stamens, staminodes, and styles contributes to this diversity. The laminar style is a derived trait in the family Cannaceae and plays an important role in pollination as its surface is used for secondary pollen presentation. Previous work in the Zingiberales has implicated YABBY2-like genes, which function in promoting laminar outgrowth, in the evolution of stamen morphology. Here, we investigate the evolution and expression of Zingiberales YABBY2-like genes in order to understand the evolution of the laminar style in Canna. Phylogenetic analyses show that multiple duplication events have occurred in this gene lineage prior to the diversification of the Zingiberales. Reverse transcription-PCR in Canna, Costus, and Musa reveals differential expression across floral organs, taxa, and gene copies, and a role for YABBY2-like genes in the evolution of the laminar style is proposed. Selection tests indicate that almost all sites in conserved domains are under purifying selection, consistent with their functional relevance, and a motif unique to monocot YABBY2-like genes is identified. These results contribute to our understanding of the molecular mechanisms underlying the evolution of floral morphologies.

Loss of YABBY2-Like Gene Expression May Underlie the Evolution of the Laminar Style in Canna and Contribute to Floral Morphological Diversity in the Zingiberales

PubMed Central

Morioka, Kelsie; Yockteng, Roxana; Almeida, Ana M. R.; Specht, Chelsea D.

2015-01-01

The Zingiberales is an order of tropical monocots that exhibits diverse floral morphologies. The evolution of petaloid, laminar stamens, staminodes, and styles contributes to this diversity. The laminar style is a derived trait in the family Cannaceae and plays an important role in pollination as its surface is used for secondary pollen presentation. Previous work in the Zingiberales has implicated YABBY2-like genes, which function in promoting laminar outgrowth, in the evolution of stamen morphology. Here, we investigate the evolution and expression of Zingiberales YABBY2-like genes in order to understand the evolution of the laminar style in Canna. Phylogenetic analyses show that multiple duplication events have occurred in this gene lineage prior to the diversification of the Zingiberales. Reverse transcription-PCR in Canna, Costus, and Musa reveals differential expression across floral organs, taxa, and gene copies, and a role for YABBY2-like genes in the evolution of the laminar style is proposed. Selection tests indicate that almost all sites in conserved domains are under purifying selection, consistent with their functional relevance, and a motif unique to monocot YABBY2-like genes is identified. These results contribute to our understanding of the molecular mechanisms underlying the evolution of floral morphologies. PMID:26734021

A stochastic model for tumor geometry evolution during radiation therapy in cervical cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Liu, Yifang; Lee, Chi-Guhn; Chan, Timothy C. Y., E-mail: tcychan@mie.utoronto.ca

2014-02-15

Purpose: To develop mathematical models to predict the evolution of tumor geometry in cervical cancer undergoing radiation therapy. Methods: The authors develop two mathematical models to estimate tumor geometry change: a Markov model and an isomorphic shrinkage model. The Markov model describes tumor evolution by investigating the change in state (either tumor or nontumor) of voxels on the tumor surface. It assumes that the evolution follows a Markov process. Transition probabilities are obtained using maximum likelihood estimation and depend on the states of neighboring voxels. The isomorphic shrinkage model describes tumor shrinkage or growth in terms of layers of voxelsmore » on the tumor surface, instead of modeling individual voxels. The two proposed models were applied to data from 29 cervical cancer patients treated at Princess Margaret Cancer Centre and then compared to a constant volume approach. Model performance was measured using sensitivity and specificity. Results: The Markov model outperformed both the isomorphic shrinkage and constant volume models in terms of the trade-off between sensitivity (target coverage) and specificity (normal tissue sparing). Generally, the Markov model achieved a few percentage points in improvement in either sensitivity or specificity compared to the other models. The isomorphic shrinkage model was comparable to the Markov approach under certain parameter settings. Convex tumor shapes were easier to predict. Conclusions: By modeling tumor geometry change at the voxel level using a probabilistic model, improvements in target coverage and normal tissue sparing are possible. Our Markov model is flexible and has tunable parameters to adjust model performance to meet a range of criteria. Such a model may support the development of an adaptive paradigm for radiation therapy of cervical cancer.« less

Biomechanical trade-offs bias rates of evolution in the feeding apparatus of fishes

PubMed Central

Holzman, Roi; Collar, David C.; Price, Samantha A.; Hulsey, C. Darrin; Thomson, Robert C.; Wainwright, Peter C.

2012-01-01

Morphological diversification does not proceed evenly across the organism. Some body parts tend to evolve at higher rates than others, and these rate biases are often attributed to sexual and natural selection or to genetic constraints. We hypothesized that variation in the rates of morphological evolution among body parts could also be related to the performance consequences of the functional systems that make up the body. Specifically, we tested the widely held expectation that the rate of evolution for a trait is negatively correlated with the strength of biomechanical trade-offs to which it is exposed. We quantified the magnitude of trade-offs acting on the morphological components of three feeding-related functional systems in four radiations of teleost fishes. After accounting for differences in the rates of morphological evolution between radiations, we found that traits that contribute more to performance trade-offs tend to evolve more rapidly, contrary to the prediction. While ecological and genetic factors are known to have strong effects on rates of phenotypic evolution, this study highlights the role of the biomechanical architecture of functional systems in biasing the rates and direction of trait evolution. PMID:21993506

Biomechanical trade-offs bias rates of evolution in the feeding apparatus of fishes.

PubMed

Holzman, Roi; Collar, David C; Price, Samantha A; Hulsey, C Darrin; Thomson, Robert C; Wainwright, Peter C

2012-04-07

Morphological diversification does not proceed evenly across the organism. Some body parts tend to evolve at higher rates than others, and these rate biases are often attributed to sexual and natural selection or to genetic constraints. We hypothesized that variation in the rates of morphological evolution among body parts could also be related to the performance consequences of the functional systems that make up the body. Specifically, we tested the widely held expectation that the rate of evolution for a trait is negatively correlated with the strength of biomechanical trade-offs to which it is exposed. We quantified the magnitude of trade-offs acting on the morphological components of three feeding-related functional systems in four radiations of teleost fishes. After accounting for differences in the rates of morphological evolution between radiations, we found that traits that contribute more to performance trade-offs tend to evolve more rapidly, contrary to the prediction. While ecological and genetic factors are known to have strong effects on rates of phenotypic evolution, this study highlights the role of the biomechanical architecture of functional systems in biasing the rates and direction of trait evolution.

[Clinical value of MRI united-sequences examination in diagnosis and differentiation of morphological sub-type of hilar and extrahepatic big bile duct cholangiocarcinoma].

PubMed

Yin, Long-Lin; Song, Bin; Guan, Ying; Li, Ying-Chun; Chen, Guang-Wen; Zhao, Li-Ming; Lai, Li

2014-09-01

To investigate MRI features and associated histological and pathological changes of hilar and extrahepatic big bile duct cholangiocarcinoma with different morphological sub-types, and its value in differentiating between nodular cholangiocarcinoma (NCC) and intraductal growing cholangiocarcinoma (IDCC). Imaging data of 152 patients with pathologically confirmed hilar and extrahepatic big bile duct cholangiocarcinoma were reviewed, which included 86 periductal infiltrating cholangiocarcinoma (PDCC), 55 NCC, and 11 IDCC. Imaging features of the three morphological sub-types were compared. Each of the subtypes demonstrated its unique imaging features. Significant differences (P < 0.05) were found between NCC and IDCC in tumor shape, dynamic enhanced pattern, enhancement degree during equilibrium phase, multiplicity or singleness of tumor, changes in wall and lumen of bile duct at the tumor-bearing segment, dilatation of tumor upstream or downstream bile duct, and invasion of adjacent organs. Imaging features reveal tumor growth patterns of hilar and extrahepatic big bile duct cholangiocarcinoma. MRI united-sequences examination can accurately describe those imaging features for differentiation diagnosis.

Convergent, Parallel and Correlated Evolution of Trophic Morphologies in the Subfamily Schizothoracinae from the Qinghai-Tibetan Plateau

PubMed Central

Qi, Delin; Chao, Yan; Guo, Songchang; Zhao, Lanying; Li, Taiping; Wei, Fulei; Zhao, Xinquan

2012-01-01

Schizothoracine fishes distributed in the water system of the Qinghai-Tibetan plateau (QTP) and adjacent areas are characterized by being highly adaptive to the cold and hypoxic environment of the plateau, as well as by a high degree of diversity in trophic morphology due to resource polymorphisms. Although convergent and parallel evolution are prevalent in the organisms of the QTP, it remains unknown whether similar evolutionary patterns have occurred in the schizothoracine fishes. Here, we constructed for the first time a tentative molecular phylogeny of the schizothoracine fishes based on the complete sequences of the cytochrome b gene. We employed this molecular phylogenetic framework to examine the evolution of trophic morphologies. We used Pagel's maximum likelihood method to estimate the evolutionary associations of trophic morphologies and food resource use. Our results showed that the molecular and published morphological phylogenies of Schizothoracinae are partially incongruent with respect to some intergeneric relationships. The phylogenetic results revealed that four character states of five trophic morphologies and of food resource use evolved at least twice during the diversification of the subfamily. State transitions are the result of evolutionary patterns including either convergence or parallelism or both. Furthermore, our analyses indicate that some characters of trophic morphologies in the Schizothoracinae have undergone correlated evolution, which are somewhat correlated with different food resource uses. Collectively, our results reveal new examples of convergent and parallel evolution in the organisms of the QTP. The adaptation to different trophic niches through the modification of trophic morphologies and feeding behaviour as found in the schizothoracine fishes may account for the formation and maintenance of the high degree of diversity and radiations in fish communities endemic to QTP. PMID:22470515

Repeated and Time-Correlated Morphological Convergence in Cave-Dwelling Harvestmen (Opiliones, Laniatores) from Montane Western North America

PubMed Central

Derkarabetian, Shahan; Steinmann, David B.; Hedin, Marshal

2010-01-01

Background Many cave-dwelling animal species display similar morphologies (troglomorphism) that have evolved convergent within and among lineages under the similar selective pressures imposed by cave habitats. Here we study such ecomorphological evolution in cave-dwelling Sclerobuninae harvestmen (Opiliones) from the western United States, providing general insights into morphological homoplasy, rates of morphological change, and the temporal context of cave evolution. Methodology/Principal Findings We gathered DNA sequence data from three independent gene regions, and combined these data with Bayesian hypothesis testing, morphometrics analysis, study of penis morphology, and relaxed molecular clock analyses. Using multivariate morphometric analysis, we find that phylogenetically unrelated taxa have convergently evolved troglomorphism; alternative phylogenetic hypotheses involving less morphological convergence are not supported by Bayesian hypothesis testing. In one instance, this morphology is found in specimens from a high-elevation stony debris habitat, suggesting that troglomorphism can evolve in non-cave habitats. We discovered a strong positive relationship between troglomorphy index and relative divergence time, making it possible to predict taxon age from morphology. Most of our time estimates for the origin of highly-troglomorphic cave forms predate the Pleistocene. Conclusions/Significance While several regions in the eastern and central United States are well-known hotspots for cave evolution, few modern phylogenetic studies have addressed the evolution of cave-obligate species in the western United States. Our integrative studies reveal the recurrent evolution of troglomorphism in a perhaps unexpected geographic region, at surprisingly deep time depths, and in sometimes surprising habitats. Because some newly discovered troglomorphic populations represent undescribed species, our findings stress the need for further biological exploration, integrative systematic research, and conservation efforts in western US cave habitats. PMID:20479884

Prognostic factors of phyllodes tumor of the breast.

PubMed

Roa, Juan Carlos; Tapia, Oscar; Carrasco, Paula; Contreras, Enrique; Araya, Juan Carlos; Muñoz, Sergio; Roa, Iván

2006-06-01

The phyllodes tumor is characterized by its tendency to recur locally and occasionally to metastasize. The purpose of the present paper was to assess the prognostic value of clinical-morphological characteristics in patients with phyllodes tumor. Forty-seven cases of phyllodes tumors was studied; the World Health Organization classification was used and follow up was obtained. A total of 51%, 28% and 21% of the tumors were classified as benign, borderline and malignant, respectively. The adherence (P = 0.01), size >10 cm (P = 0.001), high mitotic activity (P = 0.03), infiltrative tumor margin (P = 0.0002) and type of surgery in malignant tumors (P = 0.02) proved to be good predictors of relapse. The presence of pain (P = 0.03), postmenopausal status (P < 0.04), heavy cellular pleomorphism (P = 0.007), high mitotic activity (P = 0.002), tumoral grade (P = 0.006) and metastasis (P < 0.00001) were prognostic factors of poor survival. Tumoral grade and some clinical-morphological characteristics of patients with phyllodes tumors have a significant impact on the prediction of its biological behavior.

Melanoma exosomes deliver a complex biological payload that upregulates PTPN11 to suppress T lymphocyte function

PubMed Central

Wu, Yueting; Deng, Wentao; McGinley, Emily Chambers; Klinke, David J.

2017-01-01

Summary As exosomes are emerging as a new mode of intercellular communication, we hypothesized that the payload contained within exosomes is shaped by somatic evolution. To test this, we assayed the impact on primary CD8+ T cell function, a key mechanism for anti-tumor immunity, of exosomes derived from three melanoma-related cell lines. While morphologically similar, exosomes from each cell line were functionally different, as B16F0 exosomes dose-dependently suppressed T cell proliferation. In contrast, Cloudman S91 exosomes promoted T cell proliferation and Melan-A exosomes had a negligible effect on primary CD8+ T cells. Mechanistically, transcript profiling suggested that exosomal mRNA is enriched for full-length mRNAs that target immune-related pathways. Interestingly, B16F0 exosomes were unique in that they contained both protein and mRNA for Ptpn11, which inhibited T cell proliferation. Collectively, the results suggest that upregulation of PTPN11 by B16F0 exosomes to tumor infiltrating lymphocytes would bypass the extracellular control of the immune checkpoints. PMID:27930879

Warthin Tumor-Like Mucoepidermoid Carcinoma.

PubMed

Heatley, Nicholas; Harrington, Kevin J; Thway, Khin

2018-02-01

Mucoepidermoid carcinoma (MEC) shows a wide morphologic spectrum, including epithelium with oncocytic or squamous metaplastic changes overlying a prominent cystic architecture, as well as tumor-associated lymphoid tissue. We illustrate a case of MEC of the parotid in a 17-year-old female, in which all these features occurred extensively, such that they accounted for almost the entire neoplasm, and closely mimicked Warthin tumor histologically. This highlights the need for diagnostic awareness of this particular morphologic variant of MEC, as patients could potentially be inappropriately discharged from follow-up if diagnosed with a benign neoplasm.

[Outstanding problems of normal and pathological morphology of the diffuse endocrine system].

PubMed

Iaglov, V V; Iaglova, N V

2011-01-01

The diffuse endocrine system (DES)--a mosaic-cellular endoepithelial gland--is the biggest part of the human endocrine system. Scientists used to consider cells of DES as neuroectodermal. According to modem data cells of DES are different cytogenetic types because they develop from the different embryonic blastophyllum. So that any hormone-active tumors originated from DES of the digestive, respiratory and urogenital system shouldn't be considered as neuroendocrinal tumors. The basic problems of DES morphology and pathology are the creation of scientifically substantiated histogenetic classification of DES tumors.

Endocranial morphology of Palaeocene Plesiadapis tricuspidens and evolution of the early primate brain.

PubMed

Orliac, Maeva J; Ladevèze, Sandrine; Gingerich, Philip D; Lebrun, Renaud; Smith, Thierry

2014-04-22

Expansion of the brain is a key feature of primate evolution. The fossil record, although incomplete, allows a partial reconstruction of changes in primate brain size and morphology through time. Palaeogene plesiadapoids, closest relatives of Euprimates (or crown-group primates), are crucial for understanding early evolution of the primate brain. However, brain morphology of this group remains poorly documented, and major questions remain regarding the initial phase of euprimate brain evolution. Micro-CT investigation of the endocranial morphology of Plesiadapis tricuspidens from the Late Palaeocene of Europe--the most complete plesiadapoid cranium known--shows that plesiadapoids retained a very small and simple brain. Plesiadapis has midbrain exposure, and minimal encephalization and neocorticalization, making it comparable with that of stem rodents and lagomorphs. However, Plesiadapis shares a domed neocortex and downwardly shifted olfactory-bulb axis with Euprimates. If accepted phylogenetic relationships are correct, then this implies that the euprimate brain underwent drastic reorganization during the Palaeocene, and some changes in brain structure preceded brain size increase and neocortex expansion during evolution of the primate brain.

Temporal morphologic changes in human colorectal carcinomas following xenografting.

PubMed Central

Barkla, D. H.; Tutton, P. J.

1983-01-01

The temporal morphologic changes of human colorectal carcinomas following xenografting into immunosuppressed mice were investigated by the use of light and transmission electron microscopy. The results show that colorectal carcinomas undergo a series of morphologic changes during the initial 30-day period following transplantation. During the initial 1-5-day period the majority of tumor cells die, and during the following 5-10-day period the necrotic debris created during the 1-5-day period is removed by host-supplied inflammatory cells. Only small groups of peripherally placed tumor cells survived at the end of the first 10 days. During the 10-20-day period the tumor cell populations of xenografts were reestablished by a morphologically heterogeneous population of tumor cells, and during the 20-30 day period consolidation of this process continued and some xenografts showed macroscopic evidence of growth. The authors hypothesize that human colorectal carcinomas, like the antecedent epithelium, contain subpopulations of undifferentiated cells that give rise to populations of more-differentiated cells. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Figure 8 Figure 9 Figure 10 Figure 11 Figure 12 PMID:6829710

Dietary hardness, loading behavior, and the evolution of skull form in bats.

PubMed

Santana, Sharlene E; Grosse, Ian R; Dumont, Elizabeth R

2012-08-01

The morphology and biomechanics of the vertebrate skull reflect the physical properties of diet and behaviors used in food acquisition and processing. We use phyllostomid bats, the most diverse mammalian dietary radiation, to investigate if and how changes in dietary hardness and loading behaviors during feeding shaped the evolution of skull morphology and biomechanics. When selective regimes of food hardness are modeled, we found that species consuming harder foods have evolved skull shapes that allow for more efficient bite force production. These species have shorter skulls and a greater reliance on the temporalis muscle, both of which contribute to a higher mechanical advantage at an intermediate gape angle. The evolution of cranial morphology and biomechanics also appears to be related to loading behaviors. Evolutionary changes in skull shape and the relative role of the temporalis and masseter in generating bite force are correlated with changes in the use of torsional and bending loading behaviors. Functional equivalence appears to have evolved independently among three lineages of species that feed on liquids and are not obviously morphologically similar. These trends in cranial morphology and biomechanics provide insights into behavioral and ecological factors shaping the skull of a trophically diverse clade of mammals. © 2012 The Author(s). Evolution© 2012 The Society for the Study of Evolution.

Bi-stage time evolution of nano-morphology on inductively coupled plasma etched fused silica surface caused by surface morphological transformation

NASA Astrophysics Data System (ADS)

Jiang, Xiaolong; Zhang, Lijuan; Bai, Yang; Liu, Ying; Liu, Zhengkun; Qiu, Keqiang; Liao, Wei; Zhang, Chuanchao; Yang, Ke; Chen, Jing; Jiang, Yilan; Yuan, Xiaodong

2017-07-01

In this work, we experimentally investigate the surface nano-roughness during the inductively coupled plasma etching of fused silica, and discover a novel bi-stage time evolution of surface nano-morphology. At the beginning, the rms roughness, correlation length and nano-mound dimensions increase linearly and rapidly with etching time. At the second stage, the roughening process slows down dramatically. The switch of evolution stage synchronizes with the morphological change from dual-scale roughness comprising long wavelength underlying surface and superimposed nano-mounds to one scale of nano-mounds. A theoretical model based on surface morphological change is proposed. The key idea is that at the beginning, etched surface is dual-scale, and both larger deposition rate of etch inhibitors and better plasma etching resistance at the surface peaks than surface valleys contribute to the roughness development. After surface morphology transforming into one-scale, the difference of plasma resistance between surface peaks and valleys vanishes, thus the roughening process slows down.

Modelling morphology evolution during solidification of IPP in processing conditions

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pantani, R., E-mail: rpantani@unisa.it, E-mail: fedesantis@unisa.it, E-mail: vsperanza@unisa.it, E-mail: gtitomanlio@unisa.it; De Santis, F., E-mail: rpantani@unisa.it, E-mail: fedesantis@unisa.it, E-mail: vsperanza@unisa.it, E-mail: gtitomanlio@unisa.it; Speranza, V., E-mail: rpantani@unisa.it, E-mail: fedesantis@unisa.it, E-mail: vsperanza@unisa.it, E-mail: gtitomanlio@unisa.it

During polymer processing, crystallization takes place during or soon after flow. In most of cases, the flow field dramatically influences both the crystallization kinetics and the crystal morphology. On their turn, crystallinity and morphology affect product properties. Consequently, in the last decade, researchers tried to identify the main parameters determining crystallinity and morphology evolution during solidification In processing conditions. In this work, we present an approach to model flow-induced crystallization with the aim of predicting the morphology after processing. The approach is based on: interpretation of the FIC as the effect of molecular stretch on the thermodynamic crystallization temperature; modelingmore » the molecular stretch evolution by means of a model simple and easy to be implemented in polymer processing simulation codes; identification of the effect of flow on nucleation density and spherulites growth rate by means of simple experiments; determination of the condition under which fibers form instead of spherulites. Model predictions reproduce most of the features of final morphology observed in the samples after solidification.« less

Evolution of complex fruiting-body morphologies in homobasidiomycetes.

PubMed Central

Hibbett, David S; Binder, Manfred

2002-01-01

The fruiting bodies of homobasidiomycetes include some of the most complex forms that have evolved in the fungi, such as gilled mushrooms, bracket fungi and puffballs ('pileate-erect') forms. Homobasidiomycetes also include relatively simple crust-like 'resupinate' forms, however, which account for ca. 13-15% of the described species in the group. Resupinate homobasidiomycetes have been interpreted either as a paraphyletic grade of plesiomorphic forms or a polyphyletic assemblage of reduced forms. The former view suggests that morphological evolution in homobasidiomycetes has been marked by independent elaboration in many clades, whereas the latter view suggests that parallel simplification has been a common mode of evolution. To infer patterns of morphological evolution in homobasidiomycetes, we constructed phylogenetic trees from a dataset of 481 species and performed ancestral state reconstruction (ASR) using parsimony and maximum likelihood (ML) methods. ASR with both parsimony and ML implies that the ancestor of the homobasidiomycetes was resupinate, and that there have been multiple gains and losses of complex forms in the homobasidiomycetes. We also used ML to address whether there is an asymmetry in the rate of transformations between simple and complex forms. Models of morphological evolution inferred with ML indicate that the rate of transformations from simple to complex forms is about three to six times greater than the rate of transformations in the reverse direction. A null model of morphological evolution, in which there is no asymmetry in transformation rates, was rejected. These results suggest that there is a 'driven' trend towards the evolution of complex forms in homobasidiomycetes. PMID:12396494

RCL2, a New Fixative, Preserves Morphology and Nucleic Acid Integrity in Paraffin-Embedded Breast Carcinoma and Microdissected Breast Tumor Cells

PubMed Central

Delfour, Christophe; Roger, Pascal; Bret, Caroline; Berthe, Marie-Laurence; Rochaix, Philippe; Kalfa, Nicolas; Raynaud, Pierre; Bibeau, Frédéric; Maudelonde, Thierry; Boulle, Nathalie

2006-01-01

Methacarn and RCL2, a new noncrosslinking fixative, were compared to formalin-fixed or frozen tissue samples of the same invasive breast carcinoma and were evaluated for their effects on tissue morphology and immunohistochemistry as well as DNA and RNA integrity. The histomorphology of methacarn- or RCL2-fixed paraffin-embedded tumors was similar to that observed with the matched formalin-fixed tissues. Immunohistochemistry using various antibodies showed comparable results with either fixative, leading to accurate breast tumor diagnosis and determination of estrogen and progesterone receptors, and HER2 status. Methacarn and RCL2 fixation preserved DNA integrity as demonstrated by successful amplification and sequencing of large DNA amplicons. Similarly, high-quality RNA could be extracted from methacarn- or RCL2-fixed paraffin-embedded MCF-7 cells, whole breast tumor tissues, or microdissected breast tumor cells, as assessed by electropherogram profiles and real-time reverse transcriptase-polymerase chain reaction quantification of various genes. Moreover, tissue morphology and RNA integrity were preserved after 8 months of storage. Altogether, these results indicate that methacarn, as previously shown, and RCL2, a promising new fixative, have great potential for performing both morphological and molecular analyses on the same fixed tissue sample, even after laser-capture microdissection, and can open new doors for investigating small target lesions such as premalignant breast lesions. PMID:16645201

Molecular genetics of pancreatic neoplasms and their morphologic correlates: an update on recent advances and potential diagnostic applications.

PubMed

Reid, Michelle D; Saka, Burcu; Balci, Serdar; Goldblum, Andrew S; Adsay, N Volkan

2014-02-01

To summarize the most clinically and biologically relevant advances in molecular/genetic characteristics of various pancreatic neoplasms, with morphologic correlation. Whole-exome sequencing of numerous benign and malignant pancreatic tumors, along with the plethora of highly sensitive molecular studies now available for analyzing these tumors, provide mounting evidence to support the long-held belief that cancer is essentially a genetic disease. These genetic discoveries have not only helped to confirm the age-old, morphology-based classifications of pancreatic neoplasia but have shed new light on their mechanisms. Many of these molecular discoveries are currently being used in preoperative diagnosis. Mutations in KRAS, P16/CDKN2A, TP53, and SMAD4/DPC4 are commonly seen in ductal neoplasia but not in nonductal tumors; ductal adenocarcinomas with SMAD4/DPC4 loss are associated with widespread metastasis and poor prognosis. GNAS and RNF43 mutations have been discovered in most intraductal pancreatic mucinous neoplasms, providing critical molecular fingerprints for their diagnosis. Mutation in DAXX/ATRX is only seen in pancreatic neuroendocrine tumors, making it a useful potential marker in distinguishing these tumors from mimics. When combined with morphologic observations, molecular studies will increase our understanding of the pathogenesis and morphomolecular signatures associated with specific neoplasms and provide new horizons for precision medicine and targeted therapies.

Gastrin-releasing peptide receptor (GRPr) promotes EMT, growth, and invasion in canine prostate cancer.

PubMed

Elshafae, Said M; Hassan, Bardes B; Supsavhad, Wachiraphan; Dirksen, Wessel P; Camiener, Rachael Y; Ding, Haiming; Tweedle, Michael F; Rosol, Thomas J

2016-06-01

The gastrin-releasing peptide receptor (GRPr) is upregulated in early and late-stage human prostate cancer (PCa) and other solid tumors of the mammary gland, lung, head and neck, colon, uterus, ovary, and kidney. However, little is known about its role in prostate cancer. This study examined the effects of a heterologous GRPr agonist, bombesin (BBN), on growth, motility, morphology, gene expression, and tumor phenotype of an osteoblastic canine prostate cancer cell line (Ace-1) in vitro and in vivo. The Ace-1 cells were stably transfected with the human GRPr and tumor cells were grown in vitro and as subcutaneous and intratibial tumors in nude mice. The effect of BBN was measured on cell proliferation, cell migration, tumor growth (using bioluminescence), tumor cell morphology, bone tumor phenotype, and epithelial-mesenchymal transition (EMT) and metastasis gene expression (quantitative RT-PCR). GRPr mRNA expression was measured in primary canine prostate cancers and normal prostate glands. Bombesin (BBN) increased tumor cell proliferation and migration in vitro and tumor growth and invasion in vivo. BBN upregulated epithelial-to-mesenchymal transition (EMT) markers (TWIST, SNAIL, and SLUG mRNA) and downregulated epithelial markers (E-cadherin and β-catenin mRNA), and modified tumor cell morphology to a spindle cell phenotype. Blockade of GRPr upregulated E-cadherin and downregulated VIMENTIN and SNAIL mRNA. BBN altered the in vivo tumor phenotype in bone from an osteoblastic to osteolytic phenotype. Primary canine prostate cancers had increased GRPr mRNA expression compared to normal prostates. These data demonstrated that the GRPr is important in prostate cancer growth and progression and targeting GRPr may be a promising strategy for treatment of prostate cancer. Prostate 76:796-809, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

OncoNEM: inferring tumor evolution from single-cell sequencing data.

PubMed

Ross, Edith M; Markowetz, Florian

2016-04-15

Single-cell sequencing promises a high-resolution view of genetic heterogeneity and clonal evolution in cancer. However, methods to infer tumor evolution from single-cell sequencing data lag behind methods developed for bulk-sequencing data. Here, we present OncoNEM, a probabilistic method for inferring intra-tumor evolutionary lineage trees from somatic single nucleotide variants of single cells. OncoNEM identifies homogeneous cellular subpopulations and infers their genotypes as well as a tree describing their evolutionary relationships. In simulation studies, we assess OncoNEM's robustness and benchmark its performance against competing methods. Finally, we show its applicability in case studies of muscle-invasive bladder cancer and essential thrombocythemia.

Advances for studying clonal evolution in cancer.

PubMed

Ding, Li; Raphael, Benjamin J; Chen, Feng; Wendl, Michael C

2013-11-01

The "clonal evolution" model of cancer emerged and "evolved" amid ongoing advances in technology, especially in recent years during which next generation sequencing instruments have provided ever higher resolution pictures of the genetic changes in cancer cells and heterogeneity in tumors. It has become increasingly clear that clonal evolution is not a single sequential process, but instead frequently involves simultaneous evolution of multiple subclones that co-exist because they are of similar fitness or are spatially separated. Co-evolution of subclones also occurs when they complement each other's survival advantages. Recent studies have also shown that clonal evolution is highly heterogeneous: different individual tumors of the same type may undergo very different paths of clonal evolution. New methodological advancements, including deep digital sequencing of a mixed tumor population, single cell sequencing, and the development of more sophisticated computational tools, will continue to shape and reshape the models of clonal evolution. In turn, these will provide both an improved framework for the understanding of cancer progression and a guide for treatment strategies aimed at the elimination of all, rather than just some, of the cancer cells within a patient. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Establishment and characterization of in vivo orthotopic bioluminescent xenograft models from human osteosarcoma cell lines in Swiss nude and NSG mice.

PubMed

Marques da Costa, Maria Eugenia; Daudigeos-Dubus, Estelle; Gomez-Brouchet, Anne; Bawa, Olivia; Rouffiac, Valerie; Serra, Massimo; Scotlandi, Katia; Santos, Conceição; Geoerger, Birgit; Gaspar, Nathalie

2018-03-01

Osteosarcoma is one of the most common primary bone tumors in childhood and adolescence. Metastases occurrence at diagnosis or during disease evolution is the main therapeutic challenge. New drug evaluation to improve patient survival requires the development of various preclinical models mimicking at best the complexity of the disease and its metastatic potential. We describe here the development and characteristics of two orthotopic bioluminescent (Luc/mKate2) cell-derived xenograft (CDX) models, Saos-2-B-Luc/mKate2-CDX and HOS-Luc/mKate2-CDX, in different immune (nude and NSG mouse strains) and bone (intratibial and paratibial with periosteum activation) contexts. IVIS SpectrumCT system allowed both longitudinal computed tomography (CT) and bioluminescence real-time follow-up of primary tumor growth and metastatic spread, which was confirmed by histology. The murine immune context influenced tumor engraftment, primary tumor growth, and metastatic spread to lungs, bone, and spleen (an unusual localization in humans). Engraftment in NSG mice was found superior to that found in nude mice and intratibial bone environment more favorable to engraftment compared to paratibial injection. The genetic background of the two CDX models also led to distinct primary tumor behavior observed on CT scan. Saos-2-B-Luc/mKate2-CDX showed osteocondensed, HOS-Luc/mKate2-CDX osteolytic morphology. Bioluminescence defined a faster growth of the primary tumor and metastases in Saos-2-B-Luc/mKate2-CDX than in HOS-Luc/mKate2-CDX. The early detection of primary tumor growth and metastatic spread by bioluminescence allows an improved exploration of osteosarcoma disease at tumor progression, and metastatic spread, as well as the evaluations of anticancer treatments. Our orthotopic models with metastatic spread bring complementary information to other types of existing osteosarcoma models. © 2018 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

Extensive morphological divergence and rapid evolution of the larval neuromuscular junction in Drosophila.

PubMed

Campbell, Megan; Ganetzky, Barry

2012-03-13

Although the complexity and circuitry of nervous systems undergo evolutionary change, we lack understanding of the general principles and specific mechanisms through which it occurs. The Drosophila larval neuromuscular junction (NMJ), which has been widely used for studies of synaptic development and function, is also an excellent system for studies of synaptic evolution because the genus spans >40 Myr of evolution and the same identified synapse can be examined across the entire phylogeny. We have now characterized morphology of the NMJ on muscle 4 (NMJ4) in >20 species of Drosophila. Although there is little variation within a species, NMJ morphology and complexity vary extensively between species. We find no significant correlation between NMJ phenotypes and phylogeny for the species examined, suggesting that drift alone cannot explain the phenotypic variation and that selection likely plays an important role. However, the nature of the selective pressure is still unclear because basic parameters of synaptic function remain uniform. Whatever the mechanism, NMJ morphology is evolving rapidly in comparison with other morphological features because NMJ phenotypes differ even between several sibling species pairs. The discovery of this unexpectedly extensive divergence in NMJ morphology among Drosophila species provides unique opportunities to investigate mechanisms that regulate synaptic growth; the interrelationships between synaptic morphology, neural function, and behavior; and the evolution of nervous systems and behavior in natural populations.

Translational Implications of Tumor Heterogeneity

PubMed Central

Jamal-Hanjani, Mariam; Quezada, Sergio A.; Larkin, James; Swanton, Charles

2015-01-01

Advances in next-generation sequencing and bioinformatics have led to an unprecedented view of the cancer genome and its evolution. Genomic studies have demonstrated the complex and heterogeneous clonal landscape of tumors of different origins, and the potential impact of intratumor heterogeneity on treatment response and resistance, cancer progression and the risk of disease relapse. However, the significance of subclonal mutations, in particular mutations in driver genes, and their evolution through time and their dynamics in response to cancer therapies, is yet to be determined. The necessary tools are now available to prospectively determine whether clonal heterogeneity can be used as a biomarker of clinical outcome, and to what extent subclonal somatic alterations might influence clinical outcome. Studies that employ longitudinal tissue sampling, integrating both genomic and clinical data, have the potential to reveal the subclonal composition and track the evolution of tumors in order to address these questions, and to begin to define the breadth of genetic diversity in different tumor types, and its relevance to patient outcome. Such studies may provide further evidence for novel drug resistance mechanisms informing novel combinatorial, adaptive and tumour immune-therapies placed within the context of tumor evolution. PMID:25770293

Cancer Evolution: Mathematical Models and Computational Inference

PubMed Central

Beerenwinkel, Niko; Schwarz, Roland F.; Gerstung, Moritz; Markowetz, Florian

2015-01-01

Cancer is a somatic evolutionary process characterized by the accumulation of mutations, which contribute to tumor growth, clinical progression, immune escape, and drug resistance development. Evolutionary theory can be used to analyze the dynamics of tumor cell populations and to make inference about the evolutionary history of a tumor from molecular data. We review recent approaches to modeling the evolution of cancer, including population dynamics models of tumor initiation and progression, phylogenetic methods to model the evolutionary relationship between tumor subclones, and probabilistic graphical models to describe dependencies among mutations. Evolutionary modeling helps to understand how tumors arise and will also play an increasingly important prognostic role in predicting disease progression and the outcome of medical interventions, such as targeted therapy. PMID:25293804

Morphological evolution, ecological diversification and climate change in rodents.

PubMed

Renaud, Sabrina; Michaux, Jacques; Schmidt, Daniela N; Aguilar, Jean-Pierre; Mein, Pierre; Auffray, Jean-Christophe

2005-03-22

Among rodents, the lineage from Progonomys hispanicus to Stephanomys documents a case of increasing size and dental specialization during an approximately 9 Myr time-interval. On the contrary, some contemporaneous generalist lineages like Apodemus show a limited morphological evolution. Dental shape can be related to diet and can be used to assess the ecological changes along the lineages. Consequently, size and shape of the first upper molar were measured in order to quantify the patterns of morphological evolution along both lineages and compare them to environmental trends. Climatic changes do not have a direct influence on evolution, but they open new ecological opportunities by changing vegetation and allow the evolution of a specialist like Stephanomys. On the other hand, environmental changes are not dramatic enough to destroy the habitat of a long-term generalist like Apodemus. Hence, our results exemplify a case of an influence of climate on the evolution of specialist species, although a generalist species may persist without change.

Morphological evolution, ecological diversification and climate change in rodents

PubMed Central

Renaud, Sabrina; Michaux, Jacques; Schmidt, Daniela N; Aguilar, Jean-Pierre; Mein, Pierre; Auffray, Jean-Christophe

2005-01-01

Among rodents, the lineage from Progonomys hispanicus to Stephanomys documents a case of increasing size and dental specialization during an approximately 9 Myr time-interval. On the contrary, some contemporaneous generalist lineages like Apodemus show a limited morphological evolution. Dental shape can be related to diet and can be used to assess the ecological changes along the lineages. Consequently, size and shape of the first upper molar were measured in order to quantify the patterns of morphological evolution along both lineages and compare them to environmental trends. Climatic changes do not have a direct influence on evolution, but they open new ecological opportunities by changing vegetation and allow the evolution of a specialist like Stephanomys. On the other hand, environmental changes are not dramatic enough to destroy the habitat of a long-term generalist like Apodemus. Hence, our results exemplify a case of an influence of climate on the evolution of specialist species, although a generalist species may persist without change. PMID:15817435

Spontaneous Renal Tumors Suspected of Being Familial in Sprague-Dawley Rats

PubMed Central

Kudo, Kayoko; Hoshiya, Toru; Nakazawa, Tomomi; Saito, Tsubasa; Shimoyama, Natsumi; Suzuki, Isamu; Tamura, Kazutoshi; Seely, John Curtis

2012-01-01

Spontaneous renal tubule tumors (RTTs), with a distinctive morphological phenotype, were present in three Sprague-Dawley rats, 1 male and 2 females, out a total of 120 animals of each sex from untreated and placebo control groups in a 2-year carcinogenicity study. One female had one carcinoma, adenoma and hyperplasia, and the other female had five adenomas and many hyperplastic lesions; the male case had one carcinoma. From these cases, a biological continuum of hyperplasia, adenoma and carcinoma could be recognized. The tumors were present in the renal cortex and appeared as solid lobulated growths with occasional central necrosis. The lobules were divided by a small amount of fibrovascular tissue. Occasionally the larger tumors contained a cystic area. Tumor cells appeared distinctive and exhibited variable amounts of eosinophilic/amphophilic and vacuolated cytoplasm. Nuclei were round to oval with a prominent nucleolus. Mitotic figures were uncommon, and no distant metastasis was noted. The tumors were seen as multiple and bilateral lesions in two animals and had no apparent relationship to chronic progressive nephropathy (CPN). Foci of tubule hyperplasia were also noted to contain the same type of cellular morphology. The morphological and biological features of these 3 cases resembled the amphophilic-vacuolar (AV) variant of RTT that has been posited to be of familial origin. This is a report of spontaneous familial renal tumors in Sprague-Dawley rats from Japan. PMID:23345931

Spontaneous renal tumors suspected of being familial in sprague-dawley rats.

PubMed

Kudo, Kayoko; Hoshiya, Toru; Nakazawa, Tomomi; Saito, Tsubasa; Shimoyama, Natsumi; Suzuki, Isamu; Tamura, Kazutoshi; Seely, John Curtis

2012-12-01

Spontaneous renal tubule tumors (RTTs), with a distinctive morphological phenotype, were present in three Sprague-Dawley rats, 1 male and 2 females, out a total of 120 animals of each sex from untreated and placebo control groups in a 2-year carcinogenicity study. One female had one carcinoma, adenoma and hyperplasia, and the other female had five adenomas and many hyperplastic lesions; the male case had one carcinoma. From these cases, a biological continuum of hyperplasia, adenoma and carcinoma could be recognized. The tumors were present in the renal cortex and appeared as solid lobulated growths with occasional central necrosis. The lobules were divided by a small amount of fibrovascular tissue. Occasionally the larger tumors contained a cystic area. Tumor cells appeared distinctive and exhibited variable amounts of eosinophilic/amphophilic and vacuolated cytoplasm. Nuclei were round to oval with a prominent nucleolus. Mitotic figures were uncommon, and no distant metastasis was noted. The tumors were seen as multiple and bilateral lesions in two animals and had no apparent relationship to chronic progressive nephropathy (CPN). Foci of tubule hyperplasia were also noted to contain the same type of cellular morphology. The morphological and biological features of these 3 cases resembled the amphophilic-vacuolar (AV) variant of RTT that has been posited to be of familial origin. This is a report of spontaneous familial renal tumors in Sprague-Dawley rats from Japan.

Identifying heterogeneity in rates of morphological evolution: discrete character change in the evolution of lungfish (Sarcopterygii; Dipnoi).

PubMed

Lloyd, Graeme T; Wang, Steve C; Brusatte, Stephen L

2012-02-01

Quantifying rates of morphological evolution is important in many macroevolutionary studies, and critical when assessing possible adaptive radiations and episodes of punctuated equilibrium in the fossil record. However, studies of morphological rates of change have lagged behind those on taxonomic diversification, and most authors have focused on continuous characters and quantifying patterns of morphological rates over time. Here, we provide a phylogenetic approach, using discrete characters and three statistical tests to determine points on a cladogram (branches or entire clades) that are characterized by significantly high or low rates of change. These methods include a randomization approach that identifies branches with significantly high rates and likelihood ratio tests that pinpoint either branches or clades that have significantly higher or lower rates than the pooled rate of the remainder of the tree. As a test case for these methods, we analyze a discrete character dataset of lungfish, which have long been regarded as "living fossils" due to an apparent slowdown in rates since the Devonian. We find that morphological rates are highly heterogeneous across the phylogeny and recover a general pattern of decreasing rates along the phylogenetic backbone toward living taxa, from the Devonian until the present. Compared with previous work, we are able to report a more nuanced picture of lungfish evolution using these new methods. © 2011 The Author(s). Evolution© 2011 The Society for the Study of Evolution.

EG-07CELL CYCLE SIGNATURE AND TUMOR PHYLOGENY ARE ENCODED IN THE EVOLUTIONARY DYNAMICS OF DNA METHYLATION IN GLIOMA

PubMed Central

Mazor, Tali; Pankov, Aleksandr; Johnson, Brett E.; Hong, Chibo; Bell, Robert J.A.; Smirnov, Ivan V.; Reis, Gerald F.; Phillips, Joanna J.; Barnes, Michael; Bollen, Andrew W.; Taylor, Barry S.; Molinaro, Annette M.; Olshen, Adam B.; Song, Jun S.; Berger, Mitchel S.; Chang, Susan M.; Costello, Joseph F.

2014-01-01

The clonal evolution of tumor cell populations can be reconstructed from patterns of genetic alterations. In contrast, tumor epigenetic states, including DNA methylation, are reversible and sensitive to the tumor microenvironment, presumably precluding the use of epigenetics to discover tumor phylogeny. Here we examined the spatial and temporal dynamics of DNA methylation in a clinically and genetically characterized cohort of IDH1-mutant low-grade gliomas and their patient-matched recurrences. WHO grade II gliomas are diffuse, infiltrative tumors that frequently recur and may undergo malignant progression to a higher grade with a worse prognosis. The extent to which epigenetic alterations contribute to the evolution of low-grade gliomas, including malignant progression, is unknown. While all gliomas in the cohort exhibited the hypermethylation signature associated with IDH1 mutation, low-grade gliomas that underwent malignant progression to high-grade glioblastoma (GBM) had a unique signature of DNA hypomethylation enriched for active enhancers, as well as sites of age-related hypermethylation in the brain. Genes with promoter hypomethylation and concordant transcriptional upregulation during evolution to GBM were enriched in cell cycle function, evolving in concert with genetic alterations that deregulate the G1/S cell cycle checkpoint. Despite the plasticity of tumor epigenetic states, phyloepigenetic trees robustly recapitulated phylogenetic trees derived from somatic mutations in the same patients. These findings highlight widespread co-dependency of genetic and epigenetic events throughout the clonal evolution of initial and recurrent glioma.

Clonal evolution and tumor-initiating cells: New dimensions in cancer patient treatment.

PubMed

Apostoli, Anthony J; Ailles, Laurie

2016-01-01

Human cancer is not a uniform disease but a plethora of disparate tumor types and subtypes. The differences that exist between individual tumors (intertumoral heterogeneity) present a significant roadblock to the eradication of cancer. It has also become increasingly clear that variations across individual tumors (intratumoral heterogeneity) have important implications to cancer progression and treatment efficacy. Therefore, in order to improve patient care and develop novel chemotherapeutics, the evolving tumor landscape needs to be further explored. Next-generation sequencing (NGS) technologies are revolutionizing the cancer research arena by providing state-of-the-art, high-speed methods of genome sequencing at single-nucleotide resolution, thus enabling an unprecedented detection of tumor-specific genetic abnormalities. These anomalies can be quantified to reveal specific frequencies of DNA alterations that correspond to distinct clonal populations within a given tumor. As such, NGS approaches have also been utilized to explore the heterogeneous landscape of patient tumors as well as to match metastatic and/or recurrent growths and patient-derived engrafts. By sequencing in this manner--through time so to speak--cancer researchers can track shifting clonal populations, make important inferences about tumor evolution and potentially identify tumor subclones that could be viably targeted. This exciting new territory has important implications for the competing clonal evolution and cancer stem cell models of tumor heterogeneity, and also offers a new dimension for cancer treatment and profound hope for patients in the coming years.

Morphology-based optical separation of subpopulations from a heterogeneous murine breast cancer cell line.

PubMed

Tamura, Masato; Sugiura, Shinji; Takagi, Toshiyuki; Satoh, Taku; Sumaru, Kimio; Kanamori, Toshiyuki; Okada, Tomoko; Matsui, Hirofumi

2017-01-01

Understanding tumor heterogeneity is an urgent and unmet need in cancer research. In this study, we used a morphology-based optical cell separation process to classify a heterogeneous cancer cell population into characteristic subpopulations. To classify the cell subpopulations, we assessed their morphology in hydrogel, a three-dimensional culture environment that induces morphological changes according to the characteristics of the cells (i.e., growth, migration, and invasion). We encapsulated the murine breast cancer cell line 4T1E, as a heterogeneous population that includes highly metastatic cells, in click-crosslinkable and photodegradable gelatin hydrogels, which we developed previously. We observed morphological changes within 3 days of encapsulating the cells in the hydrogel. We separated the 4T1E cell population into colony- and granular-type cells by optical separation, in which local UV-induced degradation of the photodegradable hydrogel around the target cells enabled us to collect those cells. The obtained colony- and granular-type cells were evaluated in vitro by using a spheroid assay and in vivo by means of a tumor growth and metastasis assay. The spheroid assay showed that the colony-type cells formed compact spheroids in 2 days, whereas the granular-type cells did not form spheroids. The tumor growth assay in mice revealed that the granular-type cells exhibited lower tumor growth and a different metastasis behavior compared with the colony-type cells. These results suggest that morphology-based optical cell separation is a useful technique to classify a heterogeneous cancer cell population according to its cellular characteristics.

Melanocytoma-like melanoma may be the missing link between benign and malignant uveal melanocytic lesions in humans and dogs: a comparative study.

PubMed

Zoroquiain, Pablo; Mayo-Goldberg, Erin; Alghamdi, Sarah; Alhumaid, Sulaiman; Perlmann, Eduardo; Barros, Paulo; Mayo, Nancy; Burnier, Miguel N

2016-12-01

The cutoff presented in the current classification of canine melanocytic lesions by Wilcock and Pfeiffer is based on the clinical outcome rather than morphological concepts. Classification of tumors based on morphology or molecular signatures is the key to identifying new therapies or prognostic factors. Therefore, the aim of this study was to analyze morphological findings in canine melanocytic lesions based on classic malignant morphologic principles of neoplasia and to compare these features with human uveal melanoma (HUM) samples. In total, 64 canine and 111 human morphologically malignant melanocytic lesions were classified into two groups (melanocytoma-like or classic melanoma) based on the presence or absence of M cells, respectively. Histopathological characteristics were compared between the two groups using the χ-test, t-test, and multivariate discriminant analysis. Among the 64 canine tumors, 28 (43.7%) were classic and 36 (56.3%) were melanocytoma-like melanomas. Smaller tumor size, a higher degree of pigmentation, and lower mitotic activity distinguished melanocytoma-like from classic tumors with an accuracy of 100% for melanocytoma-like lesions. From the human series, only one case showed melanocytoma-like features and had a low risk for metastasis characteristics. Canine uveal melanoma showed a morphological spectrum with features similar to the HUM counterpart (classic melanoma) and overlapped features between uveal melanoma and melanocytoma (melanocytoma-like melanoma). Recognition that the subgroup of melanocytoma-like melanoma may represent the missing link between benign and malignant lesions could help explain the progression of uveal melanoma in dogs; these findings can potentially be translated to HUM.

A diagnostic algorithm for atypical spitzoid tumors: guidelines for immunohistochemical and molecular assessment.

PubMed

Cho-Vega, Jeong Hee

2016-07-01

Atypical spitzoid tumors are a morphologically diverse group of rare melanocytic lesions most frequently seen in children and young adults. As atypical spitzoid tumors bear striking resemblance to Spitz nevus and spitzoid melanomas clinically and histopathologically, it is crucial to determine its malignant potential and predict its clinical behavior. To date, many researchers have attempted to differentiate atypical spitzoid tumors from unequivocal melanomas based on morphological, immonohistochemical, and molecular diagnostic differences. A diagnostic algorithm is proposed here to assess the malignant potential of atypical spitzoid tumors by using a combination of immunohistochemical and cytogenetic/molecular tests. Together with classical morphological evaluation, this algorithm includes a set of immunohistochemistry assays (p16(Ink4a), a dual-color Ki67/MART-1, and HMB45), fluorescence in situ hybridization (FISH) with five probes (6p25, 8q24, 11q13, CEN9, and 9p21), and an array-based comparative genomic hybridization. This review discusses details of the algorithm, the rationale of each test used in the algorithm, and utility of this algorithm in routine dermatopathology practice. This algorithmic approach will provide a comprehensive diagnostic tool that complements conventional histological criteria and will significantly contribute to improve the diagnosis and prediction of the clinical behavior of atypical spitzoid tumors.

3D chick embryo chorioallantoic membrane model as an in vivo model to study morphological and histopathological features of feline fibrosarcomas.

PubMed

Zabielska-Koczywąs, Katarzyna; Wojtkowska, Agata; Dolka, Izabella; Małek, Anna; Walewska, Magdalena; Wojtalewicz, Anna; Żbikowski, Artur; Lechowski, Roman

2017-06-26

The chick embryo chorioallantoic membrane (CAM) model is well described in human medicine as a cost-effective, easy to perform preclinical oncological model for observing pro- and antiangiogenic response, tumor biology and metastasis. The main objective of this article was to present the modification of the CAM assay in order to evaluate tumor growth from two feline fibrosarcoma cell lines (FFS1, FFS3) and describe their morphological and histopathological features. The authors described morphological and histopathological features of two feline fibrosarcoma cell lines (FFS1 and FFS3) grown on the CAM. Tumors from the FFS1 cell line showed high malignancy (grade III), while tumors from the FFS3 cell line were grade II. Proliferation markers (Ki-67 and PCNA) were determined and the positive correlation between PCNA and tumor grade (r = 0.8247; p < 0.001) was demonstrated, as opposed to Ki-67. The results obtained indicate that PCNA may be helpful to evaluate the tumor grade, better than Ki-67, for feline fibrosarcomas. However, further investigations of proliferation marker, in bigger number of feline spontaneous fibrosarcomas and feline fibrosarcomas grown on the CAM from different cell lines, are needed to confirm these observations.

Cutaneous microcystic/reticular schwannoma: a poorly recognized entity.

PubMed

Luzar, Boštjan; Tanaka, Maiko; Schneider, Johann; Calonje, Eduardo

2016-02-01

Microcystic/ reticular schwannoma is exceptionally rare yet distinctive morphological variant of schwannoma with predilection for visceral sites lacking association with neurofibromatosis. To further delineate clinicopathological features of cutaneous microcystic/reticular schwannoma and to discuss its differential diagnosis. We analyzed three cutaneous microcystic/reticular schwannomas, occurring in two males and one female (mean age: 37.6 years). The tumors presented as a non-painful slightly raised papule (mean: 0.7 cm) on upper arm (n = 2) and back (n = 1). No recurrences were observed despite marginal excision (mean follow up: 42 months). Histopathologically, a multilobular proliferation was present in the dermis composed of bland tumor cells forming distinctive microcystic, reticular, lace-like or pseudoglandular structures, containing abundant myxoid/mucinous material. By immunohistochemistry, tumor cells lining microcystic structures corresponded to Schwann cells (diffuse S100 positive, variable GFAP positivity). A discontinuous EMA-positive perineurium was present at the periphery of some of the lobules. Cutaneous microcystic/reticular schwannoma expands the spectrum of benign peripheral nerve sheath tumors with reticular morphology encountered in the skin. Other tumors in this group include reticular perineurioma and hybrid tumors with reticular morphology, e.g. reticular perineurioma/schwannoma and reticular perineurioma/neurofibroma. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Rates of ecological divergence and body size evolution are correlated with species diversification in scaly tree ferns

PubMed Central

Ramírez-Barahona, Santiago; Barrera-Redondo, Josué; Eguiarte, Luis E.

2016-01-01

Variation in species richness across regions and between different groups of organisms is a major feature of evolution. Several factors have been proposed to explain these differences, including heterogeneity in the rates of species diversification and the age of clades. It has been frequently assumed that rapid rates of diversification are coupled to high rates of ecological and morphological evolution, leading to a prediction that remains poorly explored for most species: the positive association between ecological niche divergence, morphological evolution and species diversification. We combined a time-calibrated phylogeny with distribution, ecological and body size data for scaly tree ferns (Cyatheaceae) to test whether rates of species diversification are predicted by the rates at which clades have evolved distinct ecological niches and body sizes. We found that rates of species diversification are positively correlated with rates of ecological and morphological evolution, with rapidly diversifying clades also showing rapidly evolving ecological niches and body sizes. Our results show that rapid diversification of scaly tree ferns is associated with the evolution of species with comparable morphologies that diversified into similar, yet distinct, environments. This suggests parallel evolutionary pathways opening in different tropical regions whenever ecological and geographical opportunities arise. Accordingly, rates of ecological niche and body size evolution are relevant to explain the current patterns of species richness in this ‘ancient’ fern lineage across the tropics. PMID:27412279

Rates of ecological divergence and body size evolution are correlated with species diversification in scaly tree ferns.

PubMed

Ramírez-Barahona, Santiago; Barrera-Redondo, Josué; Eguiarte, Luis E

2016-07-13

Variation in species richness across regions and between different groups of organisms is a major feature of evolution. Several factors have been proposed to explain these differences, including heterogeneity in the rates of species diversification and the age of clades. It has been frequently assumed that rapid rates of diversification are coupled to high rates of ecological and morphological evolution, leading to a prediction that remains poorly explored for most species: the positive association between ecological niche divergence, morphological evolution and species diversification. We combined a time-calibrated phylogeny with distribution, ecological and body size data for scaly tree ferns (Cyatheaceae) to test whether rates of species diversification are predicted by the rates at which clades have evolved distinct ecological niches and body sizes. We found that rates of species diversification are positively correlated with rates of ecological and morphological evolution, with rapidly diversifying clades also showing rapidly evolving ecological niches and body sizes. Our results show that rapid diversification of scaly tree ferns is associated with the evolution of species with comparable morphologies that diversified into similar, yet distinct, environments. This suggests parallel evolutionary pathways opening in different tropical regions whenever ecological and geographical opportunities arise. Accordingly, rates of ecological niche and body size evolution are relevant to explain the current patterns of species richness in this 'ancient' fern lineage across the tropics. © 2016 The Author(s).

A Curriculum Vitae of Teeth: Evolution, Generation, Regeneration

PubMed Central

Koussoulakou, Despina S.; Margaritis, Lukas H.; Koussoulakos, Stauros L.

2009-01-01

The ancestor of recent vertebrate teeth was a tooth-like structure on the outer body surface of jawless fishes. Over the course of 500,000,000 years of evolution, many of those structures migrated into the mouth cavity. In addition, the total number of teeth per dentition generally decreased and teeth morphological complexity increased. Teeth form mainly on the jaws within the mouth cavity through mutual, delicate interactions between dental epithelium and oral ectomesenchyme. These interactions involve spatially restricted expression of several, teeth-related genes and the secretion of various transcription and signaling factors. Congenital disturbances in tooth formation, acquired dental diseases and odontogenic tumors affect millions of people and rank human oral pathology as the second most frequent clinical problem. On the basis of substantial experimental evidence and advances in bioengineering, many scientists strongly believe that a deep knowledge of the evolutionary relationships and the cellular and molecular mechanisms regulating the morphogenesis of a given tooth in its natural position, in vivo, will be useful in the near future to prevent and treat teeth pathologies and malformations and for in vitro and in vivo teeth tissue regeneration. PMID:19266065

Effect of film thickness on morphological evolution in dewetting and crystallization of polystyrene/poly(ε-caprolactone) blend films.

PubMed

Ma, Meng; He, Zhoukun; Yang, Jinghui; Chen, Feng; Wang, Ke; Zhang, Qin; Deng, Hua; Fu, Qiang

2011-11-01

In this Article, the morphological evolution in the blend thin film of polystyrene (PS)/poly(ε-caprolactone) (PCL) was investigated via mainly AFM. It was found that an enriched two-layer structure with PS at the upper layer and PCL at the bottom layer was formed during spinning coating. By changing the solution concentration, different kinds of crystal morphologies, such as finger-like, dendritic, and spherulitic-like, could be obtained at the bottom PCL layer. These different initial states led to the morphological evolution processes to be quite different from each other, so the phase separation, dewetting, and crystalline morphology of PS/PCL blend films as a function of time were studied. It was interesting to find that the morphological evolution of PS at the upper layer was largely dependent on the film thickness. For the ultrathin (15 nm) blend film, a liquid-solid/liquid-liquid dewetting-wetting process was observed, forming ribbons that rupture into discrete circular PS islands on voronoi finger-like PCL crystal. For the thick (30 nm) blend film, the liquid-liquid dewetting of the upper PS layer from the underlying adsorbed PCL layer was found, forming interconnected rim structures that rupture into discrete circular PS islands embedded in the single lamellar PCL dendritic crystal due to Rayleigh instability. For the thicker (60 nm) blend film, a two-step liquid-liquid dewetting process with regular holes decorated with dendritic PCL crystal at early annealing stage and small holes decorated with spherulite-like PCL crystal among the early dewetting holes at later annealing stage was observed. The mechanism of this unusual morphological evolution process was discussed on the basis of the entropy effect and annealing-induced phase separation.

The immunohistochemistry aspects in two cases of neurofibromatosis-associated abdominal tumors.

PubMed

Carşote, Mara; Păun, S; Neamţu, M C; Avramescu, Elena Taina; Iosif, Cristina; Terzea, Dana; Constantinoiu, S; Dănciulescu Miulescu, Ruxandra; Neamţu, Oana Maria; Poiană, Cătălina

2012-01-01

Type 1 neurofibromatosis associates various abdominal tumors as gastrointestinal stromal tumors, duodenal or pancreatic carcinoid, and adrenal tumors like pheochromocytoma. We present the immunohistochemistry report in two cases with different profile regarding the evolution. One case is a 7th decade women diagnosed with unilateral pheochromocytoma and GISTs, with a good prognosis after surgery. The other case is a 41-year-old male diagnosed with duodenal metastatic somatostatinoma after an intestinal occlusive syndrome and later the hormonal profile leaded to the diagnosis of pheochromocytoma. The patient had a fulminate evolution within six months from diagnosis.

Evolution of metastasis revealed by mutational landscapes of chemically induced skin cancers | Office of Cancer Genomics

Cancer.gov

Human tumors show a high level of genetic heterogeneity, but the processes that influence the timing and route of metastatic dissemination of the subclones are unknown. Here we have used whole-exome sequencing of 103 matched benign, malignant and metastatic skin tumors from genetically heterogeneous mice to demonstrate that most metastases disseminate synchronously from the primary tumor, supporting parallel rather than linear evolution as the predominant model of metastasis.

Validation of the Lung Subtyping Panel in Multiple Fresh-Frozen and Formalin-Fixed, Paraffin-Embedded Lung Tumor Gene Expression Data Sets.

PubMed

Faruki, Hawazin; Mayhew, Gregory M; Fan, Cheng; Wilkerson, Matthew D; Parker, Scott; Kam-Morgan, Lauren; Eisenberg, Marcia; Horten, Bruce; Hayes, D Neil; Perou, Charles M; Lai-Goldman, Myla

2016-06-01

Context .- A histologic classification of lung cancer subtypes is essential in guiding therapeutic management. Objective .- To complement morphology-based classification of lung tumors, a previously developed lung subtyping panel (LSP) of 57 genes was tested using multiple public fresh-frozen gene-expression data sets and a prospectively collected set of formalin-fixed, paraffin-embedded lung tumor samples. Design .- The LSP gene-expression signature was evaluated in multiple lung cancer gene-expression data sets totaling 2177 patients collected from 4 platforms: Illumina RNAseq (San Diego, California), Agilent (Santa Clara, California) and Affymetrix (Santa Clara) microarrays, and quantitative reverse transcription-polymerase chain reaction. Gene centroids were calculated for each of 3 genomic-defined subtypes: adenocarcinoma, squamous cell carcinoma, and neuroendocrine, the latter of which encompassed both small cell carcinoma and carcinoid. Classification by LSP into 3 subtypes was evaluated in both fresh-frozen and formalin-fixed, paraffin-embedded tumor samples, and agreement with the original morphology-based diagnosis was determined. Results .- The LSP-based classifications demonstrated overall agreement with the original clinical diagnosis ranging from 78% (251 of 322) to 91% (492 of 538 and 869 of 951) in the fresh-frozen public data sets and 84% (65 of 77) in the formalin-fixed, paraffin-embedded data set. The LSP performance was independent of tissue-preservation method and gene-expression platform. Secondary, blinded pathology review of formalin-fixed, paraffin-embedded samples demonstrated concordance of 82% (63 of 77) with the original morphology diagnosis. Conclusions .- The LSP gene-expression signature is a reproducible and objective method for classifying lung tumors and demonstrates good concordance with morphology-based classification across multiple data sets. The LSP panel can supplement morphologic assessment of lung cancers, particularly when classification by standard methods is challenging.

Wrinkling pattern evolution of cylindrical biological tissues with differential growth.

PubMed

Jia, Fei; Li, Bo; Cao, Yan-Ping; Xie, Wei-Hua; Feng, Xi-Qiao

2015-01-01

Three-dimensional surface wrinkling of soft cylindrical tissues induced by differential growth is explored. Differential volumetric growth can cause their morphological stability, leading to the formation of hexagonal and labyrinth wrinkles. During postbuckling, multiple bifurcations and morphological transitions may occur as a consequence of continuous growth in the surface layer. The physical mechanisms underpinning the morphological evolution are examined from the viewpoint of energy. Surface curvature is found to play a regulatory role in the pattern evolution. This study may not only help understand the morphogenesis of soft biological tissues, but also inspire novel routes for creating desired surface patterns of soft materials.

Identification of tumor cells infiltrating into connective tissue in esophageal cancer by multiphoton microscopy

NASA Astrophysics Data System (ADS)

Xu, Jian; Jiang, Liwei; Kang, Deyong; Wu, Xuejing; Xu, Meifang; Zhuo, Shuangmu; Zhu, Xiaoqin; Lin, Jiangbo; Chen, Jianxin

2016-10-01

Esophageal cancer is one of the most common malignancies of the gastrointestinal cancers and carries poorer prognosis than other gastrointestinal cancers. In general practice, the depth of tumor infiltration in esophageal wall is crucial to establishing appropriate treatment plan which is established by detecting the tumor infiltration depth. Connective tissue is one of the main structures that form the esophageal wall. So, identification of tumor cells infiltrating into connective tissue is helping for detecting the tumor infiltration depth. Our aim is to evaluate whether multiphoton microscopy (MPM) can be used to detect tumor cells infiltrating into connective tissue in the esophageal cancer. MPM is well-suited for real-time detecting morphologic and cellular changes in fresh tissues since many endogenous fluorophores of fresh tissues are excited through two-photon excited fluorescence (TPEF) and second harmonic generation (SHG). In this work, microstructure of tumor cells and connective tissue are first studied. Then, morphological changes of collagen fibers after the infiltration of tumor cells are shown. These results show that MPM has the ability to detect tumor cells infiltrating into connective tissue in the esophageal cancer. In the future, MPM may be a promising imaging technique for detecting tumor cells in esophageal cancer.

Sequential evolution of bacterial morphology by co-option of a developmental regulator.

PubMed

Jiang, Chao; Brown, Pamela J B; Ducret, Adrien; Brun, Yves V

2014-02-27

What mechanisms underlie the transitions responsible for the diverse shapes observed in the living world? Although bacteria exhibit a myriad of morphologies, the mechanisms responsible for the evolution of bacterial cell shape are not understood. We investigated morphological diversity in a group of bacteria that synthesize an appendage-like extension of the cell envelope called the stalk. The location and number of stalks varies among species, as exemplified by three distinct subcellular positions of stalks within a rod-shaped cell body: polar in the genus Caulobacter and subpolar or bilateral in the genus Asticcacaulis. Here we show that a developmental regulator of Caulobacter crescentus, SpmX, is co-opted in the genus Asticcacaulis to specify stalk synthesis either at the subpolar or bilateral positions. We also show that stepwise evolution of a specific region of SpmX led to the gain of a new function and localization of this protein, which drove the sequential transition in stalk positioning. Our results indicate that changes in protein function, co-option and modularity are key elements in the evolution of bacterial morphology. Therefore, similar evolutionary principles of morphological transitions apply to both single-celled prokaryotes and multicellular eukaryotes.

Correlated evolution of beak morphology and song in the neotropical woodcreeper radiation.

PubMed

Derryberry, Elizabeth Perrault; Seddon, Nathalie; Claramunt, Santiago; Tobias, Joseph Andrew; Baker, Adam; Aleixo, Alexandre; Brumfield, Robb Thomas

2012-09-01

Mating signals may diversify as a byproduct of morphological adaptation to different foraging niches, potentially driving speciation. Although many studies have focused on the direct influence of ecological and sexual selection on signal divergence, the role of indirect mechanisms remains poorly understood. Using phenotypic and molecular datasets, we explored the interplay between morphological and vocal evolution in an avian radiation characterized by dramatic beak variation, the Neotropical woodcreepers (Dendrocolaptinae). We found evidence of a trade-off between the rate of repetition of song syllables and frequency bandwidth: slow paced songs had either narrow or wide frequency bandwidths, and bandwidth decreased as song pace increased. This bounded phenotypic space for song structure supports the hypothesis that passerine birds face a motor constraint during song production. Diversification of acoustic characters within this bounded space was correlated with diversification of beak morphology. In particular, species with larger beaks produced slower songs with narrower frequency bandwidths, suggesting that ecological selection on beak morphology influences the diversification of woodcreeper songs. Because songs in turn mediate mate choice and species recognition in birds, these results indicate a broader role for ecology in avian diversification. © 2012 The Author(s). Evolution© 2012 The Society for the Study of Evolution.

Breast Cancer Subtypes: Morphologic and Biologic Characterization

PubMed Central

2016-01-01

Advances in basic science, technology and translational research have created a revolution in breast cancer diagnosis and therapy. Researchers' discoveries of genes defining variability in response to therapy and heterogeneity in clinical presentations and tumor biology are the foundation of the path to personalized medicine. The success of personalized breast cancer care depends on access to pertinent clinical information and risk factors, optimal imaging findings, well-established morphologic features, and traditional and contemporary prognostic/predictive testing. The integration of these entities provides an opportunity to identify patients who can benefit from specific therapies, and demonstrates the link between breast cancer subtypes and their association with different tumor biology. It is critical to recognize specific types of breast cancer in individual patients and design optimal personalized therapy. This article will highlight the roles of morphologic features and established tumor biomarkers on patient outcome. PMID:26756229

MuSE: accounting for tumor heterogeneity using a sample-specific error model improves sensitivity and specificity in mutation calling from sequencing data.

PubMed

Fan, Yu; Xi, Liu; Hughes, Daniel S T; Zhang, Jianjun; Zhang, Jianhua; Futreal, P Andrew; Wheeler, David A; Wang, Wenyi

2016-08-24

Subclonal mutations reveal important features of the genetic architecture of tumors. However, accurate detection of mutations in genetically heterogeneous tumor cell populations using next-generation sequencing remains challenging. We develop MuSE ( http://bioinformatics.mdanderson.org/main/MuSE ), Mutation calling using a Markov Substitution model for Evolution, a novel approach for modeling the evolution of the allelic composition of the tumor and normal tissue at each reference base. MuSE adopts a sample-specific error model that reflects the underlying tumor heterogeneity to greatly improve the overall accuracy. We demonstrate the accuracy of MuSE in calling subclonal mutations in the context of large-scale tumor sequencing projects using whole exome and whole genome sequencing.

Advances for Studying Clonal Evolution in Cancer

PubMed Central

Raphael, Benjamin J.; Chen, Feng; Wendl, Michael C.

2013-01-01

The “clonal evolution” model of cancer emerged and “evolved” amid ongoing advances in technology, especially in recent years during which next generation sequencing instruments have provided ever higher resolution pictures of the genetic changes in cancer cells and heterogeneity in tumors. It has become increasingly clear that clonal evolution is not a single sequential process, but instead frequently involves simultaneous evolution of multiple subclones that co-exist because they are of similar fitness or are spatially separated. Co-evolution of subclones also occurs when they complement each other’s survival advantages. Recent studies have also shown that clonal evolution is highly heterogeneous: different individual tumors of the same type may undergo very different paths of clonal evolution. New methodological advancements, including deep digital sequencing of a mixed tumor population, single cell sequencing, and the development of more sophisticated computational tools, will continue to shape and reshape the models of clonal evolution. In turn, these will provide both an improved framework for the understanding of cancer progression and a guide for treatment strategies aimed at the elimination of all, rather than just some, of the cancer cells within a patient. PMID:23353056

Combining routine morphology, p16(INK4a) immunohistochemistry, and in situ hybridization for the detection of human papillomavirus infection in penile carcinomas: a tissue microarray study using classifier performance analyses.

PubMed

Chaux, Alcides; Cubilla, Antonio L; Haffner, Michael C; Lecksell, Kristen L; Sharma, Rajni; Burnett, Arthur L; Netto, George J

2014-02-01

Infection by high-risk human papillomavirus (HR-HPV) plays an important role in the pathogenesis of penile cancer in approximately 50% of the patients. The gold standard for human papillomavirus (HPV) detection is the polymerase chain reaction (PCR) assay. However, technical requirements and associated costs preclude the worldwide use of PCR assays on a routine basis. Herein, we evaluated the predictive abilities of tumor morphology, immunohistochemistry for p16(INK4a) expression, and in situ hybridization (ISH) for HR-HPV detection in defining HPV status, as established by PCR. Tissue samples from 48 patients with HPV-positive penile squamous cell carcinoma (SCC) were included in 4 tissue microarrays (TMA). Sensitivities and specificities were as follows: tumor morphology, 70% and 68%; p16(INK4a) immunohistochemistry, 65% and 90%; HR-HPV ISH, 47% and 100%. Regarding combinations of the predictors, the best performance was seen when HR-HPV ISH and p16(INK4a) immunohistochemistry were combined, regardless of the tumor morphology: sensitivity, 88%; specificity, 64%; area under the receiver-operating characteristic (AUC) curve, 0.83. Combinations of tumor morphology with p16(INK4a) immunohistochemistry or with HR-HPV ISH performed similarly well. In penile SCC, both p16(INK4a) immunohistochemistry and ISH for HR-HPV increase the predictive ability of routine morphology in defining HPV status. These tests can be interpreted differentially, depending on the necessity of a higher sensitivity or a higher specificity. For research/screening studies, we recommend combining tumor morphology, p16(INK4a) immunohistochemistry, and HR-HPV ISH. To increase sensitivity, positivity in any of these predictors should be considered as indicative of HPV infection. For routine diagnosis of clinical cases, criteria should be more stringent, and, to achieve the highest specificity in classifying a case as HPV-related, all predictors should be consistently positive. The data generated in the present study could be used in algorithms for defining HPV status in penile carcinomas. Copyright © 2014 Elsevier Inc. All rights reserved.

The influence of an innovative locomotor strategy on the phenotypic diversification of triggerfish (family: Balistidae).

PubMed

Dornburg, Alex; Sidlauskas, Brian; Santini, Francesco; Sorenson, Laurie; Near, Thomas J; Alfaro, Michael E

2011-07-01

Innovations in locomotor morphology have been invoked as important drivers of vertebrate diversification, although the influence of novel locomotion strategies on marine fish diversification remains largely unexplored. Using triggerfish as a case study, we determine whether the evolution of the distinctive synchronization of enlarged dorsal and anal fins that triggerfish use to swim may have catalyzed the ecological diversification of the group. By adopting a comparative phylogenetic approach to quantify median fin and body shape integration and to assess the tempo of functional and morphological evolution in locomotor traits, we find that: (1) functional and morphological components of the locomotive system exhibit a strong signal of correlated evolution; (2) triggerfish partitioned locomotor morphological and functional spaces early in their history; and (3) there is no strong evidence that a pulse of lineage diversification accompanied the major episode of phenotypic diversification. Together these findings suggest that the acquisition of a distinctive mode of locomotion drove an early radiation of shape and function in triggerfish, but not an early radiation of species. © 2011 The Author(s). Evolution© 2011 The Society for the Study of Evolution.

Semiautomatic segmentation and follow-up of multicomponent low-grade tumors in longitudinal brain MRI studies

PubMed Central

Weizman, Lior; Sira, Liat Ben; Joskowicz, Leo; Rubin, Daniel L.; Yeom, Kristen W.; Constantini, Shlomi; Shofty, Ben; Bashat, Dafna Ben

2014-01-01

Purpose: Tracking the progression of low grade tumors (LGTs) is a challenging task, due to their slow growth rate and associated complex internal tumor components, such as heterogeneous enhancement, hemorrhage, and cysts. In this paper, the authors show a semiautomatic method to reliably track the volume of LGTs and the evolution of their internal components in longitudinal MRI scans. Methods: The authors' method utilizes a spatiotemporal evolution modeling of the tumor and its internal components. Tumor components gray level parameters are estimated from the follow-up scan itself, obviating temporal normalization of gray levels. The tumor delineation procedure effectively incorporates internal classification of the baseline scan in the time-series as prior data to segment and classify a series of follow-up scans. The authors applied their method to 40 MRI scans of ten patients, acquired at two different institutions. Two types of LGTs were included: Optic pathway gliomas and thalamic astrocytomas. For each scan, a “gold standard” was obtained manually by experienced radiologists. The method is evaluated versus the gold standard with three measures: gross total volume error, total surface distance, and reliability of tracking tumor components evolution. Results: Compared to the gold standard the authors' method exhibits a mean Dice similarity volumetric measure of 86.58% and a mean surface distance error of 0.25 mm. In terms of its reliability in tracking the evolution of the internal components, the method exhibits strong positive correlation with the gold standard. Conclusions: The authors' method provides accurate and repeatable delineation of the tumor and its internal components, which is essential for therapy assessment of LGTs. Reliable tracking of internal tumor components over time is novel and potentially will be useful to streamline and improve follow-up of brain tumors, with indolent growth and behavior. PMID:24784396

Functional versus non-functional intratumor heterogeneity in cancer

PubMed Central

Williams, Marc J.; Werner, Benjamin; Graham, Trevor A.; Sottoriva, Andrea

2016-01-01

ABSTRACT Next-generation sequencing data from human cancers are often difficult to interpret within the context of tumor evolution. We developed a mathematical model describing the accumulation of mutations under neutral evolutionary dynamics and showed that 323/904 cancers (∼30%) from multiple types were consistent with the neutral model of tumor evolution. PMID:27652316

Solid Pseudopapillary Tumor of the Pancreas: One Case with a Metastatic Evolution in a Caucasian Woman.

PubMed

Lestelle, Valentin; de Coster, Claire; Sarran, Anthony; Poizat, Flora; Delpero, Jean-Robert; Raoul, Jean-Luc

2015-01-01

We report the case of a Caucasian woman, operated on for a solid pseudopapillary tumor of the pancreas in 2009, who recurred 4 years later with multiple liver metastases requiring liver resection. This disease is infrequent, particularly among the Caucasian population, and metastatic evolution is very rare.

Warthin-like papillary renal cell carcinoma: Clinicopathologic, morphologic, immunohistochemical and molecular genetic analysis of 11 cases.

PubMed

Skenderi, Faruk; Ulamec, Monika; Vanecek, Tomas; Martinek, Petr; Alaghehbandan, Reza; Foix, Maria Pane; Babankova, Iva; Montiel, Delia Perez; Alvarado-Cabrero, Isabel; Svajdler, Marian; Dubinský, Pavol; Cempirkova, Dana; Pavlovsky, Michal; Vranic, Semir; Daum, Ondrej; Ondic, Ondrej; Pivovarcikova, Kristyna; Michalova, Kvetoslava; Hora, Milan; Rotterova, Pavla; Stehlikova, Adela; Dusek, Martin; Michal, Michal; Hes, Ondrej

2017-04-01

Oncocytic papillary renal cell carcinoma (PRCC) is a distinct subtype of PRCC, listed as a possible new variant of PRCC in the 2016 WHO classification. It is composed of papillae aligned by large single-layered eosinophilic cells showing linearly arranged oncocytoma-like nuclei. We analyzed clinicopathologic, morphologic, immunohistochemical and molecular-genetic characteristics of 11 oncocytic PRCCs with prominent tumor lymphocytic infiltrate, morphologically resembling Warthin's tumor. The patients were predominantly males (8/11, 73%), with an average age of 59years (range 14-76), and a mean tumor size of 7cm (range 1-22cm). Tumors had the features of oncocytic PRCCs with focal pseudostratification in 8/11 cases and showed dense stromal inflammatory infiltration in all cases. Papillary growth pattern was predominant, comprising more than 60% of tumor volume. Tubular and solid components were present in 5 and 3 cases, respectively. Uniform immunohistochemical positivity was found for AMACR, PAX-8, MIA, vimentin, and OSCAR. Tumors were mostly negative for carboanhydrase 9, CD117, CK20, and TTF-1. Immunohistochemical stains for DNA mismatch repair proteins MLH1 and PMS2 were retained in all cases, while MSH2 and MSH6 were negative in 1 case. Tumor infiltrating lymphocytes (TILs) consisted of both B and T cells. Chromosomal copy number variation analysis showed great variability in 5 cases, ranging from a loss of one single chromosome to complex genome rearrangements. Only one case showed gains of chromosomes 7 and 17, among other aberrations. In 4 cases no numerical imbalance was found. Follow up data was available for 9 patients (median 47.6months, range 1-132). In 6 patients no lethal progression was noted, while 3 died of disease. In conclusion, Warthin-like PRCC is morphologically very close to oncocytic PRCC, from which it differs by the presence of dense lymphoid stroma. Chromosomal numerical aberration pattern of these tumors is variable; only one case showed gains of chromosomes 7 and 17. Warthin-like PRCC is a potentially aggressive tumor since a lethal outcome was recorded in 3/9 cases. Copyright © 2017 Elsevier Inc. All rights reserved.

A model of tumor architecture and spatial interactions with tumor microenvironment in breast carcinoma

NASA Astrophysics Data System (ADS)

Ben Cheikh, Bassem; Bor-Angelier, Catherine; Racoceanu, Daniel

2017-03-01

Breast carcinomas are cancers that arise from the epithelial cells of the breast, which are the cells that line the lobules and the lactiferous ducts. Breast carcinoma is the most common type of breast cancer and can be divided into different subtypes based on architectural features and growth patterns, recognized during a histopathological examination. Tumor microenvironment (TME) is the cellular environment in which tumor cells develop. Being composed of various cell types having different biological roles, TME is recognized as playing an important role in the progression of the disease. The architectural heterogeneity in breast carcinomas and the spatial interactions with TME are, to date, not well understood. Developing a spatial model of tumor architecture and spatial interactions with TME can advance our understanding of tumor heterogeneity. Furthermore, generating histological synthetic datasets can contribute to validating, and comparing analytical methods that are used in digital pathology. In this work, we propose a modeling method that applies to different breast carcinoma subtypes and TME spatial distributions based on mathematical morphology. The model is based on a few morphological parameters that give access to a large spectrum of breast tumor architectures and are able to differentiate in-situ ductal carcinomas (DCIS) and histological subtypes of invasive carcinomas such as ductal (IDC) and lobular carcinoma (ILC). In addition, a part of the parameters of the model controls the spatial distribution of TME relative to the tumor. The validation of the model has been performed by comparing morphological features between real and simulated images.

Electrodeposition of Rhodium Nanowires Arrays and Their Morphology-Dependent Hydrogen Evolution Activity

PubMed Central

Zhang, Liqiu; Liu, Lichun; Wang, Hongdan; Shen, Hongxia; Cheng, Qiong; Yan, Chao; Park, Sungho

2017-01-01

This work reports on the electrodeposition of rhodium (Rh) nanowires with a controlled surface morphology synthesized using an anodic aluminum oxide (AAO) template. Vertically aligned Rh nanowires with a smooth and coarse morphology were successfully deposited by adjusting the electrode potential and the concentration of precursor ions and by involving a complexing reagent in the electrolyte solution. Scanning electron microscopy (SEM) and transmission electron microscopy (TEM) analyses were used to follow the morphological evolution of Rh nanowires. As a heterogeneous electrocatalyst for hydrogen evolution reactions (HER), the coarse Rh nanowire array exhibited an enhanced catalytic performance respect to smooth ones due to the larger surface area to mass ratio and the higher density of catalytically active defects, as evidenced by voltammetric measurements and TEM. Results suggest that the morphology of metallic nanomaterials could be readily engineered by electrodeposition. The controlled electrodeposition offers great potential for the development of an effective synthesis tool for heterogeneous catalysts with a superior performance for wide applications. PMID:28467375

Environmental Influence on the Evolution of Morphological Complexity in Machines

PubMed Central

Auerbach, Joshua E.; Bongard, Josh C.

2014-01-01

Whether, when, how, and why increased complexity evolves in biological populations is a longstanding open question. In this work we combine a recently developed method for evolving virtual organisms with an information-theoretic metric of morphological complexity in order to investigate how the complexity of morphologies, which are evolved for locomotion, varies across different environments. We first demonstrate that selection for locomotion results in the evolution of organisms with morphologies that increase in complexity over evolutionary time beyond what would be expected due to random chance. This provides evidence that the increase in complexity observed is a result of a driven rather than a passive trend. In subsequent experiments we demonstrate that morphologies having greater complexity evolve in complex environments, when compared to a simple environment when a cost of complexity is imposed. This suggests that in some niches, evolution may act to complexify the body plans of organisms while in other niches selection favors simpler body plans. PMID:24391483

Crystal Growth and Dissolution of Methylammonium Lead Iodide Perovskite in Sequential Deposition: Correlation between Morphology Evolution and Photovoltaic Performance.

PubMed

Hsieh, Tsung-Yu; Huang, Chi-Kai; Su, Tzu-Sen; Hong, Cheng-You; Wei, Tzu-Chien

2017-03-15

Crystal morphology and structure are important for improving the organic-inorganic lead halide perovskite semiconductor property in optoelectronic, electronic, and photovoltaic devices. In particular, crystal growth and dissolution are two major phenomena in determining the morphology of methylammonium lead iodide perovskite in the sequential deposition method for fabricating a perovskite solar cell. In this report, the effect of immersion time in the second step, i.e., methlyammonium iodide immersion in the morphological, structural, optical, and photovoltaic evolution, is extensively investigated. Supported by experimental evidence, a five-staged, time-dependent evolution of the morphology of methylammonium lead iodide perovskite crystals is established and is well connected to the photovoltaic performance. This result is beneficial for engineering optimal time for methylammonium iodide immersion and converging the solar cell performance in the sequential deposition route. Meanwhile, our result suggests that large, well-faceted methylammonium lead iodide perovskite single crystal may be incubated by solution process. This offers a low cost route for synthesizing perovskite single crystal.

Gene networks and the evolution of plant morphology.

PubMed

Das Gupta, Mainak; Tsiantis, Miltos

2018-06-06

Elaboration of morphology depends on the precise orchestration of gene expression by key regulatory genes. The hierarchy and relationship among the participating genes is commonly known as gene regulatory network (GRN). Therefore, the evolution of morphology ultimately occurs by the rewiring of gene network structures or by the co-option of gene networks to novel domains. The availability of high-resolution expression data combined with powerful statistical tools have opened up new avenues to formulate and test hypotheses on how diverse gene networks influence trait development and diversity. Here we summarize recent studies based on both big-data and genetics approaches to understand the evolution of plant form and physiology. We also discuss recent genome-wide investigations on how studying open-chromatin regions may help study the evolution of gene expression patterns. Copyright © 2018. Published by Elsevier Ltd.

Phylogenomic Insights into Animal Evolution.

PubMed

Telford, Maximilian J; Budd, Graham E; Philippe, Hervé

2015-10-05

Animals make up only a small fraction of the eukaryotic tree of life, yet, from our vantage point as members of the animal kingdom, the evolution of the bewildering diversity of animal forms is endlessly fascinating. In the century following the publication of Darwin's Origin of Species, hypotheses regarding the evolution of the major branches of the animal kingdom - their relationships to each other and the evolution of their body plans - was based on a consideration of the morphological and developmental characteristics of the different animal groups. This morphology-based approach had many successes but important aspects of the evolutionary tree remained disputed. In the past three decades, molecular data, most obviously primary sequences of DNA and proteins, have provided an estimate of animal phylogeny largely independent of the morphological evolution we would ultimately like to understand. The molecular tree that has evolved over the past three decades has drastically altered our view of animal phylogeny and many aspects of the tree are no longer contentious. The focus of molecular studies on relationships between animal groups means, however, that the discipline has become somewhat divorced from the underlying biology and from the morphological characteristics whose evolution we aim to understand. Here, we consider what we currently know of animal phylogeny; what aspects we are still uncertain about and what our improved understanding of animal phylogeny can tell us about the evolution of the great diversity of animal life. Copyright © 2015 Elsevier Ltd. All rights reserved.

Evolution in an extreme environment: developmental biases and phenotypic integration in the adaptive radiation of antarctic notothenioids.

PubMed

Hu, Yinan; Ghigliotti, Laura; Vacchi, Marino; Pisano, Eva; Detrich, H William; Albertson, R Craig

2016-06-29

Over the past 40 million years water temperatures have dramatically dropped in the Southern Ocean, which has led to the local extinction of most nearshore fish lineages. The evolution of antifreeze glycoproteins in notothenioids, however, enabled these ancestrally benthic fishes to survive and adapt as temperatures reached the freezing point of seawater (-1.86 °C). Antarctic notothenioids now represent the primary teleost lineage in the Southern Ocean and are of fundamental importance to the local ecosystem. The radiation of notothenioids has been fostered by the evolution of "secondary pelagicism", the invasion of pelagic habitats, as the group diversified to fill newly available foraging niches in the water column. While elaborate craniofacial modifications have accompanied this adaptive radiation, little is known about how these morphological changes have contributed to the evolutionary success of notothenioids. We used a 3D-morphometrics approach to investigate patterns of morphological variation in the craniofacial skeleton among notothenioids, and show that variation in head shape is best explained by divergent selection with respect to foraging niche. We document further an accelerated rate of morphological evolution in the icefish family Channichthyidae, and show that their rapid diversification was accompanied by the evolution of relatively high levels of morphological integration. Whereas most studies suggest that extensive integration should constrain phenotypic evolution, icefish stand out as a rare example of increased integration possibly facilitating evolutionary potential. Finally, we show that the unique feeding apparatus in notothenioids in general, and icefish in particular, can be traced to shifts in early developmental patterning mechanisms and ongoing growth of the pharyngeal skeleton. Our work suggests that ecological opportunity is a major factor driving craniofacial variation in this group. Further, the observation that closely related lineages can differ dramatically in integration suggests that this trait can evolve quickly. We propose that the evolution of high levels of phenotypic integration in icefishes may be considered a key innovation that facilitated their morphological evolution and subsequent ecological expansion.

Automated tracking of tumor-stroma morphology in microtissues identifies functional targets within the tumor microenvironment for therapeutic intervention

PubMed Central

Åkerfelt, Malin; Bayramoglu, Neslihan; Robinson, Sean; Toriseva, Mervi; Schukov, Hannu-Pekka; Härmä, Ville; Virtanen, Johannes; Sormunen, Raija; Kaakinen, Mika; Kannala, Juho; Eklund, Lauri; Heikkilä, Janne; Nees, Matthias

2015-01-01

Cancer-associated fibroblasts (CAFs) constitute an important part of the tumor microenvironment and promote invasion via paracrine functions and physical impact on the tumor. Although the importance of including CAFs into three-dimensional (3D) cell cultures has been acknowledged, computational support for quantitative live-cell measurements of complex cell cultures has been lacking. Here, we have developed a novel automated pipeline to model tumor-stroma interplay, track motility and quantify morphological changes of 3D co-cultures, in real-time live-cell settings. The platform consists of microtissues from prostate cancer cells, combined with CAFs in extracellular matrix that allows biochemical perturbation. Tracking of fibroblast dynamics revealed that CAFs guided the way for tumor cells to invade and increased the growth and invasiveness of tumor organoids. We utilized the platform to determine the efficacy of inhibitors in prostate cancer and the associated tumor microenvironment as a functional unit. Interestingly, certain inhibitors selectively disrupted tumor-CAF interactions, e.g. focal adhesion kinase (FAK) inhibitors specifically blocked tumor growth and invasion concurrently with fibroblast spreading and motility. This complex phenotype was not detected in other standard in vitro models. These results highlight the advantage of our approach, which recapitulates tumor histology and can significantly improve cancer target validation in vitro. PMID:26375443

The evolution of tumor metastases during clonal expansion.

PubMed

Haeno, Hiroshi; Michor, Franziska

2010-03-07

Cancer is a leading cause of morbidity and mortality in many countries. Solid tumors generally initiate at one particular site called the primary tumor, but eventually disseminate and form new colonies in other organs. The development of such metastases greatly diminishes the potential for a cure of patients and is thought to represent the final stage of the multi-stage progression of human cancer. The concept of early metastatic dissemination, however, postulates that cancer cell spread might arise early during the development of a tumor. It is important to know whether metastases are present at diagnosis since this determines treatment strategies and outcome. In this paper, we design a stochastic mathematical model of the evolution of tumor metastases in an expanding cancer cell population. We calculate the probability of metastasis at a given time during tumor evolution, the expected number of metastatic sites, and the total number of cancer cells as well as metastasized cells. Furthermore, we investigate the effect of drug administration and tumor resection on these quantities and predict the survival time of cancer patients. The model presented in this paper allows us to determine the probability and number of metastases at diagnosis and to identify the optimum treatment strategy to maximally prolong survival of cancer patients. 2009 Elsevier Ltd. All rights reserved.

The evolution, morphology, and development of fern leaves

PubMed Central

Vasco, Alejandra; Moran, Robbin C.; Ambrose, Barbara A.

2013-01-01

Leaves are lateral determinate structures formed in a predictable sequence (phyllotaxy) on the flanks of an indeterminate shoot apical meristem. The origin and evolution of leaves in vascular plants has been widely debated. Being the main conspicuous organ of nearly all vascular plants and often easy to recognize as such, it seems surprising that leaves have had multiple origins. For decades, morphologists, anatomists, paleobotanists, and systematists have contributed data to this debate. More recently, molecular genetic studies have provided insight into leaf evolution and development mainly within angiosperms and, to a lesser extent, lycophytes. There has been recent interest in extending leaf evolutionary developmental studies to other species and lineages, particularly in lycophytes and ferns. Therefore, a review of fern leaf morphology, evolution and development is timely. Here we discuss the theories of leaf evolution in ferns, morphology, and diversity of fern leaves, and experimental results of fern leaf development. We summarize what is known about the molecular genetics of fern leaf development and what future studies might tell us about the evolution of fern leaf development. PMID:24027574

Clinical significance of prominent retraction clefts in invasive urothelial carcinoma.

PubMed

Shah, Tanmay S; Kaag, Matthew; Raman, Jay D; Chan, Wilson; Tran, Truc; Kunchala, Sudhir; Shuman, Lauren; DeGraff, David J; Chen, Guoli; Warrick, Joshua I

2017-03-01

Micropapillary morphology in invasive urothelial carcinoma is an established predictor of aggressive disease. It is unknown, however, if prominent retraction is associated with more aggressive disease in the absence of classic micropapillary morphology. We reviewed a retrospective series of 309 radical cystectomy specimens with clinical follow-up data and documented the presence or absence of invasive urothelial carcinoma with prominent retraction clefts, defined as invasive carcinoma with retraction involving the majority of invasive tumor nests in at least one 100× field but without classic micropapillary morphology. Invasive carcinomas with plasmacytoid, sarcomatoid, nested, and small cell morphology were excluded, as were cases without lymph node sampling. In invasive conventional urothelial carcinoma, the presence of prominent retraction clefts was associated lymph node metastasis (odds ratio 4.7, P = .0015, Fisher exact test) but not pathologic tumor stage or several other oncologic parameters (all Ps > .10). Similarly, invasive urothelial carcinoma with micropapillary morphology had lymph node metastasis more frequently than conventional urothelial carcinoma without prominent retraction clefts (P < .001, Fisher exact test), but there was no difference in pathologic tumor stage or oncologic parameters (all Ps > .10). There was no statistically significant difference in rates of lymph node metastasis between invasive urothelial carcinoma with micropapillary morphology and conventional urothelial carcinoma with prominent retraction clefts (P = .54, Fisher exact test). The findings suggest that prominent retraction in invasive urothelial carcinoma may be associated with more aggressive disease, even in the absence of classic micropapillary morphology. Copyright © 2016 Elsevier Inc. All rights reserved.

Rates of molecular evolution in tree ferns are associated with body size, environmental temperature, and biological productivity.

PubMed

Barrera-Redondo, Josué; Ramírez-Barahona, Santiago; Eguiarte, Luis E

2018-05-01

Variation in rates of molecular evolution (heterotachy) is a common phenomenon among plants. Although multiple theoretical models have been proposed, fundamental questions remain regarding the combined effects of ecological and morphological traits on rate heterogeneity. Here, we used tree ferns to explore the correlation between rates of molecular evolution in chloroplast DNA sequences and several morphological and environmental factors within a Bayesian framework. We revealed direct and indirect effects of body size, biological productivity, and temperature on substitution rates, where smaller tree ferns living in warmer and less productive environments tend to have faster rates of molecular evolution. In addition, we found that variation in the ratio of nonsynonymous to synonymous substitution rates (dN/dS) in the chloroplast rbcL gene was significantly correlated with ecological and morphological variables. Heterotachy in tree ferns may be influenced by effective population size associated with variation in body size and productivity. Macroevolutionary hypotheses should go beyond explaining heterotachy in terms of mutation rates and instead, should integrate population-level factors to better understand the processes affecting the tempo of evolution at the molecular level. © 2018 The Author(s). Evolution © 2018 The Society for the Study of Evolution.

Morphological evolution in land plants: new designs with old genes

PubMed Central

Pires, Nuno D.; Dolan, Liam

2012-01-01

The colonization and radiation of multicellular plants on land that started over 470 Ma was one of the defining events in the history of this planet. For the first time, large amounts of primary productivity occurred on the continental surface, paving the way for the evolution of complex terrestrial ecosystems and altering global biogeochemical cycles; increased weathering of continental silicates and organic carbon burial resulted in a 90 per cent reduction in atmospheric carbon dioxide levels. The evolution of plants on land was itself characterized by a series of radical transformations of their body plans that included the formation of three-dimensional tissues, de novo evolution of a multicellular diploid sporophyte generation, evolution of multicellular meristems, and the development of specialized tissues and organ systems such as vasculature, roots, leaves, seeds and flowers. In this review, we discuss the evolution of the genes and developmental mechanisms that drove the explosion of plant morphologies on land. Recent studies indicate that many of the gene families which control development in extant plants were already present in the earliest land plants. This suggests that the evolution of novel morphologies was to a large degree driven by the reassembly and reuse of pre-existing genetic mechanisms. PMID:22232763

Morphological evolution in land plants: new designs with old genes.

PubMed

Pires, Nuno D; Dolan, Liam

2012-02-19

The colonization and radiation of multicellular plants on land that started over 470 Ma was one of the defining events in the history of this planet. For the first time, large amounts of primary productivity occurred on the continental surface, paving the way for the evolution of complex terrestrial ecosystems and altering global biogeochemical cycles; increased weathering of continental silicates and organic carbon burial resulted in a 90 per cent reduction in atmospheric carbon dioxide levels. The evolution of plants on land was itself characterized by a series of radical transformations of their body plans that included the formation of three-dimensional tissues, de novo evolution of a multicellular diploid sporophyte generation, evolution of multicellular meristems, and the development of specialized tissues and organ systems such as vasculature, roots, leaves, seeds and flowers. In this review, we discuss the evolution of the genes and developmental mechanisms that drove the explosion of plant morphologies on land. Recent studies indicate that many of the gene families which control development in extant plants were already present in the earliest land plants. This suggests that the evolution of novel morphologies was to a large degree driven by the reassembly and reuse of pre-existing genetic mechanisms.

Speciation and stasis in marine Ostracoda: Climatic modulation of evolution

USGS Publications Warehouse

Cronin, T. M.

1985-01-01

Morphologic and paleozoogeographic analysis of Cenozoic marine Ostracoda from the Atlantic, Caribbean, and Pacific indicates that climatic change modulates evolution by disrupting long-term stasis and catalyzing speciation during sustained, unidirectional climatic transitions and, conversely, by maintaining morphologic stasis during rapid, high-frequency climatic osculations. In the middle Pliocene, 4 to 3 million years ago, at least six new species of Puriana suddenly appeared as the Isthmus of Panama closed, changing oceanographic circulation and global climate. Since then morphologic stasis has characterized ancestral and descendant species during many glacial-interglacial cycles. The frequency and duration of climatic events have more impact on ostracode evolution than the magnitude of climatic changes.

The Importance of Neighborhood Scheme Selection in Agent-based Tumor Growth Modeling.

PubMed

Tzedakis, Georgios; Tzamali, Eleftheria; Marias, Kostas; Sakkalis, Vangelis

2015-01-01

Modeling tumor growth has proven a very challenging problem, mainly due to the fact that tumors are highly complex systems that involve dynamic interactions spanning multiple scales both in time and space. The desire to describe interactions in various scales has given rise to modeling approaches that use both continuous and discrete variables, known as hybrid approaches. This work refers to a hybrid model on a 2D square lattice focusing on cell movement dynamics as they play an important role in tumor morphology, invasion and metastasis and are considered as indicators for the stage of malignancy used for early prognosis and effective treatment. Considering various distributions of the microenvironment, we explore how Neumann vs. Moore neighborhood schemes affects tumor growth and morphology. The results indicate that the importance of neighborhood selection is critical under specific conditions that include i) increased hapto/chemo-tactic coefficient, ii) a rugged microenvironment and iii) ECM degradation.

Many-to-one form-to-function mapping weakens parallel morphological evolution.

PubMed

Thompson, Cole J; Ahmed, Newaz I; Veen, Thor; Peichel, Catherine L; Hendry, Andrew P; Bolnick, Daniel I; Stuart, Yoel E

2017-11-01

Evolutionary ecologists aim to explain and predict evolutionary change under different selective regimes. Theory suggests that such evolutionary prediction should be more difficult for biomechanical systems in which different trait combinations generate the same functional output: "many-to-one mapping." Many-to-one mapping of phenotype to function enables multiple morphological solutions to meet the same adaptive challenges. Therefore, many-to-one mapping should undermine parallel morphological evolution, and hence evolutionary predictability, even when selection pressures are shared among populations. Studying 16 replicate pairs of lake- and stream-adapted threespine stickleback (Gasterosteus aculeatus), we quantified three parts of the teleost feeding apparatus and used biomechanical models to calculate their expected functional outputs. The three feeding structures differed in their form-to-function relationship from one-to-one (lower jaw lever ratio) to increasingly many-to-one (buccal suction index, opercular 4-bar linkage). We tested for (1) weaker linear correlations between phenotype and calculated function, and (2) less parallel evolution across lake-stream pairs, in the many-to-one systems relative to the one-to-one system. We confirm both predictions, thus supporting the theoretical expectation that increasing many-to-one mapping undermines parallel evolution. Therefore, sole consideration of morphological variation within and among populations might not serve as a proxy for functional variation when multiple adaptive trait combinations exist. © 2017 The Author(s). Evolution © 2017 The Society for the Study of Evolution.

Warthin tumor-like papillary thyroid carcinoma with a minor dedifferentiated component: report of a case with clinicopathologic considerations.

PubMed

Amico, Paolo; Lanzafame, Salvatore; Li Destri, Giovanni; Greco, Paolo; Caltabiano, Rosario; Vecchio, Giada Maria; Magro, Gaetano

2010-01-01

Warthin tumor-like papillary thyroid carcinoma is an uncommon variant of papillary thyroid carcinoma. We report a rare case of Warthin tumor-like variant of papillary thyroid carcinoma with a dedifferentiated component consisting of a solid tumor area composed of neoplastic cells with a spindle to tall cell morphology associated with marked nuclear pleomorphism, atypical mitoses, and foci of necrosis. Although our patient presented with a locally aggressive disease (T3 N1b Mo), she is disease-free without radioiodine therapy after a 23-month follow-up period. We emphasize that Warthin tumor-like papillary thyroid carcinoma, like other morphological variants of papillary carcinoma, may occasionally undergo dedifferentiation. As this component may be only focally detectable, we suggest an extensive sampling of all large-sized (>3 cm) papillary thyroid carcinoma. Recognition of any dedifferentiated component in a Warthin tumor-like papillary thyroid carcinoma should be reported, including its percentage, because it may reflect a more aggressive clinical course.

Warthin Tumor-Like Papillary Thyroid Carcinoma with a Minor Dedifferentiated Component: Report of a Case with Clinicopathologic Considerations

PubMed Central

Amico, Paolo; Lanzafame, Salvatore; Li Destri, Giovanni; Greco, Paolo; Caltabiano, Rosario; Vecchio, Giada Maria; Magro, Gaetano

2010-01-01

Warthin tumor-like papillary thyroid carcinoma is an uncommon variant of papillary thyroid carcinoma. We report a rare case of Warthin tumor-like variant of papillary thyroid carcinoma with a dedifferentiated component consisting of a solid tumor area composed of neoplastic cells with a spindle to tall cell morphology associated with marked nuclear pleomorphism, atypical mitoses, and foci of necrosis. Although our patient presented with a locally aggressive disease (T3 N1b Mo), she is disease-free without radioiodine therapy after a 23-month follow-up period. We emphasize that Warthin tumor-like papillary thyroid carcinoma, like other morphological variants of papillary carcinoma, may occasionally undergo dedifferentiation. As this component may be only focally detectable, we suggest an extensive sampling of all large-sized (>3 cm) papillary thyroid carcinoma. Recognition of any dedifferentiated component in a Warthin tumor-like papillary thyroid carcinoma should be reported, including its percentage, because it may reflect a more aggressive clinical course. PMID:20593036

Quantifying the effects of antiangiogenic and chemotherapy drug combinations on drug delivery and treatment efficacy

PubMed Central

Yιlmaz, Defne; Phipps, Colin; Kohandel, Mohammad

2017-01-01

Tumor-induced angiogenesis leads to the development of leaky tumor vessels devoid of structural and morphological integrity. Due to angiogenesis, elevated interstitial fluid pressure (IFP) and low blood perfusion emerge as common properties of the tumor microenvironment that act as barriers for drug delivery. In order to overcome these barriers, normalization of vasculature is considered to be a viable option. However, insight is needed into the phenomenon of normalization and in which conditions it can realize its promise. In order to explore the effect of microenvironmental conditions and drug scheduling on normalization benefit, we build a mathematical model that incorporates tumor growth, angiogenesis and IFP. We administer various theoretical combinations of antiangiogenic agents and cytotoxic nanoparticles through heterogeneous vasculature that displays a similar morphology to tumor vasculature. We observe differences in drug extravasation that depend on the scheduling of combined therapy; for concurrent therapy, total drug extravasation is increased but in adjuvant therapy, drugs can penetrate into deeper regions of tumor. PMID:28922358

Quantifying the effects of antiangiogenic and chemotherapy drug combinations on drug delivery and treatment efficacy.

PubMed

Yonucu, Sirin; Yιlmaz, Defne; Phipps, Colin; Unlu, Mehmet Burcin; Kohandel, Mohammad

2017-09-01

Tumor-induced angiogenesis leads to the development of leaky tumor vessels devoid of structural and morphological integrity. Due to angiogenesis, elevated interstitial fluid pressure (IFP) and low blood perfusion emerge as common properties of the tumor microenvironment that act as barriers for drug delivery. In order to overcome these barriers, normalization of vasculature is considered to be a viable option. However, insight is needed into the phenomenon of normalization and in which conditions it can realize its promise. In order to explore the effect of microenvironmental conditions and drug scheduling on normalization benefit, we build a mathematical model that incorporates tumor growth, angiogenesis and IFP. We administer various theoretical combinations of antiangiogenic agents and cytotoxic nanoparticles through heterogeneous vasculature that displays a similar morphology to tumor vasculature. We observe differences in drug extravasation that depend on the scheduling of combined therapy; for concurrent therapy, total drug extravasation is increased but in adjuvant therapy, drugs can penetrate into deeper regions of tumor.

Cancer evolution: mathematical models and computational inference.

PubMed

Beerenwinkel, Niko; Schwarz, Roland F; Gerstung, Moritz; Markowetz, Florian

2015-01-01

Cancer is a somatic evolutionary process characterized by the accumulation of mutations, which contribute to tumor growth, clinical progression, immune escape, and drug resistance development. Evolutionary theory can be used to analyze the dynamics of tumor cell populations and to make inference about the evolutionary history of a tumor from molecular data. We review recent approaches to modeling the evolution of cancer, including population dynamics models of tumor initiation and progression, phylogenetic methods to model the evolutionary relationship between tumor subclones, and probabilistic graphical models to describe dependencies among mutations. Evolutionary modeling helps to understand how tumors arise and will also play an increasingly important prognostic role in predicting disease progression and the outcome of medical interventions, such as targeted therapy. © The Author(s) 2014. Published by Oxford University Press on behalf of the Society of Systematic Biologists.

Solid Pseudopapillary Tumor of the Pancreas: One Case with a Metastatic Evolution in a Caucasian Woman

PubMed Central

Lestelle, Valentin; de Coster, Claire; Sarran, Anthony; Poizat, Flora; Delpero, Jean-Robert; Raoul, Jean-Luc

2015-01-01

We report the case of a Caucasian woman, operated on for a solid pseudopapillary tumor of the pancreas in 2009, who recurred 4 years later with multiple liver metastases requiring liver resection. This disease is infrequent, particularly among the Caucasian population, and metastatic evolution is very rare. PMID:26557078

Correlated evolution of body and fin morphology in the cichlid fishes.

PubMed

Feilich, Kara L

2016-10-01

Body and fin shapes are chief determinants of swimming performance in fishes. Different configurations of body and fin shapes can suit different locomotor specializations. The success of any configuration is dependent upon the hydrodynamic interactions between body and fins. Despite the importance of body-fin interactions for swimming, there are few data indicating whether body and fin configurations evolve in concert, or whether these structures vary independently. The cichlid fishes are a diverse family whose well-studied phylogenetic relationships make them ideal for the study of macroevolution of ecomorphology. This study measured body, and caudal and median fin morphology from radiographs of 131 cichlid genera, using morphometrics and phylogenetic comparative methods to determine whether these traits exhibit correlated evolution. Partial least squares canonical analysis revealed that body, caudal fin, dorsal fin, and anal fin shapes all exhibited strong correlated evolution consistent with locomotor ecomorphology. Major patterns included the evolution of deep body profiles with long fins, suggestive of maneuvering specialization; and the evolution of narrow, elongate caudal peduncles with concave tails, a combination that characterizes economical cruisers. These results demonstrate that body shape evolution does not occur independently of other traits, but among a suite of other morphological changes that augment locomotor specialization. © 2016 The Author(s). Evolution © 2016 The Society for the Study of Evolution.

Morphological bubble evolution induced by air diffusion on submerged hydrophobic structures

NASA Astrophysics Data System (ADS)

Lv, Pengyu; Xiang, Yaolei; Xue, Yahui; Lin, Hao; Duan, Huiling

2017-03-01

Bubbles trapped in the cavities always play important roles in the underwater applications of structured hydrophobic surfaces. Air exchange between bubbles and surrounding water has a significant influence on the morphological bubble evolution, which in turn frequently affects the functionalities of the surfaces, such as superhydrophobicity and drag reduction. In this paper, air diffusion induced bubble evolution on submerged hydrophobic micropores under reduced pressures is investigated experimentally and theoretically. The morphological behaviors of collective and single bubbles are observed using confocal microscopy. Four representative evolution phases of bubbles are captured in situ. After depressurization, bubbles will not only grow and coalesce but also shrink and split although the applied pressure remains negative. A diffusion-based model is used to analyze the evolution behavior and the results are consistent with the experimental data. A criterion for bubble growth and shrinkage is also derived along with a phase diagram, revealing that the competition of effective gas partial pressures across the two sides of the diffusion layer dominates the bubble evolution process. Strategies for controlling the bubble evolution behavior are also proposed based on the phase diagram. The current work provides a further understanding of the general behavior of bubble evolution induced by air diffusion and can be employed to better designs of functional microstructured hydrophobic surfaces.

A New LC-MS-based Strategy to integrate chemistry, morphology, and evolution of eggplant (Solanum) species

USDA-ARS?s Scientific Manuscript database

The economically valuable giant genus Solanum, containing dozens of functional food species such as eggplant and tomato, affords an excellent system to compare and correlate metabolic chemistry with species morphology and evolution. Here, we devised a strategy based on repeatable reversed-phase LC-T...

Paired Exome Analysis Reveals Clonal Evolution and Potential Therapeutic Targets in Urothelial Carcinoma.

PubMed

Lamy, Philippe; Nordentoft, Iver; Birkenkamp-Demtröder, Karin; Thomsen, Mathilde Borg Houlberg; Villesen, Palle; Vang, Søren; Hedegaard, Jakob; Borre, Michael; Jensen, Jørgen Bjerggaard; Høyer, Søren; Pedersen, Jakob Skou; Ørntoft, Torben F; Dyrskjøt, Lars

2016-10-01

Greater knowledge concerning tumor heterogeneity and clonality is needed to determine the impact of targeted treatment in the setting of bladder cancer. In this study, we performed whole-exome, transcriptome, and deep-focused sequencing of metachronous tumors from 29 patients initially diagnosed with early-stage bladder tumors (14 with nonprogressive disease and 15 with progressive disease). Tumors from patients with progressive disease showed a higher variance of the intrapatient mutational spectrum and a higher frequency of APOBEC-related mutations. Allele-specific expression was also higher in these patients, particularly in tumor suppressor genes. Phylogenetic analysis revealed a common origin of the metachronous tumors, with a higher proportion of clonal mutations in the ancestral branch; however, 19 potential therapeutic targets were identified as both ancestral and tumor-specific alterations. Few subclones were present based on PyClone analysis. Our results illuminate tumor evolution and identify candidate therapeutic targets in bladder cancer. Cancer Res; 76(19); 5894-906. ©2016 AACR. ©2016 American Association for Cancer Research.

Hotspot mutation panel testing reveals clonal evolution in a study of 265 paired primary and metastatic tumors.

PubMed

Goswami, Rashmi S; Patel, Keyur P; Singh, Rajesh R; Meric-Bernstam, Funda; Kopetz, E Scott; Subbiah, Vivek; Alvarez, Ricardo H; Davies, Michael A; Jabbar, Kausar J; Roy-Chowdhuri, Sinchita; Lazar, Alexander J; Medeiros, L Jeffrey; Broaddus, Russell R; Luthra, Rajyalakshmi; Routbort, Mark J

2015-06-01

We used a clinical next-generation sequencing (NGS) hotspot mutation panel to investigate clonal evolution in paired primary and metastatic tumors. A total of 265 primary and metastatic tumor pairs were sequenced using a 46-gene cancer mutation panel capable of detecting one or more single-nucleotide variants as well as small insertions/deletions. Mutations were tabulated together with tumor type and percentage, mutational variant frequency, time interval between onset of primary tumor and metastasis, and neoadjuvant therapy status. Of note, 227 of 265 (85.7%) tumor metastasis pairs showed identical mutation calls. Of the tumor pairs with identical mutation calls, 160 (60.4%) possessed defining somatic mutation signatures and 67 (25.3%) did not exhibit any somatic mutations. There were 38 (14.3%) cases that showed at least one novel mutation call between the primary and metastasis. Metastases were almost two times more likely to show novel mutations (n = 20, 7.5%) than primary tumors (n = 12, 4.5%). TP53 was the most common additionally mutated gene in metastatic lesions, followed by PIK3CA and SMAD4. PIK3CA mutations were more often associated with metastasis in colon carcinoma samples. Clinical NGS hotspot panels can be useful in analyzing clonal evolution within tumors as well as in determining subclonal mutations that can expand in future metastases. PIK3CA, SMAD4, and TP53 are most often involved in clonal divergence, providing potential targets that may help guide the clinical management of tumor progression or metastases. ©2015 American Association for Cancer Research.

Mitochondrial control by DRP1 in brain tumor initiating cells.

PubMed

Xie, Qi; Wu, Qiulian; Horbinski, Craig M; Flavahan, William A; Yang, Kailin; Zhou, Wenchao; Dombrowski, Stephen M; Huang, Zhi; Fang, Xiaoguang; Shi, Yu; Ferguson, Ashley N; Kashatus, David F; Bao, Shideng; Rich, Jeremy N

2015-04-01

Brain tumor initiating cells (BTICs) co-opt the neuronal high affinity glucose transporter, GLUT3, to withstand metabolic stress. We investigated another mechanism critical to brain metabolism, mitochondrial morphology, in BTICs. BTIC mitochondria were fragmented relative to non-BTIC tumor cell mitochondria, suggesting that BTICs increase mitochondrial fission. The essential mediator of mitochondrial fission, dynamin-related protein 1 (DRP1), showed activating phosphorylation in BTICs and inhibitory phosphorylation in non-BTIC tumor cells. Targeting DRP1 using RNA interference or pharmacologic inhibition induced BTIC apoptosis and inhibited tumor growth. Downstream, DRP1 activity regulated the essential metabolic stress sensor, AMP-activated protein kinase (AMPK), and targeting AMPK rescued the effects of DRP1 disruption. Cyclin-dependent kinase 5 (CDK5) phosphorylated DRP1 to increase its activity in BTICs, whereas Ca(2+)-calmodulin-dependent protein kinase 2 (CAMK2) inhibited DRP1 in non-BTIC tumor cells, suggesting that tumor cell differentiation induces a regulatory switch in mitochondrial morphology. DRP1 activation correlated with poor prognosis in glioblastoma, suggesting that mitochondrial dynamics may represent a therapeutic target for BTICs.

Coral reefs promote the evolution of morphological diversity and ecological novelty in labrid fishes.

PubMed

Price, S A; Holzman, R; Near, T J; Wainwright, P C

2011-05-01

Although coral reefs are renowned biodiversity hotspots it is not known whether they also promote the evolution of exceptional ecomorphological diversity. We investigated this question by analysing a large functional morphological dataset of trophic characters within Labridae, a highly diverse group of fishes. Using an analysis that accounts for species relationships, the time available for diversification and model uncertainty we show that coral reef species have evolved functional morphological diversity twice as fast as non-reef species. In addition, coral reef species occupy 68.6% more trophic morphospace than non-reef species. Our results suggest that coral reef habitats promote the evolution of both trophic novelty and morphological diversity within fishes. Thus, the preservation of coral reefs is necessary, not only to safeguard current biological diversity but also to conserve the underlying mechanisms that can produce functional diversity in future. © 2011 Blackwell Publishing Ltd/CNRS.

Chemical Evidence for Evolution of galaxies

NASA Astrophysics Data System (ADS)

Dutil, Yvan

I have compiled the very best data published on abundance gradients. From this sample of 29 galaxies, some information can be gained on the mecanism of morphological evolution in disk galaxies. From this sample, I find that early-type galaxies show an identical trend in the behavior of extrapolated central abundance versus morphological type to that shown by late-type galaxies with strong bars, even in the absence of bar! On a a diagram showing extrapolated central abundance versus morphological type, two sequences appear: late-type barred galaxies and early-type galaxies (barred or not barred) fall on sequence 0.5 dex below that of normal late-type galaxies. This behavior is consistent with a scenario of morphological evolution of disk galaxies by formation and dissolution of a bar over a period of a few 10^^9 yr, where later type galaxies (Sd,Sc,Sbc, evolve into earlier-type disk galaxies trough transitory SBc and SBb phases.

An automatic brain tumor segmentation tool.

PubMed

Diaz, Idanis; Boulanger, Pierre; Greiner, Russell; Hoehn, Bret; Rowe, Lindsay; Murtha, Albert

2013-01-01

This paper introduces an automatic brain tumor segmentation method (ABTS) for segmenting multiple components of brain tumor using four magnetic resonance image modalities. ABTS's four stages involve automatic histogram multi-thresholding and morphological operations including geodesic dilation. Our empirical results, on 16 real tumors, show that ABTS works very effectively, achieving a Dice accuracy compared to expert segmentation of 81% in segmenting edema and 85% in segmenting gross tumor volume (GTV).

Morphogenesis and Complexity of the Tumor Patterns

NASA Astrophysics Data System (ADS)

Izquierdo-Kulich, E.; Nieto-Villar, J. M.

A mechanism to describe the apoptosis process at mesoscopic level through p53 is proposed in this paper. A deterministic model given by three differential equations is deduced from the mesoscopic approach, which exhibits sustained oscillations caused by a supercritical Andronov-Hopf bifurcation. Taking as hypothesis that the p53 sustained oscillation is the fundamental mechanism for apoptosis regulation; the model predicts that it is necessary a strict control of p53 to stimulated it, which is an important consideration to established new therapy strategy to fight cancer. The mathematical modeling of tumor growth allows us to describe the most important regularities of these systems. A stochastic model, based on the most important processes that take place at the level of individual cells, is proposed to predict the dynamical behavior of the expected radius of the tumor and its fractal dimension. It was found that the tumor has a characteristic fractal dimension, which contains the necessary information to predict the tumor growth until it reaches a stationary state. The mathematical modeling of tumor growth is an approach to explain the complex nature of these systems. A model that describes tumor growth was obtained by using a mesoscopic formalism and fractal dimension. This model theoretically predicts the relation between the morphology of the cell pattern and the mitosis/apoptosis quotient that helps to predict tumor growth from tumoral cells fractal dimension. The relation between the tumor macroscopic morphology and the cell pattern morphology is also determined. This could explain why the interface fractal dimension decreases with the increase of the cell pattern fractal dimension and consequently with the increase of the mitosis/apoptosis relation. Indexes to characterize tumoral cell proliferation and invasion capacities are proposed and used to predict the growth of different types of tumors. These indexes also show that the proliferation capacity is directly proportional to the invasion capacity. The proposed model assumes: i) only interface cells proliferate and invade the host, and ii) the fractal dimension of tumoral cell patterns, can reproduce the Gompertzian growth law. A mathematical model was obtained to describe the relation between the tissue morphology of cervix carcinoma and both dynamic processes of mitosis and apoptosis, and an expression to quantify the tumor aggressiveness, which in this context is associated with the tumor growth rate. The proposed model was applied to Stage III cervix carcinoma in vivo studies. In this study we found that the apoptosis rate was significantly smaller in the tumor tissues and both the mitosis rate and aggressiveness index decrease with Stage III patient's age. These quantitative results correspond to observed behavior in clinical and genetics studies. Finally, the entropy production rate was determined for avascular tumor growth. The proposed formula relates the fractal dimension of the tumor contour with the quotient between mitosis and apoptosis rate, which can be used to characterize the degree of proliferation of tumor cells. The entropy production rate was determined for fourteen tumor cell lines as a physical function of cancer robustness. The entropy production rate is a hallmark that allows us the possibility of prognosis of tumor proliferation and invasion capacities, key factors to improve cancer therapy.

Anaplastic sarcoma of the kidney.

PubMed

Labanaris, Apostolos; Zugor, Vahudin; Smiszek, Robert; Nützel, Reinhold; Kühn, Reinhard

2009-02-15

Wilms tumor can appear with a wide spectrum of morphologic features and can sometimes cover or delay the recognition of other clinicopathologic entities of the kidney. We present a case of a new tumor entity of the kidney, namely the anaplastic sarcoma of the kidney, a tumor of high malignancy.

Procedure for quantitative determination of effectiveness of photoinduced destruction of malignant tumors

NASA Astrophysics Data System (ADS)

Bizyuk, S. A.; Istomin, Yu. P.; Dzhagarov, B. M.

2006-07-01

We have developed a procedure for analysis of the functional status of blood vessels in tumor tissues using computer-assisted color scanning of tumor slices and also for a quantitative assessment of the effectiveness of photoinduced destruction of tumor tissues in animal experiments. Its major advantage is direct determination of the size of the tumor necrosis zone. The procedure has been tested in an experiment on three strains of malignant tumors with different morphologies.

Intratumoral heterogeneity and clonal evolution in blood malignancies and solid tumors.

PubMed

Varela, Ignacio; Menendez, Pablo; Sanjuan-Pla, Alejandra

2017-09-12

This meeting held at the University of Barcelona in March 2017, brought together scientists and clinicians worldwide to discuss current and future clinico-biological implications of intratumoral heterogeneity (ITH) and subclonal evolution in cancer diagnosis, patient stratification, and treatment resistance in diagnosis, treatment and follow-up. There was consensus that both longitudinal and tumor multi-region studies in matched samples are needed to better understand the dynamics of ITH. The contribution of the epigenome and microenvironment to ITH and subclone evolution remains understudied. It was recommended to combine computational, pathology and imaging tools to study the role of the microenvironment in subclone selection/evolution.

High hydrostatic pressure-induced cell death in human chondrocytes and chondrosarcoma cells.

PubMed

Naal, Florian-Dominique; Mengele, Karin; Schauwecker, Johannes; Gollwitzer, Hans; Gerdesmeyer, Ludger; Reuning, Ute; Mittelmeier, Wolfram; Gradinger, Reiner; Schmitt, Manfred; Diehl, Peter

2005-01-01

In orthopedic surgery, sterilization of bone used for reconstruction of osteoarticular defects caused by malignant tumors is carried out in different ways. At present, to devitalize tumor-bearing osteochondral segments, extracorporal irradiation or autoclaving is mainly used, although both methods have substantial disadvantages, e.g. loss of biomechanical and/or biological integrity of the bone and destabilization of the articular surface. In this regard, high hydrostatic pressure (HHP) treatment of bone is a new, advancing technology, now being used in preclinical testing to inactivate tumor cells. To find out if this technique is also suited for extracorporal inactivation of chondrocytes and chondral tumor cells, the effect of HHP on cell viability and morphology of human chondrocytes / chondrosarcoma cells was investigated in the present study. SW1353 chondrosarcoma cells and chondrocytes were subjected to HHP in the range of 50 to 350 MPa (10 min, 37 degrees C) and, subsequently, cell viability and cell morphology assessed. After exposure at 350 MPa, all HHP-treated chondral cells showed explicit morphological changes, evident by membrane ruffling and bleb formation; chondrosarcoma cells treated this way were irreversibly damaged and not alive. We anticipate that, in orthopedic surgery, HHP eventually can serve as a novel, promising technical approach for cell inactivation (including tumor cells) and allow subsequent reimplantation of the osteoarticular autograft.

THE EVOLUTION OF EARLY- AND LATE-TYPE GALAXIES IN THE COSMIC EVOLUTION SURVEY UP TO z {approx} 1.2

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pannella, Maurilio; Gabasch, Armin; Drory, Niv

2009-08-10

The Cosmic Evolution Survey (COSMOS) allows for the first time a highly significant census of environments and structures up to redshift 1, as well as a full morphological description of the galaxy population. In this paper we present a study aimed to constrain the evolution, in the redshift range 0.2 < z < 1.2, of the mass content of different morphological types and its dependence on the environmental density. We use a deep multicolor catalog, covering an area of {approx}0.7 deg{sup 2} inside the COSMOS field, with accurate photometric redshifts (i {approx}< 26.5 and {delta}z/(z {sub spec} + 1) {approx}more » 0.035). We estimate galaxy stellar masses by fitting the multicolor photometry to a grid of composite stellar population models. We quantitatively describe the galaxy morphology by fitting point-spread function convolved Sersic profiles to the galaxy surface brightness distributions down to F814 = 24 mag for a sample of 41,300 objects. We confirm an evolution of the morphological mix with redshift: the higher the redshift the more disk-dominated galaxies become important. We find that the morphological mix is a function of the local comoving density: the morphology density relation extends up to the highest redshift explored. The stellar mass function of disk-dominated galaxies is consistent with being constant with redshift. Conversely, the stellar mass function of bulge-dominated systems shows a decline in normalization with redshift. Such different behaviors of late-types and early-types stellar mass functions naturally set the redshift evolution of the transition mass. We find a population of relatively massive, early-type galaxies, having high specific star formation rate (SSFR) and blue colors which live preferentially in low-density environments. The bulk of massive (>7 x 10{sup 10} M {sub sun}) early-type galaxies have similar characteristic ages, colors, and SSFRs independently of the environment they belong to, with those hosting the oldest stars in the universe preferentially belonging to the highest density regions. The whole catalog including morphological information and stellar mass estimates analyzed in this work is made publicly available.« less

Nanocluster irradiation evolution in Fe-9%Cr ODS and ferritic-martensitic alloys

NASA Astrophysics Data System (ADS)

Swenson, M. J.; Wharry, J. P.

2017-12-01

The objective of this study is to evaluate the influence of dose rate and cascade morphology on nanocluster evolution in a model Fe-9%Cr oxide dispersion strengthened steel and the commercial ferritic/martensitic (F/M) alloys HCM12A and HT9. We present a large, systematic data set spanning the three alloys, three irradiating particle types, four orders of magnitude in dose rate, and doses ranging 1-100 displacements per atom over 400-500 °C. Nanoclusters are characterized using atom probe tomography. ODS oxide nanoclusters experience partial dissolution after irradiation due to inverse Ostwald ripening, while F/M nanoclusters undergo Ostwald ripening. Damage cascade morphology is indicative of nanocluster number density evolution. Finally, the effects of dose rate on nanocluster morphology provide evidence for a temperature dilation theory, which purports that a negative temperature shift is necessary for higher dose rate irradiations to emulate nanocluster evolution in lower dose rate irradiations.

Albumin Evolution in Frogs: A Test of the Evolutionary Clock Hypothesis

PubMed Central

Wallace, Donald G.; Maxson, Linda R.; Wilson, Allan C.

1971-01-01

Frogs are an ancient group compared to placental mammals. Yet, although there are about as many species of frogs as there are of mammals, zoologists consider that frogs have undergone only limited morphological divergence, while placental mammals have diversified greatly in morphology and way of life. The serum albumins of numerous frog species were compared by the quantitative microcomplement fixation technique. Frogs that are morphologically similar enough to merit taxonomic distinction at only the species level often exhibit differences in the serological properties of their albumins larger than those usually seen between mammals placed in distinct families or suborders. Thus, there seems to be a contrast between albumin evolution and evolution at the organismal level. The large differences between albumins among frogs can be explained by the hypothesis that albumin evolution has proceeded at the same rate in frogs as in mammals. PMID:5002283

Functional coupling constrains craniofacial diversification in Lake Tanganyika cichlids

PubMed Central

Tsuboi, Masahito; Gonzalez-Voyer, Alejandro; Kolm, Niclas

2015-01-01

Functional coupling, where a single morphological trait performs multiple functions, is a universal feature of organismal design. Theory suggests that functional coupling may constrain the rate of phenotypic evolution, yet empirical tests of this hypothesis are rare. In fish, the evolutionary transition from guarding the eggs on a sandy/rocky substrate (i.e. substrate guarding) to mouthbrooding introduces a novel function to the craniofacial system and offers an ideal opportunity to test the functional coupling hypothesis. Using a combination of geometric morphometrics and a recently developed phylogenetic comparative method, we found that head morphology evolution was 43% faster in substrate guarding species than in mouthbrooding species. Furthermore, for species in which females were solely responsible for mouthbrooding the males had a higher rate of head morphology evolution than in those with bi-parental mouthbrooding. Our results support the hypothesis that adaptations resulting in functional coupling constrain phenotypic evolution. PMID:25948565

Functional coupling constrains craniofacial diversification in Lake Tanganyika cichlids.

PubMed

Tsuboi, Masahito; Gonzalez-Voyer, Alejandro; Kolm, Niclas

2015-05-01

Functional coupling, where a single morphological trait performs multiple functions, is a universal feature of organismal design. Theory suggests that functional coupling may constrain the rate of phenotypic evolution, yet empirical tests of this hypothesis are rare. In fish, the evolutionary transition from guarding the eggs on a sandy/rocky substrate (i.e. substrate guarding) to mouthbrooding introduces a novel function to the craniofacial system and offers an ideal opportunity to test the functional coupling hypothesis. Using a combination of geometric morphometrics and a recently developed phylogenetic comparative method, we found that head morphology evolution was 43% faster in substrate guarding species than in mouthbrooding species. Furthermore, for species in which females were solely responsible for mouthbrooding the males had a higher rate of head morphology evolution than in those with bi-parental mouthbrooding. Our results support the hypothesis that adaptations resulting in functional coupling constrain phenotypic evolution.

Large Magellanic Cloud Planetary Nebula Morphology: Probing Stellar Populations and Evolution.

PubMed

Stanghellini; Shaw; Balick; Blades

2000-05-10

Planetary nebulae (PNe) in the Large Magellanic Cloud (LMC) offer the unique opportunity to study both the population and evolution of low- and intermediate-mass stars, by means of the morphological type of the nebula. Using observations from our LMC PN morphological survey, and including images available in the Hubble Space Telescope Data Archive and published chemical abundances, we find that asymmetry in PNe is strongly correlated with a younger stellar population, as indicated by the abundance of elements that are unaltered by stellar evolution (Ne, Ar, and S). While similar results have been obtained for Galactic PNe, this is the first demonstration of the relationship for extragalactic PNe. We also examine the relation between morphology and abundance of the products of stellar evolution. We found that asymmetric PNe have higher nitrogen and lower carbon abundances than symmetric PNe. Our two main results are broadly consistent with the predictions of stellar evolution if the progenitors of asymmetric PNe have on average larger masses than the progenitors of symmetric PNe. The results bear on the question of formation mechanisms for asymmetric PNe-specifically, that the genesis of PNe structure should relate strongly to the population type, and by inference the mass, of the progenitor star and less strongly on whether the central star is a member of a close binary system.

Morphological, Structural and Optical Evolution of Ag Nanostructures on c-Plane GaN Through the Variation of Deposition Amount and Temperature

NASA Astrophysics Data System (ADS)

Sui, Mao; Li, Ming-Yu; Pandey, Puran; Zhang, Quanzhen; Kunwar, Sundar; Lee, Jihoon

2018-03-01

Owing to their tunable properties, Ag nanostructures have been widely adapted in various applications and the morphological control can determine their performance and effectiveness. In this work, we demonstrate the morphological and optical evolution of Ag nanostructures on GaN (0001) by the systematic control of deposition amount at two distinctive annealing temperatures. Based on the Volmer-Weber and coalescence growth models, the nanostructure growth commenced by the thermal solid-state-dewetting evolve in terms of size, density and configuration. At 450 °C, the round-dome shaped Ag nanoparticles (regime I), irregular Ag nano-mounds (regime II) and void-layer structures (regime III) are observed along with the gradually increased deposition amount. As a sharp distinction, the solid state dewetting process occur more radically at 700 °C and also, the Ag sublimation and the effect on the nanostructure formation are observed in a clear regime shift scaled by the deposition amount. Meanwhile, a strong dependency of reflectance spectra evolution on the Ag nanostructure morphology is witnessed for both sets. In particular, Ag dipolar resonance peaks are significantly red-shifted from VIS to NIR regions along with the nanostructure evolution. The reflectance, PL and Raman intensity variation are also observed and discussed based on the evolution of Ag nanostructures.

Morphology and Evolution of Sublimation Pits on Pluto

NASA Astrophysics Data System (ADS)

Abu-Hashmeh, N.; Conrad, J. W.; Nimmo, F.; Moore, J. M.; Stern, A.; Olkin, C.; Weaver, H. A., Jr.; Ennico Smith, K.; Young, L. A.

2017-12-01

Pluto's Sputnik Planitia region hosts a geologically young surface of nitrogen ice that exhibits striking pitted terrain (Moore et al., Science 351, 2016). These pits are most likely formed by sublimation due to incident sunlight, similar to the southern polar cap of Mars (Byrne and Ingersoll, Science 299, 2003); however, their evolution over time has resulted in unique morphological characteristics. Motivated by this, we used the high-resolution mosaic strips captured by New Horizons' Long Range Reconnaissance Imager (LORRI) to map sublimation pits in the southernmost region of Sputnik Planitia. Statistical data shows pit orientations appearing North-South dominant; their morphology also indicates extensional evolution along the major axis caused by further sublimation and contact-coalescence processes. Qualitative analysis of the region yielded indications of an evolutionary path for individual pits that coalesce into each other and exhibit an elongated end-stage. Additionally, densely-pitted regions generally appear to correlate with regions containing longer pits, implying that coalescence may be an important process for elongation. We also model the evolution geometry through competing effects of diffusion (viscous relaxation) and retreat (sublimation) (Buhler and Ingersoll, LPSC Abstract #1746, 2017). The model demonstrates single-pit and coalescing-pit evolutions that influence overall length, as well as a potential ability for the pit center to move in space while the pit morphology evolves.

Sexual selection and the evolution of genital shape and complexity in water striders.

PubMed

Rowe, Locke; Arnqvist, Göran

2012-01-01

Animal genitalia show two striking but incompletely understood evolutionary trends: a great evolutionary divergence in the shape of genitalic structures, and characteristic structural complexity. Both features are thought to result from sexual selection, but explicit comparative tests are hampered by the fact that it is difficult to quantify both morphological complexity and divergence in shape. We undertake a comparative study of multiple nongenitalic and male genital traits in a clade of 15 water strider species to quantify complexity and shape divergence. We show that genital structures are more complex and their shape more divergent among species than nongenital traits. Further, intromittent genital traits are more complex and have evolved more divergently than nonintromittent genital traits. More importantly, shape and complexity of nonintromittent genital traits show correlated evolution with indices of premating sexual selection and intromittent genital traits with postmating sexual selection, suggesting that the evolution of different components of genital morphology are shaped independently by distinct forms of sexual selection. Our quantitative results provide direct comparative support for the hypothesis that sexual selection is associated with morphological complexity in genitalic traits and highlight the importance of quantifying morphological shape and complexity, rather than size in studies of genital evolution. © 2011 The Author(s). Evolution © 2011 The Society for the Study of Evolution.

Asymmetric mismatch in strain-specific genital morphology causes increased harm to Drosophila females.

PubMed

Masly, John P; Kamimura, Yoshitaka

2014-08-01

Although several evolutionary forces have been proposed to contribute to genital morphological diversification, it is unclear which might act early during the evolution of novel structural traits. We test the hypothesis that mismatch between interacting male and female secondary sexual structures gives rise to increased harm to females, consistent with the outcome predicted from a history of sexual conflict. We mate Drosophila sechellia females to males from a collection of D. mauritiana-D. sechellia interspecific genetic introgression lines that possess quantitative morphological variation in the posterior lobe of the genital arch, an external genital structure that can cause wounds to the female abdomen during mating. We find that males with smaller posterior lobes, and those that possess lobes with similarities in shape to D. mauritiana, cause more severe wounding compared to either D. sechellia males with strain-specific morphologies or introgression males that possess larger lobes or lobes with more pronounced D. sechellia features. These results suggest a possible history of sexual conflict during the evolution of the posterior lobe in D. sechellia, but also suggest a potential contribution of divergence in sensory recognition mechanisms to posterior lobe evolution. © 2014 The Author(s). Evolution © 2014 The Society for the Study of Evolution.

mDia2 and CXCL12/CXCR4 chemokine signaling intersect to drive tumor cell amoeboid morphological transitions.

PubMed

Wyse, Meghan M; Goicoechea, Silvia; Garcia-Mata, Rafael; Nestor-Kalinoski, Andrea L; Eisenmann, Kathryn M

2017-03-04

Morphological plasticity in response to environmental cues in migrating cancer cells requires F-actin cytoskeletal rearrangements. Conserved formin family proteins play critical roles in cell shape, tumor cell motility, invasion and metastasis, in part, through assembly of non-branched actin filaments. Diaphanous-related formin-2 (mDia2/Diaph3/Drf3/Dia) regulates mesenchymal-to-amoeboid morphological conversions and non-apoptotic blebbing in tumor cells by interacting with its inhibitor diaphanous-interacting protein (DIP), and disrupting cortical F-actin assembly and bundling. F-actin disruption is initiated by a CXCL12-dependent mechanism. Downstream CXCL12 signaling partners inducing mDia2-dependent amoeboid conversions remain enigmatic. We found in MDA-MB-231 tumor cells CXCL12 induces DIP and mDia2 interaction in blebs, and engages its receptor CXCR4 to induce RhoA-dependent blebbing. mDia2 and CXCR4 associate in blebs upon CXCL12 stimulation. Both CXCR4 and RhoA are required for CXCL12-induced blebbing. Neither CXCR7 nor other Rho GTPases that activate mDia2 are required for CXCL12-induced blebbing. The Rho Guanine Nucleotide Exchange Factor (GEF) Net1 is required for CXCL12-driven RhoA activation and subsequent blebbing. These results reveal CXCL12 signaling, through CXCR4, directs a Net1/RhoA/mDia-dependent signaling hub to drive cytoskeleton rearrangements to regulate morphological plasticity in tumor cells. These signaling hubs may be conserved during normal and cancer cells responding to chemotactic cues. Copyright © 2017 Elsevier Inc. All rights reserved.

Adrenocortical adenoma and carcinoma: histopathological and molecular comparative analysis.

PubMed

Stojadinovic, Alexander; Brennan, Murray F; Hoos, Axel; Omeroglu, Atilla; Leung, Denis H Y; Dudas, Maria E; Nissan, Aviram; Cordon-Cardo, Carlos; Ghossein, Ronald A

2003-08-01

We compared histomorphological features and molecular expression profiles of adrenocortical adenomas (ACAd) and carcinomas (ACCa). A critical histopathological review (mean, 11 slides per patient) was conducted of 37 ACAd and 67 ACCa. Paraffin-embedded tissue cores of ACAd (n = 33) and ACCa (n = 38) were arrayed in triplicate on tissue microarrays. Expression profiles of p53, mdm-2, p21, Bcl-2, cyclin D1, p27, and Ki-67 were investigated by immunohistochemistry and correlated with histopathology and patient outcome using standard statistical methodology. Median follow-up period was 5 years. Tumor necrosis, atypical mitoses, and >1 mitosis per 50 high-power fields were factors that were highly specific for ACCa (P <.001). Number (0 to 4) of unfavorable markers [Ki-67 (+), p21 (+), p27 (+), mdm-2(-)] expressed was significantly associated with mitotic activity and morphologic index (i.e., number of adverse morphologic features) and highly predictive of malignancy (P <.001). Ki-67 overexpression occurred in 0 ACAd and 36% ACCa (P <.001) and was significantly associated with mitotic rate and unfavorable morphologic index (P <.001). Tumor necrosis, atypical mitoses, >5 mitoses per 50 high-power fields, sinusoidal invasion, histologic index of >5, and presence of more than two unfavorable molecular markers were associated significantly with metastasis in ACCa. Well-established histopathologic criteria and Ki-67 can specifically distinguish ACCAd from ACCa. Tumor cell proliferation (Ki-67) correlates with mitotic activity and morphologic index. Tumor morphology is a better predictor of metastatic risk in ACCa than current immunohistochemistry-detected cell cycle regulatory and proliferation-associated proteins.

Adenomatous tumors of the middle ear and temporal bone: clinical, morphological and tumor biological characteristics of challenging neoplastic lesions.

PubMed

Duderstadt, M; Förster, Christine; Welkoborsky, H-J; Ostertag, H

2012-03-01

Adenomatous tumors of the middle ear and temporal bone are rare tumors. In this retrospective study, we examined nine patients who underwent surgery for an adenomatous tumor of the middle ear, mastoid cavity or eustachian tube. In seven patients, a middle ear adenoma (MEA) and in two patients an aggressive papillary tumor (APT) was diagnosed. We report the clinical, radiologic, morphologic, immunohistochemical and DNA image cytometrical characteristics that can help to correctly classify these tumors. Therapy consisted of surgical excision of the tumors in eight cases. In one elderly patient, only a large biopsy was taken, because this patient suffered from cardial and kidney disorders and was not suitable for an extended surgical approach. This patient received stereotactic radiotherapy. Seven patients underwent planned second look operation. Recurrences occurred in three patients (one with APT, two with MEA), whereas in two of these cases rather a residual tumor due to initial incomplete tumor resection occurred. By image analysis, DNA cytometry MEA were considered benign, whereas the appearance of aneuploid tumor cells in APT confirmed these tumors as low grade malignant lesions. The proliferation rates were equally low in both entities. APT and MEA are tumor entities which can only be correctly classified by a synopsis of histopathology, immunohistochemistry and DNA image cytometry. The recommended therapy is the complete tumor excision. In cases of APT, von Hippel-Lindau syndrome has to be excluded.

Adapting clinical paradigms to the challenges of cancer clonal evolution.

PubMed

Murugaesu, Nirupa; Chew, Su Kit; Swanton, Charles

2013-06-01

Emerging evidence suggests that cancer branched evolution may affect biomarker validation, clinical outcome, and emergence of drug resistance. The changing spatial and temporal nature of cancer subclonal architecture during the disease course suggests the need for longitudinal prospective studies of cancer evolution and robust and clinically implementable pathologic definitions of intratumor heterogeneity, genetic diversity, and chromosomal instability. Furthermore, subclonal heterogeneous events in tumors may evade detection through conventional biomarker strategies and influence clinical outcome. Minimally invasive methods for the study of cancer evolution and new approaches to clinical study design, incorporating understanding of the dynamics of tumor clonal architectures through treatment and during acquisition of drug resistance, have been suggested as important areas for development. Coordinated efforts will be required by the scientific and clinical trial communities to adapt to the challenges of detecting infrequently occurring somatic events that may influence clinical outcome and to understand the dynamics of cancer evolution and the waxing and waning of tumor subclones over time in advanced metastatic epithelial malignancies. Copyright © 2013 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

Quantitative Analysis of the Morphology of {101} and {001} Faceted Anatase TiO 2 Nanocrystals and Its Implication on Photocatalytic Activity

DOE Office of Scientific and Technical Information (OSTI.GOV)

Liu, Jue; Olds, Daniel; Peng, Rui

The atomistic structure and morphology (shape and size) of nanomaterials have strong influences on their physical and chemical properties. However, many characterization techniques focus exclusively on one length-scale regime or another when developing quantitative morphology/structural models. In this article, we demonstrate that powder X-ray diffraction and neutron pair distribution function (PDF) can be used to obtain accurate average morphology and atomistic structure of {001} and {101} faceted anatase TiO 2 nanocrystals based on differential evolution refinements using Debye scattering equation calculations. It is also demonstrated that the morphology polydispersity of TiO 2 nanocrystals can be effectively obtained from the diffractionmore » data via a numerical refinement routine. The morphology refinement results are in good agreement with those from transmission electron microscopy and the modeling of small angle neutron scattering data. This method is successfully used to quantify the facet-specified photocatalytic hydrogen evolution activity of anatase TiO 2 nanocrystals with different {001} to {101} ratios. It is found that the sample with an intermediate amount of both {001} and {101} facets shows the best photocatalytic hydrogen evolution reaction (HER) activity. It is expected that the simultaneous structure and morphology refinement technique can be generally used to study the relationship between morphology and functionality of nanomaterials.« less

Quantitative Analysis of the Morphology of {101} and {001} Faceted Anatase TiO 2 Nanocrystals and Its Implication on Photocatalytic Activity

DOE Office of Scientific and Technical Information (OSTI.GOV)

Liu, Jue; Olds, Daniel; Peng, Rui

The atomistic structure and morphology (shape and size) of nanomaterials have strong influences on their physical and chemical properties. However, many characterization techniques focus exclusively on one length-scale regime or another when developing quantitative morphology/structural models. In this article, we demonstrate that powder X-ray diffraction and neutron pair distribution function (PDF) can be used to obtain accurate average morphology and atomistic structure of {001} and {101} faceted anatase TiO 2 nanocrystals based on differential evolution refinements using Debye scattering equation calculations. It is also demonstrated that the morphology polydispersity of TiO 2 nanocrystals can be effectively obtained from the diffractionmore » data via a numerical refinement routine. The morphology refinement results are in good agreement with those from transmission electron microscopy and the modeling of small angle neutron scattering data. This method is successfully used to quantify the facet-specified photocatalytic hydrogen evolution activity of anatase TiO 2 nanocrystals with different {001} to {101} ratios. It is found that the sample with an intermediate amount of both {001} and {101} facets shows the best photocatalytic hydrogen evolution reaction (HER) activity. As a result, it is expected that the simultaneous structure and morphology refinement technique can be generally used to study the relationship between morphology and functionality of nanomaterials.« less

Quantitative Analysis of the Morphology of {101} and {001} Faceted Anatase TiO 2 Nanocrystals and Its Implication on Photocatalytic Activity

DOE PAGES

Liu, Jue; Olds, Daniel; Peng, Rui; ...

2017-06-14

The atomistic structure and morphology (shape and size) of nanomaterials have strong influences on their physical and chemical properties. However, many characterization techniques focus exclusively on one length-scale regime or another when developing quantitative morphology/structural models. In this article, we demonstrate that powder X-ray diffraction and neutron pair distribution function (PDF) can be used to obtain accurate average morphology and atomistic structure of {001} and {101} faceted anatase TiO 2 nanocrystals based on differential evolution refinements using Debye scattering equation calculations. It is also demonstrated that the morphology polydispersity of TiO 2 nanocrystals can be effectively obtained from the diffractionmore » data via a numerical refinement routine. The morphology refinement results are in good agreement with those from transmission electron microscopy and the modeling of small angle neutron scattering data. This method is successfully used to quantify the facet-specified photocatalytic hydrogen evolution activity of anatase TiO 2 nanocrystals with different {001} to {101} ratios. It is found that the sample with an intermediate amount of both {001} and {101} facets shows the best photocatalytic hydrogen evolution reaction (HER) activity. As a result, it is expected that the simultaneous structure and morphology refinement technique can be generally used to study the relationship between morphology and functionality of nanomaterials.« less

Evolvability of flower geometry: Convergence in pollinator-driven morphological evolution of flowers.

PubMed

Woźniak, Natalia Joanna; Sicard, Adrien

2018-07-01

Flowers represent a key innovation during plant evolution. Driven by reproductive optimization, evolution of flower morphology has been central in boosting species diversification. In most cases, this has happened through specialized interactions with animal pollinators and subsequent reduction of gene flow between specialized morphs. While radiation has led to an enormous variability in flower forms and sizes, recurrent evolutionary patterns can be observed. Here, we discuss the targets of selection involved in major trends of pollinator-driven flower evolution. We review recent findings on their adaptive values, developmental grounds and genetic bases, in an attempt to better understand the repeated nature of pollinator-driven flower evolution. This analysis highlights how structural innovation can provide flexibility in phenotypic evolution, adaptation and speciation. Copyright © 2017 Elsevier Ltd. All rights reserved.

T3 receptors in human pituitary tumors.

PubMed

Machiavelli, Gloria A; Pauni, Micaela; Heredia Sereno, Gastón M; Szijan, Irene; Basso, Armando; Burdman, José A

2009-11-01

The purpose of this work was to investigate the synthesis of T3 receptors in human tumors of the anterior pituitary gland, its relationship with the hormone synthesized and/or secreted by the tumor and the post-surgical evolution of the patient. Patients were evaluated clinically and by magnetic nuclear resonance to classify the adenoma according to their size. Hormonal concentrations in sera were determined by radioimmunoassay. Immunohistochemistry of the pituitary hormones was performed in the tumors. Tumors were obtained at surgery and immediately frozen in ice, transported to the laboratory and stored at -70 degrees C. Reverse transcription was performed with purified RNA from the tumors. Out of 33 pituitary tumors, 29 had RNA for T3 receptors synthesis (88%). They were present in different histological specimens, the tumors were grades 1-4 according to their size, and there was no relationship between the size of the tumor and the presence of T3 receptor RNAs. The post-surgical evolution of the patient was mostly dependent on the size and not on the presence of T3 receptors. The presence of thyroid hormone receptors in pituitary tumors is in line with two important characteristics of these tumors: they are histologically benign and well differentiated.

Effects of Walker 256 carcinoma on metabolic alterations during the evolution of pregnancy.

PubMed

Cintra-Gomes, M C; Cury, L; Parreira, M R; Elias, C F; Areas, M A

1990-01-01

The control of pregnant cancer patients is difficult because it involves both mother and fetus, and the metabolic alterations in the cancer host induce a massive mobilization of nutrients diverted to the neoplastic cells. The purpose of the present study was to determine the evolution of the Walker 256 carcinoma in pregnant rats and its consequences on fetal development. The results showed that the tumors displayed a very rapid rate of growth and induced a reduction in fetal weights in the pregnant tumor-bearing rats. The tumor-bearing and pregnant tumor-bearing groups showed a decrease in blood glucose and total serum protein, suggesting an increase in energy utilization of these substrates and synthetic activity by the tumoral cells. An imbalance between protein synthesis and catabolism may occur in the tumor-bearing rats which may be related to the degree of nutritional depletion.

Full three-dimensional morphology evolution of amorphous thin films for atomic layer deposition

NASA Astrophysics Data System (ADS)

Jin, Lingpeng; Li, Yawei; Hu, Zhigao; Chu, Junhao

2018-04-01

We introduce a Monte Carlo model based on random deposition and diffusion limited aggregation in order to study the morphological evolution of deposition of nanofilm, which is difficult to carry out by the experimental methods. The instantaneous evolution of morphology and the corresponding parameters are observed when employing a novel perspective, modeling the aggregation of nanoscale units. Despite simplifying the chemical details, the simulation results qualitatively describe experiments with bulky precursors, and the strong dependence of growth rate on steric hindrance is obtained. Moreover, the well know behavior that the delay before steady growth is accurately predicted and analyzed based solely on modeling. Through this work, the great influence of steric hindrance on the initial stage of ALD is described.

Nanoscale Morphology Evolution Under Ion Irradiation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Aziz, Michael J.

We showed that the half-century-old paradigm of morphological instability under irradiation due to the curvature-dependence of the sputter yield, can account neither for the phase diagram nor the amplification or decay rates that we measure in the simplest possible experimental system -- an elemental semiconductor with an amorphous surface under noble-gas ion irradiation; We showed that a model of pattern formation based on the impact-induced redistribution of atoms that do not get sputtered away explains our experimental observations; We developed a first-principles, parameter-free approach for predicting morphology evolution, starting with molecular dynamics simulations of single ion impacts, lasting picoseconds, andmore » upscaling through a rigorous crater-function formalism to develop a partial differential equation that predicts morphology evolution on time scales more than twelve orders of magnitude longer than can be covered by the molecular dynamics; We performed the first quantitative comparison of the contributions to morphological instability from sputter removal and from impact-induced redistribution of atoms that are removed, and showed that the former is negligible compared to the latter; We established a new paradigm for impact-induced morphology evolution based on crater functions that incorporate both redistribution and sputter effects; and We developed a model of nanopore closure by irradiation-induced stress and irradiationenhanced fluidity, for the near-surface irradiation regime in which nuclear stopping predominates, and showed that it explains many aspects of pore closure kinetics that we measure experimentally.« less

Dedifferentiated Liposarcoma With Epithelioid/Epithelial Features.

PubMed

Makise, Naohiro; Yoshida, Akihiko; Komiyama, Motokiyo; Nakatani, Fumihiko; Yonemori, Kan; Kawai, Akira; Fukayama, Masashi; Hiraoka, Nobuyoshi

2017-11-01

Dedifferentiated liposarcoma (DDLPS) demonstrates a variety of growth patterns, and their histologic resemblance to other spindle cell mesenchymal tumors has been widely recognized. However, epithelioid morphology in DDLPS has only rarely been documented. Here, we report 6 cases of DDLPS with striking epithelioid/epithelial features. The patients were 5 men and 1 woman with a median age of 61 years. All tumors were located in the internal trunk. During follow-up of 1 to 41 months, local recurrence, distant metastases, and tumor-related death occurred in 4, 2, and 4 patients, respectively. Beside well-differentiated liposarcoma component and conventional high-grade spindle cell morphology, all tumors focally exhibited growth comprising small or large epithelioid cells in diffuse or sheet-like proliferation. Rhabdoid cells were present in 2 cases. All 5 tumors tested harbored MDM2 amplification. Cytokeratin and/or epithelial membrane antigen were at least focally positive in all 5 tumors tested. One case contained a small focus of novel heterologous epithelial differentiation with acinar structures, wherein cytokeratin, MOC31, and claudin-4 were diffusely expressed and H3K27me3 expression was lost. DDLPS with epithelioid/epithelial features may lead to misdiagnosis of carcinoma or mesothelioma, and their diagnosis should be based on correlation with clinicopathologic and molecular findings. The epithelioid morphology in DDLPS may suggest an aggressive behavior based on this small series. In addition, we document 2 cases of MDM2-amplified undifferentiated neoplasm with epithelioid features in the internal trunk that lacked association with well-differentiated liposarcoma histology and showed rapid clinical course. Whether these latter tumors belong to DDLPS with epithelioid features requires further study.

MO-C-17A-04: Forecasting Longitudinal Changes in Oropharyngeal Tumor Morphology Throughout the Course of Head and Neck Radiation Therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yock, A; UT Graduate School of Biomedical Sciences, Houston, TX; Rao, A

2014-06-15

Purpose: To generate, evaluate, and compare models that predict longitudinal changes in tumor morphology throughout the course of radiation therapy. Methods: Two morphology feature vectors were used to describe the size, shape, and position of 35 oropharyngeal GTVs at each treatment fraction during intensity-modulated radiation therapy. The feature vectors comprised the coordinates of the GTV centroids and one of two shape descriptors. One shape descriptor was based on radial distances between the GTV centroid and 614 GTV surface landmarks. The other was based on a spherical harmonic decomposition of these distances. Feature vectors over the course of therapy were describedmore » using static, linear, and mean models. The error of these models in forecasting GTV morphology was evaluated with leave-one-out cross-validation, and their accuracy was compared using Wilcoxon signed-rank tests. The effect of adjusting model parameters at 1, 2, 3, or 5 time points (adjustment points) was also evaluated. Results: The addition of a single adjustment point to the static model decreased the median error in forecasting the position of GTV surface landmarks by 1.2 mm (p<0.001). Additional adjustment points further decreased forecast error by about 0.4 mm each. The linear model decreased forecast error compared to the static model for feature vectors based on both shape descriptors (0.2 mm), while the mean model did so only for those based on the inter-landmark distances (0.2 mm). The decrease in forecast error due to adding adjustment points was greater than that due to model selection. Both effects diminished with subsequent adjustment points. Conclusion: Models of tumor morphology that include information from prior patients and/or prior treatment fractions are able to predict the tumor surface at each treatment fraction during radiation therapy. The predicted tumor morphology can be compared with patient anatomy or dose distributions, opening the possibility of anticipatory re-planning. American Legion Auxiliary Fellowship; The University of Texas Graduate School of Biomedical Sciences at Houston.« less

[Imaging manifestations and pathologic basis for hepatic capsular retraction syndrome caused by benign and malignant liver tumors].

PubMed

Ou, Youkuan; Xiao, Enhua; Shang, Quanliang; Chen, Juan

2015-10-01

To investigate the imaging manifestations of CT, MRI and pathological basis for hepatic capsular retraction syndrome caused by benign and malignant liver tumors.
 CT or MRI images and pathological features for hepatic capsular retraction syndrome were retrospectively analyzed in 50 patients with benign and malignant liver tumors. Picture archive and communication system (PACS) was used to observe and compare the morphology, size, width, depth, edge of the capsular retraction and the status of liquid under the liver capsule. The structure, differentiation and proliferation of the tumor were analyzed under the microscope.
 There were malignant liver tumors in 44 patients and benign tumor in 6 patients. The smooth or rough for the edge of capsular retraction was significant difference between the benign tumors and the malignant tumors with three differentiated grades (all P<0.05). There were significant difference in the width and depth for capsule retraction with different amount of fibrous tissues (all P<0.05). The width and depth of capsule retraction were positively correlated to the size of the tumors (r=0.557, 0.309 respectively, both P<0.05).
 Benign and malignant hepatic tumors may appear capsule retraction syndrome, but there are morphological differences between them. The differences are closely related with the lesion size, differentiated degree of tumor and fibrous tissue proliferation.

Ovarian Brenner tumors and Walthard nests: a histologic and immunohistochemical study.

PubMed

Roma, Andres A; Masand, Ramya P

2014-12-01

Brenner tumors are composed of urothelial/transitional-type epithelium and, hence, are morphologically similar to Walthard nests and tubal/mesothelial transitional metaplasia. In this study, we analyzed immunohistochemical markers on Brenner tumors to explore Müllerian as well as Wolffian and germ cell derivation. We also attempted to explore their possible association with tubal/paratubal Walthard nests/transitional metaplasia, using the same immunostains. Thirty-two consecutive cases of Brenner tumors were identified. Thirteen (43%) of the patients had Walthard nests in the tubal/periovarian soft tissue. All Brenner tumors were diffusely positive for GATA3 (strongly positive in 30/32 and weakly positive in the remaining 2) and negative for PAX8, PAX2, and SALL4. Similarly, all Walthard nests were positive for GATA3, whereas only 3 (23%) of 13 showed occasional PAX8 expression; all were negative for PAX2 and SALL4. In our study, more than 40% of Brenner tumors had associated Walthard nests. The similar morphology and immunoprofile of Brenner tumors and Walthard nests suggest a probable link between Brenner tumors and Walthard nests. Two additional cases presented highlight small transitional lesions involving the ovary: a possible precursor lesion or the initial steps of Brenner tumor formation. Brenner tumors and most Walthard nests lacked staining for Müllerian (PAX8 and PAX2) and germ cell tumor markers (SALL4). Copyright © 2014 Elsevier Inc. All rights reserved.

Follicular morphological characteristics may be associated with invasion in follicular thyroid neoplasms with papillary-like nuclear features.

PubMed

Can, Nuray; Celik, Mehmet; Sezer, Yavuz Atakan; Ozyilmaz, Filiz; Ayturk, Semra; Tastekin, Ebru; Sut, Necdet; Gurkan, Hakan; Ustun, Funda; Bulbul, Buket Yilmaz; Guldiken, Sibel; Puyan, Fulya Oz

2017-08-20

The newly proposed nomenclature and diagnostic criteria for encapsulated follicular variant of papillary thyroid carcinoma (EFVPTC), the noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP), could improve the consistency and accuracy of diagnosing this entity. Diagnosis of NIFTP requires evaluation of the complete tumor border or capsule. The presence of tumor invasion in follicular thyroid neoplasms with papillary-like nuclear features has been recently discussed by many authors. In this study, we examined the predictive value and association of follicular morphological characteristics with the tumor invasion. In addition, we analyzed the association between tumor encapsulation and molecular profile in EFVPTC/NIFTP cases. A total of 106 cases of FVPTC were included in the study. The tumors were grouped based on the presence of tumor capsule and characteristics of tumor border, as 1) completely encapsulated tumors without invasion, 2) encapsulated tumors with invasion, 3) infiltrative tumors without a capsule. Clinicopathological features, histomorphological features [nuclear criteria, minor diagnostic features, follicles oriented perpendicular to tumor border/capsule (FOPBC)] and molecular alterations in BRAF, NRAS, and KRAS genes were evaluated. FOPBC were significantly more frequently seen in encapsulated tumors with invasion (p = 0.008). The nuclear features were not associated with the presence of encapsulation and characteristics of tumor border. BRAF mutation was more frequent in infiltrative tumors, while NRAS mutation was more frequent in encapsulated tumors, but the results were not statistically significant (p = 0.917). In conclusion, FOPBC histomorphological feature may be associated with tumor invasion in EFVPTC/NIFTP. Additionally, BRAF/KRAS/NRAS mutation analysis may prevent inadequate treatment in these patients.

Morphology Is a Link to the Past: Examining Formative and Secular Galactic Evolution through Morphology

NASA Astrophysics Data System (ADS)

Galloway, Melanie A.

Galaxy morphology is one of the primary keys to understanding a galaxy's evolutionary history. External mechanisms (environment/clustering, mergers) have a strong impact on the formative evolution of the major galactic components (disk, bulge, Hubble type), while internal instabilities created by bars, spiral arms, or other substructures drive secular evolution via the rearrangement of material within the disk. This thesis will explore several ways in which morphology impacts the dynamics and evolution of a galaxy using visual classifications from several Galaxy Zoo projects. The first half of this work will detail the motivations of using morphology to study galaxy evolution, and describe how morphology is measured, debiased, and interpreted using crowdsourced classification data via Galaxy Zoo. The second half will present scientific studies which make use of these classifications; first by focusing on the morphology of galaxies in the local Universe (z < 0.2) using data from Galaxy Zoo 2 and Galaxy Zoo UKIDSS. Last, the high-redshift Universe will be explored by examining populations of morphologies at various lookback times, from z = 0 out to z = 1 using data from Galaxy Zoo Hubble. The investigation of the physical implications of morphology in the local Universe will first be presented in Chapter 4, in a study of the impact of bars on the fueling of an active galactic nucleus (AGN). Using a sample of 19,756 disk galaxies at 0.01 < z < 0.05 imaged by the Sloan Digital Sky Survey and morphologically classified by Galaxy Zoo 2 (GZ2), the difference in AGN fraction in barred and unbarred disks was measured. A weak, but statistically significant, effect was found in that the population of AGN hosts exhibited a 16.0% increase in bar fraction as compared to their unbarred counterparts at fixed mass and color. These results are consistent with a cosmological model in which bar-driven fueling contributes to the growth of black holes, but other dynamical mechanisms must also play a significant role. Next, the morphological dependence on wavelength is studied in Chapter 5 by comparing the optical morphological classifications from GZ2 to classifications done on infrared images in GZ:UKIDSS. Consistent morphologies were found in both sets and similar bar fractions, which confirms that for most galaxies, both old and young stellar populations follow similar spatial distributions. Last, the morphological changes in galaxy populations are computed as a function of their age using classifications from Galaxy Zoo: Hubble (Chapter 6). The evolution of the passive disc population from z = 1 to z = 0.3 was studied in a sample of 20,000 galaxies from the COSMOS field and morphologically classified by the Galaxy Zoo: Hubble project. It was found that the fraction of disc galaxies that are red, as well as the fraction of red sequence galaxies that are discs, decreases for the most massive galaxies (log(M/M solar masses) > 11) but increases for lower masses. The observations are consistent with a physical scenario in which more massive galaxies are more likely to enter a red disc phase, and more massive red discs are more likely to morphologically transform into ellipticals than their less massive counterparts. Additionally, the challenges of visual classification that are particular to galaxies at high redshift were investigated. To address these biases, a new correction technique is presented using simulated images of nearby SDSS galaxies which were artificially redshifted using the FERENGI code and classified in GZH.

The new WHO 2016 classification of brain tumors-what neurosurgeons need to know.

PubMed

Banan, Rouzbeh; Hartmann, Christian

2017-03-01

The understanding of molecular alterations of tumors has severely changed the concept of classification in all fields of pathology. The availability of high-throughput technologies such as next-generation sequencing allows for a much more precise definition of tumor entities. Also in the field of brain tumors a dramatic increase of knowledge has occurred over the last years partially calling into question the purely morphologically based concepts that were used as exclusive defining criteria in the WHO 2007 classification. Review of the WHO 2016 classification of brain tumors as well as a search and review of publications in the literature relevant for brain tumor classification from 2007 up to now. The idea of incorporating the molecular features in classifying tumors of the central nervous system led the authors of the new WHO 2016 classification to encounter inevitable conceptual problems, particularly with respect to linking morphology to molecular alterations. As a solution they introduced the concept of a "layered diagnosis" to the classification of brain tumors that still allows at a lower level a purely morphologically based diagnosis while partially forcing the incorporation of molecular characteristics for an "integrated diagnosis" at the highest diagnostic level. In this context the broad availability of molecular assays was debated. On the one hand molecular antibodies specifically targeting mutated proteins should be available in nearly all neuropathological laboratories. On the other hand, different high-throughput assays are accessible only in few first-world neuropathological institutions. As examples oligodendrogliomas are now primarily defined by molecular characteristics since the required assays are generally established, whereas molecular grouping of ependymomas, found to clearly outperform morphologically based tumor interpretation, was rejected from inclusion in the WHO 2016 classification because the required assays are currently only established in a small number of institutions. In summary, while neuropathologists have now encountered various challenges in the transitional phase from the previous WHO 2007 version to the new WHO 2016 classification of brain tumors, clinical neurooncologists now face many new diagnoses allowing a clearly improved understanding that could offer them more effective therapeutic opportunities in neurooncological treatment. The new WHO 2016 classification presumably presents the highest number of modifications since the initial WHO classification of 1979 and thereby forces all professionals in the field of neurooncology to intensively understand the new concepts. This review article aims to present the basic concepts of the new WHO 2016 brain tumor classification for neurosurgeons with a focus on neurooncology.

Purification of a factor from the granules of a rat natural killer cell line (RNK) that reduces tumor cell growth and changes tumor morphology. Molecular identity with a granule serine protease (RNKP-1).

PubMed

Sayers, T J; Wiltrout, T A; Sowder, R; Munger, W L; Smyth, M J; Henderson, L E

1992-01-01

We have purified a protein from the granules of the rat NK leukemia cell line (RNK) that is cytostatic to a variety of tumor cells. This protein shows no species specificity because certain tumor cell lines of mouse, rat, and human origin were equally sensitive to its growth inhibitory effects. Treatment of sensitive cells resulted in a rounding of the cells followed by homotypic aggregation into large aggregates. The granule protein was distinct from cytolysin, Na-Cbz-Lys-thiobenzylester-esterase, or leukolexin. It had a molecular mass of 29 to 31 kDa, bound strongly to heparin, was inactivated by heating at 70 degrees C for 5 min or reduction, but was stable to trypsin treatment. By using molecular sieve chromatography, heparin agarose chromatography, and reverse phase HPLC, this protein was purified to homogeneity. The first 33 amino acids of the N-terminal amino acid sequence showed complete identity to the sequence predicted from a rat serine protease gene recently cloned and designated RNKP-1. Therefore we have purified a novel serine protease and demonstrated that it has effects on the growth and morphology of certain tumor cells. Other serine proteases that were structurally related and have substantial homology with RNKP-1 at the amino acid level showed neither growth inhibitory properties nor affected the morphology of the tumor target cells we used.

Sexual selection and genital evolution: an overview.

PubMed

Shamloul, Rany; el-Sakka, Ahmed; Bella, Anthony J

2010-05-01

Genital morphology (especially male) among the animal kingdom is characterized by extensive differences that even members of closely related species with similar general morphology may have remarkably diverse genitalia. To present the sexual medicine specialist with a basic understanding of the current hypotheses on genital evolution with an emphasis on the sexual selection theories. A review of current literature on the theories of genital evolution. Analysis of the supporting evidence for the sexual selection theories of genital evolution. Several theories have been proposed to explain genital evolution. Currently, the sexual selection theories are being considered to present valid and solid evidence explaining genital evolution. However, other theories, including sexual conflict, are still being investigated. All theories of genital evolution have their own weaknesses and strengths. Given that many complex biological mechanisms, mostly unknown yet, are involved in the process of genital evolution, it is thus reasonable to conclude that not one theory can independently explain genital evolution. It is likely that these mechanisms may prove to have synergistic rather than exclusive effects.

Efficient coarse simulation of a growing avascular tumor

PubMed Central

Kavousanakis, Michail E.; Liu, Ping; Boudouvis, Andreas G.; Lowengrub, John; Kevrekidis, Ioannis G.

2013-01-01

The subject of this work is the development and implementation of algorithms which accelerate the simulation of early stage tumor growth models. Among the different computational approaches used for the simulation of tumor progression, discrete stochastic models (e.g., cellular automata) have been widely used to describe processes occurring at the cell and subcell scales (e.g., cell-cell interactions and signaling processes). To describe macroscopic characteristics (e.g., morphology) of growing tumors, large numbers of interacting cells must be simulated. However, the high computational demands of stochastic models make the simulation of large-scale systems impractical. Alternatively, continuum models, which can describe behavior at the tumor scale, often rely on phenomenological assumptions in place of rigorous upscaling of microscopic models. This limits their predictive power. In this work, we circumvent the derivation of closed macroscopic equations for the growing cancer cell populations; instead, we construct, based on the so-called “equation-free” framework, a computational superstructure, which wraps around the individual-based cell-level simulator and accelerates the computations required for the study of the long-time behavior of systems involving many interacting cells. The microscopic model, e.g., a cellular automaton, which simulates the evolution of cancer cell populations, is executed for relatively short time intervals, at the end of which coarse-scale information is obtained. These coarse variables evolve on slower time scales than each individual cell in the population, enabling the application of forward projection schemes, which extrapolate their values at later times. This technique is referred to as coarse projective integration. Increasing the ratio of projection times to microscopic simulator execution times enhances the computational savings. Crucial accuracy issues arising for growing tumors with radial symmetry are addressed by applying the coarse projective integration scheme in a cotraveling (cogrowing) frame. As a proof of principle, we demonstrate that the application of this scheme yields highly accurate solutions, while preserving the computational savings of coarse projective integration. PMID:22587128

Understanding the "lethal" drivers of tumor-stroma co-evolution: emerging role(s) for hypoxia, oxidative stress and autophagy/mitophagy in the tumor micro-environment.

PubMed

Lisanti, Michael P; Martinez-Outschoorn, Ubaldo E; Chiavarina, Barbara; Pavlides, Stephanos; Whitaker-Menezes, Diana; Tsirigos, Aristotelis; Witkiewicz, Agnieszka; Lin, Zhao; Balliet, Renee; Howell, Anthony; Sotgia, Federica

2010-09-15

We have recently proposed a new model for understanding how tumors evolve. To achieve successful "Tumor-Stroma Co-Evolution", cancer cells induce oxidative stress in adjacent fibroblasts and possibly other stromal cells. Oxidative stress in the tumor stroma mimics the effects of hypoxia, under aerobic conditions, resulting in an excess production of reactive oxygen species (ROS). Excess stromal production of ROS drives the onset of an anti-oxidant defense in adjacent cancer cells, protecting them from apoptosis. Moreover, excess stromal ROS production has a "Bystander-Effect", leading to DNA damage and aneuploidy in adjacent cancer cells, both hallmarks of genomic instability. Finally, ROS-driven oxidative stress induces autophagy and mitophagy in the tumor micro-environment, leading to the stromal over-production of recycled nutrients (including energy-rich metabolites, such as ketones and L-lactate). These recycled nutrients or chemical building blocks then help drive mitochondrial biogenesis in cancer cells, thereby promoting the anabolic growth of cancer cells (via an energy imbalance). We also show that ketones and lactate help "fuel" tumor growth and cancer cell metastasis and can act as chemo-attractants for cancer cells. We have termed this new paradigm for accelerating tumor-stroma co-evolution, "The Autophagic Tumor Stroma Model of Cancer Cell Metabolism". Heterotypic signaling in cancer-associated fibroblasts activates the transcription factors HIF1alpha and NFκB, potentiating the onset of hypoxic and inflammatory response(s), which further upregulates the autophagic program in the stromal compartment. Via stromal autophagy, this hypoxic/inflammatory response may provide a new escape mechanism for cancer cells during anti-angiogenic therapy, further exacerbating tumor recurrence and metastasis.

Surgical Pathology of Gastrointestinal Stromal Tumors: Practical Implications of Morphologic and Molecular Heterogeneity for Precision Medicine.

PubMed

Charville, Gregory W; Longacre, Teri A

2017-11-01

Gastrointestinal stromal tumor (GIST), the most common mesenchymal neoplasm of the gastrointestinal tract, exhibits diverse histologic and clinical manifestations. With its putative origin in the gastrointestinal pacemaker cell of Cajal, GIST can arise in association with any portion of the tubular gastrointestinal tract. Morphologically, GISTs are classified as spindled or epithelioid, though each of these subtypes encompasses a broad spectrum of microscopic appearances, many of which mimic other histologic entities. Despite this morphologic ambiguity, the diagnosis of GIST is aided in many cases by immunohistochemical detection of KIT (CD117) or DOG1 expression. The natural history of GIST ranges from that of a tumor cured by surgical resection to that of a locally advanced or even widely metastatic, and ultimately fatal, disease. This clinicopathologic heterogeneity is paralleled by an underlying molecular diversity: the majority of GISTs are associated with spontaneous activating mutations in KIT, PDGFRA, or BRAF, while additional subsets are driven by genetic lesions-often inherited-of NF1 or components of the succinate dehydrogenase enzymatic complex. Specific gene mutations correlate with particular anatomic or morphologic characteristics and, in turn, with distinct clinical behaviors. Therefore, prognostication and treatment are increasingly dictated not only by morphologic clues, but also by accompanying molecular genetic features. In this review, we provide a comprehensive description of the heterogenous molecular underpinnings of GIST, including implications for the practicing pathologist with regard to morphologic identification, immunohistochemical diagnosis, and clinical management.

Punctuated Copy Number Evolution and Clonal Stasis in Triple-Negative Breast Cancer

PubMed Central

Gao, Ruli; Davis, Alexander; McDonald, Thomas O.; Sei, Emi; Shi, Xiuqing; Wang, Yong; Tsai, Pei-Ching; Casasent, Anna; Waters, Jill; Zhang, Hong; Meric-Bernstam, Funda; Michor, Franziska; Navin, Nicholas E.

2016-01-01

Aneuploidy is a hallmark of breast cancer; however, our knowledge of how these complex genomic rearrangements evolve during tumorigenesis is limited. In this study we developed a highly multiplexed single-nucleus-sequencing method to investigate copy number evolution in triple-negative breast cancer patients. We sequenced 1000 single cells from 12 patients and identified 1–3 major clonal subpopulations in each tumor that shared a common evolutionary lineage. We also identified a minor subpopulation of non-clonal cells that were classified as: 1) metastable, 2) pseudo-diploid, or 3) chromazemic. Phylogenetic analysis and mathematical modeling suggest that these data are unlikely to be explained by the gradual accumulation of copy number events over time. In contrast, our data challenge the paradigm of gradual evolution, showing that the majority of copy number aberrations are acquired at the earliest stages of tumor evolution, in short punctuated bursts, followed by stable clonal expansions that form the tumor mass. PMID:27526321

State of the art discovery with tumor profiling in pediatric oncology.

PubMed

Carroll, William L; Raetz, Elizabeth; Meyer, Julia

2015-01-01

It is an exciting era in pediatric oncology with the advent of new technologies to comprehensively characterize cancer genomes in childhood tumors. Defining the genetic landscape of pediatric tumors has not only provided critical insight into tumor evolution, but it has also offered promise for more effective treatment in some cases, such as Philadelphia chromosome-positive acute lymphoblastic leukemia (ALL) and anaplastic lymphoma kinase (ALK)-mutated tumors. However, several challenges remain as the field of genomic tumor profiling emerges. This new technology is costly, and the overall impact on survival has yet to be determined. Tumor heterogeneity and clonal evolution have also presented challenges in the development of targeted therapy. In this article, we review breakthroughs in gene sequencing methodology and discuss examples where genomic discoveries have resulted in the recognition of tumor susceptibility as well as incorporation of targeted therapy. We also discuss how broad scale comprehensive tumor analyses have demonstrated the convergence of individual genetic alterations on common relevant pathways. Although the impact of tumor profiling is best studied within the context of rigorously designed clinical trials, there is promise that there will be growing opportunities for the adaption of precision medicine in pediatric oncology in the future.

Head shape evolution in Gymnophthalmidae: does habitat use constrain the evolution of cranial design in fossorial lizards?

PubMed

Barros, F C; Herrel, A; Kohlsdorf, T

2011-11-01

Habitat usage comprises interactions between ecological parameters and organismal capacities, and the selective pressures that ultimately determine the outcome of such processes in an evolutionary scale may be conflicting when the same morphological structure is recruited for different activities. Here, we investigate the roles of diet and locomotion in the evolution of cranial design in gymnophthalmid lizards and test the hypothesis that microhabitat use drives head shape evolution, particularly in head-first burrowers. Morphological factors were analysed in relation to continuous ecological indexes (prey hardness and substrate compactness) using conventional and phylogenetic approaches. Results suggest that the evolution of head morphology in Gymnophthalmidae was shaped under the influence of microhabitat use rather than diet: burrowers have shorter heads with lower rostral angulation, independently of the prey consumed. Food preferences appear to be relatively conserved throughout the phylogeny of the group, which may have permitted the extensive radiation of gymnophthalmids into fossorial microhabitats. © 2011 The Authors. Journal of Evolutionary Biology © 2011 European Society For Evolutionary Biology.

The phallus in Tettigoniidae (Insecta: Orthoptera: Ensifera): revision of morphology and terminology, and discussion on its taxonomic importance and evolution.

PubMed

Chamorro-Rengifo, Juliana; Lopes-Andrade, Cristiano

2014-06-13

The phallus in Tettigoniidae (katydids) is a structure informative relative to the systematics of the group. Despite this, it is often not considered in descriptions of taxa. The lack of adequate descriptions of phalli is not only a gap for sytematic and morphological studies, but postpones works on the evolution of copula. Here we study the exoskeletal morphology of the phallus in katydids, its components, and revised the terminology for them. We carried out dissections for morphological comparisons, and complement the observational information with published data. We stained phalli of katydids with chlorazol black, to better contrast membranous versus sclerotized components. We demonstrate that phallic components vary at specific, generic and suprageneric levels, and that internal and external components vary in number, shape, size and position. Currently there is little comparative data to support hypotheses on the evolution of this structure, but possibly the possession of a titillator is an ancestral condition. We identify additional sclerotized components, the sclerites of the ventral fold of the dorsal lobe, which can modify the shape and function of the titillator, being also important for understanding the evolution of the phallus. Potential functional relationships based on hypothetical morphological correlations between the shape of titillator and cerci are proposed, categorized in three main groups: (i) phallus devoid of titillator and cerci simple, (ii) titillator with bifurcated or paired sclerites, and cerci adapted for grasping, and (iii) titillator with single process and/or sclerite and cerci simple, sometimes with a pointed tip. Two explanations for these hypothetical morphological correlations and morphological variation are proposed: first, species with similar structures at the postabdomen would share similar copulatory behaviour, and second, more than one selective pressure would have acted over the structures of the postabdomen.

The Evolution of the Observed Hubble Sequence over the past 6Gyr

NASA Astrophysics Data System (ADS)

Delgado-Serrano, R.; Hammer, F.; Yang, Y. B.; Puech, M.; Flores, H.; Rodrigues, M.

2011-10-01

During the past years we have confronted serious problems of methodology concerning the morphological and kinematic classification of distant galaxies. This has forced us to create a new simple and effective morphological classification methodology, in order to guarantee a morpho-kinematic correlation, make the reproducibility easier and restrict the classification subjectivity. Giving the characteristic of our morphological classification, we have thus been able to apply the same methodology, using equivalent observations, to representative samples of local and distant galaxies. It has allowed us to derive, for the first time, the distant Hubble sequence (~6 Gyr ago), and determine a morphological evolution of galaxies over the past 6 Gyr. Our results strongly suggest that more than half of the present-day spirals had peculiar morphologies, 6 Gyr ago.

Piscivory limits diversification of feeding morphology in centrarchid fishes.

PubMed

Collar, David C; O'Meara, Brian C; Wainwright, Peter C; Near, Thomas J

2009-06-01

Proximity to an adaptive peak influences a lineage's potential to diversify. We tested whether piscivory, a high quality but functionally demanding trophic strategy, represents an adaptive peak that limits morphological diversification in the teleost fish clade, Centrarchidae. We synthesized published diet data and applied a well-resolved, multilocus and time-calibrated phylogeny to reconstruct ancestral piscivory. We measured functional features of the skull and performed principal components analysis on species' values for these variables. To assess the role of piscivory on morphological diversification, we compared the fit of several models of evolution for each principal component (PC), where model parameters were allowed to vary between lineages that differed in degree of piscivory. According to the best-fitting model, two adaptive peaks influenced PC 1 evolution, one peak shared between highly and moderately piscivorous lineages and another for nonpiscivores. Brownian motion better fit PCs 2, 3, and 4, but the best Brownian models infer a slow rate of PC 2 evolution shared among all piscivores and a uniquely slow rate of PC 4 evolution in highly piscivorous lineages. These results suggest that piscivory limits feeding morphology diversification, but this effect is most severe in lineages that exhibit an extreme form of this diet.

How gastrin-releasing peptide receptor (GRPR) and αvβ3 integrin expression reflect reorganization features of tumors after hyperthermia treatments.

PubMed

Hallasch, Sandra; Frick, Sindy; Jung, Maximilian; Hilger, Ingrid

2017-07-31

The outcome of tumor treatment via hyperthermia in the clinic has been reported to be heterogeneous. Here, we assessed how the presence of gastrin-releasing peptide receptor (GRPR) and α v β 3 integrin together with the morphology of the vascularization reflects the growth behavior of tumors after hyperthermia treatment. MDA-MB-231 tumor bearing mice were treated either with high (46 °C) or low dose (42 °C) water hyperthermia for 60 min. Changes of GRPR and α v β 3 integrin expression were assessed via multiplexed optical imaging. Vascularization was reconstructed and quantified by µCT imaging after contrast agent injection. We found that high dose hyperthermia is capable of increasing the expression of GRPR, α v β 3 integrin, CD31, and Ki67 in tumors. Also the morphology of tumor vasculature changed (increased relative blood volume and small-diameter vessel density, decreased expression of α-SMA). Low dose hyperthermia induced comparatively moderate effects on the investigated protein expression pattern and vascular remodeling. We conclude that under defined circumstances, specific temperature doses affect the reorganization of tumor regrowth, which is triggered by residual "dormant" cells even though tumor volumes are transiently decreasing. Further on, GRPR, α v β 3 integrin expression are versatile tools to surveil potential tumor regrow during therapy, beyond the conventional determination of tumor volumes.

Melanoma Cells Can Adopt the Phenotype of Stromal Fibroblasts and Macrophages by Spontaneous Cell Fusion in Vitro.

PubMed

Kemény, Lajos V; Kurgyis, Zsuzsanna; Buknicz, Tünde; Groma, Gergely; Jakab, Ádám; Zänker, Kurt; Dittmar, Thomas; Kemény, Lajos; Németh, István B

2016-06-02

After the removal of primary cutaneous melanoma some patients develop local recurrences, even after having histologically tumor-free re-excision. A potential explanation behind this phenomenon is that tumor cells switch their phenotype, making their recognition via standard histopathological assessments extremely difficult. Tumor-stromal cell fusion has been proposed as a potential mechanism for tumor cells to acquire mesenchymal traits; therefore, we hypothesized that melanoma cells could acquire fibroblast- and macrophage-like phenotypes via cell fusion. We show that melanoma cells spontaneously fuse with human dermal fibroblasts and human peripheral blood monocytes in vitro. The hybrid cells' nuclei contain chromosomes from both parental cells and are indistinguishable from the parental fibroblasts or macrophages based on their morphology and immunophenotype, as they could lose the melanoma specific MART1 marker, but express the fibroblast marker smooth muscle actin or the macrophage marker CD68. Our results suggest that, by spontaneous cell fusion in vitro, tumor cells can adopt the morphology and immunophenotype of stromal cells while still carrying oncogenic, tumor-derived genetic information. Therefore, melanoma-stromal cell fusion might play a role in missing tumor cells by routine histopathological assessments.

Melanoma Cells Can Adopt the Phenotype of Stromal Fibroblasts and Macrophages by Spontaneous Cell Fusion in Vitro

PubMed Central

Kemény, Lajos V.; Kurgyis, Zsuzsanna; Buknicz, Tünde; Groma, Gergely; Jakab, Ádám; Zänker, Kurt; Dittmar, Thomas; Kemény, Lajos; Németh, István B.

2016-01-01

After the removal of primary cutaneous melanoma some patients develop local recurrences, even after having histologically tumor-free re-excision. A potential explanation behind this phenomenon is that tumor cells switch their phenotype, making their recognition via standard histopathological assessments extremely difficult. Tumor-stromal cell fusion has been proposed as a potential mechanism for tumor cells to acquire mesenchymal traits; therefore, we hypothesized that melanoma cells could acquire fibroblast- and macrophage-like phenotypes via cell fusion. We show that melanoma cells spontaneously fuse with human dermal fibroblasts and human peripheral blood monocytes in vitro. The hybrid cells’ nuclei contain chromosomes from both parental cells and are indistinguishable from the parental fibroblasts or macrophages based on their morphology and immunophenotype, as they could lose the melanoma specific MART1 marker, but express the fibroblast marker smooth muscle actin or the macrophage marker CD68. Our results suggest that, by spontaneous cell fusion in vitro, tumor cells can adopt the morphology and immunophenotype of stromal cells while still carrying oncogenic, tumor-derived genetic information. Therefore, melanoma–stromal cell fusion might play a role in missing tumor cells by routine histopathological assessments. PMID:27271591

Brain tumor classification using AFM in combination with data mining techniques.

PubMed

Huml, Marlene; Silye, René; Zauner, Gerald; Hutterer, Stephan; Schilcher, Kurt

2013-01-01

Although classification of astrocytic tumors is standardized by the WHO grading system, which is mainly based on microscopy-derived, histomorphological features, there is great interobserver variability. The main causes are thought to be the complexity of morphological details varying from tumor to tumor and from patient to patient, variations in the technical histopathological procedures like staining protocols, and finally the individual experience of the diagnosing pathologist. Thus, to raise astrocytoma grading to a more objective standard, this paper proposes a methodology based on atomic force microscopy (AFM) derived images made from histopathological samples in combination with data mining techniques. By comparing AFM images with corresponding light microscopy images of the same area, the progressive formation of cavities due to cell necrosis was identified as a typical morphological marker for a computer-assisted analysis. Using genetic programming as a tool for feature analysis, a best model was created that achieved 94.74% classification accuracy in distinguishing grade II tumors from grade IV ones. While utilizing modern image analysis techniques, AFM may become an important tool in astrocytic tumor diagnosis. By this way patients suffering from grade II tumors are identified unambiguously, having a less risk for malignant transformation. They would benefit from early adjuvant therapies.

Unraveling the Tangled Skein: The Evolution of Transcriptional Regulatory Networks in Development.

PubMed

Rebeiz, Mark; Patel, Nipam H; Hinman, Veronica F

2015-01-01

The molecular and genetic basis for the evolution of anatomical diversity is a major question that has inspired evolutionary and developmental biologists for decades. Because morphology takes form during development, a true comprehension of how anatomical structures evolve requires an understanding of the evolutionary events that alter developmental genetic programs. Vast gene regulatory networks (GRNs) that connect transcription factors to their target regulatory sequences control gene expression in time and space and therefore determine the tissue-specific genetic programs that shape morphological structures. In recent years, many new examples have greatly advanced our understanding of the genetic alterations that modify GRNs to generate newly evolved morphologies. Here, we review several aspects of GRN evolution, including their deep preservation, their mechanisms of alteration, and how they originate to generate novel developmental programs.

Does immunohistochemistry affect response to therapy and survival of inoperable non-small cell lung carcinoma patients? A survey of 145 stage III-IV consecutive cases.

PubMed

Pelosi, Giuseppe; Haspinger, Eva Regina; Bimbatti, Manuela; Leone, Giorgia; Paolini, Biagio; Fabbri, Alessandra; Tamborini, Elena; Perrone, Federica; Testi, Adele; Garassino, Marina; Maisonneuve, Patrick; de Braud, Filippo; Pilotti, Silvana; Pastorino, Ugo

2014-04-01

Whether non-small cell lung carcinoma (NSCLC) unveiled by immunohistochemistry (IHC) has the same clinical outcome as those typed by morphology is still matter of debate. A total of 145 stage III-IV, consecutive inoperable NSCLC patients treated by chemotherapy (133 cases) or EGFR tyrosine kinase inhibitor (12 cases) and including 100 biopsies, 11 surgical specimens, and 34 cytological samples had originally accounted for 120 adenocarcinomas (ADs), 19 squamous cell carcinomas (SQCs), and 6 adenosquamous carcinomas (ADSQCs) by integrating morphology and thyroid transcription factor-1 (TTF1)/p40 IHC. Thirty-two NSCLC-not otherwise specified (NSCLC-NOS) cases were identified by morphology revision of the original diagnoses, which showed solid growth pattern (P < .001), 22 ADs, 5 SQCs, and 5 ADSQCs by IHC profiling (P < .001), and 10 gene-altered tumors (3 EGFR, 5 KRAS, and 2 ALK). While no significant relationships were observed between response to therapy and original, morphology or IHC diagnoses, driver mutations and tumor differentiation by TTF1 expression, AD run better progression-free survival (PFS) or overall survival (OS) than other tumor types by morphology (P = .010 and P = .047) and IHC (P = .033 and P = .046), respectively. Furthermore, patients with NSCLC-NOS confirmed as AD by IHC tended to have poorer OS (P = .179) and PFS (P = .193) similar to that of ADSQC and SQC (P = .702 and P = .540, respectively). A category of less differentiated AD with poorer prognosis on therapy could be identified by IHC, while there were no differences for SQC or ADSQC. The terminology of "NSCLC-NOS, favor by IHC" is appropriate to alert clinicians toward more aggressive tumors.

Ovipositor morphology correlates with life history evolution in agaonid fig wasps

NASA Astrophysics Data System (ADS)

Elias, Larissa Galante; Kjellberg, Finn; Farache, Fernando Henrique Antoniolli; Almeida, Eduardo A. B.; Rasplus, Jean-Yves; Cruaud, Astrid; Peng, Yan-Qiong; Yang, Da-Rong; Pereira, Rodrigo Augusto Santinelo

2018-07-01

The high adaptive success of parasitic Hymenoptera might be related to the use of different oviposition sites, allowing niche partitioning among co-occurring species resulting in life history specialization and diversification. In this scenario, evolutionary changes in life history and resources for oviposition can be associated with changes in ovipositor structure, allowing exploitation of different substrates for oviposition. We used a formal phylogenetic framework to investigate the evolution of ovipositor morphology and life history in agaonid wasps. We sampled 24 species with different life histories belonging to all main clades of Agaonidae including representatives of all described genera of non-pollinating fig wasps (NPFW). Our results show an overall correlation between ovipositor morphology and life history in agaonid fig wasps. Ovipositor morphologies seem to be related to constraints imposed by features of the oviposition sites since ovipositor morphology has experienced convergent evolution at least four times in Sycophaginae (Agaonidae) according to the resource used. Non-galling species have more distantly spaced teeth with uneven spacing, as opposed to the observed morphology of galling species. Our results suggest that the ancestral condition for ovipositor morphology was most likely the presence of one or two apical teeth. Regarding life history, ovary galling species that oviposit in receptive figs possibly represent the ancestral condition. Different ovipositor characteristics allow exploitation of new niches and may be related to resource partitioning and species co-existence in the fig-fig wasp system.

Vulvar apocrine adenocarcinoma: a case with nodal metastasis and intranodal mucinous differentiation.

PubMed

Alsaad, Khaled O; Obaidat, Nidal; Dube, Valerie; Chapman, William; Ghazarian, Danny

2009-01-01

Primary vulvar adenocarcinomas are rare tumors, and their histogenesis is not fully understood. They are classified into extramammary Paget's disease, sweat gland carcinomas, and "breast-like" adenocarcinomas of the vulva. The latter resemble adenocarcinomas arising in the breast morphologically and immunophenotypically. Rare cases of adenocarcinoma with apocrine features have been reported, and whether these neoplasms originate from the "native apocrine" sweat glands or from "anogenital mammary-like" glands are still debatable. The presence of normal mammary-like glands in the vicinity of the tumor, the transitional malignant morphological features from normal mammary-like glands and the tumor, the breast-like histological features of the tumor, and the expression of estrogen and progesterone receptors generally suggest an origin from anogenital mammary-like glands. Absence of these features points toward native apocrine sweat glands as the source of these neoplasms. In this report, we present a patient who was initially diagnosed with Paget's disease of the right vulva, which was treated by hemi-vulvectomy, and who later presented with primary vulvar apocrine adenocarcinoma with metastasis to the inguinal lymph nodes and intranodal mucinous/colloidal differentiation: a feature, to the best of our knowledge, not reported before. We also reviewed the histogenesis of the vulvar adenocarcinomas, with emphasis on the morphological features that separate the tumors arising from the anogenital mammary-like glands in the vulva from those arising from the native vulvar sweat glands.

Visualizing tumor evolution with the fishplot package for R.

PubMed

Miller, Christopher A; McMichael, Joshua; Dang, Ha X; Maher, Christopher A; Ding, Li; Ley, Timothy J; Mardis, Elaine R; Wilson, Richard K

2016-11-07

Massively-parallel sequencing at depth is now enabling tumor heterogeneity and evolution to be characterized in unprecedented detail. Tracking these changes in clonal architecture often provides insight into therapeutic response and resistance. In complex cases involving multiple timepoints, standard visualizations, such as scatterplots, can be difficult to interpret. Current data visualization methods are also typically manual and laborious, and often only approximate subclonal fractions. We have developed an R package that accurately and intuitively displays changes in clonal structure over time. It requires simple input data and produces illustrative and easy-to-interpret graphs suitable for diagnosis, presentation, and publication. The simplicity, power, and flexibility of this tool make it valuable for visualizing tumor evolution, and it has potential utility in both research and clinical settings. The fishplot package is available at https://github.com/chrisamiller/fishplot .

Resolving phylogenetic incongruence to articulate homology and phenotypic evolution: a case study from Nematoda

PubMed Central

Ragsdale, Erik J.; Baldwin, James G.

2010-01-01

Modern morphology-based systematics, including questions of incongruence with molecular data, emphasizes analysis over similarity criteria to assess homology. Yet detailed examination of a few key characters, using new tools and processes such as computerized, three-dimensional ultrastructural reconstruction of cell complexes, can resolve apparent incongruence by re-examining primary homologies. In nematodes of Tylenchomorpha, a parasitic feeding phenotype is thus reconciled with immediate free-living outgroups. Closer inspection of morphology reveals phenotypes congruent with molecular-based phylogeny and points to a new locus of homology in mouthparts. In nematode models, the study of individually homologous cells reveals a conserved modality of evolution among dissimilar feeding apparati adapted to divergent lifestyles. Conservatism of cellular components, consistent with that of other body systems, allows meaningful comparative morphology in difficult groups of microscopic organisms. The advent of phylogenomics is synergistic with morphology in systematics, providing an honest test of homology in the evolution of phenotype. PMID:20106846

Evolution of the structure and function of the vertebrate tongue

PubMed Central

Iwasaki, Shin-ichi

2002-01-01

Abstract Studies of the comparative morphology of the tongues of living vertebrates have revealed how variations in the morphology and function of the organ might be related to evolutional events. The tongue, which plays a very important role in food intake by vertebrates, exhibits significant morphological variations that appear to represent adaptation to the current environmental conditions of each respective habitat. This review examines the fundamental importance of morphology in the evolution of the vertebrate tongue, focusing on the origin of the tongue and on the relationship between morphology and environmental conditions. Tongues of various extant vertebrates, including those of amphibians, reptiles, birds and mammals, were analysed in terms of gross anatomy and microanatomy by light microscopy and by scanning and transmission electron microscopy. Comparisons of tongue morphology revealed a relationship between changes in the appearance of the tongue and changes in habitat, from a freshwater environment to a terrestrial environment, as well as a relationship between the extent of keratinization of the lingual epithelium and the transition from a moist or wet environment to a dry environment. The lingual epithelium of amphibians is devoid of keratinization while that of reptilians is keratinized to different extents. Reptiles live in a variety of habitats, from seawater to regions of high temperature and very high or very low humidity. Keratinization of the lingual epithelium is considered to have been acquired concomitantly with the evolution of amniotes. The variations in the extent of keratinization of the lingual epithelium, which is observed between various amniotes, appear to be secondary, reflecting the environmental conditions of different species. PMID:12171472

Evolution of the structure and function of the vertebrate tongue.

PubMed

Iwasaki, Shin-ichi

2002-07-01

Studies of the comparative morphology of the tongues of living vertebrates have revealed how variations in the morphology and function of the organ might be related to evolutional events. The tongue, which plays a very important role in food intake by vertebrates, exhibits significant morphological variations that appear to represent adaptation to the current environmental conditions of each respective habitat. This review examines the fundamental importance of morphology in the evolution of the vertebrate tongue, focusing on the origin of the tongue and on the relationship between morphology and environmental conditions. Tongues of various extant vertebrates, including those of amphibians, reptiles, birds and mammals, were analysed in terms of gross anatomy and microanatomy by light microscopy and by scanning and transmission electron microscopy. Comparisons of tongue morphology revealed a relationship between changes in the appearance of the tongue and changes in habitat, from a freshwater environment to a terrestrial environment, as well as a relationship between the extent of keratinization of the lingual epithelium and the transition from a moist or wet environment to a dry environment. The lingual epithelium of amphibians is devoid of keratinization while that of reptilians is keratinized to different extents. Reptiles live in a variety of habitats, from seawater to regions of high temperature and very high or very low humidity. Keratinization of the lingual epithelium is considered to have been acquired concomitantly with the evolution of amniotes. The variations in the extent of keratinization of the lingual epithelium, which is observed between various amniotes, appear to be secondary, reflecting the environmental conditions of different species.

Angiofibroma of soft tissue: clinicopathologic study of 2 cases of a recently characterized benign soft tissue tumor.

PubMed

Zhao, Ming; Sun, Ke; Li, Changshui; Zheng, Jiangjiang; Yu, Jingjing; Jin, Jie; Xia, Wenping

2013-01-01

Angiofibroma of soft tissue is a very recently characterized, histologically distinctive benign mesenchymal neoplasm of unknown cellular origin composed of 2 principal components, the spindle cell component and very prominent stromal vasculatures. It usually occurs in middle-aged adults, with a female predominance. Herein, we describe the clinical and pathologic details of 2 other examples of this benign tumor. Both patients were middle-aged male and presented with a slow-growing, painless mass located in the deep-seated soft tissue of thigh and left posterior neck region, respectively. Grossly, both tumors were well-demarcated, partial encapsulated of a grayish-white color with firm consistence. Histologically, one case showed morphology otherwise identical to those have been described before, whereas the other case showed in areas being more cellular than most examples of this subtype tumor had, with the lesional cells frequently exhibiting short fascicular, vaguely storiform and occasionally swirling arrangements, which posed a challenging differential diagnosis. Immunostains performed on both tumors did not confirm any specific cell differentiation with lesional cells only reactive for vimentin and focally desmin and negative for all the other markers tested. This report serves to broaden the morphologic spectrum of angiofibroma of soft tumor. Awareness of this tumor is important to prevent misdiagnosis as other more aggressive soft tissue tumor.

Geomorphological evolution of landslides near an active normal fault in northern Taiwan, as revealed by lidar and unmanned aircraft system data

NASA Astrophysics Data System (ADS)

Chang, Kuo-Jen; Chan, Yu-Chang; Chen, Rou-Fei; Hsieh, Yu-Chung

2018-03-01

Several remote sensing techniques, namely traditional aerial photographs, an unmanned aircraft system (UAS), and airborne lidar, were used in this study to decipher the morphological features of obscure landslides in volcanic regions and how the observed features may be used for understanding landslide occurrence and potential hazard. A morphological reconstruction method was proposed to assess landslide morphology based on the dome-shaped topography of the volcanic edifice and the nature of its morphological evolution. Two large-scale landslides in the Tatun volcano group in northern Taiwan were targeted to more accurately characterize the landslide morphology through airborne lidar and UAS-derived digital terrain models and images. With the proposed reconstruction method, the depleted volume of the two landslides was estimated to be at least 820 ± 20 × 106 m3. Normal faulting in the region likely played a role in triggering the two landslides, because there are extensive geological and historical records of an active normal fault in this region. The subsequent geomorphological evolution of the two landslides is thus inferred to account for the observed morphological and tectonic features that are indicative of resulting in large and life-threatening landslides, as characterized using the recent remote sensing techniques.

A reappraisal of hemangiopericytoma of bone; analysis of cases reclassified as synovial sarcoma and solitary fibrous tumor of bone.

PubMed

Verbeke, Sofie L J; Fletcher, Christopher D M; Alberghini, Marco; Daugaard, Søren; Flanagan, Adrienne M; Parratt, Tim; Kroon, Herman M; Hogendoorn, Pancras C W; Bovée, Judith V M G

2010-06-01

Hemangiopericytoma (HPC) was first described as a neoplasm with distinct morphologic features, presumably composed of pericytes. In soft tissue, it is accepted that most such lesions are solitary fibrous tumors (SFTs), monophasic synovial sarcomas (SSs), or myofibromatoses. It is unclear whether HPC of bone exists. We reviewed 9 primary "HPC" of bone from 4 institutions diagnosed between 1952 and 2002. Immunohistochemistry was performed for CD31, CD34, von Willebrand factor, smooth muscle actin, keratin AE1/AE3, and epithelial membrane antigen. There were 4 male and 5 female patients between 21 and 73 years. All tumors were located within bone, either sited within spine or extremities. All tumors showed thin-walled branching vessels surrounded by undifferentiated spindle or round cells. These cells showed variation in their morphologic pattern: 6 tumors showed a pattern-less architecture and varying cellularity, consistent with SFT; 3 of 5 cases examined were CD34-positive. Three tumors showed more densely packed sheets and fascicles of poorly differentiated cells, resembling SS, of which 2 showed focal staining for keratin AE1/AE3 or epithelial membrane antigen. Fluorescent in-situ hybridization confirmed the presence of SS18 rearrangement in 1 of 2 tumors examined. In conclusion, similar to their soft-tissue counterpart, HPC-like features in bone are a nonspecific growth pattern rather than a true diagnosis. We confirm the existence of 2 entities: SFT and SS of bone. Both are characterized by distinct morphology and immunohistochemical profile. SFT of bone is located within spine and has a better prognosis, whereas SS of bone is located within long bones having a poor prognosis.

The morphologic and immunohistochemical spectrum of papillary renal cell carcinoma: study including 132 cases with pure type 1 and type 2 morphology as well as tumors with overlapping features.

PubMed

Chevarie-Davis, Myriam; Riazalhosseini, Yasser; Arseneault, Madeleine; Aprikian, Armen; Kassouf, Wassim; Tanguay, Simon; Latour, Mathieu; Brimo, Fadi

2014-07-01

Papillary renal cell carcinomas (pRCC) are classically divided into type 1 and 2 tumors. However, many cases do not fulfill all the criteria for either type. We describe the clinical, morphologic, and immunohistochemical (IHC) features of 132 pRCCs to better characterize the frequency and nature of tumors with overlapping features. Cases were reviewed and classified; IHC evaluation of CK7, EMA, TopoIIα, napsin A, and AMACR was performed on 95 cases. The frequencies of type 1, type 2, and "overlapping" pRCC were 25%, 28%, and 47%, respectively. The 2 categories of "overlapping" tumors were: (1) cases with bland cuboidal cells but no basophilic cytoplasm (type A); and (2) cases with predominantly type 1 histology admixed with areas showing prominent nucleoli (type B). The pathologic stage of "overlapping" cases showed concordance with type 1 tumors. Using the 2 discriminatory markers (CK7, EMA), "type A" cases were similar to type 1. Although the high-nuclear grade areas of "type B" tumors showed some staining differences from their low-nuclear grade counterpart, their IHC profile was closer to type 1. Single nucleotide polymorphism array results, although preliminary and restricted to only 9 cases (3 with overlapping features), also seemed to confirm those findings. In conclusion, we demonstrate that variations in cytoplasmic quality and/or presence of high-grade nuclei in tumors otherwise displaying features of type 1 pRCCs are similar in stage and IHC profile those with classic type 1 histology, suggesting that their spectrum might be wider than originally described.

Whole-genome and multisector exome sequencing of primary and post-treatment glioblastoma reveals patterns of tumor evolution

PubMed Central

Kim, Hoon; Zheng, Siyuan; Amini, Seyed S.; Virk, Selene M.; Mikkelsen, Tom; Brat, Daniel J.; Grimsby, Jonna; Sougnez, Carrie; Muller, Florian; Hu, Jian; Sloan, Andrew E.; Cohen, Mark L.; Van Meir, Erwin G.; Scarpace, Lisa; Laird, Peter W.; Weinstein, John N.; Lander, Eric S.; Gabriel, Stacey; Getz, Gad; Meyerson, Matthew; Chin, Lynda; Barnholtz-Sloan, Jill S.

2015-01-01

Glioblastoma (GBM) is a prototypical heterogeneous brain tumor refractory to conventional therapy. A small residual population of cells escapes surgery and chemoradiation, resulting in a typically fatal tumor recurrence ∼7 mo after diagnosis. Understanding the molecular architecture of this residual population is critical for the development of successful therapies. We used whole-genome sequencing and whole-exome sequencing of multiple sectors from primary and paired recurrent GBM tumors to reconstruct the genomic profile of residual, therapy resistant tumor initiating cells. We found that genetic alteration of the p53 pathway is a primary molecular event predictive of a high number of subclonal mutations in glioblastoma. The genomic road leading to recurrence is highly idiosyncratic but can be broadly classified into linear recurrences that share extensive genetic similarity with the primary tumor and can be directly traced to one of its specific sectors, and divergent recurrences that share few genetic alterations with the primary tumor and originate from cells that branched off early during tumorigenesis. Our study provides mechanistic insights into how genetic alterations in primary tumors impact the ensuing evolution of tumor cells and the emergence of subclonal heterogeneity. PMID:25650244

EVOLUTION OF SARCOMA 37 IN CF1 RATS. BIOLOGICAL ASPECTS OF THE SPONTANEOUS CURE OF TUMORS STUDIED AFTER IRRADIATION AND ADMINISTRATION OF IMMUNE SERUM. Evolucao do sarcoma 37 em muganhos CF1. Aspectos biologicos da cura espontianea do tumor estudados apos irradiacao e administracao de soro imune (in Portuguese)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Clode, William H.

Transplants of sarcoma 37 were studied in regard to spontaneous regression of the tumor after irradiation and after the administration of immune serum. The following results were obtained: 1. Of 809 animals, 99% developed the tumor after transplantation; 2. The number of cells transplanted did not influence the growth rate, the percentage of spontaneous regressions, or the life spans of the animals; 3. Reimplantation of the tumor into mice which had previously rejected the tumor resulted in very few successful transplants; 4. The resistance of these mice to further attempts at implantation could not be altered by previous irradiation; 5.more » Animals transplanted for the first time suffer a faster evolution of the tumor, shortened life span, and a diminution of spontaneous regressions if they have been irradiated prior to transplantation (400r whole body); and, 6. Resistance to tumor growth could not be transferred passively in serum of mice which had rejected the tumor.« less

Clownfishes evolution below and above the species level

PubMed Central

Litsios, Glenn; Faye, Laurélène; Salamin, Nicolas

2018-01-01

The difference between rapid morphological evolutionary changes observed in populations and the long periods of stasis detected in the fossil record has raised a decade-long debate about the exact role played by intraspecific mechanisms at the interspecific level. Although they represent different scales of the same evolutionary process, micro- and macroevolution are rarely studied together and few empirical studies have compared the rates of evolution and the selective pressures between both scales. Here, we analyse morphological, genetic and ecological traits in clownfishes at different evolutionary scales and demonstrate that the tempo of molecular and morphological evolution at the species level can be, to some extent, predicted from parameters estimated below the species level, such as the effective population size or the rate of evolution within populations. We also show that similar codons in the gene of the rhodopsin RH1, a light-sensitive receptor protein, are under positive selection at the intra and interspecific scales, suggesting that similar selective pressures are acting at both levels. PMID:29467260

Germinoma with an extensive rhabdoid cell component centered at the corpus callosum.

PubMed

Tajima, Shogo; Koda, Kenji

2017-03-01

Intracranial germinomas comprise 0.5-2.0 % of all central nervous system (CNS) tumors and 50-60 % of CNS germ cell tumors. They most frequently originate in the pineal gland and the suprasellar region. The corpus callosum is an extremely uncommon location for germinoma formation. Herein, we report about a 20-year-old man with a germinoma centered at the corpus callosum and that extended to both cerebral hemispheres. In addition to its location, this case is unique in that the amount of tumor cells with rhabdoid morphology exceeded that of tumor cells with typical morphology. The rhabdoid cell component showed an immunophenotype compatible with germinoma. While the presence of rhabdoid cells is generally regarded as a sign of aggressive behavior, the patient has been doing well for at least 4 years since undergoing radiation therapy and chemotherapy. The cellular composition of germinoma might not critically affect prognosis with adequate treatment.

TFE3-Expressing Perivascular Epithelioid Cell Neoplasm (PEComa) of the Sella Turcica.

PubMed

Hyrcza, Martin D; Winer, Daniel A; Shago, Mary; Au, Karolyn; Zadeh, Gelareh; Asa, Sylvia L; Mete, Ozgur

2017-03-01

We report a primary central nervous system (CNS) perivascular epithelioid cell tumor (PEComa) in a middle-aged female patient. The tumor occurred in suprasellar location with secondary extension into the sella turcica. The patient presented with intracranial hemorrhage and an altered level of consciousness. The tumor had morphologic features matching those of other previously described TFE3-translocated PEComas, including epithelioid morphology, diffuse and strong nuclear immunoreactivity for TFE3, and minimal staining with myoid markers. The TFE3 break-apart FISH testing showed a slight splitting of one of the TFE3 signals in 49.5 % of nuclei. This case illustrates that PEComas should be added to the growing list of mesenchymal tumors that can be encountered in the CNS and specifically in the vicinity of the pituitary gland. The recognition of this entity is of significance given their underlying pathogenesis and possible management implications.

Co-evolution of somatic variation in primary and metastatic colorectal cancer may expand biopsy indications in the molecular era.

PubMed

Kim, Richard; Schell, Michael J; Teer, Jamie K; Greenawalt, Danielle M; Yang, Mingli; Yeatman, Timothy J

2015-01-01

Metastasis is thought to be a clonal event whereby a single cell initiates the development of a new tumor at a distant site. However the degree to which primary and metastatic tumors differ on a molecular level remains unclear. To further evaluate these concepts, we used next generation sequencing (NGS) to assess the molecular composition of paired primary and metastatic colorectal cancer tissue specimens. 468 colorectal tumor samples from a large personalized medicine initiative were assessed by targeted gene sequencing of 1,321 individual genes. Eighteen patients produced genomic profiles for 17 paired primary:metastatic (and 2 metastatic:metastatic) specimens. An average of 33.3 mutations/tumor were concordant (shared) between matched samples, including common well-known genes (APC, KRAS, TP53). An average of 2.3 mutations/tumor were discordant (unshared) among paired sites. KRAS mutational status was always concordant. The overall concordance rate for mutations was 93.5%; however, nearly all (18/19 (94.7%)) paired tumors showed at least one mutational discordance. Mutations were seen in: TTN, the largest gene (5 discordant pairs), ADAMTS20, APC, MACF1, RASA1, TP53, and WNT2 (2 discordant pairs), SMAD2, SMAD3, SMAD4, FBXW7, and 66 others (1 discordant pair). Whereas primary and metastatic tumors displayed little variance overall, co-evolution produced incremental mutations in both. These results suggest that while biopsy of the primary tumor alone is likely sufficient in the chemotherapy-naïve patient, additional biopsies of primary or metastatic disease may be necessary to precisely tailor therapy following chemotherapy resistance or insensitivity in order to adequately account for tumor evolution.

Co-Evolution of Somatic Variation in Primary and Metastatic Colorectal Cancer May Expand Biopsy Indications in the Molecular Era

PubMed Central

Kim, Richard; Schell, Michael J.; Teer, Jamie K.; Greenawalt, Danielle M.; Yang, Mingli; Yeatman, Timothy J.

2015-01-01

Introduction Metastasis is thought to be a clonal event whereby a single cell initiates the development of a new tumor at a distant site. However the degree to which primary and metastatic tumors differ on a molecular level remains unclear. To further evaluate these concepts, we used next generation sequencing (NGS) to assess the molecular composition of paired primary and metastatic colorectal cancer tissue specimens. Methods 468 colorectal tumor samples from a large personalized medicine initiative were assessed by targeted gene sequencing of 1,321 individual genes. Eighteen patients produced genomic profiles for 17 paired primary:metastatic (and 2 metastatic:metastatic) specimens. Results An average of 33.3 mutations/tumor were concordant (shared) between matched samples, including common well-known genes (APC, KRAS, TP53). An average of 2.3 mutations/tumor were discordant (unshared) among paired sites. KRAS mutational status was always concordant. The overall concordance rate for mutations was 93.5%; however, nearly all (18/19 (94.7%)) paired tumors showed at least one mutational discordance. Mutations were seen in: TTN, the largest gene (5 discordant pairs), ADAMTS20, APC, MACF1, RASA1, TP53, and WNT2 (2 discordant pairs), SMAD2, SMAD3, SMAD4, FBXW7, and 66 others (1 discordant pair). Conclusions Whereas primary and metastatic tumors displayed little variance overall, co-evolution produced incremental mutations in both. These results suggest that while biopsy of the primary tumor alone is likely sufficient in the chemotherapy-naïve patient, additional biopsies of primary or metastatic disease may be necessary to precisely tailor therapy following chemotherapy resistance or insensitivity in order to adequately account for tumor evolution. PMID:25974029

Fast and robust brain tumor segmentation using level set method with multiple image information.

PubMed

Lok, Ka Hei; Shi, Lin; Zhu, Xianlun; Wang, Defeng

2017-01-01

Brain tumor segmentation is a challenging task for its variation in intensity. The phenomenon is caused by the inhomogeneous content of tumor tissue and the choice of imaging modality. In 2010 Zhang developed the Selective Binary Gaussian Filtering Regularizing Level Set (SBGFRLS) model that combined the merits of edge-based and region-based segmentation. To improve the SBGFRLS method by modifying the singed pressure force (SPF) term with multiple image information and demonstrate effectiveness of proposed method on clinical images. In original SBGFRLS model, the contour evolution direction mainly depends on the SPF. By introducing a directional term in SPF, the metric could control the evolution direction. The SPF is altered by statistic values enclosed by the contour. This concept can be extended to jointly incorporate multiple image information. The new SPF term is expected to bring a solution for blur edge problem in brain tumor segmentation. The proposed method is validated with clinical images including pre- and post-contrast magnetic resonance images. The accuracy and robustness is compared with sensitivity, specificity, DICE similarity coefficient and Jaccard similarity index. Experimental results show improvement, in particular the increase of sensitivity at the same specificity, in segmenting all types of tumors except for the diffused tumor. The novel brain tumor segmentation method is clinical-oriented with fast, robust and accurate implementation and a minimal user interaction. The method effectively segmented homogeneously enhanced, non-enhanced, heterogeneously-enhanced, and ring-enhanced tumor under MR imaging. Though the method is limited by identifying edema and diffuse tumor, several possible solutions are suggested to turn the curve evolution into a fully functional clinical diagnosis tool.

Evolution processes of the corrosion behavior and structural characteristics of plasma electrolytic oxidation coatings on AZ31 magnesium alloy

NASA Astrophysics Data System (ADS)

Chen, Dong; Wang, Ruiqiang; Huang, Zhiquan; Wu, Yekang; Zhang, Yi; Wu, Guorui; Li, Dalong; Guo, Changhong; Jiang, Guirong; Yu, Shengxue; Shen, Dejiu; Nash, Philip

2018-03-01

Evolution processes of the corrosion behavior and structural characteristics of the plasma electrolytic oxidation (PEO) coated AZ31 magnesium alloy were investigated by using scanning electron microscope (SEM) equipped with energy dispersive X-ray spectroscopy (EDS), X-ray diffraction (XRD), potentio-dynamic polarization curves and electrochemical impedance spectroscopy (EIS) measurements. Detached coating samples were fabricated by an electrochemical method and more details of the internal micro-structure of coatings were clearly observed on the fractured cross-section morphologies of the samples compared to general polished cross-section morphologies. Evolution mechanisms of the coating corrosion behavior in relation to the evolution of micro-structural characteristics were discussed in detail.

Cranial morphology of Javanese Homo erectus: new evidence for continuous evolution, specialization, and terminal extinction.

PubMed

Kaifu, Yousuke; Aziz, Fachroel; Indriati, Etty; Jacob, Teuku; Kurniawan, Iwan; Baba, Hisao

2008-10-01

Our current knowledge of the evolution of Homo during the early to middle Pleistocene is far from complete. This is not only because of the small number of fossil samples available, but also due to the scarcity of standardized datasets which are reliable in terms of landmark identification, interobserver error, and other distorting factors. This study aims to accurately describe the cranial morphological changes of H. erectus in Java using a standardized set of measurements taken by the authors from 18 adult crania from Sangiran, Trinil, Sambungmacan, and Ngandong. The identification of some obscure landmarks was aided by the use of micro-CT imaging. While recent studies tend to emphasize evolutionary conservatism in Javanese H. erectus, our results reinforce the theory that chronologically later groups experienced distinct morphological changes in a number of cranial traits. Some of these changes, particularly those related to brain size expansion, are similar to those observed for the genus Homo as a whole, whereas others are apparently unique specializations restricted to Javanese H. erectus. Such morphological specializations in Java include previously undescribed anteroposterior lengthening of the midcranial base and an anterior shift of the posterior temporal muscle, which might have influenced the morphology of the angular torus and supramastoid sulcus. Analyses of morphological variation indicate that the three crania from Sambungmacan variously fill the morphological gap between the chronologically earlier (Bapang-AG, Bapang Formation above the Grenzbank zone in Sangiran) and later (Ngandong) morphotypes of Java. At least one of the Bapang-AG crania, Sangiran 17, also exhibits a few characteristics which potentially indicate evolution toward the Ngandong condition. These strongly suggest the continuous, gradual morphological evolution of Javanese H. erectus from the Bapang-AG to Ngandong periods. The development of some unique features in later Javanese H. erectus supports the hypothesis that this Javanese lineage went extinct without making significant contributions to the ancestry of modern humans.

Effect of electromagnetic microwave radiation on the growth of Ehrlich ascites carcinoma.

PubMed

Kryukova, O V; Pyankov, V F; Kopylov, A F; Khlebopros, R G

2016-09-01

Daily exposure of mouse recipients of Ehrlich ascites carcinoma to electromagnetic radiation of the microwave range leads to a change in the dynamics of tumor growth by decreasing the total number of cells. The number of tumor cells with blebbing morphological signs after microwave radiation increases gradually with tumor growth. The maximum content of tumor cells in the state of blebbing is observed during active proliferation in tumor-recipient mice of the control group (without irradiation).

Primitive neuroectodermal tumors of the central nervous system.

PubMed

Becker, L E; Hinton, D

1983-06-01

Primitive neuroectodermal tumors are morphologically similar malignant tumors arising in intracranial and peripheral sites of the nervous system, showing varying degrees of cellular differentiation with a tendency to disseminate along cerebrospinal fluid pathways. They occur primarily in children and young adults. Under the designation primitive neuroectodermal tumors are included medulloblastomas and tumors that may differentiate in other directions, such as medulloepithelioma, neuroblastoma, polar spongioblastoma, pineoblastoma, ependymoblastoma, retinoblastoma, and olfactory neuroblastoma. From a practical, histologic point of view, these tumors are often indistinguishable from one another and are best thought of as primitive neuroectodermal tumors with or without differentiating features.

Pediatric Renal Neoplasms.

PubMed

Ranganathan, Sarangarajan

2009-03-01

Renal tumors in childhood consist of a diverse group of tumors ranging from the most common Wilms' tumor, to the uncommon and often fatal rhabdoid tumor. Diagnosis is based on morphologic features and aided by ancillary techniques such as immunohistochemistry and cytogenetics. Molecular techniques have helped identify a group of pediatric renal cell carcinomas that have specific translocations, called translocation-associated carcinomas. Differential diagnosis of the various tumors is discussed. Pathogenesis and nephroblastomatosis, the precursor lesions of Wilms tumor, also are discussed briefly, as are the handling of these tumor specimens and prognostic factors. Copyright © 2009 Elsevier Inc. All rights reserved.

INHIBITION OF INDUCED DIFFERENTIATION OF C3H/1OT 1/2 CLONE 8 MOUSE EMBRYO CELLS BY TUMOR PROMOTERS

EPA Science Inventory

C3H/10T 1/2 cells were induced to differentiate into muscle cells by treatment with 5-azacytidine, and the effects of tumor promoters, nonpromoters, and inhibitors of tumor promotion on this induced differentiation were investigated. Cell morphology was dramatically changed withi...

Improvement of hyperandrogenism, oligo-ovulation, and ovarian morphology in a patient with polycystic ovary syndrome: possible role of ovarian wedge resection.

PubMed

Zhang, YuanYuan; Luo, SuiYu; Gong, ZhiQuan; Feng, XiaoYa; Wang, ZiYi; Zhu, HaoHui; Wang, Yu

2018-06-01

Polycystic ovary syndrome (PCOS) is an endocrinological abnormality which typically presents as hormones disorder and/or infertility. It has received more and more attention in recent years though its pathogenesis is still unclear. Ovarian mucinous adenoma is a rarely pathological type which generates from epithelial cell of ovary. Here we present a patient with PCOS and ovarian mucinous tumor (occasionally discovered by cesarean section) receiving a complete relief after benign ovarian tumor excision. In this case, tumor excision played as a partial resection of ovary which might result in the normalized concentration level of hormones and morphology of ovary. This report suggests that therapeutic strategies for PCOS should be considered more carefully and individually.

Blood-Based Analyses of Cancer: Circulating Tumor Cells and Circulating Tumor DNA

PubMed Central

Haber, Daniel A.; Velculescu, Victor E.

2015-01-01

The ability to study nonhematologic cancers through noninvasive sampling of blood is one of the most exciting and rapidly advancing fields in cancer diagnostics. This has been driven both by major technologic advances, including the isolation of intact cancer cells and the analysis of cancer cell–derived DNA from blood samples, and by the increasing application of molecularly driven therapeutics, which rely on such accurate and timely measurements of critical biomarkers. Moreover, the dramatic efficacy of these potent cancer therapies drives the selection for additional genetic changes as tumors acquire drug resistance, necessitating repeated sampling of cancer cells to adjust therapy in response to tumor evolution. Together, these advanced noninvasive diagnostic capabilities and their applications in guiding precision cancer therapies are poised to change the ways in which we select and monitor cancer treatments. Significance Recent advances in technologies to analyze circulating tumor cells and circulating tumor DNA are setting the stage for real-time, noninvasive monitoring of cancer and providing novel insights into cancer evolution, invasion, and metastasis. PMID:24801577

The Production of 3D Tumor Spheroids for Cancer Drug Discovery

PubMed Central

Sant, Shilpa; Johnston, Paul A.

2017-01-01

New cancer drug approval rates are ≤ 5% despite significant investments in cancer research, drug discovery and development. One strategy to improve the rate of success of new cancer drugs transitioning into the clinic would be to more closely align the cellular models used in the early lead discovery with pre-clinical animal models and patient tumors. For solid tumors, this would mandate the development and implementation of three dimensional (3D) in vitro tumor models that more accurately recapitulate human solid tumor architecture and biology. Recent advances in tissue engineering and regenerative medicine have provided new techniques for 3D spheroid generation and a variety of in vitro 3D cancer models are being explored for cancer drug discovery. Although homogeneous assay methods and high content imaging approaches to assess tumor spheroid morphology, growth and viability have been developed, the implementation of 3D models in HTS remains challenging due to reasons that we discuss in this review. Perhaps the biggest obstacle to achieve acceptable HTS assay performance metrics occurs in 3D tumor models that produce spheroids with highly variable morphologies and/or sizes. We highlight two methods that produce uniform size-controlled 3D multicellular tumor spheroids that are compatible with cancer drug research and HTS; tumor spheroids formed in ultra-low attachment microplates, or in polyethylene glycol dimethacrylate hydrogel microwell arrays. PMID:28647083

Intersections between immune responses and morphological regulation in plants.

PubMed

Uchida, Naoyuki; Tasaka, Masao

2010-06-01

Successful plant pathogens have developed strategies to interfere with the defence mechanisms of their host plants through evolution. Conversely, host plants have evolved systems to counteract pathogen attack. Some pathogens induce pathogenic symptoms on plants that include morphological changes in addition to interference with plant growth. Recent studies, based on molecular biology and genetics using Arabidopsis thaliana, have revealed that factors derived from pathogens can modulate host systems and/or host factors that play important roles in the morphological regulation of host plants. Other reports, meanwhile, have shown that factors known to have roles in plant morphology also function in plant immune responses. Evolutionary conservation of these factors and systems implies that host-pathogen interactions and the evolution they drive have yielded tight links between morphological processes and immune responses. In this review, recent findings about these topics are introduced and discussed.

The role of habitat shift in the evolution of lizard morphology: evidence from tropical Tropidurus

PubMed Central

Vitt, Laurie J.; Caldwell, Janalee P.; Zani, Peter A.; Titus, Tom A.

1997-01-01

We compared morphology of two geographically close populations of the tropical lizard Tropidurus hispidus to test the hypothesis that habitat structure influences the evolution of morphology and ecology at the population level. T. hispidus isolated on a rock outcrop surrounded by tropical forest use rock crevices for refuge and appear dorsoventrally compressed compared with those in open savanna. A principal components analysis revealed that the populations were differentially distributed along an axis representing primarily three components of shape: body width, body height, and hind-leg length. Morphological divergence was supported by a principal components analysis of size-free morphological variables. Mitochondrial DNA sequences of ATPase 6 indicate that these populations are closely related relative to other T. hispidus, the rock outcrop morphology and ecology are derived within T. hispidus, and morphological and ecological divergence has occurred more rapidly than genetic divergence. This suggests that natural selection can rapidly adjust morphology and ecology in response to a recent history of exposure to habitats differing in structure, a result heretofore implied from comparative studies among lizard species. PMID:9108063

The role of habitat shift in the evolution of lizard morphology: evidence from tropical Tropidurus.

PubMed

Vitt, L J; Caldwell, J P; Zani, P A; Titus, T A

1997-04-15

We compared morphology of two geographically close populations of the tropical lizard Tropidurus hispidus to test the hypothesis that habitat structure influences the evolution of morphology and ecology at the population level. T. hispidus isolated on a rock outcrop surrounded by tropical forest use rock crevices for refuge and appear dorsoventrally compressed compared with those in open savanna. A principal components analysis revealed that the populations were differentially distributed along an axis representing primarily three components of shape: body width, body height, and hind-leg length. Morphological divergence was supported by a principal components analysis of size-free morphological variables. Mitochondrial DNA sequences of ATPase 6 indicate that these populations are closely related relative to other T. hispidus, the rock outcrop morphology and ecology are derived within T. hispidus, and morphological and ecological divergence has occurred more rapidly than genetic divergence. This suggests that natural selection can rapidly adjust morphology and ecology in response to a recent history of exposure to habitats differing in structure, a result heretofore implied from comparative studies among lizard species.

Body shape transformation along a shared axis of anatomical evolution in labyrinth fishes (Anabantoidei).

PubMed

Collar, David C; Quintero, Michelle; Buttler, Bernardo; Ward, Andrea B; Mehta, Rita S

2016-03-01

Major morphological transformations, such as the evolution of elongate body shape in vertebrates, punctuate evolutionary history. A fundamental step in understanding the processes that give rise to such transformations is identification of the underlying anatomical changes. But as we demonstrate in this study, important insights can also be gained by comparing these changes to those that occur in ancestral and closely related lineages. In labyrinth fishes (Anabantoidei), rapid evolution of a highly derived torpedo-shaped body in the common ancestor of the pikehead (Luciocephalus aura and L. pulcher) occurred primarily through exceptional elongation of the head, with secondary contributions involving reduction in body depth and lengthening of the precaudal vertebral region. This combination of changes aligns closely with the primary axis of anatomical diversification in other anabantoids, revealing that pikehead evolution involved extraordinarily rapid change in structures that were ancestrally labile. Finer-scale examination of the anatomical components that determine head elongation also shows alignment between the pikehead evolutionary trajectory and the primary axis of cranial diversification in anabantoids, with much higher evolutionary rates leading to the pikehead. Altogether, our results show major morphological transformation stemming from extreme change along a shared morphological axis in labyrinth fishes. © 2016 The Author(s). Evolution © 2016 The Society for the Study of Evolution.

Early bursts of body size and shape evolution are rare in comparative data.

PubMed

Harmon, Luke J; Losos, Jonathan B; Jonathan Davies, T; Gillespie, Rosemary G; Gittleman, John L; Bryan Jennings, W; Kozak, Kenneth H; McPeek, Mark A; Moreno-Roark, Franck; Near, Thomas J; Purvis, Andy; Ricklefs, Robert E; Schluter, Dolph; Schulte Ii, James A; Seehausen, Ole; Sidlauskas, Brian L; Torres-Carvajal, Omar; Weir, Jason T; Mooers, Arne Ø

2010-08-01

George Gaylord Simpson famously postulated that much of life's diversity originated as adaptive radiations-more or less simultaneous divergences of numerous lines from a single ancestral adaptive type. However, identifying adaptive radiations has proven difficult due to a lack of broad-scale comparative datasets. Here, we use phylogenetic comparative data on body size and shape in a diversity of animal clades to test a key model of adaptive radiation, in which initially rapid morphological evolution is followed by relative stasis. We compared the fit of this model to both single selective peak and random walk models. We found little support for the early-burst model of adaptive radiation, whereas both other models, particularly that of selective peaks, were commonly supported. In addition, we found that the net rate of morphological evolution varied inversely with clade age. The youngest clades appear to evolve most rapidly because long-term change typically does not attain the amount of divergence predicted from rates measured over short time scales. Across our entire analysis, the dominant pattern was one of constraints shaping evolution continually through time rather than rapid evolution followed by stasis. We suggest that the classical model of adaptive radiation, where morphological evolution is initially rapid and slows through time, may be rare in comparative data.

Computer simulation of morphological evolution and rafting of {gamma}{prime} particles in Ni-based superalloys under applied stresses

DOE Office of Scientific and Technical Information (OSTI.GOV)

Li, D.Y.; Chen, L.Q.

Mechanical properties of Ni-based superalloys are strongly affected by the morphology, distribution, and size of {gamma}{prime} precipitates in the {gamma} matrix. The main purpose of this paper is to propose a continuum field approach for modeling the morphology and rafting kinetics of coherent precipitates under applied stresses. This approach can be used to simulate the temporal evolution of arbitrary morphologies and microstructures without any a priori assumption. Recently, the authors applied this approach to the selected variant growth in Ni-Ti alloys under applied stresses using an inhomogeneous modulus approximation. For the {gamma}{prime} precipitates in Ni-based superalloys, the eigenstrain is dilatational,more » and hence the {gamma}{prime} morphological evolution can be affected by applied stresses only when the elastic modulus is inhomogeneous. In the present work, the elastic inhomogeneity was taken into account by reformulating a sharp-interface elasticity theory developed recently by Khachaturyan et al. in terms of diffuse interfaces. Although the present work is for a {gamma}{prime} {minus} {gamma} system, this model is general in a sense that it can be applied to other alloy systems containing coherent ordered intermetallic precipitates with elastic inhomogeneity.« less

Divergent morphological and acoustic traits in sympatric communities of Asian barbets

PubMed Central

Tamma, Krishnapriya

2016-01-01

The opposing effects of environmental filtering and competitive interactions may influence community assembly and coexistence of related species. Competition, both in the domain of ecological resources, and in the sensory domain (for example, acoustic interference) may also result in sympatric species evolving divergent traits and niches. Delineating these scenarios within communities requires understanding trait distributions and phylogenetic structure within the community, as well as patterns of trait evolution. We report that sympatric assemblages of Asian barbets (frugivorous canopy birds) consist of a random phylogenetic sample of species, but are divergent in both morphological and acoustic traits. Additionally, we find that morphology is more divergent than expected under Brownian evolution, whereas vocal frequency evolution is close to the pattern expected under Brownian motion (i.e. a random walk). Together, these patterns are consistent with a role for competition or competitive exclusion in driving community assembly. Phylogenetic patterns of morphological divergence between related species suggest that these traits are key in species coexistence. Because vocal frequency and size are correlated in barbets, we therefore hypothesize that frequency differences between sympatric barbets are a by-product of their divergent morphologies. PMID:27853589

The morphological state space revisited: what do phylogenetic patterns in homoplasy tell us about the number of possible character states?

PubMed Central

Hoyal Cuthill, Jennifer F.

2015-01-01

Biological variety and major evolutionary transitions suggest that the space of possible morphologies may have varied among lineages and through time. However, most models of phylogenetic character evolution assume that the potential state space is finite. Here, I explore what the morphological state space might be like, by analysing trends in homoplasy (repeated derivation of the same character state). Analyses of ten published character matrices are compared against computer simulations with different state space models: infinite states, finite states, ordered states and an ‘inertial' model, simulating phylogenetic constraints. Of these, only the infinite states model results in evolution without homoplasy, a prediction which is not generally met by real phylogenies. Many authors have interpreted the ubiquity of homoplasy as evidence that the number of evolutionary alternatives is finite. However, homoplasy is also predicted by phylogenetic constraints on the morphological distance that can be traversed between ancestor and descendent. Phylogenetic rarefaction (sub-sampling) shows that finite and inertial state spaces do produce contrasting trends in the distribution of homoplasy. Two clades show trends characteristic of phylogenetic inertia, with decreasing homoplasy (increasing consistency index) as we sub-sample more distantly related taxa. One clade shows increasing homoplasy, suggesting exhaustion of finite states. Different clades may, therefore, show different patterns of character evolution. However, when parsimony uninformative characters are excluded (which may occur without documentation in cladistic studies), it may no longer be possible to distinguish inertial and finite state spaces. Interestingly, inertial models predict that homoplasy should be clustered among comparatively close relatives (parallel evolution), whereas finite state models do not. If morphological evolution is often inertial in nature, then homoplasy (false homology) may primarily occur between close relatives, perhaps being replaced by functional analogy at higher taxonomic scales. PMID:26640650

The evolution of floral nectaries in Disa (Orchidaceae: Disinae): recapitulation or diversifying innovation?

PubMed

Hobbhahn, Nina; Johnson, Steven D; Bytebier, Benny; Yeung, Edward C; Harder, Lawrence D

2013-11-01

The Orchidaceae have a history of recurring convergent evolution in floral function as nectar production has evolved repeatedly from an ancestral nectarless state. However, orchids exhibit considerable diversity in nectary type, position and morphology, indicating that this convergence arose from alternative adaptive solutions. Using the genus Disa, this study asks whether repeated evolution of floral nectaries involved recapitulation of the same nectary type or diversifying innovation. Epidermis morphology of closely related nectar-producing and nectarless species is also compared in order to identify histological changes that accompanied the gain or loss of nectar production. The micromorphology of nectaries and positionally equivalent tissues in nectarless species was examined with light and scanning electron microscopy. This information was subjected to phylogenetic analyses to reconstruct nectary evolution and compare characteristics of nectar-producing and nectarless species. Two nectary types evolved in Disa. Nectar exudation by modified stomata in floral spurs evolved twice, whereas exudation by a secretory epidermis evolved six times in different perianth segments. The spur epidermis of nectarless species exhibited considerable micromorphological variation, including strongly textured surfaces and non-secreting stomata in some species. Epidermis morphology of nectar-producing species did not differ consistently from that of rewardless species at the magnifications used in this study, suggesting that transitions from rewardlessness to nectar production are not necessarily accompanied by visible morphological changes but only require sub-cellular modification. Independent nectary evolution in Disa involved both repeated recapitulation of secretory epidermis, which is present in the sister genus Brownleea, and innovation of stomatal nectaries. These contrasting nectary types and positional diversity within types imply weak genetic, developmental or physiological constraints in ancestral, nectarless Disa. Such functional convergence generated by morphologically diverse solutions probably also underlies the extensive diversity of nectary types and positions in the Orchidaceae.

Predictive genomics: a cancer hallmark network framework for predicting tumor clinical phenotypes using genome sequencing data.

PubMed

Wang, Edwin; Zaman, Naif; Mcgee, Shauna; Milanese, Jean-Sébastien; Masoudi-Nejad, Ali; O'Connor-McCourt, Maureen

2015-02-01

Tumor genome sequencing leads to documenting thousands of DNA mutations and other genomic alterations. At present, these data cannot be analyzed adequately to aid in the understanding of tumorigenesis and its evolution. Moreover, we have little insight into how to use these data to predict clinical phenotypes and tumor progression to better design patient treatment. To meet these challenges, we discuss a cancer hallmark network framework for modeling genome sequencing data to predict cancer clonal evolution and associated clinical phenotypes. The framework includes: (1) cancer hallmarks that can be represented by a few molecular/signaling networks. 'Network operational signatures' which represent gene regulatory logics/strengths enable to quantify state transitions and measures of hallmark traits. Thus, sets of genomic alterations which are associated with network operational signatures could be linked to the state/measure of hallmark traits. The network operational signature transforms genotypic data (i.e., genomic alterations) to regulatory phenotypic profiles (i.e., regulatory logics/strengths), to cellular phenotypic profiles (i.e., hallmark traits) which lead to clinical phenotypic profiles (i.e., a collection of hallmark traits). Furthermore, the framework considers regulatory logics of the hallmark networks under tumor evolutionary dynamics and therefore also includes: (2) a self-promoting positive feedback loop that is dominated by a genomic instability network and a cell survival/proliferation network is the main driver of tumor clonal evolution. Surrounding tumor stroma and its host immune systems shape the evolutionary paths; (3) cell motility initiating metastasis is a byproduct of the above self-promoting loop activity during tumorigenesis; (4) an emerging hallmark network which triggers genome duplication dominates a feed-forward loop which in turn could act as a rate-limiting step for tumor formation; (5) mutations and other genomic alterations have specific patterns and tissue-specificity, which are driven by aging and other cancer-inducing agents. This framework represents the logics of complex cancer biology as a myriad of phenotypic complexities governed by a limited set of underlying organizing principles. It therefore adds to our understanding of tumor evolution and tumorigenesis, and moreover, potential usefulness of predicting tumors' evolutionary paths and clinical phenotypes. Strategies of using this framework in conjunction with genome sequencing data in an attempt to predict personalized drug targets, drug resistance, and metastasis for cancer patients, as well as cancer risks for healthy individuals are discussed. Accurate prediction of cancer clonal evolution and clinical phenotypes will have substantial impact on timely diagnosis, personalized treatment and personalized prevention of cancer. Crown Copyright © 2014. Published by Elsevier Ltd. All rights reserved.

Genetic and evolutionary analysis of the Drosophila larval neuromuscular junction

NASA Astrophysics Data System (ADS)

Campbell, Megan

Although evolution of brains and behaviors is of fundamental biological importance, we lack comprehensive understanding of the general principles governing these processes or the specific mechanisms and molecules through which the evolutionary changes are effected. Because synapses are the basic structural and functional units of nervous systems, one way to address these problems is to dissect the genetic and molecular pathways responsible for morphological evolution of a defined synapse. I have undertaken such an analysis by examining morphology of the larval neuromuscular junction (NMJ) in wild caught D. melanogaster as well as in over 20 other species of Drosophila. Whereas variation in NMJ morphology within a species is limited, I discovered a surprisingly extensive variation among different species. Compared with evolution of other morphological traits, NMJ morphology appears to be evolving very rapidly. Moreover, my data indicate that natural selection rather than genetic drift is primarily responsible for evolution of NMJ morphology. To dissect underlying molecular mechanisms that may govern NMJ growth and evolutionary divergence, I focused on a naturally occurring variant in D. melanogaster that causes NMJ overgrowth. I discovered that the variant mapped to Mob2, a gene encoding a kinase adapter protein originally described in yeast as a member of the Mitotic Exit Network (MEN). I have subsequently examined mutations in the Drosophila orthologs of all the core components of the yeast MEN and found that all of them function as part of a common pathway that acts presynaptically to negatively regulate NMJ growth. As in the regulation of yeast cytokinesis, these components of the MEN appear to act ultimately by regulating actin dynamics during the process of bouton growth and division. These studies have thus led to the discovery of an entirely new role for the MEN---regulation of synaptic growth---that is separate from its function in cell division. This work has identified a rich source of material for discovery of novel genes and mechanisms that regulate synaptic growth and development, and has also provided new insights into the mechanisms that underlie morphological evolution of nervous systems.

Cranial base evolution within the hominin clade

PubMed Central

Nevell, L; Wood, B

2008-01-01

The base of the cranium (i.e. the basioccipital, the sphenoid and the temporal bones) is of particular interest because it undergoes significant morphological change within the hominin clade, and because basicranial morphology features in several hominin species diagnoses. We use a parsimony analysis of published cranial and dental data to predict the cranial base morphology expected in the hypothetical last common ancestor of the Pan–Homo clade. We also predict the primitive condition of the cranial base for the hominin clade, and document the evolution of the cranial base within the major subclades within the hominin clade. This analysis suggests that cranial base morphology has continued to evolve in the hominin clade, both before and after the emergence of the genus Homo. PMID:18380865

Morphological basis for the evolution of acoustic diversity in oscine songbirds.

PubMed

Riede, Tobias; Goller, Franz

2014-03-22

Acoustic properties of vocalizations arise through the interplay of neural control with the morphology and biomechanics of the sound generating organ, but in songbirds it is assumed that the main driver of acoustic diversity is variation in telencephalic motor control. Here we show, however, that variation in the composition of the vibrating tissues, the labia, underlies diversity in one acoustic parameter, fundamental frequency (F0) range. Lateral asymmetry and arrangement of fibrous proteins in the labia into distinct layers is correlated with expanded F0 range of species. The composition of the vibrating tissues thus represents an important morphological foundation for the generation of a broad F0 range, indicating that morphological specialization lays the foundation for the evolution of complex acoustic repertoires.

[Morphological changes in tongue cancer after cryosurgery].

PubMed

Zhou, X D; Mao, T Q

1993-01-01

Tca 8113 (human tongue cancer cell line) cell transplanted tumors in nude mice were treated with cryosurgery for three freeze-thaw cycles. Tumor samples were obtained by biopsies pre- and post-cryosurgery for morphological study. The results showed intercellular adhesion damage, nuclear pyknosis, cell death, etc. One week after, the deep parts of the frozen samples were similar to that of the untreated ones. Our study indicates the change of biomembrance may be also important as of nuclei in cell death and may play an important role in the treatment of cancer by cryochemistry.

Morphological and niche divergence of pinyon pines.

PubMed

Ortiz-Medrano, Alejandra; Scantlebury, Daniel Patrick; Vázquez-Lobo, Alejandra; Mastretta-Yanes, Alicia; Piñero, Daniel

2016-05-01

The environmental variables that define a species ecological niche should be associated with the evolutionary patterns present in the adaptations that resulted from living in these conditions. Thus, when comparing across species, we can expect to find an association between phylogenetically independent phenotypic characters and ecological niche evolution. Few studies have evaluated how organismal phenotypes might mirror patterns of niche evolution if these phenotypes reflect adaptations. Doing so could contribute on the understanding of the origin and maintenance of phenotypic diversity observed in nature. Here, we show the pattern of niche evolution of the pinyon pine lineage (Pinus subsection Cembroides); then, we suggest morphological adaptations possibly related to niche divergence, and finally, we test for correlation between ecological niche and morphology. We demonstrate that niche divergence is the general pattern within the clade and that it is positively correlated with adaptation.

Quantitative Imaging in Cancer Evolution and Ecology

PubMed Central

Grove, Olya; Gillies, Robert J.

2013-01-01

Cancer therapy, even when highly targeted, typically fails because of the remarkable capacity of malignant cells to evolve effective adaptations. These evolutionary dynamics are both a cause and a consequence of cancer system heterogeneity at many scales, ranging from genetic properties of individual cells to large-scale imaging features. Tumors of the same organ and cell type can have remarkably diverse appearances in different patients. Furthermore, even within a single tumor, marked variations in imaging features, such as necrosis or contrast enhancement, are common. Similar spatial variations recently have been reported in genetic profiles. Radiologic heterogeneity within tumors is usually governed by variations in blood flow, whereas genetic heterogeneity is typically ascribed to random mutations. However, evolution within tumors, as in all living systems, is subject to Darwinian principles; thus, it is governed by predictable and reproducible interactions between environmental selection forces and cell phenotype (not genotype). This link between regional variations in environmental properties and cellular adaptive strategies may permit clinical imaging to be used to assess and monitor intratumoral evolution in individual patients. This approach is enabled by new methods that extract, report, and analyze quantitative, reproducible, and mineable clinical imaging data. However, most current quantitative metrics lack spatialness, expressing quantitative radiologic features as a single value for a region of interest encompassing the whole tumor. In contrast, spatially explicit image analysis recognizes that tumors are heterogeneous but not well mixed and defines regionally distinct habitats, some of which appear to harbor tumor populations that are more aggressive and less treatable than others. By identifying regional variations in key environmental selection forces and evidence of cellular adaptation, clinical imaging can enable us to define intratumoral Darwinian dynamics before and during therapy. Advances in image analysis will place clinical imaging in an increasingly central role in the development of evolution-based patient-specific cancer therapy. © RSNA, 2013 PMID:24062559

Greater than the sum of its parts: single-nucleus sequencing identifies convergent evolution of independent EGFR mutants in GBM.

PubMed

Gini, Beatrice; Mischel, Paul S

2014-08-01

Single-cell sequencing approaches are needed to characterize the genomic diversity of complex tumors, shedding light on their evolutionary paths and potentially suggesting more effective therapies. In this issue of Cancer Discovery, Francis and colleagues develop a novel integrative approach to identify distinct tumor subpopulations based on joint detection of clonal and subclonal events from bulk tumor and single-nucleus whole-genome sequencing, allowing them to infer a subclonal architecture. Surprisingly, the authors identify convergent evolution of multiple, mutually exclusive, independent EGFR gain-of-function variants in a single tumor. This study demonstrates the value of integrative single-cell genomics and highlights the biologic primacy of EGFR as an actionable target in glioblastoma. ©2014 American Association for Cancer Research.

[Imaging of odontogenic tumors of the maxilla].

PubMed

Martin-Duverneuil, N; Sahli-Amor, M; Chiras, J

2009-05-01

Odontogenic tumors of the maxilla are frequent, mainly represented by cysts of the jaw. However, this group of tumors include a large number of potentially intricate pathologies whose evolution is dominated by frequent recurrences justifying long-term follow-up. When such a lesion is discovered, evaluation of imaging features combined with an extensive knowledge of the different patterns of other lesions (particularly their potentially evolutive patterns related to growth) can often suggest the diagnosis. While definitive diagnosis frequently relies on histology, it is not rare that the patterns are so intricate that final diagnosis is based on a correlation between clinical, imaging and histological findings.

Correlated evolution of personality, morphology and performance

PubMed Central

Kern, Elizabeth M. A.; Robinson, Detric; Gass, Erika; Godwin, John; Langerhans, R. Brian

2018-01-01

Evolutionary change in one trait can elicit evolutionary changes in other traits due to genetic correlations. This constrains the independent evolution of traits and can lead to unpredicted ecological and evolutionary outcomes. Animals might frequently exhibit genetic associations among behavioural and morphological-physiological traits, because the physiological mechanisms behind animal personality can have broad multitrait effects and because many selective agents influence the evolution of multiple types of traits. However, we currently know little about genetic correlations between animal personalities and nonbehavioural traits. We tested for associations between personality, morphology and locomotor performance by comparing zebrafish (Danio rerio) collected from the wild and then selectively bred for either a proactive or reactive stress coping style (‘bold’ or ‘shy’ phenotypes). Based on adaptive hypotheses of correlational selection in the wild, we predicted that artificial selection for boldness would produce correlated evolutionary responses of larger caudal regions and higher fast-start escape performance (and the opposite for shyness). After four to seven generations, morphology and locomotor performance differed between personality lines: bold zebrafish exhibited a larger caudal region and higher fast-start performance than fish in the shy line, matching predictions. Individual-level phenotypic correlations suggested that pleiotropy or physical gene linkage likely explained the correlated response of locomotor performance, while the correlated response of body shape may have reflected linkage disequilibrium, which is breaking down each generation in the laboratory. Our results indicate that evolution of personality can result in concomitant changes in morphology and whole-organism performance, and vice versa. PMID:29398712

Testing Convergence Versus History: Convergence Dominates Phenotypic Evolution for over 150 Million Years in Frogs.

PubMed

Moen, Daniel S; Morlon, Hélène; Wiens, John J

2016-01-01

Striking evolutionary convergence can lead to similar sets of species in different locations, such as in cichlid fishes and Anolis lizards, and suggests that evolution can be repeatable and predictable across clades. Yet, most examples of convergence involve relatively small temporal and/or spatial scales. Some authors have speculated that at larger scales (e.g., across continents), differing evolutionary histories will prevent convergence. However, few studies have compared the contrasting roles of convergence and history, and none have done so at large scales. Here we develop a two-part approach to test the scale over which convergence can occur, comparing the relative importance of convergence and history in macroevolution using phylogenetic models of adaptive evolution. We apply this approach to data from morphology, ecology, and phylogeny from 167 species of anuran amphibians (frogs) from 10 local sites across the world, spanning ~160 myr of evolution. Mapping ecology on the phylogeny revealed that similar microhabitat specialists (e.g., aquatic, arboreal) have evolved repeatedly across clades and regions, producing many evolutionary replicates for testing for morphological convergence. By comparing morphological optima for clades and microhabitat types (our first test), we find that convergence associated with microhabitat use dominates frog morphological evolution, producing recurrent ecomorphs that together encompass all sampled species in each community in each region. However, our second test, which examines whether and how much species differ from their inferred optima, shows that convergence is incomplete: that is, phenotypes of most species are still somewhat distant from the estimated optimum for each microhabitat, seemingly because of insufficient time for more complete adaptation (an effect of history). Yet, these effects of history are related to past ecologies, and not clade membership. Overall, our study elucidates the dominant drivers of morphological evolution across a major vertebrate clade and shows that evolution can be repeatable at much greater temporal and spatial scales than commonly thought. It also provides an analytical framework for testing other potential examples of large-scale convergence. © The Author(s) 2015. Published by Oxford University Press, on behalf of the Society of Systematic Biologists. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

TFE3 break-apart FISH has a higher sensitivity for Xp11.2 translocation-associated renal cell carcinoma compared with TFE3 or cathepsin K immunohistochemical staining alone: expanding the morphologic spectrum.

PubMed

Rao, Qiu; Williamson, Sean R; Zhang, Shaobo; Eble, John N; Grignon, David J; Wang, Mingsheng; Zhou, Xiao-Jun; Huang, Wenbin; Tan, Puay-Hoon; Maclennan, Gregory T; Cheng, Liang

2013-06-01

Renal cell carcinoma (RCC) associated with Xp11.2 translocation is uncommon, characterized by several different translocations involving the TFE3 gene. We assessed the utility of break-apart fluorescence in situ hybridization (FISH) in establishing the diagnosis for suspected or unclassified cases with negative or equivocal TFE3 immunostaining by analyzing 24 renal cancers with break-apart TFE3 FISH and comparing the molecular findings with the results of TFE3 and cathepsin K immunostaining in the same tumors. Ten tumors were originally diagnosed as Xp11.2 RCC on the basis of positive TFE3 immunostaining, and 14 were originally considered unclassified RCCs with negative or equivocal TFE3 staining, but with a range of features suspicious for Xp11.2 RCC. Seventeen cases showed TFE3 rearrangement associated with Xp11.2 translocation by FISH, including all 13 tumors with moderate or strong TFE3 (n=10) or cathepsin K (n=7) immunoreactivity. FISH-positive cases showed negative or equivocal immunoreactivity for TFE3 or cathepsin K in 7 and 10 tumors, respectively (both=3). None had positive immunohistochemistry but negative FISH. Morphologic features were typical for Xp11.2 RCC in 10/17 tumors. Unusual features included 1 melanotic Xp11.2 renal cancer, 1 tumor with mixed features of Xp11.2 RCC and clear cell RCC, and other tumors mimicking clear cell RCC, multilocular cystic RCC, or high-grade urothelial carcinoma. Morphology mimicking high-grade urothelial carcinoma has not been previously reported in these tumors. Psammoma bodies, hyalinized stroma, and intracellular pigment were preferentially identified in FISH-positive cases compared with FISH-negative cases. Our results support the clinical application of a TFE3 break-apart FISH assay for diagnosis and confirmation of Xp11.2 RCC and further expand the histopathologic spectrum of these neoplasms to include tumors with unusual features. A renal tumor with pathologic or clinical features highly suggestive of translocation-associated RCC but exhibiting negative or equivocal TFE3 immunostaining should be evaluated by TFE3 FISH assay to fully assess this possibility.

Phylogeny-based comparative methods question the adaptive nature of sporophytic specializations in mosses.

PubMed

Huttunen, Sanna; Olsson, Sanna; Buchbender, Volker; Enroth, Johannes; Hedenäs, Lars; Quandt, Dietmar

2012-01-01

Adaptive evolution has often been proposed to explain correlations between habitats and certain phenotypes. In mosses, a high frequency of species with specialized sporophytic traits in exposed or epiphytic habitats was, already 100 years ago, suggested as due to adaptation. We tested this hypothesis by contrasting phylogenetic and morphological data from two moss families, Neckeraceae and Lembophyllaceae, both of which show parallel shifts to a specialized morphology and to exposed epiphytic or epilithic habitats. Phylogeny-based tests for correlated evolution revealed that evolution of four sporophytic traits is correlated with a habitat shift. For three of them, evolutionary rates of dual character-state changes suggest that habitat shifts appear prior to changes in morphology. This suggests that they could have evolved as adaptations to new habitats. Regarding the fourth correlated trait the specialized morphology had already evolved before the habitat shift. In addition, several other specialized "epiphytic" traits show no correlation with a habitat shift. Besides adaptive diversification, other processes thus also affect the match between phenotype and environment. Several potential factors such as complex genetic and developmental pathways yielding the same phenotypes, differences in strength of selection, or constraints in phenotypic evolution may lead to an inability of phylogeny-based comparative methods to detect potential adaptations.

Adaptation and Convergent Evolution within the Jamesonia-Eriosorus Complex in High-Elevation Biodiverse Andean Hotspots

PubMed Central

Sánchez-Baracaldo, Patricia; Thomas, Gavin H.

2014-01-01

The recent uplift of the tropical Andes (since the late Pliocene or early Pleistocene) provided extensive ecological opportunity for evolutionary radiations. We test for phylogenetic and morphological evidence of adaptive radiation and convergent evolution to novel habitats (exposed, high-altitude páramo habitats) in the Andean fern genera Jamesonia and Eriosorus. We construct time-calibrated phylogenies for the Jamesonia-Eriosorus clade. We then use recent phylogenetic comparative methods to test for evolutionary transitions among habitats, associations between habitat and leaf morphology, and ecologically driven variation in the rate of morphological evolution. Páramo species (Jamesonia) display morphological adaptations consistent with convergent evolution in response to the demands of a highly exposed environment but these adaptations are associated with microhabitat use rather than the páramo per se. Species that are associated with exposed microhabitats (including Jamesonia and Eriorsorus) are characterized by many but short pinnae per frond whereas species occupying sheltered microhabitats (primarily Eriosorus) have few but long pinnae per frond. Pinnae length declines more rapidly with altitude in sheltered species. Rates of speciation are significantly higher among páramo than non-páramo lineages supporting the hypothesis of adaptation and divergence in the unique Páramo biodiversity hotspot. PMID:25340770

Adaptation and convergent evolution within the Jamesonia-Eriosorus complex in high-elevation biodiverse Andean hotspots.

PubMed

Sánchez-Baracaldo, Patricia; Thomas, Gavin H

2014-01-01

The recent uplift of the tropical Andes (since the late Pliocene or early Pleistocene) provided extensive ecological opportunity for evolutionary radiations. We test for phylogenetic and morphological evidence of adaptive radiation and convergent evolution to novel habitats (exposed, high-altitude páramo habitats) in the Andean fern genera Jamesonia and Eriosorus. We construct time-calibrated phylogenies for the Jamesonia-Eriosorus clade. We then use recent phylogenetic comparative methods to test for evolutionary transitions among habitats, associations between habitat and leaf morphology, and ecologically driven variation in the rate of morphological evolution. Páramo species (Jamesonia) display morphological adaptations consistent with convergent evolution in response to the demands of a highly exposed environment but these adaptations are associated with microhabitat use rather than the páramo per se. Species that are associated with exposed microhabitats (including Jamesonia and Eriorsorus) are characterized by many but short pinnae per frond whereas species occupying sheltered microhabitats (primarily Eriosorus) have few but long pinnae per frond. Pinnae length declines more rapidly with altitude in sheltered species. Rates of speciation are significantly higher among páramo than non-páramo lineages supporting the hypothesis of adaptation and divergence in the unique Páramo biodiversity hotspot.

Computational Examination of Orientation-Dependent Morphological Evolution during the Electrodeposition and Electrodissolution of Magnesium

DOE PAGES

DeWitt, S.; Hahn, N.; Zavadil, K.; ...

2015-12-30

Here a new model of electrodeposition and electrodissolution is developed and applied to the evolution of Mg deposits during anode cycling. The model captures Butler-Volmer kinetics, facet evolution, the spatially varying potential in the electrolyte, and the time-dependent electrolyte concentration. The model utilizes a diffuse interface approach, employing the phase field and smoothed boundary methods. Scanning electron microscope (SEM) images of magnesium deposited on a gold substrate show the formation of faceted deposits, often in the form of hexagonal prisms. Orientation-dependent reaction rate coefficients were parameterized using the experimental SEM images. Three-dimensional simulations of the growth of magnesium deposits yieldmore » deposit morphologies consistent with the experimental results. The simulations predict that the deposits become narrower and taller as the current density increases due to the depletion of the electrolyte concentration near the sides of the deposits. Increasing the distance between the deposits leads to increased depletion of the electrolyte surrounding the deposit. Two models relating the orientation-dependence of the deposition and dissolution reactions are presented. Finally, the morphology of the Mg deposit after one deposition-dissolution cycle is significantly different between the two orientation-dependence models, providing testable predictions that suggest the underlying physical mechanisms governing morphology evolution during deposition and dissolution.« less

Synchrotron radiation microimaging in rabbit models of cancer for preclinical testing

NASA Astrophysics Data System (ADS)

Umetani, Keiji; Uesugi, Kentaro; Kobatake, Makito; Yamamoto, Akira; Yamashita, Takenori; Imai, Shigeki

2009-10-01

Preclinical laboratory animal imaging modalities such as microangiography and micro-computed tomography (micro-CT) have been developed at the SPring-8 BL20B2 bending magnet beamline. The objective of this paper is to demonstrate the usefulness of microangiography systems for physiological examinations of live animals and micro-CT systems for postmortem morphological examinations. Synchrotron radiation microangiography and micro-CT with contrast agents present the main advantageous capability of depicting the anatomy of small blood vessels with tens of micrometers' diameter. This paper reports two imaging instrument types and their respective applications to preclinical imaging of tumor angiogenic blood vessels in tumor-bearing rabbits, where tumor angiogenesis is characterized morphologically by an increased number of blood vessels. A microangiography system with spatial resolution around 10 μm has been used for therapeutically evaluating angiogenic vessels in a rabbit model of cancer for evaluating embolization materials in transcatheter arterial embolization and for radiation therapy. After an iodine contrast agent was injected into an artery, in vivo imaging was carried out using a high-resolution real-time detector incorporating an X-ray direct-conversion-type SATICON pickup tube. On the other hand, a micro-CT system capably performed three-dimensional visualization of tumor angiogenic blood vessels using tumor-transplanted rabbit specimens with a barium sulfate contrast agent injected into the blood vessels. For specimen imaging, a large-field high-resolution micro-CT system based on a 10-megapixel CCD camera was developed to study tumor-associated alterations in angioarchitecture. Evidence of increased vascularity by tumor angiogenesis and decreased vascularity by tumor treatments was achieved by physiological evaluation of angiogenic small blood vessels in microangiographic imaging and by morphological assessment in micro-CT imaging. These results demonstrate the accuracy and usefulness of microangiography and micro-CT systems for quantitative examination of animals' angioarchitecture, respectively, during live and postmortem examinations.

MUC4 is a highly sensitive and specific marker for low-grade fibromyxoid sarcoma.

PubMed

Doyle, Leona A; Möller, Emely; Dal Cin, Paola; Fletcher, Christopher D M; Mertens, Fredrik; Hornick, Jason L

2011-05-01

Low-grade fibromyxoid sarcoma (LGFMS) is a distinctive fibroblastic neoplasm that is characterized by alternating collagenous and myxoid areas, deceptively bland spindle cell morphology, a whorling architecture, and a t(7;16) translocation involving FUS and CREB3L2. Owing to variable morphology and a lack of discriminatory markers, LGFMS can be difficult to distinguish from benign mesenchymal tumors and other low-grade sarcomas. Gene expression profiling has identified differential upregulation of the mucin 4 (MUC4) gene in LGFMS compared with histologically similar tumors. MUC4 is a transmembrane glycoprotein that functions in cell growth signaling pathways; aberrant MUC4 expression has been reported in various carcinomas. We investigated MUC4 protein expression by immunohistochemistry in LGFMS and in other soft tissue tumors to determine the potential diagnostic use of this novel marker. Whole-tissue sections of 309 tumors were evaluated: 49 LGFMSs (all with FUS gene rearrangement confirmed by fluorescence in situ hybridization), 40 soft tissue perineuriomas, 40 myxofibrosarcomas, 20 cellular myxomas, 20 solitary fibrous tumors, 20 low-grade malignant peripheral nerve sheath tumors, 20 cases of desmoid fibromatosis, 20 neurofibromas, 20 schwannomas, 20 monophasic synovial sarcomas, 20 cases of dermatofibrosarcoma protuberans, 10 myxoid liposarcomas, and 10 extraskeletal myxoid chondrosarcomas. The LGFMS cases included 7 with marked hypercellularity, 4 with prominent hemangiopericytoma-like vessels, 3 with giant collagen rosettes, 3 with epithelioid morphology, 2 with focal nuclear pleomorphism, and 2 with areas of sclerosing epithelioid fibrosarcoma. All 49 LGFMS cases (100%) showed cytoplasmic staining for MUC4, which was usually diffuse and intense. All the other tumor types were negative for MUC4, apart from 6 (30%) monophasic synovial sarcomas. In conclusion, MUC4 is a highly sensitive and quite specific immunohistochemical marker for LGFMS, and can be helpful to distinguish this tumor type from histologic mimics.

Morphology, development, and evolution of fetal membranes and placentation in squamate reptiles.

PubMed

Blackburn, Daniel G; Flemming, Alexander F

2009-09-15

Current studies on fetal membranes of reptiles are providing insight into three major historical transformations: evolution of the amniote egg, evolution of viviparity, and evolution of placentotrophy. Squamates (lizards and snakes) are ideal for such studies because their fetal membranes sustain embryos in oviparous species and contribute to placentas in viviparous species. Ultrastructure of the fetal membranes in oviparous corn snakes (Pituophis guttatus) shows that the chorioallantois is specialized for gas exchange and the omphalopleure, for water absorption. Transmission and scanning electron microscopic studies of viviparous thamnophine snakes (Thamnophis, Storeria) have revealed morphological specializations for gas exchange and absorption in the intra-uterine environment that represent modifications of features found in oviparous species. Thus, fetal membranes in oviparous species show morphological differentiation for distinct functions that have been recruited and enhanced under viviparous conditions. The ultimate in specialization of fetal membranes is found in viviparous skinks of South America (Mabuya) and Africa (Trachylepis, Eumecia), in which placentotrophy accounts for nearly all of the nutrients for development. Ongoing research on these lizards has revealed morphological specializations of the chorioallantoic placenta through which nutrient transfer is accomplished. In addition, African Trachylepis show an invasive form of implantation, in which uterine epithelium is replaced by invading chorionic cells. Ongoing analysis of these lizards shows how integration of multiple lines of evidence can provide insight into the evolution of developmental and reproductive specializations once thought to be confined to eutherian mammals.

Galaxy evolution in clusters since z=1

NASA Astrophysics Data System (ADS)

Aragón-Salamanca, A.

2011-11-01

It is now 30 years since Alan Dressler published his seminal paper onthe morphology-density relation. Although there is still much to learnon the effect of the environment on galaxy evolution, extensive progress has been made since then both observationally and theoretically.Galaxy clusters provide some of the most extreme environments in which galaxies evolve, making them excellent laboratories to study the age old question of "nature'' vs. "nurture'' in galaxy evolution. Here I review some of the key observational results obtained during the last decade on the evolution of the morphology, structure, dynamics, star-formation history and stellar populations of cluster galaxies since the time when the universe was half its present age.Many of the results presented here have been obtainedwithin the ESO Distant Cluster Survey (EDisCS) and Space Telescope A901/02 Galaxy Evolution Survey (STAGES) collaborations.

[Clinicopathological features of uterine neoplasms with perivascular epithelioid cell differentiation].

PubMed

Lu, Hai-zhen; Zhang, Hong-tu; Liu, Xiu-yun; Xue, Xin-hua; Xie, Yong-qiang; Liu, Shang-mei; Su, Qin

2009-03-01

To study the neoplasm with perivascular epithelioid cell differentiation (PEComa) with respect to their morphologic, immunohistochemical and clinical phenotypes. Three PEComas were included in this study, one located at the left uterine horn, and two presented as a mass in the uterine corpus. The tumors were examined by histopathology and immunohistochemistry. The lesions were composed of spindle, blunt epithelioid cells, with foci of, or scattered, cells showing adipose differentiation in two cases. The myomelanocytic differentiation was demonstrated, proving the diagnosis as PEComa. Mild nuclear atypia and focal necrosis was observed in one lesion, and the rest two showed malignant morphologic phenotypes including moderate nuclear atypia and coagulative necrosis. The mitotic and Ki67-labelling indices ranged from 0.5/10 HPF to 14/10 HPF and 0.6% to 7.0%, respectively. All of the three patients remain alive. Malignant nature of the two lesions with worrisome morphology was confirmed by occurrence of metastases after hysterectomy. PEComa is a rare tumor, occurring preferentially in the uterus. It is regarded as a tumor with uncertain malignant potential, but a minority of them shows malignant clinical behaviors. Some pathologic parameters including large tumor size, sheet-like necrosis, marked nuclear atypia, elevated mitotic index (> or = 10/10 HPF), aberrant mitotic figure and vascular invasion may help to establish a diagnosis of malignant PEComa.

Biomorphodynamics: Physical-biological feedbacks that shape landscapes

USGS Publications Warehouse

Murray, A.B.; Knaapen, M.A.F.; Tal, M.; Kirwan, M.L.

2008-01-01

Plants and animals affect morphological evolution in many environments. The term "ecogeomorphology" describes studies that address such effects. In this opinion article we use the term "biomorphodynamics" to characterize a subset of ecogeomorphologic studies: those that investigate not only the effects of organisms on physical processes and morphology but also how the biological processes depend on morphology and physical forcing. The two-way coupling precipitates feedbacks, leading to interesting modes of behavior, much like the coupling between flow/sediment transport and morphology leads to rich morphodynamic behaviors. Select examples illustrate how even the basic aspects of some systems cannot be understood without considering biomorphodynamic coupling. Prominent examples include the dynamic interactions between vegetation and flow/sediment transport that can determine river channel patterns and the multifaceted biomorphodynamic feedbacks shaping tidal marshes and channel networks. These examples suggest that the effects of morphology and physical processes on biology tend to operate over the timescale of the evolution of the morphological pattern. Thus, in field studies, which represent a snapshot in the pattern evolution, these effects are often not as obvious as the effects of biology on physical processes. However, numerical modeling indicates that the influences on biology from physical processes can play a key role in shaping landscapes and that even local and temporary vegetation disturbances can steer large-scale, long-term landscape evolution. The prevalence of biomorphodynamic research is burgeoning in recent years, driven by societal need and a confluence of complex systems-inspired modeling approaches in ecology and geomorphology. To make fundamental progress in understanding the dynamics of many landscapes, our community needs to increasingly learn to look for two-way, biomorphodynamic feedbacks and to collect new types of data to support the modeling of such emergent interactions. Copyright 2008 by the American Geophysical Union.

Effect of polyvinylpyrrolidone on mesoporous silica morphology and esterification of lauric acid with 1-butanol catalyzed by immobilized enzyme

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhang, Jinyu; Zhou, Guowei, E-mail: guoweizhou@hotmail.com; Jiang, Bin

2014-05-01

Mesoporous silica materials with a range of morphology evolution, i.e., from curved rod-shaped mesoporous silica to straight rod-shaped mesoporous silica, were successfully prepared using polyvinylpyrrolidone (PVP) and triblock copolymer as dual template. The effects of PVP molecular weight and concentration on mesoporous silica structure parameters were studied. Results showed that surface area and pore volume continuously decreased with increased PVP molecular weight. Mesoporous silica prepared with PVP K30 also possessed larger pore diameter, interplanar spacing (d{sub 100}), and cell parameter (a{sub 0}) than that prepared with PVP K15 and PVP K90. In addition, with increased PVP concentration, d{sub 100} andmore » a{sub 0} continuously decreased. The mechanism of morphology evolution caused by the change in PVP concentration was investigated. The conversion rate of lauric acid with 1-butanol catalyzed by immobilized Porcine pancreatic lipase (PPL) was also evaluated. Results showed that PPL immobilized on amino-functionalized straight rod-shaped mesoporous silica maintained 50% of its esterification conversion rate even after five cycles of use with a maximum conversion rate was about 90.15%. - Graphical abstract: Curved rod-shaped mesoporous silica can be obtained at low and the highest PVP concentration, while straight rod-shaped mesoporous silica can be obtained at higher PVP concentration. - Highlights: • Mesoporous silica with morphology evolution from CRMS to SRMS were prepared. • Effects of PVP molecular weight and concentration on silica morphology were studied. • A possible mechanism for the formation of morphology evolution SiO{sub 2} was proposed. • Esterification of lauric acid with 1-butanol catalyzed by immobilized PPL.« less

Bryophyte-Feeders in a Basal Brachyceran Lineage (Diptera: Rhagionidae: Spaniinae): Adult Oviposition Behavior and Changes in the Larval Mouthpart Morphology Accompanied with the Diet Shifts

PubMed Central

Kato, Makoto

2016-01-01

Dipteran larval morphology exhibits overwhelming variety, affected by their diverse feeding habits and habitat use. In particular, larval mouthpart morphology is associated with feeding behavior, providing key taxonomic traits. Despite most larval Brachycera being carnivorous, a basal brachyceran family, Rhagionidae, contains bryophyte-feeding taxa with multiple feeding habits. To elucidate the life history, biology, and morphological evolution of the bryophyte-feeding rhagionids, the larval feeding behavior and morphology, and the adult oviposition behavior of four species belonging to three genera of Spaniinae (Spania Meigen, Litoleptis Chillcott and Ptiolina Zetterstedt) are described. Moreover, changes of the larval morphology associated with the evolution of bryophyte-feeding are traced by molecular phylogenetic analyses. Spania and Litoleptis (thallus-miners of thallose liverworts) share a toothed form of apical mandibular sclerite with an orifice on its dorsal surface, which contrasts to those of the other members of Rhagionidae possessing a blade-like mandibular hook with an adoral groove; whereas, Ptiolina (stem borer of mosses) exhibits a weak groove on the adoral surface of mandible and highly sclerotized maxilla with toothed projections. Based on the larval feeding behavior of the thallus-miners, it is inferred that the toothed mandibles with the dorsal orifice facilitate scraping plant tissue and then imbibing it with a great deal of the sap. A phylogeny indicated that the bryophyte-feeding genera formed a clade with Spaniopsis and was sister to Symphoromyia, which presumably are detritivores. This study indicates that the loss or reduction of adoral mandibular groove and mandibular brush is coincident with the evolution of bryophyte-feeding, and it is subsequently followed by the occurrence of dorsal mandibular orifice and the loss of creeping welts accompanying the evolution of thallus-mining. PMID:27812169

Size and habit evolution of PETN crystals - a lattice Monte Carlo study

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zepeda-Ruiz, L A; Maiti, A; Gee, R

2006-02-28

Starting from an accurate inter-atomic potential we develop a simple scheme of generating an ''on-lattice'' molecular potential of short range, which is then incorporated into a lattice Monte Carlo code for simulating size and shape evolution of nanocrystallites. As a specific example, we test such a procedure on the morphological evolution of a molecular crystal of interest to us, e.g., Pentaerythritol Tetranitrate, or PETN, and obtain realistic facetted structures in excellent agreement with experimental morphologies. We investigate several interesting effects including, the evolution of the initial shape of a ''seed'' to an equilibrium configuration, and the variation of growth morphologymore » as a function of the rate of particle addition relative to diffusion.« less

Impact of MLH1 expression on tumor evolution after curative surgical tumor resection in a murine orthotopic xenograft model for human MSI colon cancer.

PubMed

Meunier, Katy; Ferron, Marianne; Calmel, Claire; Fléjou, Jean-François; Pocard, Marc; Praz, Françoise

2017-09-01

Colorectal cancers (CRCs) displaying microsatellite instability (MSI) most often result from MLH1 deficiency. The aim of this study was to assess the impact of MLH1 expression per se on tumor evolution after curative surgical resection using a xenograft tumor model. Transplantable tumors established with the human MLH1-deficient HCT116 cell line and its MLH1-complemented isogenic clone, mlh1-3, were implanted onto the caecum of NOD/SCID mice. Curative surgical resection was performed at day 10 in half of the animals. The HCT116-derived tumors were more voluminous compared to the mlh1-3 ones (P = .001). Lymph node metastases and peritoneal carcinomatosis occurred significantly more often in the group of mice grafted with HCT116 (P = .007 and P = .035, respectively). Mlh1-3-grafted mice did not develop peritoneal carcinomatosis or liver metastasis. After surgical resection, lymph node metastases only arose in the group of mice implanted with HCT116 and the rate of cure was significantly lower than in the mlh1-3 group (P = .047). The murine orthotopic xenograft model based on isogenic human CRC cell lines allowed us to reveal the impact of MLH1 expression on tumor evolution in mice who underwent curative surgical resection and in mice whose tumor was left in situ. Our data indicate that the behavior of MLH1-deficient CRC is not only governed by mutations arising in genes harboring microsatellite repeated sequences but also from their defect in MLH1 as such. © 2017 Wiley Periodicals, Inc.

VDJ-Seq: Deep Sequencing Analysis of Rearranged Immunoglobulin Heavy Chain Gene to Reveal Clonal Evolution Patterns of B Cell Lymphoma.

PubMed

Jiang, Yanwen; Nie, Kui; Redmond, David; Melnick, Ari M; Tam, Wayne; Elemento, Olivier

2015-12-28

Understanding tumor clonality is critical to understanding the mechanisms involved in tumorigenesis and disease progression. In addition, understanding the clonal composition changes that occur within a tumor in response to certain micro-environment or treatments may lead to the design of more sophisticated and effective approaches to eradicate tumor cells. However, tracking tumor clonal sub-populations has been challenging due to the lack of distinguishable markers. To address this problem, a VDJ-seq protocol was created to trace the clonal evolution patterns of diffuse large B cell lymphoma (DLBCL) relapse by exploiting VDJ recombination and somatic hypermutation (SHM), two unique features of B cell lymphomas. In this protocol, Next-Generation sequencing (NGS) libraries with indexing potential were constructed from amplified rearranged immunoglobulin heavy chain (IgH) VDJ region from pairs of primary diagnosis and relapse DLBCL samples. On average more than half million VDJ sequences per sample were obtained after sequencing, which contain both VDJ rearrangement and SHM information. In addition, customized bioinformatics pipelines were developed to fully utilize sequence information for the characterization of IgH-VDJ repertoire within these samples. Furthermore, the pipeline allows the reconstruction and comparison of the clonal architecture of individual tumors, which enables the examination of the clonal heterogeneity within the diagnosis tumors and deduction of clonal evolution patterns between diagnosis and relapse tumor pairs. When applying this analysis to several diagnosis-relapse pairs, we uncovered key evidence that multiple distinctive tumor evolutionary patterns could lead to DLBCL relapse. Additionally, this approach can be expanded into other clinical aspects, such as identification of minimal residual disease, monitoring relapse progress and treatment response, and investigation of immune repertoires in non-lymphoma contexts.

Morphological and functional diversity in therizinosaur claws and the implications for theropod claw evolution.

PubMed

Lautenschlager, Stephan

2014-06-22

Therizinosaurs are a group of herbivorous theropod dinosaurs from the Cretaceous of North America and Asia, best known for their iconically large and elongate manual claws. However, among Therizinosauria, ungual morphology is highly variable, reflecting a general trend found in derived theropod dinosaurs (Maniraptoriformes). A combined approach of shape analysis to characterize changes in manual ungual morphology across theropods and finite-element analysis to assess the biomechanical properties of different ungual shapes in therizinosaurs reveals a functional diversity related to ungual morphology. While some therizinosaur taxa used their claws in a generalist fashion, other taxa were functionally adapted to use the claws as grasping hooks during foraging. Results further indicate that maniraptoriform dinosaurs deviated from the plesiomorphic theropod ungual morphology resulting in increased functional diversity. This trend parallels modifications of the cranial skeleton in derived theropods in response to dietary adaptation, suggesting that dietary diversification was a major driver for morphological and functional disparity in theropod evolution.

Pericytic tumors of the kidney-a clinicopathologic analysis of 17 cases.

PubMed

Sirohi, Deepika; Smith, Steven C; Epstein, Jonathan I; Balzer, Bonnie L; Simko, Jeffry P; Balitzer, Dana; Benhamida, Jamal; Kryvenko, Oleksandr N; Gupta, Nilesh S; Paluru, Swetha; da Cunha, Isabela Werneck; Leal, Daniel N; Williamson, Sean R; de Peralta-Venturina, Mariza; Amin, Mahul B

2017-06-01

The pericytic (perivascular myoid cell) family of tumors is a distinctive group of mesenchymal neoplasms encountered in superficial sites and only rarely seen in viscera. The pericytic family subtends a spectrum of lesions, namely, glomus tumors and variants; myopericytoma, including myofibroma; and angioleiomyoma. In light of the contemporary classification of pericytic lesions, we identified and reviewed 17 cases of renal pericytic tumors from the files of 6 referral centers. These tumors presented over an age range of 17 to 76 years (mean 46.7, median 53), with essentially equal male-female ratio. History of hypertension (available in 11 patients) was noted in 7 (64%), which persisted even after surgical resection, including in 2 younger patients (17 and 30 years). The tumors (1.7-11.0 cm) included glomus tumors (n=11); glomangiomyoma (n=1); glomus tumor with atypical features (n=1); and angioleiomyoma (n=1), as well as tumors showing features overlapping pericytic tumor subtypes (n=3). The histomorphology observed in these renal examples closely resembled that of their soft tissue counterparts, a subset with symplastic changes and atypical features, and pericytic immunophenotype. Despite large size and deep site, no progression was identified during a median of 7 months follow-up (1-62 months). In context of prior reported experience, our series identifies a wide morphologic spectrum, including lesions presenting composite morphologies. Taken with the experience of others, our series further corroborates that malignant behavior is rare, and that criteria associated with aggression among soft tissue pericytic tumors may not be predictive for those in the kidney. Copyright © 2017 Elsevier Inc. All rights reserved.

Homoplasious colony morphology and mito-nuclear phylogenetic discordance among Eastern Pacific octocorals.

PubMed

Ament-Velásquez, Sandra L; Breedy, Odalisca; Cortés, Jorge; Guzman, Hector M; Wörheide, Gert; Vargas, Sergio

2016-05-01

Octocorals are a diverse and ecologically important group of cnidarians. However, the phylogenetic relationships of many octocoral groups are not well understood and are based mostly on mitochondrial sequence data. In addition, the discovery and description of new gorgonian species displaying unusual or intermediate morphologies and uncertain phylogenetic affinities further complicates the study of octocoral systematics and raises questions about the role played by processes such as plasticity, crypsis, and convergence in the evolution of this group of organisms. Here, we use nuclear (i.e. 28S rDNA) and mitochondrial (mtMutS) markers and a sample of Eastern Pacific gorgonians thought to be remarkable from a morphological point of view to shed light on the morphological diversification among these organisms. Our study reveals the loss of the anastomosed colony morphology in two unrelated lineages of the seafan genus Pacifigorgia and offers strong evidence for the independent evolution of a whip-like morphology in two lineages of Eastern Pacific Leptogorgia. Additionally, our data revealed one instance of mito-nuclear discordance in the genera Leptogorgia and Eugorgia, which may be the results of incomplete lineage sorting or ancient hybridization-introgression events. Our study stresses the importance of comprehensive taxonomic sampling and the use of independent sources of evidence to address the phylogenetic relationships and clarifying the evolution of octocorals. Copyright © 2016 Elsevier Inc. All rights reserved.

Mechanistic Selection and Growth of Twinned Bicrystalline Primary Si in Near Eutectic Al-Si Alloys

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jung, Choonho

2006-01-01

Morphological evolution and selection of angular primary silicon is investigated in near-eutectic Al-Si alloys. Angular silicon arrays are grown directionally in a Bridgman furnace at velocities in the regime of 10 -3 m/sec and with a temperature gradient of 7.5 x 10 3 K/m. Under these conditions, the primary Si phase grows as an array of twinned bicrystalline dendrites, where the twinning gives rise to a characteristic 8-pointed star-shaped primary morphology. While this primary Si remains largely faceted at the growth front, a complex structure of coherent symmetric twin boundaries enables various adjustment mechanisms which operate to optimize the characteristicmore » spacings within the primary array. In the work presented here, this primary silicon growth morphology is examined in detail. In particular, this thesis describes the investigation of: (1) morphological selection of the twinned bicrystalline primary starshape morphology; (2) primary array behavior, including the lateral propagation of the starshape grains and the associated evolution of a strong <100> texture; (3) the detailed structure of the 8-pointed star-shaped primary morphology, including the twin boundary configuration within the central core; (4) the mechanisms of lateral propagation and spacing adjustment during array evolution; and (5) the thermosolutal conditions (i.e. operating state) at the primary growth front, including composition and phase fraction in the vicinity of the primary tip.« less

Malignant perivascular epithelioid cell tumor (PEComa) of cervix with TFE3 gene rearrangement: a case report.

PubMed

Liu, Feifei; Zhang, Renya; Wang, Zi-Yu; Xia, Qiuyuan; Shen, Qin; Shi, Shanshan; Tu, Pin; Shi, Qunli; Zhou, Xiaojun; Rao, Qiu

2014-01-01

In this study, we reported the first PEComa arising within the cervix with TFE3 gene rearrangement and aggressive biological behavior. Morphologically, the tumor showed infiltrative growth into the surrounding parenchyma. The majority of tumor cells were arrayed in sheets, alveolar structures, or nests separated by delicate fibrovascular septa. There was marked intratumoral hemorrhage, necrosis, and stromal calcifications. The tumor cells had abundant clear cytoplasm, focally containing finely granular dark brown pigment, morphologically considered to be melanin. Immunohistochemically, the tumor cells demonstrated moderately (2+) or strongly (3+) positive staining for TFE3, HMB45, and Melan A but negative for CKpan, SMA, S100, PAX8, and PAX2. The presence of Ki-67 protein demonstrated a moderate proliferation rate, with a few Ki-67-positive nuclei. Using a recently developed TFE3 split FISH assay, the presence of TFE3 rearrangement was demonstrated. All these clinicopathologic features are suggestive of TFE3-rearranged PEComas of the cervix. Our results both expand the known characteristics of primary cervix PEComas and add to the data regarding TFE3 rearrangement-associated PEComas.

Visualizing Clonal Evolution in Cancer.

PubMed

Krzywinski, Martin

2016-06-02

Rapid and inexpensive single-cell sequencing is driving new visualizations of cancer instability and evolution. Krzywinski discusses how to present clone evolution plots in order to visualize temporal, phylogenetic, and spatial aspects of a tumor in a single static image. Copyright © 2016 Elsevier Inc. All rights reserved.

Graphene Functionalized with Arginine Decreases the Development of Glioblastoma Multiforme Tumor in a Gene-Dependent Manner

PubMed Central

Sawosz, Ewa; Jaworski, Sławomir; Kutwin, Marta; Vadalasetty, Krishna Prasad; Grodzik, Marta; Wierzbicki, Mateusz; Kurantowicz, Natalia; Strojny, Barbara; Hotowy, Anna; Lipińska, Ludwika; Jagiełło, Joanna; Chwalibog, André

2015-01-01

Our previous studies revealed that graphene had anticancer properties in experiments in vitro with glioblastoma multiforme (GBM) cells and in tumors cultured in vivo. We hypothesized that the addition of arginine or proline to graphene solutions might counteract graphene agglomeration and increase the activity of graphene. Experiments were performed in vitro with GBM U87 cells and in vivo with GBM tumors cultured on chicken embryo chorioallantoic membranes. The measurements included cell morphology, mortality, viability, tumor morphology, histology, and gene expression. The cells and tumors were treated with reduced graphene oxide (rGO) and rGO functionalized with arginine (rGO + Arg) or proline (rGO + Pro). The results confirmed the anticancer effect of graphene on GBM cells and tumor tissue. After functionalization with amino acids, nanoparticles were distributed more specifically, and the flakes of graphene were less agglomerated. The molecule of rGO + Arg did not increase the expression of TP53 in comparison to rGO, but did not increase the expression of MDM2 or the MDM2/TP53 ratio in the tumor, suggesting that arginine may block MDM2 expression. The expression of NQO1, known to be a strong protector of p53 protein in tumor tissue, was greatly increased. The results indicate that the complex of rGO + Arg has potential in GBM therapy. PMID:26512645

Angiofibroma of soft tissue: clinicopathologic study of 2 cases of a recently characterized benign soft tissue tumor

PubMed Central

Zhao, Ming; Sun, Ke; Li, Changshui; Zheng, Jiangjiang; Yu, Jingjing; Jin, Jie; Xia, Wenping

2013-01-01

Angiofibroma of soft tissue is a very recently characterized, histologically distinctive benign mesenchymal neoplasm of unknown cellular origin composed of 2 principal components, the spindle cell component and very prominent stromal vasculatures. It usually occurs in middle-aged adults, with a female predominance. Herein, we describe the clinical and pathologic details of 2 other examples of this benign tumor. Both patients were middle-aged male and presented with a slow-growing, painless mass located in the deep-seated soft tissue of thigh and left posterior neck region, respectively. Grossly, both tumors were well-demarcated, partial encapsulated of a grayish-white color with firm consistence. Histologically, one case showed morphology otherwise identical to those have been described before, whereas the other case showed in areas being more cellular than most examples of this subtype tumor had, with the lesional cells frequently exhibiting short fascicular, vaguely storiform and occasionally swirling arrangements, which posed a challenging differential diagnosis. Immunostains performed on both tumors did not confirm any specific cell differentiation with lesional cells only reactive for vimentin and focally desmin and negative for all the other markers tested. This report serves to broaden the morphologic spectrum of angiofibroma of soft tumor. Awareness of this tumor is important to prevent misdiagnosis as other more aggressive soft tissue tumor. PMID:24133600

Benign and Malignant Brenner Tumors Show an Absence of TERT Promoter Mutations That Are Commonly Present in Urothelial Carcinoma.

PubMed

Khani, Francesca; Diolombi, Mairo L; Khattar, Pallavi; Huang, Weihua; Fallon, John T; Epstein, Jonathan I; Zhong, Minghao

2016-09-01

Brenner tumors are uncommon ovarian neoplasms, which have morphologic and immunophenotypical features of transitional cell (urothelial) differentiation. The origin of Brenner tumors is perplexing, but they are believed to arise from transitional cell metaplasia occurring within the ovary and/or fallopian tube, although it is controversial whether this metaplasia is truly along transitional cell lines. Recently, TERT promoter mutations have been identified in urothelial carcinoma (UC) with high frequency (approximately 70%), and the current literature suggests a potential diagnostic and/or prognostic role of these mutations in UC. Molecular evidence supporting that Brenner tumors represent neoplasms exhibiting transitional cell differentiation is scant. To explore this further, we investigated a series of 19 Brenner tumors of the ovary (15 benign and 4 malignant) for the presence of TERT promoter mutations after genomic DNA extraction from formalin-fixed paraffin-embedded tissue blocks and standard polymerase chain reaction sequencing. TERT promoter mutations were not identified in any of the cases (0/19). The absence of TERT promoter mutations in Brenner tumors suggests that despite the morphologic and some immunophenotypical resemblance to non-neoplastic and neoplastic transitional epithelium, Brenner tumors may exhibit a molecularly distinct pathogenesis. The findings also may portend diagnostic utility in rare cases wherein it is difficult to distinguish a primary malignant Brenner tumor of the ovary from metastatic UC.

Relationship between Expression of Onco-Related miRNAs and the Endoscopic Appearance of Colorectal Tumors

PubMed Central

Nakagawa, Yoshihito; Akao, Yukihiro; Taniguchi, Kohei; Kamatani, Akemi; Tahara, Tomomitsu; Kamano, Toshiaki; Nakano, Naoko; Komura, Naruomi; Ikuno, Hirokazu; Ohmori, Takafumi; Jodai, Yasutaka; Miyata, Masahiro; Nagasaka, Mistuo; Shibata, Tomoyuki; Ohmiya, Naoki; Hirata, Ichiro

2015-01-01

Accumulating data indicates that certain microRNAs (miRNAs or miRs) are differently expressed in samples of tumors and paired non-tumorous samples taken from the same patients with colorectal tumors. We examined the expression of onco-related miRNAs in 131 sporadic exophytic adenomas or early cancers and in 52 sporadic flat elevated adenomas or early cancers to clarify the relationship between the expression of the miRNAs and the endoscopic morphological appearance of the colorectal tumors. The expression levels of miR-143, -145, and -34a were significantly reduced in most of the exophytic tumors compared with those in the flat elevated ones. In type 2 cancers, the miRNA expression profile was very similar to that of the exophytic tumors. The expression levels of miR-7 and -21 were significantly up-regulated in some flat elevated adenomas compared with those in exophytic adenomas. In contrast, in most of the miR-143 and -145 down-regulated cases of the adenoma-carcinoma sequence and in some of the de novo types of carcinoma, the up-regulation of oncogenic miR-7 and/or -21 contributed to the triggering mechanism leading to the carcinogenetic process. These findings indicated that the expression of onco-related miRNA was associated with the morphological appearance of colorectal tumors. PMID:25584614

Three-dimensional culture of a mixed mullerian tumor of the ovary: expression of in vivo characteristics

NASA Technical Reports Server (NTRS)

Goodwin, T. J.; Prewett, T. L.; Spaulding, G. F.; Becker, J. L.

1997-01-01

The Rotating-Wall Vessel (RWV) is a novel in vitro cell culture system used to successfully culture a cell line derived from a heterologous mixed mullerian tumor cell of the ovary. Although the original tumor was comprised of both epithelial and mesodermal components, long-term culture in conventional flasks established a cell line from this tumor with homogeneous epitheliallike growth characteristics (1). Cells from Passage 36 were seeded into a Rotating-Wall Vessel containing Cytodex-3 microcarrier beads. Scanning electron micrographs of tumor cells cultured for 32 d in the RWV showed the presence of heterogeneous cell populations organized into three-dimensional tissuelike architecture. Immunocytochemical analysis confirmed the cellular heterogeneity, as demonstrated by expression of both epithelial and mesenchymal antigens. Reverse transcription polymerase chain reaction amplification demonstrated the presence of mRNA for cellular oncogenes HER-2/neu, H-ras, K-ras, and tumor suppressor p53. Thus, there are two advantages to propagation of tissue in the RWV culture system:(a) tissue diversification representing populations present in the original tumor, and (b) the three-dimensional freedom to organize tissues morphologically akin to those observed in vivo. These data indicate that the RWV culture system is suitable for generating large quantities of ovarian tumor cells in vitro that are amenable to immunocytochemical, oncogenic, morphologic characteristics demonstrated in vivo.

Whole-genome and multisector exome sequencing of primary and post-treatment glioblastoma reveals patterns of tumor evolution.

PubMed

Kim, Hoon; Zheng, Siyuan; Amini, Seyed S; Virk, Selene M; Mikkelsen, Tom; Brat, Daniel J; Grimsby, Jonna; Sougnez, Carrie; Muller, Florian; Hu, Jian; Sloan, Andrew E; Cohen, Mark L; Van Meir, Erwin G; Scarpace, Lisa; Laird, Peter W; Weinstein, John N; Lander, Eric S; Gabriel, Stacey; Getz, Gad; Meyerson, Matthew; Chin, Lynda; Barnholtz-Sloan, Jill S; Verhaak, Roel G W

2015-03-01

Glioblastoma (GBM) is a prototypical heterogeneous brain tumor refractory to conventional therapy. A small residual population of cells escapes surgery and chemoradiation, resulting in a typically fatal tumor recurrence ∼ 7 mo after diagnosis. Understanding the molecular architecture of this residual population is critical for the development of successful therapies. We used whole-genome sequencing and whole-exome sequencing of multiple sectors from primary and paired recurrent GBM tumors to reconstruct the genomic profile of residual, therapy resistant tumor initiating cells. We found that genetic alteration of the p53 pathway is a primary molecular event predictive of a high number of subclonal mutations in glioblastoma. The genomic road leading to recurrence is highly idiosyncratic but can be broadly classified into linear recurrences that share extensive genetic similarity with the primary tumor and can be directly traced to one of its specific sectors, and divergent recurrences that share few genetic alterations with the primary tumor and originate from cells that branched off early during tumorigenesis. Our study provides mechanistic insights into how genetic alterations in primary tumors impact the ensuing evolution of tumor cells and the emergence of subclonal heterogeneity. © 2015 Kim et al.; Published by Cold Spring Harbor Laboratory Press.

Unpacking boxes: Integration of molecular, morphological and ecological approaches reveals extensive patterns of reticulate evolution in box eucalypts.

PubMed

Flores-Rentería, Lluvia; Rymer, Paul D; Riegler, Markus

2017-03-01

Reticulate evolution by hybridization is considered a common process shaping the evolution of many plant species, however, reticulation could also be due to incomplete lineage sorting in biodiverse systems. For our study we selected a group of closely related plant taxa with contrasting yet partially overlapping geographic distributions and different population sizes, to distinguish between reticulated patterns due to hybridization and incomplete lineage sorting. We predicted that sympatric or proximal populations of different species are more likely to have gene flow than geographically distant populations of the same widespread species. Furthermore, for species with restricted distributions, and therefore, small effective population sizes, we predicted complete lineage sorting. Eastern grey box eucalypt species (Eucalyptus supraspecies Moluccanae) provide an ideal system to explore patterns of reticulate evolution. They form a diverse, recently evolved and phylogenetically undefined group within Eucalyptus, with overlapping morphological features and hybridization in nature. We used a multi-faceted approach, combining analyses of chloroplast and nuclear DNA, as well as seedling morphology, flowering time and ecological spatial differentiation in order to test for species delimitation and reticulate evolution in this group. The multiple layers of results were consistent and suggested a lack of monophyly at different hierarchical levels due to multidirectional gene flow among several species, challenging species delimitation. Chloroplast and nuclear haplotypes were shared among different species in geographic proximity, consistent with hybridization zones. Furthermore, species with restricted distributions appeared better resolved due to lineage sorting in the absence of hybridization. We conclude that a combination of molecular, morphological and ecological approaches is required to disentangle patterns of reticulate evolution in the box eucalypts. Published by Elsevier Inc.

[Undifferentiated soft tissue tumor with rhabdoid phenotype (extra-renal rhabdoid tumor). Report of a congenital case associated with medulloblastoma in a brother].

PubMed

Costes, V; Medioni, D; Durand, L; Sarran, N; Marguerite, G; Baldet, P

1997-03-01

We report a case of congenital cervical rhabdoid tumor with association of a medulloblastoma in a brother. The immunohistochemical features of this tumor are compatible with a neuroectodermal differentiation (MIC 2+, Leu 7+). Extrarenal rhabdoid tumors share a common morphology but do not represent a single entity with only one histogenesis. Most of them are now considered to be of neuroectodermal origin. In our case, the association with a medulloblastoma in a brother seems to confirm this concept.

Analysis of 3D OCT images for diagnosis of skin tumors

NASA Astrophysics Data System (ADS)

Raupov, Dmitry S.; Myakinin, Oleg O.; Bratchenko, Ivan A.; Zakharov, Valery P.; Khramov, Alexander G.

2018-04-01

Skin cancer is one of the fastest growing type of cancer. It represents the most commonly diagnosed malignancy, surpassing lung, breast, colorectal and prostate cancer. So, diagnostics for different types of skin cancer on early stages is a very high challenge for medicine industry. New optical imaging techniques have been developed in order to improve diagnostics precision. Optical coherence tomography (OCT) is based on low-coherence interferometry to detect the intensity of backscattered infrared light from biological tissues by measuring the optical path length. OCT provides the advantage of real-time, in vivo, low-cost imaging of suspicious lesions without having to proceed directly to a tissue biopsy. The post-processing techniques can be used for improving the precision of diagnostics and providing solutions to overcome limitations for OCT. Image processing can include noise filtration and evaluation of textural, geometric, morphological, spectral, statistic and other features. The main idea of this investigation is using information received from multiple analyze on 2D- and 3D-OCT images for skin tumors differentiating. At first, we tested the computer algorithm on OCT data hypercubes and separated B- and C-scans. Combination of 2D and 3D data give us an opportunity to receive common information about tumor (geometric and morphological characteristics) and use more powerful algorithms for features evaluation (fractal and textural) on these separated scans. These groups of features provide closer connection to classical wide-used ABCDE criteria (Asymmetry, Border irregularity, Color, Diameter, Evolution). We used a set of features consisting of fractal dimension, Haralick's, Gabor's, Tamura's, Markov random fields, geometric features and many others. We could note about good results on the test sets in differentiation between BCC and Nevus, MM and Healthy Skin. We received dividing MM from Healthy Skin with sensitivity more 90% and specificity more 92% (168 B-scans from 8 species) by using three Haralick's features like Contrast, Correlation and Energy. The results are very promising to be tested for new cases and new bigger sets of OCT images.

Stasis and convergence characterize morphological evolution in eupolypod II ferns.

PubMed

Sundue, Michael A; Rothfels, Carl J

2014-01-01

Patterns of morphological evolution at levels above family rank remain underexplored in the ferns. The present study seeks to address this gap through analysis of 79 morphological characters for 81 taxa, including representatives of all ten families of eupolypod II ferns. Recent molecular phylogenetic studies demonstrate that the evolution of the large eupolypod II clade (which includes nearly one-third of extant fern species) features unexpected patterns. The traditional 'athyrioid' ferns are scattered across the phylogeny despite their apparent morphological cohesiveness, and mixed among these seemingly conservative taxa are morphologically dissimilar groups that lack any obvious features uniting them with their relatives. Maximum-likelihood and maximum-parsimony character optimizations are used to determine characters that unite the seemingly disparate groups, and to test whether the polyphyly of the traditional athyrioid ferns is due to evolutionary stasis (symplesiomorphy) or convergent evolution. The major events in eupolypod II character evolution are reviewed, and character and character state concepts are reappraised, as a basis for further inquiries into fern morphology. Characters were scored from the literature, live plants and herbarium specimens, and optimized using maximum-parsimony and maximum-likelihood, onto a highly supported topology derived from maximum-likelihood and Bayesian analysis of molecular data. Phylogenetic signal of characters were tested for using randomization methods and fitdiscrete. The majority of character state changes within the eupolypod II phylogeny occur at the family level or above. Relative branch lengths for the morphological data resemble those from molecular data and fit an ancient rapid radiation model (long branches subtended by very short backbone internodes), with few characters uniting the morphologically disparate clades. The traditional athyrioid ferns were circumscribed based upon a combination of symplesiomorphic and homoplastic characters. Petiole vasculature consisting of two bundles is ancestral for eupolypods II and a synapomorphy for eupolypods II under deltran optimization. Sori restricted to one side of the vein defines the recently recognized clade comprising Rhachidosoraceae through Aspleniaceae, and sori present on both sides of the vein is a synapomorphy for the Athyriaceae sensu stricto. The results indicate that a chromosome base number of x =41 is synapomorphic for all eupolypods, a clade that includes over two-thirds of extant fern species. The integrated approach synthesizes morphological studies with current phylogenetic hypotheses and provides explicit statements of character evolution in the eupolypod II fern families. Strong character support is found for previously recognized clades, whereas few characters support previously unrecognized clades. Sorus position appears to be less complicated than previously hypothesized, and linear sori restricted to one side of the vein support the clade comprising Aspleniaceae, Diplaziopsidaceae, Hemidictyaceae and Rachidosoraceae - a lineage only recently identified. Despite x =41 being a frequent number among extant species, to our knowledge it has not previously been demonstrated as the ancestral state. This is the first synapomorphy proposed for the eupolypod clade, a lineage comprising 67 % of extant fern species. This study provides some of the first hypotheses of character evolution at the family level and above in light of recent phylogenetic results, and promotes further study in an area that remains open for original observation.

Stasis and convergence characterize morphological evolution in eupolypod II ferns

PubMed Central

Sundue, Michael A.; Rothfels, Carl J.

2014-01-01

Background and Aims Patterns of morphological evolution at levels above family rank remain underexplored in the ferns. The present study seeks to address this gap through analysis of 79 morphological characters for 81 taxa, including representatives of all ten families of eupolypod II ferns. Recent molecular phylogenetic studies demonstrate that the evolution of the large eupolypod II clade (which includes nearly one-third of extant fern species) features unexpected patterns. The traditional ‘athyrioid’ ferns are scattered across the phylogeny despite their apparent morphological cohesiveness, and mixed among these seemingly conservative taxa are morphologically dissimilar groups that lack any obvious features uniting them with their relatives. Maximum-likelihood and maximum-parsimony character optimizations are used to determine characters that unite the seemingly disparate groups, and to test whether the polyphyly of the traditional athyrioid ferns is due to evolutionary stasis (symplesiomorphy) or convergent evolution. The major events in eupolypod II character evolution are reviewed, and character and character state concepts are reappraised, as a basis for further inquiries into fern morphology. Methods Characters were scored from the literature, live plants and herbarium specimens, and optimized using maximum-parsimony and maximum-likelihood, onto a highly supported topology derived from maximum-likelihood and Bayesian analysis of molecular data. Phylogenetic signal of characters were tested for using randomization methods and fitdiscrete. Key Results The majority of character state changes within the eupolypod II phylogeny occur at the family level or above. Relative branch lengths for the morphological data resemble those from molecular data and fit an ancient rapid radiation model (long branches subtended by very short backbone internodes), with few characters uniting the morphologically disparate clades. The traditional athyrioid ferns were circumscribed based upon a combination of symplesiomorphic and homoplastic characters. Petiole vasculature consisting of two bundles is ancestral for eupolypods II and a synapomorphy for eupolypods II under deltran optimization. Sori restricted to one side of the vein defines the recently recognized clade comprising Rhachidosoraceae through Aspleniaceae, and sori present on both sides of the vein is a synapomorphy for the Athyriaceae sensu stricto. The results indicate that a chromosome base number of x =41 is synapomorphic for all eupolypods, a clade that includes over two-thirds of extant fern species. Conclusions The integrated approach synthesizes morphological studies with current phylogenetic hypotheses and provides explicit statements of character evolution in the eupolypod II fern families. Strong character support is found for previously recognized clades, whereas few characters support previously unrecognized clades. Sorus position appears to be less complicated than previously hypothesized, and linear sori restricted to one side of the vein support the clade comprising Aspleniaceae, Diplaziopsidaceae, Hemidictyaceae and Rachidosoraceae – a lineage only recently identified. Despite x =41 being a frequent number among extant species, to our knowledge it has not previously been demonstrated as the ancestral state. This is the first synapomorphy proposed for the eupolypod clade, a lineage comprising 67 % of extant fern species. This study provides some of the first hypotheses of character evolution at the family level and above in light of recent phylogenetic results, and promotes further study in an area that remains open for original observation. PMID:24197753

Modern mammal origins: evolutionary grades in the Early Cretaceous of North America.

PubMed

Jacobs, L L; Winkler, D A; Murry, P A

1989-07-01

Major groups of modern mammals have their origins in the Mesozoic Era, yet the mammalian fossil record is generally poor for that time interval. Fundamental morphological changes that led to modern mammals are often represented by small samples of isolated teeth. Fortunately, functional wear facets on teeth allow prediction of the morphology of occluding teeth that may be unrepresented by fossils. A major step in mammalian evolution occurred in the Early Cretaceous with the evolution of tribosphenic molars, which characterize marsupials and placentals, the two most abundant and diverse extant groups of mammals. A tooth from the Early Cretaceous (110 million years before present) of Texas tests previous predictions (based on lower molars) of the morphology of upper molars in early tribosphenic dentitions. The lingual cusp (protocone) is primitively without shear facets, as expected, but the cheek side of the tooth is derived (advanced) in having distinctive cusps along the margin. The tooth, although distressingly inadequate to define many features of the organism, demonstrates unexpected morphological diversity at a strategic stage of mammalian evolution and falsifies previous claims of the earliest occurrence of true marsupials.

The potential influence of morphology on the evolutionary divergence of an acoustic signal

PubMed Central

Pitchers, W. R.; Klingenberg, C.P.; Tregenza, Tom; Hunt, J.; Dworkin, I.

2014-01-01

The evolution of acoustic behaviour and that of the morphological traits mediating its production are often coupled. Lack of variation in the underlying morphology of signalling traits has the potential to constrain signal evolution. This relationship is particularly likely in field crickets, where males produce acoustic advertisement signals to attract females by stridulating with specialized structures on their forewings. In this study, we characterise the size and geometric shape of the forewings of males from six allopatric populations of the black field cricket (Teleogryllus commodus) known to have divergent advertisement calls. We sample from each of these populations using both wild-caught and common-garden reared cohorts, allowing us to test for multivariate relationships between wing morphology and call structure. We show that the allometry of shape has diverged across populations. However, there was a surprisingly small amount of covariation between wing shape and call structure within populations. Given the importance of male size for sexual selection in crickets, the divergence we observe among populations has the potential to influence the evolution of advertisement calls in this species. PMID:25223712

Recent speciation in the Indo-West Pacific: rapid evolution of gamete recognition and sperm morphology in cryptic species of sea urchin.

PubMed Central

Landry, C; Geyer, L B; Arakaki, Y; Uehara, T; Palumbi, Stephen R

2003-01-01

The rich species diversity of the marine Indo-West Pacific (IWP) has been explained largely on the basis of historical observation of large-scale diversity gradients. Careful study of divergence among closely related species can reveal important new information about the pace and mechanisms of their formation, and can illuminate the genesis of biogeographic patterns. Young species inhabiting the IWP include urchins of the genus Echinometra, which diverged over the past 1-5 Myr. Here, we report the most recent divergence of two cryptic species of Echinometra inhabiting this region. Mitochondrial cytochrome oxidase 1 (CO1) sequence data show that in Echinometra oblonga, species-level divergence in sperm morphology, gamete recognition proteins and gamete compatibility arose between central and western Pacific populations in the past 250 000 years. Divergence in sperm attachment proteins suggests rapid evolution of the fertilization system. Divergence of sperm morphology may be a common feature of free-spawning animals, and offers opportunities to simultaneously understand genetic divergence, changes in protein expression patterns and morphological evolution in traits directly related to reproductive isolation. PMID:12964987

Observing Clonal Dynamics across Spatiotemporal Axes: A Prelude to Quantitative Fitness Models for Cancer.

PubMed

McPherson, Andrew W; Chan, Fong Chun; Shah, Sohrab P

2018-02-01

The ability to accurately model evolutionary dynamics in cancer would allow for prediction of progression and response to therapy. As a prelude to quantitative understanding of evolutionary dynamics, researchers must gather observations of in vivo tumor evolution. High-throughput genome sequencing now provides the means to profile the mutational content of evolving tumor clones from patient biopsies. Together with the development of models of tumor evolution, reconstructing evolutionary histories of individual tumors generates hypotheses about the dynamics of evolution that produced the observed clones. In this review, we provide a brief overview of the concepts involved in predicting evolutionary histories, and provide a workflow based on bulk and targeted-genome sequencing. We then describe the application of this workflow to time series data obtained for transformed and progressed follicular lymphomas (FL), and contrast the observed evolutionary dynamics between these two subtypes. We next describe results from a spatial sampling study of high-grade serous (HGS) ovarian cancer, propose mechanisms of disease spread based on the observed clonal mixtures, and provide examples of diversification through subclonal acquisition of driver mutations and convergent evolution. Finally, we state implications of the techniques discussed in this review as a necessary but insufficient step on the path to predictive modelling of disease dynamics. Copyright © 2018 Cold Spring Harbor Laboratory Press; all rights reserved.

Differential Diagnosis of Benign Spindle Cell Lesions.

PubMed

Magro, Gaetano

2018-03-01

Spindle cell lesions of the breast cover a wide spectrum of diseases ranging from reactive tumor-like lesions to high-grade malignant tumors. The recognition of the benign spindle cell tumor-like lesions (nodular fasciitis; reactive spindle cell nodule after biopsy, inflammatory pseudotumor/inflammatory myofibroblastic tumor; fascicular variant of pseudoangiomatous stromal hyperplasia) and tumors (myofibroblastoma, benign fibroblastic spindle cell tumor, leiomyoma, schwannoma, spindle cell lipoma, solitary fibrous tumor, myxoma) is crucial to avoid confusion with morphologically similar but more aggressive bland-appearing spindle cell tumors, such as desmoid-type fibromatosis, low-grade (fibromatosis-like) spindle cell carcinoma, low-grade fibrosarcoma/myofibroblastic sarcoma and dermatofibrosarcoma protuberans. Copyright © 2017 Elsevier Inc. All rights reserved.

A gene network model accounting for development and evolution of mammalian teeth

PubMed Central

Salazar-Ciudad, Isaac; Jernvall, Jukka

2002-01-01

Generation of morphological diversity remains a challenge for evolutionary biologists because it is unclear how an ultimately finite number of genes involved in initial pattern formation integrates with morphogenesis. Ideally, models used to search for the simplest developmental principles on how genes produce form should account for both developmental process and evolutionary change. Here we present a model reproducing the morphology of mammalian teeth by integrating experimental data on gene interactions and growth into a morphodynamic mechanism in which developing morphology has a causal role in patterning. The model predicts the course of tooth-shape development in different mammalian species and also reproduces key transitions in evolution. Furthermore, we reproduce the known expression patterns of several genes involved in tooth development and their dynamics over developmental time. Large morphological effects frequently can be achieved by small changes, according to this model, and similar morphologies can be produced by different changes. This finding may be consistent with why predicting the morphological outcomes of molecular experiments is challenging. Nevertheless, models incorporating morphology and gene activity show promise for linking genotypes to phenotypes. PMID:12048258

Secular Evolution of Galaxies

NASA Astrophysics Data System (ADS)

Falcón-Barroso, Jesús; Knapen, Johan H.

2013-10-01

Preface; 1. Secular evolution in disk galaxies John Kormendy; 2. Galaxy morphology Ronald J. Buta; 3. Dynamics of secular evolution James Binney; 4. Bars and secular evolution in disk galaxies: theoretical input E. Athanassoula; 5. Stellar populations Reynier F. Peletier; 6. Star formation rate indicators Daniela Calzetti; 7. The evolving interstellar medium Jacqueline van Gorkom; 8. Evolution of star formation and gas Nick Z. Scoville; 9. Cosmological evolution of galaxies Isaac Shlosman.

Reconstitution of the NF1 GAP-related domain in NF1-deficient human Schwann cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Thomas, Stacey L.; Neuroscience Program, Loyola University Medical Center, Maywood, IL; Department of Anatomy and Cell Biology, University of Illinois Chicago, Chicago, IL

Schwann cells derived from peripheral nerve sheath tumors from individuals with Neurofibromatosis Type 1 (NF1) are deficient for the protein neurofibromin, which contains a GAP-related domain (NF1-GRD). Neurofibromin-deficient Schwann cells have increased Ras activation, increased proliferation in response to certain growth stimuli, increased angiogenic potential, and altered cell morphology. This study examined whether expression of functional NF1-GRD can reverse the transformed phenotype of neurofibromin-deficient Schwann cells from both benign and malignant peripheral nerve sheath tumors. We reconstituted the NF1-GRD using retroviral transduction and examined the effects on cell morphology, growth potential, and angiogenic potential. NF1-GRD reconstitution resulted in morphologic changes,more » a 16-33% reduction in Ras activation, and a 53% decrease in proliferation in neurofibromin-deficient Schwann cells. However, NF1-GRD reconstitution was not sufficient to decrease the in vitro angiogenic potential of the cells. This study demonstrates that reconstitution of the NF1-GRD can at least partially reverse the transformation of human NF1 tumor-derived Schwann cells.« less

Automated Morphological and Morphometric Analysis of Mass Spectrometry Imaging Data: Application to Biomarker Discovery

NASA Astrophysics Data System (ADS)

Picard de Muller, Gaël; Ait-Belkacem, Rima; Bonnel, David; Longuespée, Rémi; Stauber, Jonathan

2017-12-01

Mass spectrometry imaging datasets are mostly analyzed in terms of average intensity in regions of interest. However, biological tissues have different morphologies with several sizes, shapes, and structures. The important biological information, contained in this highly heterogeneous cellular organization, could be hidden by analyzing the average intensities. Finding an analytical process of morphology would help to find such information, describe tissue model, and support identification of biomarkers. This study describes an informatics approach for the extraction and identification of mass spectrometry image features and its application to sample analysis and modeling. For the proof of concept, two different tissue types (healthy kidney and CT-26 xenograft tumor tissues) were imaged and analyzed. A mouse kidney model and tumor model were generated using morphometric - number of objects and total surface - information. The morphometric information was used to identify m/z that have a heterogeneous distribution. It seems to be a worthwhile pursuit as clonal heterogeneity in a tumor is of clinical relevance. This study provides a new approach to find biomarker or support tissue classification with more information. [Figure not available: see fulltext.

Morphological basis for the evolution of acoustic diversity in oscine songbirds

PubMed Central

Riede, Tobias; Goller, Franz

2014-01-01

Acoustic properties of vocalizations arise through the interplay of neural control with the morphology and biomechanics of the sound generating organ, but in songbirds it is assumed that the main driver of acoustic diversity is variation in telencephalic motor control. Here we show, however, that variation in the composition of the vibrating tissues, the labia, underlies diversity in one acoustic parameter, fundamental frequency (F0) range. Lateral asymmetry and arrangement of fibrous proteins in the labia into distinct layers is correlated with expanded F0 range of species. The composition of the vibrating tissues thus represents an important morphological foundation for the generation of a broad F0 range, indicating that morphological specialization lays the foundation for the evolution of complex acoustic repertoires. PMID:24500163

Correlated effects of preparation parameters and thickness on morphology and optical properties of ZnO very thin films

NASA Astrophysics Data System (ADS)

Gilliot, Mickaël; Hadjadj, Aomar

2015-08-01

Nano-granular ZnO layers have been grown using a sol-gel synthesis and spin-coating deposition process. Thin films with thicknesses ranging from 15 to 150 nm have been obtained by varying the number of deposition cycles and prepared with different synthesis conditions. Morphologies and optical properties have been carefully investigated by joint spectroscopic ellipsometry and atomic force microscopy. A correlation between the evolution of optical properties and grains morphology has been observed. It is shown that both synthesis temperature and concentration similarly allow us to change the correlated growth and properties evolution rate. Thickness variation associated to choice of synthesis parameters could be a useful way to tune morphology and optical properties of the nanostructured ZnO layers.

Evolution of limited seed dispersal ability on gypsum islands.

PubMed

Schenk, John J

2013-09-01

Dispersal is a major feature of plant evolution that has many advantages but is not always favored. Wide dispersal, for example, leads to greater seed loss in oceanic-island endemics, and evolution has favored morphologies that limit dispersal. I tested the hypothesis that selection favored limited dispersal on gypsum islands in western North America, where edaphic communities are sparsely vegetated except for a specialized flora that competes poorly with the surrounding flora. • I applied a series of comparative phylogenetic approaches to gypsophilic species of Mentzelia section Bartonia (Loasaceae) to investigate the evolution of limited dispersal function in seed wings, which increase primary dispersal by wind. Through these tests, I determined whether narrowed wings were selected for in gypsophilic species. • Gypsophily was derived four to seven times. Seed area was not significantly correlated with gypsophily or wing area. Wing area was significantly smaller in the derived gypsum endemics, supporting the hypothesis in favor of limited dispersal function. A model-fitting approach identified two trait optima in wing area, with gypsum endemics having a lower optimum. • Evolution into novel ecologies influences morphological evolution. Morphological characters have been selected for limited dispersal following evolution onto gypsum islands. Selection for limited dispersal ability has occurred across animals and plants, both in oceanic and terrestrial systems, which suggests that reduced dispersal ability may be a general process: selection favors limited dispersal if the difference in survival between the habitat of the parent and the surrounding area is great enough.

Morphological and Star Formation Evolution to z = 1

NASA Astrophysics Data System (ADS)

Hammer, F.

The decrease, since z = 1, of the rest-frame UV luminosity density is related to global changes in morphology, color and emission lines properties of galaxies. This is apparently followed by a similar decrease of the rest-frame IR luminosity density. I discuss the relative contribution from the different galaxy morphological types to the observed evolution. The main contributors are compact galaxies observed in large number at optical wavelengths, and the sparse population of extincted & powerful starbursts observed by ISO. This latter population is made of large and massive galaxies mostly found in interacting systems, some of which could be leading to the formation of massive ellipticals at z < 1.

Plasticity first: molecular signatures of a complex morphological trait in filamentous cyanobacteria.

PubMed

Koch, Robin; Kupczok, Anne; Stucken, Karina; Ilhan, Judith; Hammerschmidt, Katrin; Dagan, Tal

2017-08-31

Filamentous cyanobacteria that differentiate multiple cell types are considered the peak of prokaryotic complexity and their evolution has been studied in the context of multicellularity origins. Species that form true-branching filaments exemplify the most complex cyanobacteria. However, the mechanisms underlying the true-branching morphology remain poorly understood despite of several investigations that focused on the identification of novel genes or pathways. An alternative route for the evolution of novel traits is based on existing phenotypic plasticity. According to that scenario - termed genetic assimilation - the fixation of a novel phenotype precedes the fixation of the genotype. Here we show that the evolution of transcriptional regulatory elements constitutes a major mechanism for the evolution of new traits. We found that supplementation with sucrose reconstitutes the ancestral branchless phenotype of two true-branching Fischerella species and compared the transcription start sites (TSSs) between the two phenotypic states. Our analysis uncovers several orthologous TSSs whose transcription level is correlated with the true-branching phenotype. These TSSs are found in genes that encode components of the septosome and elongasome (e.g., fraC and mreB). The concept of genetic assimilation supplies a tenable explanation for the evolution of novel traits but testing its feasibility is hindered by the inability to recreate and study the evolution of present-day traits. We present a novel approach to examine transcription data for the plasticity first route and provide evidence for its occurrence during the evolution of complex colony morphology in true-branching cyanobacteria. Our results reveal a route for evolution of the true-branching phenotype in cyanobacteria via modification of the transcription level of pre-existing genes. Our study supplies evidence for the 'plasticity-first' hypothesis and highlights the importance of transcriptional regulation in the evolution of novel traits.

Tempo and mode of performance evolution across multiple independent origins of adhesive toe pads in lizards.

PubMed

Hagey, Travis J; Uyeda, Josef C; Crandell, Kristen E; Cheney, Jorn A; Autumn, Kellar; Harmon, Luke J

2017-10-01

Understanding macroevolutionary dynamics of trait evolution is an important endeavor in evolutionary biology. Ecological opportunity can liberate a trait as it diversifies through trait space, while genetic and selective constraints can limit diversification. While many studies have examined the dynamics of morphological traits, diverse morphological traits may yield the same or similar performance and as performance is often more proximately the target of selection, examining only morphology may give an incomplete understanding of evolutionary dynamics. Here, we ask whether convergent evolution of pad-bearing lizards has followed similar evolutionary dynamics, or whether independent origins are accompanied by unique constraints and selective pressures over macroevolutionary time. We hypothesized that geckos and anoles each have unique evolutionary tempos and modes. Using performance data from 59 species, we modified Brownian motion (BM) and Ornstein-Uhlenbeck (OU) models to account for repeated origins estimated using Bayesian ancestral state reconstructions. We discovered that adhesive performance in geckos evolved in a fashion consistent with Brownian motion with a trend, whereas anoles evolved in bounded performance space consistent with more constrained evolution (an Ornstein-Uhlenbeck model). Our results suggest that convergent phenotypes can have quite distinctive evolutionary patterns, likely as a result of idiosyncratic constraints or ecological opportunities. © 2017 The Author(s). Evolution © 2017 The Society for the Study of Evolution.

[Magnetic resonance imaging of brain tumors].

PubMed

Prayer, Daniela; Brugger, P C

2002-01-01

Investigating intracranial tumors, different MR-related methods permit not only morphological visualization of lesions but also give insights into their metabolism, resulting in information about the biological qualities of the respective tumor. Magnetic resonance protocols are selected based on the type and timing of onset of clinical signs. Combined information from imaging studies and spectroscopy facilitates the differential diagnosis between blastomatous and non-blastomatous lesions before and after therapy.

Assessment of Parametrial Response by Growth Pattern in Patients With International Federation of Gynecology and Obstetrics Stage IIB and IIIB Cervical Cancer: Analysis of Patients From a Prospective, Multicenter Trial (EMBRACE)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yoshida, Kenji; Kobe University Graduate School of Medicine, Kobe; Jastaniyah, Noha

Purpose: To assess disease response along the parametrial space according to tumor morphology in patients with International Federation of Gynecology and Obstetrics (FIGO) stage IIB and IIIB cervical cancer at the time of image-guided adaptive brachytherapy. Methods and Materials: Patients with FIGO stage IIB and IIIB cervical cancer registered as of November 2013 in the EMBRACE study were evaluated. Tumors were stratified according to morphologic subtype on magnetic resonance imaging (expansive and infiltrative), and the characteristics of those subtypes were analyzed. Parametrial involvement at diagnosis and at brachytherapy was evaluated, and the response to chemo-radiotherapy was classified as good, moderate,more » or poor. The response grade was compared between the 2 groups and analyzed with regard to tumor volumes, and dosimetric parameters. Results: A total of 452 patients were evaluated, of whom 186 had expansive growth type and 266 had infiltrative morphology. Patients with infiltrative tumors had more extensive disease, as indicated by a higher rate of FIGO stage IIIB disease, as well as radiologic evidence of extension into the distal parametrial space and to the pelvic side wall on magnetic resonance imaging. Cervical necrosis was more common in the infiltrative group. Good response was more common in the expansive group (34% vs 24%; P=.02), and poor response was more common in the infiltrative group (11% and 19%; P=.02). Mean gross tumor volume at diagnosis was equal in both groups (51.7 cm{sup 3}). The high-risk clinical target volume was larger in infiltrative tumors (37.9 cm{sup 3} vs 33.3 cm{sup 3}, P=.005). The mean high-risk clinical target volume D{sub 90} was slightly higher in expansive tumors (92.7 Gy and 89.4 Gy, P<.001). Conclusion: Infiltrative tumors are more advanced at presentation and respond less favorably to chemo-radiotherapy when compared with expansive tumors that are more or less equivalent in size. The use of image-guided adaptive brachytherapy allows achieving reasonably high doses in both groups.« less

The morphological development of newly inundated intertidal areas: the mechanisms driving the early evolution of an estuarine environment designed and constructed by humans

NASA Astrophysics Data System (ADS)

Dale, Jonathan; Burgess, Heidi; Cundy, Andrew

2017-04-01

Intertidal saltmarsh and mudflat habitats are of global importance due to the ecosystem, economic and cultural services they provide. These services include wildlife habitat provision and species diversity, immobilisation of pollutants and protection from coastal flooding. Saltmarsh and mudflat environments are, however, being lost and degraded due to erosion caused by rising sea levels and increased storminess. These losses are exacerbated by anthropogenic influences including land reclamation, increased coastal development and the construction of coastal flood defences which prevent the landwards migration of saltmarsh and mudflat environments, resulting in coastal squeeze. To compensate for saltmarsh and mudflat losses areas of the coastal hinterland are being inundated by breaching defences and constructing new defences inland, thus extending or constructing new estuarine environments; a processes known as de-embankment or managed realignment. Morphological engineering and landscaping within managed realignment sites prior to site inundation varies depending on the aims of the scheme. However, there is a shortage of data on the morphological evolution within these sites post site inundation impeding the ability of coastal engineers to effectively design and construct future sites. To date there has been a focus on the colonisation of marine macro fauna and flora within newly inundated managed realignment sites, which can be relatively rapid and easily quantified. Little is known of the morphological evolution in response to altered sedimentary processes, its driving mechanisms and therefore the success and ecological sustainability of these sites. This study evaluates the post-inundation morphological development of the largest open coast managed realignment site in Europe, at Medmerry on the south coast of the United Kingdom. Inundated in September 2013, the Medmerry Managed Realignment Site consists of a mosaic of former agricultural land and areas of lower elevation excavated during site construction, drained by a series of natural and engineered channels. Results indicate different rates and patterns of sedimentation and resulting morphology across the site. Near the breach continuous sedimentation of > 15cm over a 1 year period was measured, compared to rhythmic periods of accretion and erosion inland. These variations have been related to site design, former land-use and different sediment sources. The evolution of developing creek networks, formed by pluvial action and sediment "piping", are controlled by unconformities found in the sub-surface sediment related to Holocene site evolution. Analysis of the sedimentary processes and subsequent morphological development of these areas provides a new insight into coastal and estuarine evolution in an anthropogenically designed and constructed estuarine environment.

Morphology control of zinc regeneration for zinc-air fuel cell and battery

NASA Astrophysics Data System (ADS)

Wang, Keliang; Pei, Pucheng; Ma, Ze; Xu, Huachi; Li, Pengcheng; Wang, Xizhong

2014-12-01

Morphology control is crucial both for zinc-air batteries and for zinc-air fuel cells during zinc regeneration. Zinc dendrite should be avoided in zinc-air batteries and zinc pellets are yearned to be formed for zinc-air fuel cells. This paper is mainly to analyze the mechanism of shape change and to control the zinc morphology during charge. A numerical three-dimensional model for zinc regeneration is established with COMSOL software on the basis of ionic transport theory and electrode reaction electrochemistry, and some experiments of zinc regeneration are carried out. The deposition process is qualitatively analyzed by the kinetics Monte Carlo method to study the morphological change from the electrocrystallization point of view. Morphological evolution of deposited zinc under different conditions of direct currents and pulse currents is also investigated by simulation. The simulation shows that parametric variables of the flowing electrolyte, the surface roughness and the structure of the electrode, the charging current and mode affect morphological evolution. The uniform morphology of deposited zinc is attained at low current, pulsating current or hydrodynamic electrolyte, and granular morphology is obtained by means of an electrode of discrete columnar structure in combination with high current and flowing electrolyte.

Dynamic Patterns of Clonal Evolution in Tumor Vasculature Underlie Alterations in Lymphocyte-Endothelial Recognition to Foster Tumor Immune Escape.

PubMed

Corey, Daniel M; Rinkevich, Yuval; Weissman, Irving L

2016-03-15

Although tumor blood vessels have been a major therapeutic target for cancer chemotherapy, little is known regarding the stepwise development of the tumor microenvironment. Here, we use a multicolor Cre-dependent marker system to trace clonality within the tumor microenvironment to show that tumor blood vessels follow a pattern of dynamic clonal evolution. In an advanced melanoma tumor microenvironment, the vast majority of tumor vasculature clones are derived from a common precursor. Quantitative lineage analysis reveals founder clones diminish in frequency and are replaced by subclones as tumors evolve. These tumor-specific blood vessels are characterized by a developmental switch to a more invasive and immunologically silent phenotype. Gene expression profiling and pathway analysis reveals selection for traits promoting upregulation of alternative angiogenic programs such as unregulated HGF-MET signaling and enhanced autocrine signaling through VEGF and PDGF. Furthermore, we show a developmental switch in the expression of functionally significant primary lymphocyte adhesion molecules on tumor endothelium, such as the loss in expression of the mucosal addressin MAdCAM-1, whose counter receptor a4β7 on lymphocytes controls lymphocyte homing. Changes in adhesive properties on tumor endothelial subclones are accompanied by decreases in expression of lymphocyte chemokines CXCL16, CXCL13, CXCL12, CXCL9, CXCL10, and CCL19. These evolutionary patterns in the expressed genetic program within tumor endothelium will have both a quantitative and functional impact on lymphocyte distribution that may well influence tumor immune function and underlie escape mechanisms from current antiangiogenic pharmacotherapies. ©2015 American Association for Cancer Research.

Morphological Perspectives on Galaxy Evolution since z~1.5

NASA Astrophysics Data System (ADS)

Rutkowski, Michael

Galaxies represent a fundamental catalyst in the "lifecycle'' of matter in the Universe, and the study of galaxy assembly and evolution provides unique insight into the physical processes governing the transformation of matter from atoms to gas to stars. With the Hubble Space Telescope, the astrophysical community is able to study the formation and evolution of galaxies, at an unrivaled spatial resolution, over more than 90% of cosmic time. Here, I present results from two complementary studies of galaxy evolution in the local and intermediate redshift Universe which used new and archival HST images. First, I use archival broad-band HST WFPC2 optical images of local (d < 63 Mpc) Seyfert-type galaxies to test the observed correlation between visually-classified host galaxy dust morphology and AGN class. Using quantitative parameters for classifying galaxy morphology, I do not measure a strong correlation between the galaxy morphology and AGN class. This result could imply that the Unified Model of AGN provides a sufficient model for the observed diversity of AGN, but this result could also indicate the quantitative techniques are insufficient for characterizing the dust morphology of local galaxies. To address the latter, I develop a new automated method using an inverse unsharp masking technique coupled to Source Extractor to detect and measure dust morphology. I measure no strong trends with dust-morphology and AGN class using this method, and conclude that the Unified Model remains sufficient to explain the diversity of AGN. Second, I use new UV-optical-near IR broad-band images obtained with the HST WFC3 in the Early Release Science (ERS) program to study the evolution of massive, early-type galaxies. These galaxies were once considered to be "red and dead'', as a class uniformly devoid of recent star formation, but observations of these galaxies in the local Universe at UV wavelengths have revealed a significant fraction (30%) of ETGs to have recently formed a small fraction (5--10%) of their stellar mass in young stars. I extend the study of recent star formation in ETGs to intermediate-redshift 0.35 intermediate-redshift 0.35 < z < 1.5 with the ERS data. Comparing the mass fraction and age of young stellar populations identified in these ETGs from two-component SED analysis with the morphology of the ETG and the frequency of companions, I find that at this redshift many ETGs are likely to have experienced a minor burst of recent star formation. The mechanisms driving this recent star formation are varied, and evidence for both minor merger driven recent star formation as well as the evolution of transitioning ETGs is identified.

The Brassica oleracea genome reveals the asymmetrical evolution of polyploid genomes

PubMed Central

Liu, Shengyi; Liu, Yumei; Yang, Xinhua; Tong, Chaobo; Edwards, David; Parkin, Isobel A. P.; Zhao, Meixia; Ma, Jianxin; Yu, Jingyin; Huang, Shunmou; Wang, Xiyin; Wang, Junyi; Lu, Kun; Fang, Zhiyuan; Bancroft, Ian; Yang, Tae-Jin; Hu, Qiong; Wang, Xinfa; Yue, Zhen; Li, Haojie; Yang, Linfeng; Wu, Jian; Zhou, Qing; Wang, Wanxin; King, Graham J; Pires, J. Chris; Lu, Changxin; Wu, Zhangyan; Sampath, Perumal; Wang, Zhuo; Guo, Hui; Pan, Shengkai; Yang, Limei; Min, Jiumeng; Zhang, Dong; Jin, Dianchuan; Li, Wanshun; Belcram, Harry; Tu, Jinxing; Guan, Mei; Qi, Cunkou; Du, Dezhi; Li, Jiana; Jiang, Liangcai; Batley, Jacqueline; Sharpe, Andrew G; Park, Beom-Seok; Ruperao, Pradeep; Cheng, Feng; Waminal, Nomar Espinosa; Huang, Yin; Dong, Caihua; Wang, Li; Li, Jingping; Hu, Zhiyong; Zhuang, Mu; Huang, Yi; Huang, Junyan; Shi, Jiaqin; Mei, Desheng; Liu, Jing; Lee, Tae-Ho; Wang, Jinpeng; Jin, Huizhe; Li, Zaiyun; Li, Xun; Zhang, Jiefu; Xiao, Lu; Zhou, Yongming; Liu, Zhongsong; Liu, Xuequn; Qin, Rui; Tang, Xu; Liu, Wenbin; Wang, Yupeng; Zhang, Yangyong; Lee, Jonghoon; Kim, Hyun Hee; Denoeud, France; Xu, Xun; Liang, Xinming; Hua, Wei; Wang, Xiaowu; Wang, Jun; Chalhoub, Boulos; Paterson, Andrew H

2014-01-01

Polyploidization has provided much genetic variation for plant adaptive evolution, but the mechanisms by which the molecular evolution of polyploid genomes establishes genetic architecture underlying species differentiation are unclear. Brassica is an ideal model to increase knowledge of polyploid evolution. Here we describe a draft genome sequence of Brassica oleracea, comparing it with that of its sister species B. rapa to reveal numerous chromosome rearrangements and asymmetrical gene loss in duplicated genomic blocks, asymmetrical amplification of transposable elements, differential gene co-retention for specific pathways and variation in gene expression, including alternative splicing, among a large number of paralogous and orthologous genes. Genes related to the production of anticancer phytochemicals and morphological variations illustrate consequences of genome duplication and gene divergence, imparting biochemical and morphological variation to B. oleracea. This study provides insights into Brassica genome evolution and will underpin research into the many important crops in this genus. PMID:24852848

Did Lizards Follow Unique Pathways in Sex Chromosome Evolution?

PubMed Central

Gleeson, Dianne; Georges, Arthur

2018-01-01

Reptiles show remarkable diversity in modes of reproduction and sex determination, including high variation in the morphology of sex chromosomes, ranging from homomorphic to highly heteromorphic. Additionally, the co-existence of genotypic sex determination (GSD) and temperature-dependent sex determination (TSD) within and among sister clades makes this group an attractive model to study and understand the evolution of sex chromosomes. This is particularly so with Lizards (Order Squamata) which, among reptiles, show extraordinary morphological diversity. They also show no particular pattern of sex chromosome degeneration of the kind observed in mammals, birds and or even in snakes. We therefore speculate that sex determination sensu sex chromosome evolution is labile and rapid and largely follows independent trajectories within lizards. Here, we review the current knowledge on the evolution of sex chromosomes in lizards and discuss how sex chromosome evolution within that group differs from other amniote taxa, facilitating unique evolutionary pathways. PMID:29751579

Life on the rocks: habitat use drives morphological and performance evolution in lizards.

PubMed

Goodman, Brett A; Miles, Donald B; Schwarzkopf, Lin

2008-12-01

As a group, lizards occupy a vast array of habitats worldwide, yet there remain relatively few cases where habitat use (ecology), morphology, and thus, performance, are clearly related. The best known examples include: increased limb length in response to increased arboreal perch diameter in anoles and increased limb length in response to increased habitat openness for some skinks. Rocky habitats impose strong natural selection on specific morphological characteristics, which differs from that imposed on terrestrial species, because moving about on inclined substrates of irregular sizes and shapes constrains locomotor performance in predictable ways. We quantified habitat use, morphology, and performance of 19 species of lizards (family Scincidae, subfamily Lygosominae) from 23 populations in tropical Australia. These species use habitats with considerable variation in rock availability. Comparative phylogenetic analyses revealed that occupation of rock-dominated habitats correlated with the evolution of increased limb length, compared to species from forest habitats that predominantly occupied leaf litter. Moreover, increased limb length directly affected performance, with species from rocky habitats having greater sprinting, climbing, and clinging ability than their relatives from less rocky habitats. Thus, we found that the degree of rock use is correlated with both morphological and performance evolution in this group of tropical lizards.

"Atypical" Pleomorphic Lipomatous Tumor: A Clinicopathologic, Immunohistochemical and Molecular Study of 21 Cases, Emphasizing its Relationship to Atypical Spindle Cell Lipomatous Tumor and Suggesting a Morphologic Spectrum (Atypical Spindle Cell/Pleomorphic Lipomatous Tumor).

PubMed

Creytens, David; Mentzel, Thomas; Ferdinande, Liesbeth; Lecoutere, Evelyne; van Gorp, Joost; Atanesyan, Lilit; de Groot, Karel; Savola, Suvi; Van Roy, Nadine; Van Dorpe, Jo; Flucke, Uta

2017-11-01

The classification of the until recently poorly explored group of atypical adipocytic neoplasms with spindle cell features, for which recently the term atypical spindle cell lipomatous tumor (ASLT) has been proposed, remains challenging. Recent studies have proposed ASLT as a unique entity with (in at least a significant subset of cases) a specific genetic background, namely deletions/losses of 13q14, including RB1 and its flanking genes RCBTB2, DLEU1, and ITM2B. Similar genetic aberrations have been reported in pleomorphic liposarcomas (PLSs). This prompted us to investigate a series of 21 low-grade adipocytic neoplasms with a pleomorphic lipoma-like appearance, but with atypical morphologic features (including atypical spindle cells, pleomorphic [multinucleated] cells, pleomorphic lipoblasts and poor circumscription), for which we propose the term "atypical" pleomorphic lipomatous tumor (APLT). Five cases of PLS were also included in this study. We used multiplex ligation-dependent probe amplification to evaluate genetic changes of 13q14. In addition, array-based comparative genomic hybridization was performed on 4 APLTs and all PLSs. Multiplex ligation-dependent probe amplification showed consistent loss of RB1 and its flanking gene RCBTB2 in all cases of APLT. This genetic alteration was also present in all PLSs, suggesting genetic overlap, in addition to morphologic overlap, with APLTs. However, array-based comparative genomic hybridization demonstrated more complex genetic alterations with more losses and gains in PLSs compared with APLTs. APLTs arose in the subcutis (67%) more frequently than in the deep (subfascial) soft tissues (33%). With a median follow-up of 42 months, recurrences were documented in 2 of 12 APLTs for which a long follow-up was available. Herein, we also demonstrate that APLTs share obvious overlapping morphologic, immunohistochemical, genetic and clinical characteristics with the recently defined ASLT, suggesting that they are related lesions that form a spectrum (atypical spindle cell/pleomorphic lipomatous tumor).

Scintigraphic and sonographic diagnosis of neonatal mesoblastic nephroma: case report

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sacks, G.; Mitchell, M.; Fleischer, A.C.

1983-06-01

The morphologic characteristics of mesoblastic nephroma result in a scintigraphic appearance which distinguishes this benign neonatal tumor from Wilms' tumor. This case report describes a patient in whom the use of scintigraphy and real-time sonography permitted preoperative diagnosis of mesoblastic nephroma.

Mitochondrial Control by DRP1 in Brain Tumor Initiating Cells

PubMed Central

Xie, Qi; Wu, Qiulian; Horbinski, Craig M.; Flavahan, William A.; Yang, Kailin; Zhou, Wenchao; Dombrowski, Stephen M.; Huang, Zhi; Fang, Xiaoguang; Shi, Yu; Ferguson, Ashley N.; Kashatus, David F.; Bao, Shideng; Rich, Jeremy N.

2015-01-01

Brain tumor initiating cells (BTICs) coopt the neuronal high affinity GLUT3 glucose transporter to withstand metabolic stress. Here, we investigated another mechanism critical to brain metabolism, mitochondrial morphology. BTICs displayed mitochondrial fragmentation relative to non-BTICs, suggesting that BTICs have increased mitochondrial fission. The essential mediator of mitochondrial fission, dynamin-related protein 1 (DRP1), was activated in BTICs and inhibited in non-BTICs. Targeting DRP1 using RNA interference or pharmacologic inhibition induced BTIC apoptosis and inhibited tumor growth. Downstream, DRP1 activity regulated the essential metabolic stress sensor, AMP-activated protein kinase (AMPK), and AMPK targeting rescued the effects of DRP1 disruption. Cyclin-dependent kinase 5 (CDK5) phosphorylated DRP1 to increase its activity in BTICs, whereas Ca2+–calmodulin-dependent protein kinase 2 (CAMK2) inhibited DRP1 in non-BTICs, suggesting tumor cell differentiation induces a regulatory switch in mitochondrial morphology. DRP1 activation correlates with poor prognosis in glioblastoma, suggesting mitochondrial dynamics may represent a therapeutic target for BTICs. PMID:25730670

Mesenteric Primitive Myxoid Mesenchymal Tumor in a 7-Month-Old Boy.

PubMed

Chacon, Daniella; Correa, Catalina; Luengas, Juan P

2018-05-01

Mesenteric tumors are rare, especially in the pediatric population. We present a case of a 7-month-old boy with an incidental abdominal mass identified as a Primitive Myxoid Mesenchymal Tumor of Infancy derived from the small bowel mesentery. This neoplasm is part of a spectrum of myofibroblastic lesions, with distinct clinical, morphologic, IHQ reactivity, and an aggressive clinical course. There is a paucity of evidence for the management of these tumors, and surgical resection remains the mainstay of treatment.

Feline vaccine-associated fibrosarcoma: morphologic distinctions.

PubMed

Couto, S S; Griffey, S M; Duarte, P C; Madewell, B R

2002-01-01

Forty-four primary feline vaccine-associated fibrosarcomas and 16 recurrences were examined histologically for detailed morphologic characterization with emphasis on tumor grade, presence of neoplastic multinucleated giant cells, presence and proportion of T and B lymphocytes within the tumor, and thin and intermediate filament contents of neoplastic and stromal cells. The microvascularity and proliferation rates of central and peripheral areas of the tumors were also quantified by computerized image analysis. For primary fibrosarcomas, 11 of 44 (25%) were grade I, 21 of 44 (47.7%) were grade II, and 12 of 44 (27.3%) were grade III. The recurrences followed a similar pattern: 4 of 16 (25%) were grade I, 8 of 16 (50%) were grade II, and 4 of 16 (25%) were grade III. A positive correlation was found between the presence of neoplastic multinucleated giant cells and tumor grade. These cells were present in 9 of 12 (75%) of grade III and none of the grade I tumors. Prominent peritumoral lymphoid aggregates or follicles were present in 59% of the tumors, and many contained high proportions of T lymphocytes, varying from 19 to 87%. All fibrosarcomas were immunoreactive for vimentin and 28 of 44 (64%) were reactive for alpha-smooth muscle actin. The actin-positive cells were either part of the tumor or formed a capsule around tumor nodules. The peripheral vascularity was significantly higher than the central vascular density but no difference was found in tumor cell proliferation rates between the two areas. Centrally located, fluid-filled micro- or macrocavitations were frequently observed in the large vaccine sarcomas and probably formed secondary to rapid tumor growth and central necrosis.

Developmental studies of the lamprey and hierarchical evolutionary steps towards the acquisition of the jaw

PubMed Central

Kuratani, Shigeru

2005-01-01

The evolution of animal morphology can be understood as a series of changes in developmental programs. Among vertebrates, some developmental stages are conserved across species, representing particular developmental constraints. One of the most conserved stages is the vertebrate pharyngula, in which similar embryonic morphology is observed and the Hox code is clearly expressed. The oral developmental program also appears to be constrained to some extent, as both its morphology and the the Hox-code-default state of the oropharyngeal region are well conserved between the lamprey and gnathostome embryos. These features do not by themselves explain the evolution of jaws, but should be regarded as a prerequisite for evolutionary diversification of the mandibular arch. By comparing the pharyngula morphology of the lamprey and gnathostomes, it has become clear that the oral pattern is not entirely identical; in particular, the positional differentiation of the rostral ectomesenchyme is shifted between these animals. Therefore, the jaw seems to have arisen as an evolutionary novelty by overriding ancestral constraints, a process in which morphological homologies are partially lost. This change involves the heterotopic shift of tissue interaction, which appears to have been preceded by the transition from monorhiny to diplorhiny, as well as separation of the hypophysis. When gene expression patterns are compared between the lamprey and gnathostomes, cell-autonomously functioning genes tend to be associated with identical cell types or equivalent anatomical domains, whereas growth-factor-encoding genes have changed their expression domains during evolution. Thus, the heterotopic evolution may be based on changes in the regulation of signalling-molecule-encoding genes. PMID:16313390

New insights into the earliest stages of colorectal tumorigenesis.

PubMed

Sievers, Chelsie K; Grady, William M; Halberg, Richard B; Pickhardt, Perry J

2017-08-01

Tumors in the large intestine have been postulated to arise via a stepwise accumulation of mutations, a process that takes up to 20 years. Recent advances in lineage tracing and DNA sequencing, however, are revealing new evolutionary models that better explain the vast amount of heterogeneity observed within and across colorectal tumors. Areas covered: A review of the literature supporting a novel model of colorectal tumor evolution was conducted. The following commentary examines the basic science and clinical evidence supporting a modified view of tumor initiation and progression in the colon. Expert commentary: The proposed 'cancer punctuated equilibrium' model of tumor evolution better explains the variability seen within and across polyps of the colon and rectum. Small colorectal polyps (6-9mm) followed longitudinally by interval imaging with CT colonography have been reported to have multiple fates: some growing, some remaining static in size, and others regressing in size over time. This new model allows for this variability in growth behavior and supports the hypothesis that some tumors can be 'born to be bad' as originally postulated by Sottoriva and colleagues, with very early molecular events impacting tumor fitness and growth behavior in the later stages of the disease process.

Hepatocellular carcinoma arising in adenoma: similar immunohistochemical and cytogenetic features in adenoma and hepatocellular carcinoma portions of the tumor

PubMed Central

Paradis, Valerie; Pote, Nicolas; Jakate, Shriram; Ferrell, Linda D

2016-01-01

Well-differentiated hepatocellular carcinoma in non-cirrhotic liver can show morphological features similar to hepatocellular adenoma. In rare instances, hepatocellular carcinoma can arise in the setting of hepatocellular adenoma. This study compares the immunohistochemical and cytogenetic features of the hepatocellular adenoma-like and hepatocellular carcinoma portions of these tumors. Immunohistochemistry for β-catenin, glutamine synthetase, serum amyloid A protein, glypican-3, and heat-shock protein 70 was done in 11 cases of hepatocellular carcinoma arising in hepatocellular adenoma in non-cirrhotic liver. Tumors with nuclear β-catenin and/or diffuse glutamine synthetase were considered β-catenin activated. Fluorescence in situ hybridization (FISH) was done in nine cases for gains of chromosomes 1, 8 and MYC. There were seven men (33–75 years) and four women (29–65 years). Focal atypical morphological features were seen in hepatocellular adenoma-like areas in 7 (64%) cases. Hepatocellular adenoma-like areas showed features of inflammatory hepatocellular adenoma in 7 (64%) cases; 4 of these were also serum amyloid A-positive in the hepatocellular carcinoma portion. β-catenin activation, heat-shock protein 70 positivity, and chromosomal gains on FISH were seen in the hepatocellular adenoma portion in 55%, 40%, and 56% of cases, and 73%, 60%, and 78% of cases in the hepatocellular carcinoma portion, respectively. In conclusion, the hepatocellular adenoma-like portion of most cases of hepatocellular carcinoma arising in hepatocellular adenoma shows features typically seen in hepatocellular carcinoma such as focal morphological abnormalities, β-catenin activation, heat-shock protein 70 expression, and chromosomal gains. Hepatocellular adenoma-like areas in these tumors, especially in men and older women, may represent an extremely well-differentiated variant of hepatocellular carcinoma, whereas the morphologically recognizable hepatocellular carcinoma portion represents a relatively higher grade component of the tumor. PMID:24743216

Clinicopathological analysis of endometrial carcinomas harboring somatic POLE exonuclease domain mutations.

PubMed

Hussein, Yaser R; Weigelt, Britta; Levine, Douglas A; Schoolmeester, J Kenneth; Dao, Linda N; Balzer, Bonnie L; Liles, Georgia; Karlan, Beth; Köbel, Martin; Lee, Cheng-Han; Soslow, Robert A

2015-04-01

The Cancer Genome Atlas described four major genomic groups of endometrial carcinomas, including a POLE ultramutated subtype comprising ∼10% of endometrioid adenocarcinoma, characterized by POLE exonuclease domain mutations, ultrahigh somatic mutation rates, and favorable outcome. Our aim was to examine the morphological and clinicopathological features of ultramutated endometrial carcinomas harboring somatic POLE exonuclease domain mutations. Hematoxylin and eosin slides and pathology reports for 8/17 POLE-mutated endometrial carcinomas described in the Cancer Genome Atlas study were studied; for the remaining cases, virtual whole slide images publicly available at cBioPortal (www.cbioportal.org) were examined. A second cohort of eight POLE mutated endometrial carcinomas from University of Calgary was also studied. Median age was 55 years (range 33-87 years). Nineteen patients presented as stage I, 1 stage II, and 5 stage III. The majority of cases (24 of the 25) demonstrated defining morphological features of endometrioid differentiation. The studied cases were frequently high grade (60%) and rich in tumor-infiltrating lymphocytes and/or peri-tumoral lymphocytes (84%); many tumors showed morphological heterogeneity (52%) and ambiguity (16%). Foci demonstrating severe nuclear atypia led to concern for serous carcinoma in 28% of cases. At the molecular level, the majority of the Cancer Genome Atlas POLE-mutated tumors were microsatellite stable (65%), and TP53 mutations were present in 35% of cases. They also harbored mutations in PTEN (94%), FBXW7 (82%), ARID1A (76%), and PIK3CA (71%). All patients from both cohorts were alive without disease, and none of the patients developed recurrence at the time of follow-up (median 33 months; range 2-102 months). In conclusion, the recognition of ultramutated endometrial carcinomas with POLE exonuclease domain mutation is important given their favorable outcome. Our histopathological review revealed that these tumors are commonly high grade, have obvious lymphocytic infiltrates, and can show ambiguous morphology. As they frequently harbor TP53 mutations, it is important not to misclassify them as serous carcinoma.

Intratumor DNA methylation heterogeneity reflects clonal evolution in aggressive prostate cancer.

PubMed

Brocks, David; Assenov, Yassen; Minner, Sarah; Bogatyrova, Olga; Simon, Ronald; Koop, Christina; Oakes, Christopher; Zucknick, Manuela; Lipka, Daniel Bernhard; Weischenfeldt, Joachim; Feuerbach, Lars; Cowper-Sal Lari, Richard; Lupien, Mathieu; Brors, Benedikt; Korbel, Jan; Schlomm, Thorsten; Tanay, Amos; Sauter, Guido; Gerhäuser, Clarissa; Plass, Christoph

2014-08-07

Despite much evidence on epigenetic abnormalities in cancer, it is currently unclear to what extent epigenetic alterations can be associated with tumors' clonal genetic origins. Here, we show that the prostate intratumor heterogeneity in DNA methylation and copy-number patterns can be explained by a unified evolutionary process. By assaying multiple topographically distinct tumor sites, premalignant lesions, and lymph node metastases within five cases of prostate cancer, we demonstrate that both DNA methylation and copy-number heterogeneity consistently reflect the life history of the tumors. Furthermore, we show cases of genetic or epigenetic convergent evolution and highlight the diversity in the evolutionary origins and aberration spectrum between tumor and metastatic subclones. Importantly, DNA methylation can complement genetic data by serving as a proxy for activity at regulatory domains, as we show through identification of high epigenetic heterogeneity at androgen-receptor-bound enhancers. Epigenome variation thereby expands on the current genome-centric view on tumor heterogeneity. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

Deterministic Evolutionary Trajectories Influence Primary Tumor Growth: TRACERx Renal.

PubMed

Turajlic, Samra; Xu, Hang; Litchfield, Kevin; Rowan, Andrew; Horswell, Stuart; Chambers, Tim; O'Brien, Tim; Lopez, Jose I; Watkins, Thomas B K; Nicol, David; Stares, Mark; Challacombe, Ben; Hazell, Steve; Chandra, Ashish; Mitchell, Thomas J; Au, Lewis; Eichler-Jonsson, Claudia; Jabbar, Faiz; Soultati, Aspasia; Chowdhury, Simon; Rudman, Sarah; Lynch, Joanna; Fernando, Archana; Stamp, Gordon; Nye, Emma; Stewart, Aengus; Xing, Wei; Smith, Jonathan C; Escudero, Mickael; Huffman, Adam; Matthews, Nik; Elgar, Greg; Phillimore, Ben; Costa, Marta; Begum, Sharmin; Ward, Sophia; Salm, Max; Boeing, Stefan; Fisher, Rosalie; Spain, Lavinia; Navas, Carolina; Grönroos, Eva; Hobor, Sebastijan; Sharma, Sarkhara; Aurangzeb, Ismaeel; Lall, Sharanpreet; Polson, Alexander; Varia, Mary; Horsfield, Catherine; Fotiadis, Nicos; Pickering, Lisa; Schwarz, Roland F; Silva, Bruno; Herrero, Javier; Luscombe, Nick M; Jamal-Hanjani, Mariam; Rosenthal, Rachel; Birkbak, Nicolai J; Wilson, Gareth A; Pipek, Orsolya; Ribli, Dezso; Krzystanek, Marcin; Csabai, Istvan; Szallasi, Zoltan; Gore, Martin; McGranahan, Nicholas; Van Loo, Peter; Campbell, Peter; Larkin, James; Swanton, Charles

2018-04-19

The evolutionary features of clear-cell renal cell carcinoma (ccRCC) have not been systematically studied to date. We analyzed 1,206 primary tumor regions from 101 patients recruited into the multi-center prospective study, TRACERx Renal. We observe up to 30 driver events per tumor and show that subclonal diversification is associated with known prognostic parameters. By resolving the patterns of driver event ordering, co-occurrence, and mutual exclusivity at clone level, we show the deterministic nature of clonal evolution. ccRCC can be grouped into seven evolutionary subtypes, ranging from tumors characterized by early fixation of multiple mutational and copy number drivers and rapid metastases to highly branched tumors with >10 subclonal drivers and extensive parallel evolution associated with attenuated progression. We identify genetic diversity and chromosomal complexity as determinants of patient outcome. Our insights reconcile the variable clinical behavior of ccRCC and suggest evolutionary potential as a biomarker for both intervention and surveillance. Copyright © 2018 Francis Crick Institute. Published by Elsevier Inc. All rights reserved.

The effect of bedload transport rates on bedform and planform morphological development in a laboratory meandering stream under varying flow conditions

NASA Astrophysics Data System (ADS)

Sullivan, C.; Good, R. G. R.; Binns, A. D.

2017-12-01

Sediment transport processes in streams provides valuable insight into the temporal evolution of planform and bedform geometry. The majority of previous experimental research in the literature has focused on bedload transport and corresponding bedform development in rectangular, confined channels, which does not consider planform adjustment processes in streams. In contrast, research conducted with laboratory streams having movable banks can investigate planform development in addition to bedform development, which is more representative of natural streams. The goal of this research is to explore the relationship between bedload transport rates and the morphological adjustments in meandering streams. To accomplish this, a series of experimental runs were conducted in a 5.6 m by 1.9 m river basin flume at the University of Guelph to analyze the bedload impacts on bed formations and planform adjustments in response to varying flow conditions. In total, three experimental runs were conducted: two runs using steady state conditions and one run using unsteady flow conditions in the form of a symmetrical hydrograph implementing quasi steady state flow. The runs were performed in a series of time-steps in order to monitor the evolution of the stream morphology and the bedload transport rates. Structure from motion (SfM) was utilized to capture the channel morphology after each time-step, and Agisoft PhotoScan software was used to produce digital elevation models to analyze the morphological evolution of the channel with time. Bedload transport rates were quantified using a sediment catch at the end of the flume. Although total flow volumes were similar for each run, the morphological evolution and bedload transport rates in each run varied. The observed bedload transport rates from the flume are compared with existing bedload transport formulas to assess their accuracy with respect to sediment transport in unconfined meandering channels. The measured sediment transport rates varied from the existing equations, which can be attributed to the sediment characteristics, planform morphology and bed formations. The results from this research provide greater knowledge of morphological processes in natural meandering streams to improve the capabilities of computational modelling and river engineering practice.

The role of calcium and predation on plate morph evolution in the three-spined stickleback (Gasterosteus aculeatus).

PubMed

Smith, Carl; Spence, Rowena; Barber, Iain; Przybylski, Mirosław; Wootton, Robert J

2014-09-01

While the genetic basis to plate morph evolution of the three-spined stickleback (Gasterosteus aculeatus) is well described, the environmental variables that select for different plate and spine morphs are incompletely understood. Using replicate populations of three-spined sticklebacks on North Uist, Scotland, we previously investigated the role of predation pressure and calcium limitation on the adaptive evolution of stickleback morphology and behavior. While dissolved calcium proved a significant predictor of plate and spine morph, predator abundance did not. Ecol. Evol., xxx, 2014 and xxx performed a comparable analysis to our own to address the same question. They failed to detect a significant effect of dissolved calcium on morphological evolution, but did establish a significant effect of predation; albeit in the opposite direction to their prediction.

The morphologies of breast cancer cell lines in three-dimensionalassays correlate with their profiles of gene expression

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kenny, Paraic A.; Lee, Genee Y.; Myers, Connie A.

2007-01-31

3D cell cultures are rapidly becoming the method of choice for the physiologically relevant modeling of many aspects of non-malignant and malignant cell behavior ex vivo. Nevertheless, only a limited number of distinct cell types have been evaluated in this assay to date. Here we report the first large scale comparison of the transcriptional profiles and 3D cell culture phenotypes of a substantial panel of human breast cancer cell lines. Each cell line adopts a colony morphology of one of four main classes in 3D culture. These morphologies reflect, at least in part, the underlying gene expression profile and proteinmore » expression patterns of the cell lines, and distinct morphologies were also associated with tumor cell invasiveness and with cell lines originating from metastases. We further demonstrate that consistent differences in genes encoding signal transduction proteins emerge when even tumor cells are cultured in 3D microenvironments.« less

Decoupled diversification dynamics of feeding morphology following a major functional innovation in marine butterflyfishes.

PubMed

Konow, Nicolai; Price, Samantha; Abom, Richard; Bellwood, David; Wainwright, Peter

2017-08-16

The diversity of fishes on coral reefs is influenced by the evolution of feeding innovations. For instance, the evolution of an intramandibular jaw joint has aided shifts to corallivory in Chaetodon butterflyfishes following their Miocene colonization of coral reefs. Today, over half of all Chaetodon species consume coral, easily the largest concentration of corallivores in any reef fish family. In contrast with Chaetodon , other chaetodontids, including the long-jawed bannerfishes, remain less intimately associated with coral and mainly consume other invertebrate prey. Here, we test (i) if intramandibular joint (IMJ) evolution in Chaetodon has accelerated feeding morphological diversification, and (ii) if cranial and post-cranial traits were affected similarly. We measured 19 cranial functional morphological traits, gut length and body elongation for 33 Indo-Pacific species. Comparisons of Brownian motion rate parameters revealed that cranial diversification was about four times slower in Chaetodon butterflyfishes with the IMJ than in other chaetodontids. However, the rate of gut length evolution was significantly faster in Chaetodon , with no group-differences for body elongation. The contrasting patterns of cranial and post-cranial morphological evolution stress the importance of comprehensive datasets in ecomorphology. The IMJ appears to enhance coral feeding ability in Chaetodon and represents a design breakthrough that facilitates this trophic strategy. Meanwhile, variation in gut anatomy probably reflects diversity in how coral tissues are procured and assimilated. Bannerfishes, by contrast, retain a relatively unspecialized gut for processing invertebrate prey, but have evolved some of the most extreme cranial mechanical innovations among bony fishes for procuring elusive prey. © 2017 The Author(s).

Ancestral State Reconstruction Reveals Rampant Homoplasy of Diagnostic Morphological Characters in Urticaceae, Conflicting with Current Classification Schemes

PubMed Central

Wu, Zeng-Yuan; Milne, Richard I.; Chen, Chia-Jui; Liu, Jie; Wang, Hong; Li, De-Zhu

2015-01-01

Urticaceae is a family with more than 2000 species, which contains remarkable morphological diversity. It has undergone many taxonomic reorganizations, and is currently the subject of further systematic studies. To gain more resolution in systematic studies and to better understand the general patterns of character evolution in Urticaceae, based on our previous phylogeny including 169 accessions comprising 122 species across 47 Urticaceae genera, we examined 19 diagnostic characters, and analysed these employing both maximum-parsimony and maximum-likelihood approaches. Our results revealed that 16 characters exhibited multiple state changes within the family, with ten exhibiting >eight changes and three exhibiting between 28 and 40. Morphological synapomorphies were identified for many clades, but the diagnostic value of these was often limited due to reversals within the clade and/or homoplasies elsewhere. Recognition of the four clades comprising the family at subfamily level can be supported by a small number carefully chosen defining traits for each. Several non-monophyletic genera appear to be defined only by characters that are plesiomorphic within their clades, and more detailed work would be valuable to find defining traits for monophyletic clades within these. Some character evolution may be attributed to adaptive evolution in Urticaceae due to shifts in habitat or vegetation type. This study demonstrated the value of using phylogeny to trace character evolution, and determine the relative importance of morphological traits for classification. PMID:26529598

Morphology and behaviour: functional links in development and evolution

PubMed Central

Bertossa, Rinaldo C.

2011-01-01

Development and evolution of animal behaviour and morphology are frequently addressed independently, as reflected in the dichotomy of disciplines dedicated to their study distinguishing object of study (morphology versus behaviour) and perspective (ultimate versus proximate). Although traits are known to develop and evolve semi-independently, they are matched together in development and evolution to produce a unique functional phenotype. Here I highlight similarities shared by both traits, such as the decisive role played by the environment for their ontogeny. Considering the widespread developmental and functional entanglement between both traits, many cases of adaptive evolution are better understood when proximate and ultimate explanations are integrated. A field integrating these perspectives is evolutionary developmental biology (evo-devo), which studies the developmental basis of phenotypic diversity. Ultimate aspects in evo-devo studies—which have mostly focused on morphological traits—could become more apparent when behaviour, ‘the integrator of form and function’, is integrated into the same framework of analysis. Integrating a trait such as behaviour at a different level in the biological hierarchy will help to better understand not only how behavioural diversity is produced, but also how levels are connected to produce functional phenotypes and how these evolve. A possible framework to accommodate and compare form and function at different levels of the biological hierarchy is outlined. At the end, some methodological issues are discussed. PMID:21690124

Iterative adaptive radiations of fossil canids show no evidence for diversity-dependent trait evolution.

PubMed

Slater, Graham J

2015-04-21

A long-standing hypothesis in adaptive radiation theory is that ecological opportunity constrains rates of phenotypic evolution, generating a burst of morphological disparity early in clade history. Empirical support for the early burst model is rare in comparative data, however. One possible reason for this lack of support is that most phylogenetic tests have focused on extant clades, neglecting information from fossil taxa. Here, I test for the expected signature of adaptive radiation using the outstanding 40-My fossil record of North American canids. Models implying time- and diversity-dependent rates of morphological evolution are strongly rejected for two ecologically important traits, body size and grinding area of the molar teeth. Instead, Ornstein-Uhlenbeck processes implying repeated, and sometimes rapid, attraction to distinct dietary adaptive peaks receive substantial support. Diversity-dependent rates of morphological evolution seem uncommon in clades, such as canids, that exhibit a pattern of replicated adaptive radiation. Instead, these clades might best be thought of as deterministic radiations in constrained Simpsonian subzones of a major adaptive zone. Support for adaptive peak models may be diagnostic of subzonal radiations. It remains to be seen whether early burst or ecological opportunity models can explain broader adaptive radiations, such as the evolution of higher taxa.

Evidence for the involvement of Globosa-like gene duplications and expression divergence in the evolution of floral morphology in the Zingiberales.

PubMed

Bartlett, Madelaine E; Specht, Chelsea D

2010-07-01

*The MADS box transcription factor family has long been identified as an important contributor to the control of floral development. It is often hypothesized that the evolution of floral development across angiosperms and within specific lineages may occur as a result of duplication, functional diversification, and changes in regulation of MADS box genes. Here we examine the role of Globosa (GLO)-like genes, members of the B-class MADS box gene lineage, in the evolution of floral development within the monocot order Zingiberales. *We assessed changes in perianth and stamen whorl morphology in a phylogenetic framework. We identified GLO homologs (ZinGLO1-4) from 50 Zingiberales species and investigated the evolution of this gene lineage. Expression of two GLO homologs was assessed in Costus spicatus and Musa basjoo. *Based on the phylogenetic data and expression results, we propose several family-specific losses and gains of GLO homologs that appear to be associated with key morphological changes. The GLO-like gene lineage has diversified concomitant with the evolution of the dimorphic perianth and the staminodial labellum. *Duplications and expression divergence within the GLO-like gene lineage may have played a role in floral diversification in the Zingiberales.

Iterative adaptive radiations of fossil canids show no evidence for diversity-dependent trait evolution

NASA Astrophysics Data System (ADS)

Slater, Graham J.

2015-04-01

A long-standing hypothesis in adaptive radiation theory is that ecological opportunity constrains rates of phenotypic evolution, generating a burst of morphological disparity early in clade history. Empirical support for the early burst model is rare in comparative data, however. One possible reason for this lack of support is that most phylogenetic tests have focused on extant clades, neglecting information from fossil taxa. Here, I test for the expected signature of adaptive radiation using the outstanding 40-My fossil record of North American canids. Models implying time- and diversity-dependent rates of morphological evolution are strongly rejected for two ecologically important traits, body size and grinding area of the molar teeth. Instead, Ornstein-Uhlenbeck processes implying repeated, and sometimes rapid, attraction to distinct dietary adaptive peaks receive substantial support. Diversity-dependent rates of morphological evolution seem uncommon in clades, such as canids, that exhibit a pattern of replicated adaptive radiation. Instead, these clades might best be thought of as deterministic radiations in constrained Simpsonian subzones of a major adaptive zone. Support for adaptive peak models may be diagnostic of subzonal radiations. It remains to be seen whether early burst or ecological opportunity models can explain broader adaptive radiations, such as the evolution of higher taxa.

Evolution of extreme body size disparity in monitor lizards (Varanus).

PubMed

Collar, David C; Schulte, James A; Losos, Jonathan B

2011-09-01

Many features of species' biology, including life history, physiology, morphology, and ecology are tightly linked to body size. Investigation into the causes of size divergence is therefore critical to understanding the factors shaping phenotypic diversity within clades. In this study, we examined size evolution in monitor lizards (Varanus), a clade that includes the largest extant lizard species, the Komodo dragon (V. komodoensis), as well as diminutive species that are nearly four orders of magnitude smaller in adult body mass. We demonstrate that the remarkable body size disparity of this clade is a consequence of different selective demands imposed by three major habitat use patterns-arboreality, terrestriality, and rock-dwelling. We reconstructed phylogenetic relationships and ancestral habitat use and applied model selection to determine that the best-fitting evolutionary models for species' adult size are those that infer oppositely directed adaptive evolution associated with terrestriality and rock-dwelling, with terrestrial lineages evolving extremely large size and rock-dwellers becoming very small. We also show that habitat use affects the evolution of several ecologically important morphological traits independently of body size divergence. These results suggest that habitat use exerts a strong, multidimensional influence on the evolution of morphological size and shape disparity in monitor lizards. © 2011 The Author(s).

From forest and agro-ecosystems to the microecosystems of the human body: what can landscape ecology tell us about tumor growth, metastasis, and treatment options?

PubMed

Daoust, Simon P; Fahrig, Lenore; Martin, Amanda E; Thomas, Frédéric

2013-01-01

Cancer is now understood to be a process that follows Darwinian evolution. Heterogeneous populations of cancerous cells that make up the tumor inhabit the tissue 'microenvironment', where ecological interactions analogous to predation and competition for resources drive the somatic evolution of cancer. The tumor microenvironment plays a crucial role in the tumor genesis, development, and metastasis processes, as it creates the microenvironmental selection forces that ultimately determine the cellular characteristics that result in the greatest fitness. Here, we explore and offer new insights into the spatial aspects of tumor-microenvironment interactions through the application of landscape ecology theory to tumor growth and metastasis within the tissue microhabitat. We argue that small tissue microhabitats in combination with the spatial distribution of resources within these habitats could be important selective forces driving tumor invasiveness. We also contend that the compositional and configurational heterogeneity of components in the tissue microhabitat do not only influence resource availability and functional connectivity but also play a crucial role in facilitating metastasis and may serve to explain, at least in part, tissue tropism in certain cancers. This novel work provides a compelling argument for the necessity of taking into account the structure of the tissue microhabitat when investigating tumor progression.

Quantification of tumor morphology via 3D histology: application to oral cavity cancers

NASA Astrophysics Data System (ADS)

Doyle, Scott; Brandwein-Gensler, Margaret; Tomaszewski, John

2016-03-01

Traditional histopathology quantifies disease through the study of glass slides, i.e. two-dimensional samples that are representative of the overall process. We hypothesize that 3D reconstruction can enhance our understanding of histopathologic interpretations. To test this hypothesis, we perform a pilot study of the risk model for oral cavity cancer (OCC), which stratifies patients into low-, intermediate-, and high-risk for locoregional disease-free survival. Classification is based on study of hematoxylin and eosin (H and E) stained tissues sampled from the resection specimens. In this model, the Worst Pattern of Invasion (WPOI) is assessed, representing specific architectural features at the interface between cancer and non-cancer tissue. Currently, assessment of WPOI is based on 2D sections of tissue, representing complex 3D structures of tumor growth. We believe that by reconstructing a 3D model of tumor growth and quantifying the tumor-host interface, we can obtain important diagnostic information that is difficult to assess in 2D. Therefore, we introduce a pilot study framework for visualizing tissue architecture and morphology in 3D from serial sections of histopathology. This framework can be used to enhance predictive models for diseases where severity is determined by 3D biological structure. In this work we utilize serial H and E-stained OCC resections obtained from 7 patients exhibiting WPOI-3 (low risk of recurrence) through WPOI-5 (high risk of recurrence). A supervised classifier automatically generates a map of tumor regions on each slide, which are then co-registered using an elastic deformation algorithm. A smooth 3D model of the tumor region is generated from the registered maps, which is suitable for quantitative tumor interface morphology feature extraction. We report our preliminary models created with this system and suggest further enhancements to traditional histology scoring mechanisms that take spatial architecture into consideration.

The secret origins and surprising fates of pancreas tumors

PubMed Central

Bailey, Jennifer M.; DelGiorno, Kathleen E.; Crawford, Howard C.

2014-01-01

Pancreatic ductal adenocarcinoma (PDA) is especially deadly due to its recalcitrance to current therapies. One of the unique qualities of PDA that may contribute to this resistance is a striking plasticity of differentiation states starting at tumor formation and continuing throughout tumor progression, including metastasis. Here, we explore the earliest steps of tumor formation and neoplastic progression and how this results in a fascinating cellular heterogeneity that is probably critical for tumor survival and progression. We hypothesize that reinforcing differentiation pathways run awry or targeting morphologically and molecularly distinct tumor stem-like cells may hold promise for future treatments of this deadly disease. PMID:24583923

Feline vaccine-associated fibrosarcoma: an ultrastructural study of 20 tumors (1996-1999).

PubMed

Madewell, B R; Griffey, S M; McEntee, M C; Leppert, V J; Munn, R J

2001-03-01

Twenty feline vaccine-associated sarcomas were examined by transmission electron microscopy. Tumors contained pleomorphic spindle cells, histiocytoid cells, and giant cells. Most tumors contained myofibroblasts, which had morphologic features similar to those of fibroblasts. These cells were further distinguished by subplasmalemmal dense plaques and thin cytoplasmic actin myofilaments organized as elongated bundles concentrated at irregular intervals forming characteristic dense bodies. Intracellular crystalline particulate material was found in 5 of the 20 tumors. Energy dispersive X-ray spectroscopy was used to identify the crystalline material within one tumor as aluminum-based. One tumor from a feline leukemia virus-infected cat contained budding and immature retroviral particles.

How cancer shapes evolution, and how evolution shapes cancer

PubMed Central

Casás-Selves, Matias; DeGregori, James

2013-01-01

Evolutionary theories are critical for understanding cancer development at the level of species as well as at the level of cells and tissues, and for developing effective therapies. Animals have evolved potent tumor suppressive mechanisms to prevent cancer development. These mechanisms were initially necessary for the evolution of multi-cellular organisms, and became even more important as animals evolved large bodies and long lives. Indeed, the development and architecture of our tissues were evolutionarily constrained by the need to limit cancer. Cancer development within an individual is also an evolutionary process, which in many respects mirrors species evolution. Species evolve by mutation and selection acting on individuals in a population; tumors evolve by mutation and selection acting on cells in a tissue. The processes of mutation and selection are integral to the evolution of cancer at every step of multistage carcinogenesis, from tumor genesis to metastasis. Factors associated with cancer development, such as aging and carcinogens, have been shown to promote cancer evolution by impacting both mutation and selection processes. While there are therapies that can decimate a cancer cell population, unfortunately, cancers can also evolve resistance to these therapies, leading to the resurgence of treatment-refractory disease. Understanding cancer from an evolutionary perspective can allow us to appreciate better why cancers predominantly occur in the elderly, and why other conditions, from radiation exposure to smoking, are associated with increased cancers. Importantly, the application of evolutionary theory to cancer should engender new treatment strategies that could better control this dreaded disease. PMID:23705033

High-temperature morphological evolution of lithographically introduced cavities in silicon carbide

DOE Office of Scientific and Technical Information (OSTI.GOV)

Narushima, Takayuki; Glaeser, Andreas M.

2000-12-01

Internal cavities of controlled geometry and crystallography were introduced in 6H silicon carbide single crystals by combining lithographic methods, ion beam etching, and solid-state diffusion bonding. The morphological evolution of these internal cavities (negative crystals) in response to anneals of up to 128 h duration at 1900 degrees C was examined using optical microscopy. Surface energy anisotropy and faceting have a strong influence on both the geometric and kinetic characteristics of evolution. Decomposition of 12{bar 1}0 cavity edges into 101{bar 0} facets was observed after 16 h anneals, indicating that 12{bar 1}0 faces are not components of the Wulff shape.more » The shape evolution kinetics of penny-shaped cavities were also investigated. Experimentally observed evolution rates decreased much more rapidly with those predicted by a model in which surface diffusion is assumed to be rate-limiting. This suggests that the development of facets, and the associated loss of ledges and terraces during the initial stages of evolution results in an evolution process limited by the nucleation rate of attachment/detachment sites (ledges) on the facets.« less

The First Molecular Phylogeny of Strepsiptera (Insecta) Reveals an Early Burst of Molecular Evolution Correlated with the Transition to Endoparasitism

PubMed Central

McMahon, Dino P.; Hayward, Alexander; Kathirithamby, Jeyaraney

2011-01-01

A comprehensive model of evolution requires an understanding of the relationship between selection at the molecular and phenotypic level. We investigate this in Strepsiptera, an order of endoparasitic insects whose evolutionary biology is poorly studied. We present the first molecular phylogeny of Strepsiptera, and use this as a framework to investigate the association between parasitism and molecular evolution. We find evidence of a significant burst in the rate of molecular evolution in the early history of Strepsiptera. The evolution of morphological traits linked to parasitism is significantly correlated with the pattern in molecular rate. The correlated burst in genotypic-phenotypic evolution precedes the main phase of strepsipteran diversification, which is characterised by the return to a low and even molecular rate, and a period of relative morphological stability. These findings suggest that the transition to endoparasitism led to relaxation of selective constraint in the strepsipteran genome. Our results indicate that a parasitic lifestyle can affect the rate of molecular evolution, although other causal life-history traits correlated with parasitism may also play an important role. PMID:21738621

A subserosal, pedunculated, multilocular uterine leiomyoma with ovarian tumor-like morphology and histological architecture of adenomatoid tumors: a case report and review of the literature.

PubMed

Yorita, Kenji; Tanaka, Yu; Hirano, Koki; Kai, Yuka; Arii, Kaoru; Nakatani, Kimiko; Ito, Satoshi; Imai, Toshiya; Fukunaga, Masaharu; Kuroda, Naoto

2016-12-20

Uterine leiomyomas are common uterine tumors, and typical cases of leiomyoma are easily diagnosed by imaging study. However, uterine leiomyomas are often altered by degenerative changes, which can cause difficulty and confusion in their clinical diagnosis. We describe the 17th reported case of a uterine leiomyoma clinically diagnosed as an ovarian tumor; however, the present case shows the most detailed radiological evaluation, including contrast-enhanced magnetic resonance imaging. We first show that a uterine leiomyoma can histologically mimic an adenomatoid tumor. A 47-year-old premenopausal, nulliparous Japanese woman with a history of type 2 diabetes mellitus, hypertension, and hyperlipidemia had lower abdominal pain. Ultrasonography confirmed a 6-cm mass in the right-sided space of the pelvic cavity. Magnetic resonance imaging evaluation showed that a multilocular mass was present near the uterus, and a mucinous ovarian tumor was considered. Emergency surgery due to acute abdomen was performed under the diagnosis of pedicle torsion of the ovarian tumor. During surgery, a pedunculated uterine mass without stalk torsion was seen. The mass grossly contained serous and hemorrhagic fluids in the cavities, and pathology examination confirmed that the mass was a leiomyoma with hydropic and cystic degeneration. Anastomosing thin cord-like arrangements of the leiomyoma cells mimicked the architecture of adenomatoid tumors. The tumor cells were positive for the microphthalmia transcription factor but negative for other melanoma markers. Three days postoperatively, she was discharged without sequelae. Marked intratumoral deposition of fluids may induce the multilocular morphology of a tumor, and the cellular arrangement of the tumor cells with hydropic degeneration mimicked an adenomatoid tumor in this case. Clinicians need to be aware that a subserosal leiomyoma with cystic and hydropic degeneration can mimic an ovarian tumor, and pathologists should be aware that such leiomyomas can mimic adenomatoid tumors. Additionally, perivascular epithelioid cell tumors should not be diagnosed only based on its immunoreactivity for the microphthalmia transcription factor.

Receptor Tyrosine Kinases as Targets for Treatment of Peripheral Nerve Sheath Tumors in NF 1 Patients

DTIC Science & Technology

2007-03-01

EGFR patterns by interphase cytogenetics (FISH) in malignant peripheral nerve sheath tumor (MPNST) and morphologically similar spindle cell neoplasms ...Armstrong,F., Delsol,G., Dastugue,N. and Brousset,P. (2003) Chronic myeloproliferative disorders with rearrangement of the platelet-derived growth

Distinct biological subtypes and patterns of genome evolution in lymphoma revealed by circulating tumor DNA.

PubMed

Scherer, Florian; Kurtz, David M; Newman, Aaron M; Stehr, Henning; Craig, Alexander F M; Esfahani, Mohammad Shahrokh; Lovejoy, Alexander F; Chabon, Jacob J; Klass, Daniel M; Liu, Chih Long; Zhou, Li; Glover, Cynthia; Visser, Brendan C; Poultsides, George A; Advani, Ranjana H; Maeda, Lauren S; Gupta, Neel K; Levy, Ronald; Ohgami, Robert S; Kunder, Christian A; Diehn, Maximilian; Alizadeh, Ash A

2016-11-09

Patients with diffuse large B cell lymphoma (DLBCL) exhibit marked diversity in tumor behavior and outcomes, yet the identification of poor-risk groups remains challenging. In addition, the biology underlying these differences is incompletely understood. We hypothesized that characterization of mutational heterogeneity and genomic evolution using circulating tumor DNA (ctDNA) profiling could reveal molecular determinants of adverse outcomes. To address this hypothesis, we applied cancer personalized profiling by deep sequencing (CAPP-Seq) analysis to tumor biopsies and cell-free DNA samples from 92 lymphoma patients and 24 healthy subjects. At diagnosis, the amount of ctDNA was found to strongly correlate with clinical indices and was independently predictive of patient outcomes. We demonstrate that ctDNA genotyping can classify transcriptionally defined tumor subtypes, including DLBCL cell of origin, directly from plasma. By simultaneously tracking multiple somatic mutations in ctDNA, our approach outperformed immunoglobulin sequencing and radiographic imaging for the detection of minimal residual disease and facilitated noninvasive identification of emergent resistance mutations to targeted therapies. In addition, we identified distinct patterns of clonal evolution distinguishing indolent follicular lymphomas from those that transformed into DLBCL, allowing for potential noninvasive prediction of histological transformation. Collectively, our results demonstrate that ctDNA analysis reveals biological factors that underlie lymphoma clinical outcomes and could facilitate individualized therapy. Copyright © 2016, American Association for the Advancement of Science.

The mitochondrial phylogeny of an ancient lineage of ray-finned fishes (Polypteridae) with implications for the evolution of body elongation, pelvic fin loss, and craniofacial morphology in Osteichthyes

PubMed Central

2010-01-01

Background The family Polypteridae, commonly known as "bichirs", is a lineage that diverged early in the evolutionary history of Actinopterygii (ray-finned fish), but has been the subject of far less evolutionary study than other members of that clade. Uncovering patterns of morphological change within Polypteridae provides an important opportunity to evaluate if the mechanisms underlying morphological evolution are shared among actinoptyerygians, and in fact, perhaps the entire osteichthyan (bony fish and tetrapods) tree of life. However, the greatest impediment to elucidating these patterns is the lack of a well-resolved, highly-supported phylogenetic tree of Polypteridae. In fact, the interrelationships of polypterid species have never been subject to molecular phylogenetic analysis. Here, we infer the first molecular phylogeny of bichirs, including all 12 recognized species and multiple subspecies using Bayesian analyses of 16S and cyt-b mtDNA. We use this mitochondrial phylogeny, ancestral state reconstruction, and geometric morphometrics to test whether patterns of morphological evolution, including the evolution of body elongation, pelvic fin reduction, and craniofacial morphology, are shared throughout the osteichthyan tree of life. Results Our molecular phylogeny reveals 1) a basal divergence between Erpetoichthys and Polypterus, 2) polyphyly of P. endlicheri and P. palmas, and thus 3) the current taxonomy of Polypteridae masks its underlying genetic diversity. Ancestral state reconstructions suggest that pelvic fins were lost independently in Erpetoichthys, and unambiguously estimate multiple independent derivations of body elongation and shortening. Our mitochondrial phylogeny suggested species that have lower jaw protrusion and up-righted orbit are closely related to each other, indicating a single transformation of craniofacial morphology. Conclusion The mitochondrial phylogeny of polypterid fish provides a strongly-supported phylogenetic framework for future comparative evolutionary, physiological, ecological, and genetic analyses. Indeed, ancestral reconstruction and geometric morphometric analyses revealed that the patterns of morphological evolution in Polypteridae are similar to those seen in other osteichthyans, thus implying the underlying genetic and developmental mechanisms responsible for those patterns were established early in the evolutionary history of Osteichthyes. We propose developmental and genetic mechanisms to be tested under the light of this new phylogenetic framework. PMID:20100320

Clinicopathologic Diversity of Undifferentiated Sarcoma With BCOR-CCNB3 Fusion: Analysis of 11 Cases With a Reappraisal of the Utility of Immunohistochemistry for BCOR and CCNB3.

PubMed

Matsuyama, Atsuji; Shiba, Eisuke; Umekita, Yoshihisa; Nosaka, Kanae; Kamio, Takihiro; Yanai, Hiroyuki; Miyasaka, Chika; Watanabe, Reiko; Ito, Ichiro; Tamaki, Tomoko; Hayashi, Shinichi; Hisaoka, Masanori

2017-12-01

Undifferentiated sarcoma harboring the BCOR-CCNB3 fusion is characterized by its predilection to affect skeletons of adolescent males, cellular small round/spindle cell morphology, and CCNB3 immunoreactivity. We analyzed 11 cases of BCOR-CCNB3 sarcoma, 10 of which were identified in a reverse transcription-polymerase chain reaction-based screen of 85 patient samples recorded in our database as unclassified small round or spindle cell sarcomas. BCOR rearrangements were confirmed by fluorescence in situ hybridization in 8 tumors. All patients were males aged between 6 and 31 years. In addition to 5 tumors in soft tissue and 4 in the axial or appendicular skeletons, which are typical locations, a tumor was located in the paranasal sinus and another in the lung. Microscopically, the tumors comprised proliferating atypical spindle and/or small round cells with diverse morphologic features such as small concentric whorls, myxoid stroma, a hemangiopericytomatous appearance, and/or hyalinized collagen resembling a solitary fibrous tumor, and angiomatous or slit-like spaces containing extravasated erythrocytes. Tumor cells were immunoreactive to CCNB3 (9/11), BCOR (10/10), TLE1 (6/10), bcl-2 (9/11), CD99 (8/10), CD56 (8/10), c-kit (4/10), and cyclin D1 (10/10). In an immunohistochemical analysis of an additional 412 small round or spindle cell tumors, CCNB3 was detected in 6 (1.5%) and BCOR in 18 (4.4%). Our analysis highlights the varying clinicopathologic features of this tumor, which partially overlap with other small round or spindle cell tumors, including solitary fibrous tumor and vascular tumors. Because CCNB3 and BCOR immunohistochemistry lacks adequate sensitivity and specificity, a molecular genetic approach remains essential for diagnosis.

Establishment and Characterization of Novel Human Primary and Metastatic Anaplastic Thyroid Cancer Cell Lines and Their Genomic Evolution Over a Year as a Primagraft

PubMed Central

Okamoto, Ryoko; Nagata, Yasunobu; Kanojia, Deepika; Venkatesan, Subhashree; M. T., Anand; Braunstein, Glenn D.; Said, Jonathan W.; Doan, Ngan B.; Ho, Quoc; Akagi, Tadayuki; Gery, Sigal; Liu, Li-zhen; Tan, Kar Tong; Chng, Wee Joo; Yang, Henry; Ogawa, Seishi; Koeffler, H. Phillip

2015-01-01

Context: Anaplastic thyroid cancer (ATC) has no effective treatment, resulting in a high rate of mortality. We established cell lines from a primary ATC and its lymph node metastasis, and investigated the molecular factors and genomic changes associated with tumor growth. Objective: The aim of the study was to understand the molecular and genomic changes of highly aggressive ATC and its clonal evolution to develop rational therapies. Design: We established unique cell lines from primary (OGK-P) and metastatic (OGK-M) ATC specimen, as well as primagraft from the metastatic ATC, which was serially xeno-transplanted for more than 1 year in NOD scid gamma mice were established. These cell lines and primagraft were used as tools to examine gene expression, copy number changes, and somatic mutations using RNA array, SNP Chip, and whole exome sequencing. Results: Mice carrying sc (OGK-P and OGK-M) tumors developed splenomegaly and neutrophilia with high expression of cytokines including CSF1, CSF2, CSF3, IL-1β, and IL-6. Levels of HIF-1α and its targeted genes were also elevated in these tumors. The treatment of tumor carrying mice with Bevacizumab effectively decreased tumor growth, macrophage infiltration, and peripheral WBCs. SNP chip analysis showed homozygous deletion of exons 3–22 of the PARD3 gene in the cells. Forced expression of PARD3 decreased cell proliferation, motility, and invasiveness, restores cell-cell contacts and enhanced cell adhesion. Next generation exome sequencing identified the somatic changes present in the primary, metastatic, and primagraft tumors demonstrating evolution of the mutational signature over the year of passage in vivo. Conclusion: To our knowledge, we established the first paired human primary and metastatic ATC cell lines offering unique possibilities for comparative functional investigations in vitro and in vivo. Our exome sequencing also identified novel mutations, as well as clonal evolution in both the metastasis and primagraft. PMID:25365311

Origin and evolution of Petrocosmea (Gesneriaceae) inferred from both DNA sequence and novel findings in morphology with a test of morphology-based hypotheses.

PubMed

Qiu, Zhi-Jing; Lu, Yuan-Xue; Li, Chao-Qun; Dong, Yang; Smith, James F; Wang, Yin-Zheng

2015-07-03

Petrocosmea Oliver (Gesneriaceae) currently comprises 38 species with four non-nominate varieties, nearly all of which have been described solely from herbarium specimens. However, the dried specimens have obscured the full range of extremely diverse morphological variation that exists in the genus and has resulted in a poor subgeneric classification system that does not reflect the evolutionary history of this group. It is important to develop innovative methods to find new morphological traits and reexamine and reevaluate the traditionally used morphological data based on new hypothesis. In addition, Petrocosmea is a mid-sized genus but exhibits extreme diverse floral variants. This makes the genus of particular interest in addressing the question whether there are any key factors that is specifically associated with their evolution and diversification. Here we present the first phylogenetic analyses of the genus based on dense taxonomic sampling and multiple genes combined with a comprehensive morphological investigation. Maximum-parsimony, maximum likelihood and Bayesian analyses of molecular data from two nuclear DNA and six cpDNA regions support the monophyly of Petrocosmea and recover five major clades within the genus, which is strongly corroborated by the reconstruction of ancestral states for twelve new morphological characters directly observed from living material. Ancestral area reconstruction shows that its most common ancestor was likely located east and southeast of the Himalaya-Tibetan plateau. The origin of Petrocosmea from a potentially Raphiocarpus-like ancestor might have involved a series of morphological modifications from caulescent to acaulescent habit as well as from a tetrandrous flower with a long corolla-tube to a diandrous flower with a short corolla-tube, also evident in the vestigial caulescent habit and transitional floral form in clade A that is sister to the remainder of the genus. Among the five clades in Petrocosmea, the patterns of floral morphological differentiation are consistent with discontinuous lineage-associated morphotypes as a repeated adaptive response to alternative environments. Our results suggest that the lineage-specific morphological differentiations reflected in the upper lip, a functional organ for insect pollination, are likely adaptive responses to pollinator shifts. We further recognize that the floral morphological diversification in Petrocosmea involves several evolutionary phenomena, i.e. evolutionary successive specialization, reversals, parallel evolution, and convergent evolution, which are probably associated with adaptation to pollination against the background of heterogeneous abiotic and biotic environments in the eastern wing regions of Himalaya-Tibetan plateau.

Eco-evolution in size-structured ecosystems: simulation case study of rapid morphological changes in alewife.

PubMed

Kang, Jung Koo; Thibert-Plante, Xavier

2017-02-27

Over the last 300 years, interactions between alewives and zooplankton communities in several lakes in the U.S. have caused the alewives' morphology to transition rapidly from anadromous to landlocked. Lakes with landlocked alewives contain smaller-bodied zooplankton than those without alewives. Landlocked adult alewives display smaller body sizes, narrower gapes, smaller inter-gill-raker spacings, reach maturity at an earlier age, and are less fecund than anadromous alewives. Additionally, landlocked alewives consume pelagic prey exclusively throughout their lives whereas anadromous alewives make an ontogenetic transition from pelagic to littoral prey. These rapid, well-documented changes in the alewives' morphology provide important insights into the morphological evolution of fish. Predicting the morphological evolution of fish is crucial for fisheries and ecosystem management, but the involvement of multiple trophic interactions make predictions difficult. To obtain an improved understanding of rapid morphological change in fish, we developed an individual-based model that simulated rapid changes in the body size and gill-raker count of a fish species in a hypothetical, size-structured prey community. Model parameter values were based mainly on data from empirical studies on alewives. We adopted a functional trait approach; consequently, the model explicitly describes the relationships between prey body size, alewife body size, and alewife gill-raker count. We sought to answer two questions: (1) How does the impact of alewife populations on prey feed back to impact alewife size and gill raker number under several alternative scenarios? (2) Will the trajectory of the landlocked alewives' morphological evolution change after 150-300 years in freshwater? Over the first 250 years, the alewives' numbers of gill-rakers only increased when reductions in their body size substantially improved their ability to forage for small prey. Additionally, alewives' gill-raker counts increased more rapidly as the adverse effects of narrow gill-raker spacings on foraging for large prey were made less severe. For the first 150-250 years, alewives' growth decreased monotonically, and their gill-raker number increased monotonically. After the first 150-250 years, however, the alewives exhibited multiple evolutionary morphological trajectories in different trophic settings. In several of these settings, their evolutionary trajectories even reversed after the first 150-250 years. Alewives affected the abundance and morphology of their prey, which in turn changed the abundance and morphology of the alewives. Complex low-trophic-level interactions can alter the abundance and characteristics of alewives. This study suggests that the current morphology of recently (∼300 years)-landlocked alewives may not represent an evolutionarily stable state.

Molecular Pathogenesis and Diagnostic, Prognostic and Predictive Molecular Markers in Sarcoma.

PubMed

Mariño-Enríquez, Adrián; Bovée, Judith V M G

2016-09-01

Sarcomas are infrequent mesenchymal neoplasms characterized by notable morphological and molecular heterogeneity. Molecular studies in sarcoma provide refinements to morphologic classification, and contribute diagnostic information (frequently), prognostic stratification (rarely) and predict therapeutic response (occasionally). Herein, we summarize the major molecular mechanisms underlying sarcoma pathogenesis and present clinically useful diagnostic, prognostic and predictive molecular markers for sarcoma. Five major molecular alterations are discussed, illustrated with representative sarcoma types, including 1. the presence of chimeric transcription factors, in vascular tumors; 2. abnormal kinase signaling, in gastrointestinal stromal tumor; 3. epigenetic deregulation, in chondrosarcoma, chondroblastoma, and other tumors; 4. deregulated cell survival and proliferation, due to focal copy number alterations, in dedifferentiated liposarcoma; 5. extreme genomic instability, in conventional osteosarcoma as a representative example of sarcomas with highly complex karyotype. Copyright © 2016 Elsevier Inc. All rights reserved.

Mutation patterns in small cell and non-small cell lung cancer patients suggest a different level of heterogeneity between primary and metastatic tumors.

PubMed

Saber, Ali; Hiltermann, T Jeroen N; Kok, Klaas; Terpstra, M Martijn; de Lange, Kim; Timens, Wim; Groen, Harry J M; van den Berg, Anke

2017-02-01

Several studies have shown heterogeneity in lung cancer, with parallel existence of multiple subclones characterized by their own specific mutational landscape. The extent to which minor clones become dominant in distinct metastasis is not clear. The aim of our study was to gain insight in the evolution pattern of lung cancer by investigating genomic heterogeneity between primary tumor and its distant metastases. Whole exome sequencing (WES) was performed on 24 tumor and five normal samples of two small cell lung carcinoma (SCLC) and three non-SCLC (NSCLC) patients. Validation of somatic variants in these 24 and screening of 33 additional samples was done by single primer enrichment technology. For each of the three NSCLC patients, about half of the mutations were shared between all tumor samples, whereas for SCLC patients, this percentage was around 95. Independent validation of the non-ubiquitous mutations confirmed the WES data for the vast majority of the variants. Phylogenetic trees indicated more distance between the tumor samples of the NSCLC patients as compared to the SCLC patients. Analysis of 30 independent DNA samples of 16 biopsies used for WES revealed a low degree of intra-tumor heterogeneity of the selected sets of mutations. In the primary tumors of all five patients, variable percentages (19-67%) of the seemingly metastases-specific mutations were present albeit at low read frequencies. Patients with advanced NSCLC have a high percentage of non-ubiquitous mutations indicative of branched evolution. In contrast, the low degree of heterogeneity in SCLC suggests a parallel and linear model of evolution. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

The evolutionary history of Mimosa (Leguminosae): toward a phylogeny of the sensitive plants.

PubMed

Simon, Marcelo F; Grether, Rosaura; de Queiroz, Luciano P; Särkinen, Tiina E; Dutra, Valquíria F; Hughes, Colin E

2011-07-01

Large genera provide remarkable opportunities to investigate patterns of morphological evolution and historical biogeography in plants. A molecular phylogeny of the species-rich and morphologically and ecologically diverse genus Mimosa was generated to evaluate its infrageneric classification, reconstruct the evolution of a set of morphological characters, and establish the relationships of Old World species to the rest of the genus. We used trnD-trnT plastid sequences for 259 species of Mimosa (ca. 50% of the total) to reconstruct the phylogeny of the genus. Six morphological characters (petiolar nectary, inflorescence type, number of stamens, number of petals, pollen type, and seismonasty) were optimized onto the molecular tree. Mimosa was recovered as a monophyletic clade nested within the Piptadenia group and includes the former members of Schrankia, corroborating transfer of that genus to Mimosa. Although we found good support for several infrageneric groups, only one section (Mimadenia) was recovered as monophyletic. All but one of the morphological characters analyzed showed high levels of homoplasy. High levels of geographic structure were found, with species from the same area tending to group together in the phylogeny. Old World species of Mimosa form a monophyletic clade deeply nested within New World groups, indicating recent (6-10 Ma) long-distance dispersal. Although based on a single plastid region, our results establish a preliminary phylogenetic framework for Mimosa that can be used to infer patterns of morphological evolution and relationships and which provides pointers toward a revised infrageneric classification.

Effects of annealing temperature and duration on the morphological and optical evolution of self-assembled Pt nanostructures on c-plane sapphire.

PubMed

Sui, Mao; Li, Ming-Yu; Kunwar, Sundar; Pandey, Puran; Zhang, Quanzhen; Lee, Jihoon

2017-01-01

Metallic nanostructures (NSs) have been widely adapted in various applications and their physical, chemical, optical and catalytic properties are strongly dependent on their surface morphologies. In this work, the morphological and optical evolution of self-assembled Pt nanostructures on c-plane sapphire (0001) is demonstrated by the control of annealing temperature and dwelling duration with the distinct thickness of Pt films. The formation of Pt NSs is led by the surface diffusion, agglomeration and surface and interface energy minimization of Pt thin films, which relies on the growth parameters such as system temperature, film thickness and annealing duration. The Pt layer of 10 nm shows the formation of overlaying NPs below 650°C and isolated Pt nanoparticles above 700°C based on the enhanced surface diffusion and Volmer-Weber growth model whereas larger wiggly nanostructures are formed with 20 nm thick Pt layers based on the coalescence growth model. The morphologies of Pt nanostructures demonstrate a sharp distinction depending on the growth parameters applied. By the control of dwelling duration, the gradual transition from dense Pt nanoparticles to networks-like and large clusters is observed as correlated to the Rayleigh instability and Ostwald ripening. The various Pt NSs show a significant distinction in the reflectance spectra depending on the morphology evolution: i.e. the enhancement in UV-visible and NIR regions and the related optical properties are discussed in conjunction with the Pt NSs morphology and the surface coverage.

Molecular phylogeny of Gymnocalycium (Cactaceae): assessment of alternative infrageneric systems, a new subgenus, and trends in the evolution of the genus.

PubMed

Demaio, Pablo H; Barfuss, Michael H J; Kiesling, Roberto; Till, Walter; Chiapella, Jorge O

2011-11-01

The South American genus Gymnocalycium (Cactoideae-Trichocereae) demonstrates how the sole use of morphological data in Cactaceae results in conflicts in assessing phylogeny, constructing a taxonomic system, and analyzing trends in the evolution of the genus. Molecular phylogenetic analysis was performed using parsimony and Bayesian methods on a 6195-bp data matrix of plastid DNA sequences (atpI-atpH, petL-psbE, trnK-matK, trnT-trnL-trnF) of 78 samples, including 52 species and infraspecific taxa representing all the subgenera of Gymnocalycium. We assessed morphological character evolution using likelihood methods to optimize characters on a Bayesian tree and to reconstruct possible ancestral states. The results of the phylogenetic study confirm the monophyly of the genus, while supporting overall the available infrageneric classification based on seed morphology. Analysis showed the subgenera Microsemineum and Macrosemineum to be polyphyletic and paraphyletic. Analysis of morphological characters showed a tendency toward reduction of stem size, reduction in quantity and hardiness of spines, increment of seed size, development of napiform roots, and change from juicy and colorful fruits to dry and green fruits. Gymnocalycium saglionis is the only species of Microsemineum and a new name is required to identify the clade including the remaining species of Microsemineum; we propose the name Scabrosemineum in agreement with seed morphology. Identifying morphological trends and environmental features allows for a better understanding of the events that might have influenced the diversification of the genus.

Morphology Evolution of Polymer Blends under Intense Shear During High Speed Thin-Wall Injection Molding.

PubMed

Zhou, Yi; Yu, Feilong; Deng, Hua; Huang, Yajiang; Li, Guangxian; Fu, Qiang

2017-06-29

The morphology evolution under shear during different processing is indeed an important issue regarding the phase morphology control as well as final physical properties of immiscible polymer blends. High-speed thin wall injection molding (HSTWIM) has recently been demonstrated as an effective method to prepare alternating multilayered structure. To understand the formation mechanism better and explore possible phase morphology for different blends under HSTWIM, the relationship between the morphology evolution of polymer blends based on polypropylene (PP) under HSTWIM and some intrinsic properties of polymer blends, including viscosity ratio, interfacial tension, and melt elasticity, is systematically investigated in this study. Blends based on PP containing polyethylene (PE), ethylene vinyl alcohol copolymer (EVOH), and polylactic acid (PLA) are used as examples. Compatibilizer has also been added into respective blends to alter their interfacial interaction. It is demonstrated that dispersed phase can be deformed into a layered-like structure if interfacial tension, viscosity ratio, and melt elasticity are relatively small. While some of these values are relatively large, these dispersed droplets are not easily deformed under HSTWIM, forming ellipsoidal or fiber-like structure. The addition of a moderate amount of compatibilizer into these blends is shown to be able to reduce interfacial tension and the size of dispersed phase, thus, allowing more deformation on the dispersed phase. Such a study could provide some guidelines on phase morphology control of immiscible polymer blends under shear during various processing methods.

Exploiting temporal collateral sensitivity in tumor clonal evolution

PubMed Central

Zhao, Boyang; Sedlak, Joseph C.; Srinivas, Raja; Creixell, Pau; Pritchard, Justin R.; Tidor, Bruce; Lauffenburger, Douglas A.; Hemann, Michael T.

2016-01-01

SUMMARY The prevailing approach to addressing secondary drug resistance in cancer focuses on treating the resistance mechanisms at relapse. However, the dynamic nature of clonal evolution, along with potential fitness costs and cost compensations, may present exploitable vulnerabilities; a notion that we term ‘temporal collateral sensitivity’. Using a combined pharmacological screen and drug resistance selection approach in a murine model of Ph+ acute lymphoblastic leukemia, we indeed find that temporal and/or persistent collateral sensitivity to non-classical BCR-ABL1 drugs arises in emergent tumor subpopulations during the evolution of resistance toward initial treatment with BCR-ABL1 targeted inhibitors. We determined the sensitization mechanism via genotypic, phenotypic, signaling, and binding measurements in combination with computational models, and demonstrated significant overall survival extension in mice. Additional stochastic mathematical models and small molecule screens extended our insights, indicating the value of focusing on evolutionary trajectories and pharmacological profiles to identify new strategies to treat dynamic tumor vulnerabilities. PMID:26924578

Dynamics of Tumor Heterogeneity Derived from Clonal Karyotypic Evolution.

PubMed

Laughney, Ashley M; Elizalde, Sergi; Genovese, Giulio; Bakhoum, Samuel F

2015-08-04

Numerical chromosomal instability is a ubiquitous feature of human neoplasms. Due to experimental limitations, fundamental characteristics of karyotypic changes in cancer are poorly understood. Using an experimentally inspired stochastic model, based on the potency and chromosomal distribution of oncogenes and tumor suppressor genes, we show that cancer cells have evolved to exist within a narrow range of chromosome missegregation rates that optimizes phenotypic heterogeneity and clonal survival. Departure from this range reduces clonal fitness and limits subclonal diversity. Mapping of the aneuploid fitness landscape reveals a highly favorable, commonly observed, near-triploid state onto which evolving diploid- and tetraploid-derived populations spontaneously converge, albeit at a much lower fitness cost for the latter. Finally, by analyzing 1,368 chromosomal translocation events in five human cancers, we find that karyotypic evolution also shapes chromosomal translocation patterns by selecting for more oncogenic derivative chromosomes. Thus, chromosomal instability can generate the heterogeneity required for Darwinian tumor evolution. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Exploiting Temporal Collateral Sensitivity in Tumor Clonal Evolution.

PubMed

Zhao, Boyang; Sedlak, Joseph C; Srinivas, Raja; Creixell, Pau; Pritchard, Justin R; Tidor, Bruce; Lauffenburger, Douglas A; Hemann, Michael T

2016-03-24

The prevailing approach to addressing secondary drug resistance in cancer focuses on treating the resistance mechanisms at relapse. However, the dynamic nature of clonal evolution, along with potential fitness costs and cost compensations, may present exploitable vulnerabilities-a notion that we term "temporal collateral sensitivity." Using a combined pharmacological screen and drug resistance selection approach in a murine model of Ph(+) acute lymphoblastic leukemia, we indeed find that temporal and/or persistent collateral sensitivity to non-classical BCR-ABL1 drugs arises in emergent tumor subpopulations during the evolution of resistance toward initial treatment with BCR-ABL1-targeted inhibitors. We determined the sensitization mechanism via genotypic, phenotypic, signaling, and binding measurements in combination with computational models and demonstrated significant overall survival extension in mice. Additional stochastic mathematical models and small-molecule screens extended our insights, indicating the value of focusing on evolutionary trajectories and pharmacological profiles to identify new strategies to treat dynamic tumor vulnerabilities. Copyright © 2016 Elsevier Inc. All rights reserved.

Exosomes from human colorectal cancer induce a tumor-like behavior in colonic mesenchymal stromal cells

PubMed Central

Lugini, Luana; Valtieri, Mauro; Federici, Cristina; Cecchetti, Serena; Meschini, Stefania; Condello, Maria; Signore, Michele; Fais, Stefano

2016-01-01

Background Cancer cells, including colorectal cancer ones (CRC), release high amounts of nanovesicles (exosomes), delivering biochemical messages for paracrine or systemic crosstalk. Mesenchymal stromal cells (MSCs) have been shown to play contradicting roles in tumor progression. Results CRC exosomes induce in cMSCs: i) atypical morphology, higher proliferation, migration and invasion; ii) formation of spheroids; iii) an acidic extracellular environment associated with iv) a plasma membrane redistribution of vacuolar H+-ATPase and increased expression of CEA. Colon cancer derived MSCs, which were isolated from tumor masses, produce umbilicated spheroids, a future frequently observed in the inner core of rapidly growing tumors and recapitulate the changes observed in normal colonic MSCs exposed to CRC exosomes. Materials and Methods Tissue specific colonic (c)MSCs were exposed to primary or metastatic CRC exosomes and analysed by light and electron microscopy, proliferation in 2D and 3D cultures, migration and invasion assays, Western blot and confocal microscopy for vacuolar H+-ATPase expression. Conclusions CRC exosomes are able to induce morphological and functional changes in colonic MSCs, which may favour tumor growth and its malignant progression. Our results suggest that exosomes are actively involved in cancer progression and that inhibiting tumor exosome release may represent a way to interfere with cancer. PMID:27418137

Exosomes from human colorectal cancer induce a tumor-like behavior in colonic mesenchymal stromal cells.

PubMed

Lugini, Luana; Valtieri, Mauro; Federici, Cristina; Cecchetti, Serena; Meschini, Stefania; Condello, Maria; Signore, Michele; Fais, Stefano

2016-08-02

Cancer cells, including colorectal cancer ones (CRC), release high amounts of nanovesicles (exosomes), delivering biochemical messages for paracrine or systemic crosstalk. Mesenchymal stromal cells (MSCs) have been shown to play contradicting roles in tumor progression. CRC exosomes induce in cMSCs: i) atypical morphology, higher proliferation, migration and invasion; ii) formation of spheroids; iii) an acidic extracellular environment associated with iv) a plasma membrane redistribution of vacuolar H+-ATPase and increased expression of CEA. Colon cancer derived MSCs, which were isolated from tumor masses, produce umbilicated spheroids, a future frequently observed in the inner core of rapidly growing tumors and recapitulate the changes observed in normal colonic MSCs exposed to CRC exosomes. Tissue specific colonic (c)MSCs were exposed to primary or metastatic CRC exosomes and analysed by light and electron microscopy, proliferation in 2D and 3D cultures, migration and invasion assays, Western blot and confocal microscopy for vacuolar H+-ATPase expression. CRC exosomes are able to induce morphological and functional changes in colonic MSCs, which may favour tumor growth and its malignant progression. Our results suggest that exosomes are actively involved in cancer progression and that inhibiting tumor exosome release may represent a way to interfere with cancer.

Flow Correlated Percolation during Vascular Remodeling in Growing Tumors

NASA Astrophysics Data System (ADS)

Lee, D.-S.; Rieger, H.; Bartha, K.

2006-02-01

A theoretical model based on the molecular interactions between a growing tumor and a dynamically evolving blood vessel network describes the transformation of the regular vasculature in normal tissues into a highly inhomogeneous tumor specific capillary network. The emerging morphology, characterized by the compartmentalization of the tumor into several regions differing in vessel density, diameter, and necrosis, is in accordance with experimental data for human melanoma. Vessel collapse due to a combination of severely reduced blood flow and solid stress exerted by the tumor leads to a correlated percolation process that is driven towards criticality by the mechanism of hydrodynamic vessel stabilization.

Testicular juvenile granulosa cell tumor in a newborn: case report and review of the literature.

PubMed

Alexiev, Borislav A; Alaish, Samuel M; Sun, Chen-Chih

2007-07-01

Juvenile granulosa cell tumor of the testis of neonates and infants is an uncommon lesion frequently associated with abnormal sex chromosome and ambiguous genitalia. This report describes a juvenile granulosa cell tumor arising in the testis of a neonate. Chromosome analysis of the tumor showed a normal male karyotype 46 XY. Histopathology and immunohistochemical studies revealed the occurrence of 2 well-differentiated epithelial-like and smooth muscle-like components in the neoplasm. The morphologic clues leading to the correct diagnosis of juvenile granulosa cell tumor and the possible histogenesis are briefly discussed.

A Giant Heart Tumor in Neonate with Clinical Signs of Pierre - Robin Syndrome

PubMed Central

Bejiqi, Ramush; Retkoceri, Ragip; Xhema-Bejiqi, Hana; Bejiqi, Rinor; Maloku, Arlinda

2017-01-01

Introduction: Pierre Robin syndrome is a congenital condition of facial abnormalities in humans. The three main features are: cleft palate, retrognathia and glossoptosis. Rarely heart tumors are associated with syndromes, mostly are isolated. Case report: In this presentation we describe a 3-weeks-old girl with Pierre-Robin syndrome and giant left ventricle tumor, diagnosed initially by transthoracic echocardiography. The purpose of this report is to review the literature on the fetuses and neonates with cardiac tumors in an attempt to determine the various ways which cardiac tumors differ clinically and morphologically in this age group. PMID:28790548

HPV- and non-HPV-related subtypes of penile squamous cell carcinoma (SCC): Morphological features and differential diagnosis according to the new WHO classification (2015).

PubMed

Sanchez, Diego F; Cañete, Sofía; Fernández-Nestosa, María José; Lezcano, Cecilia; Rodríguez, Ingrid; Barreto, José; Alvarado-Cabrero, Isabel; Cubilla, Antonio L

2015-05-01

The majority of penile carcinomas are squamous cell carcinomas originating in the squamous mucosa covering the glans, coronal sulcus, or inner surface of the foreskin, the 3 latter sites comprising the penile anatomical compartments. There is a variegated spectrum of subtypes of penile squamous cell carcinomas according to recent classification schemes. Currently, because of etiological and prognostic considerations, 2 morphologically and molecularly distinctive groups of subtypes of penile SCCs based on the presence of HPV were delineated. The predominant cell composition of tumors associated with HPV is the basaloid cell, which is the hallmark and best tissue marker for the virus. Tumors negative for the virus, however, are preferentially of lower grade and keratinizing maturing neoplasms with the exception of sarcomatoid carcinoma. HPV is detected in research studies by PCR or in situ hybridization (ISH) technologies, but p16 immunohistochemical stain is an adequate and less-expensive surrogate that is useful in the routine practice of pathology. The aim of this review is to demonstrate the variable morphological phenotypic expression of penile tumors separating non-HPV- and HPV-related neoplasms and to add morphological information that will justify subclassifying squamous cell carcinomas in a number of special subtypes. A brief discussion of the differential diagnosis in each category is also provided. Copyright © 2015 Elsevier Inc. All rights reserved.

Model of human recurrent respiratory papilloma on chicken embryo chorioallantoic membrane for tumor angiogenesis research.

PubMed

Uloza, Virgilijus; Kuzminienė, Alina; Palubinskienė, Jolita; Balnytė, Ingrida; Ulozienė, Ingrida; Valančiūtė, Angelija

2017-07-01

We aimed to develop a chick embryo chorioallantoic membrane (CAM) model of recurrent respiratory papilloma (RPP) and to evaluate its morphological and morphometric characteristics, together with angiogenic features. Fresh RRP tissue samples obtained from 13 patients were implanted in 174 chick embryo CAMs. Morphological, morphometric, and angiogenic changes in the CAM and chorionic epithelium were evaluated up until 7 days after the implantation. Immunohistochemical analysis (34βE12, Ki-67, MMP-9, PCNA, and Sambucus nigra staining) was performed to detect cytokeratins and endothelial cells and to evaluate proliferative capacity of the RRP before and after implantation on the CAM. The implanted RRP tissue samples survived on CAM in 73% of cases while retaining their essential morphologic characteristics and proliferative capacity of the original tumor. Implants induced thickening of both the CAM (241-560%, p=0.001) and the chorionic epithelium (107-151%, p=0.001), while the number of blood vessels (37-85%, p=0.001) in the CAM increased. The results of the present study confirmed that chick embryo CAM is a relevant host for serving as a medium for RRP fresh tissue implantation. The CAM assay demonstrated the specific RRP tumor growth pattern after implantation and provided the first morphological and morphometric characterization of the RRP CAM model that opens new horizons in studying this disease.

pH and Amphiphilic Structure Direct Supramolecular Behavior in Biofunctional Assemblies

DOE PAGES

Moyer, Tyson J.; Finbloom, Joel A.; Chen, Feng; ...

2014-10-13

Supramolecular self-assembly offers promising new ways to control nanostructure morphology and respond to external stimuli. A pH-sensitive self-assembled system was developed to both control nanostructure shape and respond to the acidic microenvironment of tumors using self-assembling peptide amphiphiles (PAs). Here, by incorporating an oligo-histidine H 6 sequence, we developed two PAs that self-assembled into distinct morphologies on the nanoscale, either as nanofibers or spherical micelles, based on the incorporation of the aliphatic tail on the N-terminus or near the C-terminus, respectively. Both cylinder and sphere-forming PAs demonstrated reversible disassembly between pH 6.0 and 6.5 upon protonation of the histidine residuesmore » in acidic solutions. These PAs were then characterized and assessed for their potential to encapsulate hydrophobic chemotherapies. The H 6-based nanofiber assemblies encapsulated camptothecin (CPT) with up to 60% efficiency, a 7-fold increase in CPT encapsulation relative to spherical micelles. Additionally, pH-sensitive nanofibers showed improved tumor accumulation over both spherical micelles and nanofibers that did not change morphologies in acidic environments. We have demonstrated that the morphological transitions upon changes in pH of supramolecular nanostructures affect drug encapsulation and tumor accumulation. Lastly, our findings also suggest that these supramolecular events can be tuned by molecular design to improve the pharmacologic properties of nanomedicines.« less

Apoptosis-Like Death in Bacteria Induced by HAMLET, a Human Milk Lipid-Protein Complex

PubMed Central

Hakansson, Anders P.; Roche-Hakansson, Hazeline; Mossberg, Ann-Kristin; Svanborg, Catharina

2011-01-01

Background Apoptosis is the primary means for eliminating unwanted cells in multicellular organisms in order to preserve tissue homeostasis and function. It is characterized by distinct changes in the morphology of the dying cell that are orchestrated by a series of discrete biochemical events. Although there is evidence of primitive forms of programmed cell death also in prokaryotes, no information is available to suggest that prokaryotic death displays mechanistic similarities to the highly regulated programmed death of eukaryotic cells. In this study we compared the characteristics of tumor and bacterial cell death induced by HAMLET, a human milk complex of alpha-lactalbumin and oleic acid. Methodology/Principal Findings We show that HAMLET-treated bacteria undergo cell death with mechanistic and morphologic similarities to apoptotic death of tumor cells. In Jurkat cells and Streptococcus pneumoniae death was accompanied by apoptosis-like morphology such as cell shrinkage, DNA condensation, and DNA degradation into high molecular weight fragments of similar sizes, detected by field inverse gel electrophoresis. HAMLET was internalized into tumor cells and associated with mitochondria, causing a rapid depolarization of the mitochondrial membrane and bound to and induced depolarization of the pneumococcal membrane with similar kinetic and magnitude as in mitochondria. Membrane depolarization in both systems required calcium transport, and both tumor cells and bacteria were found to require serine protease activity (but not caspase activity) to execute cell death. Conclusions/Significance Our results suggest that many of the morphological changes and biochemical responses associated with apoptosis are present in prokaryotes. Identifying the mechanisms of bacterial cell death has the potential to reveal novel targets for future antimicrobial therapy and to further our understanding of core activation mechanisms of cell death in eukaryote cells. PMID:21423701

Apoptosis-like death in bacteria induced by HAMLET, a human milk lipid-protein complex.

PubMed

Hakansson, Anders P; Roche-Hakansson, Hazeline; Mossberg, Ann-Kristin; Svanborg, Catharina

2011-03-10

Apoptosis is the primary means for eliminating unwanted cells in multicellular organisms in order to preserve tissue homeostasis and function. It is characterized by distinct changes in the morphology of the dying cell that are orchestrated by a series of discrete biochemical events. Although there is evidence of primitive forms of programmed cell death also in prokaryotes, no information is available to suggest that prokaryotic death displays mechanistic similarities to the highly regulated programmed death of eukaryotic cells. In this study we compared the characteristics of tumor and bacterial cell death induced by HAMLET, a human milk complex of alpha-lactalbumin and oleic acid. We show that HAMLET-treated bacteria undergo cell death with mechanistic and morphologic similarities to apoptotic death of tumor cells. In Jurkat cells and Streptococcus pneumoniae death was accompanied by apoptosis-like morphology such as cell shrinkage, DNA condensation, and DNA degradation into high molecular weight fragments of similar sizes, detected by field inverse gel electrophoresis. HAMLET was internalized into tumor cells and associated with mitochondria, causing a rapid depolarization of the mitochondrial membrane and bound to and induced depolarization of the pneumococcal membrane with similar kinetic and magnitude as in mitochondria. Membrane depolarization in both systems required calcium transport, and both tumor cells and bacteria were found to require serine protease activity (but not caspase activity) to execute cell death. Our results suggest that many of the morphological changes and biochemical responses associated with apoptosis are present in prokaryotes. Identifying the mechanisms of bacterial cell death has the potential to reveal novel targets for future antimicrobial therapy and to further our understanding of core activation mechanisms of cell death in eukaryote cells.

Tumor evolutionary directed graphs and the history of chronic lymphocytic leukemia.

PubMed

Wang, Jiguang; Khiabanian, Hossein; Rossi, Davide; Fabbri, Giulia; Gattei, Valter; Forconi, Francesco; Laurenti, Luca; Marasca, Roberto; Del Poeta, Giovanni; Foà, Robin; Pasqualucci, Laura; Gaidano, Gianluca; Rabadan, Raul

2014-12-11

Cancer is a clonal evolutionary process, caused by successive accumulation of genetic alterations providing milestones of tumor initiation, progression, dissemination, and/or resistance to certain therapeutic regimes. To unravel these milestones we propose a framework, tumor evolutionary directed graphs (TEDG), which is able to characterize the history of genetic alterations by integrating longitudinal and cross-sectional genomic data. We applied TEDG to a chronic lymphocytic leukemia (CLL) cohort of 70 patients spanning 12 years and show that: (a) the evolution of CLL follows a time-ordered process represented as a global flow in TEDG that proceeds from initiating events to late events; (b) there are two distinct and mutually exclusive evolutionary paths of CLL evolution; (c) higher fitness clones are present in later stages of the disease, indicating a progressive clonal replacement with more aggressive clones. Our results suggest that TEDG may constitute an effective framework to recapitulate the evolutionary history of tumors.

Remodeling the Vascular Microenvironment of Glioblastoma with α-Particles.

PubMed

Behling, Katja; Maguire, William F; Di Gialleonardo, Valentina; Heeb, Lukas E M; Hassan, Iman F; Veach, Darren R; Keshari, Kayvan R; Gutin, Philip H; Scheinberg, David A; McDevitt, Michael R

2016-11-01

Tumors escape antiangiogenic therapy by activation of proangiogenic signaling pathways. Bevacizumab is approved for the treatment of recurrent glioblastoma, but patients inevitably develop resistance to this angiogenic inhibitor. We previously investigated targeted α-particle therapy with 225 Ac-E4G10 as an antivascular approach and showed increased survival and tumor control in a high-grade transgenic orthotopic glioblastoma model. Here, we investigated changes in tumor vascular morphology and functionality caused by 225 Ac-E4G10. We investigated remodeling of the tumor microenvironment in transgenic Ntva glioblastoma mice using a therapeutic 7.4-kBq dose of 225 Ac-E4G10. Immunofluorescence and immunohistochemical analyses imaged morphologic changes in the tumor blood-brain barrier microenvironment. Multicolor flow cytometry quantified the endothelial progenitor cell population in the bone marrow. Diffusion-weighted MR imaged functional changes in the tumor vascular network. The mechanism of drug action is a combination of remodeling of the glioblastoma vascular microenvironment, relief of edema, and depletion of regulatory T and endothelial progenitor cells. The primary remodeling event is the reduction of both endothelial and perivascular cell populations. Tumor-associated edema and necrosis were lessened, resulting in increased perfusion and reduced diffusion. Pharmacologic uptake of dasatinib into tumor was enhanced after α-particle therapy. Targeted antivascular α-particle radiation remodels the glioblastoma vascular microenvironment via a multimodal mechanism of action and provides insight into the vascular architecture of platelet-derived growth factor-driven glioblastoma. © 2016 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

Using High-Resolution Comparison of Bedrock Properties and Channel Morphology to Empirically Characterize Erodibility in Fluvial Settings

NASA Astrophysics Data System (ADS)

Chilton, K.; Spotila, J. A.

2017-12-01

Bedrock erodibility exerts a primary control on landscape evolution and fluvial morphodynamics, but the relationships between erodibility and the many factors that influence it (rock strength, spacing and orientation of discontinuities, weathering susceptibility, erosive process, etc.) remain poorly defined. This results in oversimplification of erodibility in landscape evolution models, the primary example being the stream power incision model, which groups together factors which may influence erodibility into a single coefficient. There is therefore need to better define how bedrock properties influence erodibility and, in turn, channel form and evolution. This study seeks to deconvolve the relationships between bedrock material properties and erodibility by quantifying empirical relationships between substrate characteristics and bedrock channel morphology (slope, steepness index, width, form) at a high spatial resolution (5-10 m scale) in continuous and mixed alluvial-bedrock channels. We specifically focus on slowly eroding channels with minimal evidence for landscape transience, such that variations in channel morphology are mainly due to bedrock properties. We also use channels cut into sedimentary rock, which exhibit extreme variation (yet predictability and continuity) in discontinuity spacing. Here we present preliminary data comparing the morphology and bedrock properties of 1st through 4th order channels in the tectonically inactive Valley and Ridge province of the Appalachian Mountains, SW Virginia. Field surveys of channel slope, width, substrate, and form consist of 0.5 km long, continuous stream reaches through different intervals of tilted Paleozoic siliciclastic stratigraphy. Some surveys exhibit nearly complete bedrock exposure, whereas others are predominantly mixed, with localized bedrock reaches in high-slope knickzones. We statistically analyze relationships between fluvial morphology and lithology, strength (based on field and laboratory measurements), and discontinuity spacing and orientation. Results are informative for models of landscape evolution, and specifically provide insight into the controls on erosive process dominance (i.e., plucking vs. abrasion) and on the development and evolution of knickpoints in non-transient settings.

Complex and changing patterns of natural selection explain the evolution of the human hip.

PubMed

Grabowski, Mark; Roseman, Charles C

2015-08-01

Causal explanations for the dramatic changes that occurred during the evolution of the human hip focus largely on selection for bipedal function and locomotor efficiency. These hypotheses rest on two critical assumptions. The first-that these anatomical changes served functional roles in bipedalism-has been supported in numerous analyses showing how postcranial changes likely affected locomotion. The second-that morphological changes that did play functional roles in bipedalism were the result of selection for that behavior-has not been previously explored and represents a major gap in our understanding of hominin hip evolution. Here we use evolutionary quantitative genetic models to test the hypothesis that strong directional selection on many individual aspects of morphology was responsible for the large differences observed across a sample of fossil hominin hips spanning the Plio-Pleistocene. Our approach uses covariance among traits and the differences between relatively complete fossils to estimate the net selection pressures that drove the major transitions in hominin hip evolution. Our findings show a complex and changing pattern of natural selection drove hominin hip evolution, and that many, but not all, traits hypothesized to play functional roles in bipedalism evolved as a direct result of natural selection. While the rate of evolutionary change for all transitions explored here does not exceed the amount expected if evolution was occurring solely through neutral processes, it was far above rates of evolution for morphological traits in other mammalian groups. Given that stasis is the norm in the mammalian fossil record, our results suggest that large shifts in the adaptive landscape drove hominin evolution. Copyright © 2015 Elsevier Ltd. All rights reserved.

Morphological evolution of Bi2Se3 nanocrystalline materials synthesized by microwave assisted solvothermal method

NASA Astrophysics Data System (ADS)

Bera, Sumit; Behera, P.; Mishra, A. K.; Krishnan, M.; Patidar, M. M.; Singh, D.; Gangrade, M.; Venkatesh, R.; Deshpande, U. P.; Phase, D. M.; Ganesan, V.

2018-04-01

Structural, morphological and spectroscopic properties of Bi2Se3 nanoparticles synthesized by microwave assisted solvothermal method were investigated systematically. A controlled synthesis of different morphologies by a small variation in synthesis procedure is demonstrated. Powder X-ray diffraction (XRD) confirmed the formation of single phase. Crystallite and particle size reductions were studied with XRD and AFM (Atomic Force Microscopy). Different morphologies such as hexagonal nanoflakes with cross section of around˜6µm, nanoflower and octahedral agglomerated crystals of nearly ˜60 nm size have been observed in scanning electron microscope while varying the microwave assisted synthesis procedures. A significant blue shift observed in diffuse reflectance spectroscopy evidences the energy gap tuning as a result of morphological evolution. The difference in morphology observed in this three fast, facile and scalable synthesis is advantageous for tuning the thermoelectric figure of merit and for probing the surface states of these topological insulators. Low temperature resistivity remains similar for all three variants depicting a 2D character as evidenced by a -lnT term of localization.

The evolution of morphological diversity in continental assemblages of passerine birds.

PubMed

Jønsson, Knud Andreas; Lessard, Jean-Philippe; Ricklefs, Robert E

2015-04-01

Understanding geographic variation in the species richness and lineage composition of regional biotas is a long-standing goal in ecology. Why do some evolutionary lineages proliferate while others do not, and how do new colonists fit into an established fauna? Here, we analyze the morphological structure of assemblages of passerine birds in four biogeographic regions to examine the relative influence of colonization history and niche-based processes on continental communities of passerine birds. Using morphological traits related to habitat choice, foraging technique, and movement, we quantify the morphological spaces occupied by different groups of passerine birds. We further quantify morphological overlap between groups by multivariate discriminant analysis and null model analyses of trait dispersion. Finally, we use subclade disparity through time to assess the temporal component of morphological evolution. We find mixed support for the prediction, based on priority, that first colonizers constrain subsequent colonizers. Indeed, our results show that the assembly of continental communities is idiosyncratic with regards to the diversification of new clades and the filling of morphospace. © 2015 The Author(s).

A Monte Carlo-finite element model for strain energy controlled microstructural evolution - 'Rafting' in superalloys

NASA Technical Reports Server (NTRS)

Gayda, J.; Srolovitz, D. J.

1989-01-01

This paper presents a specialized microstructural lattice model, MCFET (Monte Carlo finite element technique), which simulates microstructural evolution in materials in which strain energy has an important role in determining morphology. The model is capable of accounting for externally applied stress, surface tension, misfit, elastic inhomogeneity, elastic anisotropy, and arbitrary temperatures. The MCFET analysis was found to compare well with the results of analytical calculations of the equilibrium morphologies of isolated particles in an infinite matrix.

Feasibility of intraoperative imaging during Mohs surgery with reflectance confocal microscopy

NASA Astrophysics Data System (ADS)

Flores, Eileen S.; Cordova, Miguel; Kose, Kivanc; Phillips, William; Nehal, Kishwer; Rajadhyaksha, Milind

2014-03-01

Mohs surgery for the removal of non-melanoma skin cancers (NMSCs) is performed in stages, while being guided by the examination for residual tumor with frozen pathology. However, preparation of frozen pathology at each stage is timeconsuming and labor-intensive. Real-time intraoperative reflectance confocal microscopy (RCM) may enable rapid detection of residual tumor directly in surgical wounds on patients. We report initial feasibility on twenty-one patients, using 35% AlCl3 for nuclear contrast. Imaging was performed in quadrants in the wound, to simulate the Mohs surgeon's examination of pathology. Images and videos of the epidermal and dermal margins were found to be of clinically acceptable quality. Bright nuclear morphology was identified at the epidermal margin. The presence of residual BCC/SCC tumor and normal skin features could be detected in the peripheral and deep dermal margins. Nuclear morphology was detectable in residual BCC/SCC tumors. Intraoperative RCM imaging may enable detection of residual tumor, directly on Mohs patients, and may serve as an adjunct for frozen pathology. However, a stronger source of contrast will be necessary, and also a smaller device with an automated approach for imaging in the entire wound in a rapid and controlled manner for clinical utility.

Experimental investigation of the penetration of ultrasound nanobubbles in a gastric cancer xenograft.

PubMed

Fan, Xiaozhou; Wang, Luofu; Guo, Yanli; Tong, Haipeng; Li, Lang; Ding, Jun; Huang, Haiyun

2013-08-16

Nanobubbles as a type of ultrasound contrast agent have attracted much interest in recent years due to their many advantages, such as strong penetrating power and high stability. However, there is still insufficient morphological evidence concerning gas-filled nanobubbles in tumor tissue spaces and tumor angiogenesis. We used a gastric cancer xenograft as an example to study this question. Nanobubbles with a particle size of 435.2 ± 60.53 nm were prepared and compared with SonoVue® microbubbles in vitro and in vivo, and they exhibited a superior contrast imaging effect. After excluding the impact of the nanobubbles in blood vessels through saline flush, we used an ultrasound burst and frozen sectioning to investigate the distribution of nanobubbles in the gastric cancer xenografts and confirmed this by transmission electron microscopy. Preliminary results showed that the nanobubbles were able to pass through the gaps between the endothelial cells in the tumor vascular system to enter the tissue space. These findings could provide morphological evidence for extravascular ultrasound imaging of tumors and serve as a foundation for the application of nanobubbles in extravascular tumor-targeted ultrasonic diagnostics and therapy.

Experimental investigation of the penetration of ultrasound nanobubbles in a gastric cancer xenograft

NASA Astrophysics Data System (ADS)

Fan, Xiaozhou; Wang, Luofu; Guo, Yanli; Tong, Haipeng; Li, Lang; Ding, Jun; Huang, Haiyun

2013-08-01

Nanobubbles as a type of ultrasound contrast agent have attracted much interest in recent years due to their many advantages, such as strong penetrating power and high stability. However, there is still insufficient morphological evidence concerning gas-filled nanobubbles in tumor tissue spaces and tumor angiogenesis. We used a gastric cancer xenograft as an example to study this question. Nanobubbles with a particle size of 435.2 ± 60.53 nm were prepared and compared with SonoVue® microbubbles in vitro and in vivo, and they exhibited a superior contrast imaging effect. After excluding the impact of the nanobubbles in blood vessels through saline flush, we used an ultrasound burst and frozen sectioning to investigate the distribution of nanobubbles in the gastric cancer xenografts and confirmed this by transmission electron microscopy. Preliminary results showed that the nanobubbles were able to pass through the gaps between the endothelial cells in the tumor vascular system to enter the tissue space. These findings could provide morphological evidence for extravascular ultrasound imaging of tumors and serve as a foundation for the application of nanobubbles in extravascular tumor-targeted ultrasonic diagnostics and therapy.

Three-Dimensional Morphological and Chemical Evolution of Nanoporous Stainless Steel by Liquid Metal Dealloying [3D Morphological and Chemical Evolution of Nanoporous Stainless Steel by Liquid Metal Dealloying

DOE PAGES

Zhao, Chonghang; Wada, Takeshi; De Andrade, Vincent; ...

2017-09-04

Nanoporous materials, especially those fabricated by liquid metal dealloying processes, possess great potential in a wide range of applications due to their high surface area, bicontinuous structure with both open pores for transport and solid phase for conductivity or support, and low material cost. Here, we used X-ray nanotomography and X-ray fluorescence microscopy to reveal the three-dimensional (3D) morphology and elemental distribution within materials. Focusing on nanoporous stainless steel, we evaluated the 3D morphology of the dealloying front and established a quantitative processing-structure-property relationship at a later stage of dealloying. The morphological differences of samples created by liquid metal dealloyingmore » and aqueous dealloying methods were also discussed. Here, we concluded that it is particularly important to consider the dealloying, coarsening, and densification mechanisms in influencing the performance-determining, critical 3D parameters, such as tortuosity, pore size, porosity, curvature, and interfacial shape.« less

Three-Dimensional Morphological and Chemical Evolution of Nanoporous Stainless Steel by Liquid Metal Dealloying [3D Morphological and Chemical Evolution of Nanoporous Stainless Steel by Liquid Metal Dealloying

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhao, Chonghang; Wada, Takeshi; De Andrade, Vincent

Nanoporous materials, especially those fabricated by liquid metal dealloying processes, possess great potential in a wide range of applications due to their high surface area, bicontinuous structure with both open pores for transport and solid phase for conductivity or support, and low material cost. Here, we used X-ray nanotomography and X-ray fluorescence microscopy to reveal the three-dimensional (3D) morphology and elemental distribution within materials. Focusing on nanoporous stainless steel, we evaluated the 3D morphology of the dealloying front and established a quantitative processing-structure-property relationship at a later stage of dealloying. The morphological differences of samples created by liquid metal dealloyingmore » and aqueous dealloying methods were also discussed. Here, we concluded that it is particularly important to consider the dealloying, coarsening, and densification mechanisms in influencing the performance-determining, critical 3D parameters, such as tortuosity, pore size, porosity, curvature, and interfacial shape.« less

Genomic architecture and evolution of clear cell renal cell carcinomas defined by multiregion sequencing

PubMed Central

Varela, Ignacio; Fisher, Rosalie; McGranahan, Nicholas; Matthews, Nicholas; Santos, Claudio R; Martinez, Pierre; Phillimore, Benjamin; Begum, Sharmin; Rabinowitz, Adam; Spencer-Dene, Bradley; Gulati, Sakshi; Bates, Paul A; Stamp, Gordon; Pickering, Lisa; Gore, Martin; Nicol, David L; Hazell, Steven; Futreal, P Andrew; Stewart, Aengus; Swanton, Charles

2015-01-01

Clear cell renal carcinomas (ccRCCs) can display intratumor heterogeneity (ITH). We applied multiregion exome sequencing (M-seq) to resolve the genetic architecture and evolutionary histories of ten ccRCCs. Ultra-deep sequencing identified ITH in all cases. We found that 73–75% of identified ccRCC driver aberrations were subclonal, confounding estimates of driver mutation prevalence. ITH increased with the number of biopsies analyzed, without evidence of saturation in most tumors. Chromosome 3p loss and VHL aberrations were the only ubiquitous events. The proportion of C>T transitions at CpG sites increased during tumor progression. M-seq permits the temporal resolution of ccRCC evolution and refines mutational signatures occurring during tumor development. PMID:24487277

Modern mammal origins: evolutionary grades in the Early Cretaceous of North America.

PubMed Central

Jacobs, L L; Winkler, D A; Murry, P A

1989-01-01

Major groups of modern mammals have their origins in the Mesozoic Era, yet the mammalian fossil record is generally poor for that time interval. Fundamental morphological changes that led to modern mammals are often represented by small samples of isolated teeth. Fortunately, functional wear facets on teeth allow prediction of the morphology of occluding teeth that may be unrepresented by fossils. A major step in mammalian evolution occurred in the Early Cretaceous with the evolution of tribosphenic molars, which characterize marsupials and placentals, the two most abundant and diverse extant groups of mammals. A tooth from the Early Cretaceous (110 million years before present) of Texas tests previous predictions (based on lower molars) of the morphology of upper molars in early tribosphenic dentitions. The lingual cusp (protocone) is primitively without shear facets, as expected, but the cheek side of the tooth is derived (advanced) in having distinctive cusps along the margin. The tooth, although distressingly inadequate to define many features of the organism, demonstrates unexpected morphological diversity at a strategic stage of mammalian evolution and falsifies previous claims of the earliest occurrence of true marsupials. Images PMID:2740336

Intraclass Evolution and Classification of the Colpodea (Ciliophora)

PubMed Central

FOISSNER, WILHELM; STOECK, THORSTEN; AGATHA, SABINE; DUNTHORN, MICAH

2012-01-01

Using nine new taxa and statistical inferences based on morphological and molecular data, we analyze the evolution within the class Colpodea. The molecular and cladistic analyses show four well-supported clades: platyophryids, bursariomorphids, cyrtolophosidids, and colpodids. There is a widespread occurrence of homoplasies, affecting even conspicuous morphological characteristics, e.g. the inclusion of the micronucleus in the perinuclear space of the macronucleus. The most distinct changes in the morphological classification are the lack of a basal divergence into two subclasses and the split of the cyrtolophosidids into two main clades, differing mainly by the presence vs. absence of an oral cavity. The most complex clade is that of the colpodids. We partially reconcile the morphological and molecular data using evolutionary systematics, providing a scenario in which the colpodids evolved from a Bardeliella-like ancestor and the genus Colpoda performed an intense adaptive radiation, giving rise to three main clades: Colpodina n. subord., Grossglockneriina, and Bryophryina. Three new taxa are established: Colpodina n. subord., Tillinidae n. fam., and Ottowphryidae n. fam. Colpodean evolution and classification are far from being understood because sequences are lacking for most species and half of their diversity is possibly undescribed. PMID:21762424

Morphological characteristics and medium-term evolution of the beaches between Ceuta and Cabo Negro (Morocco)

NASA Astrophysics Data System (ADS)

Anfuso, G.; Martínez Del Pozo, J. A.; Nachite, D.; Benavente, J.; Macias, A.

2007-05-01

This work presents the results of a combined study on the beach morphology and the evolution at short- and medium-term of the littoral between Ceuta and Cabo Negro (Morocco). It is an interesting sector showing a great increase of human occupation and coastal structures. The monitoring program allowed for the reconstruction of the beach morphological behavior and the seasonal changes. The studied beaches presented reflective profiles recording little seasonality, with the most notable morphological changes being strictly related to storms. Surf Similarity and Surf Scaling parameters highlighted the existence of intermediate and reflective beach states, characterized by plunging breakers. Aerial photographs and a satellite image have been geo-referenced and elaborated with GIS tools to reconstruct the short- and medium-term evolution of the littoral and the sediment transport pathways. The littoral showed important erosion at short- and medium-term related to a negative sedimentary budget because of offshore transport. Sand accumulation was recorded close to the main ports, i.e., Marina Smir and Marina Kabila. These port structures constituted impermeable, fixed limits, which divided the studied area into littoral cells. Other free, transit limits were also observed.

The evolutionary origins of Syngnathidae: pipefishes and seahorses.

PubMed

Wilson, A B; Orr, J W

2011-06-01

Despite their importance as evolutionary and ecological model systems, the phylogenetic relationships among gasterosteiforms remain poorly understood, complicating efforts to understand the evolutionary origins of the exceptional morphological and behavioural diversity of this group. The present review summarizes current knowledge on the origin and evolution of syngnathids, a gasterosteiform family with a highly developed form of male parental care, combining inferences based on morphological and molecular data with paleontological evidence documenting the evolutionary history of the group. Molecular methods have provided new tools for the study of syngnathid relationships and have played an important role in recent conservation efforts. Despite recent insights into syngnathid evolution, however, a survey of the literature reveals a strong taxonomic bias towards studies on the species-rich genera Hippocampus and Syngnathus, with a lack of data for many morphologically unique members of the family. The study of the evolutionary pressures responsible for generating the high diversity of syngnathids would benefit from a wider perspective, providing a comparative framework in which to investigate the evolution of the genetic, morphological and behavioural traits of the group as a whole. © 2011 The Authors. Journal of Fish Biology © 2011 The Fisheries Society of the British Isles.

A six-gene phylogeny provides new insights into choanoflagellate evolution.

PubMed

Carr, Martin; Richter, Daniel J; Fozouni, Parinaz; Smith, Timothy J; Jeuck, Alexandra; Leadbeater, Barry S C; Nitsche, Frank

2017-02-01

Recent studies have shown that molecular phylogenies of the choanoflagellates (Class Choanoflagellatea) are in disagreement with their traditional taxonomy, based on morphology, and that Choanoflagellatea requires considerable taxonomic revision. Furthermore, phylogenies suggest that the morphological and ecological evolution of the group is more complex than has previously been recognized. Here we address the taxonomy of the major choanoflagellate order Craspedida, by erecting four new genera. The new genera are shown to be morphologically, ecologically and phylogenetically distinct from other choanoflagellate taxa. Furthermore, we name five novel craspedid species, as well as formally describe ten species that have been shown to be either misidentified or require taxonomic revision. Our revised phylogeny, including 18 new species and sequence data for two additional genes, provides insights into the morphological and ecological evolution of the choanoflagellates. We examine the distribution within choanoflagellates of these two additional genes, EF-1A and EFL, closely related translation GTPases which are required for protein synthesis. Mapping the presence and absence of these genes onto the phylogeny highlights multiple events of gene loss within the choanoflagellates. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Trophic specialization drives morphological evolution in sea snakes.

PubMed

Sherratt, Emma; Rasmussen, Arne R; Sanders, Kate L

2018-03-01

Viviparous sea snakes are the most rapidly speciating reptiles known, yet the ecological factors underlying this radiation are poorly understood. Here, we reconstructed dated trees for 75% of sea snake species and quantified body shape (forebody relative to hindbody girth), maximum body length and trophic diversity to examine how dietary specialization has influenced morphological diversification in this rapid radiation. We show that sea snake body shape and size are strongly correlated with the proportion of burrowing prey in the diet. Specialist predators of burrowing eels have convergently evolved a 'microcephalic' morphotype with dramatically reduced forebody relative to hindbody girth and intermediate body length. By comparison, snakes that predominantly feed on burrowing gobies are generally short-bodied and small-headed, but there is no evidence of convergent evolution. The eel specialists also exhibit faster rates of size and shape evolution compared to all other sea snakes, including those that feed on gobies. Our results suggest that trophic specialization to particular burrowing prey (eels) has invoked strong selective pressures that manifest as predictable and rapid morphological changes. Further studies are needed to examine the genetic and developmental mechanisms underlying these dramatic morphological changes and assess their role in sea snake speciation.

Early animal evolution: emerging views from comparative biology and geology

NASA Technical Reports Server (NTRS)

Knoll, A. H.; Carroll, S. B.

1999-01-01

The Cambrian appearance of fossils representing diverse phyla has long inspired hypotheses about possible genetic or environmental catalysts of early animal evolution. Only recently, however, have data begun to emerge that can resolve the sequence of genetic and morphological innovations, environmental events, and ecological interactions that collectively shaped Cambrian evolution. Assembly of the modern genetic tool kit for development and the initial divergence of major animal clades occurred during the Proterozoic Eon. Crown group morphologies diversified in the Cambrian through changes in the genetic regulatory networks that organize animal ontogeny. Cambrian radiation may have been triggered by environmental perturbation near the Proterozoic-Cambrian boundary and subsequently amplified by ecological interactions within reorganized ecosystems.

Advances in planetary geology

NASA Technical Reports Server (NTRS)

Woronow, A. (Editor)

1981-01-01

Three dissertations are provided covering (1) the stochastic evolution of asteroidal regoliths and the origin of brecciated and gas-rich meteorites; (2) ridge systems on Mars; and (3) the morphology and evolution of Ganymede and Callisto.

The role of calcium and predation on plate morph evolution in the three-spined stickleback (Gasterosteus aculeatus)

PubMed Central

Smith, Carl; Spence, Rowena; Barber, Iain; Przybylski, Mirosław; Wootton, Robert J

2014-01-01

While the genetic basis to plate morph evolution of the three-spined stickleback (Gasterosteus aculeatus) is well described, the environmental variables that select for different plate and spine morphs are incompletely understood. Using replicate populations of three-spined sticklebacks on North Uist, Scotland, we previously investigated the role of predation pressure and calcium limitation on the adaptive evolution of stickleback morphology and behavior. While dissolved calcium proved a significant predictor of plate and spine morph, predator abundance did not. Ecol. Evol., xxx, 2014 and xxx performed a comparable analysis to our own to address the same question. They failed to detect a significant effect of dissolved calcium on morphological evolution, but did establish a significant effect of predation; albeit in the opposite direction to their prediction. PMID:25478147

The Ecology and Evolution of Cancer: The Ultra-Microevolutionary Process.

PubMed

Wu, Chung-I; Wang, Hurng-Yi; Ling, Shaoping; Lu, Xuemei

2016-11-23

Although tumorigenesis has been accepted as an evolutionary process ( 20 , 102 ), many forces may operate differently in cancers than in organisms, as they evolve at vastly different time scales. Among such forces, natural selection, here defined as differential cellular proliferation among distinct somatic cell genotypes, is particularly interesting because its action might be thwarted in multicellular organisms ( 20 , 29 ). In this review, selection is analyzed in two stages of cancer evolution: Stage I is the evolution between tumors and normal tissues, and Stage II is the evolution within tumors. The Cancer Genome Atlas (TCGA) data show a low degree of convergent evolution in Stage I, where genetic changes are not extensively shared among cases. An equally important, albeit much less highlighted, discovery using TCGA data is that there is almost no net selection in cancer evolution. Both positive and negative selection are evident but they neatly cancel each other out, rendering total selection ineffective in the absence of recombination. The efficacy of selection is even lower in Stage II, where neutral (non-Darwinian) evolution is increasingly supported by high-density sampling studies ( 81 , 123 ). Because natural selection is not a strong deterministic force, cancers usually evolve divergently even in similar tissue environments.

Coupling biomechanics to a cellular level model: an approach to patient-specific image driven multi-scale and multi-physics tumor simulation.

PubMed

May, Christian P; Kolokotroni, Eleni; Stamatakos, Georgios S; Büchler, Philippe

2011-10-01

Modeling of tumor growth has been performed according to various approaches addressing different biocomplexity levels and spatiotemporal scales. Mathematical treatments range from partial differential equation based diffusion models to rule-based cellular level simulators, aiming at both improving our quantitative understanding of the underlying biological processes and, in the mid- and long term, constructing reliable multi-scale predictive platforms to support patient-individualized treatment planning and optimization. The aim of this paper is to establish a multi-scale and multi-physics approach to tumor modeling taking into account both the cellular and the macroscopic mechanical level. Therefore, an already developed biomodel of clinical tumor growth and response to treatment is self-consistently coupled with a biomechanical model. Results are presented for the free growth case of the imageable component of an initially point-like glioblastoma multiforme tumor. The composite model leads to significant tumor shape corrections that are achieved through the utilization of environmental pressure information and the application of biomechanical principles. Using the ratio of smallest to largest moment of inertia of the tumor material to quantify the effect of our coupled approach, we have found a tumor shape correction of 20% by coupling biomechanics to the cellular simulator as compared to a cellular simulation without preferred growth directions. We conclude that the integration of the two models provides additional morphological insight into realistic tumor growth behavior. Therefore, it might be used for the development of an advanced oncosimulator focusing on tumor types for which morphology plays an important role in surgical and/or radio-therapeutic treatment planning. Copyright © 2011 Elsevier Ltd. All rights reserved.

Morphological Evolution of Gyroid-Forming Block Copolymer Thin Films with Varying Solvent Evaporation Rate.

PubMed

Wu, Yi-Hsiu; Lo, Ting-Ya; She, Ming-Shiuan; Ho, Rong-Ming

2015-08-05

In this study, we aim to examine the morphological evolution of block copolymer (BCP) nanostructured thin films through solvent evaporation at different rates for solvent swollen polystyrene-block-poly(l-lactide) (PS-PLLA). Interesting phase transitions from disorder to perpendicular cylinder and then gyroid can be found while using a partially selective solvent for PS to swell PS-PLLA thin film followed by solvent evaporation. During the transitions, gyroid-forming BCP thin film with characteristic crystallographic planes of (111)G, (110)G, and (211)G parallel to air surface can be observed, and will gradually transform into coexisting (110)G and (211)G planes, and finally transforms to (211)G plane due to the preferential segregation of constituted block to the surface (i.e., the thermodynamic origin for self-assembly) that affects the relative amount of each component at the air surface. With the decrease on the evaporation rate, the disorder phase will transform to parallel cylinder and then directly to (211)G without transition to perpendicular cylinder phase. Most importantly, the morphological evolution of PS-PLLA thin films is strongly dependent upon the solvent removal rate only in the initial stage of the evaporation process due to the anisotropy of cylinder structure. Once the morphology is transformed back to the isotropic gyroid structure after long evaporation, the morphological evolution will only relate to the variation of the surface composition. Similar phase transitions at the substrate can also be obtained by controlling the ratio of PLLA-OH to PS-OH homopolymers to functionalize the substrate. As a result, the fabrication of well-defined nanostructured thin films with controlled orientation can be achieved by simple swelling and deswelling with controlled evaporation rate.

Waterfalls drive parallel evolution in a freshwater goby

PubMed Central

Kano, Yuichi; Nishida, Shin; Nakajima, Jun

2012-01-01

Waterfalls may affect fish distribution and genetic structure within drainage networks even to the extent of leading evolutionary events. Here, parallel evolution was studied by focusing on waterfall and the landlocked freshwater goby Rhinogobius sp. YB (YB), which evolved from amphidromous R. brunneus (BR). The fish fauna was surveyed at 30 sites in 11 rivers on Iriomote Island, Japan, the geography of which was characterized by terraces/tablelands with many waterfalls. We found that all YB individuals were distributed only above waterfalls (height 6.8–58.7 m), whereas BR, and other fishes, were mostly distributed below waterfalls. Mitochondrial DNA analysis showed that every YB local population above the waterfall was independently evolved from BR. In contrast, cluster analysis of nine morphological characters, such as fin color and body pattern, showed that the morphology of YB individuals held a similarity beyond the genetic divergence, suggesting parallel evolution has occurred relating to their morphology. Genetic distance between each YB local population and BR was significantly correlated with waterfall height (r2 = 0.94), suggesting that the waterfalls have been heightened due to the constant geological erosion and that their height represents the isolation period of YB local populations from BR (ca. 11,000–88,000 years). Each local population of BR was once landlocked in upstream by waterfall formation, consequently evolving to YB in each site. Although the morphology of YB had a high degree of similarity among local populations, finer scale analysis showed that the morphology of YB was significantly correlated with the genetic distance from BR. Consequently, there could be simultaneous multiple phases of allopatric/parallel evolution of the goby due to variations in waterfall height on this small island. PMID:22957183

The macroevolutionary consequences of phenotypic integration: from development to deep time.

PubMed

Goswami, A; Smaers, J B; Soligo, C; Polly, P D

2014-08-19

Phenotypic integration is a pervasive characteristic of organisms. Numerous analyses have demonstrated that patterns of phenotypic integration are conserved across large clades, but that significant variation also exists. For example, heterochronic shifts related to different mammalian reproductive strategies are reflected in postcranial skeletal integration and in coordination of bone ossification. Phenotypic integration and modularity have been hypothesized to shape morphological evolution, and we extended simulations to confirm that trait integration can influence both the trajectory and magnitude of response to selection. We further demonstrate that phenotypic integration can produce both more and less disparate organisms than would be expected under random walk models by repartitioning variance in preferred directions. This effect can also be expected to favour homoplasy and convergent evolution. New empirical analyses of the carnivoran cranium show that rates of evolution, in contrast, are not strongly influenced by phenotypic integration and show little relationship to morphological disparity, suggesting that phenotypic integration may shape the direction of evolutionary change, but not necessarily the speed of it. Nonetheless, phenotypic integration is problematic for morphological clocks and should be incorporated more widely into models that seek to accurately reconstruct both trait and organismal evolution.

Disparate rates, differing fates: tempo and mode of evolution changed from the Precambrian to the Phanerozoic

NASA Technical Reports Server (NTRS)

Schopf, J. W.

1994-01-01

Over the past quarter century, detailed genus- and species-level similarities in cellular morphology between described taxa of Precambrian microfossils and extant cyanobacteria have been noted and regarded as biologically and taxonomically significant by numerous workers world-wide. Such similarities are particularly well documented for members of the Oscillatoriaceae and Chroococcaceae, the two most abundant and widespread Precambrian cyanobacterial families. For species of two additional families, the Entophysalidaceae and Pleurocapsaceae, species-level morphologic similarities are supported by in-depth fossil-modern comparisons of environment, taphonomy, development, and behavior. Morphologically and probably physiologically as well, such cyanobacterial "living fossils" have exhibited an extraordinarily slow (hypobradytelic) rate of evolutionary change, evidently a result of the broad ecologic tolerance characteristic of many members of the group and a striking example of G. G. Simpson's [Simpson, G.G. (1944) Tempo and Mode in Evolution (Columbia Univ. Press, New York)] "rule of the survival of the relatively unspecialized." In both tempo and mode of evolution, much of the Precambrian history of life--that dominated by microscopic cyanobacteria and related prokaryotes--appears to have differed markedly from the more recent Phanerozoic evolution megascopic, horotelic, adaptationally specialized eukaryotes.

The macroevolutionary consequences of phenotypic integration: from development to deep time

PubMed Central

Goswami, A.; Smaers, J. B.; Soligo, C.; Polly, P. D.

2014-01-01

Phenotypic integration is a pervasive characteristic of organisms. Numerous analyses have demonstrated that patterns of phenotypic integration are conserved across large clades, but that significant variation also exists. For example, heterochronic shifts related to different mammalian reproductive strategies are reflected in postcranial skeletal integration and in coordination of bone ossification. Phenotypic integration and modularity have been hypothesized to shape morphological evolution, and we extended simulations to confirm that trait integration can influence both the trajectory and magnitude of response to selection. We further demonstrate that phenotypic integration can produce both more and less disparate organisms than would be expected under random walk models by repartitioning variance in preferred directions. This effect can also be expected to favour homoplasy and convergent evolution. New empirical analyses of the carnivoran cranium show that rates of evolution, in contrast, are not strongly influenced by phenotypic integration and show little relationship to morphological disparity, suggesting that phenotypic integration may shape the direction of evolutionary change, but not necessarily the speed of it. Nonetheless, phenotypic integration is problematic for morphological clocks and should be incorporated more widely into models that seek to accurately reconstruct both trait and organismal evolution. PMID:25002699

Reappraisal of Morphologic Differences Between Renal Medullary Carcinoma, Collecting Duct Carcinoma, and Fumarate Hydratase-deficient Renal Cell Carcinoma.

PubMed

Ohe, Chisato; Smith, Steven C; Sirohi, Deepika; Divatia, Mukul; de Peralta-Venturina, Mariza; Paner, Gladell P; Agaimy, Abbas; Amin, Mitual B; Argani, Pedram; Chen, Ying-Bei; Cheng, Liang; Colecchia, Maurizio; Compérat, Eva; Werneck da Cunha, Isabela; Epstein, Jonathan I; Gill, Anthony J; Hes, Ondřej; Hirsch, Michelle S; Jochum, Wolfram; Kunju, Lakshmi P; Maclean, Fiona; Magi-Galluzzi, Cristina; McKenney, Jesse K; Mehra, Rohit; Nesi, Gabriella; Osunkoya, Adeboye O; Picken, Maria M; Rao, Priya; Reuter, Victor E; de Oliveira Salles, Paulo Guilherme; Schultz, Luciana; Tickoo, Satish K; Tomlins, Scott A; Trpkov, Kiril; Amin, Mahul B

2018-03-01

Renal medullary carcinomas (RMCs) and collecting duct carcinomas (CDCs) are rare subsets of lethal high-stage, high-grade distal nephron-related adenocarcinomas with a predilection for the renal medullary region. Recent findings have established an emerging group of fumarate hydratase (FH)-deficient tumors related to hereditary leiomyomatosis and renal cell carcinoma (HLRCC-RCCs) syndrome within this morphologic spectrum. Recently developed, reliable ancillary testing has enabled consistent separation between these tumor types. Here, we present the clinicopathologic features and differences in the morphologic patterns between RMC, CDC, and FH-deficient RCC in consequence of these recent developments. This study included a total of 100 cases classified using contemporary criteria and ancillary tests. Thirty-three RMCs (SMARCB1/INI1-deficient, hemoglobinopathy), 38 CDCs (SMARCB1/INI1-retained), and 29 RCCs defined by the FH-deficient phenotype (FH/2SC or FH/2SC with FH mutation, regardless of HLRCC syndromic stigmata/history) were selected. The spectrum of morphologic patterns was critically evaluated, and the differences between the morphologic patterns present in the 3 groups were analyzed statistically. Twenty-five percent of cases initially diagnosed as CDC were reclassified as FH-deficient RCC on the basis of our contemporary diagnostic approach. Among the different overlapping morphologic patterns, sieve-like/cribriform and reticular/yolk sac tumor-like patterns favored RMCs, whereas intracystic papillary and tubulocystic patterns favored FH-deficient RCC. The tubulopapillary pattern favored both CDCs and FH-deficient RCCs, and the multinodular infiltrating papillary pattern favored CDCs. Infiltrating glandular and solid sheets/cords/nested patterns were not statistically different among the 3 groups. Viral inclusion-like macronucleoli, considered as a hallmark of HLRCC-RCCs, were observed significantly more frequently in FH-deficient RCCs. Despite the overlapping morphology found among these clinically aggressive infiltrating high-grade adenocarcinomas of the kidney, reproducible differences in morphology emerged between these categories after rigorous characterization. Finally, we recommend that definitive diagnosis of CDC should only be made if RMC and FH-deficient RCC are excluded.

[Neuroendocrine tumors of digestive system: morphologic spectrum and cell proliferation (Ki67 index)].

PubMed

Delektorskaia, V V; Kushliskiĭ, N E

2013-01-01

This review deals with the analysis of up-to-date concepts ofdiferent types of human neuroendocrine tumors of the digestive system. It summarizes the information on the specifics of recent histological classifications and criteria of morphological diagnosis accounting histological, ultrastructural and immunohistochemical parameters. Current issues of the nomenclature as well as various systems of grading and staging are discussed. In the light of these criteria the results of the own research clinical value of the determination of cell proliferation in primary and metastatic gastroenteropancreatic neuroendocrine neoplasms on the basis of evaluation of the Ki67 antigen expression are also presented.

Evolution of the hominin knee and ankle.

PubMed

Frelat, Mélanie A; Shaw, Colin N; Sukhdeo, Simone; Hublin, Jean-Jacques; Benazzi, Stefano; Ryan, Timothy M

2017-07-01

The dispersal of the genus Homo out of Africa approximately 1.8 million years ago (Ma) has been understood within the context of changes in diet, behavior, and bipedal locomotor efficiency. While various morphological characteristics of the knee and ankle joints are considered part of a suite of traits indicative of, and functionally related to, habitual bipedal walking, the timing and phylogenetic details of these morphological changes remain unclear. To evaluate the timing of knee and ankle joint evolution, we apply geometric morphometric methods to three-dimensional digital models of the proximal and distal tibiae of fossil hominins, Holocene Homo sapiens, and extant great apes. Two sets of landmarks and curve semilandmarks were defined on each specimen. Because some fossils were incomplete, digital reconstructions were carried out independently to estimate missing landmarks and semilandmarks. Group shape variation was evaluated through shape-and form-space principal component analysis and fossil specimens were projected to assess variation in the morphological space computed from the extant comparative sample. We show that a derived proximal tibia (knee) similar to that seen in living H. sapiens evolved with early Homo at ∼2 Ma. In contrast, derived characteristics in the distal tibia appear later, probably with the arrival of Homo erectus. These results suggest a dissociation of the morphologies of the proximal and distal tibia, perhaps indicative of divergent functional demands and, consequently, selective pressures at these joints. It appears that longer distance dispersals that delivered the Dmanisi hominins to Georgia by 1.8 Ma and H. erectus to east-southeast Asia by 1.6 Ma were facilitated by the evolution of a morphologically derived knee complex comparable to that of recent humans and an ankle that was morphologically primitive. This research sets the foundation for additional paleontological, developmental, and functional research to better understand the mechanisms underlying the evolution of bipedalism. Copyright © 2017 Elsevier Ltd. All rights reserved.

Tumors of the Testis: Morphologic Features and Molecular Alterations.

PubMed

Howitt, Brooke E; Berney, Daniel M

2015-12-01

This article reviews the most frequently encountered tumor of the testis; pure and mixed malignant testicular germ cell tumors (TGCT), with emphasis on adult (postpubertal) TGCTs and their differential diagnoses. We additionally review TGCT in the postchemotherapy setting, and findings to be integrated into the surgical pathology report, including staging of testicular tumors and other problematic issues. The clinical features, gross pathologic findings, key histologic features, common differential diagnoses, the use of immunohistochemistry, and molecular alterations in TGCTs are discussed. Copyright © 2015 Elsevier Inc. All rights reserved.

[Periosteal reactions in bone tumors (author's transl)].

PubMed

Heuck, F

1979-08-01

Morphology of solid, lamellar and spicular periosteal reactions of benign and malignant primary and metastatic bone tumors in x-ray-pictures with regard to common and specific characteristics of different bone tumors is presented. The specific behaviour of the periosteum itself and of the subperiosteal region as an expression of the reactive biodynamics in skeletal neoplasia is demonstrated; and the diagnostic value of the radiograph is explained. The possibilities but also the limitations of sophisticated radiologic image analysis in establishing a differential diagnosis and a diagnosis of bone tumors and other bone lesions are discussed.

Integrated Multiregional Analysis Proposing a New Model of Colorectal Cancer Evolution.

PubMed

Uchi, Ryutaro; Takahashi, Yusuke; Niida, Atsushi; Shimamura, Teppei; Hirata, Hidenari; Sugimachi, Keishi; Sawada, Genta; Iwaya, Takeshi; Kurashige, Junji; Shinden, Yoshiaki; Iguchi, Tomohiro; Eguchi, Hidetoshi; Chiba, Kenichi; Shiraishi, Yuichi; Nagae, Genta; Yoshida, Kenichi; Nagata, Yasunobu; Haeno, Hiroshi; Yamamoto, Hirofumi; Ishii, Hideshi; Doki, Yuichiro; Iinuma, Hisae; Sasaki, Shin; Nagayama, Satoshi; Yamada, Kazutaka; Yachida, Shinichi; Kato, Mamoru; Shibata, Tatsuhiro; Oki, Eiji; Saeki, Hiroshi; Shirabe, Ken; Oda, Yoshinao; Maehara, Yoshihiko; Komune, Shizuo; Mori, Masaki; Suzuki, Yutaka; Yamamoto, Ken; Aburatani, Hiroyuki; Ogawa, Seishi; Miyano, Satoru; Mimori, Koshi

2016-02-01

Understanding intratumor heterogeneity is clinically important because it could cause therapeutic failure by fostering evolutionary adaptation. To this end, we profiled the genome and epigenome in multiple regions within each of nine colorectal tumors. Extensive intertumor heterogeneity is observed, from which we inferred the evolutionary history of the tumors. First, clonally shared alterations appeared, in which C>T transitions at CpG site and CpG island hypermethylation were relatively enriched. Correlation between mutation counts and patients' ages suggests that the early-acquired alterations resulted from aging. In the late phase, a parental clone was branched into numerous subclones. Known driver alterations were observed frequently in the early-acquired alterations, but rarely in the late-acquired alterations. Consistently, our computational simulation of the branching evolution suggests that extensive intratumor heterogeneity could be generated by neutral evolution. Collectively, we propose a new model of colorectal cancer evolution, which is useful for understanding and confronting this heterogeneous disease.

Alternate pathways of body shape evolution translate into common patterns of locomotor evolution in two clades of lizards.

PubMed

Bergmann, Philip J; Irschick, Duncan J

2010-06-01

Body shape has a fundamental impact on organismal function, but it is unknown how functional morphology and locomotor performance and kinematics relate across a diverse array of body shapes. We showed that although patterns of body shape evolution differed considerably between lizards of the Phrynosomatinae and Lerista, patterns of locomotor evolution coincided between clades. Specifically, we found that the phrynosomatines evolved a stocky phenotype through body widening and limb shortening, whereas Lerista evolved elongation through body lengthening and limb shortening. In both clades, relative limb length played a key role in locomotor evolution and kinematic strategies, with long-limbed species moving faster and taking longer strides. In Lerista, the body axis also influenced locomotor evolution. Similar patterns of locomotor evolution were likely due to constraints on how the body can move. However, these common patterns of locomotor evolution between the two clades resulted in different kinematic strategies and levels of performance among species because of their morphological differences. Furthermore, we found no evidence that distinct body shapes are adaptations to different substrates, as locomotor kinematics did not change on loose or solid substrates. Our findings illustrate the importance of studying kinematics to understand the mechanisms of locomotor evolution and phenotype-function relationships.

A bizarre theropod from the Early Cretaceous of Japan highlighting mosaic evolution among coelurosaurians

PubMed Central

Azuma, Yoichi; Xu, Xing; Shibata, Masateru; Kawabe, Soichiro; Miyata, Kazunori; Imai, Takuya

2016-01-01

Our understanding of coelurosaurian evolution, particularly of bird origins, has been greatly improved, mainly due to numerous recently discovered fossils worldwide. Nearly all these discoveries are referable to the previously known coelurosaurian subgroups. Here, we report a new theropod, Fukuivenator paradoxus, gen. et sp. nov., based on a nearly complete specimen from the Lower Cretaceous Kitadani Formation of the Tetori Group, Fukui, Japan. While Fukuivenator possesses a large number of morphological features unknown in any other theropod, it has a combination of primitive and derived features seen in different theropod subgroups, notably dromaeosaurid dinosaurs. Computed-tomography data indicate that Fukuivenator possesses inner ears whose morphology is intermediate between those of birds and non-avian dinosaurs. Our phylogenetic analysis recovers Fukuivenator as a basally branching maniraptoran theropod, yet is unable to refer it to any known coelurosaurian subgroups. The discovery of Fukuivenator considerably increases the morphological disparity of coelurosaurian dinosaurs and highlights the high levels of homoplasy in coelurosaurian evolution. PMID:26908367

Morphological Evolution of Pit-Patterned Si(001) Substrates Driven by Surface-Energy Reduction

NASA Astrophysics Data System (ADS)

Salvalaglio, Marco; Backofen, Rainer; Voigt, Axel; Montalenti, Francesco

2017-09-01

Lateral ordering of heteroepitaxial islands can be conveniently achieved by suitable pit-patterning of the substrate prior to deposition. Controlling shape, orientation, and size of the pits is not trivial as, being metastable, they can significantly evolve during deposition/annealing. In this paper, we exploit a continuum model to explore the typical metastable pit morphologies that can be expected on Si(001), depending on the initial depth/shape. Evolution is predicted using a surface-diffusion model, formulated in a phase-field framework, and tackling surface-energy anisotropy. Results are shown to nicely reproduce typical metastable shapes reported in the literature. Moreover, long time scale evolutions of pit profiles with different depths are found to follow a similar kinetic pathway. The model is also exploited to treat the case of heteroepitaxial growth involving two materials characterized by different facets in their equilibrium Wulff's shape. This can lead to significant changes in morphologies, such as a rotation of the pit during deposition as evidenced in Ge/Si experiments.

Morphological Evolution of Pit-Patterned Si(001) Substrates Driven by Surface-Energy Reduction.

PubMed

Salvalaglio, Marco; Backofen, Rainer; Voigt, Axel; Montalenti, Francesco

2017-09-29

Lateral ordering of heteroepitaxial islands can be conveniently achieved by suitable pit-patterning of the substrate prior to deposition. Controlling shape, orientation, and size of the pits is not trivial as, being metastable, they can significantly evolve during deposition/annealing. In this paper, we exploit a continuum model to explore the typical metastable pit morphologies that can be expected on Si(001), depending on the initial depth/shape. Evolution is predicted using a surface-diffusion model, formulated in a phase-field framework, and tackling surface-energy anisotropy. Results are shown to nicely reproduce typical metastable shapes reported in the literature. Moreover, long time scale evolutions of pit profiles with different depths are found to follow a similar kinetic pathway. The model is also exploited to treat the case of heteroepitaxial growth involving two materials characterized by different facets in their equilibrium Wulff's shape. This can lead to significant changes in morphologies, such as a rotation of the pit during deposition as evidenced in Ge/Si experiments.

Quantitative DNA Methylation Profiling in Cancer.

PubMed

Ammerpohl, Ole; Haake, Andrea; Kolarova, Julia; Siebert, Reiner

2016-01-01

Epigenetic mechanisms including DNA methylation are fundamental for the regulation of gene expression. Epigenetic alterations can lead to the development and the evolution of malignant tumors as well as the emergence of phenotypically different cancer cells or metastasis from one single tumor cell. Here we describe bisulfite pyrosequencing, a technology to perform quantitative DNA methylation analyses, to detect aberrant DNA methylation in malignant tumors.

From forest and agro-ecosystems to the microecosystems of the human body: what can landscape ecology tell us about tumor growth, metastasis, and treatment options?

PubMed Central

Daoust, Simon P; Fahrig, Lenore; Martin, Amanda E; Thomas, Frédéric

2013-01-01

Cancer is now understood to be a process that follows Darwinian evolution. Heterogeneous populations of cancerous cells that make up the tumor inhabit the tissue ‘microenvironment’, where ecological interactions analogous to predation and competition for resources drive the somatic evolution of cancer. The tumor microenvironment plays a crucial role in the tumor genesis, development, and metastasis processes, as it creates the microenvironmental selection forces that ultimately determine the cellular characteristics that result in the greatest fitness. Here, we explore and offer new insights into the spatial aspects of tumor–microenvironment interactions through the application of landscape ecology theory to tumor growth and metastasis within the tissue microhabitat. We argue that small tissue microhabitats in combination with the spatial distribution of resources within these habitats could be important selective forces driving tumor invasiveness. We also contend that the compositional and configurational heterogeneity of components in the tissue microhabitat do not only influence resource availability and functional connectivity but also play a crucial role in facilitating metastasis and may serve to explain, at least in part, tissue tropism in certain cancers. This novel work provides a compelling argument for the necessity of taking into account the structure of the tissue microhabitat when investigating tumor progression. PMID:23396712

Melanoma: Genetic Abnormalities, Tumor Progression, Clonal Evolution and Tumor Initiating Cells.

PubMed

Testa, Ugo; Castelli, Germana; Pelosi, Elvira

2017-11-20

Melanoma is an aggressive neoplasia issued from the malignant transformation of melanocytes, the pigment-generating cells of the skin. It is responsible for about 75% of deaths due to skin cancers. Melanoma is a phenotypically and molecularly heterogeneous disease: cutaneous, uveal, acral, and mucosal melanomas have different clinical courses, are associated with different mutational profiles, and possess distinct risk factors. The discovery of the molecular abnormalities underlying melanomas has led to the promising improvement of therapy, and further progress is expected in the near future. The study of melanoma precursor lesions has led to the suggestion that the pathway of tumor evolution implies the progression from benign naevi, to dysplastic naevi, to melanoma in situ and then to invasive and metastatic melanoma. The gene alterations characterizing melanomas tend to accumulate in these precursor lesions in a sequential order. Studies carried out in recent years have, in part, elucidated the great tumorigenic potential of melanoma tumor cells. These findings have led to speculation that the cancer stem cell model cannot be applied to melanoma because, in this malignancy, tumor cells possess an intrinsic plasticity, conferring the capacity to initiate and maintain the neoplastic process to phenotypically different tumor cells.

Melanoma: Genetic Abnormalities, Tumor Progression, Clonal Evolution and Tumor Initiating Cells

PubMed Central

Castelli, Germana; Pelosi, Elvira

2017-01-01

Melanoma is an aggressive neoplasia issued from the malignant transformation of melanocytes, the pigment-generating cells of the skin. It is responsible for about 75% of deaths due to skin cancers. Melanoma is a phenotypically and molecularly heterogeneous disease: cutaneous, uveal, acral, and mucosal melanomas have different clinical courses, are associated with different mutational profiles, and possess distinct risk factors. The discovery of the molecular abnormalities underlying melanomas has led to the promising improvement of therapy, and further progress is expected in the near future. The study of melanoma precursor lesions has led to the suggestion that the pathway of tumor evolution implies the progression from benign naevi, to dysplastic naevi, to melanoma in situ and then to invasive and metastatic melanoma. The gene alterations characterizing melanomas tend to accumulate in these precursor lesions in a sequential order. Studies carried out in recent years have, in part, elucidated the great tumorigenic potential of melanoma tumor cells. These findings have led to speculation that the cancer stem cell model cannot be applied to melanoma because, in this malignancy, tumor cells possess an intrinsic plasticity, conferring the capacity to initiate and maintain the neoplastic process to phenotypically different tumor cells. PMID:29156643

The vascular disrupting agent ZD6126 shows increased antitumor efficacy and enhanced radiation response in large, advanced tumors

DOE Office of Scientific and Technical Information (OSTI.GOV)

Siemann, Dietmar W.; Rojiani, Amyn M.

2005-07-01

Purpose: ZD6126 is a vascular-targeting agent that induces selective effects on the morphology of proliferating and immature endothelial cells by disrupting the tubulin cytoskeleton. The efficacy of ZD6126 was investigated in large vs. small tumors in a variety of animal models. Methods and Materials: Three rodent tumor models (KHT, SCCVII, RIF-1) and three human tumor xenografts (Caki-1, KSY-1, SKBR3) were used. Mice bearing leg tumors ranging in size from 0.1-2.0 g were injected intraperitoneally with a single 150 mg/kg dose of ZD6126. The response was assessed by morphologic and morphometric means as well as an in vivo to in vitromore » clonogenic cell survival assay. To examine the impact of tumor size on the extent of enhancement of radiation efficacy by ZD6126, KHT sarcomas of three different sizes were irradiated locally with a range of radiation doses, and cell survival was determined. Results: All rodent tumors and human tumor xenografts evaluated showed a strong correlation between increasing tumor size and treatment effect as determined by clonogenic cell survival. Detailed evaluation of KHT sarcomas treated with ZD6126 showed a reduction in patent tumor blood vessels that was {approx}20% in small (<0.3 g) vs. >90% in large (>1.0 g) tumors. Histologic assessment revealed that the extent of tumor necrosis after ZD6126 treatment, although minimal in small KHT sarcomas, became more extensive with increasing tumor size. Clonogenic cell survival after ZD6126 exposure showed a decrease in tumor surviving fraction from approximately 3 x 10{sup -1} to 1 x 10{sup -4} with increasing tumor size. When combined with radiotherapy, ZD6126 treatment resulted in little enhancement of the antitumor effect of radiation in small (<0.3 g) tumors but marked increases in cell kill in tumors larger than 1.0 g. Conclusions: Because bulky neoplastic disease is typically the most difficult to manage, the present findings provide further support for the continued development of vascular disrupting agents such as ZD6126 as a vascular-targeted approach to cancer therapy.« less

Coastal Foredune Evolution, Part 1: Environmental Factors and Forcing Processes Affecting Morphological Evolution

DTIC Science & Technology

2017-02-01

ERDC/CHL CHETN-II-56 February 2017 Approved for public release; distribution is unlimited. Coastal Foredune Evolution, Part 1: Environmental... Coastal and Hydraulics Engineering Technical Note (CHETN) is the first of two CHETNs focused on improving technologies to forecast coastal foredune...morphodynamic evolution of coastal foredunes. Part 2 reviews modeling approaches to forecast these changes and develops a probabilistic modeling framework to

Concentration gradient induced morphology evolution of silica nanostructure growth on photoresist-derived carbon micropatterns

NASA Astrophysics Data System (ADS)

Liu, Dan; Shi, Tielin; Xi, Shuang; Lai, Wuxing; Liu, Shiyuan; Li, Xiaoping; Tang, Zirong

2012-09-01

The evolution of silica nanostructure morphology induced by local Si vapor source concentration gradient has been investigated by a smart design of experiments. Silica nanostructure or their assemblies with different morphologies are obtained on photoresist-derived three-dimensional carbon microelectrode array. At a temperature of 1,000°C, rope-, feather-, and octopus-like nanowire assemblies can be obtained along with the Si vapor source concentration gradient flow. While at 950°C, stringlike assemblies, bamboo-like nanostructures with large joints, and hollow structures with smaller sizes can be obtained along with the Si vapor source concentration gradient flow. Both vapor-liquid-solid and vapor-quasiliquid-solid growth mechanisms have been applied to explain the diverse morphologies involving branching, connecting, and batch growth behaviors. The present approach offers a potential method for precise design and controlled synthesis of nanostructures with different features.

Controllable synthesis, morphology evolution and electrochemical properties of LiFePO4 cathode materials for Li-ion batteries.

PubMed

Song, Jianjun; Wang, Lin; Shao, Guangjie; Shi, Meiwu; Ma, Zhipeng; Wang, Guiling; Song, Wei; Liu, Shuang; Wang, Caixia

2014-05-07

Monodispersed LiFePO4 nanocrystals with diverse morphologies were successfully synthesized via a mild and controllable solvothermal approach with a mixture of ethylene glycol and oleic acid as the solvent. Morphology evolution of LiFePO4 nanoparticles from nanoplates to nanorods can be simply realized by varying the volume ratio of oleic acid to ethylene glycol. Moreover, the mechanism of competitive adsorption between ethylene glycol and oleic acid was proposed for the formation of different morphologies. Electrochemical measurements show that the LiFePO4/C nanorods have an initial discharge capacity of 155 mA h g(-1) at 0.5 C with a capacity retention of 80% at a high rate of 5 C, which confirms that LiFePO4/C nanorods exhibit excellent rate capability and cycling stability.

On the effects of cluster density and concentration on the horizontal branch morphology - The origin of the blue tails

NASA Technical Reports Server (NTRS)

Fusi Pecci, F.; Ferraro, F. R.; Bellazzini, M.; Djorgovski, S.; Piotto, G.; Buonanno, R.

1993-01-01

Possible relationships between horizontal branch (HB) morphology in Galactic globular clusters and the cluster structure and dynamical evolution are investigated. New HB observables are defined and determined using a theoretical framework deduced from HB models. Data for 53 Galactic globular clusters are used to obtain correlations between the observables. It is found that the net length of the HB and the presence and extent of blue tails in particular are correlated with the cluster density and concentrations, in the sense of more concentrated or denser clusters having bluer and longer HB morphologies. This effect is especially strong for the intermediate metallicity clusters. Thus, the cluster environment can affect the stellar evolution leading to the HB and therefore the HB morphology. This result is interpreted in terms of an enhanced mass removal from the HB progenitors.

Evolution of nanodot morphology on polycarbonate (PC) surfaces by 40 keV Ar{sup +}

DOE Office of Scientific and Technical Information (OSTI.GOV)

Goyal, Meetika, E-mail: meetika89@gmail.com; Chawla, Mahak; Gupta, Divya

In the present paper we have discussed the effect of 40 keV Ar{sup +} ions irradiation on nanoscale surface morphology of Polycarbonate (PC) substrate. Specimens were sputtered at off normal incidences of 30°, 40° and 50° with the fluence of 1 × 10{sup 16} Ar{sup +}cm{sup −2}. The topographical behaviour of specimens was studied by using Atomic Force Microscopy (AFM) technique. AFM study demonstrates the evolution of nano dot morphology on PC specimens on irradiating with 1 × 10{sup 16} Ar{sup +}cm{sup −2}. Average size of dots varied from 37-95 nm in this specified range of incidence while density of dotsmore » varied from 0.17-3.0 × 107 dotscm{sup −2}. Such variations in morphological features have been supported by estimation of ion range and sputtering yield through SRIM simulations.« less

Lattice-based model of ductal carcinoma in situ suggests rules for breast cancer progression to an invasive state.

PubMed

Boghaert, Eline; Radisky, Derek C; Nelson, Celeste M

2014-12-01

Ductal carcinoma in situ (DCIS) is a heterogeneous group of non-invasive lesions of the breast that result from abnormal proliferation of mammary epithelial cells. Pathologists characterize DCIS by four tissue morphologies (micropapillary, cribriform, solid, and comedo), but the underlying mechanisms that distinguish the development and progression of these morphologies are not well understood. Here we explored the conditions leading to the emergence of the different morphologies of DCIS using a two-dimensional multi-cell lattice-based model that incorporates cell proliferation, apoptosis, necrosis, adhesion, and contractility. We found that the relative rates of cell proliferation and apoptosis governed which of the four morphologies emerged. High proliferation and low apoptosis favored the emergence of solid and comedo morphologies. In contrast, low proliferation and high apoptosis led to the micropapillary morphology, whereas high proliferation and high apoptosis led to the cribriform morphology. The natural progression between morphologies cannot be investigated in vivo since lesions are usually surgically removed upon detection; however, our model suggests probable transitions between these morphologies during breast cancer progression. Importantly, cribriform and comedo appear to be the ultimate morphologies of DCIS. Motivated by previous experimental studies demonstrating that tumor cells behave differently depending on where they are located within the mammary duct in vivo or in engineered tissues, we examined the effects of tissue geometry on the progression of DCIS. In agreement with our previous experimental work, we found that cells are more likely to invade from the end of ducts and that this preferential invasion is regulated by cell adhesion and contractility. This model provides additional insight into tumor cell behavior and allows the exploration of phenotypic transitions not easily monitored in vivo.

Morphological features of tongue squamous cell carcinoma diagnosed in Dolj County population between 2012-2014.

PubMed

Mărăşescu, Petre Costin; Turcu, Adina Andreea; Mercuţ, Veronica; Scrieciu, Monica; Mărgăritescu, Claudiu; Ionovici, Nina; Sălan, Alex Ioan; Mărăşescu, Felicia Ioana; Stan, Mihaela Cristina

2018-01-01

Tongue squamous carcinoma can be found in many forms, having a lot of risk factors, and whose morphological characteristics can be used as a prognostic. The purpose of this study was to histologically characterize a number of 54 patients diagnosed between 2012-2014, with tongue squamous carcinoma. Surgical resection specimens of tongue tumors were processed by paraffin inclusion technique. The diagnose samples were reevaluated according to the World Health Organization (WHO) criteria for head and neck tumors diagnosis, by screening the Hematoxylin-Eosin staining sections. The most common histopathological variety of tongue carcinoma observed in our cases was the non-keratinized form, the basaloid and sarcomatoid types of carcinoma being ranked on the last places. The study outlined the prevalence of non-keratinized forms of tongue squamous carcinoma and all types of tumoral invasion patterns have been observed in different percentages.

Evolution of Avian Tumor Viruses

USDA-ARS?s Scientific Manuscript database

Virus-induced neoplastic diseases of poultry, namely Marek’s disease (MD), induced by a herpesvirus, and the avian leukosis and reticuloendotheliosis induced by retroviruses, can cause significant economic losses from tumor mortality as well as poor performance. Successful control of MD is and has ...

[Clinico-morphological peculiarities of thyroid cancer among children exposed to the Chernobyl disaster radiation].

PubMed

Iakovleva, I N; Shishkov, R V; Poliakov, V G; Pankova, P A

2008-01-01

The paper deals with a comparison of clinico-morphological patterns of sporadic thyroid cancer and that in pediatric patients exposed to radiation during the Chernobyl disaster. The latter are highly prone to both local and regional metastatic spread to the lymph nodes (intrathyroid distribution--61%; extension through capsule--42%, and metastases to the neck lymph nodes--66%). However, these data do not differ significantly from those for intact areas. Yet, cancer occurs in exposed cohorts at an earlier stage: its incidence at age 4-6 is 2-3.5 higher and that of relapse such as presentation of latent metastases to the lymph nodes and tumor foci development in residual tumor tissue is 1.6 times the average. Also, morphological patterns have changed: typical papillary cancer incidence has dropped by half while the diffuse follicular variety has grown 1.8-fold.

Lineage diversification and morphological evolution in a large-scale continental radiation: the neotropical ovenbirds and woodcreepers (aves: Furnariidae).

PubMed

Derryberry, Elizabeth P; Claramunt, Santiago; Derryberry, Graham; Chesser, R Terry; Cracraft, Joel; Aleixo, Alexandre; Pérez-Emán, Jorge; Remsen, J V; Brumfield, Robb T

2011-10-01

Patterns of diversification in species-rich clades provide insight into the processes that generate biological diversity. We tested different models of lineage and phenotypic diversification in an exceptional continental radiation, the ovenbird family Furnariidae, using the most complete species-level phylogenetic hypothesis produced to date for a major avian clade (97% of 293 species). We found that the Furnariidae exhibit nearly constant rates of lineage accumulation but show evidence of constrained morphological evolution. This pattern of sustained high rates of speciation despite limitations on phenotypic evolution contrasts with the results of most previous studies of evolutionary radiations, which have found a pattern of decelerating diversity-dependent lineage accumulation coupled with decelerating or constrained phenotypic evolution. Our results suggest that lineage accumulation in tropical continental radiations may not be as limited by ecological opportunities as in temperate or island radiations. More studies examining patterns of both lineage and phenotypic diversification are needed to understand the often complex tempo and mode of evolutionary radiations on continents. © 2011 The Author(s). Evolution© 2011 The Society for the Study of Evolution.

Understanding cellular architecture in cancer cells

NASA Astrophysics Data System (ADS)

Bianco, Simone; Tang, Chao

2011-03-01

Understanding the development of cancer is an important goal for today's science. The morphology of cellular organelles, such as the nucleus, the nucleoli and the mitochondria, which is referred to as cellular architecture or cytoarchitecture, is an important indicator of the state of the cell. In particular, there are striking difference between the cellular architecture of a healthy cell versus a cancer cell. In this work we present a dynamical model for the evolution of organelles morphology in cancer cells. Using a dynamical systems approach, we describe the evolution of a cell on its way to cancer as a trajectory in a multidimensional morphology state. The results provided by this work may increase our insight on the mechanism of tumorigenesis and help build new therapeutic strategies.

Morphological evolution of copper nanoparticles: Microemulsion reactor system versus batch reactor system

NASA Astrophysics Data System (ADS)

Xia, Ming; Tang, Zengmin; Kim, Woo-Sik; Yu, Taekyung; Park, Bum Jun

2017-07-01

In the synthesis of nanoparticles, the reaction rate is important to determine the morphology of nanoparticles. We investigated morphology evolution of Cu nanoparticles in this two different reactors, microemulsion reactor and batch reactor. In comparison with the batch reactor system, the enhanced mass and heat transfers in the emulsion system likely led to the relatively short nucleation time and the highly homogeneous environment in the reaction mixture, resulting in suppressing one or two dimensional growth of the nanoparticles. We believe that this work can offer a good model system to quantitatively understand the crystal growth mechanism that depends strongly on the local monomer concentration, the efficiency of heat transfer, and the relative contribution of the counter ions (Br- and Cl-) as capping agents.

Beyond neutral and forbidden links: morphological matches and the assembly of mutualistic hawkmoth-plant networks.

PubMed

Sazatornil, Federico D; Moré, Marcela; Benitez-Vieyra, Santiago; Cocucci, Andrea A; Kitching, Ian J; Schlumpberger, Boris O; Oliveira, Paulo E; Sazima, Marlies; Amorim, Felipe W

2016-11-01

A major challenge in evolutionary ecology is to understand how co-evolutionary processes shape patterns of interactions between species at community level. Pollination of flowers with long corolla tubes by long-tongued hawkmoths has been invoked as a showcase model of co-evolution. Recently, optimal foraging models have predicted that there might be a close association between mouthparts' length and the corolla depth of the visited flowers, thus favouring trait convergence and specialization at community level. Here, we assessed whether hawkmoths more frequently pollinate plants with floral tube lengths similar to their proboscis lengths (morphological match hypothesis) against abundance-based processes (neutral hypothesis) and ecological trait mismatches constraints (forbidden links hypothesis), and how these processes structure hawkmoth-plant mutualistic networks from five communities in four biogeographical regions of South America. We found convergence in morphological traits across the five communities and that the distribution of morphological differences between hawkmoths and plants is consistent with expectations under the morphological match hypothesis in three of the five communities. In the two remaining communities, which are ecotones between two distinct biogeographical areas, interactions are better predicted by the neutral hypothesis. Our findings are consistent with the idea that diffuse co-evolution drives the evolution of extremely long proboscises and flower tubes, and highlight the importance of morphological traits, beyond the forbidden links hypothesis, in structuring interactions between mutualistic partners, revealing that the role of niche-based processes can be much more complex than previously known. © 2016 The Authors. Journal of Animal Ecology © 2016 British Ecological Society.

Pathology of carcinoma in situ of the urinary bladder and related lesions.

PubMed

Farrow, G M

1992-01-01

In the United States, nearly all cases of bladder cancer are of the transitional cell type, and epidemiological evidence indicates that among these, approximately 80% present initially as more or less well-differentiated, superficial papillary neoplasms with a tendency for multifocal or diffuse involvement of the urothelial surface and/or recurrent tumor episodes, but with limited potential for invasive growth or a lethal outcome. Bladder tumors with lethal potential generally begin as poorly differentiated, sessile growths that are usually invasive at first diagnosis. Carcinoma in situ is a change that must be elicited among intact surface cells before progressive proliferation results in a tumor mass. Evidence for such an association is both temporal and spatial. Since most transitional cell carcinomas begin as well-differentiated tumors, i.e., resembling normal urothelium, recognition of early neoplastic alteration before a papillary structure forms is unlikely and most of the evidence is spatial based upon urothelial changes adjacent to papillary tumors. The morphologic definition of carcinoma in situ is arbitrary and generally defined as a total replacement of the urothelial surface by cells which bear morphologic features of carcinoma, but which lack architectural alteration other than an increase in the number of cell layers, i.e., a flat lesion. The Union Internationále Contra Cancer/American Joint Committee on Cancer (UICC/AJCC) staging scheme for bladder cancer distinguishes non-invasive papillary growths as Ta and carcinoma in situ as Tis. Because detection of carcinoma in situ, either by cytology or biopsy, depends upon recognizable malignant morphologic characteristics, studies of the lesion tend to be limited to the higher grade or more anaplastic examples.(ABSTRACT TRUNCATED AT 250 WORDS)

Renal cell carcinoma, unclassified with medullary phenotype: poorly differentiated adenocarcinomas overlapping with renal medullary carcinoma.

PubMed

Sirohi, Deepika; Smith, Steven C; Ohe, Chisato; Colombo, Piergiuseppe; Divatia, Mukul; Dragoescu, Ema; Rao, Priya; Hirsch, Michelle S; Chen, Ying-Bei; Mehra, Rohit; Amin, Mahul B

2017-09-01

Renal medullary carcinoma (RMC) is a highly aggressive renal cell carcinoma arising in the collecting system and requiring careful correlation with status of sickle cell trait. A panel of international experts has recently proposed provisional diagnostic terminology, renal cell carcinoma, unclassified, with medullary phenotype, based on encountering an extraordinarily rare tumor with RMC morphology and immunophenotype in an individual proven not to have a hemoglobinopathy. Herein, we extend this observation to a cohort of 5 such tumors, morphologically similar to RMC, lacking SMARCB1 expression by immunohistochemistry, but each without evidence of a hemoglobinopathy. The tumors arose in 4 men and 1 woman with a mean age of 44 years, occurring in 3 left and 2 right kidneys. Clinically, aggression was apparent with involvement of perinephric adipose tissue in all 5 cases, nodal metastasis in 4 of 5 cases, and death of disease in 4 of 5 cases within 3-27 months. Histologic sections showed poorly differentiated adenocarcinoma, often with solid and nested growth patterns, as well as infiltrative glandular, tubulopapillary, cribriform, or reticular growth. Rhabdoid and sarcomatoid cytomorphology was seen in a subset. All tumors showed PAX8 nuclear positivity and SMARCB1 loss, with OCT3/4 expression in 4 of 5 cases. In summary, this first series of renal cell carcinoma, unclassified, with medullary phenotype documents tumors with morphologic, immunophenotypic, and prognostic features of RMC occurring in individuals without sickle cell trait. Although greater biologic and molecular understanding is needed, the available evidence points to these cases representing a sporadic counterpart to sickle cell trait-associated RMC. Copyright © 2017 Elsevier Inc. All rights reserved.

Variation of Keratin 7 Expression and Other Phenotypic Characteristics of Independent Isolates of Cadmium Transformed Human Urothelial Cells (UROtsa)

PubMed Central

Somji, Seema; Zhou, Xu Dong; Mehus, Aaron; Sens, Mary Ann; Garrett, Scott H.; Lutz, Krista L.; Dunlevy, Jane R.; Zheng, Yun; Sens, Donald. A.

2009-01-01

This laboratory has shown that a human urothelial cell line (UROtsa) transformed by cadmium (Cd+2) produced subcutaneous tumor heterotransplants that resemble human transitional cell carcinoma (TCC). In the present study, additional Cd+2 transformed cell lines were isolated to determine if independent exposures of the cell line to Cd+2 would result in malignantly transformed cell lines possessing similar phenotypic properties. Seven independent isolates were isolated and assessed for their doubling times, morphology, ability to heterotransplant subcutaneously and in the peritoneal cavity of nude mice and for the expression keratin 7. The 7 cell lines all displayed an epithelial morphology with no evidence of squamous differentiation. Doubling times were variable among the isolates, being significantly reduced or similar to the parental cells. All 7 isolates were able to form subcutaneous tumor heterotransplants with a TCC morphology and all heterotransplants displayed areas of squamous differentiation of the transitional cells. The degree of squamous differentiation varied among the isolates. In contrast to subcutaneous tumor formation, only 1 isolate of the Cd+2 transformed cells (UTCd#1) was able to effectively colonize multiple sites within the peritoneal cavity. An analysis of keratin 7 expression showed no correlation with squamous differentiation for the subcutaneous heterotransplants generated from the 7 cell lines. Keratin 7 was expressed in 6 of the 7 cell lines and their subcutaneous tumor heterotransplants. Keratin 7 was not expressed in the cell line that was able to form tumors within the peritoneal cavity. These results show that individual isolates of Cd+2 transformed cells have both similarities and differences in their phenotype. PMID:19921857

Evolution of cooperation among tumor cells.

PubMed

Axelrod, Robert; Axelrod, David E; Pienta, Kenneth J

2006-09-05

The evolution of cooperation has a well established theoretical framework based on game theory. This approach has made valuable contributions to a wide variety of disciplines, including political science, economics, and evolutionary biology. Existing cancer theory suggests that individual clones of cancer cells evolve independently from one another, acquiring all of the genetic traits or hallmarks necessary to form a malignant tumor. It is also now recognized that tumors are heterotypic, with cancer cells interacting with normal stromal cells within the tissue microenvironment, including endothelial, stromal, and nerve cells. This tumor cell-stromal cell interaction in itself is a form of commensalism, because it has been demonstrated that these nonmalignant cells support and even enable tumor growth. Here, we add to this theory by regarding tumor cells as game players whose interactions help to determine their Darwinian fitness. We marshal evidence that tumor cells overcome certain host defenses by means of diffusible products. Our original contribution is to raise the possibility that two nearby cells can protect each other from a set of host defenses that neither could survive alone. Cooperation can evolve as by-product mutualism among genetically diverse tumor cells. Our hypothesis supplements, but does not supplant, the traditional view of carcinogenesis in which one clonal population of cells develops all of the necessary genetic traits independently to form a tumor. Cooperation through the sharing of diffusible products raises new questions about tumorigenesis and has implications for understanding observed phenomena, designing new experiments, and developing new therapeutic approaches.

ClonEvol: clonal ordering and visualization in cancer sequencing.

PubMed

Dang, H X; White, B S; Foltz, S M; Miller, C A; Luo, J; Fields, R C; Maher, C A

2017-12-01

Reconstruction of clonal evolution is critical for understanding tumor progression and implementing personalized therapies. This is often done by clustering somatic variants based on their cellular prevalence estimated via bulk tumor sequencing of multiple samples. The clusters, consisting of the clonal marker variants, are then ordered based on their estimated cellular prevalence to reconstruct clonal evolution trees, a process referred to as 'clonal ordering'. However, cellular prevalence estimate is confounded by statistical variability and errors in sequencing/data analysis, and therefore inhibits accurate reconstruction of the clonal evolution. This problem is further complicated by intra- and inter-tumor heterogeneity. Furthermore, the field lacks a comprehensive visualization tool to facilitate the interpretation of complex clonal relationships. To address these challenges we developed ClonEvol, a unified software tool for clonal ordering, visualization, and interpretation. ClonEvol uses a bootstrap resampling technique to estimate the cellular fraction of the clones and probabilistically models the clonal ordering constraints to account for statistical variability. The bootstrapping allows identification of the sample founding- and sub-clones, thus enabling interpretation of clonal seeding. ClonEvol automates the generation of multiple widely used visualizations for reconstructing and interpreting clonal evolution. ClonEvol outperformed three of the state of the art tools (LICHeE, Canopy and PhyloWGS) for clonal evolution inference, showing more robust error tolerance and producing more accurate trees in a simulation. Building upon multiple recent publications that utilized ClonEvol to study metastasis and drug resistance in solid cancers, here we show that ClonEvol rediscovered relapsed subclones in two published acute myeloid leukemia patients. Furthermore, we demonstrated that through noninvasive monitoring ClonEvol recapitulated the emerging subclones throughout metastatic progression observed in the tumors of a published breast cancer patient. ClonEvol has broad applicability for longitudinal monitoring of clonal populations in tumor biopsies, or noninvasively, to guide precision medicine. ClonEvol is written in R and is available at https://github.com/ChrisMaherLab/ClonEvol. © The Author 2017. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Are rates of species diversification and body size evolution coupled in the ferns?

PubMed

Testo, Weston L; Sundue, Michael A

2018-03-01

Understanding the relationship between phenotypic evolution and lineage diversification is a central goal of evolutionary biology. To extend our understanding of the role morphological evolution plays in the diversification of plants, we examined the relationship between leaf size evolution and lineage diversification across ferns. We tested for an association between body size evolution and lineage diversification using a comparative phylogenetic approach that combined a time-calibrated phylogeny and leaf size data set for 2654 fern species. Rates of leaf size change and lineage diversification were estimated using BAMM, and rate correlations were performed for rates obtained for all families and individual species. Rates and patterns of rate-rate correlation were also analyzed separately for terrestrial and epiphytic taxa. We find no significant correlation between rates of leaf area change and lineage diversification, nor was there a difference in this pattern when growth habit is considered. Our results are consistent with the findings of an earlier study that reported decoupled rates of body size evolution and diversification in the Polypodiaceae, but conflict with a recent study that reported a positive correlation between body size evolution and lineage diversification rates in the tree fern family Cyatheaceae. Our findings indicate that lineage diversification in ferns is largely decoupled from shifts in body size, in contrast to several other groups of organisms. Speciation in ferns appears to be primarily driven by hybridization and isolation along elevational gradients, rather than adaptive radiations featuring prominent morphological restructuring. The exceptional diversity of leaf morphologies in ferns appears to reflect a combination of ecophysiological constraints and adaptations that are not key innovations. © 2018 Botanical Society of America.

Primary Renal Hybrid Low-grade Fibromyxoid Sarcoma-Sclerosing Epithelioid Fibrosarcoma: An Unusual Pediatric Case With EWSR1-CREB3L1 Fusion.

PubMed

Mok, Yingting; Pang, Yin Huei; Sanjeev, Jain Sudhanshi; Kuick, Chik Hong; Chang, Kenneth Tou-En

2018-01-01

Low-grade fibromyxoid sarcoma (LGFMS) and sclerosing epithelioid fibrosarcoma (SEF) are rare tumors with distinct sets of morphological features, both characterized by MUC4 immunoreactivity. Tumors exhibiting features of both entities are considered hybrid LGFMS-SEF lesions. While the majority of LGFMS cases are characterized by FUS-CREB3L2 gene fusions, most cases of pure SEF show EWSR1 gene rearrangements. In the largest study of hybrid LGFMS-SEF tumors to date, all cases exhibited FUS rearrangements, a similar genetic profile to LGFMS. We herein describe the clinicopathological features and genetic findings of a case of primary renal hybrid LGFMS-SEF occurring in a 10-year-old child, with disseminated metastases. Fusion gene detection using a next-generation sequencing-based anchored multiplex PCR technique (Archer FusionPlex Sarcoma Panel) was performed on both the primary renal tumor that showed the morphology of a LGFMS, and a cervical metastasis that showed the morphology of SEF. An EWSR1-CREB3L1 gene fusion occurring between exon 11 of EWSR1 and exon 6 of CREB3L1 was present in both the LGFMS and SEF components. This unusual case provides evidence that a subset of hybrid LGFMS-SEF harbor EWSR1-CREB3L1 gene fusions. In this case, these features were associated with an aggressive clinical course, with disease-associated mortality occurring within 12 months of diagnosis.

Genomic Evolution of Breast Cancer Metastasis and Relapse

DOE PAGES

Yates, Lucy R.; Knappskog, Stian; Wedge, David; ...

2017-08-14

Patterns of genomic evolution between primary and metastatic breast cancer have not been studied in large numbers, despite patients with metastatic breast cancer having dismal survival. We sequenced whole genomes or a panel of 365 genes on 299 samples from 170 patients with locally relapsed or metastatic breast cancer. Several lines of analysis indicate that clones seeding metastasis or relapse disseminate late from primary tumors, but continue to acquire mutations, mostly accessing the same mutational processes active in the primary tumor. Most distant metastases acquired driver mutations not seen in the primary tumor, drawing from a wider repertoire of cancermore » genes than early drivers. Lastly, these include a number of clinically actionable alterations and mutations inactivating SWI-SNF and JAK2-STAT3 pathways.« less

Genomic Evolution of Breast Cancer Metastasis and Relapse

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yates, Lucy R.; Knappskog, Stian; Wedge, David

Patterns of genomic evolution between primary and metastatic breast cancer have not been studied in large numbers, despite patients with metastatic breast cancer having dismal survival. We sequenced whole genomes or a panel of 365 genes on 299 samples from 170 patients with locally relapsed or metastatic breast cancer. Several lines of analysis indicate that clones seeding metastasis or relapse disseminate late from primary tumors, but continue to acquire mutations, mostly accessing the same mutational processes active in the primary tumor. Most distant metastases acquired driver mutations not seen in the primary tumor, drawing from a wider repertoire of cancermore » genes than early drivers. Lastly, these include a number of clinically actionable alterations and mutations inactivating SWI-SNF and JAK2-STAT3 pathways.« less

[Malignant peripheral nerve sheath tumor with perineural differentiation (malignant perineurinoma) of the cervix uteri].

PubMed

Dolzhikov, A A; Mukhina, T S

2014-01-01

The paper describes a case of a malignant peripheral nerve sheath tumor with perineural differentiation and at the rare site of the cervix uteri in a 57-year-old patient. The diagnosis was established on the basis of extensive immunohistochemical examination, by excluding the similar neoplasms and detecting an immunophenotype characteristic of perineural differentiation. There are data available in the literature on the morphological and immunophenotypical characteristics of this tumor.

Apoptosis and tumor cell death in response to HAMLET (human alpha-lactalbumin made lethal to tumor cells).

PubMed

Hallgren, Oskar; Aits, Sonja; Brest, Patrick; Gustafsson, Lotta; Mossberg, Ann-Kristin; Wullt, Björn; Svanborg, Catharina

2008-01-01

HAMLET (human alpha-lactalbumin made lethal to tumor cells) is a molecular complex derived from human milk that kills tumor cells by a process resembling programmed cell death. The complex consists of partially unfolded alpha-lactalbumin and oleic acid, and both the protein and the fatty acid are required for cell death. HAMLET has broad antitumor activity in vitro, and its therapeutic effect has been confirmed in vivo in a human glioblastoma rat xenograft model, in patients with skin papillomas and in patients with bladder cancer. The mechanisms of tumor cell death remain unclear, however. Immediately after the encounter with tumor cells, HAMLET invades the cells and causes mitochondrial membrane depolarization, cytochrome c release, phosphatidyl serine exposure, and a low caspase response. A fraction of the cells undergoes morphological changes characteristic of apoptosis, but caspase inhibition does not rescue the cells and Bcl-2 overexpression or altered p53 status does not influence the sensitivity of tumor cells to HAMLET. HAMLET also creates a state of unfolded protein overload and activates 20S proteasomes, which contributes to cell death. In parallel, HAMLET translocates to tumor cell nuclei, where high-affinity interactions with histones cause chromatin disruption, loss of transcription, and nuclear condensation. The dying cells also show morphological changes compatible with macroautophagy, and recent studies indicate that macroautophagy is involved in the cell death response to HAMLET. The results suggest that HAMLET, like a hydra with many heads, may interact with several crucial cellular organelles, thereby activating several forms of cell death, in parallel. This complexity might underlie the rapid death response of tumor cells and the broad antitumor activity of HAMLET.

Histologic and immunohistochemical assessment of penile carcinomas in a North American population.

PubMed

Mentrikoski, Mark J; Stelow, Edward B; Culp, Stephen; Frierson, Henry F; Cathro, Helen P

2014-10-01

Penile squamous cell carcinoma (SCC) is sometimes an aggressive disease that has a variable worldwide incidence, in part due to differing rates of inflammatory and infectious risk factors. In the developed world, penile SCC is a rare malignancy, and most studies therefore originate in less developed countries. The current study was undertaken to examine the morphologic and immunohistochemical features of penile SCC from a region with low disease incidence. Sixty-two complete or partial penectomy specimens from 59 patients were reviewed. Twenty-six patients had metastasis, 3 had recurrent disease, and 7 were dead due to tumor. Most patients were uncircumcised (72%). Twenty-two percent of carcinomas were associated with lichen sclerosis. Perineural invasion was significantly associated with metastasis (P=0.007). Most SCCs (65%) had the usual keratinizing morphology, and these tumors were significantly associated with the differentiated form of intraepithelial lesion (P<0.0001), p53 positivity (P=0.002), cyclin D1 positivity (P=0.007), and EGFR overexpression (P=0.003). Human papilloma virus (HPV)-associated tumors accounted for 27% and were basaloid (8%), warty (10%), mixed (6%), or lymphoepithelioma-like carcinoma (4%) variants. These were significantly associated with p16 expression (P<0.0001) and the undifferentiated form of intraepithelial lesion (P<0.001). Among all SCCs, there was no difference in the immunohistochemical or in situ hybridization profile between primary tumors and metastases. Although penile SCC is rare in the United States, the tumor variants, immunohistochemical profiles, and proportion of HPV-associated tumors are similar to those in less developed countries. Two distinct pathways appear to lead to carcinogenesis; one is related to underlying chronic inflammatory states, involves p53 mutation, cyclin D1 overexpression, and culminates in classic keratinizing SCC. The other pathway involves high-risk HPV infection, demonstrates strong p16 expression, and results in SCC with varied, but distinctive morphologies.

Biogeography, phylogeny, and morphological evolution of central Texas cave and spring salamanders

PubMed Central

2013-01-01

Background Subterranean faunal radiations can result in complex patterns of morphological divergence involving both convergent or parallel phenotypic evolution and cryptic species diversity. Salamanders of the genus Eurycea in central Texas provide a particularly challenging example with respect to phylogeny reconstruction, biogeography and taxonomy. These predominantly aquatic species inhabit karst limestone aquifers and spring outflows, and exhibit a wide range of morphological and genetic variation. We extensively sampled spring and cave populations of six Eurycea species within this group (eastern Blepsimolge clade), to reconstruct their phylogenetic and biogeographic history using mtDNA and examine patterns and origins of cave- and surface-associated morphological variation. Results Genetic divergence is generally low, and many populations share ancestral haplotypes and/or show evidence of introgression. This pattern likely indicates a recent radiation coupled with a complex history of intermittent connections within the aquatic karst system. Cave populations that exhibit the most extreme troglobitic morphologies show no or very low divergence from surface populations and are geographically interspersed among them, suggesting multiple instances of rapid, parallel phenotypic evolution. Morphological variation is diffuse among cave populations; this is in contrast to surface populations, which form a tight cluster in morphospace. Unexpectedly, our analyses reveal two distinct and previously unrecognized morphological groups encompassing multiple species that are not correlated with spring or cave habitat, phylogeny or geography, and may be due to developmental plasticity. Conclusions The evolutionary history of this group of spring- and cave-dwelling salamanders reflects patterns of intermittent isolation and gene flow influenced by complex hydrogeologic dynamics that are characteristic of karst regions. Shallow genetic divergences among several species, evidence of genetic exchange, and nested relationships across morphologically disparate cave and spring forms suggests that cave invasion was recent and many troglobitic morphologies arose independently. These patterns are consistent with an adaptive-shift hypothesis of divergence, which has been proposed to explain diversification in other karst fauna. While cave and surface forms often do not appear to be genetically isolated, morphological diversity within and among populations may be maintained by developmental plasticity, selection, or a combination thereof. PMID:24044519

Secular Evolution in Barred Galaxies: Observations

NASA Astrophysics Data System (ADS)

Merrifield, M.

2002-12-01

This paper describes a framework for studying galaxy morphology, particularly bar strength, in a quantitative manner, and presents applications of this approach that reveal observational evidence for secular evolution in bar morphology. The distribution of bar strength in galaxies is quite strongly bimodal, suggesting that barred and unbarred systems are distinct entities, and that any evolution between these two states must occur on a relatively rapid timescale. Bars' strengths appear to be correlated with their pattern speeds, implying that these structures weaken as they start to slow, and disappear entirely before the bars have slowed significantly. There is also tantalizing evidence that bars are rare beyond a redshift of z ~ 0.7, indicating that galaxies have only recently evolved to a point where bars can readily form.

Acute Leukemia with a Translocation T(4;11)(q21;q23): a Distinct Clinicopathological Entity: Report of a Case with Cytogenetic Clonal Evolution and Review of 146 Cases of the Literature.

PubMed

Léglise, M C; Rivière, D; Brière, J

1990-01-01

We present a cytogenetic clonal evolution that correlates morphological and immunological shifts in a case of a patient with a t(4;11) (q21;q23) acute leukemia. We take this opportunity to review 146 cases reported so far, with special reference to morphology, immunophenotyping, cytogenetics, clinical characteristics and evolution. Particular features are underlined, and prognosis, leukemic stem cell origin, chromosomal breakpoints and genes involved are discussed. A relationship between this type of leukemia and exposure to carcinogens is suggested by a high rate of secondary leukemia in adults and a high frequency in newborns and infants.

Clonal status of actionable driver events and the timing of mutational processes in cancer evolution

PubMed Central

McGranahan, Nicholas; Favero, Francesco; de Bruin, Elza C.; Birkbak, Nicolai Juul; Szallasi, Zoltan; Swanton, Charles

2015-01-01

Deciphering whether actionable driver mutations are found in all or a subset of tumor cells will likely be required to improve drug development and precision medicine strategies. We analyzed nine cancer types to determine the subclonal frequencies of driver events, to time mutational processes during cancer evolution, and to identify drivers of subclonal expansions. Although mutations in known driver genes typically occurred early in cancer evolution, we also identified later subclonal “actionable” mutations, including BRAF(V600E), IDH1(R132H), PIK3CA(E545K), EGFR(L858R), and KRAS(G12D), which may compromise the efficacy of targeted therapy approaches. More than 20% of IDH1 mutations in glioblastomas, and 15% of mutations in genes in the PI3K(phosphatidylinositol 3-kinase)–AKT–mTOR (mammalian target of rapamycin) signaling axis across all tumor types were subclonal. Mutations in the RAS–MEK (mitogen-activated protein kinase kinase) signaling axis were less likely to be subclonal than mutations in genes associated with PI3K-AKT-mTORsignaling. Analysis of late mutations revealed a link between APOBEC-mediated mutagenesis and the acquisition of subclonal driver mutations and uncovered putative cancer genes involved in subclonal expansions, including CTNNA2 and ATXN1. Our results provide a pan-cancer census of driver events within the context of intratumor heterogeneity and reveal patterns of tumor evolution across cancers. The frequent presence of subclonal driver mutations suggests the need to stratify targeted therapy response according to the proportion of tumor cells in which the driver is identified. PMID:25877892

Tubulocystic Carcinoma of the Kidney with Poorly Differentiated Foci: A Frequent Morphologic Pattern of Fumarate Hydratase-Deficient Renal Cell Carcinoma

PubMed Central

Smith, Steven C; Trpkov, Kiril; Chen, Ying-Bei; Mehra, Rohit; Sirohi, Deepika; Ohe, Chisato; Cani, Andi K; Hovelson, Daniel H; Omata, Kei; McHugh, Jonathan B; Jochum, Wolfram; Colecchia, Maurizio; Amin, Mitual; Divatia, Mukul K; Hes, Ondřej; Menon, Santosh; da Cunha, Isabela Werneck; Tripodi, Sergio; Brimo, Fadi; Gill, Anthony J; Osunkoya, Adeboye O; Magi-Galluzzi, Cristina; Sibony, Mathilde; Williamson, Sean R; Nesi, Gabriella; Picken, Maria M; Maclean, Fiona; Agaimy, Abbas; Cheng, Liang; Epstein, Jonathan I; Reuter, Victor E; Tickoo, Satish K; Tomlins, Scott A; Amin, Mahul B

2017-01-01

An emerging group of high grade renal cell carcinomas (RCCs), particularly carcinomas arising in the hereditary leiomyomatosis renal cell carcinoma syndrome (HLRCC), show fumarate hydratase (FH) gene mutation and loss of function. Based on similar cytomorphology and clinicopathologic features between these tumors and cases described as tubulocystic carcinomas with poorly differentiated foci of infiltrative adenocarcinoma (TC-PD), we hypothesized a relationship between these entities. First, 29 RCCs with morphology of TC-PD were identified retrospectively and assessed for FH expression and aberrant succination (2SC) by immunohistochemistry (IHC), with targeted next generation sequencing (NGS) of 409 genes—including FH—performed on a subset. The 29 TC-PD RCCs included 21 males and 8 females, aged 16-86 years (median 46), with tumors measuring 3-21 cm (median 9) arising in the right (n=16) and left (n=13) kidneys. Family history or stigmata of HLRCC were identified in only 3 (12%). These tumors were aggressive, with 79% showing perinephric extension, nodal involvement in 41%, and metastasis in 86%. Of these, 16 (55%) demonstrated loss of FH by IHC (14/14 with positive 2SC). In contrast, 5 (17%) showed a wild type immunoprofile of FH+/2SC-. An intriguing group of 8 (28%) showed variable FH± positivity, but with strong/diffuse 2SC+. NGS revealed 8 cases with FH mutations, including 5 FH-/2SC+ and 3 FH±/2SC+ cases, but none in FH+/2SC- cases. Secondly, we retrospectively reviewed the morphology of two well-characterized cohorts of RCCs with FH-deficiency determined by IHC or sequencing (n=23 and n=9), unselected for TC-PD pattern, identifying the TC-PD morphology in 10 (31%). We conclude that RCCs with TC-PD morphology are enriched for FH deficiency, and we recommend additional work up, including referral to genetic counseling, for prospective cases. Additionally, based on these and other observations, we propose the term “FH-deficient RCC” as a provisional term for tumors with a combination of suggestive morphology and immunophenotype but where genetic confirmation is unavailable upon diagnosis. This term will serve as a provisional nomenclature that will enable triage of individual cases for genetic counseling and testing, while designating these cases for prospective studies of their relationship to HLRCC. PMID:27635946

Morphological response contributes to patient selection for rescue liver resection in chemotherapy patients with initially un-resectable colorectal liver metastasis.

PubMed

Suzuki, Koichi; Muto, Yuta; Ichida, Kosuke; Fukui, Taro; Takayama, Yuji; Kakizawa, Nao; Kato, Takaharu; Hasegawa, Fumi; Watanabe, Fumiaki; Kaneda, Yuji; Kikukawa, Rina; Saito, Masaaki; Tsujinaka, Shingo; Futsuhara, Kazushige; Takata, Osamu; Noda, Hiroshi; Miyakura, Yasuyuki; Kiyozaki, Hirokazu; Konishi, Fumio; Rikiyama, Toshiki

2017-08-01

Morphological response is considered an improved surrogate to the Response Evaluation Criteria in Solid Tumors (RECIST) model with regard to predicting the prognosis for patients with colorectal liver metastases. However, its use as a decision-making tool for surgical intervention has not been examined. The present study assessed the morphological response in 50 patients who underwent chemotherapy with or without bevacizumab for initially un-resectable colorectal liver metastases. Changes in tumor morphology between heterogeneous with uncertain borders and homogeneous with clear borders were defined as an optimal response (OR). Patients were also assessed as having an incomplete response (IR), and an absence of marked changes was assessed as no response (NR). No significant difference was observed in progression-free survival (PFS) between complete response/partial response (CR/PR) and stable disease/progressive disease (SD/PD), according to RECIST. By contrast, PFS for OR/IR patients was significantly improved compared with that for NR patients (13.2 vs. 8.7 months; P=0.0426). Exclusion of PD enhanced the difference in PFS between OR/IR and NR patients (15.1 vs. 9.3 months; P<0.0001), whereas no difference was observed between CR/PR and SD. The rate of OR and IR in patients treated with bevacizumab was 47.4% (9/19), but only 19.4% (6/31) for patients that were not administered bevacizumab. Comparison of the survival curves between OR/IR and NR patients revealed similar survival rates at 6 months after chemotherapy, but the groups exhibited different survival rates subsequent to this period of time. Patients showing OR/IR within 6 months appeared to be oncologically stable and could be considered as candidates for surgical intervention, including rescue liver resection. Comparing the pathological and morphological features of the tumor with representative optimal response, living tumor cells were revealed to be distributed within the area of vascular reconstruction induced by bevacizumab, resulting in a predictive value for prognosis in the patients treated with bevacizumab. The present findings provided the evidence for physicians to consider patients with previously un-resectable metastatic colorectal cancer as candidates for surgical treatment. Morphological response is a useful decision-making tool for evaluating these patients for rescue liver resection following chemotherapy.

Evolution of cranial telescoping in echolocating whales (Cetacea: Odontoceti).

PubMed

Churchill, Morgan; Geisler, Jonathan H; Beatty, Brian L; Goswami, Anjali

2018-05-01

Odontocete (echolocating whale) skulls exhibit extreme posterior displacement and overlapping of facial bones, here referred to as retrograde cranial telescoping. To examine retrograde cranial telescoping across 40 million years of whale evolution, we collected 3D scans of whale skulls spanning odontocete evolution. We used a sliding semilandmark morphometric approach with Procrustes superimposition and PCA to capture and describe the morphological variation present in the facial region, followed by Ancestral Character State Reconstruction (ACSR) and evolutionary model fitting on significant components to determine how retrograde cranial telescoping evolved. The first PC score explains the majority of variation associated with telescoping and reflects the posterior migration of the external nares and premaxilla alongside expansion of the maxilla and frontal. The earliest diverging fossil odontocetes were found to exhibit a lesser degree of cranial telescoping than later diverging but contemporary whale taxa. Major shifts in PC scores and centroid size are identified at the base of Odontoceti, and early burst and punctuated equilibrium models best fit the evolution of retrograde telescoping. This indicates that the Oligocene was a period of unusually high diversity and evolution in whale skull morphology, with little subsequent evolution in telescoping. © 2018 The Author(s). Evolution © 2018 The Society for the Study of Evolution.

Morphological evolution of Ge/Si(001) quantum dot rings formed at the rim of wet-etched pits.

PubMed

Grydlik, Martyna; Brehm, Moritz; Schäffler, Friedrich

2012-10-30

We demonstrate the formation of Ge quantum dots in ring-like arrangements around predefined {111}-faceted pits in the Si(001) substrate. We report on the complex morphological evolution of the single quantum dots contributing to the rings by means of atomic force microscopy and demonstrate that by careful adjustment of the epitaxial growth parameters, such rings containing densely squeezed islands can be grown with large spatial distances of up to 5 μm without additional nucleation of randomly distributed quantum dots between the rings.

Cellular angiofibroma with atypia or sarcomatous transformation: clinicopathologic analysis of 13 cases.

PubMed

Chen, Eleanor; Fletcher, Christopher D M

2010-05-01

Cellular angiofibroma is a mesenchymal neoplasm that is characterized by a bland spindle cell component, morphologically reminiscent of spindle cell lipoma, and thick-walled vessels. The tumor occurs equally in men and women and usually arises in the inguino-scrotal or vulvovaginal regions. An earlier study of 51 cases from our group showed that the tumor follows a benign course without any tendency for recurrence. In 1 case, an intralesional microscopic nodule of pleomorphic liposarcoma was observed. The biologic significance of atypia or sarcomatous transformation in cellular angiofibroma remains uncertain. In this study, we characterized clinicopathologic features in 13 cases of cellular angiofibroma with morphologic atypia or sarcomatous transformation. Thirteen cases with atypia or sarcomatous transformation among 154 usual cellular angiofibromas identified between 1993 and 2009 were retrieved from consultation files. There were 12 females and 1 male ranging in age from 39 to 71 years (median age, 46 y). Tumor size ranged from 1.2 to 7.5 cm. In 11 cases, the tumors occurred in the vulva. One case each occurred in the paratesticular and hip regions. Most tumors were located in subcutaneous tissue. There were 4 cases of cellular angiofibroma with atypia. Three showed severely atypical cells as scattered foci within the cellular angiofibroma. One case showed a discrete nodule of atypical cells. There were 9 cases of cellular angiofibroma with morphologic features of sarcomatous transformation. In each case, abrupt transition to a discrete sarcomatous component was seen. Of these 9 cases, the sarcomatous component in 2 cases showed features of pleomorphic liposarcoma with multivacuolated lipoblasts readily identified. Three of these 9 cases showed discrete nodule(s) closely resembling atypical lipomatous tumor within usual cellular angiofibroma. In the remaining 4 cases, the sarcomatous component was composed of pleomorphic spindle cells arranged in various patterns. By immunohistochemistry, atypical cells and sarcomatous areas showed either multifocal or more diffuse p16 expression compared with either scattered or negative expression in the conventional cellular angiofibroma. The 3 cases with atypical lipomatous tumor-like areas were negative for MDM-2 and CDK4. Follow-up information was available for 7 patients (range from 2 to 75 mo; median: 14 mo). Six patients did not develop recurrence or metastasis. One patient died of metastatic carcinoma of unknown primary site 27 months after the diagnosis of cellular angiofibroma with sarcomatous transformation. Cellular angiofibroma with atypia or morphologic sarcomatous transformation occurs predominantly in the subcutaneous tissue of the vulva and, as yet, shows no evident tendency to recur based on limited clinical follow-up available for 7 cases. The sarcomatous component can show variable features including atypical lipomatous tumor, pleomorphic liposarcoma, and pleomorphic sarcoma NOS. Overexpression of p16 in the atypical cells and sarcomatous component suggests a possible underlying molecular mechanism.

Clonal evolution in relapsed and refractory diffuse large B-cell lymphoma is characterized by high dynamics of subclones.

PubMed

Melchardt, Thomas; Hufnagl, Clemens; Weinstock, David M; Kopp, Nadja; Neureiter, Daniel; Tränkenschuh, Wolfgang; Hackl, Hubert; Weiss, Lukas; Rinnerthaler, Gabriel; Hartmann, Tanja N; Greil, Richard; Weigert, Oliver; Egle, Alexander

2016-08-09

Little information is available about the role of certain mutations for clonal evolution and the clinical outcome during relapse in diffuse large B-cell lymphoma (DLBCL). Therefore, we analyzed formalin-fixed-paraffin-embedded tumor samples from first diagnosis, relapsed or refractory disease from 28 patients using next-generation sequencing of the exons of 104 coding genes. Non-synonymous mutations were present in 74 of the 104 genes tested. Primary tumor samples showed a median of 8 non-synonymous mutations (range: 0-24) with the used gene set. Lower numbers of non-synonymous mutations in the primary tumor were associated with a better median OS compared with higher numbers (28 versus 15 months, p=0.031). We observed three patterns of clonal evolution during relapse of disease: large global change, subclonal selection and no or minimal change possibly suggesting preprogrammed resistance. We conclude that targeted re-sequencing is a feasible and informative approach to characterize the molecular pattern of relapse and it creates novel insights into the role of dynamics of individual genes.