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Sample records for early tumor development

  1. Polo-like kinase 1 is essential for early embryonic development and tumor suppression.

    PubMed

    Lu, Lin-Yu; Wood, Jamie L; Minter-Dykhouse, Katherine; Ye, Lin; Saunders, Thomas L; Yu, Xiaochun; Chen, Junjie

    2008-11-01

    Polo-like kinases (Plks) are serine/threonine kinases that are highly conserved in organisms from yeasts to humans. Previous reports have shown that Plk1 is critical for all stages of mitosis and may play a role in DNA replication during S phase. While much work has focused on Plk1, little is known about the physiological function of Plk1 in vivo. To address this question, we generated Plk1 knockout mice. Plk1 homozygous null mice were embryonic lethal, and early Plk1(-/-) embryos failed to survive after the eight-cell stage. Immunocytochemistry studies revealed that Plk1-null embryos were arrested outside the mitotic phase, suggesting that Plk1 is important for proper cell cycle progression. It has been postulated that Plk1 is a potential oncogene, due to its overexpression in a variety of tumors and tumor cell lines. While the Plk1 heterozygotes were healthy at birth, the incidence of tumors in these animals was threefold greater than that in their wild-type counterparts, demonstrating that the loss of one Plk1 allele accelerates tumor formation. Collectively, our data support that Plk1 is important for early embryonic development and may function as a haploinsufficient tumor suppressor.

  2. Cysts mark the early stage of metastatic tumor development in non-small cell lung cancer

    PubMed Central

    Thakur, Chitra; Rapp, Ulf R.; Rudel, Thomas

    2018-01-01

    Identifying metastatic tumor growth at an early stage has been one of the biggest challenges in the treatment of lung cancer. By genetic lineage tracing approach in a conditional model of Non-Small Cell Lung Cancer (NSCLC) in mice, we demonstrate that cystic lesions represent an early stage of metastatic invasion. We generated a mouse model for NSCLC which incorporated a heritable DsRed fluorescent tag driven by the ubiquitous CAG promoter in the alveolar type II cells of the lung. We found early cystic lesions in a secondary organ (liver) that lacked the expression of bona fide lung makers namely Scgb1a1 and surfactant protein C Sftpc and were DsRed positive hence identifying lung as their source of origin. This demonstrates the significant potential of alveolar type II cells in orchestrating the process of metastasis, rendering it as one of the target cell types of the lung of therapeutic importance in human NSCLC. PMID:29464089

  3. Early-in-life dietary zinc deficiency and supplementation and mammary tumor development in adulthood female rats.

    PubMed

    da Silva, Flávia R M; Grassi, Tony F; Zapaterini, Joyce R; Bidinotto, Lucas T; Barbisan, Luis F

    2017-06-01

    Zinc deficiency during pregnancy and postnatal life can adversely increase risk of developing human diseases at adulthood. The present study was designed to evaluate whether dietary zinc deficiency or supplementation during the pregnancy, lactation and juvenile stages interferes in the development of mammary tumors induced by 7,12-dimethylbenzanthracene (DMBA) in female Sprague-Dawley (SD) rats. Pregnant female SD rats were allocated into three groups: zinc-adequate diet (ZnA - 35-mg/kg chow), zinc-deficient diet (ZnD - 3-mg/kg chow) or zinc-supplemented diet (ZnS - 180-mg/kg chow) during gestational day 10 (GD 10) until the litters' weaning. Female offspring received the same diets as their dams until postnatal day (PND) 51. At PND 51, the animals received a single dose of DMBA (50 mg/kg, ig) and zinc-adequate diets. At PND 180, female were euthanized, and tumor samples were processed for histological evaluation and gene expression microarray analysis. The ZnD induced a significant reduction in female offspring body weight evolution and in mammary gland development. At late in life, the ZnD or ZnS did not alter the latency, incidence, multiplicity, volume or histological types of mammary tumors in relation to the ZnA group. However, the total tumor number in ZnS group was higher than in ZnA group, accompanied by distinct expression of 4 genes up- and 15 genes down-regulated. The present findings indicate that early-in-life dietary zinc supplementation, differently to zinc deficiency, has a potential to modify the susceptibility to the development of mammary tumors induced by DMBA. Copyright © 2017 Elsevier Inc. All rights reserved.

  4. How Numbers, Nature, and Immune Status of Foxp3+ Regulatory T-Cells Shape the Early Immunological Events in Tumor Development

    PubMed Central

    Darrasse-Jèze, Guillaume; Podsypanina, Katrina

    2013-01-01

    The influence of CD4+CD25+Foxp3+ regulatory T-cells (Tregs) on cancer progression has been demonstrated in a large number of preclinical models and confirmed in several types of malignancies. Neoplastic processes trigger an increase of Treg numbers in draining lymph nodes, spleen, blood, and tumors, leading to the suppression of anti-tumor responses. Treg-depletion before or early in tumor development may lead to complete tumor eradication and extends survival of mice and humans. However this strategy is ineffective in established tumors, highlighting the critical role of the early Treg-tumor encounters. In this review, after discussing old and new concepts of immunological tumor tolerance, we focus on the nature (thymus-derived vs. peripherally derived) and status (naïve or activated/memory) of the regulatory T-cells at tumor emergence. The recent discoveries in this field suggest that the activation status of Tregs and effector T-cells (Teffs) at the first encounter with the tumor are essential to shape the fate and speed of the immune response across a variety of tumor models. The relative timing of activation/recruitment of anti-tumor cells vs. tolerogenic cells at tumor emergence appears to be crucial in the identification of tumor cells as friend or foe, which has broad implications for the design of cancer immunotherapies. PMID:24133490

  5. Microwave tumor ablation: cooperative academic-industry development of a high-power gas-cooled system with early clinical results

    NASA Astrophysics Data System (ADS)

    Brace, Christopher L.; Ziemlewicz, Timothy J.; Schefelker, Rick; Hinshaw, J. L.; Lubner, Meghan G.; Lee, Fred T.

    2013-02-01

    Microwave tumor ablation continues to evolve into a viable treatment option for many cancers. Current systems are poised to supplant radiofrequency ablation as the dominant percutaneous thermal therapy. Here is provided an overview of technical details and early clinical results with a high-powered, gas-cooled microwave ablation system. The system was developed with academic-industry collaboration using federal and private funding. The generator comprises three synchronous channels that each produce up to 140W at 2.45GHz. A mountable power distribution module facilitates CT imaging guidance and monitoring and reduces clutter in the sterile field. Cryogenic carbon-dioxide cools the coaxial applicator, permitting a thin applicator profile (~1.5 mm diameter) and high power delivery. A total of 106 liver tumors were treated (96 malignant, 10 benign) from December 2010 to June 2012 at a single academic institution. Mean tumor size +/- standard deviation was 2.5+/-1.3cm (range 0.5-13.9cm). Treatment time was 5.4+/-3.3min (range 1-20min). Median follow-up was 6 months (range 1-16 months). Technical success was reported in 100% of cases. Local tumor progression was noted in 4/96 (4.3%) of malignancies. The only major complication was a pleural effusion that was treated with thoracentesis. Microwave ablation with this system is an effective treatment for liver cancer. Compared to previous data from the same institution, these results suggest an increased efficacy and equivalent safety to RF ablation. Additional data from the lung and kidney support this conclusion.

  6. Early Developments, 1998.

    ERIC Educational Resources Information Center

    Little, Loyd, Ed.

    1998-01-01

    This document consists of the two 1998 issues of a journal reporting new research in early child development conducted by the Frank Porter Graham Child Development Center at the University of North Carolina at Chapel Hill. In the Spring 1998 issue, articles highlight the Center's diverse cross-cultural projects and global research, training and…

  7. A Decade of Experience in Developing Preclinical Models of Advanced- or Early-Stage Spontaneous Metastasis to Study Antiangiogenic Drugs, Metronomic Chemotherapy, and the Tumor Microenvironment.

    PubMed

    Kerbel, Robert S

    2015-01-01

    The clinical circumstance of treating spontaneous metastatic disease, after resection of primary tumors, whether advanced/overt or microscopic in nature, is seldom modeled in mice and may be a major factor in explaining the frequent discordance between preclinical and clinical therapeutic outcomes where the trend is "overprediction" of positive results in preclinical mouse model studies. To evaluate this hypothesis, a research program was initiated a decade ago to develop multiple models of metastasis in mice, using variants of human tumor cell lines selected in vivo for enhanced spontaneous metastatic aggressiveness after surgical resection of established orthotopic primary tumors. These models have included breast, renal, and colorectal carcinomas; ovarian cancer (but without prior surgery); and malignant melanoma. They have been used primarily for experimental therapeutic investigations involving various antiangiogenic drugs alone or with chemotherapy, especially "metronomic" low-dose chemotherapy. The various translational studies undertaken have revealed a number of clinically relevant findings. These include the following: (i) the potential of metronomic chemotherapy, especially when combined with a vascular endothelial growth factor pathway targeting drug to successfully treat advanced metastatic disease; (ii) the development of relapsed spontaneous brain metastases in mice with melanoma or breast cancer whose systemic metastatic disease is successfully controlled for a period with a given therapy; (iii) foreshadowing the failure of adjuvant antiangiogenic drug-based phase III trials; (iv) recapitulating the failure of oral antiangiogenic tyrosine kinase inhibitors plus standard chemotherapy in contrast to the modest successes of antiangiogenic antibodies plus chemotherapy in metastatic breast cancer; and (v) revealing "vessel co-option" and absence of angiogenesis as a determinant of intrinsic resistance or minimal responsiveness to antiangiogenic therapy

  8. Early Childhood Development.

    ERIC Educational Resources Information Center

    Koh, Edgar, Ed.

    1989-01-01

    Focused on early childhood development, this "UNICEF Intercom" asserts that developmental programs should aim to give children a fair chance at growth beyond survival. First presented are moral, scientific, social equity, economic, population, and programatic arguments for looking beyond the fundamental objective of saving young lives.…

  9. Early Program Development

    1971-01-01

    This 1971 artist's concept shows a Nuclear Shuttle and an early Space Shuttle docked with an Orbital Propellant Depot. As envisioned by Marshall Space Flight Center Program Development persornel, an orbital modular propellant storage depot, supplied periodically by the Space Shuttle or Earth-to-orbit fuel tankers, would be critical in making available large amounts of fuel to various orbital vehicles and spacecraft.

  10. Early Program Development

    1970-01-01

    This artist's concept from 1970 shows a Nuclear Shuttle docked to an Orbital Propellant Depot and an early Space Shuttle. As envisioned by Marshall Space Flight Center Program Development plarners, the Nuclear Shuttle, in either manned or unmanned mode, would deliver payloads to lunar orbit or other destinations then return to Earth orbit for refueling and additonal missions.

  11. Renal Tumors: Technical Success and Early Clinical Experience with Radiofrequency Ablation of 18 Tumors

    SciT

    Sabharwal, Rohan, E-mail: rohan50000@yahoo.com; Vladica, Philip

    2006-04-15

    Purpose. To evaluate the feasibility, safety, and technical efficacy of image-guided radiofrequency ablation (RFA) for the treatment of small peripheral renal tumors and to report our early results with this treatment modality. Methods. Twenty-two RFA sessions for 18 tumors were performed in 11 patients with renal tumors. Indications included coexistent morbidity, high surgical or anesthetic risk, solitary kidney, and hereditary predisposition to renal cell carcinoma. Ten patients had CT-guided percutaneous RFA performed on an outpatient basis. One patient had open intraoperative ultrasound-guided RFA. Technical success was defined as elimination of areas that enhanced at imaging within the entire tumor. Withmore » the exception of one patient with renal insufficiency who required gadolinium-enhanced MRI, the remaining patients underwent contrast-enhanced CT for post-treatment follow-up assessment. Follow-up was performed after 2-4 weeks and then at 3, 6, 12 months, and every 12 months thereafter. Results. Fourteen (78%) of 18 tumors were successfully ablated with one session. Three of the remaining four tumors required two sessions for successful ablation. One tumor will require a third session for areas of persistent enhancement. Mean patient age was 72.82 {+-} 10.43 years. Mean tumor size was 1.95 {+-} 0.79 cm. Mean follow-up time was 10.91 months. All procedures were performed without any major complications. Conclusions. Our early experience with percutaneous image-guided radiofrequency ablation demonstrates it to be a feasible, safe, noninvasive, and effective treatment of small peripheral renal tumors.« less

  12. Early Postoperative Perils of Intraventricular Tumors: An Observational Comparative Study.

    PubMed

    Schär, Ralph T; Schwarz, Christa; Söll, Nicole; Raabe, Andreas; Z'Graggen, Werner J; Beck, Jürgen

    2018-05-01

    Early postoperative patient surveillance after removal of intraventricular tumors is often hindered by delayed awakening and prolonged somnolence. The objective of this study was to analyze the incidence of early critical postoperative events after elective craniotomy for intraventricular tumors in adults compared with extraventricular lesions. An observational comparative study was conducted on adult patients who had undergone first-time elective craniotomy between November 2011 and August 2016. Patients were stratified into extraventricular lesions (group 1) and intraventricular tumors (group 2). The rates of late extubation, early postoperative seizures, emergency head computed tomography (CT) scans, and urgent surgical intervention within 48 hours and mortality within 30 days of surgery were analyzed from a prospective database. A total of 977 elective craniotomies were analyzed, including 951 (97.3%) in group 1 and 26 (2.7%) in group 2. Emergency CT scans were ordered significantly more frequently in group 2 (34.6% vs. 8.4%; odds ratio, 5.76; 95% confidence interval [CI], 2.49-13.35; P = 0.0002), and the incidence of urgent surgical intervention was significantly higher in group 2 (11.5% vs. 0.8%; odds ratio, 15.38; 95% CI, 3.83-61.72; P = 0.002). The main reason for urgent surgical intervention in group 2 was acute obstructive hydrocephalus. Overall surgical mortality after 30 days was 0.3% (3 cases in group 1, no cases in group 2). Intraventricular tumors are at significantly higher risk for early emergency head CT and urgent surgical intervention. This patient cohort might benefit from routine intraoperative and early postoperative imaging, as well as intraoperative extraventricular drain placement. Copyright © 2018 Elsevier Inc. All rights reserved.

  13. Monitoring Daily Dynamics of Early Tumor Response to Targeted Therapy by Detecting Circulating Tumor DNA in Urine

    PubMed Central

    Husain, Hatim; Melnikova, Vladislava O.; Kosco, Karena; Woodward, Brian; More, Soham; Pingle, Sandeep C.; Weihe, Elizabeth; Park, Ben Ho; Tewari, Muneesh; Erlander, Mark G.; Cohen, Ezra; Lippman, Scott M.; Kurzrock, Razelle

    2017-01-01

    Purpose Non-invasive drug biomarkers for the early assessment of tumor response can enable adaptive therapeutic decision-making and proof-of-concept studies for investigational drugs. Circulating tumor DNA (ctDNA) is released into the circulation by tumor cell turnover and has been shown to be detectable in urine. Experimental Design We tested the hypothesis that dynamic changes in epidermal growth factor receptor (EGFR) activating (exon 19del and L858R) and resistance (T790M) mutation levels detected in urine could inform tumor response within days of therapy for advanced non-small cell lung cancer (NSCLC) patients receiving osimertinib, a second line third generation anti-EGFR tyrosine kinase inhibitor. Results Eight of nine evaluable NSCLC patients had detectable T790M-mutant DNA fragments in pre-treatment baseline samples. Daily monitoring of mutations in urine indicated a pattern of intermittent spikes throughout week 1 suggesting apoptosis with an overall decrease in fragment numbers between baselines to day 7 preceding radiographic response assessed at 6-12 weeks. Conclusions These findings suggest drug-induced tumor apoptosis within days of initial dosing. Daily sampling of ctDNA may enable early assessment of patient response and proof-of-concept studies for drug development. PMID:28420725

  14. Early Adolescent Ego Development.

    ERIC Educational Resources Information Center

    James, Michael A.

    1980-01-01

    Presented are the theoretical characteristics of social identity in early adolescence (ages 10 to 15). It is suggested that no longer is identity thought to begin with adolescence, but may have its beginnings in the preteen years. The article draws heavily on Eriksonian concepts. (Editor/KC)

  15. Early Program Development

    1969-01-01

    As part of the Space Task Group's recommendations for more commonality and integration in America's space program, Marshall Space Flight Center engineers proposed an orbiting propellant storage facility to augment Space Shuttle missions. In this artist's concept from 1969 an early version of the Space Shuttle is shown refueling at the facility.

  16. Mesenchymal stem cells in tumor development

    PubMed Central

    Cuiffo, Benjamin G.; Karnoub, Antoine E.

    2012-01-01

    Mesenchymal stem cells (MSCs) are multipotent progenitor cells that participate in the structural and functional maintenance of connective tissues under normal homeostasis. They also act as trophic mediators during tissue repair, generating bioactive molecules that help in tissue regeneration following injury. MSCs serve comparable roles in cases of malignancy and are becoming increasingly appreciated as critical components of the tumor microenvironment. MSCs home to developing tumors with great affinity, where they exacerbate cancer cell proliferation, motility, invasion and metastasis, foster angiogenesis, promote tumor desmoplasia and suppress anti-tumor immune responses. These multifaceted roles emerge as a product of reciprocal interactions occurring between MSCs and cancer cells and serve to alter the tumor milieu, setting into motion a dynamic co-evolution of both tumor and stromal tissues that favors tumor progression. Here, we summarize our current knowledge about the involvement of MSCs in cancer pathogenesis and review accumulating evidence that have placed them at the center of the pro-malignant tumor stroma. PMID:22863739

  17. Early developments in gene-expression profiling of breast tumors: potential for increasing black-white patient disparities in breast cancer outcomes?

    PubMed

    Odierna, Donna H; Afable-Munsuz, Aimee; Ikediobi, Ogechi; Beattie, Mary; Knight, Sara; Ko, Michelle; Wilson, Adrienne; Ponce, Ninez A

    2011-11-01

    New prognostic tests, such as gene-expression profiling (GEP) of breast tumors, are expected to prolong survival and improve the quality of life for many breast cancer patients. In this article, we argue that GEP has not been adequately validated in minority populations, and that both biological and social factors might affect the broad utility of these tests in diverse populations. We suggest that the widespread use of this technology could potentially lead to suboptimal treatment for black women, resulting in a further increase in black-white patient disparities in treatment response, morbidity and mortality rates. We argue for the need to build a large and diverse evidence base for GEP and other emerging technologies in personalized medicine.

  18. Resveratrol inhibits uveal melanoma tumor growth via early mitochondrial dysfunction.

    PubMed

    van Ginkel, Paul R; Darjatmoko, Soesiawati R; Sareen, Dhruv; Subramanian, Lalita; Bhattacharya, Saswati; Lindstrom, Mary J; Albert, Daniel M; Polans, Arthur S

    2008-04-01

    To test the efficacy of resveratrol, a nontoxic plant product, in the treatment of uveal melanoma. The effect of oral administration and peritumor injection of resveratrol was tested on tumor growth in two animal models of uveal melanoma. The mechanism of resveratrol action on uveal melanoma cells was studied in vitro in a cell-viability assay: with JC-1 dye, to measure mitochondrial membrane potential; by Western blot analysis, to analyze the cellular redistribution of cytochrome c and Smac/diablo; and in a fluorescence assay with specific substrates, to measure activation of different caspases. Resveratrol treatment inhibited tumor growth in animal models of uveal melanoma. Since oral administration resulted in relatively low bioavailability of resveratrol, the effect of increased local levels was tested by peritumor injection of the drug. This method resulted in tumor cell death and tumor regression. In vitro experiments with multiple uveal melanoma cell lines demonstrate that resveratrol causes a decrease in cell viability, resulting at least in part from an increase in apoptosis through a mitochondrial pathway. An early event in drug action is the direct targeting of mitochondria by resveratrol, which leads to a decrease in mitochondrial membrane potential and the eventual activation of caspase-3. These data suggest that resveratrol can inhibit tumor growth and can induce apoptosis via the intrinsic mitochondrial pathway and that by further increasing bioavailability of resveratrol the potency of the drug can be increased, leading to tumor regression. The nontoxic nature of the drug at levels needed for therapy make resveratrol an attractive candidate for the treatment of uveal melanoma.

  19. Early Program Development

    1969-01-01

    This 1969 artist's concept illustrates the use of three major elements of NASA's Integrated program, as proposed by President Nixon's Space Task Group. In Phases I and II, a Space Tug with a manipulator-equipped crew module removes a cargo module from an early Space Shuttle Orbiter and docks with it. In Phases III and IV, the Space Tug with attached cargo module flys toward a Nuclear Shuttle. As a result of the Space Task Group's recommendations for more commonality and integration in the American space program, Marshall Space Flight Center engineers studied many of the spacecraft depicted here.

  20. Lin28 sustains early renal progenitors and induces Wilms tumor

    PubMed Central

    Urbach, Achia; Yermalovich, Alena; Zhang, Jin; Spina, Catherine S.; Zhu, Hao; Perez-Atayde, Antonio R.; Shukrun, Rachel; Charlton, Jocelyn; Sebire, Neil; Mifsud, William; Dekel, Benjamin; Pritchard-Jones, Kathy; Daley, George Q.

    2014-01-01

    Wilms Tumor, the most common pediatric kidney cancer, evolves from the failure of terminal differentiation of the embryonic kidney. Here we show that overexpression of the heterochronic regulator Lin28 during kidney development in mice markedly expands nephrogenic progenitors by blocking their final wave of differentiation, ultimately resulting in a pathology highly reminiscent of Wilms tumor. Using lineage-specific promoters to target Lin28 to specific cell types, we observed Wilms tumor only when Lin28 is aberrantly expressed in multiple derivatives of the intermediate mesoderm, implicating the cell of origin as a multipotential renal progenitor. We show that withdrawal of Lin28 expression reverts tumorigenesis and markedly expands the numbers of glomerulus-like structures and that tumor formation is suppressed by enforced expression of Let-7 microRNA. Finally, we demonstrate overexpression of the LIN28B paralog in a significant percentage of human Wilms tumor. Our data thus implicate the Lin28/Let-7 pathway in kidney development and tumorigenesis. PMID:24732380

  1. Early Program Development

    1970-01-01

    In 1970, NASA initiated Phase A contracts to study alternate Space Shuttle designs in addition to the two-stage fully-reusable Space Shuttle system already under development. A number of alternate systems were developed to ensure the development of the optimum earth-to-orbit system, including the Stage-and-a-half Chemical Interorbital Shuttle, shown here. The concept would utilize a reusable marned spacecraft with an onboard propulsion system attached to an expendable fuel tank to provide supplementary propellants.

  2. Does Tumor Development Follow a Programmed Path?

    NASA Astrophysics Data System (ADS)

    Austin, Robert

    2011-03-01

    The initiation and progression of a tumor is a complex process, resembling the growth of a embryo in terms of the stages of development and increasing differentiation and somatic evolution of constituent cells in the community of cells that constitute the tumor. Typically we view cancer cells as rogue individuals violating the rules of the games played within an organism, but I would suggest that what we see is a programmed and algorithmic process. I will then question If tumor progression is dominated by the random acquisition of successive survival traits, or by a systematic and sequential unpacking of ``weapons'' from a pre-adapted ``toolkit'' of genetic and epigenetic potentialities? Can we then address this hypothesis by data mining solid tumors layer by layer? Support of the NSF and the NCI is gratefully acknowledged.

  3. Development in Early Childhood.

    ERIC Educational Resources Information Center

    Elkind, David

    1991-01-01

    Reviews some of the major cognitive, social, and emotional achievements of young children and discusses some of their limitations. Divides description of development into intellectual, language, social, and emotional development. Notes that this division represents adult categories of thought and does not represent young children's actual modes of…

  4. Selection of early-occurring mutations dictates hormone-independent progression in mouse mammary tumor lines.

    PubMed

    Gattelli, Albana; Zimberlin, María N; Meiss, Roberto P; Castilla, Lucio H; Kordon, Edith C

    2006-11-01

    Mice harboring three mouse mammary tumor virus (MMTV) variants develop pregnancy-dependent (PD) tumors that progress to pregnancy-independent (PI) behavior through successive passages. Herein, we identified 10 predominant insertions in PI transplants from 8 independent tumor lines. These mutations were also detected in small cell populations in the early PD passages. In addition, we identified a new viral insertion upstream of the gene Rspo3, which is overexpressed in three of the eight independent tumor lines and codes for a protein very similar to the recently described protein encoded by Int7. This study suggests that during progression towards hormone independence, clonal expansion of cells with specific mutations might be more relevant than the occurrence of new MMTV insertions.

  5. Selection of Early-Occurring Mutations Dictates Hormone-Independent Progression in Mouse Mammary Tumor Lines▿

    PubMed Central

    Gattelli, Albana; Zimberlin, María N.; Meiss, Roberto P.; Castilla, Lucio H.; Kordon, Edith C.

    2006-01-01

    Mice harboring three mouse mammary tumor virus (MMTV) variants develop pregnancy-dependent (PD) tumors that progress to pregnancy-independent (PI) behavior through successive passages. Herein, we identified 10 predominant insertions in PI transplants from 8 independent tumor lines. These mutations were also detected in small cell populations in the early PD passages. In addition, we identified a new viral insertion upstream of the gene Rspo3, which is overexpressed in three of the eight independent tumor lines and codes for a protein very similar to the recently described protein encoded by Int7. This study suggests that during progression towards hormone independence, clonal expansion of cells with specific mutations might be more relevant than the occurrence of new MMTV insertions. PMID:16971449

  6. Early Program Development

    1970-01-01

    This artist's concept from 1970 shows a Nuclear Shuttle taking on fuel from an orbiting Liquid Hydrogen Depot. As envisioned by Marshall Space Flight Center Program Development persornel, the Nuclear Shuttle would deliver payloads to lunar orbit or other destinations then return to Earth orbit for refueling and additional missions.

  7. Early Program Development

    1970-01-01

    This 1970 artist's concept shows a Nuclear Shuttle in flight. As envisioned by Marshall Space Flight Center Program Development engineers, the Nuclear Shuttle would deliver payloads to lunar orbit or other destinations then return to Earth orbit for refueling and additional missions.

  8. Early Program Development

    1971-01-01

    In this 1971 artist's concept, the Nuclear Shuttle is shown in various space-based applications. As envisioned by Marshall Space Flight Center Program Development persornel, the Nuclear Shuttle would deliver payloads to geosychronous Earth orbits or lunar orbits then return to low Earth orbit for refueling. A cluster of Nuclear Shuttle units could form the basis for planetary missions.

  9. Early Program Development

    1971-01-01

    This 1971 artist's concept shows the Nuclear Shuttle in both its lunar logistics configuraton and geosynchronous station configuration. As envisioned by Marshall Space Flight Center Program Development persornel, the Nuclear Shuttle would deliver payloads to lunar orbits or other destinations then return to Earth orbit for refueling and additional missions.

  10. Early Program Development

    1963-01-01

    This artist's concept from 1963 shows a proposed NERVA (Nuclear Engine for Rocket Vehicle Application) incorporating the NRX-A1, the first NERVA-type cold flow reactor. The NERVA engine, based on Kiwi nuclear reactor technology, was intended to power a RIFT (Reactor-In-Flight-Test) nuclear stage, for which Marshall Space Flight Center had development responsibility.

  11. Early Program Development

    2004-04-15

    This artist's concept illustrates the NERVA (Nuclear Engine for Rocket Vehicle Application) engine's hot bleed cycle in which a small amount of hydrogen gas is diverted from the thrust nozzle, thus eliminating the need for a separate system to drive the turbine. The NERVA engine, based on KIWI nuclear reactor technology, would power a RIFT (Reactor-In-Flight-Test) nuclear stage, for which the Marshall Space Flight Center had development responsibility.

  12. Early Program Development

    1970-01-01

    In this 1970 artist's concept, the Nuclear Shuttle is shown in its lunar and geosynchronous orbit configuration and in its planetary mission configuration. As envisioned by Marshall Space Flight Center Program Development plarners, the Nuclear Shuttle would deliver payloads to lunar orbit or other destinations then return to Earth orbit for refueling. A cluster of Nuclear Shuttle units could form the basis for planetary missions.

  13. Early Program Development

    1996-06-20

    Engineers at one of MSFC's vacuum chambers begin testing a microthruster model. The purpose of these tests are to collect sufficient data that will enabe NASA to develop microthrusters that will move the Space Shuttle, a future space station, or any other space related vehicle with the least amount of expended energy. When something is sent into outer space, the forces that try to pull it back to Earth (gravity) are very small so that it only requires a very small force to move very large objects. In space, a force equal to a paperclip can move an object as large as a car. Microthrusters are used to produce these small forces.

  14. Biomechanics of Early Cardiac Development

    PubMed Central

    Goenezen, Sevan; Rennie, Monique Y.

    2012-01-01

    Biomechanics affect early cardiac development, from looping to the development of chambers and valves. Hemodynamic forces are essential for proper cardiac development, and their disruption leads to congenital heart defects. A wealth of information already exists on early cardiac adaptations to hemodynamic loading, and new technologies, including high resolution imaging modalities and computational modeling, are enabling a more thorough understanding of relationships between hemodynamics and cardiac development. Imaging and modeling approaches, used in combination with biological data on cell behavior and adaptation, are paving the road for new discoveries on links between biomechanics and biology and their effect on cardiac development and fetal programming. PMID:22760547

  15. Primordial odontogenic tumor: Subepithelial expression of Syndecan-1 and Ki-67 suggests origin during early odontogenesis.

    PubMed

    Bologna-Molina, R; Mikami, T; Pereira-Prado, V; Tapia-Repetto, G; Pires, F R; Carlos, R; Mosqueda-Taylor, A

    2018-03-01

    Primordial odontogenic tumor (POT) is composed of variably cellular myxoid connective tissue, surrounded by cuboidal to columnar odontogenic epithelium resembling the inner epithelium of the enamel organ, which often invaginates into the underlying connective tissue. The tumor is delimited at least partially by a thin fibrous capsule. It derives from the early stages of tooth development. Syndecan-1 is a heparan sulfate proteoglycan that has a physiological role in several cellular functions, including maintenance of the epithelial architecture, cell-to-cell adhesion and interaction of cells with extracellular matrix, and with diverse growth factors, stimulating cell proliferation. Ki-67 is considered the gold standard as a cell proliferation marker. The aim of this study was to examine the expression of Syndecan-1 and Ki-67 proliferation index in POT and normal tooth germs to better understand the biological behavior of this tumor. Results showed that Syndecan-1 was more intensely expressed in subepithelial mesenchymal areas of POT, in a pattern that resembles the early stages of tooth development. The cell proliferation index (4.1%) suggests that POT is a slow growing tumor. Syndecan-1 expression in tooth germs in late cap and early bell stages was similar to POT, showing immunopositivity in subepithelial mesenchymal condensed areas. The immunohistochemical findings showed a pattern in which the population of subepithelial mesenchymal cells exhibited greater proliferative activity than the central portion of the dental papilla. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd. All rights reserved.

  16. Recent developments in testicular germ cell tumor research.

    PubMed

    van de Geijn, Gert-Jan M; Hersmus, Remko; Looijenga, Leendert H J

    2009-03-01

    Testicular germ cell tumors of adolescents and adults (TGCTs; the so-called type II variant) are the most frequent malignancies found in Caucasian males between 20 and 40 years of age. The incidence has increased over the last decades. TGCTs are divided into seminomas and nonseminomas, the latter consisting of the subgroups embryonal carcinoma, yolk-sac tumor, teratoma, and choriocarcinoma. The pathogenesis starts in utero, involving primordial germ cells/gonocytes that are blocked in their differentiation, and develops via the precursor lesion carcinoma in situ toward invasiveness. TGCTs are totipotent and can be considered as stem cell tumors. The developmental capacity of their cell of origin, the primordial germ cells/gonocyte, is demonstrated by the different tumor histologies of the invasive TGCTs. Seminoma represents the germ cell lineage, and embryonal carcinoma is the undifferentiated component, being the stem cell population of the nonseminomas. Somatic differentiation is seen in the teratomas (all lineages), whereas yolk-sac tumors and choriocarcinoma represent extra-embryonal differentiation. Seminomas are highly sensitive to irradiation and (DNA damaging) chemotherapy, whereas most nonseminomatous elements are less susceptible to radiation, although still sensitive to chemotherapy, with the exception of teratoma. To allow early diagnosis and follow up, appropriate markers are mandatory to discriminate between the different subgroups. In this review, a summary will be given related to several recent developments in TGCT research, especially selected because of their putative clinical impact.

  17. Telomere lengthening early in development.

    PubMed

    Liu, Lin; Bailey, Susan M; Okuka, Maja; Muñoz, Purificación; Li, Chao; Zhou, Lingjun; Wu, Chao; Czerwiec, Eva; Sandler, Laurel; Seyfang, Andreas; Blasco, Maria A; Keefe, David L

    2007-12-01

    Stem cells and cancer cells maintain telomere length mostly through telomerase. Telomerase activity is high in male germ line and stem cells, but is low or absent in mature oocytes and cleavage stage embryos, and then high again in blastocysts. How early embryos reset telomere length remains poorly understood. Here, we show that oocytes actually have shorter telomeres than somatic cells, but their telomeres lengthen remarkably during early cleavage development. Moreover, parthenogenetically activated oocytes also lengthen their telomeres, thus the capacity to elongate telomeres must reside within oocytes themselves. Notably, telomeres also elongate in the early cleavage embryos of telomerase-null mice, demonstrating that telomerase is unlikely to be responsible for the abrupt lengthening of telomeres in these cells. Coincident with telomere lengthening, extensive telomere sister-chromatid exchange (T-SCE) and colocalization of the DNA recombination proteins Rad50 and TRF1 were observed in early cleavage embryos. Both T-SCE and DNA recombination proteins decrease in blastocyst stage embryos, whereas telomerase activity increases and telomeres elongate only slowly. We suggest that telomeres lengthen during the early cleavage cycles following fertilization through a recombination-based mechanism, and that from the blastocyst stage onwards, telomerase only maintains the telomere length established by this alternative mechanism.

  18. Nanotechnology-Based Strategies for Early Cancer Diagnosis Using Circulating Tumor Cells as a Liquid Biopsy

    PubMed Central

    Huang, Qinqin; Wang, Yin; Chen, Xingxiang; Wang, Yimeng; Li, Zhiqiang; Du, Shiming; Wang, Lianrong; Chen, Shi

    2018-01-01

    Circulating tumor cells (CTCs) are cancer cells that shed from a primary tumor and circulate in the bloodstream. As a form of “tumor liquid biopsy”, CTCs provide important information for the mechanistic investigation of cancer metastasis and the measurement of tumor genotype evolution during treatment and disease progression. However, the extremely low abundance of CTCs in the peripheral blood and the heterogeneity of CTCs make their isolation and characterization major technological challenges. Recently, nanotechnologies have been developed for sensitive CTC detection; such technologies will enable better cell and molecular characterization and open up a wide range of clinical applications, including early disease detection and evaluation of treatment response and disease progression. In this review, we summarize the nanotechnology-based strategies for CTC isolation, including representative nanomaterials (such as magnetic nanoparticles, gold nanoparticles, silicon nanopillars, nanowires, nanopillars, carbon nanotubes, dendrimers, quantum dots, and graphene oxide) and microfluidic chip technologies that incorporate nanoroughened surfaces and discuss their key challenges and perspectives in CTC downstream analyses, such as protein expression and genetic mutations that may reflect tumor aggressiveness and patient outcome. PMID:29291161

  19. Technical Insights into Highly Sensitive Isolation and Molecular Characterization of Fixed and Live Circulating Tumor Cells for Early Detection of Tumor Invasion.

    PubMed

    Laget, Sophie; Broncy, Lucile; Hormigos, Katia; Dhingra, Dalia M; BenMohamed, Fatima; Capiod, Thierry; Osteras, Magne; Farinelli, Laurent; Jackson, Stephen; Paterlini-Bréchot, Patrizia

    2017-01-01

    Circulating Tumor Cells (CTC) and Circulating Tumor Microemboli (CTM) are Circulating Rare Cells (CRC) which herald tumor invasion and are expected to provide an opportunity to improve the management of cancer patients. An unsolved technical issue in the CTC field is how to obtain highly sensitive and unbiased collection of these fragile and heterogeneous cells, in both live and fixed form, for their molecular study when they are extremely rare, particularly at the beginning of the invasion process. We report on a new protocol to enrich from blood live CTC using ISET® (Isolation by SizE of Tumor/Trophoblastic Cells), an open system originally developed for marker-independent isolation of fixed tumor cells. We have assessed the impact of our new enrichment method on live tumor cells antigen expression, cytoskeleton structure, cell viability and ability to expand in culture. We have also explored the ISET® in vitro performance to collect intact fixed and live cancer cells by using spiking analyses with extremely low number of fluorescent cultured cells. We describe results consistently showing the feasibility of isolating fixed and live tumor cells with a Lower Limit of Detection (LLOD) of one cancer cell per 10 mL of blood and a sensitivity at LLOD ranging from 83 to 100%. This very high sensitivity threshold can be maintained when plasma is collected before tumor cells isolation. Finally, we have performed a comparative next generation sequencing (NGS) analysis of tumor cells before and after isolation from blood and culture. We established the feasibility of NGS analysis of single live and fixed tumor cells enriched from blood by our system. This study provides new protocols for detection and characterization of CTC collected from blood at the very early steps of tumor invasion.

  20. Technical Insights into Highly Sensitive Isolation and Molecular Characterization of Fixed and Live Circulating Tumor Cells for Early Detection of Tumor Invasion

    PubMed Central

    Laget, Sophie; Dhingra, Dalia M.; BenMohamed, Fatima; Capiod, Thierry; Osteras, Magne; Farinelli, Laurent; Jackson, Stephen; Paterlini-Bréchot, Patrizia

    2017-01-01

    Circulating Tumor Cells (CTC) and Circulating Tumor Microemboli (CTM) are Circulating Rare Cells (CRC) which herald tumor invasion and are expected to provide an opportunity to improve the management of cancer patients. An unsolved technical issue in the CTC field is how to obtain highly sensitive and unbiased collection of these fragile and heterogeneous cells, in both live and fixed form, for their molecular study when they are extremely rare, particularly at the beginning of the invasion process. We report on a new protocol to enrich from blood live CTC using ISET® (Isolation by SizE of Tumor/Trophoblastic Cells), an open system originally developed for marker-independent isolation of fixed tumor cells. We have assessed the impact of our new enrichment method on live tumor cells antigen expression, cytoskeleton structure, cell viability and ability to expand in culture. We have also explored the ISET® in vitro performance to collect intact fixed and live cancer cells by using spiking analyses with extremely low number of fluorescent cultured cells. We describe results consistently showing the feasibility of isolating fixed and live tumor cells with a Lower Limit of Detection (LLOD) of one cancer cell per 10 mL of blood and a sensitivity at LLOD ranging from 83 to 100%. This very high sensitivity threshold can be maintained when plasma is collected before tumor cells isolation. Finally, we have performed a comparative next generation sequencing (NGS) analysis of tumor cells before and after isolation from blood and culture. We established the feasibility of NGS analysis of single live and fixed tumor cells enriched from blood by our system. This study provides new protocols for detection and characterization of CTC collected from blood at the very early steps of tumor invasion. PMID:28060956

  1. Cognitive Development in Early Readers.

    ERIC Educational Resources Information Center

    Briggs, Chari; Elkind, David

    Some studies of early readers are discussed. It is pointed out that study of early readers has relevance for practical and theoretical issues in psychology and education. Of interest in this document are the following questions: (1) Are there any special talents or traits distinguishing early from non-early readers? (2) Do children who read early…

  2. [Early childhood growth and development].

    PubMed

    Arce, Melitón

    2015-01-01

    This article describes and discusses issues related to the process of childhood growth and development, with emphasis on the early years, a period in which this process reaches critical speed on major structures and functions of the human economy. We reaffirm that this can contribute to the social availability of a generation of increasingly better adults, which in turn will be able to contribute to building a better world and within it a society that enjoys greater prosperity. In the first chapter, we discuss the general considerations on the favorable evolution of human society based on quality of future adults, meaning the accomplishments that today’s children will gain. A second chapter mentions the basics of growth and development in the different fields and the various phenomena that occur in it. In the third we refer to lost opportunities and negative factors that can affect delaying the process and thereby result in not obtaining the expected accomplishments. In the fourth, conclusions and recommendations are presented confirming the initial conception that good early child care serves to build a better society and some recommendations are formulated to make it a good practice.

  3. Early ultrasonographic evaluation of tumor thrombus level during sunitinib therapy for renal cell carcinoma.

    PubMed

    Sano, Futoshi; Fusayasu, Syusei; Otake, Shinji; Yamanaka, Hiroyuki; Tatenuma, Tomoyuki; Sakata, Ryoko; Makiyama, Kazuhide; Nakaigawa, Noboru; Yao, Masahiro; Kubota, Yoshinobu

    2013-10-01

    A 72-year-old man presenting with a 14-cm left renal mass, an inferior vena cava (IVC) tumor thrombus, and pulmonary metastases underwent renal mass biopsy that revealed clear cell renal cell carcinoma. Because of metastases and the extent of the tumor thrombus, sunitinib was administered, which resulted in a marked reduction in the tumor thrombus (from level III to level II after 11 weeks of treatment). Ultrasonography, preceding computed tomography, showed a slight shrinkage of the tumor thrombus level in the first 2 weeks. Therefore, ultrasound may be advantageous to monitor the IVC tumor thrombus level during the early phase of targeted therapy.

  4. Early skin toxicity predicts better outcomes, and early tumor shrinkage predicts better response after cetuximab treatment in advanced colorectal cancer.

    PubMed

    Kogawa, T; Doi, A; Shimokawa, M; Fouad, T M; Osuga, T; Tamura, F; Mizushima, T; Kimura, T; Abe, S; Ihara, H; Kukitsu, T; Sumiyoshi, T; Yoshizaki, N; Hirayama, M; Sasaki, T; Kawarada, Y; Kitashiro, S; Okushiba, S; Kondo, H; Tsuji, Y

    2015-03-01

    Cetuximab-containing treatments for metastatic colorectal cancer have been shown to have higher overall response rates and longer progression-free and overall survival than other systemic therapies. Cetuximab-related manifestations, including severe skin toxicity and early tumor shrinkage, have been shown to be predictors of response to cetuximab. We hypothesized that early skin toxicity is a predictor of response and better outcomes in patients with advanced colorectal carcinoma. We retrospectively evaluated 62 patients with colorectal adenocarcinoma who had unresectable tumors and were treated with cetuximab in our institution. Skin toxicity grade was evaluated on each treatment day. Tumor size was evaluated using computed tomography prior to treatment and 4-8 weeks after the start of treatment with cetuximab.Patients with early tumor shrinkage after starting treatment with cetuximab had a significantly higher overall response rate (P = 0.0001). Patients with early skin toxicity showed significantly longer overall survival (P = 0.0305), and patients with higher skin toxicity grades had longer progression-free survival (P = 0.0168).We have shown that early tumor shrinkage, early onset of skin toxicity, and high skin toxicity grade are predictors of treatment efficacy and/or outcome in patients with advanced colorectal carcinoma treated with cetuximab.

  5. [The development of novel tumor targeting delivery strategy].

    PubMed

    Gao, Hui-le; Jiang, Xin-guo

    2016-02-01

    Tumor is one of the most serious threats for human being. Although many anti-tumor drugs are approved for clinical use, the treatment outcome is still modest because of the poor tumor targeting efficiency and low accumulation in tumor. Therefore, it is important to deliver anti-tumor drug into tumor efficiently, elevate drug concentration in tumor tissues and reduce the drug distribution in normal tissues. And it has been one of the most attractive directions of pharmaceutical academy and industry. Many kinds of strategies, especially various nanoparticulated drug delivery systems, have been developed to address the critical points of complex tumor microenvironment, which are partially or mostly satisfied for tumor treatment. In this paper, we carefully reviewed the novel targeting delivery strategies developed in recent years. The most powerful method is passive targeting delivery based on the enhanced permeability and retention(EPR) effect, and most commercial nanomedicines are based on the EPR effect. However, the high permeability and retention require different particle sizes, thus several kinds of size-changeable nanoparticles are developed, such as size reducible particles and assemble particles, to satisfy the controversial requirement for particle size and enhance both tumor retention and penetration. Surface charge reversible nanoparticles also shows a high efficiency because the anionic charge in blood circulation and normal organs decrease the unintended internalization. The charge can change into positive in tumor microenvironment, facilitating drug uptake by tumor cells. Additionally, tumor microenvironment responsive drug release is important to decrease drug side effect, and many strategies are developed, such as p H sensitive release and enzyme sensitive release. Except the responsive nanoparticles, shaping tumor microenvironment could attenuate the barriers in drug delivery, for example, decreasing tumor collagen intensity and normalizing tumor

  6. Utility of Early Post-operative High Resolution Volumetric MR Imaging after Transsphenoidal Pituitary Tumor Surgery

    PubMed Central

    Patel, Kunal S.; Kazam, Jacob; Tsiouris, Apostolos J.; Anand, Vijay K.; Schwartz, Theodore H.

    2014-01-01

    Objective Controversy exists over the utility of early post-operative magnetic resonance imaging (MRI) after transsphenoidal pituitary surgery for macroadenomas. We investigate whether valuable information can be derived from current higher resolution scans. Methods Volumetric MRI scans were obtained in the early (<10 days) and late (>30 days) post-operative periods in a series of patients undergoing transsphenoidal pituitary surgery. The volume of the residual tumor, resection cavity, and corresponding visual field tests were recorded at each time point. Statistical analyses of changes in tumor volume and cavity size were calculated using the late MRI as the gold standard. Results 40 patients met the inclusion criteria. Pre-operative tumor volume averaged 8.8 cm3. Early postoperative assessment of average residual tumor volume (1.18 cm3) was quite accurate and did not differ statistically from late post-operative volume (1.23 cm3, p=.64), indicating the utility of early scans to measure residual tumor. Early scans were 100% sensitive and 91% specific for predicting ≥ 98% resection (p<.001, Fisher’s exact test). The average percent decrease in cavity volume from pre-operative MRI (tumor volume) to early post-operative imaging was 45% with decreases in all but 3 patients. There was no correlation between the size of the early cavity and the visual outcome. Conclusions Early high resolution volumetric MRI is valuable in determining the presence or absence of residual tumor. Cavity volume almost always decreases after surgery and a lack of decrease should alert the surgeon to possible persistent compression of the optic apparatus that may warrant re-operation. PMID:25045791

  7. Taiwanese Early Childhood Educators' Professional Development

    ERIC Educational Resources Information Center

    Hsu, Ching-Yun

    2008-01-01

    This study was designed based on a qualitative paradigm to explore the professional development of Taiwanese early childhood educators. The method of phenomenology was employed. The main research question addressed was "How do early childhood educators construe their professional development experience?" Seven Taiwanese early childhood…

  8. Early Childhood Diplomacy: Policy Planning for Early Childhood Development

    ERIC Educational Resources Information Center

    Vargas-Barón, Emily; Diehl, Kristel

    2018-01-01

    Children who are well nurtured, appropriately cared for, and provided with positive learning opportunities in their early years have a better chance of becoming healthy and productive citizens of nations and of the world. This article reviews the art and science of policy planning for early childhood development (ECD) from a diplomacy perspective.…

  9. Germline Mutations of Inhibins in Early-Onset Ovarian Epithelial Tumors

    PubMed Central

    Tournier, Isabelle; Marlin, Régine; Walton, Kelly; Charbonnier, Françoise; Coutant, Sophie; Théry, Jean-Christophe; Charbonnier, Camille; Spurrell, Cailyn; Vezain, Myriam; Ippolito, Lorena; Bougeard, Gaëlle; Roman, Horace; Tinat, Julie; Sabourin, Jean-Christophe; Stoppa-Lyonnet, Dominique; Caron, Olivier; Bressac-de Paillerets, Brigitte; Vaur, Dominique; King, Mary-Claire; Harrison, Craig; Frebourg, Thierry

    2014-01-01

    To identify novel genetic bases of early-onset epithelial ovarian tumors, we used the trio exome sequencing strategy in a patient without familial history of cancer who presented metastatic serous ovarian adenocarcinomas at 21 years of age. We identified a single de novo mutation (c.1157A>G/p.Asn386Ser) within the INHBA gene encoding the βA-subunit of inhibins/activins, which play a key role in ovarian development. In vitro, this mutation alters the ratio of secreted activins and inhibins. In a second patient with early-onset serous borderline papillary cystadenoma, we identified an unreported germline mutation (c.179G>T/p.Arg60Leu) of the INHA gene encoding the α-subunit, the partner of the βA-subunit. This mutation also alters the secreted activin/inhibin ratio, by disrupting both inhibin A and inhibin B biosynthesis. In a cohort of 62 cases, we detected an additional unreported germline mutation of the INHBA gene (c.839G>A/p.Gly280Glu). Our results strongly suggest that inhibin mutations contribute to the genetic determinism of epithelial ovarian tumors. PMID:24302632

  10. Rate of local tumor progression following radiofrequency ablation of pathologically early hepatocellular carcinoma.

    PubMed

    Hao, Yoshiteru; Numata, Kazushi; Ishii, Tomohiro; Fukuda, Hiroyuki; Maeda, Shin; Nakano, Masayuki; Tanaka, Katsuaki

    2017-05-07

    To evaluate whether pathologically early hepatocellular carcinoma (HCC) exhibited local tumor progression after radiofrequency ablation (RFA) less often than typical HCC. Fifty pathologically early HCCs [tumor diameter (mm): mean, 15.8; range, 10-23; follow-up days after RFA: median, 1213; range, 216-2137] and 187 typical HCCs [tumor diameter (mm): mean, 15.6; range, 6-30; follow-up days after RFA: median, 1116; range, 190-2328] were enrolled in this retrospective study. The presence of stromal invasion (namely, tumor cell invasion into the intratumoral portal tracts) was considered to be the most important pathologic finding for the diagnosis of early HCCs. Typical HCC was defined as the presence of a hyper-vascular lesion accompanied by delayed washout using contrast-enhanced computed tomography or contrast-enhanced magnetic resonance imaging. Follow-up examinations were performed at 3-mo intervals to monitor for signs of local tumor progression. The local tumor progression rates of pathologically early HCCs and typical HCCs were then determined using the Kaplan-Meier method. During the follow-up period for the 50 pathologically early HCCs, 49 (98%) of the nodules did not exhibit local tumor progression. However, 1 nodule (2%) was associated with a local tumor progression found 636 d after RFA. For the 187 typical HCCs, 46 (24.6%) of the nodules exhibited local recurrence after RFA. The follow-up period until the local tumor progression of typical HCC was a median of 605 d, ranging from 181 to 1741 d. Among the cases with typical HCCs, local tumor progression had occurred in 7.0% (7/187), 16.0% (30/187), 21.9% (41/187) and 24.6% (46/187) of the cases at 1, 2, 3 and 4 years, respectively. Pathologically early HCC was statistically associated with a lower rate of local tumor progression, compared with typical HCC, when evaluated using a log-rank test ( P = 0.002). The rate of local tumor progression for pathologically early HCCs after RFA was significantly lower

  11. Rate of local tumor progression following radiofrequency ablation of pathologically early hepatocellular carcinoma

    PubMed Central

    Hao, Yoshiteru; Numata, Kazushi; Ishii, Tomohiro; Fukuda, Hiroyuki; Maeda, Shin; Nakano, Masayuki; Tanaka, Katsuaki

    2017-01-01

    AIM To evaluate whether pathologically early hepatocellular carcinoma (HCC) exhibited local tumor progression after radiofrequency ablation (RFA) less often than typical HCC. METHODS Fifty pathologically early HCCs [tumor diameter (mm): mean, 15.8; range, 10-23; follow-up days after RFA: median, 1213; range, 216-2137] and 187 typical HCCs [tumor diameter (mm): mean, 15.6; range, 6-30; follow-up days after RFA: median, 1116; range, 190-2328] were enrolled in this retrospective study. The presence of stromal invasion (namely, tumor cell invasion into the intratumoral portal tracts) was considered to be the most important pathologic finding for the diagnosis of early HCCs. Typical HCC was defined as the presence of a hyper-vascular lesion accompanied by delayed washout using contrast-enhanced computed tomography or contrast-enhanced magnetic resonance imaging. Follow-up examinations were performed at 3-mo intervals to monitor for signs of local tumor progression. The local tumor progression rates of pathologically early HCCs and typical HCCs were then determined using the Kaplan-Meier method. RESULTS During the follow-up period for the 50 pathologically early HCCs, 49 (98%) of the nodules did not exhibit local tumor progression. However, 1 nodule (2%) was associated with a local tumor progression found 636 d after RFA. For the 187 typical HCCs, 46 (24.6%) of the nodules exhibited local recurrence after RFA. The follow-up period until the local tumor progression of typical HCC was a median of 605 d, ranging from 181 to 1741 d. Among the cases with typical HCCs, local tumor progression had occurred in 7.0% (7/187), 16.0% (30/187), 21.9% (41/187) and 24.6% (46/187) of the cases at 1, 2, 3 and 4 years, respectively. Pathologically early HCC was statistically associated with a lower rate of local tumor progression, compared with typical HCC, when evaluated using a log-rank test (P = 0.002). CONCLUSION The rate of local tumor progression for pathologically early HCCs after

  12. Serum IGF-1, IGFBP-3 levels and circulating tumor cells (CTCs) in early breast cancer patients.

    PubMed

    Papadakis, Georgios Z; Mavroudis, Dimitrios; Georgoulias, Vasilios; Souglakos, John; Alegakis, Athanasios K; Samonis, George; Bagci, Ulas; Makrigiannakis, Antonis; Zoras, Odysseas

    2017-04-01

    Insulin-like growth factor (IGF)-axis is involved in human oncogenesis and metastasis development for various solid tumors including breast cancer. Aim of this study was to assess the association between IGF-1, IGF-binding protein-3 (IGFBP-3) serum levels and the presence of circulating tumor cells (CTCs) in the peripheral blood of women diagnosed with early breast cancer (EBC), before and after adjuvant chemotherapy. 171 patients with early-stage breast adenocarcinomas were retrospectively evaluated. Immunoradiometric (IRMA) assays were employed for the in-vitro determination of IGF-1 and IGFBP-3 serum levels in blood samples collected after surgical treatment and before initiation of adjuvant chemotherapy. CTCs' presence was assessed through detection of cytokeratin-19 (CK-19) mRNA transcripts using quantitative real time reverse transcription polymerase chain reaction (RT-PCR). IGF-1, IGFBP-3 serum levels were correlated with CTCs' presence before and after adjuvant chemotherapy as well as with tumor characteristics including tumor size, axillary lymph node status, oestrogen (ER)/progestorene (PR) and human epidermural growth factor receptor 2 (HER2) receptor status. Log-rank test was applied to investigate possible association between IGF-1, IGFBP-3 serum levels and disease-free interval (DFI) and overall survival (OS). Before initiation of adjuvant therapy IGF-1, IGFBP-3 serum levels were moderately associated (Spearman's rho=0.361, p<0.001) with each other, while presenting significant differences across age groups (all p values<0.05). IGF-1 serum levels did not correlate with the presence of CTCs before initiation (p=0.558) or after completion (p=0.474) of adjuvant chemotherapy. Similarly, IGFBP-3 serum levels did not show significant association with detectable CTCs either before (p=0.487) or after (p=0.134) completion of adjuvant chemotherapy. There was no statistically significant association between the clinical outcome of patients in terms of DFI, OS

  13. Early predicted time to normalization of tumor markers predicts outcome in poor-prognosis nonseminomatous germ cell tumors.

    PubMed

    Fizazi, Karim; Culine, Stéphane; Kramar, Andrew; Amato, Robert J; Bouzy, Jeannine; Chen, Isan; Droz, Jean-Pierre; Logothetis, Christopher J

    2004-10-01

    The prognostic relevance of the rate of decline of serum alpha-fetoprotein (AFP) and human chorionic gonadotropin (HCG) during the first 3 weeks of chemotherapy for nonseminomatous germ cell tumors (NSGCT) was studied in the context of the International Germ Cell Cancer Collaborative Group (IGCCCG) classification. Data from 653 patients prospectively recruited in clinical trials were studied. Tumor markers were obtained before chemotherapy and 3 weeks later. Decline rates were calculated using a logarithmic formula and expressed as a predicted time to normalization (TTN). A favorable TTN was defined when both AFP and HCG had a favorable decline rate, including cases with normal values. The median follow-up was 50 months (range, 2 to 151 months). Tumor decline rate expressed as a predicted TTN was associated with both progression-free survival (PFS; P <.0001) and overall survival (OS; P <.0001). The 4-year PFS rates were 64% and 38% in patients from the poor-prognosis group who had a favorable and an unfavorable TTN, respectively. The 4-year OS rates were 83% and 58%, respectively. This effect was independent from the initial tumor marker values, the primary tumor site, and the presence of nonpulmonary visceral metastases: tumor marker decline rate remained a strong predictor for both PFS (hazard ratio = 2.5; P =.01) and OS (hazard ratio = 4.6; P =.002) in patients from the IGCCCG poor-prognosis group in multivariate analysis. Early predicted time to tumor marker normalization is an independent prognostic factor in patients with poor-prognosis NSGCT and may be a useful tool in the therapeutic management of these patients.

  14. Kentucky's Statewide Early Childhood Professional Development System

    ERIC Educational Resources Information Center

    Rous, Beth; Grove, Jaime; Townley, Kim

    2007-01-01

    Public school systems have recently become major players in providing services for children in their early years. In addition, a number of other services are available to young children including child care, Head Start, and Early Head Start programs. The link between program quality and professional development of early care and education…

  15. Up-regulation of mismatch repair genes MSH6, PMS2 and MLH1 parallels development of genetic instability and is linked to tumor aggressiveness and early PSA recurrence in prostate cancer.

    PubMed

    Wilczak, Waldemar; Rashed, Semin; Hube-Magg, Claudia; Kluth, Martina; Simon, Ronald; Büscheck, Franziska; Clauditz, Till Sebastian; Grupp, Katharina; Minner, Sarah; Tsourlakis, Maria Christina; Möller-Koop, Christina; Graefen, Markus; Adam, Meike; Haese, Alexander; Wittmer, Corinna; Sauter, Guido; Izbicki, Jakob Robert; Huland, Hartwig; Schlomm, Thorsten; Steurer, Stefan; Krech, Till; Lebok, Patrick

    2017-01-01

    DNA mismatch repair (MMR) is integral to the maintenance of genetic stability. We aimed to evaluate the clinical impact of MMR gene expression in prostate cancer. The MMR genes MSH6, MLH1 and PMS2 were analyzed by immunohistochemistry on a tissue microarray containing 11152 prostate cancer specimens. Results were compared with ETS-related gene status and deletions of PTEN, 3p13, 5q21 and 6q15. MSH6, MLH1 and PMS2 expression was detectable in 89.5%, 85.4% and 85.0% of cancers and was particularly strong in cancers with advanced pathological tumor stage (P < 0.0001 each), high Gleason grade (P < 0.0001 each), nodal metastasis (P ≤ 0.0083) and early biochemical recurrence (P < 0.0001). High levels of MMR gene expression paralleled features of genetic instability, such as the number of genomic deletions per cancer; strong expression of all three MMR genes was found in 24%, 29%, 30%, 33% and 42% of cancers with no, one, two, three or four to five deletions (P < 0.0001). The prognostic value of the analyzed MMR genes was largely driven by the subset of cancers lacking ERG fusion (P < 0.0001), while the prognostic impact of MMR gene overexpression was only marginal in ERG-positive cancers. Multivariate analyses suggested an independent prognostic relevance of MMR genes in ERG-negative prostate cancers when compared with prognostic parameters available at the time of initial biopsy. In conclusion, MMR overexpression is common in prostate cancer and is linked to poor outcome as well as features indicating genetic instability. ERG fusion should be analyzed along with MMR gene expression in potential clinical tests. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  16. Improving efficacy of metastatic tumor segmentation to facilitate early prediction of ovarian cancer patients' response to chemotherapy

    NASA Astrophysics Data System (ADS)

    Danala, Gopichandh; Wang, Yunzhi; Thai, Theresa; Gunderson, Camille C.; Moxley, Katherine M.; Moore, Kathleen; Mannel, Robert S.; Cheng, Samuel; Liu, Hong; Zheng, Bin; Qiu, Yuchen

    2017-02-01

    Accurate tumor segmentation is a critical step in the development of the computer-aided detection (CAD) based quantitative image analysis scheme for early stage prognostic evaluation of ovarian cancer patients. The purpose of this investigation is to assess the efficacy of several different methods to segment the metastatic tumors occurred in different organs of ovarian cancer patients. In this study, we developed a segmentation scheme consisting of eight different algorithms, which can be divided into three groups: 1) Region growth based methods; 2) Canny operator based methods; and 3) Partial differential equation (PDE) based methods. A number of 138 tumors acquired from 30 ovarian cancer patients were used to test the performance of these eight segmentation algorithms. The results demonstrate each of the tested tumors can be successfully segmented by at least one of the eight algorithms without the manual boundary correction. Furthermore, modified region growth, classical Canny detector, and fast marching, and threshold level set algorithms are suggested in the future development of the ovarian cancer related CAD schemes. This study may provide meaningful reference for developing novel quantitative image feature analysis scheme to more accurately predict the response of ovarian cancer patients to the chemotherapy at early stage.

  17. Tumor development in Japanese patients with Lynch syndrome

    PubMed Central

    Horiguchi, Shin-ichiro; Yamada, Rin; Takao, Misato; Iijima, Takeru; Wakaume, Rika; Aruga, Tomoyuki; Tabata, Taku; Koizumi, Koichi

    2018-01-01

    Background Lynch syndrome (LS) patients have a high risk of developing various tumors. This study aimed to clarify the characteristics of tumors developing in LS patients. Methods This is a retrospective review of 55 LS patients treated at Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital. Results The median age at the diagnosis of the first malignant tumor and first LS-related tumor was 44 (range, 19−65) and 44 (range, 24−66) years, respectively. Of the 55 LS patients with developing malignant tumors, 45 (93.8%) developed an LS-related tumor as the first malignant tumor. Colorectal cancer (CRC) developed in 47 patients (85.4%), followed by endometrial cancer (n = 13, 56.5%) in females and gastric cancer (n = 10, 18.1%). In 6 gastric cancer patients, Helicobacter pylori was detected in resected specimens. Twenty-nine patients (52.7%) developed CRC and extra-colonic tumors; of these, 15 patients (48.3%) had mutations in MLH1, 10 (58.8%) in MSH2, and 4 (57.1%) in MSH6. At the age of 50, the cumulative incidence was 50.9% [95% confidence interval (CI), 36.9−63.3%] for CRC, 17.4% (95% CI, 5.2−35.6%) for endometrial cancer, and 5.5% (95% CI, 1.4−13.8%) for gastric cancer. Eight gastric cancer, one breast cancer patient, five bladder cancer patients, and one prostate cancer patient demonstrated loss of expression of the mismatch repair (MMR) protein; patients with thyroid cancer, spindle cell sarcoma, and giant cell tumors did not demonstrate this. Conclusion Gastric cancer incidence was high in Japanese patients with LS and associated with H. pylori infection. MMR protein deficiency caused the development of malignant tumors in LS patients. PMID:29672549

  18. Measurement of changes in blood oxygenation using Multispectral Optoacoustic Tomography (MSOT) allows assessment of tumor development

    NASA Astrophysics Data System (ADS)

    Tomaszewski, Michal R.; Quiros-Gonzalez, Isabel; Joseph, James; Bohndiek, Sarah E.

    2016-03-01

    The ability to evaluate tumor oxygenation in the clinic could indicate prognosis and enable treatment monitoring, since oxygen deficient cancer cells are more resistant to chemotherapy and radiotherapy. MultiSpectral Optoacoustic Tomography (MSOT) is a hybrid technique combining the high contrast of optical imaging with the spatial resolution and penetration depth similar to ultrasound. We aim to demonstrate that MSOT can be used to monitor the development of tumor vasculature. To establish the relationship between MSOT derived imaging biomarkers and biological changes during tumor development, we performed MSOT on nude mice (n=10) bearing subcutaneous xenograft U87 glioblastoma tumors using a small animal optoacoustic tomography system. The mice were maintained under inhalation anesthesia during imaging and respired oxygen content was modified between 21% and 100%. The measurements from early (week 4) and late (week 7) stages of tumor development were compared. To further explore the functionality of the blood vessels, we examined the evolution of changes in the abundance of oxy- and deoxyhemoglobin in the tumors in response to a gas challenge. We found that the kinetics of the change in oxygen saturation (SO2) were significantly different between small tumors and the healthy blood vessels in nearby normal tissue (p=0.0054). Furthermore, we showed that there was a significant difference in the kinetics of the gas challenge between small and large tumors (p=0.0015). We also found that the tumor SO2 was significantly correlated (p=0.0057) with the tumor necrotic fraction as assessed by H&E staining in histology. In the future, this approach may be of use in the clinic as a method for tumor staging and assessment of treatment response.

  19. Diffuse optical measurements of head and neck tumor hemodynamics for early prediction of radiation therapy (Conference Presentation)

    NASA Astrophysics Data System (ADS)

    Dong, Lixin; Kudrimoti, Mahesh; Irwin, Daniel; Chen, Li; Shang, Yu; Li, Xingzhe; Stevens, Scott D.; Shelton, Brent J.; Yu, Guoqiang

    2016-03-01

    Radiation therapy is a principal modality for head and neck cancers and its efficacy depends on tumor hemodynamics. Our laboratory developed a hybrid diffuse optical instrument allowing for simultaneous measurements of tumor blood flow and oxygenation. In this study, the clinically involved cervical lymph node was monitored by the hybrid instrument once a week over the treatment period of seven weeks. Based on treatment outcomes within one year, patients were classified into a complete response group (CR) and an incomplete response group (IR) with remote metastasis and/or local recurrence. A linear mixed models was used to compare tumor hemodynamic responses to the treatment between the two groups. Interestingly, we found that human papilloma virus (HPV-16) status largely affected tumor hemodynamic responses. For HPV-16 negative tumors, significant differences in blood flow index (BFI, p = 0.007) and reduced scattering coefficient (μs', p = 0.0005) were observed between the two groups; IR tumors exhibited higher μs' values and a continuous increase in BFI over the treatment period. For HPV-16 positive tumors, oxygenated hemoglobin concentration ([HbO2]) and blood oxygen saturation (StO2) were significant different (p = 0.003 and 0.01, respectively); IR group showed lower [HbO2] and StO2. Our results imply HPV-16 negative tumors with higher density of vasculature (μs') and higher blood flow show poor responses to radiotherapy and HPV-16 positive tumors with lower tissue oxygenation level (lower StO2 and [HbO2]) exhibit poor treatment outcomes. Our diffuse optical measurements show the great potential for early prediction of radiotherapy in head and neck cancers.

  20. Tumor-associated macrophages drive spheroid formation during early transcoelomic metastasis of ovarian cancer

    PubMed Central

    Yin, Mingzhu; Li, Xia; Tan, Shu; Zhou, Huanjiao Jenny; Ji, Weidong; Bellone, Stefania; Xu, Xiaocao; Zhang, Haifeng; Santin, Alessandro D.; Lou, Ge

    2016-01-01

    Tumor-associated macrophages (TAMs) can influence ovarian cancer growth, migration, and metastasis, but the detailed mechanisms underlying ovarian cancer metastasis remain unclear. Here, we have shown a strong correlation between TAM-associated spheroids and the clinical pathology of ovarian cancer. Further, we have determined that TAMs promote spheroid formation and tumor growth at early stages of transcoelomic metastasis in an established mouse model for epithelial ovarian cancer. M2 macrophage–like TAMs were localized in the center of spheroids and secreted EGF, which upregulated αMβ2 integrin on TAMs and ICAM-1 on tumor cells to promote association between tumor cells and TAM. Moreover, EGF secreted by TAMs activated EGFR on tumor cells, which in turn upregulated VEGF/VEGFR signaling in surrounding tumor cells to support tumor cell proliferation and migration. Pharmacological blockade of EGFR or antibody neutralization of ICAM-1 in TAMs blunted spheroid formation and ovarian cancer progression in mouse models. These findings suggest that EGF secreted from TAMs plays a critical role in promoting early transcoelomic metastasis of ovarian cancer. As transcoelomic metastasis is also associated with many other cancers, such as pancreatic and colon cancers, our findings uncover a mechanism for TAM-mediated spheroid formation and provide a potential target for the treatment of ovarian cancer and other transcoelomic metastatic cancers. PMID:27721235

  1. Etiology and early pathogenesis of malignant testicular germ cell tumors: towards possibilities for preinvasive diagnosis

    PubMed Central

    Elzinga-Tinke, Jenny E; Dohle, Gert R; Looijenga, Leendert HJ

    2015-01-01

    Malignant testicular germ cell tumors (TGCT) are the most frequent cancers in Caucasian males (20–40 years) with an 70% increasing incidence the last 20 years, probably due to combined action of (epi)genetic and (micro)environmental factors. It is expected that TGCT have carcinoma in situ (CIS) as their common precursor, originating from an embryonic germ cell blocked in its maturation process. The overall cure rate of TGCT is more than 90%, however, men surviving TGCT can present long-term side effects of systemic cancer treatment. In contrast, men diagnosed and treated for CIS only continue to live without these long-term side effects. Therefore, early detection of CIS has great health benefits, which will require an informative screening method. This review described the etiology and early pathogenesis of TGCT, as well as the possibilities of early detection and future potential of screening men at risk for TGCT. For screening, a well-defined risk profile based on both genetic and environmental risk factors is needed. Since 2009, several genome wide association studies (GWAS) have been published, reporting on single-nucleotide polymorphisms (SNPs) with significant associations in or near the genes KITLG, SPRY4, BAK1, DMRT1, TERT, ATF7IP, HPGDS, MAD1L1, RFWD3, TEX14, and PPM1E, likely to be related to TGCT development. Prenatal, perinatal, and postnatal environmental factors also influence the onset of CIS. A noninvasive early detection method for CIS would be highly beneficial in a clinical setting, for which specific miRNA detection in semen seems to be very promising. Further research is needed to develop a well-defined TGCT risk profile, based on gene-environment interactions, combined with noninvasive detection method for CIS. PMID:25791729

  2. Microdissecting the Genetic Events in Nephrogenic Rests and Wilms’ Tumor Development

    PubMed Central

    Charles, Adrian K.; Brown, Keith W.; Berry, P. Jeremy

    1998-01-01

    Nephrogenic rests are precursor lesions associated with about 40% of Wilms’ tumors. This study identifies genetic steps occurring in the development of Wilms’ tumor. Thirty-four Wilms’ tumors with nephrogenic rests and/or areas of anaplasia were microdissected from paraffin sections to determine whether and at what stage loss of heterozygosity (LOH) occurred, using polymerase chain reaction-based polymorphic markers at 11p13, 11p15, and 16q. LOH at these loci have been identified in Wilms’ tumors and are associated with identified or putative tumor suppressor genes. Three cystic nephromas/cystic partially differentiated nephroblastomas were also examined. LOH was detected in six cases at 11p13 and in six cases at 11p15, and two of these cases had LOH at both loci. All intralobar rests showing LOH also showed LOH in the tumor. A case with a small perilobar rest showed LOH of 11p13 only in the tumor. Five cases showing LOH at 16q were identified (this was identified only in the tumor, and not in the associated rest), and three of these had recurrence of the tumor. Two cases had a WT1 mutation (one germline and the other somatic), as well as LOH in both the intralobar rest and the tumor. A cystic partially differentiated nephroblastoma showed loss at 11p13 and 11p15, as well as at 16q. This study suggests that LOH at 11p13 and 11p15 and WT1 mutations are early events but that LOH at 16q occurs late in the pathogenesis of Wilms’ tumor. Intralobar and perilobar nephrogenic rests are known to have different biological behaviors, and this study suggests that they are genetically different. A multistep model of Wilms’ tumor pathogenesis is supported by these findings. PMID:9736048

  3. The Development of STAR Early Literacy. Report.

    ERIC Educational Resources Information Center

    School Renaissance Inst., Inc., Madison, WI.

    This report describes the development and testing of a computerized early literacy diagnostic assessment for students in prekindergarten to grade 3 that can measure skills across a variety of preliteracy and reading domains. The STAR Early Literacy assessment was developed by a team of more than 50 people, including literacy experts,…

  4. Critical Issues in Early Childhood Professional Development

    ERIC Educational Resources Information Center

    Zaslow, Martha, Ed.; Martinez-Beck, Ivelisse, Ed.

    2005-01-01

    Effective teaching leads to positive student outcomes, and professional development for early childhood teachers is key to improving both. But what exactly is meant by "professional development"? What effect does it have on school readiness? Which models and approaches really work? This is the book the early childhood field needs to take the…

  5. Loss of Desmocollin 3 in Skin Tumor Development and Progression

    PubMed Central

    Chen, Jiangli; O’Shea, Charlene; Fitzpatrick, James E.; Koster, Maranke I.; Koch, Peter J.

    2011-01-01

    Desmocollin 3 (DSC3) is a desmosomal cadherin that is required for maintaining cell adhesion in the epidermis as demonstrated by the intra-epidermal blistering observed in Dsc3 null skin. Recently, it has been suggested that deregulated expression of DSC3 occurs in certain human tumor types. It is not clear whether DSC3 plays a role in the development or progression of cancers arising in stratified epithelia such as the epidermis. To address this issue, we generated a mouse model in which Dsc3 expression is ablated in K-Ras oncogene-induced skin tumors. Our results demonstrate that loss of Dsc3 leads to an increase in K-Ras induced skin tumors. We hypothesize that acantholysis-induced epidermal hyperplasia in the Dsc3 null epidermis facilitates Ras-induced tumor development. Further, we demonstrate that spontaneous loss of DSC3 expression is a common occurrence during human and mouse skin tumor progression. This loss occurs in tumor cells invading the dermis. Interestingly, other desmosomal proteins are still expressed in tumor cells that lack DSC3, suggesting a specific function of DSC3 loss in tumor progression. While loss of DSC3 on the skin surface leads to epidermal blistering, it does not appear to induce loss of cell-cell adhesion in tumor cells invading the dermis, most likely due to a protection of these cells within the dermis from mechanical stress. We thus hypothesize that DSC3 can contribute to the progression of tumors both by cell adhesion-dependent (skin surface) and likely by cell adhesion-independent (invading tumor cells) mechanisms. PMID:21681825

  6. Early experience using the da Vinci Surgical System for the treatment of mediastinal tumors.

    PubMed

    Kajiwara, Naohiro; Taira, Masahiro; Yoshida, Koichi; Hagiwara, Masaru; Kakihana, Masatoshi; Usuda, Jitsuo; Uchida, Osamu; Ohira, Tatsuo; Kawate, Norihiko; Ikeda, Norihiko

    2011-10-01

    The da Vinci Surgical System has been used in only a few cases for treating mediastinal tumors in Japan. Recently, we used the da Vinci Surgical System for various types of anterior and middle mediastinal tumors in clinical practice. We report our early experience using the da Vinci Surgical System. Seven patients gave written informed consent to undergo robotic surgery for mediastinal tumor dissection using the da Vinci Surgical System. We evaluated the safety and feasibility of this system for the surgical treatment of mediastinal tumors. Two specialists in thoracic surgery who are certified to use the da Vinci S Surgical System and another specialist acted as an assistant performed the tumor dissection. We were able to access difficult-to-reach areas, such as the mediastinum, safely. All the resected tumors were classified as benign tumors histologically. The average da Vinci setting time was 14.0 min, the average working time was 55.7 min, and the average overall operating time was 125.9 min. The learning curve for the da Vinci setup and manipulation time was short. Robotic surgery enables mediastinal tumor dissection in certain cases more safely and easily than conventional video-assisted thoracoscopic surgery and less invasively than open thoracotomy.

  7. RNA-Sequencing of Primary Retinoblastoma Tumors Provides New Insights and Challenges Into Tumor Development.

    PubMed

    Elchuri, Sailaja V; Rajasekaran, Swetha; Miles, Wayne O

    2018-01-01

    Retinoblastoma is rare tumor of the retina caused by the homozygous loss of the Retinoblastoma 1 tumor suppressor gene (RB1). Loss of the RB1 protein, pRB, results in de-regulated activity of the E2F transcription factors, chromatin changes and developmental defects leading to tumor development. Extensive microarray profiles of these tumors have enabled the identification of genes sensitive to pRB disruption, however, this technology has a number of limitations in the RNA profiles that they generate. The advent of RNA-sequencing has enabled the global profiling of all of the RNA within the cell including both coding and non-coding features and the detection of aberrant RNA processing events. In this perspective, we focus on discussing how RNA-sequencing of rare Retinoblastoma tumors will build on existing data and open up new area's to improve our understanding of the biology of these tumors. In particular, we discuss how the RB-research field may be to use this data to determine how RB1 loss results in the expression of; non-coding RNAs, causes aberrant RNA processing events and how a deeper analysis of metabolic RNA changes can be utilized to model tumor specific shifts in metabolism. Each section discusses new opportunities and challenges associated with these types of analyses and aims to provide an honest assessment of how understanding these different processes may contribute to the treatment of Retinoblastoma.

  8. Control of early seed development.

    PubMed

    Chaudhury, A M; Koltunow, A; Payne, T; Luo, M; Tucker, M R; Dennis, E S; Peacock, W J

    2001-01-01

    Seed development requires coordinated expression of embryo and endosperm and has contributions from both sporophytic and male and female gametophytic genes. Genetic and molecular analyses in recent years have started to illuminate how products of these multiple genes interact to initiate seed development. Imprinting or differential expression of paternal and maternal genes seems to be involved in controlling seed development, presumably by controlling gene expression in developing endosperm. Epigenetic processes such as chromatin remodeling and DNA methylation affect imprinting of key seed-specific genes; however, the identity of many of these genes remains unknown. The discovery of FIS genes has illuminated control of autonomous endosperm development, a component of apomixis, which is an important developmental and agronomic trait. FIS genes are targets of imprinting, and the genes they control in developing endosperm are also regulated by DNA methylation and chromatin remodeling genes. These results define some exciting future areas of research in seed development.

  9. Quantitative Evaluation of Tumor Early Response to a Vascular-Disrupting Agent with Dynamic PET.

    PubMed

    Guo, Ning; Zhang, Fan; Zhang, Xiaomeng; Guo, Jinxia; Lang, Lixin; Kiesewetter, Dale O; Niu, Gang; Li, Quanzheng; Chen, Xiaoyuan

    2015-12-01

    The purpose of this study is to evaluate the early response of tumors to a vascular-disrupting agent (VDA) VEGF121/recombinant toxin gelonin (rGel) using dynamic [(18)F]FPPRGD2 positron emission tomography (PET) and kinetic parameter estimation. Two tumor xenograft models: U87MG (highly vascularized) and A549 (moderately vascularized), were selected, and both were randomized into treatment and control groups. Sixty-minute dynamic PET scans with [(18)F]FPPRGD2 that targets to integrin αvβ3 were performed at days 0 (baseline), 1, and 3 since VEGF121/rGel treatment started. Dynamic PET-derived binding potential (BPND) and parametric maps were compared with tumor uptake (%ID/g) and the static PET image at 1 h after the tracer administration. The growth of U87MG tumor was obviously delayed upon VEGF121/rGel treatment. A549 tumor was not responsive to the same treatment. BPND of treated U87MG tumors decreased significantly at day 1 (p < 0.05), and the difference was more significant at day 3 (p < 0.01), compared with the control group. However, the tracer uptake (%ID/g) derived from static images at 1-h time point did not show significant difference between the treated and control tumors until day 3. Little difference in tracer uptake (%ID/g) or BPND was found between treated and control A549 tumors. Considering the tracer retention in tumor and the slower clearance due to damaged tumor vasculature after treatment, BPND representing the actual specific binding portion appears to be more sensitive and accurate than the semiquantitative parameters (such as %ID/g) derived from static images to assess the early response of tumor to VDA treatment. Quantitative analysis based on dynamic PET with [(18)F]FPPRGD2 shows advantages in distinguishing effective from ineffective treatment during the course of VEGF121/rGel therapy at early stage and is therefore more sensitive in assessing therapy response than static PET.

  10. Early treatment with metformin induces resistance against tumor growth in adult rats

    PubMed Central

    Trombini, Amanda B; Franco, Claudinéia CS; Miranda, Rosiane A; de Oliveira, Júlio C; Barella, Luiz F; Prates, Kelly V; de Souza, Aline A; Pavanello, Audrei; Malta, Ananda; Almeida, Douglas L; Tófolo, Laize P; Rigo, Kesia P; Ribeiro, Tatiane AS; Fabricio, Gabriel S; de Sant’Anna, Juliane R; Castro-Prado, Marialba AA; de Souza, Helenir Medri; de Morais, Hely; Mathias, Paulo CF

    2015-01-01

    It is known that antidiabetic drug metformin, which is used worldwide, has anti-cancer effects and can be used to prevent cancer growth. We tested the hypothesis that tumor cell growth can be inhibited by early treatment with metformin. For this purpose, adult rats chronically treated with metformin in adolescence or in adulthood were inoculated with Walker 256 carcinoma cells. Adult rats that were treated with metformin during adolescence presented inhibition of tumor growth, and animals that were treated during adult life did not demonstrate any changes in tumor growth. Although we do not have data to disclose a molecular mechanism to the preventive metformin effect, we present, for the first time, results showing that cancer growth in adult life is dependent on early life intervention, thus supporting a new therapeutic prevention for cancer. PMID:26024008

  11. WE-FG-202-02: Exploration of High-Resolution Quantitative Ultrasonic Micro-Vascular Imaging for Early Assessment of Radiotherapy Tumor Response

    SciT

    Kasoji, S; Rivera, J; Dayton, P

    Purpose: Currently, we cannot predict an individual patient’s response to a given radiotherapy which normally is not detected for weeks to months post-treatment. As a result, precious time is wasted for patients with unresponsive tumors who could have switched to an alternative treatment much earlier. Presently, no early treatment response detection method exists that is effective, low-cost, non-invasive, and safe. We hypothesize that changes in tumor microvasculature predict tumor response to radiotherapy earlier than tumor volume changes. Recent radiobiology research suggests tumors undergo vascular remodeling in response to radiation well before manifesting changes in tumor volume. We propose monitoring tumormore » microvasculature post-radiation using Acoustic Angiography (AA), a novel ultrasound imaging modality developed and patented in-house. In this study, we investigate whether changes in tumor microvasculature, measured using AA, can be an early indicator of high-dose radiotherapy success, compared to changes in tumor volume. Methods: Fibrosarcoma xenograft tumor tissue was subcutaneously implanted into rodent flanks (N=10). Animal tumors (N=8) were irradiated with a single treatment of 15Gy using a clinical LINAC at 100SSD and 2×2cm field size. Two untreated rats were left as tumor controls. AA imaging was performed immediately posttreatment and every third day thereafter for 30 days, or until tumors disappeared. Tumor volumes and vascular densities were measured from anatomical b-mode ultrasound and AA images, respectively. Results: Statistical differences in vascular density between treatment responders and non-responders were observed on Day 10 (p=0.005), whereas statistical differences in tumor volume were not observed until Day 19 (p=0.02). Conclusions: Tumor vascularity differences may be observed substantially earlier than differences in tumor size. In addition, significant early increases in vascular density were observed in non

  12. Decursin inhibits vasculogenesis in early tumor progression by suppression of endothelial progenitor cell differentiation and function.

    PubMed

    Jung, Seok Yun; Choi, Jin Hwa; Kwon, Sang-Mo; Masuda, Haruchika; Asahara, Takayuki; Lee, You-Mie

    2012-05-01

    Endothelial progenitor cells (EPCs) contribute to the tumor vasculature during tumor progression. Decursin isolated from the herb Angelica gigas is known to possess potent anti-inflammatory activities. Recently, we reported that decursin is a novel candidate for an angiogenesis inhibitor [Jung et al., 2009]. In this study, we investigated whether decursin regulates EPC differentiation and function to inhibit tumor vasculogenesis. We isolated AC133+ cells from human cord blood and decursin significantly decreased the number of EPC colony forming units of human cord blood-derived AC133+ cells that produce functional EPC progenies. Decursin dose-dependently decreased the cell number of EPC committing cells as demonstrated by EPC expansion studies. Decursin inhibited EPC differentiation from progenitor cells into spindle-shaped EPC colonies. Additionally, decursin inhibited proliferation and migration of early EPCs isolated from mouse bone marrow. Furthermore, decursin suppressed expression of angiopoietin-2, angiopoietin receptor Tie-2, Flk-1 (vascular endothelial growth factor receptor-2), and endothelial nitric oxide synthase in mouse BM derived EPCs in a dose-dependent manner. Decursin suppressed tube formation ability of EPCs in collaboration with HUVEC. Decursin (4 mg/kg) inhibited tumor-induced mobilization of circulating EPCs (CD34 + /VEGFR-2+ cells) from bone marrow and early incorporation of Dil-Ac-LDL-labeled or green fluorescent protein (GFP)+ EPCs into neovessels of xenograft Lewis lung carcinoma tumors in wild-type- or bone-marrow-transplanted mice. Accordingly, decursin attenuated EPC-derived endothelial cells in neovessels of Lewis lung carcinoma tumor masses grown in mice. Together, decursin likely affects EPC differentiation and function, thereby inhibiting tumor vasculogenesis in early tumorigenesis. Copyright © 2012 Wiley Periodicals, Inc.

  13. Tumor Marker Usage and Medical Care Costs Among Older Early-Stage Breast Cancer Survivors

    PubMed Central

    Ramsey, Scott D.; Henry, N. Lynn; Gralow, Julie R.; Mirick, Dana K.; Barlow, William; Etzioni, Ruth; Mummy, David; Thariani, Rahber; Veenstra, David L.

    2015-01-01

    Purpose Although American Society of Clinical Oncology guidelines discourage the use of tumor marker assessment for routine surveillance in nonmetastatic breast cancer, their use in practice is uncertain. Our objective was to determine use of tumor marker tests such as carcinoembryonic antigen and CA 15-3/CA 27.29 and associated Medicare costs in early-stage breast cancer survivors. Methods By using Surveillance, Epidemiology, and End Results-Medicare records for patients diagnosed with early-stage breast cancer between 2001 and 2007, tumor marker usage within 2 years after diagnosis was identified by billing codes. Logistic regression models were used to identify clinical and demographic factors associated with use of tumor markers. To determine impact on costs of care, we used multivariable regression, controlling for other factors known to influence total medical costs. Results We identified 39,650 eligible patients. Of these, 16,653 (42%) received at least one tumor marker assessment, averaging 5.7 tests over 2 years, with rates of use per person increasing over time. Factors significantly associated with use included age at diagnosis, diagnosis year, stage at diagnosis, race/ethnicity, geographic region, and urban/rural status. Rates of advanced imaging, but not biopsies, were significantly higher in the assessment group. Medical costs for patients who received at least one test were approximately 29% greater than costs for those who did not, adjusting for other factors. Conclusion Breast cancer tumor markers are frequently used among women with early-stage disease and are associated with an increase in both diagnostic procedures and total cost of care. A better understanding of factors driving the use of and the potential benefits and harms of surveillance-based tumor marker testing is needed. PMID:25332254

  14. Bi-model processing for early detection of breast tumor in CAD system

    NASA Astrophysics Data System (ADS)

    Mughal, Bushra; Sharif, Muhammad; Muhammad, Nazeer

    2017-06-01

    Early screening of skeptical masses in mammograms may reduce mortality rate among women. This rate can be further reduced upon developing the computer-aided diagnosis system with decrease in false assumptions in medical informatics. This method highlights the early tumor detection in digitized mammograms. For improving the performance of this system, a novel bi-model processing algorithm is introduced. It divides the region of interest into two parts, the first one is called pre-segmented region (breast parenchyma) and other is the post-segmented region (suspicious region). This system follows the scheme of the preprocessing technique of contrast enhancement that can be utilized to segment and extract the desired feature of the given mammogram. In the next phase, a hybrid feature block is presented to show the effective performance of computer-aided diagnosis. In order to assess the effectiveness of the proposed method, a database provided by the society of mammographic images is tested. Our experimental outcomes on this database exhibit the usefulness and robustness of the proposed method.

  15. Label-free nanoplasmonic sensing of tumor-associate autoantibodies for early diagnosis of colorectal cancer.

    PubMed

    Soler, Maria; Estevez, M-Carmen; Villar-Vazquez, Roi; Casal, J Ignacio; Lechuga, Laura M

    2016-08-03

    Colorectal cancer is treatable and curable when detected at early stages. However there is a lack of less invasive and more specific screening and diagnosis methods which would facilitate its prompt identification. Blood circulating autoantibodies which are immediately produced by the immune system at tumor appearance have become valuable biomarkers for preclinical diagnosis of cancer. In this work, we present the rapid and label-free detection of colorectal cancer autoantibodies directly in blood serum or plasma using a recently developed nanoplasmonic biosensor. Our nanoplasmonic device offers sensitive and real-time quantification of autoantibodies with excellent selectivity and reproducibility, achieving limits of detection around 1 nM (150-160 ng mL(-1)). A preliminary evaluation of clinical samples of colorectal cancer patients has shown good correlation with ELISA. These results demonstrate the reliability of the nanobiosensor strategy and pave the way towards the achievement of a sensitive diagnostic tool for early detection of colorectal cancer. Copyright © 2016 Elsevier B.V. All rights reserved.

  16. Clinical significance of tumor cavitation in surgically resected early-stage primary lung cancer.

    PubMed

    Tomizawa, Kenji; Shimizu, Shigeki; Ohara, Shuta; Fujino, Toshio; Nishino, Masaya; Sesumi, Yuichi; Kobayashi, Yoshihisa; Sato, Katsuaki; Chiba, Masato; Shimoji, Masaki; Suda, Kenichi; Takemoto, Toshiki; Mitsudomi, Tetsuya

    2017-10-01

    The prognostic impact of tumor cavitation is unclear in patients with early-stage primary lung cancer. The aim of the present study was to examine the clinicopathological features and prognoses of patients with pathological stage I-IIA (p-stage I-IIA) primary lung cancers harboring tumor cavitation. This study was conducted according to the eighth edition of the TNM classification for lung cancer. We examined 602 patients with p-stage I-IIA primary lung cancer out of 890 patients who underwent pulmonary resection from January 2007 through March 2014 and searched for the presence of tumor cavitation, which is defined as the presence of air space within the primary tumor. A total of 59 out of the 602 patients had tumor cavitation (10%). Compared with patients without tumor cavitation, those with tumor cavitation had a significantly higher frequency of the following characteristics: high serum carcinoembryonic antigen (CEA) level (≥5ng/ml, p=0.027), interstitial pneumonia (p=0.0001), high SUVmax value on FDG-PET scan (≥4.2, p=0.023), tumors located in the lower lobe (p=0.024), large tumor size (>3cm, p=0.002), vascular invasion (66% vs 17%, p<0.0001) and non-adenocarcinoma histology (p=0.025). The overall survival period of patients with tumor cavitation was significantly shorter than that of patients without tumor cavitation (log-rank test: p<0.0001, 5-year OS rate: 56% vs 81%). Tumor cavitation was found to be an independent and significant factor associated with poor prognosis in the multivariate analysis (hazard ratio: 1.76, 95% confidence interval: 1.02-3.10, p=0.042). Tumor cavitation is an independent factor for poor prognosis in patients with resected p-stage I-IIA primary lung cancer. Based on our analyses, patients with tumor cavitation should be regarded as a separate cohort that requires more intensive follow-up. Copyright © 2017 Elsevier B.V. All rights reserved.

  17. Tumor-targeted SN38 inhibits growth of early stage non-small cell lung cancer (NSCLC) in a KRas/p53 transgenic mouse model.

    PubMed

    Deneka, Alexander Y; Haber, Leora; Kopp, Meghan C; Gaponova, Anna V; Nikonova, Anna S; Golemis, Erica A

    2017-01-01

    Non-small cell lung cancer (NSCLC) is the leading cause of cancer death worldwide, with a 5-year survival of only ~16%. Potential strategies to address NSCLC mortality include improvements in early detection and prevention, and development of new therapies suitable for use in patients with early and late stage diagnoses. Controlling the growth of early stage tumors could yield significant clinical benefits for patients with comorbidities that make them poor candidates for surgery: however, many drugs that limit cancer growth are not useful in the setting of long-term use or in comorbid patients, because of associated toxicities. In this study, we explored the use of a recently described small molecule agent, STA-8666, as a potential agent for controlling early stage tumor growth. STA-8666 uses a cleavable linker to merge a tumor-targeting moiety that binds heat shock protein 90 (HSP90) with the cytotoxic chemical SN38, and has been shown to have high efficacy and low toxicity, associated with efficient tumor targeting, in preclinical studies using patient-derived and other xenograft models for pancreatic, bladder, and small cell lung cancer. Using a genetically engineered model of NSCLC arising from induced mutation of KRas and knockout of Trp53, we continuously dosed mice with STA-8666 from immediately after tumor induction for 15 weeks. STA-8666 significantly slowed the rate of tumor growth, and was well tolerated over this extended dosing period. STA-8666 induced DNA damage and apoptosis, and reduced proliferation and phosphorylation of the proliferation-associated protein ERK1/2, selectively in tumor tissue. In contrast, STA-8666 did not affect tumor features, such as degree of vimentin staining, associated with epithelial-mesenchymal transition (EMT), or downregulate tumor expression of HSP90. These data suggest STA-8666 and other similar targeted compounds may be useful additions to control the growth of early stage NSCLC in patient populations.

  18. Phase transition in tumor growth: I avascular development

    NASA Astrophysics Data System (ADS)

    Izquierdo-Kulich, E.; Rebelo, I.; Tejera, E.; Nieto-Villar, J. M.

    2013-12-01

    We propose a mechanism for avascular tumor growth based on a simple chemical network. This model presents a logistic behavior and shows a “second order” phase transition. We prove the fractal origin of the empirical logistics and Gompertz constant and its relation to mitosis and apoptosis rate. Finally, the thermodynamics framework developed demonstrates the entropy production rate as a Lyapunov function during avascular tumor growth.

  19. Exome sequencing of bilateral testicular germ cell tumors suggests independent development lineages.

    PubMed

    Brabrand, Sigmund; Johannessen, Bjarne; Axcrona, Ulrika; Kraggerud, Sigrid M; Berg, Kaja G; Bakken, Anne C; Bruun, Jarle; Fosså, Sophie D; Lothe, Ragnhild A; Lehne, Gustav; Skotheim, Rolf I

    2015-02-01

    Intratubular germ cell neoplasia, the precursor of testicular germ cell tumors (TGCTs), is hypothesized to arise during embryogenesis from developmentally arrested primordial germ cells (PGCs) or gonocytes. In early embryonal life, the PGCs migrate from the yolk sac to the dorsal body wall where the cell population separates before colonizing the genital ridges. However, whether the malignant transformation takes place before or after this separation is controversial. We have explored the somatic exome-wide mutational spectra of bilateral TGCT to provide novel insight into the in utero critical time frame of malignant transformation and TGCT pathogenesis. Exome sequencing was performed in five patients with bilateral TGCT (eight tumors), of these three patients in whom both tumors were available (six tumors) and two patients each with only one available tumor (two tumors). Selected loci were explored by Sanger sequencing in 71 patients with bilateral TGCT. From the exome-wide mutational spectra, no identical mutations in any of the three bilateral tumor pairs were identified. Exome sequencing of all eight tumors revealed 87 somatic non-synonymous mutations (median 10 per tumor; range 5-21), some in already known cancer genes such as CIITA, NEB, platelet-derived growth factor receptor α (PDGFRA), and WHSC1. SUPT6H was found recurrently mutated in two tumors. We suggest independent development lineages of bilateral TGCT. Thus, malignant transformation into intratubular germ cell neoplasia is likely to occur after the migration of PGCs. We reveal possible drivers of TGCT pathogenesis, such as mutated PDGFRA, potentially with therapeutic implications for TGCT patients. Copyright © 2014 Neoplasia Press, Inc. Published by Elsevier Inc. All rights reserved.

  20. Diffuse optical measurements of head and neck tumor hemodynamics for early prediction of chemoradiation therapy outcomes

    NASA Astrophysics Data System (ADS)

    Dong, Lixin; Kudrimoti, Mahesh; Irwin, Daniel; Chen, Li; Kumar, Sameera; Shang, Yu; Huang, Chong; Johnson, Ellis L.; Stevens, Scott D.; Shelton, Brent J.; Yu, Guoqiang

    2016-08-01

    This study used a hybrid near-infrared diffuse optical instrument to monitor tumor hemodynamic responses to chemoradiation therapy for early prediction of treatment outcomes in patients with head and neck cancer. Forty-seven patients were measured once per week to evaluate the hemodynamic status of clinically involved cervical lymph nodes as surrogates for the primary tumor response. Patients were classified into two groups: complete response (CR) (n=29) and incomplete response (IR) (n=18). Tumor hemodynamic responses were found to be associated with clinical outcomes (CR/IR), wherein the associations differed depending on human papillomavirus (HPV-16) status. In HPV-16 positive patients, significantly lower levels in tumor oxygenated hemoglobin concentration ([HbO2]) at weeks 1 to 3, total hemoglobin concentration at week 3, and blood oxygen saturation (StO2) at week 3 were found in the IR group. In HPV-16 negative patients, significantly higher levels in tumor blood flow index and reduced scattering coefficient (μs‧) at week 3 were observed in the IR group. These hemodynamic parameters exhibited significantly high accuracy for early prediction of clinical outcomes, within the first three weeks of therapy, with the areas under the receiver operating characteristic curves (AUCs) ranging from 0.83 to 0.96.

  1. Ultrasonic RF time series for early assessment of the tumor response to chemotherapy.

    PubMed

    Lin, Qingguang; Wang, Jianwei; Li, Qing; Lin, Chunyi; Guo, Zhixing; Zheng, Wei; Yan, Cuiju; Li, Anhua; Zhou, Jianhua

    2018-01-05

    Ultrasound radio-frequency (RF) time series have been shown to carry tissue typing information. To evaluate the potential of RF time series for early prediction of tumor response to chemotherapy, 50MCF-7 breast cancer-bearing nude mice were randomized to receive cisplatin and paclitaxel (treatment group; n = 26) or sterile saline (control group; n = 24). Sequential ultrasound imaging was performed on days 0, 3, 6, and 8 of treatment to simultaneously collect B-mode images and RF data. Six RF time series features, slope, intercept, S1, S2, S3 , and S4 , were extracted during RF data analysis and contrasted with microstructural tumor changes on histopathology. Chemotherapy administration reduced tumor growth relative to control on days 6 and 8. Compared with day 0, intercept, S1 , and S2 were increased while slope was decreased on days 3, 6, and 8 in the treatment group. Compared with the control group, intercept, S1, S2, S3 , and S4 were increased, and slope was decreased, on days 3, 6, and 8 in the treatment group. Tumor cell density decreased significantly in the latter on day 3. We conclude that ultrasonic RF time series analysis provides a simple way to noninvasively assess the early tumor response to chemotherapy.

  2. Diffuse optical measurements of head and neck tumor hemodynamics for early prediction of chemoradiation therapy outcomes

    PubMed Central

    Dong, Lixin; Kudrimoti, Mahesh; Irwin, Daniel; Chen, Li; Kumar, Sameera; Shang, Yu; Huang, Chong; Johnson, Ellis L.; Stevens, Scott D.; Shelton, Brent J.; Yu, Guoqiang

    2016-01-01

    Abstract. This study used a hybrid near-infrared diffuse optical instrument to monitor tumor hemodynamic responses to chemoradiation therapy for early prediction of treatment outcomes in patients with head and neck cancer. Forty-seven patients were measured once per week to evaluate the hemodynamic status of clinically involved cervical lymph nodes as surrogates for the primary tumor response. Patients were classified into two groups: complete response (CR) (n=29) and incomplete response (IR) (n=18). Tumor hemodynamic responses were found to be associated with clinical outcomes (CR/IR), wherein the associations differed depending on human papillomavirus (HPV-16) status. In HPV-16 positive patients, significantly lower levels in tumor oxygenated hemoglobin concentration ([HbO2]) at weeks 1 to 3, total hemoglobin concentration at week 3, and blood oxygen saturation (StO2) at week 3 were found in the IR group. In HPV-16 negative patients, significantly higher levels in tumor blood flow index and reduced scattering coefficient (μs′) at week 3 were observed in the IR group. These hemodynamic parameters exhibited significantly high accuracy for early prediction of clinical outcomes, within the first three weeks of therapy, with the areas under the receiver operating characteristic curves (AUCs) ranging from 0.83 to 0.96. PMID:27564315

  3. How much tumor surgery do early-career orthopaedic oncologists perform?

    PubMed

    Miller, Benjamin J; Rajani, Rajiv; Leddy, Lee; Carmody Soni, Emily E; White, Jeremy R

    2015-02-01

    There are few data on the types of procedures orthopaedic oncologists perform in their first years of practice. Because fellowships are graduating fellows each year and the number of tumor patients is limited, defining the practice patterns of early-career orthopaedic oncologists may help diminish early employment discontent and enhance workforce discussions. The aim of the study was to use the objective case log volumes of a cross-section of early career orthopaedic oncologists to describe (1) the number of operations performed annually; (2) the proportion of tumor, trauma, adult reconstruction, and other operations for individual participants, (3) individual practice characteristics that were associated with the number of tumor procedures; and (4) the sources of satisfaction and challenges in each individual's career and surgical practice. Fifteen fellowship-trained orthopaedic oncologists out of a potential pool of 33 (45%) in their first 4 years of practice responded to a survey by submitting complete operative case lists for a 2-year period. We recorded the type of procedure and determined associations between the annual number of tumor operations and total operative caseload, years in practice, and some details of individual practice patterns. Each participant completed a survey regarding practice-related sources of stress and satisfaction. A total of 5611 surgical cases were available for review. For the entire cohort, there were 3303 (59%) tumor procedures, 973 (17%) trauma, 890 (16%) adult reconstruction, and 445 (8%) other. The median annual number of total operations was 214 (range, 63-356) and median annual number of tumor operations was 135 (range, 47-216). The median proportion of tumor operations in an individual practice was 56% (range, 43%-94%). The annual number of tumor operations correlated with the total annual number of operations (r = 0.73, p < 0.001). Sources of stress and satisfaction were similar to the general membership of the

  4. Monitoring early tumor response to drug therapy with diffuse optical tomography

    NASA Astrophysics Data System (ADS)

    Flexman, Molly L.; Vlachos, Fotios; Kim, Hyun Keol; Sirsi, Shashank R.; Huang, Jianzhong; Hernandez, Sonia L.; Johung, Tessa B.; Gander, Jeffrey W.; Reichstein, Ari R.; Lampl, Brooke S.; Wang, Antai; Borden, Mark A.; Yamashiro, Darrell J.; Kandel, Jessica J.; Hielscher, Andreas H.

    2012-01-01

    Although anti-angiogenic agents have shown promise as cancer therapeutics, their efficacy varies between tumor types and individual patients. Providing patient-specific metrics through rapid noninvasive imaging can help tailor drug treatment by optimizing dosages, timing of drug cycles, and duration of therapy--thereby reducing toxicity and cost and improving patient outcome. Diffuse optical tomography (DOT) is a noninvasive three-dimensional imaging modality that has been shown to capture physiologic changes in tumors through visualization of oxygenated, deoxygenated, and total hemoglobin concentrations, using non-ionizing radiation with near-infrared light. We employed a small animal model to ascertain if tumor response to bevacizumab (BV), an anti-angiogenic agent that targets vascular endothelial growth factor (VEGF), could be detected at early time points using DOT. We detected a significant decrease in total hemoglobin levels as soon as one day after BV treatment in responder xenograft tumors (SK-NEP-1), but not in SK-NEP-1 control tumors or in non-responder control or BV-treated NGP tumors. These results are confirmed by magnetic resonance imaging T2 relaxometry and lectin perfusion studies. Noninvasive DOT imaging may allow for earlier and more effective control of anti-angiogenic therapy.

  5. Autophagy-deficient mice develop multiple liver tumors

    PubMed Central

    Takamura, Akito; Komatsu, Masaaki; Hara, Taichi; Sakamoto, Ayako; Kishi, Chieko; Waguri, Satoshi; Eishi, Yoshinobu; Hino, Okio; Tanaka, Keiji; Mizushima, Noboru

    2011-01-01

    Autophagy is a major pathway for degradation of cytoplasmic proteins and organelles, and has been implicated in tumor suppression. Here, we report that mice with systemic mosaic deletion of Atg5 and liver-specific Atg7−/− mice develop benign liver adenomas. These tumor cells originate autophagy-deficient hepatocytes and show mitochondrial swelling, p62 accumulation, and oxidative stress and genomic damage responses. The size of the Atg7−/− liver tumors is reduced by simultaneous deletion of p62. These results suggest that autophagy is important for the suppression of spontaneous tumorigenesis through a cell-intrinsic mechanism, particularly in the liver, and that p62 accumulation contributes to tumor progression. PMID:21498569

  6. Early circulating tumor DNA dynamics and clonal selection with palbociclib and fulvestrant for breast cancer.

    PubMed

    O'Leary, Ben; Hrebien, Sarah; Morden, James P; Beaney, Matthew; Fribbens, Charlotte; Huang, Xin; Liu, Yuan; Bartlett, Cynthia Huang; Koehler, Maria; Cristofanilli, Massimo; Garcia-Murillas, Isaac; Bliss, Judith M; Turner, Nicholas C

    2018-03-01

    CDK4/6 inhibition substantially improves progression-free survival (PFS) for women with advanced estrogen receptor-positive breast cancer, although there are no predictive biomarkers. Early changes in circulating tumor DNA (ctDNA) level may provide early response prediction, but the impact of tumor heterogeneity is unknown. Here we use plasma samples from patients in the randomized phase III PALOMA-3 study of CDK4/6 inhibitor palbociclib and fulvestrant for women with advanced breast cancer and show that relative change in PIK3CA ctDNA level after 15 days treatment strongly predicts PFS on palbociclib and fulvestrant (hazard ratio 3.94, log-rank p = 0.0013). ESR1 mutations selected by prior hormone therapy are shown to be frequently sub clonal, with ESR1 ctDNA dynamics offering limited prediction of clinical outcome. These results suggest that early ctDNA dynamics may provide a robust biomarker for CDK4/6 inhibitors, with early ctDNA dynamics demonstrating divergent response of tumor sub clones to treatment.

  7. Time resolved optical system for an early detection of prostate tumor

    NASA Astrophysics Data System (ADS)

    Hervé, Lionel; Laidevant, Aurélie; Debourdeau, Mathieu; Boutet, Jérôme; Dinten, Jean-Marc

    2011-02-01

    We developed an endorectal time-resolved optical probe aiming at an early detection of prostate tumors targeted by fluorescent markers. Optical fibers are embedded inside a clinical available ultrasound endorectal probe. Excitation light is driven sequentially from a femtosecond laser (775 nm) into 6 source fibers. 4 detection fibers collect the medium responses at the excitation and fluorescence wavelength (850 nm) by the mean of 4 photomultipliers associated with a 4 channel time-correlated single photon counting card. We also developed the method to process the experimental data. This involves the numerical computation of the forward model, the creation of robust features which are automatically correctly from numerous experimental possible biases and the reconstruction of the inclusion by using the intensity and mean time of these features. To evaluate our system performance, we acquired measurements of a 40 μL ICG inclusion (10 μmol.L-1) at various lateral and depth locations in a phantom. Analysis of results showed we correctly reconstructed the fluorophore for the lateral positions (16 mm range) and for a distance to the probe going up to 1.5 cm. Precision of localization was found to be around 1 mm which complies well with precision specifications needed for the clinical application.

  8. A Mouse to Human Search for Plasma Proteome Changes Associated with Pancreatic Tumor Development

    PubMed Central

    Faca, Vitor M; Song, Kenneth S; Wang, Hong; Zhang, Qing; Krasnoselsky, Alexei L; Newcomb, Lisa F; Plentz, Ruben R; Gurumurthy, Sushma; Redston, Mark S; Pitteri, Sharon J; Pereira-Faca, Sandra R; Ireton, Renee C; Katayama, Hiroyuki; Glukhova, Veronika; Phanstiel, Douglas; Brenner, Dean E; Anderson, Michelle A; Misek, David; Scholler, Nathalie; Urban, Nicole D; Barnett, Matt J; Edelstein, Cim; Goodman, Gary E; Thornquist, Mark D; McIntosh, Martin W; DePinho, Ronald A; Bardeesy, Nabeel; Hanash, Samir M

    2008-01-01

    Background The complexity and heterogeneity of the human plasma proteome have presented significant challenges in the identification of protein changes associated with tumor development. Refined genetically engineered mouse (GEM) models of human cancer have been shown to faithfully recapitulate the molecular, biological, and clinical features of human disease. Here, we sought to exploit the merits of a well-characterized GEM model of pancreatic cancer to determine whether proteomics technologies allow identification of protein changes associated with tumor development and whether such changes are relevant to human pancreatic cancer. Methods and Findings Plasma was sampled from mice at early and advanced stages of tumor development and from matched controls. Using a proteomic approach based on extensive protein fractionation, we confidently identified 1,442 proteins that were distributed across seven orders of magnitude of abundance in plasma. Analysis of proteins chosen on the basis of increased levels in plasma from tumor-bearing mice and corroborating protein or RNA expression in tissue documented concordance in the blood from 30 newly diagnosed patients with pancreatic cancer relative to 30 control specimens. A panel of five proteins selected on the basis of their increased level at an early stage of tumor development in the mouse was tested in a blinded study in 26 humans from the CARET (Carotene and Retinol Efficacy Trial) cohort. The panel discriminated pancreatic cancer cases from matched controls in blood specimens obtained between 7 and 13 mo prior to the development of symptoms and clinical diagnosis of pancreatic cancer. Conclusions Our findings indicate that GEM models of cancer, in combination with in-depth proteomic analysis, provide a useful strategy to identify candidate markers applicable to human cancer with potential utility for early detection. PMID:18547137

  9. Regulation of early Xenopus development by ErbB signaling

    PubMed Central

    Nie, Shuyi; Chang, Chenbei

    2008-01-01

    ErbB signaling has long been implicated in cancer formation and progression and is shown to regulate cell division, migration and death during tumorigenesis. The functions of the ErbB pathway during early vertebrate embryogenesis, however, are not well understood. Here we report characterization of ErbB activities during early frog development. Gain-of-function analyses show that EGFR, ErbB2 and ErbB4 induce ectopic tumor-like cell mass that contains increased numbers of mitotic cells. Both the muscle and the neural markers are expressed in these ectopic protrusions. ErbBs also induce mesodermal markers in ectodermal explants. Loss-of-function studies using carboxyl terminal-truncated dominant-negative ErbB receptors demonstrate that blocking ErbB signals leads to defective gastrulation movements and malformation of the embryonic axis with a reduction in the head structures in early frog embryos. These data, together with the observation that ErbBs are expressed early during frog embryogenesis, suggest that ErbBs regulate cell proliferation, movements and embryonic patterning during early Xenopus development. PMID:16258939

  10. Early childhood development in deprived urban settlements.

    PubMed

    Nair, M K C; Radhakrishnan, S Rekha

    2004-03-01

    Poverty, the root cause of the existence of slums or settlement colonies in urban areas has a great impact on almost all aspects of life of the urban poor, especially the all-round development of children. Examples from countries, across the globe provide evidence of improved early child development, made possible through integrated slum improvement programs, are few in numbers. The observed 2.5% prevalence of developmental delay in the less than 2 year olds of deprived urban settlements, the presence of risk factors for developmental delay like low birth weight, birth asphyxia, coupled with poor environment of home and alternate child care services, highlights the need for simple cost effective community model for promoting early child development. This review on early child development focuses on the developmental status of children in the deprived urban settlements, who are yet to be on the priority list of Governments and international agencies working for the welfare of children, the contributory nature-nurture factors and replicable working models like infant stimulation, early detection of developmental delay in infancy itself, developmental screening of toddlers, skill assessment for preschool children, school readiness programs, identification of mental sub-normality and primary education enhancement program for primary school children. Further, the review probes feasible intervention strategies through community owned early child care and development facilities, utilizing existing programs like ICDS, Urban Basic Services and by initiating services like Development Friendly Well Baby Clinics, Community Extension services, Child Development Referral Units at district hospitals and involving trained manpower like anganwadi/creche workers, public health nurses and developmental therapists. With the decentralization process the local self-government at municipalities and city corporations are financially equipped to be the prime movers to initiate, monitor and

  11. Tumor laterality in early ovarian cancer: influence on left-right asymmetry of pelvic lymph nodes.

    PubMed

    Mujezinović, Faris; Takac, Iztok

    2010-01-01

    AIM AND BACKGROUND.:To determine whether left-right asymmetry was present in cases of early ovarian cancer and whether or not the difference between number of removed lymph nodes on both sides of the pelvis is associated with tumor laterality. We extracted from the medical data base cases of early ovarian cancer with lymphadenectomy who had been treated between 1994 and 2008. The sample was divided in three groups according to the left-right laterality of the tumor in the pelvis (bilateral, left sided, right sided). For each case, we subtracted the number of dissected lymph nodes on the left side from the number of dissected lymph nodes on the right side of the pelvis (N(Right side) - N(Left side)). We used one sample t test to determine whether the mean of differences for each group was different from zero. Results. We extracted 48 cases with early ovarian cancer who had undergone lymphadenectomy. The average number of dissected lymph nodes was 24 (SD, 12). In 3 cases, we confirmed the presence of lymph node metastasis (6.3%). In 2 of the upstaged cases, tumor and involved lymph nodes were on the right side of the pelvis. In the third case, the tumor was on the left side, whereas involved lymph nodes were on both sides of the pelvis. For bilateral tumors, tumors on the left, and those on the right side of the pelvis, the mean difference was -0.5 (95% CI, -9.9 to 8.9; t, -0.137; P = 0.90), 0.32 (95% CI, -3.8 to 4.5; t, 0.16; P = 0.87) and 3.5 (95% CI, 0.03 to 7.01; t, 2.09; P = 0.048), respectively. When the tumor was on the left or on both sides of the pelvis, there was no significant difference in the number of removed lymph nodes. In contrast, when the tumor was on the right side, the number of removed lymph nodes was significantly higher on the right hemipelvis than on the left hemipelvis.

  12. Early Brain Development Research Review and Update

    ERIC Educational Resources Information Center

    Schiller, Pam

    2010-01-01

    Thanks to imaging technology used in neurobiology, people have access to useful and critical information regarding the development of the human brain. This information allows them to become much more effective in helping children in their early development. In fact, when people base their practices on the findings from medical science research,…

  13. Developing vascular and hypoxia based theranostics in solid tumors

    NASA Astrophysics Data System (ADS)

    Koonce, Nathan A.

    Tissue hypoxia was recognized for its biological attenuating effects on ionizing radiation over a century ago and is a characteristic feature of many solid tumors. Clinical and experimental evidence indicates tumor hypoxia plays diverse and key roles in tumor progression, angiogenesis, and resistance to chemotherapy/radiotherapy. Hypoxia has known effects on progression and resistance to several standard treatment approaches and the significant history of study might suggest diagnostic imaging and therapeutic interventions would be routine in oncological practice. Curiously, this is not the case and the research results involved in this report will attempt to better understand and contribute to why this gap in knowledge exists and a rationale for harnessing the potential of detecting and targeting hypoxia. Despite the addition of oxygen and reversal of hypoxia being known as the best radiosensitizer, hypoxia remains unexploited in clinical cancer therapy. The studies reported herein detail development of a novel imaging technique to detect a subtype of tumor hypoxia, vascular hypoxia or hypoxemia, with a 17-fold increase (p<0.05) in uptake of pimonidazole targeted microbubbles observed compared to controls. This technique creates the potential to study the role of hypoxemia in progression and therapeutic response. Additionally, description of a nanoparticle-based therapy that targets tumor areas associated with tumor hypoxia and the tumor microenvironment in general is reported. TNF-loaded nanoparticles combined with radiotherapy resulted in a 5.25-fold growth delay that was found to be synergistic (p<0.05) and suggests clinical evaluation is warranted. An additional study to evaluate an approach to use thermal ablation of intratumoral hypoxia by an image-guided technique developed in our group is described along with a sequence dependence of radiation preceding ablation. A final study on the use of galectin-1 antagonist to significantly decrease (p<0.05) hypoxia

  14. 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

  15. Autophagy-deficient breast cancer shows early tumor recurrence and escape from dormancy

    PubMed Central

    Aqbi, Hussein F.; Tyutyunyk-Massey, Liliya; Keim, Rebecca C.; Butler, Savannah E.; Thekkudan, Theresa; Joshi, Supriya; Smith, Timothy M.; Bandyopadhyay, Dipankar; Idowu, Michael O.; Bear, Harry D.; Payne, Kyle K.; Gewirtz, David A.; Manjili, Masoud H.

    2018-01-01

    Breast cancer patients who initially respond to cancer therapies often succumb to distant recurrence of the disease. It is not clear why people with the same type of breast cancer respond to treatments differently; some escape from dormancy and relapse earlier than others. In addition, some tumor clones respond to immunotherapy while others do not. We investigated how autophagy plays a role in accelerating or delaying recurrence of neu-overexpressing mouse mammary carcinoma (MMC) following adriamycin (ADR) treatment, and in affecting response to immunotherapy. We explored two strategies: 1) transient blockade of autophagy with chloroquine (CQ), which blocks fusion of autophagosomes and lysosomes during ADR treatment, and 2) permanent inhibition of autophagy by a stable knockdown of ATG5 (ATG5KD), which inhibits the formation of autophagosomes in MMC during and after ADR treatment. We found that while CQ prolonged tumor dormancy, but that stable knockdown of autophagy resulted in early escape from dormancy and recurrence. Interestingly, ATG5KD MMC contained an increased frequency of ADR-induced polyploid-like cells and rendered MMC resistant to immunotherapy. On the other hand, a transient blockade of autophagy did not affect the sensitivity of MMC to immunotherapy. Our observations suggest that while chemotherapy-induced autophagy may facilitate tumor relapse, cell-intrinsic autophagy delays tumor relapse, in part, by inhibiting the formation of polyploid-like tumor dormancy. PMID:29774126

  16. Docosahexaenoic acid conjugated near infrared flourescence probe for in vivo early tumor diagnosis

    NASA Astrophysics Data System (ADS)

    Li, Siwen; Cao, Jie; Qin, Jingyi; Zhang, Xin; Achilefu, Samuel; Qian, Zhiyu; Gu, Yueqing

    2013-02-01

    Docosahexaenoic acid(DHA) is an omega-3 C22 natural fatty acid with six cis double bonds and as a constituent of membranes used as a precursor for metabolic and biochemical path ways. In this manuscript,we describe the synthesis of near-infrared(NIR) flourescence ICG-Der-01 labeled DHA for in vitro and vivo tumor targeting.The structure of the probe was intensively characterized by UV and MS. The in vitro and vivo tumor targeting abilities of the DHA-based NIR probes were investigeted in MCF-7 cells and MCF-7 xenograft mice model differently by confocal microscopy and CCD camera. The cell cytotoxicity were tested in tumor cells MCF-7 .The results shows that the DHA-based NIR probes have high affinity with the tumor both in vitro and vivo.In addition ,we also found that the DHA-based NIR probes have the apparent cytotoxicity on MCF-7 cells .which demonstrated that DHA was conjugated with other antitumor drug could increase the abilities of antirumor efficacy .So DHA-ICG-Der-01 is a promising optical agent for diagnosis of tumors especially in their early stage.

  17. Canine tumor development and crude incidence of tumors by breed based on domestic dogs in Gifu prefecture

    PubMed Central

    KOMAZAWA, Satoshi; SAKAI, Hiroki; ITOH, Yusuke; KAWABE, Mifumi; MURAKAMI, Mami; MORI, Takashi; MARUO, Kohji

    2016-01-01

    We analyzed the status of tumor development in dogs by breed based on tumor cases that presented to the Department of Veterinary Pathology of the Gifu University for diagnostic examinations over eight years (2005–2012). We also calculated the crude incidence of tumors in dogs by breed based on the results of a survey conducted in 2011 in Gifu Prefecture. The most common sites of tumor development included the skin, digestive organs and mammary glands. Smaller dogs showed a tendency to have a higher incidence of breast tumors. We thus identified dog breeds with a higher crude incidence of tumors (Bernese mountain dog, golden retriever, corgi, etc.) and those with a lower crude incidence of tumors (Pomeranian, poodle, Chihuahua, etc.). Unlike the current trends for domestic dogs in the US and Europe, Japan has a higher number of small dogs as pets; it is therefore necessary to develop a policy for canine cancer specific to Japan. PMID:27150207

  18. Early executive function predicts reasoning development.

    PubMed

    Richland, Lindsey E; Burchinal, Margaret R

    2013-01-01

    Analogical reasoning is a core cognitive skill that distinguishes humans from all other species and contributes to general fluid intelligence, creativity, and adaptive learning capacities. Yet its origins are not well understood. In the study reported here, we analyzed large-scale longitudinal data from the Study of Early Child Care and Youth Development to test predictors of growth in analogical-reasoning skill from third grade to adolescence. Our results suggest an integrative resolution to the theoretical debate regarding contributory factors arising from smaller-scale, cross-sectional experiments on analogy development. Children with greater executive-function skills (both composite and inhibitory control) and vocabulary knowledge in early elementary school displayed higher scores on a verbal analogies task at age 15 years, even after adjusting for key covariates. We posit that knowledge is a prerequisite to analogy performance, but strong executive-functioning resources during early childhood are related to long-term gains in fundamental reasoning skills.

  19. Bioecological Theory, Early Child Development and the Validation of the Population-Level Early Development Instrument

    ERIC Educational Resources Information Center

    Guhn, Martin; Goelman, Hillel

    2011-01-01

    The Early Development Instrument (EDI; Janus and Offord in "Canadian Journal of Behavioural Science" 39:1-22, 2007) project is a Canadian population-level, longitudinal research project, in which teacher ratings of Kindergarten children's early development and wellbeing are linked to health and academic achievement variables at the…

  20. Early Phonological Development: Creating an Assessment Test

    ERIC Educational Resources Information Center

    Stoel-Gammon, Carol; Williams, A. Lynn

    2013-01-01

    This paper describes a new protocol for assessing the phonological systems of two-year-olds with typical development and older children with delays in vocabulary acquisition. The test (Profiles of Early Expressive Phonological Skills ("PEEPS"), Williams & Stoel-Gammon, in preparation) differs from currently available assessments in…

  1. Early Intervention, Maternal Development and Children's Play.

    ERIC Educational Resources Information Center

    Slaughter, Diana T.

    The purposes of this longitudinal study of early intervention with 83 black mother-child dyads were (a) to test the thesis that sociocultural transmission influences childhood development in educationally significant ways, and (b) to describe the process through which such transmission can occur. Two social intervention programs were contrasted;…

  2. The Early Years: Development, Learning and Teaching.

    ERIC Educational Resources Information Center

    Boulton-Lewis, Gillian, Ed.; Catherwood, Di, Ed.

    Designed for teachers, students, caregivers, and health professionals who work with children from birth to age 8, this book provides a review of recent research and theories of development and learning in the early childhood years, with an emphasis on implications for effective teaching. Where appropriate, the book takes an Australian perspective,…

  3. EARLY CRANIOFACIAL DEVELOPMENT: LIFE AMONG THE SIGNALS

    EPA Science Inventory

    Early Craniofacial Development: Life Among the Signals. Sid Hunter and Keith Ward. Reproductive Toxicology Division, NHEERL, US EPA, RTP, NC, 27711

    Haloacetic acids (HAA) are chemicals formed during drinking water disinfection and present in finished tap water. Exposure o...

  4. c-Jun N-terminal kinase in pancreatic tumor stroma augments tumor development in mice.

    PubMed

    Sato, Takeshi; Shibata, Wataru; Hikiba, Yohko; Kaneta, Yoshihiro; Suzuki, Nobumi; Ihara, Sozaburo; Ishii, Yasuaki; Sue, Soichiro; Kameta, Eri; Sugimori, Makoto; Yamada, Hiroaki; Kaneko, Hiroaki; Sasaki, Tomohiko; Ishii, Tomohiro; Tamura, Toshihide; Kondo, Masaaki; Maeda, Shin

    2017-11-01

    Pancreatic ductal adenocarcinoma (PDAC) is a life-threatening disease and there is an urgent need to develop improved therapeutic approaches. The role of c-Jun N-terminal kinase (JNK) in PDAC stroma is not well defined even though dense desmoplastic reactions are characteristic of PDAC histology. We aimed to explore the role of JNK in PDAC stroma in mice. We crossed Ptf1a Cre/+ ;Kras G12D/+ mice with JNK1 -/- mice to generate Ptf1a Cre/+ ;Kras G12D/+ ;JNK1 -/- (Kras;JNK1 -/- ) mice. Tumor weight was significantly lower in Kras;JNK1 -/- mice than in Kras;JNK1 +/- mice, whereas histopathological features were similar. We also transplanted a murine PDAC cell line (mPC) with intact JNK1 s.c. into WT and JNK1 -/- mice. Tumor diameters were significantly smaller in JNK1 -/- mice. Phosphorylated JNK (p-JNK) was activated in α-smooth muscle actin (SMA)-positive cells in tumor stroma, and mPC-conditioned medium activated p-JNK in tumor-associated fibroblasts (TAF) in vitro. Relative expression of Ccl20 was downregulated in stimulated TAF. Ccl20 is an important chemokine that promotes CD8 + T-cell infiltration by recruitment of dendritic cells, and the number of CD8 + T cells was decreased in Kras;JNK1 +/- mice compared with Kras;JNK1 -/- mice. These results suggest that the cancer secretome decreases Ccl20 secretion from TAF by activation of JNK, and downregulation of Ccl20 secretion might be correlated with reduction of infiltrating CD8 + T cells. Therefore, we concluded that inhibition of activated JNK in pancreatic tumor stroma could be a potential therapeutic target to increase Ccl20 secretion from TAF and induce accumulation of CD8 + T cells, which would be expected to enhance antitumor immunity. © 2017 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

  5. The prognostic role of tumor size in early breast cancer in the era of molecular biology.

    PubMed

    Kasangian, Anaid Anna; Gherardi, Giorgio; Biagioli, Elena; Torri, Valter; Moretti, Anna; Bernardin, Elena; Cordovana, Andrea; Farina, Gabriella; Bramati, Annalisa; Piva, Sheila; Dazzani, Maria Chiara; Paternò, Emanuela; La Verde, Nicla Maria

    2017-01-01

    The prognosis of early breast cancer (EBC) depends on patient and tumor characteristics. The association between tumor size, the largest diameter in TNM staging, and prognosis is well recognized. According to TNM, tumors classified as T2, could have very different volumes; e.g. a tumor of 2.1 cm has a volume of 4500 mm3, while a tumor of 4.9 cm has a volume of 60.000 mm3 even belonging to the same class. The aim of the study is to establish if the prognostic role of tumor size, expressed as diameter and volume, has been overshadowed by other factors. The primary objective is to evaluate the association between tumor dimensions and overall survival (OS) / disease free survival (DFS), in our institution from January 1st 2005 to September 30th 2013 in a surgical T1-T2 population. Volume was evaluated with the measurement of three half-diameters of the tumor (a, b and c), and calculated using the following formula: 4/3π x a x b x c. 341 patients with T1-T2 EBC were included. 86.5% were treated with conservative surgery. 85.1% had a Luminal subtype, 9.1% were Triple negative and 7.4% were HER2 positive. Median volume was 942 mm3 (range 0.52-31.651.2). 44 patients (12.9%) relapsed and 23 patients died. With a median follow-up of 6.5 years, the univariate analysis for DFS showed an association between age, tumor size, volume, histological grading and molecular subtype. The multivariate analysis confirmed the statistically significant association only for molecular subtype (p 0.005), with a worse prognosis for Triple negative and HER2 positive subtypes compared with Luminal (HR: 2.65; 95%CI: 1.34-5.22). Likewise for OS, an association was shown by the multivariate analysis solely for molecular subtype (HER2 and Triple negative vs. Luminal. HR: 2.83; 95% CI:1.46-5.49; p 0.002). In our study, the only parameter that strongly influences survival is molecular subtype. These findings encourage clinicians to choose adjuvant treatment not based on dimensional criteria but on

  6. Novel methylation panel for the early detection of colorectal tumors in stool DNA.

    PubMed

    Azuara, Daniel; Rodriguez-Moranta, Francisco; de Oca, Javier; Soriano-Izquierdo, Antonio; Mora, Josefina; Guardiola, Jordi; Biondo, Sebastiano; Blanco, Ignacio; Peinado, Miguel Angel; Moreno, Victor; Esteller, Manel; Capellá, Gabriel

    2010-07-01

    Previous studies showed that the assessment of promoter hypermethylation of a limited number of genes in tumor biopsies may identify the majority of colorectal tumors. This study aimed to assess the clinical usefulness of a panel of methylation biomarkers in stool DNA in the identification of colorectal tumors, using methylation-specific melting curve analysis (MS-MCA), a technique that simultaneously analyzes all cytosine-phosphate-guanine (CpG) residues within a promoter. The promoter methylation status of 4 tumor-related genes (RARB2, p16INK4a, MGMT, and APC) was analyzed in DNA stool samples and corresponding tissues in an initial set of 12 patients with newly diagnosed primary colorectal carcinomas and 20 patients with newly diagnosed colorectal adenomas, using methylation-specific polymerase chain reaction. Results were replicated in a set of 82 patients (20 healthy subjects, 16 patients with inflammatory bowel disease (IBD), 20 patients with adenomas, and 26 patients with carcinomas), using MS-MCA analyses. In the initial set, >or= 1 positive methylation marker was detected in the stools of 9 of 12 patients (75%) with carcinomas and 12 of 20 patients (60%) with adenomas, with no false-positive results. Stool analyses missed 7 methylated lesions (25%). In the replication set, stool DNA testing detected 16 of 26 carcinomas (62%) and 8 of 20 adenomas (40%). The MS-MCAs missed 14 methylated tumors (37%). No aberrant methylation was evident in healthy subjects, but the RARB2 marker was positive in 2 of 15 stool samples (13%) of patients with IBD. Analysis via MS-MCA of a panel of methylation markers in stool DNA may offer a good alternative in the early, noninvasive detection of colorectal tumors.

  7. [A Case of Early Gastric Cancer with Nodular Tumor-like Scalp Metastasis].

    PubMed

    Song, Young Wook; Kim, Woo Sub; Yun, Gee Young; Park, Sun Wook; Kang, Sun Hyung; Moon, Hee Seok; Sung, Jae Kyu; Jeong, Hyun Yong

    2016-07-25

    Many neoplasms, including lung cancer, breast cancer, melanoma, and gastrointestinal tract malignancy, possess potential for skin metastasis. Skin metastases can represent the first presentation of such malignancies and may be observed incidentally during routine exam. Skin metastases from gastric adenocarcinoma are uncommon, with a prevalence rate of 0.04-0.8%. Cutaneous metastases from gastric cancer are generally observed as the initial symptom of advanced gastric cancer. Early detection and treatment can increase patient survival. A 42-year-old woman visited our department with nodule about 1 cm in size on the right frontal scalp noticed incidentally after laparoscopy-assisted distal gastrectomy and adjuvant systemic chemo-therapy for early gastric cancer about 16 months prior. The patient was diagnosed with skin metastasis from gastric adenocarcinoma. Complete excision of the skin lesion and additional chemotherapy were performed. Herein, we report a case of nodular tumor-like scalp metastasis from early gastric cancer with a brief review of the literature.

  8. Prostate Tumor Antigen Discovery: Development of a Novel Genetic Approach

    DTIC Science & Technology

    2001-12-01

    HIV infection and AIDS), 20 MUC-1 (associated with breast cancer), EBNA-1 (associated with Epstein Barr Virus infection), CA19.9 (associated with... developed with DCs transfected with RNA from LNCaP cell lines. These studies established the feasibility of using PSA as a vaccine for prostate cancer...effective as an adjunct therapy for this malignancy. There are several road blocks to developing a successful cancer vaccine . Products of tumor cells that are

  9. Prognostic significance of an early decline in serum alpha-fetoprotein during chemotherapy for ovarian yolk sac tumors.

    PubMed

    de la Motte Rouge, Thibault; Pautier, Patricia; Genestie, Catherine; Rey, Annie; Gouy, Sébastien; Leary, Alexandra; Haie-Meder, Christine; Kerbrat, Pierre; Culine, Stéphane; Fizazi, Karim; Lhommé, Catherine

    2016-09-01

    The ovarian yolk sac tumor (OYST) is a very rare malignancy arising in young women. Our objective was to determine whether an early decline in serum alpha-fetoprotein (AFP) during chemotherapy has a prognostic impact. This retrospective study is based on prospectively recorded OYST cases at Gustave Roussy (Cancer Treatment Center). Survival curves were estimated using the Kaplan-Meier method. The serum AFP decline was calculated with the formula previously developed and validated in male patients with poor prognosis non-seminomatous germ cell tumors. Univariate and multivariate analyses were performed using the log-rank test and logistic regression, respectively. Data on AFP were available to calculate an early AFP decline in 57 patients. All patients had undergone surgery followed by chemotherapy. The 5-year overall survival (OS) and event-free survival (EFS) rates were 86% (95% CI: 74%-93%) and 84% (95% CI: 73%-91%), respectively. The disease stage, presence of ascites at presentation, use of the BEP regimen, serum AFP half-life and an early AFP decline were significantly predictive factors for OS and EFS in the univariate analysis. The OS rate was 100% and 49% (95% CI: 26%-72%) in patients with a favorable AFP decline and in those with an unfavorable decline, respectively (p<0.001). In the multivariate analysis, only the presence of ascites at diagnosis (RR=7.3, p=0.03) and an unfavorable early AFP decline (RR=16.9, p<0.01) were significant negative predictive factors for OS. An early AFP decline during chemotherapy is an independent prognostic factor in patients with OYSTs. No conflict of interest. Copyright © 2016. Published by Elsevier Inc.

  10. Cancer vaccine development: Designing tumor cells for greater immunogenicity

    PubMed Central

    Bozeman, Erica N.; Shashidharamurthy, Rangaiah; Paulos, Simon A.; Palaniappan, Ravi; D’Souza, Martin; Selvaraj, Periasamy

    2014-01-01

    Cancer vaccine development is one of the most hopeful and exhilarating areas in cancer research. For this reason, there has been a growing interest in the development and application of novel immunotherapies for the treatment of cancer with the focus being on stimulating the immune system to target tumor cells specifically while leaving normal cells unharmed. From such research has emerged a host of promising immunotherapies such as dendritic cell-based vaccines, cytokine therapies and gene transfer technology. These therapies seek to counteract the poor immunogenicity of tumors by augmenting the host’s immune system with a variety of immunostimulatory proteins such as cytokines and costimulatory molecules. While such therapies have proven effective in the induction of anti-tumor immunity in animal models, they are less than optimal and pose a high risk of clinical infeasibility. Herein, we further discuss these immunotherapies as well as a feasible and efficient alternative that, in pre-clinical animal models, allows for the expression of specific immunostimulatory molecules on the surface of tumor cells by a novel protein transfer technology. PMID:20036822

  11. Breastfeeding, parenting, and early cognitive development.

    PubMed

    Gibbs, Benjamin G; Forste, Renata

    2014-03-01

    To explain why breastfeeding is associated with children's cognitive development. By using a nationally representative longitudinal survey of early childhood (N = 7500), we examined how breastfeeding practices, the early introduction of solid foods, and putting an infant to bed with a bottle were associated with cognitive development across early childhood. We also explored whether this link can be explained by parenting behaviors and maternal education. There is a positive relationship between predominant breastfeeding for 3 months or more and child reading skills, but this link is the result of cognitively supportive parenting behaviors and greater levels of education among women who predominantly breastfed. We found little-to-no relationship between infant feeding practices and the cognitive development of children with less-educated mothers. Instead, reading to a child every day and being sensitive to a child's development were significant predictors of math and reading readiness outcomes. Although breastfeeding has important benefits in other settings, the encouragement of breastfeeding to promote school readiness does not appear to be a key intervention point. Promoting parenting behaviors that improve child cognitive development may be a more effective and direct strategy for practitioners to adopt, especially for disadvantaged children. Copyright © 2014 Mosby, Inc. All rights reserved.

  12. Clinical development of BLZ-100 for real-time optical imaging of tumors during resection

    NASA Astrophysics Data System (ADS)

    Franklin, Heather L.; Miller, Dennis M.; Hedges, Teresa; Perry, Jeff; Parrish-Novak, Julia

    2016-03-01

    Complete initial resection can give cancer patients the best opportunity for long-term survival. There is unmet need in surgical oncology for optical imaging that enables simple and precise visualization of tumors and consistent contrast with surrounding normal tissues. Near-infrared (NIR) contrast agents and camera systems that can detect them represent an area of active research and development. The investigational Tumor Paint agent BLZ-100 is a conjugate of a chlorotoxin peptide and the NIR dye indocyanine green (ICG) that has been shown to specifically bind to a broad range of solid tumors. Clinical efficacy studies with BLZ-100 are in progress, a necessary step in bringing the product into clinical practice. To ensure a product that will be useful for and accepted by surgeons, the early clinical development of BLZ- 100 incorporates multiple tumor types and imaging devices so that surgeon feedback covers the range of anticipated clinical uses. Key contrast agent characteristics include safety, specificity, flexibility in timing between dose and surgery, and breadth of tumor types recognized. Imaging devices should use wavelengths that are optimal for the contrast agent, be sensitive enough that contrast agent dosing can be adjusted for optimal contrast, include real-time video display of fluorescence and white light image, and be simple for surgeons to use with minimal disruption of surgical flow. Rapid entry into clinical studies provides the best opportunity for early surgeon feedback, enabling development of agents and devices that will gain broad acceptance and provide information that helps surgeons achieve more complete and precise resections.

  13. Nurturing care: promoting early childhood development.

    PubMed

    Britto, Pia R; Lye, Stephen J; Proulx, Kerrie; Yousafzai, Aisha K; Matthews, Stephen G; Vaivada, Tyler; Perez-Escamilla, Rafael; Rao, Nirmala; Ip, Patrick; Fernald, Lia C H; MacMillan, Harriet; Hanson, Mark; Wachs, Theodore D; Yao, Haogen; Yoshikawa, Hirokazu; Cerezo, Adrian; Leckman, James F; Bhutta, Zulfiqar A

    2017-01-07

    The UN Sustainable Development Goals provide a historic opportunity to implement interventions, at scale, to promote early childhood development. Although the evidence base for the importance of early childhood development has grown, the research is distributed across sectors, populations, and settings, with diversity noted in both scope and focus. We provide a comprehensive updated analysis of early childhood development interventions across the five sectors of health, nutrition, education, child protection, and social protection. Our review concludes that to make interventions successful, smart, and sustainable, they need to be implemented as multi-sectoral intervention packages anchored in nurturing care. The recommendations emphasise that intervention packages should be applied at developmentally appropriate times during the life course, target multiple risks, and build on existing delivery platforms for feasibility of scale-up. While interventions will continue to improve with the growth of developmental science, the evidence now strongly suggests that parents, caregivers, and families need to be supported in providing nurturing care and protection in order for young children to achieve their developmental potential. Copyright © 2017 Elsevier Ltd. All rights reserved.

  14. Early childhood development: putting knowledge into action.

    PubMed

    2000-11-01

    As part of its continuing mission to serve trustees and staff of health foundations and corporate giving programs, Grantmakers In Health (GIH) convened a select group of grantmakers and national experts who have made a major commitment to improve the health and well being of young children. The roundtable explored the latest research examining early childhood development, as well as public and private programs serving families with young children. The discussion ultimately centered upon the importance of grantmaker involvement to improve early childhood development, including the services delivered to young children and their families, training for professionals, and continued research and evaluation. This report brings together key points from the day's discussion with factual information on demographic, health and human services, and public policy trends drawn from a background paper prepared for the meeting. When available, recent findings, facts, and figures have been incorporated.

  15. QCD development in the early universe

    SciT

    Gromov, N. A., E-mail: gromov@dm.komisc.ru

    The high-energy limit of Quantum Chromodynamics is generated by the contraction of its gauge groups. Contraction parameters are taken identical with those of the Electroweak Model and tend to zero when energy increases. At the infinite energy limit all quarks lose masses and have only one color degree of freedom. The limit model represents the development of Quantum Chromodynamics in the early Universe from the Big Bang up to the end of several milliseconds.

  16. Early tumor detection afforded by in vivo imaging of near-infrared II fluorescence.

    PubMed

    Tao, Zhimin; Dang, Xiangnan; Huang, Xing; Muzumdar, Mandar D; Xu, Eric S; Bardhan, Neelkanth Manoj; Song, Haiqin; Qi, Ruogu; Yu, Yingjie; Li, Ting; Wei, Wei; Wyckoff, Jeffrey; Birrer, Michael J; Belcher, Angela M; Ghoroghchian, P Peter

    2017-07-01

    Cell-intrinsic reporters such as luciferase (LUC) and red fluorescent protein (RFP) have been commonly utilized in preclinical studies to image tumor growth and to monitor therapeutic responses. While extrinsic reporters that emit near infrared I (NIR-I: 650-950 nm) or near-infrared II (NIR-II: 1000-1700 nm) optical signals have enabled minimization of tissue autofluorescence and light scattering, it has remained unclear as to whether their use has afforded more accurate tumor imaging in small animals. Here, we developed a novel optical imaging construct comprised of rare earth lanthanide nanoparticles coated with biodegradable diblock copolymers and doped with organic fluorophores, generating NIR-I and NIR-II emissive bands upon optical excitation. Simultaneous injection of multiple spectrally-unique nanoparticles into mice bearing tumor implants established via intraperitoneal dissemination of LUC + /RFP + OVCAR-8 ovarian cancer cells enabled direct comparisons of imaging with extrinsic vs. intrinsic reporters, NIR-II vs. NIR-I signals, as well as targeted vs. untargeted exogenous contrast agents in the same animal and over time. We discovered that in vivo optical imaging at NIR-II wavelengths facilitates more accurate detection of smaller and earlier tumor deposits, offering enhanced sensitivity, improved spatial contrast, and increased depths of tissue penetration as compared to imaging with visible or NIR-I fluorescent agents. Our work further highlights the hitherto underappreciated enhancements in tumor accumulation that may be achieved with intraperitoneal as opposed to intravenous administration of nanoparticles. Lastly, we found discrepancies in the fidelity of tumor uptake that could be obtained by utilizing small molecules for in vivo as opposed to in vitro targeting of nanoparticles to disseminated tumors. Copyright © 2017 Elsevier Ltd. All rights reserved.

  17. Detection of early pregnancy factor-like activity in women with gestational trophoblastic tumors.

    PubMed

    Mehta, A R; Shahani, S K

    1987-07-01

    The presence of immunosuppressive early pregnancy factor (EPF) in the maternal serum has so far been associated with gestation. Its presence in the serum of women with gestational trophoblastic tumors was investigated. The results indicate that while EPF activity was detected in the serum of women with choriocarcinoma, no such activity was detected in the serum of women with hydatidiform mole, leading to the novel use of EPF as a marker to distinguish these two clinical situations. Results of the experiments also suggest that EPF moiety present in the maternal serum during pregnancy may be of different molecular entity than that present in the serum of women with choriocarcinoma.

  18. In Vivo Tagging of Lung Epithelial Cells To Define the Early Steps of Tumor Cell Dissemination

    DTIC Science & Technology

    2015-12-01

    was interbred with Nkx2.1-CreERT2 knock-in mouse strain, containing a tamoxifen -inducible lineage specific Cre recombinase, to generate adult lung...KrasG12D(L/-); Lkb1(L/L) mice 7 days after tamoxifen injections show that KrasG12D mice develop isolated tumors one week after the end of tamoxifen ...SA2a-b) (timeframe months 6-10 by Drs Kathuria, Cao, Ramirez, and Kotton). 1. First we will induce tumors by tamoxifen injection of Kras G12D /Lkb1L/L

  19. Transcriptional mutagenesis: causes and involvement in tumor development

    PubMed Central

    Brégeon, Damien; Doetsch, Paul W.

    2013-01-01

    The majority of normal cells in a human do not multiply continuously but are quiescent and devote most of their energy to gene transcription. When DNA damages in the transcribed strand of an active gene are bypassed by an RNA polymerase, they can miscode at the damaged site and produce mutant transcripts. This process known as transcriptional mutagenesis can lead to the production of mutant proteins that could be important in tumor development. PMID:21346784

  20. Conditional Deletion of the Pten Gene in the Mouse Prostate Induces Prostatic Intraepithelial Neoplasms at Early Ages but a Slow Progression to Prostate Tumors

    PubMed Central

    Zhu, Chunfang; Lee, Suk Hyung; Ye, Ding-Wei; Luong, Richard; Sun, Zijie

    2013-01-01

    The PTEN tumor suppressor gene is frequently inactivated in human prostate cancer. Using Osr1 (odd skipped related 1)-Cre mice, we generated a novel conditional Pten knockout mouse strain, PtenLoxP:Osr1-Cre. Conditional biallelic and monoallelic Pten knockout mice were viable. Deletion of Pten expression was detected in the prostate of PtenLoxP/LoxP:Osr1-Cre mice as early as 2 weeks of age. Intriguingly, PtenLoxP/LoxP:Osr1-Cre mice develop high-grade prostatic intraepithelial neoplasms (PINs) with high penetrance as early as one-month of age, and locally invasive prostatic tumors after 12-months of age. PtenLoxP/+:Osr1-Cre mice show only mild oncogenic changes after 8-weeks of age. Castration of PtenLoxP/LoxP:Osr1-Cre mice shows no significant regression of prostate tumors, although a shift of androgen receptor (AR) staining from the nuclei to cytoplasm is observed in Pten null tumor cells of castrated mice. Enhanced Akt activity is observed in Pten null tumor cells of castrated PtenLoxP/LoxP:Osr1-Cre. This study provides a novel mouse model that can be used to investigate a primary role of Pten in initiating oncogenic transformation in the prostate and to examine other genetic and epigenetic changes that are required for tumor progression in the mouse prostate. PMID:23308230

  1. Early colonial health developments in Mauritius.

    PubMed

    Parahoo, K A

    1986-01-01

    The historical development of Mauritius and in particular the early developments in health care are crucial to an understanding of the contemporary health system. The introduction of major epidemic diseases through the movements of French soldiers to and from India and the immigration of indentured laborers from India account for the high mortality and morbidity rates in the 18th and 19th centuries and later. The colonial economy created and fortified the dependence on a single cash crop and on imported food. It also contributed toward the impoverization of large sections of the Mauritian population. The colonial era is also responsible for initiating a three tier system of health care.

  2. Mouse Mammary Tumor Virus c-rel Transgenic Mice Develop Mammary Tumors

    PubMed Central

    Romieu-Mourez, Raphaëlle; Kim, Dong W.; Min Shin, Sang; Demicco, Elizabeth G.; Landesman-Bollag, Esther; Seldin, David C.; Cardiff, Robert D.; Sonenshein, Gail E.

    2003-01-01

    Amplification, overexpression, or rearrangement of the c-rel gene, encoding the c-Rel NF-κB subunit, has been reported in solid and hematopoietic malignancies. For example, many primary human breast cancer tissue samples express high levels of nuclear c-Rel. While the Rev-T oncogene v-rel causes tumors in birds, the ability of c-Rel to transform in vivo has not been demonstrated. To directly test the role of c-Rel in breast tumorigenesis, mice were generated in which overexpression of mouse c-rel cDNA was driven by the hormone-responsive mouse mammary tumor virus long terminal repeat (MMTV-LTR) promoter, and four founder lines identified. In the first cycle of pregnancy, the expression of transgenic c-rel mRNA was observed, and levels of c-Rel protein were increased in the mammary gland. Importantly, 31.6% of mice developed one or more mammary tumors at an average age of 19.9 months. Mammary tumors were of diverse histology and expressed increased levels of nuclear NF-κB. Analysis of the composition of NF-κB complexes in the tumors revealed aberrant nuclear expression of multiple subunits, including c-Rel, p50, p52, RelA, RelB, and the Bcl-3 protein, as observed previously in human primary breast cancers. Expression of the cancer-related NF-κB target genes cyclin D1, c-myc, and bcl-xl was significantly increased in grossly normal transgenic mammary glands starting the first cycle of pregnancy and increased further in mammary carcinomas compared to mammary glands from wild-type mice or virgin transgenic mice. In transient transfection analysis in untransformed breast epithelial cells, c-Rel-p52 or -p50 heterodimers either potently or modestly induced cyclin D1 promoter activity, respectively. Lastly, stable overexpression of c-Rel resulted in increased cyclin D1 and NF-κB p52 and p50 subunit protein levels. These results indicate for the first time that dysregulated expression of c-Rel, as observed in breast cancers, is capable of contributing to mammary

  3. Poor Prognosis Indicated by Venous Circulating Tumor Cell Clusters in Early-Stage Lung Cancers.

    PubMed

    Murlidhar, Vasudha; Reddy, Rishindra M; Fouladdel, Shamileh; Zhao, Lili; Ishikawa, Martin K; Grabauskiene, Svetlana; Zhang, Zhuo; Lin, Jules; Chang, Andrew C; Carrott, Philip; Lynch, William R; Orringer, Mark B; Kumar-Sinha, Chandan; Palanisamy, Nallasivam; Beer, David G; Wicha, Max S; Ramnath, Nithya; Azizi, Ebrahim; Nagrath, Sunitha

    2017-09-15

    Early detection of metastasis can be aided by circulating tumor cells (CTC), which also show potential to predict early relapse. Because of the limited CTC numbers in peripheral blood in early stages, we investigated CTCs in pulmonary vein blood accessed during surgical resection of tumors. Pulmonary vein (PV) and peripheral vein (Pe) blood specimens from patients with lung cancer were drawn during the perioperative period and assessed for CTC burden using a microfluidic device. From 108 blood samples analyzed from 36 patients, PV had significantly higher number of CTCs compared with preoperative Pe ( P < 0.0001) and intraoperative Pe ( P < 0.001) blood. CTC clusters with large number of CTCs were observed in 50% of patients, with PV often revealing larger clusters. Long-term surveillance indicated that presence of clusters in preoperative Pe blood predicted a trend toward poor prognosis. Gene expression analysis by RT-qPCR revealed enrichment of p53 signaling and extracellular matrix involvement in PV and Pe samples. Ki67 expression was detected in 62.5% of PV samples and 59.2% of Pe samples, with the majority (72.7%) of patients positive for Ki67 expression in PV having single CTCs as opposed to clusters. Gene ontology analysis revealed enrichment of cell migration and immune-related pathways in CTC clusters, suggesting survival advantage of clusters in circulation. Clusters display characteristics of therapeutic resistance, indicating the aggressive nature of these cells. Thus, CTCs isolated from early stages of lung cancer are predictive of poor prognosis and can be interrogated to determine biomarkers predictive of recurrence. Cancer Res; 77(18); 5194-206. ©2017 AACR . ©2017 American Association for Cancer Research.

  4. Validation of a recombinant human bactericidal/permeability-increasing protein (hBPI) expression vector using murine mammary gland tumor cells and the early development of hBPI transgenic goat embryos.

    PubMed

    Gui, Tao; Liu, Xing; Tao, Jia; Chen, Jianwen; Li, Yunsheng; Zhang, Meiling; Wu, Ronghua; Zhang, Yuanliang; Peng, Kaisong; Liu, Ya; Zhang, Xiaorong; Zhang, Yunhai

    2013-12-01

    Human bactericidal/permeability-increasing protein (hBPI) is the only antibacterial peptide which acts against both gram-negative bacteria and neutralizes endotoxins in human polymorphonuclear neutrophils; therefore, hBPI is of great value in clinical applications. In the study, we constructed a hBPI expression vector (pBC1-Loxp-Neo-Loxp-hBPI) containing the full-length hBPI coding sequence which could be specifically expressed in the mammary gland. To validate the function of the vector, in vitro cultured C127 (mouse mammary Carcinoma Cells) were transfected with the vector, and the transgenic cell clones were selected to express hBPI by hormone induction. The mRNA and protein expression of hBPI showed that the constructed vector was effective and suitable for future application in producing mammary gland bioreactor. Then, female and male goat fibroblasts were transfected with the vector, and two male and two female transgenic clonal cell lines were obtained. Using the transgenic cell lines as nuclear donors for somatic cell nuclear transfer, the reconstructed goat embryos produced from all four clones could develop to blastocysts in vitro. In conclusion, we constructed and validated an efficient mammary gland-specific hBPI expression vector, pBC1-Loxp-Neo-Loxp-hBPI, and transgenic hBPI goat embryos were successfully produced, laying foundations for future production of recombinant hBPI in goat mammary gland. Copyright © 2013 Elsevier B.V. All rights reserved.

  5. [A Comparison Study on Early Damage Detection of Left Ventricular Function Based on Doppler Imaging Method for Children with Tumor].

    PubMed

    Liu, Ying; Zhang, Haowei; Zhang, Hang

    2015-12-01

    The early damage detection and evaluation are of great significance in treatment and prognosis to the left ventricular function for children with tumor. In this paper, it is reported that the early damage of the left ventricular function was observed by pulsed wave Doppler (PWD) and tissue Doppler imaging (TDI) in our laboratory. Eighty children half a year to fourteen years old were included in this study. The cardiac function indices in chemotherapy group and control group were measured and compared. The results showed that there was significant difference in mitral and tricuspid annulus flow spectrum between the two groups. Compared with PWD,TDI is more prompt, objective and accurate in detecting early damage of left ventricular function in children with tumor. And TDI is a good method for early identification of ventricular function damage in children with tumor.

  6. Early Cognitive Outcomes Following Proton Radiation in Pediatric Patients With Brain and Central Nervous System Tumors

    SciT

    Pulsifer, Margaret B., E-mail: mpulsifer@mgh.harvard.edu; Sethi, Roshan V.; Kuhlthau, Karen A.

    Purpose: To report, from a longitudinal study, cognitive outcome in pediatric patients treated with proton radiation therapy (PRT) for central nervous system (CNS) tumors. Methods and Materials: Sixty patients receiving PRT for medulloblastoma (38.3%), gliomas (18.3%), craniopharyngioma (15.0%), ependymoma (11.7%), and other CNS tumors (16.7%) were administered age-appropriate measures of cognitive abilities at or near PRT initiation (baseline) and afterward (follow-up). Patients were aged ≥6 years at baseline to ensure consistency in neurocognitive measures. Results: Mean age was 12.3 years at baseline; mean follow-up interval was 2.5 years. Treatment included prior surgical resection (76.7%) and chemotherapy (61.7%). Proton radiation therapy included craniospinal irradiationmore » (46.7%) and partial brain radiation (53.3%). At baseline, mean Wechsler Full Scale IQ was 104.6; means of all 4 Index scores were also in the average range. At follow-up, no significant change was observed in mean Wechsler Full Scale IQ, Verbal Comprehension, Perceptual Reasoning/Organization, or Working Memory. However, Processing Speed scores declined significantly (mean 5.2 points), with a significantly greater decline for subjects aged <12 years at baseline and those with the highest baseline scores. Cognitive outcome was not significantly related to gender, extent of radiation, radiation dose, tumor location, histology, socioeconomic status, chemotherapy, or history of surgical resection. Conclusions: Early cognitive outcomes after PRT for pediatric CNS tumors are encouraging, compared with published outcomes from photon radiation therapy.« less

  7. Pharmacogenomics in early-phase clinical development

    PubMed Central

    Burt, Tal; Dhillon, Savita

    2015-01-01

    Pharmacogenomics (PGx) offers the promise of utilizing genetic fingerprints to predict individual responses to drugs in terms of safety, efficacy and pharmacokinetics. Early-phase clinical trial PGx applications can identify human genome variations that are meaningful to study design, selection of participants, allocation of resources and clinical research ethics. Results can inform later-phase study design and pipeline developmental decisions. Nevertheless, our review of the clinicaltrials.gov database demonstrates that PGx is rarely used by drug developers. Of the total 323 trials that included PGx as an outcome, 80% have been conducted by academic institutions after initial regulatory approval. Barriers for the application of PGx are discussed. We propose a framework for the role of PGx in early-phase drug development and recommend PGx be universally considered in study design, result interpretation and hypothesis generation for later-phase studies, but PGx results from underpowered studies should not be used by themselves to terminate drug-development programs. PMID:23837482

  8. The developing hypopharyngeal microbiota in early life.

    PubMed

    Mortensen, Martin Steen; Brejnrod, Asker Daniel; Roggenbuck, Michael; Abu Al-Soud, Waleed; Balle, Christina; Krogfelt, Karen Angeliki; Stokholm, Jakob; Thorsen, Jonathan; Waage, Johannes; Rasmussen, Morten Arendt; Bisgaard, Hans; Sørensen, Søren Johannes

    2016-12-30

    The airways of healthy humans harbor a distinct microbial community. Perturbations in the microbial community have been associated with disease, yet little is known about the formation and development of a healthy airway microbiota in early life. Our goal was to understand the establishment of the airway microbiota within the first 3 months of life. We investigated the hypopharyngeal microbiota in the unselected COPSAC 2010 cohort of 700 infants, using 16S rRNA gene sequencing of hypopharyngeal aspirates from 1 week, 1 month, and 3 months of age. Our analysis shows that majority of the hypopharyngeal microbiota of healthy infants belong to each individual's core microbiota and we demonstrate five distinct community pneumotypes. Four of these pneumotypes are dominated by the genera Staphylococcus, Streptococcus, Moraxella, and Corynebacterium, respectively. Furthermore, we show temporal pneumotype changes suggesting a rapid development towards maturation of the hypopharyngeal microbiota and a significant effect from older siblings. Despite an overall common trajectory towards maturation, individual infants' microbiota are more similar to their own, than to others, over time. Our findings demonstrate a consolidation of the population of indigenous bacteria in healthy airways and indicate distinct trajectories in the early development of the hypopharyngeal microbiota.

  9. Study Protocol: Early Stereotactic Gamma Knife Radiosurgery to Residual Tumor After Surgery of Newly Diagnosed Glioblastoma (Gamma-GBM).

    PubMed

    Brehmer, Stefanie; Grimm, Mario Alexander; Förster, Alex; Seiz-Rosenhagen, Marcel; Welzel, Grit; Stieler, Florian; Wenz, Frederik; Groden, Christoph; Mai, Sabine; Hänggi, Daniel; Giordano, Frank Anton

    2018-04-24

    Glioblastoma (GBM) is the most common malignant brain tumor in adult patients. Tumor recurrence commonly occurs around the resection cavity, especially after subtotal resection (STR). Consequently, the extent of resection correlates with overall survival (OS), suggesting that depletion of postoperative tumor remnants will improve outcome. To assess safety and efficacy of adding stereotactic radiosurgery (SRS) to the standard treatment of GBM in patients with postoperative residual tumor. Gamma-GBM is a single center, open-label, prospective, single arm, phase II study that includes patients with newly diagnosed GBM (intraoperative via frozen sections) who underwent STR (residual tumor will be identified by native and contrast enhanced T1-weighted magnetic resonance imaging scans). All patients will receive SRS with 15 Gy (prescribed to the 50% isodose enclosing all areas of residual tumor) early (within 24-72 h) after surgery. Thereafter, all patients undergo standard-of-care therapy for GBM (radiochemotherapy with 60 Gy external beam radiotherapy [EBRT] plus concomitant temozolomide and 6 cycles of adjuvant temozolomide chemotherapy). The primary outcome is median progression-free survival, secondary outcomes are median OS, occurrence of radiation induced acute (<3 wk), early delayed (<3 mo), and late (>3 mo post-SRS) neurotoxicity and incidence of symptomatic radionecrosis. We expect to detect efficacy and safety signals by the immediate application of SRS to standard-of-care therapy in newly diagnosed GBM. Early postoperative SRS to areas of residual tumor could bridge the therapeutic gap between surgery and adjuvant therapies.

  10. Early androgen exposure and human gender development.

    PubMed

    Hines, Melissa; Constantinescu, Mihaela; Spencer, Debra

    2015-01-01

    During early development, testosterone plays an important role in sexual differentiation of the mammalian brain and has enduring influences on behavior. Testosterone exerts these influences at times when the testes are active, as evidenced by higher concentrations of testosterone in developing male than in developing female animals. This article critically reviews the available evidence regarding influences of testosterone on human gender-related development. In humans, testosterone is elevated in males from about weeks 8 to 24 of gestation and then again during early postnatal development. Individuals exposed to atypical concentrations of testosterone or other androgenic hormones prenatally, for example, because of genetic conditions or because their mothers were prescribed hormones during pregnancy, have been consistently found to show increased male-typical juvenile play behavior, alterations in sexual orientation and gender identity (the sense of self as male or female), and increased tendencies to engage in physically aggressive behavior. Studies of other behavioral outcomes following dramatic androgen abnormality prenatally are either too small in their numbers or too inconsistent in their results, to provide similarly conclusive evidence. Studies relating normal variability in testosterone prenatally to subsequent gender-related behavior have produced largely inconsistent results or have yet to be independently replicated. For studies of prenatal exposures in typically developing individuals, testosterone has been measured in single samples of maternal blood or amniotic fluid. These techniques may not be sufficiently powerful to consistently detect influences of testosterone on behavior, particularly in the relatively small samples that have generally been studied. The postnatal surge in testosterone in male infants, sometimes called mini-puberty, may provide a more accessible opportunity for measuring early androgen exposure during typical development. This

  11. Rapid Copper Acquisition by Developing Murine Mesothelioma: Decreasing Bioavailable Copper Slows Tumor Growth, Normalizes Vessels and Promotes T Cell Infiltration

    PubMed Central

    Crowe, Andrew; Jackaman, Connie; Beddoes, Katie M.; Ricciardo, Belinda; Nelson, Delia J.

    2013-01-01

    Copper, an essential trace element acquired through nutrition, is an important co-factor for pro-angiogenic factors including vascular endothelial growth factor (VEGF). Decreasing bioavailable copper has been used as an anti-angiogenic and anti-cancer strategy with promising results. However, the role of copper and its potential as a therapy in mesothelioma is not yet well understood. Therefore, we monitored copper levels in progressing murine mesothelioma tumors and analyzed the effects of lowering bioavailable copper. Copper levels in tumors and organs were assayed using atomic absorption spectrophotometry. Mesothelioma tumors rapidly sequestered copper at early stages of development, the copper was then dispersed throughout growing tumor tissues. These data imply that copper uptake may play an important role in early tumor development. Lowering bioavailable copper using the copper chelators, penicillamine, trientine or tetrathiomolybdate, slowed in vivo mesothelioma growth but did not provide any cures similar to using cisplatin chemotherapy or anti-VEGF receptor antibody therapy. The impact of copper lowering on tumor blood vessels and tumor infiltrating T cells was measured using flow cytometry and confocal microscopy. Copper lowering was associated with reduced tumor vessel diameter, reduced endothelial cell proliferation (reduced Ki67 expression) and lower surface ICAM/CD54 expression implying reduced endothelial cell activation, in a process similar to endothelial normalization. Copper lowering was also associated with a CD4+ T cell infiltrate. In conclusion, these data suggest copper lowering is a potentially useful anti-mesothelioma treatment strategy that slows tumor growth to provide a window of opportunity for inclusion of other treatment modalities to improve patient outcomes. PMID:24013775

  12. Systematic review: Tumor-associated antigen autoantibodies and ovarian cancer early detection.

    PubMed

    Fortner, Renée Turzanski; Damms-Machado, Antje; Kaaks, Rudolf

    2017-11-01

    Tumor-associated autoantibodies (AAbs), produced as an immune response to tumor-associated antigens (TAAs), are a novel pathway of early detection markers. We conducted a systematic review on AAbs and ovarian cancer to summarize the diagnostic performance of individual AAbs and AAb panels. A total of 29 studies including 85 AAbs were included; 27 of the studies were conducted in prevalent cases and cancer-free controls and 2 investigations included pre-diagnosis samples. The majority of studies were hypothesis-driven, evaluating AAbs to target TAAs; 10 studies used screening approaches such as serological expression cloning (SEREX) and nucleic acid-programmable protein arrays (NAPPA). The highest sensitivities for individual AAbs were reported for RhoGDI-AAbs (89.5%) and TUBA1C-AAbs (89%); however, specificity levels were relatively low (80% and 75%, respectively). High sensitivities at high specificities were reported for HOXA7-AAbs for detection of moderately differentiated ovarian tumors (66.7% sensitivity at 100% specificity) and IL8-AAbs in stage I-II ovarian cancer (65.5% sensitivity at 98% specificity). A panel of 11 AAbs (ICAM3, CTAG2, p53, STYXL1, PVR, POMC, NUDT11, TRIM39, UHMK1, KSR1, and NXF3) provided 45% sensitivity at 98% specificity for serous ovarian cancer, when at least 2 AAbs were above a threshold of 95% specificity. Twelve of the AAbs identified in this review were investigated in more than one study. Data on diagnostic discrimination by tumor histology and stage at diagnosis are sparse. Limited data suggest select AAb markers improve diagnostic discrimination when combined with markers such as CA125 and HE4. AAbs for ovarian cancer early detection is an emerging area, and large-scale, prospective investigations considering histology and stage are required for discovery and validation. However, data to date suggests panels of AAbs may eventually reach sufficient diagnostic discrimination to allow earlier detection of disease as a complement to

  13. Detection of Wilms' tumor antigen--specific CTL in tumor-draining lymph nodes of patients with early breast cancer.

    PubMed

    Gillmore, Roopinder; Xue, Shao-An; Holler, Angelika; Kaeda, Jaspal; Hadjiminas, Dimitri; Healy, Vourneen; Dina, Roberto; Parry, Suzanne C; Bellantuono, Ilaria; Ghani, Yasmeen; Coombes, R Charles; Waxman, Jonathan; Stauss, Hans J

    2006-01-01

    The Wilms' tumor antigen (WT1) is overexpressed in approximately 90% of breast tumors and, thus, is a potential target antigen for the immunotherapy of breast cancer. We have tested the working hypotheses that WT1 can be immunogenic in patients with breast cancer and can stimulate CTL of sufficient avidity to kill tumor cells. Paired tumor-draining lymph node and peripheral blood samples were analyzed from five HLA-A2-positive patients with stage I/II breast cancer. Fluorescent HLA-A*0201/WT1 tetramers were used to quantify WT1-specific CTL and the functional capacity of the CTL was assessed using cytotoxicity assays and intracellular cytokine staining. WT1 tetramer-binding T cells expanded from all lymph node samples but none of the corresponding peripheral blood samples. Functional assays were carried out on T cells from the patient who had yielded the highest frequency of HLA-A*0201/WT1 tetramer-positive cells. The cytotoxicity assays showed WT1 peptide--specific killing activity of the CTL, whereas intracellular cytokine staining confirmed that the tetramer--positive T cells produced IFN-gamma after stimulation with WT1 peptide. These WT1-specific T cells killed HLA-A2-positive breast cancer cell lines treated with IFN-gamma but no killing was observed with untreated tumor cells. These results show that WT1-specific CTL can be expanded from the tumor-draining lymph nodes of breast cancer patients and that they can display peptide-specific effector function. However, the CTL only killed IFN-gamma-treated tumor targets expressing high levels of HLA-A2 and not tumor cells with low HLA expression. This suggests that induction of autologous WT1-specific CTL may offer only limited tumor protection and that strategies that allow a high level of peptide/MHC complex presentation and/or improve CTL avidity may be required.

  14. Early Literacy and Early Numeracy: The Value of Including Early Literacy Skills in the Prediction of Numeracy Development

    ERIC Educational Resources Information Center

    Purpura, David J.; Hume, Laura E.; Sims, Darcey M.; Lonigan, Cristopher J.

    2011-01-01

    The purpose of this study was to examine whether early literacy skills uniquely predict early numeracy skills development. During the first year of the study, 69 3- to 5-year-old preschoolers were assessed on the Preschool Early Numeracy Skills (PENS) test and the Test of Preschool Early Literacy Skills (TOPEL). Participants were assessed again a…

  15. Characterizing Tumor Heterogeneity With Functional Imaging and Quantifying High-Risk Tumor Volume for Early Prediction of Treatment Outcome: Cervical Cancer as a Model

    SciT

    Mayr, Nina A., E-mail: Nina.Mayr@osumc.edu; Huang Zhibin; Wang, Jian Z.

    2012-07-01

    Purpose: Treatment response in cancer has been monitored by measuring anatomic tumor volume (ATV) at various times without considering the inherent functional tumor heterogeneity known to critically influence ultimate treatment outcome: primary tumor control and survival. This study applied dynamic contrast-enhanced (DCE) functional MRI to characterize tumors' heterogeneous subregions with low DCE values, at risk for treatment failure, and to quantify the functional risk volume (FRV) for personalized early prediction of treatment outcome. Methods and Materials: DCE-MRI was performed in 102 stage IB{sub 2}-IVA cervical cancer patients to assess tumor perfusion heterogeneity before and during radiation/chemotherapy. FRV represents the totalmore » volume of tumor voxels with critically low DCE signal intensity (<2.1 compared with precontrast image, determined by previous receiver operator characteristic analysis). FRVs were correlated with treatment outcome (follow-up: 0.2-9.4, mean 6.8 years) and compared with ATVs (Mann-Whitney, Kaplan-Meier, and multivariate analyses). Results: Before and during therapy at 2-2.5 and 4-5 weeks of RT, FRVs >20, >13, and >5 cm{sup 3}, respectively, significantly predicted unfavorable 6-year primary tumor control (p = 0.003, 7.3 Multiplication-Sign 10{sup -8}, 2.0 Multiplication-Sign 10{sup -8}) and disease-specific survival (p = 1.9 Multiplication-Sign 10{sup -4}, 2.1 Multiplication-Sign 10{sup -6}, 2.5 Multiplication-Sign 10{sup -7}, respectively). The FRVs were superior to the ATVs as early predictors of outcome, and the differentiating power of FRVs increased during treatment. Discussion: Our preliminary results suggest that functional tumor heterogeneity can be characterized by DCE-MRI to quantify FRV for predicting ultimate long-term treatment outcome. FRV is a novel functional imaging heterogeneity parameter, superior to ATV, and can be clinically translated for personalized early outcome prediction before or as early as 2

  16. Gadolinium-Loaded Solid Lipid Nanoparticles as a Tumor-Absorbable Contrast Agent for Early Diagnosis of Colorectal Tumors Using Magnetic Resonance Colonography.

    PubMed

    Sun, Jihong; Zhang, Shizheng; Jiang, Shaojie; Bai, Weixian; Liu, Fei; Yuan, Hong; Ji, Jiansong; Luo, Jingfeng; Han, Guocan; Chen, Lumin; Jin, Yin; Hu, Peng; Yu, Lei; Yang, Xiaoming

    2016-09-01

    Magnetic resonance (MR) contrast agents focusing on special functions are required to improve cancer diagnosis, particularly in the early stages. Here, we designed multifunctional solid lipid nanoparticles (SLNs) with simultaneous loading of gadolinium (Gd) diethylenetriaminepentaacetic acid (Gd-DTPA) and octadecylamine fluorescein isothiocyanate (FITC) to obtain Gd-FITC-SLNs as a tumor-absorbable nanoparticle contrast agent for the histological confirmation of MR imaging (MRI) findings. Colorectal tumors were evaluated in vitro and in vivo via direct uptake of this contrast agent, which displayed reasonable T1 relaxivity and no significant cytotoxicity at the experimental concentrations in human colon carcinoma cells (HT29) and mouse colon carcinoma cells (CT26). In vitro cell uptake experiments demonstrated that contrast agent absorption by the two types of cancer cells was concentration-dependent in the safe concentration range. During in vivo MRI, transrectal infusion of Gd-FITC-SLNs showed more significant enhancement at the tumor site compared with the infusion of Gd-DTPA in female C57/BL mice with azoxymethane/dextran sulfate sodium-induced colorectal highgrade intraepithelial neoplasia. Subsequent confocal fluorescence microscopy demonstrated Gd-FITC-SLNs as highly concentrated green fluorescent spots distributed from the tumor capsule into the tumor. This study establishes the "proof-of-principle" of a new MRI technique wherein colorectal tumors are enhanced via direct absorption or uptake of the nanoparticle contrast agent.

  17. Role of ribosomal protein mutations in tumor development (Review)

    PubMed Central

    GOUDARZI, KAVEH M.; LINDSTRÖM, MIKAEL S.

    2016-01-01

    Ribosomes are cellular machines essential for protein synthesis. The biogenesis of ribosomes is a highly complex and energy consuming process that initiates in the nucleolus. Recently, a series of studies applying whole-exome or whole-genome sequencing techniques have led to the discovery of ribosomal protein gene mutations in different cancer types. Mutations in ribosomal protein genes have for example been found in endometrial cancer (RPL22), T-cell acute lymphoblastic leukemia (RPL10, RPL5 and RPL11), chronic lymphocytic leukemia (RPS15), colorectal cancer (RPS20), and glioma (RPL5). Moreover, patients suffering from Diamond-Blackfan anemia, a bone marrow failure syndrome caused by mutant ribosomal proteins are also at higher risk for developing leukemia, or solid tumors. Different experimental models indicate potential mechanisms whereby ribosomal proteins may initiate cancer development. In particular, deregulation of the p53 tumor suppressor network and altered mRNA translation are mechanisms likely to be involved. We envisage that changes in expression and the occurrence of ribosomal protein gene mutations play important roles in cancer development. Ribosome biology constitutes a re-emerging vital area of basic and translational cancer research. PMID:26892688

  18. Development of Life on Early Mars

    NASA Technical Reports Server (NTRS)

    Gibson, Everett K.; McKay, David S.; Thomas-Keprta, Kathie L.; Clemett, Simon J.; Wentworth, Susan J.

    2009-01-01

    Exploration of Mars has begun to unveil the history of the planet. Combinations of remote sensing, in situ compositional measurements and photographic observations have shown Mars had a dynamic and active geologic evolution. Mars geologic evolution encompassed conditions that were suitable for supporting life. A habitable planet must have water, carbon and energy sources along with a dynamic geologic past. Mars meets all of these requirements. The first 600 My of Martian history were ripe for life to develop because of the abundance of (i) Water- as shown by carved canyons and oceans or lakes with the early presence of near surface water shown by precipitated carbonates in ALH84001, well-dated at 3.9 Gy, (ii) Energy from the original accretional processes, a molten core which generated a strong magnetic field leaving a permanent record in the early crust, active volcanism continuing throughout Martian history, and continuing impact processes, (iii) Carbon, water and a likely thicker atmosphere from extensive volcanic outgassing (i.e. H20, CO2, CH4, CO, O2, N2, H2S, SO2, etc.) and (iv) crustal tectonics as revealed by faulting and possible plate movement reflected by the magnetic pattern in the crust [1]. The question arises: "Why would life not develop from these favorable conditions on Mars in its first 600 My?" During this period, environmental near-surface conditions on Mars were more favorable to life than at any later time. Standing bodies of water, precipitation and flowing surface water, and possibly abundant hydrothermal energy would favor the formation of early life. (Even if life developed elsewhere on Earth, Venus, or on other bodies-it was transported to Mars where surface conditions were suitable for life to evolve). The commonly stated requirement that life would need hundreds of millions of year to get started is only an assumption; we know of no evidence that requires such a long interval for the development of life, if the proper habitable

  19. Cell fate regulation in early mammalian development

    NASA Astrophysics Data System (ADS)

    Oron, Efrat; Ivanova, Natalia

    2012-08-01

    Preimplantation development in mammals encompasses a period from fertilization to implantation and results in formation of a blastocyst composed of three distinct cell lineages: epiblast, trophectoderm and primitive endoderm. The epiblast gives rise to the organism, while the trophectoderm and the primitive endoderm contribute to extraembryonic tissues that support embryo development after implantation. In many vertebrates, such as frog or fish, maternally supplied lineage determinants are partitioned within the egg. Cell cleavage that follows fertilization results in polarization of these factors between the individual blastomeres, which become restricted in their developmental fate. In contrast, the mouse oocyte and zygote lack clear polarity and, until the eight-cell stage, individual blastomeres retain the potential to form all lineages. How are cell lineages specified in the absence of a maternally supplied blueprint? This is a fundamental question in the field of developmental biology. The answer to this question lies in understanding the cell-cell interactions and gene networks involved in embryonic development prior to implantation and using this knowledge to create testable models of the developmental processes that govern cell fates. We provide an overview of classic and contemporary models of early lineage development in the mouse and discuss the emerging body of work that highlights similarities and differences between blastocyst development in the mouse and other mammalian species.

  20. How Early Hormones Shape Gender Development

    PubMed Central

    Berenbaum, Sheri A.; Beltz, Adriene M.

    2015-01-01

    Many important psychological characteristics show sex differences, and are influenced by sex hormones at different developmental periods. We focus on the role of sex hormones in early development, particularly the differential effects of prenatal androgens on aspects of gender development. Increasing evidence confirms that prenatal androgens have facilitative effects on male-typed activity interests and engagement (including child toy preferences and adult careers), and spatial abilities, but relatively minimal effects on gender identity. Recent emphasis has been directed to the psychological mechanisms underlying these effects (including sex differences in propulsive movement, and androgen effects on interest in people versus things), and neural substrates of androgen effects (including regional brain volumes, and neural responses to mental rotation, sexually arousing stimuli, emotion, and reward). Ongoing and planned work is focused on understanding the ways in which hormones act jointly with the social environment across time to produce varying trajectories of gender development, and clarifying mechanisms by which androgens affect behaviors. Such work will be facilitated by applying lessons from other species, and by expanding methodology. Understanding hormonal influences on gender development enhances knowledge of psychological development generally, and has important implications for basic and applied questions, including sex differences in psychopathology, women’s underrepresentation in science and math, and clinical care of individuals with variations in gender expression. PMID:26688827

  1. High-Throughput Sequencing of Germline and Tumor From Men with Early-Onset Metastatic Prostate Cancer

    DTIC Science & Technology

    2016-12-01

    AWARD NUMBER: W81XWH-13-1-0371 TITLE: High-Throughput Sequencing of Germline and Tumor From Men with Early- Onset Metastatic Prostate Cancer...DATES COVERED 30 Sep 2013 - 29 Sep 2016 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER High-Throughput Sequencing of Germline and Tumor From Men with...presenting with metastatic prostate cancer at a young age (before age 60 years). Whole exome sequencing identified a panel of germline variants that have

  2. Early effects of combretastatin A4 phosphate assessed by anatomic and carbogen-based functional magnetic resonance imaging on rat bladder tumors implanted in nude mice.

    PubMed

    Thomas, Carole D; Walczak, Christine; Kaffy, Julia; Pontikis, Renée; Jouanneau, Jacqueline; Volk, Andreas

    2006-07-01

    Combretastatin A4 phosphate (CA4P) causes rapid disruption of the tumor vasculature and is currently being evaluated for antivascular therapy. We describe the initial results obtained with a noninvasive multiparametric magnetic resonance imaging (MRI) approach to assess the early effects of CA4P on rat bladder tumors implanted on nude mice. MRI (4.7 T) comprised a fast spin-echo sequence for growth curve assessment; a multislice multiecho sequence for T2 measurement before, 15 minutes after, and 24 hours after CA4P (100 mg/kg); and a fast T2w* gradient-echo sequence to assess MR signal modification under carbogen breathing before, 35 minutes after, and 24 hours after CA4P. The tumor fraction with increased T2w* signal intensity under carbogen (T+) was used to quantify CA4P effect on functional vasculature. CA4P slowed tumor growth over 24 hours and accelerated necrosis development. T+ decrease was observed already at 35 minutes post-CA4P. Early T2 increase was observed in regions becoming necrotic at 24 hours post-CA4P, as confirmed by high T2 and histology. These regions exhibited, under carbogen, a switch from T2w* signal increase before CA4P to a decrease postCA4P. The combination of carbogen-based functional MRI and T2 measurement may be useful for the early follow-up of antivascular therapy without the administration of contrast agents.

  3. Proton Radiotherapy for Pediatric Central Nervous System Germ Cell Tumors: Early Clinical Outcomes

    SciT

    MacDonald, Shannon M., E-mail: smacdonald@partners.or; Trofimov, Alexei; Safai, Sairos

    Purpose: To report early clinical outcomes for children with central nervous system (CNS) germ cell tumors treated with protons; to compare dose distributions for intensity-modulated photon radiotherapy (IMRT), three-dimensional conformal proton radiation (3D-CPT), and intensity-modulated proton therapy with pencil beam scanning (IMPT) for whole-ventricular irradiation with and without an involved-field boost. Methods and Materials: All children with CNS germinoma or nongerminomatous germ cell tumor who received treatment at the Massachusetts General Hospital between 1998 and 2007 were included in this study. The IMRT, 3D-CPT, and IMPT plans were generated and compared for a representative case. Results: Twenty-two patients were treatedmore » with 3D-CPT. At a median follow-up of 28 months, there were no CNS recurrences; 1 patient had a recurrence outside the CNS. Local control, progression-free survival, and overall survival rates were 100%, 95%, and 100%, respectively. Comparable tumor volume coverage was achieved with IMRT, 3D-CPT, and IMPT. Substantial normal tissue sparing was seen with any form of proton therapy as compared with IMRT. The use of IMPT may yield additional sparing of the brain and temporal lobes. Conclusions: Preliminary disease control with proton therapy compares favorably to the literature. Dosimetric comparisons demonstrate the advantage of proton radiation over IMRT for whole-ventricle radiation. Superior dose distributions were accomplished with fewer beam angles utilizing 3D-CPT and scanned protons. Intensity-modulated proton therapy with pencil beam scanning may improve dose distribution as compared with 3D-CPT for this treatment.« less

  4. A New Paradigm for Ovarian Sex Cord-Stromal Tumor Development

    DTIC Science & Technology

    2016-05-01

    1 AWARD NUMBER: W81XWH-15-1-0082 TITLE: A New Paradigm for Ovarian Sex Cord-Stromal Tumor Development PRINCIPAL INVESTIGATOR: Qinglei Li...5a. CONTRACT NUMBER A New Paradigm for Ovarian Sex Cord-Stromal Tumor Development 5b. GRANT NUMBER W81XWH-15-1-0082 5c. PROGRAM ELEMENT NUMBER 6...role of sustained activation of oocyte TGFBR1 in ovarian tumor development using an in vitro approach. 2. Keywords Ovarian tumor, Sex cord

  5. Methylsulfonylmethane suppresses hepatic tumor development through activation of apoptosis

    PubMed Central

    Kim, Joo-Hyun; Shin, Hye-Jun; Ha, Hye-Lin; Park, Young-Ho; Kwon, Tae-Ho; Jung, Mi-Ra; Moon, Hyung-Bae; Cho, Eun-Sang; Son, Hwa-Young; Yu, Dae-Yeul

    2014-01-01

    AIM: To investigate the effect of methylsulfonylmethane (MSM), recently reported to have anti-cancer effects, in liver cancer cells and transgenic mice. METHODS: Three liver cancer cell lines, HepG2, Huh7-Mock and Huh7-H-rasG12V, were used. Cell growth was measured by Cell Counting Kit-8 and soft agar assay. Western blot analysis was used to detect caspases, poly (ADP-ribose) polymerase (PARP), and B-cell lymphoma 2 (Bcl-2) expressions. For in vivo study, we administered MSM to H-ras12V transgenic mice for 3 mo. RESULTS: MSM decreased the growth of HepG2, Huh7-Mock and Huh7-H-rasG12V cells in a dose-dependent manner. That was correlated with significantly increased apoptosis and reduced cell numbers in MSM treated cells. Cleaved caspase-8, cleaved caspase-3 and cleaved PARP were remarkably increased in the liver cancer cells treated with 500 mmol/L of MSM; however, Bcl-2 was slightly decreased in 500 mmol/L. Liver tumor development was greatly inhibited in the H-ras12V transgenic mice treated with MSM, compared to control, by showing reduced tumor size and number. Cleaved PARP was significantly increased in non-tumor treated with MSM compared to control. CONCLUSION: Liver injury was also significantly attenuated in the mice treated with MSM. Taken together, all the results suggest that MSM has anti-cancer effects through inducing apoptosis in liver cancer. PMID:24575169

  6. Early Vascular Ageing - A Concept in Development.

    PubMed

    M Nilsson, Peter

    2015-04-01

    Cardiovascular disease (CVD) is a prevalent condition in the elderly, often associated with metabolic disturbance and type 2 diabetes. For a number of years, research dedicated to understand atherosclerosis dominated, and for many good reasons, this pathophysiological process being proximal to the CVD events. In recent years, research has been devoted to an earlier stage of vascular pathology named arteriosclerosis (arterial stiffness) and the new concept of early vascular ageing (EVA), developed by a group of mostly European researchers. This overview describes recent developments in research dedicated to EVA and new emerging aspects found in studies of families at high cardiovascular risk. There are new aspects related to genetics, telomere biology and the role of gut microbiota. However, there is still no unifying definition available of EVA and no direct treatment, but rather only recommendations for conventional cardiovascular risk factor control. New interventions are being developed - not only new antihypertensive drugs, but also new drugs for vascular protection - the selective angiotensin-II (AT2) agonist Compound 21 (C21). Human studies are eagerly awaited. Even new functional food products could have the potential to positively influence cardiometabolic regulation, to be confirmed.

  7. Early detection of tumor cells by innate immune cells leads to T(reg) recruitment through CCL22 production by tumor cells.

    PubMed

    Faget, Julien; Biota, Cathy; Bachelot, Thomas; Gobert, Michael; Treilleux, Isabelle; Goutagny, Nadège; Durand, Isabelle; Léon-Goddard, Sophie; Blay, Jean Yves; Caux, Christophe; Ménétrier-Caux, Christine

    2011-10-01

    In breast carcinomas, patient survival seems to be negatively affected by the recruitment of regulatory T cells (T(reg)) within lymphoid aggregates by CCL22. However, the mechanisms underpinning this process, which may be of broader significance in solid tumors, have yet to be described. In this study, we determined how CCL22 production is controlled in tumor cells. In human breast carcinoma cell lines, CCL22 was secreted at low basal levels that were strongly increased in response to inflammatory signals [TNF-α, IFN-γ, and interleukin (IL)-1β], contrasting with CCL17. Primary breast tumors and CD45(+) infiltrating immune cells appeared to cooperate in driving CCL22 secretion, as shown clearly in cocultures of breast tumor cell lines and peripheral blood mononuclear cells (PBMC) or their supernatants. We determined that monocyte-derived IL-1β and TNF-α are key players as monocyte depletion or neutralization of these cytokines attenuated secretion of CCL22. However, when purified monocytes were used, exogenous human IFN-γ was also required to generate this response suggesting a role for IFN-γ-producing cells within PBMCs. In this setting, we found that human IFN-γ could be replaced by the addition of (i) IL-2 or K562-activated natural killer (NK) cells or (ii) resting NK cells in the presence of anti-MHC class I antibody. Taken together, our results show a dialogue between NK and tumor cells leading to IFN-γ secretion, which in turn associates with monocyte-derived IL-1β and TNF-α to drive production of CCL22 by tumor cells and subsequent recruitment of T(reg). As one validation of this conclusion in primary breast tumors, we showed that NK cells and macrophages tend to colocalize within tumors. In summary, our findings suggest that at early times during tumorigenesis, the detection of tumor cells by innate effectors (monocytes and NK cells) imposes a selection for CCL22 secretion that recruits T(reg) to evade this early antitumor immune response.

  8. Renal transplantation-related risk factors for the development of uterine adenomatoid tumors.

    PubMed

    Mizutani, Teruyuki; Yamamuro, Osamu; Kato, Noriko; Hayashi, Kazumasa; Chaya, Junya; Goto, Norihiko; Tsuzuki, Toyonori

    2016-08-01

    •We analyzed the epidemiological factors for clinical manifestations of uterine adenomatoid tumors.•Renal transplantation with immunosuppression therapy is risk factor for the development of uterine adenomatoid tumors.•The length of time on dialysis is risk factor for the development of uterine adenomatoid tumors.

  9. Simultaneous detection of circulating immunological parameters and tumor biomarkers in early stage breast cancer patients during adjuvant chemotherapy.

    PubMed

    Rovati, B; Mariucci, S; Delfanti, S; Grasso, D; Tinelli, C; Torre, C; De Amici, M; Pedrazzoli, P

    2016-06-01

    Chemotherapy-induced immune suppression has mainly been studied in patients with advanced cancer, but the influence of chemotherapy on the immune system in early stage cancer patients has so far not been studied systematically. The aim of the present study was to monitor the immune system during anthracycline- and taxane-based adjuvant chemotherapy in early stage breast cancer patients, to assess the impact of circulating tumor cells on selected immune parameters and to reveal putative angiogenic effects of circulating endothelial cells. Peripheral blood samples from 20 early stage breast cancer patients were analyzed using a flow cytometric multi-color of antibodies to enumerate lymphocyte and dendritic cell subsets, as well as endothelial and tumor cells. An enzyme-linked immunosorbent assay (ELISA) was used to measure the levels of various serological factors. During chemotherapy, all immunological parameters and angiogenesis surrogate biomarkers showed significant decreases. The numbers of circulating tumor cells showed significant inverse correlations with the numbers of T helper cells, a lymphocyte subset directly related to effective anti-tumor responses. Reduced T helper cell numbers may contribute to systemic immunosuppression and, as such, the activation of dormant tumor cells. From our results we conclude that adjuvant chemotherapy suppresses immune function in early stage breast cancer patients. In addition, we conclude that the presence of circulating tumor cells, defined as pan-cytokeratin(+), CD326(+), CD45(-) cells, may serve as an important indicator of a patient's immune status. Further investigations are needed to firmly define circulating tumor cells as a predictor for the success of breast cancer adjuvant chemotherapy.

  10. Calcium at fertilization and in early development

    PubMed Central

    Whitaker, Michael

    2012-01-01

    Fertilization calcium waves are introduced and the evidence from which we can infer general mechanisms of these waves is presented. The two main classes of hypothesis put forward to explain the generation of the fertilization calcium wave are set out and it is concluded that initiation of the fertilization calcium wave can be most generally explained in inverterbrates by a mechanism in which an activating substance enters the egg from the sperm on sperm-egg fusion, activating the egg by stimulating phospholipase C activation through a src family kinase pathway and in mammals by the diffusion of a sperm-specific phospholipase C from sperm to egg on sperm-egg fusion. The fertilization calcium wave is then set into the context of cell cycle control and the mechanism of repetitive calcium spiking in mammalian eggs is investigated. Evidence that calcium signals control cell division in early embryos is reviewed, and it is concluded that calcium signals are essential at all three stages of cell division in early embryos. Evidence that phosphoinositide signalling pathways control the resumption of meiosis during oocyte maturation is considered. It is concluded on balance that the evidence points to a need for phosphoinositide/calcium signalling during resumption of meiosis. Changes to the calcium signalling machinery occur during meiosis to enable the production of a calcium wave in the mature oocyte when it is fertilized; evidence that the shape and structure of the endoplasmic reticulum alters dynamically during maturation and after fertilization is reviewed and the link between ER dynamics and the cytoskeleton is discussed. There is evidence that calcium signalling plays a key part in the development of patterning in early embryos. Morphogenesis in ascidian, frog and zebrafish embryos is briefly described to provide the developmental context in which calcium signals act. Intracellular calcium waves that may play a role in axis formation in ascidian are discussed

  11. Early Years Practitioners' Views on Early Personal, Social and Emotional Development

    ERIC Educational Resources Information Center

    Aubrey, Carol; Ward, Karen

    2013-01-01

    Current policy guidance stresses the need for early identification of obstacles to learning and appropriate intervention. New standards for learning (Early Years Foundation Stage) place personal, social and emotional development (PSED) as central to learning and development. This paper reports a survey and follow-up interviews with early years…

  12. Tumor necrosis factor-alpha expression in peripheral blood mononuclear cells correlates with early childhood social interaction in autism spectrum disorder.

    PubMed

    Makinodan, Manabu; Iwata, Keiko; Ikawa, Daisuke; Yamashita, Yasunori; Yamamuro, Kazuhiko; Toritsuka, Michihiro; Kimoto, Sohei; Okumura, Kazuki; Yamauchi, Takahira; Yoshino, Hiroki; Tsujii, Masatsugu; Sugiyama, Toshiro; Tsuchiya, Kenji; Mori, Norio; Matsuzaki, Hideo; Kishimoto, Toshifumi

    2017-03-01

    Autism spectrum disorder is a neurodevelopmental disorder characterized by impaired social interaction, poor communication skills, and repetitive/restrictive behaviors. Elevated blood levels of pro-inflammatory cytokines have been reported in subjects with autism spectrum disorder. On the other hand, early childhood adverse experience also increases blood levels of these cytokines. Since social experience of children with autism spectrum disorder is generally unlike to typically developing children, we hypothesized that social interaction during childhood contribute to pro-inflammatory cytokine expression in subjects with autism spectrum disorder. We compared revised Autism Diagnostic Interview scores and expression levels of pro-inflammatory cytokines in peripheral blood mononuclear cells of subjects with autism spectrum disorder (n = 30). The score of domain A on the revised Autism Diagnostic Interview, indicating social interaction impairment in early childhood, was negatively correlated with tumor necrosis factor-α mRNA expression level in peripheral blood mononuclear cells but not interleukin-1β or -6. Consistently, tumor necrosis factor-α mRNA expression was markedly low in subjects with autism spectrum disorder compared to typically developing children who presumably experienced the regular levels of social interaction. These findings suggest that the low blood levels of tumor necrosis factor-α mRNA in subjects with autism spectrum disorder might be due to impaired social interaction in early childhood. Copyright © 2016 Elsevier Ltd. All rights reserved.

  13. The murine SNF5/INI1 chromatin remodeling factor is essential for embryonic development and tumor suppression.

    PubMed

    Klochendler-Yeivin, A; Fiette, L; Barra, J; Muchardt, C; Babinet, C; Yaniv, M

    2000-12-01

    The assembly of eukaryotic DNA into nucleosomes and derived higher order structures constitutes a barrier for transcription, replication and repair. A number of chromatin remodeling complexes, as well as histone acetylation, were shown to facilitate gene activation. To investigate the function of two closely related mammalian SWI/SNF complexes in vivo, we inactivated the murine SNF5/INI1 gene, a common subunit of these two complexes. Mice lacking SNF5 protein stop developing at the peri-implantation stage, showing that the SWI/SNF complex is essential for early development and viability of early embryonic cells. Furthermore, heterozygous mice develop nervous system and soft tissue sarcomas. In these tumors the wild-type allele was lost, providing further evidence that SNF5 functions as a tumor suppressor gene in certain cell types.

  14. The murine SNF5/INI1 chromatin remodeling factor is essential for embryonic development and tumor suppression

    PubMed Central

    Klochendler-Yeivin, Agnes; Fiette, Laurence; Barra, Jaqueline; Muchardt, Christian; Babinet, Charles; Yaniv, Moshe

    2000-01-01

    The assembly of eukaryotic DNA into nucleosomes and derived higher order structures constitutes a barrier for transcription, replication and repair. A number of chromatin remodeling complexes, as well as histone acetylation, were shown to facilitate gene activation. To investigate the function of two closely related mammalian SWI/SNF complexes in vivo, we inactivated the murine SNF5/INI1 gene, a common subunit of these two complexes. Mice lacking SNF5 protein stop developing at the peri-implantation stage, showing that the SWI/SNF complex is essential for early development and viability of early embryonic cells. Furthermore, heterozygous mice develop nervous system and soft tissue sarcomas. In these tumors the wild-type allele was lost, providing further evidence that SNF5 functions as a tumor suppressor gene in certain cell types. PMID:11263494

  15. ENaC/DEG in Tumor Development and Progression

    PubMed Central

    Liu, Cui; Zhu, Li-Li; Xu, Si-Guang; Ji, Hong-Long; Li, Xiu-Min

    2016-01-01

    The epithelial Na+ channel/degenerin (ENaC/DEG) superfamily, including the acid-sensing ion channels (ASICs), is characterized by a high degree of similarity in structure but highly diverse in physiological functions. These ion channels have been shown to be important in several physiological functions of normal epithelial cells, including salt homeostasis, fluid transportation and cell mobility. There is increasing evidence suggesting that ENaC/DEG channels are critically engaged in cancer cell biology, such as proliferation, migration, invasion and apoptosis, playing a role in tumor development and progression. In this review, we will discuss recent studies showing the role of ENaC and ASIC channels in epithelial cells and its relationship to the oncogenesis. PMID:27698929

  16. Early wound site seeding in a patient with CNS high-grade neuroepithelial tumor with BCOR alteration: A case report.

    PubMed

    Kirkman, Matthew A; Pickles, Jessica C; Fairchild, Amy R; Avery, Aimee; Pietsch, Torsten; Jacques, Thomas S; Aquilina, Kristian

    2018-05-30

    Advances in molecular profiling have facilitated the emergence of newly defined entities of central nervous system tumor, including CNS high-grade neuroepithelial tumor with BCOR alteration (CNS HGNET-BCOR). Relatively little is known about the clinical behaviour of these newly-characterized tumors. We describe a pediatric male patient with CNS HGNET-BCOR who developed seeding of the tumor into the site of the surgical wound within months of surgery for resection of a residual posterior fossa tumor. This case emphasises three important points. First, CNS HGNET-BCOR can be aggressive tumors that necessitate close clinical and radiological surveillance. Second, surveillance imaging in such cases should incorporate the surgical incision site into the field of view, and this should be closely scrutinised to ensure the timely detection of wound site seeding. Third, wound site seeding may still occur despite the use of meticulous surgical techniques. Copyright © 2018. Published by Elsevier Inc.

  17. Harvey Cushing's Approaches to Tumors in His Early Career: From the Skull Base to the Cranial Vault

    PubMed Central

    Pendleton, Courtney; Raza, Shaan M.; Gallia, Gary L.; Quiñones-Hinojosa, Alfredo

    2011-01-01

    In this report, we review Dr. Cushing's early surgical cases at the Johns Hopkins Hospital, revealing details of his early operative approaches to tumors of the skull base and cranial vault. Following Institutional Review Board approval, and through the courtesy of the Alan Mason Chesney Archives, we reviewed the Johns Hopkins Hospital surgical files from 1896 to 1912. Participants included four adult patients and one child who underwent surgical resection of bony tumors of the skull base and the cranial vault. The main outcome measures were operative approach and condition recorded at the time of discharge. The indications for surgery included unspecified malignant tumor of the basal meninges and temporal bone, basal cell carcinoma, osteoma of the posterior skull base, and osteomas of the frontal and parietofrontal cranial vault. While Cushing's experience with selected skull base pathology has been previously reported, the breadth of his contributions to operative approaches to the skull base has been neglected. PMID:22470271

  18. Early Parental Depression and Child Language Development

    ERIC Educational Resources Information Center

    Paulson, James F.; Keefe, Heather A.; Leiferman, Jenn A.

    2009-01-01

    Objective: To examine the effects of early maternal and paternal depression on child expressive language at age 24 months and the role that parent-to-child reading may play in this pathway. Participants and methods: The 9-month and 24-month waves from a national prospective study of children and their families, the Early Childhood Longitudinal…

  19. Association of Vascular Endothelial Growth Factor Expression with Tumor Angiogenesis and with Early Relapse in Primary Breast Cancer

    PubMed Central

    Hoshina, Seigo; Takayanagi, Toshiaki; Tominaga, Takeshi

    1994-01-01

    Angiogenesis is an independent prognostic indicator in breast cancer. In this report, the relationship between expression of vascular endothclial growth factor (VEGF; a selective mitogen for endothelial cells) and the microvessel density was examined in 103 primary breast cancers. The expression of VEGF was evaluated by immunocytochemical staining using anti‐VEGF antibody. The microvessel density, which was determined by immunostaining for factor VIII antigen, in VEGF‐rich tumors was clearly higher than that in VEGF‐poor tumors (P<0.01). There was a good correlation between VEGF expression and the increment of microvessel density. Furthermore, postoperative survey demonstrated that the relapse‐free survival rate of VEGF‐rich tumors was significantly worse than that of VEGF‐poor tumors. It was suggested that the expression of VEGF is closely associated with the promotion of angiogenesis and with early relapse in primary breast cancer. PMID:7525523

  20. The early research and development of ebselen.

    PubMed

    Parnham, Michael J; Sies, Helmut

    2013-11-01

    Ebselen (2-phenyl-1,2-benzisoselenazol-3(2H)-one; PZ-51, DR-3305), is an organoselenium compound with glutathione peroxidase (GPx)-like, thiol-dependent, hydroperoxide reducing activity. As an enzyme mimic for activity of the selenoenzyme GPx, this compound has proved to be highly useful in research on mechanisms in redox biology. Furthermore, the reactivity of ebselen with protein thiols has helped to identify novel, selective targets for inhibitory actions on several enzymes of importance in pharmacology and toxicology. Importantly, the selenium in ebselen is not released and thus is not bioavailable, ebselen metabolites being excreted in bile and urine. As a consequence, initial concerns about selenium toxicity, fortunately, were unfounded. Potential applications in medical settings have been explored, notably in brain ischemia and stroke. More recently, there has been a surge in interest as new medical applications have been taken into consideration. The first publication on the biochemical effects of ebselen appeared 30 years ago (Müller et al.), which prompted the authors to retrace the early development from their perspective. It is a fascinating example of fruitful interaction between research-oriented industry and academia. Copyright © 2013 Elsevier Inc. All rights reserved.

  1. Parental Obesity and Early Childhood Development.

    PubMed

    Yeung, Edwina H; Sundaram, Rajeshwari; Ghassabian, Akhgar; Xie, Yunlong; Buck Louis, Germaine

    2017-02-01

    Previous studies identified associations between maternal obesity and childhood neurodevelopment, but few examined paternal obesity despite potentially distinct genetic/epigenetic effects related to developmental programming. Upstate KIDS (2008-2010) recruited mothers from New York State (excluding New York City) at ∼4 months postpartum. Parents completed the Ages and Stages Questionnaire (ASQ) when their children were 4, 8, 12, 18, 24, 30, and 36 months of age corrected for gestation. The ASQ is validated to screen for delays in 5 developmental domains (ie, fine motor, gross motor, communication, personal-social functioning, and problem-solving ability). Analyses included 3759 singletons and 1062 nonrelated twins with ≥1 ASQs returned. Adjusted odds ratios (aORs) and 95% confidence intervals were estimated by using generalized linear mixed models accounting for maternal covariates (ie, age, race, education, insurance, marital status, parity, and pregnancy smoking). Compared with normal/underweight mothers (BMI <25), children of obese mothers (26% with BMI ≥30) had increased odds of failing the fine motor domain (aOR 1.67; confidence interval 1.12-2.47). The association remained after additional adjustment for paternal BMI (1.67; 1.11-2.52). Paternal obesity (29%) was associated with increased risk of failing the personal-social domain (1.75; 1.13-2.71), albeit attenuated after adjustment for maternal obesity (aOR 1.71; 1.08-2.70). Children whose parents both had BMI ≥35 were likely to additionally fail the problem-solving domain (2.93; 1.09-7.85). Findings suggest that maternal and paternal obesity are each associated with specific delays in early childhood development, emphasizing the importance of family information when screening child development. Copyright © 2017 by the American Academy of Pediatrics.

  2. Parental Obesity and Early Childhood Development

    PubMed Central

    Sundaram, Rajeshwari; Ghassabian, Akhgar; Xie, Yunlong; Buck Louis, Germaine

    2017-01-01

    BACKGROUND: Previous studies identified associations between maternal obesity and childhood neurodevelopment, but few examined paternal obesity despite potentially distinct genetic/epigenetic effects related to developmental programming. METHODS: Upstate KIDS (2008–2010) recruited mothers from New York State (excluding New York City) at ∼4 months postpartum. Parents completed the Ages and Stages Questionnaire (ASQ) when their children were 4, 8, 12, 18, 24, 30, and 36 months of age corrected for gestation. The ASQ is validated to screen for delays in 5 developmental domains (ie, fine motor, gross motor, communication, personal-social functioning, and problem-solving ability). Analyses included 3759 singletons and 1062 nonrelated twins with ≥1 ASQs returned. Adjusted odds ratios (aORs) and 95% confidence intervals were estimated by using generalized linear mixed models accounting for maternal covariates (ie, age, race, education, insurance, marital status, parity, and pregnancy smoking). RESULTS: Compared with normal/underweight mothers (BMI <25), children of obese mothers (26% with BMI ≥30) had increased odds of failing the fine motor domain (aOR 1.67; confidence interval 1.12–2.47). The association remained after additional adjustment for paternal BMI (1.67; 1.11–2.52). Paternal obesity (29%) was associated with increased risk of failing the personal-social domain (1.75; 1.13–2.71), albeit attenuated after adjustment for maternal obesity (aOR 1.71; 1.08–2.70). Children whose parents both had BMI ≥35 were likely to additionally fail the problem-solving domain (2.93; 1.09–7.85). CONCLUSIONS: Findings suggest that maternal and paternal obesity are each associated with specific delays in early childhood development, emphasizing the importance of family information when screening child development. PMID:28044047

  3. Early Re-Do Surgery for Glioblastoma Is a Feasible and Safe Strategy to Achieve Complete Resection of Enhancing Tumor

    PubMed Central

    Schucht, Philippe; Murek, Michael; Jilch, Astrid; Seidel, Kathleen; Hewer, Ekkehard; Wiest, Roland; Raabe, Andreas; Beck, Jürgen

    2013-01-01

    Background Complete resection of enhancing tumor as assessed by early (<72 hours) postoperative MRI is regarded as the optimal result in glioblastoma surgery. As yet, there is no consensus on standard procedure if post-operative imaging reveals unintended tumor remnants. Objective The current study evaluated the feasibility and safety of an early re-do surgery aimed at completing resections with the aid of 5-ALA fluorescence and neuronavigation after detection of enhancing tumor remnants on post-operative MRI. Methods From October 2008 to October 2012 a single center institutional protocol offered a second surgery within one week to patients with unintentional incomplete glioblastoma resection. We report on the feasibility of the use 5-ALA fluorescence guidance, the extent of resection (EOR) rates and complications of early re-do surgery. Results Nine of 151 patients (6%) with glioblastoma resections had an unintentional tumor remnant with a volume >0.175 cm3. 5-ALA guided re-do surgery completed the resection (CRET) in all patients without causing neurological deficits, infections or other complications. Patients who underwent a re-do surgery remained hospitalized between surgeries, resulting in a mean length of hospital stay of 11 days (range 7-15), compared to 9 days for single surgery (range 3-23; p=0.147). Conclusion Our early re-do protocol led to complete resection of all enhancing tumor in all cases without any new neurological deficits and thus provides a similar oncological result as intraoperative MRI (iMRI). The repeated use of 5-ALA induced fluorescence, used for identification of small remnants, remains highly sensitive and specific in the setting of re-do surgery. Early re-do surgery is a feasible and safe strategy to complete unintended subtotal resections. PMID:24348904

  4. Androgen dependent mechanisms of pro-angiogenic networks in placental and tumor development.

    PubMed

    Metzler, Veronika M; de Brot, Simone; Robinson, Robert S; Jeyapalan, Jennie N; Rakha, Emad; Walton, Thomas; Gardner, David S; Lund, Emma F; Whitchurch, Jonathan; Haigh, Daisy; Lochray, Jack M; Robinson, Brian D; Allegrucci, Cinzia; Fray, Rupert G; Persson, Jenny L; Ødum, Niels; Miftakhova, Regina R; Rizvanov, Albert A; Hughes, Ieuan A; Tadokoro-Cuccaro, Rieko; Heery, David M; Rutland, Catrin S; Mongan, Nigel P

    2017-08-01

    The placenta and tumors share important characteristics, including a requirement to establish effective angiogenesis. In the case of the placenta, optimal angiogenesis is required to sustain the blood flow required to maintain a successful pregnancy, whereas in tumors establishing new blood supplies is considered a key step in supporting metastases. Therefore the development of novel angiogenesis inhibitors has been an area of active research in oncology. A subset of the molecular processes regulating angiogenesis are well understood in the context of both early placentation and tumorigenesis. In this review we focus on the well-established role of androgen regulation of angiogenesis in cancer and relate these mechanisms to placental angiogenesis. The physiological actions of androgens are mediated by the androgen receptor (AR), a ligand dependent transcription factor. Androgens and the AR are essential for normal male embryonic development, puberty and lifelong health. Defects in androgen signalling are associated with a diverse range of clinical disorders in men and women including disorders of sex development (DSD), polycystic ovary syndrome in women and many cancers. We summarize the diverse molecular mechanisms of androgen regulation of angiogenesis and infer the potential significance of these pathways to normal and pathogenic placental function. Finally, we offer potential research applications of androgen-targeting molecules developed to treat cancer as investigative tools to help further delineate the role of androgen signalling in placental function and maternal and offspring health in animal models. Copyright © 2017 Elsevier Ltd. All rights reserved.

  5. Elevated S100A9 expression in tumor stroma functions as an early recurrence marker for early-stage oral cancer patients through increased tumor cell invasion, angiogenesis, macrophage recruitment and interleukin-6 production

    PubMed Central

    Fang, Wei-Yu; Chen, Yi-Wen; Hsiao, Jenn-Ren; Liu, Chiang-Shin; Kuo, Yi-Zih; Wang, Yi-Ching; Chang, Kung-Chao; Tsai, Sen-Tien; Chang, Mei-Zhu; Lin, Siao-Han; Wu, Li-Wha

    2015-01-01

    S100A9 is a calcium-binding protein with two EF-hands and frequently deregulated in several cancer types, however, with no clear role in oral cancer. In this report, the expression of S100A9 in cancer and adjacent tissues from 79 early-stage oral cancer patients was detected by immunohistochemical staining. Although S100A9 protein was present in both tumor and stromal cells, only the early-stage oral cancer patients with high stromal expression had reduced recurrence-free survival. High stromal S100A9 expression was also significantly associated with non-well differentiation and recurrence. In addition to increasing cell migration and invasion, ectopic S100A9 expression in tumor cells promoted xenograft tumorigenesis as well as the dominant expression of myeloid cell markers and pro-inflammatory IL-6. The expression of S100A9 in one stromal component, monocytes, stimulated the aggressiveness of co-cultured oral cancer cells. We also detected the elevation of serum S100A9 levels in early-stage oral cancer patients of a separate cohort of 73 oral cancer patients. The release of S100A9 protein into extracellular milieu enhanced tumor cell invasion, transendothelial monocyte migration and angiogenic activity. S100A9-mediated release of IL-6 requires the crosstalk of tumor cells with monocytes through the activation of NF-κB and STAT-3. Early-stage oral cancer patients with both high S100A9 expression and high CD68+ immune infiltrates in stroma had shortest recurrence-free survival, suggesting the use of both S100A9 and CD68 as poor prognostic markers for oral cancer. Together, both intracellular and extracellular S100A9 exerts a tumor-promoting action through the activation of oral cancer cells and their associated stroma in oral carcinogenesis. PMID:26315114

  6. Elevated S100A9 expression in tumor stroma functions as an early recurrence marker for early-stage oral cancer patients through increased tumor cell invasion, angiogenesis, macrophage recruitment and interleukin-6 production.

    PubMed

    Fang, Wei-Yu; Chen, Yi-Wen; Hsiao, Jenn-Ren; Liu, Chiang-Shin; Kuo, Yi-Zih; Wang, Yi-Ching; Chang, Kung-Chao; Tsai, Sen-Tien; Chang, Mei-Zhu; Lin, Siao-Han; Wu, Li-Wha

    2015-09-29

    S100A9 is a calcium-binding protein with two EF-hands and frequently deregulated in several cancer types, however, with no clear role in oral cancer. In this report, the expression of S100A9 in cancer and adjacent tissues from 79 early-stage oral cancer patients was detected by immunohistochemical staining. Although S100A9 protein was present in both tumor and stromal cells, only the early-stage oral cancer patients with high stromal expression had reduced recurrence-free survival. High stromal S100A9 expression was also significantly associated with non-well differentiation and recurrence. In addition to increasing cell migration and invasion, ectopic S100A9 expression in tumor cells promoted xenograft tumorigenesis as well as the dominant expression of myeloid cell markers and pro-inflammatory IL-6. The expression of S100A9 in one stromal component, monocytes, stimulated the aggressiveness of co-cultured oral cancer cells. We also detected the elevation of serum S100A9 levels in early-stage oral cancer patients of a separate cohort of 73 oral cancer patients. The release of S100A9 protein into extracellular milieu enhanced tumor cell invasion, transendothelial monocyte migration and angiogenic activity. S100A9-mediated release of IL-6 requires the crosstalk of tumor cells with monocytes through the activation of NF-κB and STAT-3. Early-stage oral cancer patients with both high S100A9 expression and high CD68+ immune infiltrates in stroma had shortest recurrence-free survival, suggesting the use of both S100A9 and CD68 as poor prognostic markers for oral cancer. Together, both intracellular and extracellular S100A9 exerts a tumor-promoting action through the activation of oral cancer cells and their associated stroma in oral carcinogenesis.

  7. Adult Brain and Spine Tumor Research and Development

    Cancer.gov

    Chief, Dr. Mark Gilbert and Senior Investigator, Dr. Terri Armstrong, of the NCI Center for Cancer Research, Neuro-Oncology Branch, will be joined by moderator and Chief Executive Officer, David Arons of the National Brain Tumor Society led a discussion on adult brain and spine tumor research and treatment.

  8. Tumor-related interleukins: old validated targets for new anti-cancer drug development.

    PubMed

    Setrerrahmane, Sarra; Xu, Hanmei

    2017-09-19

    In-depth knowledge of cancer molecular and cellular mechanisms have revealed a strong regulation of cancer development and progression by the inflammation which orchestrates the tumor microenvironment. Immune cells, residents or recruited, in the inflammation milieu can have rather contrasting effects during cancer development. Accumulated clinical and experimental data support the notion that acute inflammation could exert an immunoprotective effect leading to tumor eradication. However, chronic immune response promotes tumor growth and invasion. These reactions are mediated by soluble mediators or cytokines produced by either host immune cells or tumor cells themselves. Herein, we provide an overview of the current understanding of the role of the best-validated cytokines involved in tumor progression, IL-1, IL-4 and IL-6; in addition to IL-2 cytokines family, which is known to promote tumor eradication by immune cells. Furthermore, we summarize the clinical attempts to block or bolster the effect of these tumor-related interleukins in anti-cancer therapy development.

  9. Impact of Early Postnatal Androgen Exposure on Voice Development

    PubMed Central

    Grisa, Leila; Leonel, Maria L.; Gonçalves, Maria I. R.; Pletsch, Francisco; Sade, Elis R.; Custódio, Gislaine; Zagonel, Ivete P. S.; Longui, Carlos A.; Figueiredo, Bonald C.

    2012-01-01

    Background The impact of early postnatal androgen exposure on female laryngeal tissue may depend on certain characteristics of this exposure. We assessed the impact of the dose, duration, and timing of early androgen exposure on the vocal development of female subjects who had been treated for adrenocortical tumor (ACT) in childhood. Methods The long-term effects of androgen exposure on the fundamental vocal frequency (F0), vocal pitch, and final height and the presence of virilizing signs were examined in 9 adult (age, 18.4 to 33.5 years) and 10 adolescent (13.6 to 17.8 years) female ACT patients. We also compared the current values with values obtained 0.9 years to 7.4 years after these subjects had undergone ACT surgery, a period during which they had shown normal androgen levels. Results Of the 19 subjects, 17 (89%) had been diagnosed with ACT before 4 years of age, 1 (5%) at 8.16 years, and 1 (5%) at 10.75 years. Androgen exposure (2 to 30 months) was sufficiently strong to cause pubic hair growth in all subjects and clitoromegaly in 74% (14/19) of the subjects, but did not reduce their height from the target value. Although androgen exposure induced a remarkable reduction in F0 (132 Hz) and moderate pitch virilization in 1 subject and partial F0 virilization, resulting in F0 of 165 and 169 Hz, in 2 subjects, the majority had normal F0 ranging from 189 to 245 Hz. Conclusions Female laryngeal tissue is less sensitive to androgen exposure between birth and adrenarche than during other periods. Differential larynx sensitivity to androgen exposure in childhood and F0 irreversibility in adulthood are age-, concentration-, duration-, and timing-dependent events that may also be affected by exposure to inhibitory or stimulatory hormones. Further studies are required to better characterize each of these factors. PMID:23284635

  10. Photodetection of early cancer by laser-induced fluorescence of a tumor-selective dye: apparatus design and realization

    NASA Astrophysics Data System (ADS)

    Wagnieres, Georges A.; Depeursinge, Christian D.; Monnier, Philippe; Savary, Jean-Francois; Cornaz, Piet F.; Chatelain, Andre; van den Bergh, Hubert

    1990-07-01

    An apparatus is designed and realized to detect "early" cancer at the surface of the hollow organs in the human body by endoscopic means. The tumor is localized by the laser induced fluorescence of a dye (HPD) which concentrates selectively in the neoplastic tissue after intravenous injection. Fluorescence contrast between the tumor and its normal surroundings is enhanced by subtracting the background autofluorescence which occurs in both types of tissue. This is done by means of 2-color digital images manipulation in real-time. Preliminary clinical tests of the apparatus demonstrated the detection of carcinoma in situ in the esophagus.

  11. Early Intervention Paraprofessional Standards: Development and Field Validation

    ERIC Educational Resources Information Center

    Banerjee, Rashida; Chopra, Ritu V.; DiPalma, Geraldine

    2017-01-01

    Personnel standards are the foundations for how states and nations approve a program, engage in systemic assessment, and provide effective professional development to its early childhood professionals. However, despite the extensive use of paraprofessionals in early intervention/early childhood special education programs, there is a lack of…

  12. Development of stereotactic mass spectrometry for brain tumor surgery.

    PubMed

    Agar, Nathalie Y R; Golby, Alexandra J; Ligon, Keith L; Norton, Isaiah; Mohan, Vandana; Wiseman, Justin M; Tannenbaum, Allen; Jolesz, Ferenc A

    2011-02-01

    Surgery remains the first and most important treatment modality for the majority of solid tumors. Across a range of brain tumor types and grades, postoperative residual tumor has a great impact on prognosis. The principal challenge and objective of neurosurgical intervention is therefore to maximize tumor resection while minimizing the potential for neurological deficit by preserving critical tissue. To introduce the integration of desorption electrospray ionization mass spectrometry into surgery for in vivo molecular tissue characterization and intraoperative definition of tumor boundaries without systemic injection of contrast agents. Using a frameless stereotactic sampling approach and by integrating a 3-dimensional navigation system with an ultrasonic surgical probe, we obtained image-registered surgical specimens. The samples were analyzed with ambient desorption/ionization mass spectrometry and validated against standard histopathology. This new approach will enable neurosurgeons to detect tumor infiltration of the normal brain intraoperatively with mass spectrometry and to obtain spatially resolved molecular tissue characterization without any exogenous agent and with high sensitivity and specificity. Proof of concept is presented in using mass spectrometry intraoperatively for real-time measurement of molecular structure and using that tissue characterization method to detect tumor boundaries. Multiple sampling sites within the tumor mass were defined for a patient with a recurrent left frontal oligodendroglioma, World Health Organization grade II with chromosome 1p/19q codeletion, and mass spectrometry data indicated a correlation between lipid constitution and tumor cell prevalence. The mass spectrometry measurements reflect a complex molecular structure and are integrated with frameless stereotaxy and imaging, providing 3-dimensional molecular imaging without systemic injection of any agents, which can be implemented for surgical margins delineation of

  13. Insulin-like growth factors and insulin: at the crossroad between tumor development and longevity.

    PubMed

    Novosyadlyy, Ruslan; Leroith, Derek

    2012-06-01

    Numerous lines of evidence indicate that insulin-like growth factor signaling plays an important role in the regulation of life span and tumor development. In the present paper, the role of individual components of insulin-like growth factor signaling in aging and tumor development has been extensively analyzed. The molecular mechanisms underlying aging and tumor development are frequently overlapping. Although the link between reduced insulin-like growth factor signaling and suppressed tumor growth and development is well established, it remains unclear whether extended life span results from direct suppression of insulin-like growth factor signaling or this effect is caused by indirect mechanisms such as improved insulin sensitivity.

  14. Surgeon Annual and Cumulative Volumes Predict Early Postoperative Outcomes After Brain Tumor Resection.

    PubMed

    Ramakrishna, Rohan; Hsu, Wei-Chun; Mao, Jialin; Sedrakyan, Art

    2018-06-01

    Surgeon volume has been previously shown to affect patient outcomes. However, data related to neuro-oncologic surgery are limited and do not include neurologic morbidities as an outcomes measure. In this study, we aimed to determine if 5-year surgeon cumulative and annual volumes predict early postoperative outcomes in patients after brain tumor surgery. A population-based cohort of patients (n = 10,258) undergoing brain tumor resection between 2005 and 2014 were included for study using the New York Statewide Planning and Research Cooperation System. Surgeons were categorized by their cumulative and annual surgical volume. Patients treated by high cumulative/high annual (HC/HA) volume surgeons had shorter length of stay (median, 5 days vs. 8 days vs. 8 days vs. 6 days, respectively; P < 0.01), lower charges (median, 70,025 vs. $77,043 vs. $93,715 vs. $77,018 respectively; P < 0.01) and less nonroutine discharge (41% vs. 48% vs. 50.9% vs. 43.9% respectively; P < 0.01) compared with patients treated by surgeons from the low cumulative/low annual (LC/LA), LC/HA, HC/LA groups. Similarly, HC/HA volume surgeons also had lower rate of hydrocephalus (9.9% vs. 10.4% vs. 13.7% respectively; P = 0.02), medical complications (6.9% vs. 11.2% vs. 11.5% respectively; P < 0.01), neurologic complications (44.1% vs. 46.8% vs. 48.1% respectively; P = 0.03), 30-day reoperation (5.1% vs. 6.9% vs. 7.1% respectively; P < 0.01) and 30-day death (3.3% vs. 5.4% vs. 5.2%; P < 0.01) compared with LC/LA and LC/HA volume surgeons. There is some evidence for improved postoperative outcomes when surgery is performed by HC and HA volume surgeons. This finding suggests that subspecialization in surgical neuro-oncology should be considered. Copyright © 2018 Elsevier Inc. All rights reserved.

  15. Hepatocellular Carcinoma Screening Associated with Early Tumor Detection and Improved Survival Among Patients with Cirrhosis in the US.

    PubMed

    Singal, Amit G; Mittal, Sahil; Yerokun, Olutola A; Ahn, Chul; Marrero, Jorge A; Yopp, Adam C; Parikh, Neehar D; Scaglione, Steve J

    2017-09-01

    Professional societies recommend hepatocellular carcinoma screening in patients with cirrhosis, but high-quality data evaluating its effectiveness to improve early tumor detection and survival in "real world" clinical practice are needed. We aim to characterize the association between hepatocellular carcinoma screening and early tumor detection, curative treatment, and overall survival among patients with cirrhosis. We performed a retrospective cohort study of patients diagnosed with hepatocellular carcinoma between June 2012 and May 2013 at 4 health systems in the US. Patients were categorized in the screening group if hepatocellular carcinoma was detected by imaging performed for screening purposes. Generalized linear models and multivariate Cox regression with frailty adjustment were used to compare early detection, curative treatment, and survival between screen-detected and non-screen-detected patients. Among 374 hepatocellular carcinoma patients, 42% (n = 157) were detected by screening. Screen-detected patients had a significantly higher proportion of early tumors (Barcelona Clinic Liver Cancer stage A 63.1% vs 36.4%, P <.001) and were more likely to undergo curative treatment (31% vs 13%, P = .02). Hepatocellular carcinoma screening was significantly associated with improved survival in multivariate analysis (hazards ratio 0.41; 95% confidence interval, 0.26-0.65) after adjusting for patient demographics, Child-Pugh class, and performance status. Median survival of screen-detected patients was 14.6 months, compared with 6.0 months for non-screen-detected patients, with the difference remaining significant after adjusting for lead-time bias (hazards ratio 0.59, 95% confidence interval, 0.37-0.93). Hepatocellular carcinoma screening is associated with increased early tumor detection and improved survival; however, a minority of hepatocellular carcinoma patients are detected by screening. Interventions to increase screening use in patients with cirrhosis may

  16. Early Increases in Superantigen-Specific Foxp3+ Regulatory T Cells during Mouse Mammary Tumor Virus Infection▿ †

    PubMed Central

    Cabrera, Gabriel; Burzyn, Dalia; Mundiñano, Juliana; Courreges, M. Cecilia; Camicia, Gabriela; Lorenzo, Daniela; Costa, Héctor; Ross, Susan R.; Nepomnaschy, Irene; Piazzon, Isabel

    2008-01-01

    Mouse mammary tumor virus (MMTV) is a milk-borne betaretrovirus that has developed strategies to exploit and subvert the host immune system. Here, we show in a natural model of MMTV infection that the virus causes early and progressive increases in superantigen (SAg)-specific Foxp3+ regulatory T cells (Treg) in Peyer's patches (PP). These increases were shown to be dependent on the presence of dendritic cells. CD4+ CD25+ T cells from the PP of infected mice preferentially suppress the proliferative response of T cells to SAg-expressing antigen-presenting cells ex vivo. We investigated the influence of the depletion of CD25+ cells at different stages of the infection. When CD25+ cells were depleted before MMTV infection, an increase in the number of PP SAg-cognate Foxp3− T cells was found at day 6 of infection. Since the SAg response is associated with viral amplification, the possibility exists that Treg cells attenuate the increase in viral load at the beginning of the infection. In contrast, depletion of CD25+ cells once the initial SAg response has developed caused a lower viral load, suggesting that at later stages Treg cells may favor viral persistence. Thus, our results indicated that Treg cells play an important and complex role during MMTV infection. PMID:18495774

  17. Early Developments in Argumentation in Physics.

    ERIC Educational Resources Information Center

    Bazerman, Charles

    An evaluation of four seventeenth and eighteenth century essays on optics revealed early trends in the evolution of scientific articles. The later articles showed a growing tendency to (1) separate practice from pure knowledge, (2) organize information around problems of knowledge and theory rather than around chronological events, (3) emphasize…

  18. The Development of Self-Regulation across Early Childhood

    ERIC Educational Resources Information Center

    Montroy, Janelle J.; Bowles, Ryan P.; Skibbe, Lori E.; McClelland, Megan M.; Morrison, Frederick J.

    2016-01-01

    The development of early childhood self-regulation is often considered an early life marker for later life successes. Yet little longitudinal research has evaluated whether there are different trajectories of self-regulation development across children. This study investigates the development of behavioral self-regulation between the ages of 3 and…

  19. Early Development and the Brain: Teaching Resources for Educators

    ERIC Educational Resources Information Center

    Gilkerson, Linda, Ed.; Klein, Rebecca, Ed.

    2008-01-01

    This nine-unit curriculum translates current scientific research on early brain development into practical suggestions to help early childhood professionals understand the reciprocal link between caregiving and brain development. The curriculum was created and extensively field-tested by the Erikson Institute Faculty Development Project on the…

  20. Parents' Role in the Early Head Start Children's Language Development

    ERIC Educational Resources Information Center

    Griswold, Cecelia Smalls

    2014-01-01

    The development of language during a child's early years has been linked to parental involvement. While Early Head Start (EHS) researchers have theorized that parental involvement is an important factor in language development, there has been little research on how parents view their roles in the language development process. The purpose of this…

  1. Classroom Effects of an Early Childhood Educator Professional Development Partnership

    ERIC Educational Resources Information Center

    Algozzine, Bob; Babb, Julie; Algozzine, Kate; Mraz, Maryann; Kissel, Brian; Spano, Sedra; Foxworth, Kimberly

    2011-01-01

    We evaluated an Early Childhood Educator Professional Development (ECEPD) project that provided high-quality, sustained, and intensive professional development designed to support developmentally appropriate instruction for preschool-age children based on the best available research on early childhood pedagogy, child development, and preschool…

  2. Tumor-specific CD4+ T cells develop cytotoxic activity and eliminate virus-induced tumor cells in the absence of regulatory T cells.

    PubMed

    Akhmetzyanova, Ilseyar; Zelinskyy, Gennadiy; Schimmer, Simone; Brandau, Sven; Altenhoff, Petra; Sparwasser, Tim; Dittmer, Ulf

    2013-02-01

    The important role of tumor-specific cytotoxic CD8(+) T cells is well defined in the immune control of the tumors, but the role of effector CD4(+) T cells is poorly understood. In the current research, we have used a murine retrovirus-induced tumor cell line of C57BL/6 mouse origin, namely FBL-3 cells, as a model to study basic mechanisms of immunological control and escape during tumor formation. This study shows that tumor-specific CD4(+) T cells are able to protect against virus-induced tumor cells. We show here that there is an expansion of tumor-specific CD4(+) T cells producing cytokines and cytotoxic molecule granzyme B (GzmB) in the early phase of tumor growth. Importantly, we demonstrate that in vivo depletion of regulatory T cells (Tregs) and CD8(+) T cells in FBL-3-bearing DEREG transgenic mice augments IL-2 and GzmB production by CD4(+) T cells and increases FV-specific CD4(+) T-cell effector and cytotoxic responses leading to the complete tumor regression. Therefore, the capacity to reject tumor acquired by tumor-reactive CD4(+) T cells largely depends on the direct suppressive activity of Tregs. We suggest that a cytotoxic CD4(+) T-cell immune response may be induced to enhance resistance against oncovirus-associated tumors.

  3. Early impact of social isolation and breast tumor progression in mice.

    PubMed

    Madden, Kelley S; Szpunar, Mercedes J; Brown, Edward B

    2013-03-01

    Evidence from cancer patients and animal models of cancer indicates that exposure to psychosocial stress can promote tumor growth and metastasis, but the pathways underlying stress-induced cancer pathogenesis are not fully understood. Social isolation has been shown to promote tumor progression. We examined the impact of social isolation on breast cancer pathogenesis in adult female severe combined immunodeficiency (SCID) mice using the human breast cancer cell line, MDA-MB-231, a high β-adrenergic receptor (AR) expressing line. When group-adapted mice were transferred into single housing (social isolation) one week prior to MB-231 tumor cell injection into a mammary fat pad (orthotopic), no alterations in tumor growth or metastasis were detected compared to group-housed mice. When social isolation was delayed until tumors were palpable, tumor growth was transiently increased in singly-housed mice. To determine if sympathetic nervous system activation was associated with increased tumor growth, spleen and tumor norepinephrine (NE) was measured after social isolation, in conjunction with tumor-promoting macrophage populations. Three days after transfer to single housing, spleen weight was transiently increased in tumor-bearing and non-tumor-bearing mice in conjunction with reduced splenic NE concentration and elevated CD11b+Gr-1+ macrophages. At day 10 after social isolation, no changes in spleen CD11b+ populations or NE were detected in singly-housed mice. In the tumors, social isolation increased CD11b+Gr-1+, CD11b+Gr-1-, and F4/80+ macrophage populations, with no change in tumor NE. The results indicate that a psychological stressor, social isolation, elicits dynamic but transient effects on macrophage populations that may facilitate tumor growth. The transiency of the changes in peripheral NE suggest that homeostatic mechanisms may mitigate the impact of social isolation over time. Studies are underway to define the neuroendocrine mechanisms underlying the

  4. VEGFR2-Targeted Ultrasound Imaging Agent Enhances the Detection of Ovarian Tumors at Early Stage in Laying Hens, a Preclinical Model of Spontaneous Ovarian Cancer.

    PubMed

    Barua, Animesh; Yellapa, Aparna; Bahr, Janice M; Machado, Sergio A; Bitterman, Pincas; Basu, Sanjib; Sharma, Sameer; Abramowicz, Jacques S

    2015-07-01

    Tumor-associated neoangiogenesis (TAN) is an early event in ovarian cancer (OVCA) development. Increased expression of vascular endothelial growth factor receptor 2 (VEGFR2) by TAN vessels presents a potential target for early detection by ultrasound imaging. The goal of this study was to examine the suitability of VEGFR2-targeted ultrasound contrast agents in detecting spontaneous OVCA in laying hens. Effects of VEGFR2-targeted contrast agents in enhancing the intensity of ultrasound imaging from spontaneous ovarian tumors in hens were examined in a cross-sectional study. Enhancement in the intensity of ultrasound imaging was determined before and after injection of VEGFR2-targeted contrast agents. All ultrasound images were digitally stored and analyzed off-line. Following scanning, ovarian tissues were collected and processed for histology and detection of VEGFR2-expressing microvessels. Enhancement in visualization of ovarian morphology was detected by gray-scale imaging following injection of VEGFR2-targeted contrast agents. Compared with pre-contrast, contrast imaging enhanced the intensities of ultrasound imaging significantly (p < 0.0001) irrespective of the pathological status of ovaries. In contrast to normal hens, the intensity of ultrasound imaging was significantly (p < 0.0001) higher in hens with early stage OVCA and increased further in hens with late stage OVCA. Higher intensities of ultrasound imaging in hens with OVCA were positively correlated with increased (p < 0.0001) frequencies of VEGFR2-expressing microvessels. The results of this study suggest that VEGFR2-targeted contrast agents enhance the visualization of spontaneous ovarian tumors in hens at early and late stages of OVCA. The laying hen may be a suitable model to test new imaging agents and develop targeted therapeutics. © The Author(s) 2014.

  5. Clinical Development of VEGF Signaling Pathway Inhibitors in Childhood Solid Tumors

    PubMed Central

    Yamashiro, Darrell J.; Fox, Elizabeth

    2011-01-01

    Angiogenesis is a target shared by both adult epithelial cancers and the mesenchymal or embryonal tumors of childhood. Development of antiangiogenic agents for the pediatric population has been complicated by largely theoretical concern for toxicities specific to the growing child and prioritization among the many antiangiogenic agents being developed for adults. This review summarizes the mechanism of action and preclinical data relevant to childhood cancers and early-phase clinical trials in childhood solid tumors. Single-agent adverse event profiles in adults and children are reviewed with emphasis on cardiovascular, bone health, and endocrine side effects. In addition, pharmacological factors that may be relevant for prioritizing clinical trials of these agents in children are reviewed. Considerations for further clinical evaluation should include preclinical data, relative potency, efficacy in adults, and the current U.S. Food and Drug Administration approval status. Toxicity profiles of vascular endothelial growth factor (VEGF) signaling pathway inhibitors may be age dependent and ultimately, their utility in the treatment of childhood cancer will require combination with standard cytotoxic drugs or other molecularly targeted agents. In combination studies, toxicity profiles, potential drug interactions, and late effects must be considered. Studies to assess the long-term impact of VEGF signaling pathway inhibitors on cardiovascular, endocrine, and bone health in children with cancer are imperative if these agents are to be administered to growing children and adolescents with newly diagnosed cancers. PMID:22042784

  6. Early literacy and early numeracy: the value of including early literacy skills in the prediction of numeracy development.

    PubMed

    Purpura, David J; Hume, Laura E; Sims, Darcey M; Lonigan, Christopher J

    2011-12-01

    The purpose of this study was to examine whether early literacy skills uniquely predict early numeracy skills development. During the first year of the study, 69 3- to 5-year-old preschoolers were assessed on the Preschool Early Numeracy Skills (PENS) test and the Test of Preschool Early Literacy Skills (TOPEL). Participants were assessed again a year later on the PENS test and on the Applied Problems and Calculation subtests of the Woodcock-Johnson III Tests of Achievement. Three mixed effect regressions were conducted using Time 2 PENS, Applied Problems, and Calculation as the dependent variables. Print Knowledge and Vocabulary accounted for unique variance in the prediction of Time 2 numeracy scores. Phonological Awareness did not uniquely predict any of the mathematics domains. The findings of this study identify an important link between early literacy and early numeracy development. Copyright © 2011 Elsevier Inc. All rights reserved.

  7. Tumor-host signaling interaction reveals a systemic, age-dependent splenic immune influence on tumor development

    PubMed Central

    Beheshti, Afshin; Wage, Justin; McDonald, J. Tyson; Lamont, Clare; Peluso, Michael; Hahnfeldt, Philip; Hlatky, Lynn

    2015-01-01

    The concept of age-dependent host control of cancer development raises the natural question of how these effects manifest across the host tissue/organ types with which a tumor interacts, one important component of which is the aging immune system. To investigate this, changes in the spleen, an immune nexus in the mouse, was examined for its age-dependent interactive influence on the carcinogenesis process. The model is the C57BL/6 male mice (adolescent, young adult, middle-aged, and old or 68, 143, 551 and 736 days old respectively) with and without a syngeneic murine tumor implant. Through global transcriptome analysis, immune-related functions were found to be key regulators in the spleen associated with tumor progression as a function of age with CD2, CD3ε, CCL19, and CCL5 being the key molecules involved. Surprisingly, other than CCL5, all key factors and immune-related functions were not active in spleens from non-tumor bearing old mice. Our findings of age-dependent tumor-spleen signaling interaction suggest the existence of a global role of the aging host in carcinogenesis. Suggested is a new avenue for therapeutic improvement that capitalizes on the pervasive role of host aging in dictating the course of this disease. PMID:26497558

  8. Early Effects of Combretastatin A4 Phosphate Assessed by Anatomic and Carbogen-Based Functional Magnetic Resonance Imaging on Rat Bladder Tumors Implanted in Nude Mice1

    PubMed Central

    Thomas, Carole D.; Walczak, Christine; Kaffy, Julia; Pontikis, Renée; Jouanneau, Jacqueline; Volk, Andreas

    2006-01-01

    Abstract Combretastatin A4 phosphate (CA4P) causes rapid disruption of the tumor vasculature and is currently being evaluated for antivascular therapy. We describe the initial results obtained with a noninvasive multi-parametric magnetic resonance imaging (MRI) approach to assess the early effects of CA4P on rat bladder tumors implanted on nude mice. MRI (4.7 T) comprised a fast spin-echo sequence for growth curve assessment; a multislice multiecho sequence for T2 measurement before, 15 minutes after, and 24 hours after CA4P (100 mg/kg); and a fast T2w* gradient-echo sequence to assess MR signal modification under carbogen breathing before, 35 minutes after, and 24 hours after CA4P. The tumor fraction with increased T2w* signal intensity under carbogen (T+) was used to quantify CA4P effect on functional vasculature. CA4P slowed tumor growth over 24 hours and accelerated necrosis development. T+ decrease was observed already at 35 minutes post-CA4P. Early T2 increase was observed in regions becoming necrotic at 24 hours post-CA4P, as confirmed by high T2 and histology. These regions exhibited, under carbogen, a switch from T2w* signal increase before CA4P to a decrease post-CA4P. The combination of carbogen-based functional MRI and T2 measurement may be useful for the early follow-up of antivascular therapy without the administration of contrast agents. PMID:16867221

  9. Conceptions of and Early Childhood Educators' Experiences in Early Childhood Professional Development Programs: A Qualitative Metasynthesis

    ERIC Educational Resources Information Center

    Brown, Christopher P.; Englehardt, Joanna

    2016-01-01

    Policy makers and early childhood stakeholders across the United States continue to seek policy solutions that improve early educators' instruction of young children. A primary vehicle for attaining this goal is professional development. This has led to an influx of empirical studies that seek to develop a set of best practices for professional…

  10. Constructivist Early Education for Moral Development.

    ERIC Educational Resources Information Center

    DeVries, Rheta; Hildebrandt, Carolyn; Zan, Betty

    2000-01-01

    Examines role that constructivist teachers play in fostering moral development in young children. Traces development of perspective taking, autonomy, and self- regulation, and examines effects of different teaching and parenting practices on children's character development. Provides suggestions for teachers to promote optimal moral development by…

  11. Hepatitis B virus X protein shifts human hepatic transforming growth factor (TGF)-beta signaling from tumor suppression to oncogenesis in early chronic hepatitis B.

    PubMed

    Murata, Miki; Matsuzaki, Koichi; Yoshida, Katsunori; Sekimoto, Go; Tahashi, Yoshiya; Mori, Shigeo; Uemura, Yoshiko; Sakaida, Noriko; Fujisawa, Junichi; Seki, Toshihito; Kobayashi, Kazuki; Yokote, Koutaro; Koike, Kazuhiko; Okazaki, Kazuichi

    2009-04-01

    Hepatitis B virus X (HBx) protein is suspected to participate in oncogenesis during chronic hepatitis B progression. Transforming growth factor beta (TGF-beta) signaling involves both tumor suppression and oncogenesis. TGF-beta activates TGF-beta type I receptor (TbetaRI) and c-Jun N-terminal kinase (JNK), which differentially phosphorylate the mediator Smad3 to become C-terminally phosphorylated Smad3 (pSmad3C) and linker-phosphorylated Smad3 (pSmad3L). Reversible shifting of Smad3-mediated signaling between tumor suppression and oncogenesis in HBx-expressing hepatocytes indicated that TbetaRI-dependent pSmad3C transmitted a tumor-suppressive TGF-beta signal, while JNK-dependent pSmad3L promoted cell growth. We used immunostaining, immunoblotting, and in vitro kinase assay to compare pSmad3L- and pSmad3C-mediated signaling in biopsy specimens representing chronic hepatitis, cirrhosis, or hepatocellular carcinoma (HCC) from 90 patients chronically infected with hepatitis B virus (HBV) with signaling in liver specimens from HBx transgenic mice. In proportion to plasma HBV DNA levels, early chronic hepatitis B specimens showed prominence of pSmad3L in hepatocytic nuclei. HBx-activated JNK/pSmad3L/c-Myc oncogenic pathway was enhanced, while the TbetaRI/pSmad3C/p21(WAF1) tumor-suppressive pathway was impaired as human and mouse HBx-associated hepatocarcinogenesis progressed. Of 28 patients with chronic hepatitis B who showed strong oncogenic pSmad3L signaling, six developed HCC within 12 years; only one of 32 patients showing little pSmad3L developed HCC. In contrast, seven of 30 patients with little Smad3C phosphorylation developed HCC, while no patient who retained hepatocytic tumor-suppressive pSmad3C developed HCC within 12 years. HBx shifts hepatocytic TGF-beta signaling from the tumor-suppressive pSmad3C pathway to the oncogenic pSmad3L pathway in early carcinogenic process. Hepatocytic pSmad3L and pSmad3C assessment in HBV-infected liver specimens should prove

  12. Redefining Leadership: Lessons from an Early Education Leadership Development Initiative

    ERIC Educational Resources Information Center

    Douglass, Anne

    2018-01-01

    This study examined how experienced early educators developed as change agents in the context of a leadership development program. Unlike in many other professions, experienced early educators lack opportunities to grow throughout their careers and access the supports they need to lead change in their classrooms, organizations, the profession, and…

  13. Promoting Professional Development for Physical Therapists in Early Intervention

    ERIC Educational Resources Information Center

    Catalino, Tricia; Chiarello, Lisa A.; Long, Toby; Weaver, Priscilla

    2015-01-01

    Early intervention service providers are expected to form cohesive teams to build the capacity of a family to promote their child's development. Given the differences in personnel preparation across disciplines of service providers, the Early Childhood Personnel Center is creating integrated and comprehensive professional development models for…

  14. Investments for Future: Early Childhood Development and Education

    ERIC Educational Resources Information Center

    Kartal, Hulya

    2007-01-01

    Investments relevant to the first years of life are directly connected to the future of societies. It can be argued that investments for early childhood development and education are one of the best ways of decreasing social inequality caused by adverse environments which hinder development in early ages and tackling poverty by reducing the rate…

  15. Assessing Home Environment for Early Child Development in Pakistan

    ERIC Educational Resources Information Center

    Nadeem, Sanober; Rafique, Ghazala; Khowaja, Liaquat; Yameen, Anjum

    2014-01-01

    Family environment plays a very important role in early child development and the availability of stimulating material in the early years of a child's life is crucial for optimising development. The Home Observation for Measurement of the Environment (HOME) inventory is one of the most widely used measures to assess the quality and quantity of…

  16. Early Communication Development and Intervention for Children with Autism

    ERIC Educational Resources Information Center

    Landa, Rebecca

    2007-01-01

    Autism is a neurodevelopmental disorder defined by impairments in social and communication development, accompanied by stereotyped patterns of behavior and interest. The focus of this paper is on the early development of communication in autism, and early intervention for impairments in communication associated with this disorder. An overview of…

  17. G protein-coupled receptor 30 in tumor development.

    PubMed

    Wang, Dengfeng; Hu, Lina; Zhang, Guonan; Zhang, Lin; Chen, Chen

    2010-08-01

    Estrogen plays several important physiological and pathological functions in not only reproductive system but many other systems as well. Its transcriptional activation has been traditionally described as being mediated by classic nuclear estrogen receptors (ERs). It is however established recently that a novel functional estrogen transmembrane receptor, G protein-coupled receptor 30 (GPR30), modulates both rapid non-genomic events and genomic transcriptional events of estrogen. It has been demonstrated that GPR30 promotes the progress of estrogen-related tumors through mitogen-activated protein kinase (MAPK) signaling pathways. Effects mediated by GPR30 are maintained when classic ERs are absent or blocked. In addition, GPR30 is involved in drug resistance, which is often occurring during cancer treatments. All these new findings strongly imply that GPR30 may be an important therapeutic target for estrogen-related tumors. Simultaneously blocking both GPR30 and classic ERs may be a better strategy for the treatment of estrogen-related tumors.

  18. Comparative transcriptomics of early dipteran development

    PubMed Central

    2013-01-01

    Background Modern sequencing technologies have massively increased the amount of data available for comparative genomics. Whole-transcriptome shotgun sequencing (RNA-seq) provides a powerful basis for comparative studies. In particular, this approach holds great promise for emerging model species in fields such as evolutionary developmental biology (evo-devo). Results We have sequenced early embryonic transcriptomes of two non-drosophilid dipteran species: the moth midge Clogmia albipunctata, and the scuttle fly Megaselia abdita. Our analysis includes a third, published, transcriptome for the hoverfly Episyrphus balteatus. These emerging models for comparative developmental studies close an important phylogenetic gap between Drosophila melanogaster and other insect model systems. In this paper, we provide a comparative analysis of early embryonic transcriptomes across species, and use our data for a phylogenomic re-evaluation of dipteran phylogenetic relationships. Conclusions We show how comparative transcriptomics can be used to create useful resources for evo-devo, and to investigate phylogenetic relationships. Our results demonstrate that de novo assembly of short (Illumina) reads yields high-quality, high-coverage transcriptomic data sets. We use these data to investigate deep dipteran phylogenetic relationships. Our results, based on a concatenation of 160 orthologous genes, provide support for the traditional view of Clogmia being the sister group of Brachycera (Megaselia, Episyrphus, Drosophila), rather than that of Culicomorpha (which includes mosquitoes and blackflies). PMID:23432914

  19. History and early development of INCAP.

    PubMed

    Scrimshaw, Nevin S

    2010-02-01

    Nevin Scrimshaw was the founding Director of the Institute of Nutrition of Central America and Panama (INCAP), serving as Director from 1949 to 1961. In this article, he reviews the history of the founding of INCAP, including the role of the Rockefeller and Kellogg Foundations, the Central American governments, and the Pan American Health Organization. The objectives pursued by INCAP in its early years were to assess the nutrition and related health problems of Central America, to carry out research to find practical solutions to these problems, and to provide technical assistance to its member countries to implement solutions. INCAP pursued a strategy of selecting promising Central Americans for advanced education and training in the US who assumed positions of leadership on their return. After this early phase, talented non-Central Americans of diverse origins were brought to INCAP, as well as additional researchers from the region. Growth of INCAP, as reflected in its annual budget and in the physical plant, was rapid and this was accompanied by high scientific productivity. Several field studies were launched that contributed impetus and design elements for the Oriente Longitudinal Study, which is the focus of this supplement.

  20. Developments in early intervention for psychosis in Hong Kong.

    PubMed

    Wong, G H Y; Hui, C L M; Wong, D Y; Tang, J Y M; Chang, W C; Chan, S K W; Lee, E H M; Xu, J Q; Lin, J J X; Lai, D C; Tam, W; Kok, J; Chung, D W S; Hung, S F; Chen, E Y H

    2012-09-01

    The year 2011 marked the 10-year milestone of early intervention for psychosis in Hong Kong. Since 2001, the landscape of early psychosis services has changed markedly in Hong Kong. Substantial progress has been made in the areas of early intervention service implementation, knowledge generation, and public awareness promotion. Favourable outcomes attributable to the early intervention service are supported by solid evidence from local clinical research studies; early intervention service users showed improved functioning, ameliorated symptoms, and decreased hospitalisation and suicide rates. Continued development of early intervention in Hong Kong over the decade includes the introduction and maturation of several key platforms, such as the Hospital Authority Early Assessment Service for Young People with Psychosis programme, the Psychosis Studies and Intervention Unit by the University of Hong Kong, the Hong Kong Early Psychosis Intervention Society, the Jockey Club Early Psychosis Project, and the postgraduate Psychological Medicine (Psychosis Studies) programme. In this paper, we reviewed some of the major milestones in local service development with reference to features of the Hong Kong mental health system. We describe chronologically the implementation and consolidation of public early intervention services as well as recent progresses in public awareness work that are tied in with knowledge generation and transfer, and outline the prospects for early intervention in the next decade and those that follow.

  1. Sex Role Development in Early Adolescence.

    ERIC Educational Resources Information Center

    Wittig, Michele Andrisin

    1983-01-01

    Research involving adolescent identification with and development of sex roles is reviewed in the areas of cognitive skills and personality traits, theories of sex role development, and minority group adolescent sex role development. Emerging issues and educational implications in these areas are discussed. (CJ)

  2. Development of Advanced Technologies for Complete Genomic and Proteomic Characterization of Quantized Human Tumor Cells

    DTIC Science & Technology

    2014-07-01

    establishment of Glioblastoma ( GBM ) cell lines from GBM patient’s tumor samples and quantized cell populations of each of the parental GBM cell lines, we... GBM patients are now well established and from the basis of the molecular characterization of the tumor development and signatures presented by these...analysis of these quantized cell sub populations and have begun to assemble the protein signatures of GBM tumors underpinned by the comprehensive

  3. Maternal high fat diet promotion of mammary tumor risk in adult progeny is associated with early expansion of mammary cancer stem-like cells and increased maternal oxidative environment

    Many adult chronic diseases might be programmed during early life by maternal nutritional history. Here, we evaluated effects of maternal high fat diet on mammary gland development and tumor formation in adult progeny. Female Wnt-1 transgenic mice exposed to high fat (HFD, 45% kcal fat) or control C...

  4. The development of Wilms tumor: from WT1 and microRNA to animal models.

    PubMed

    Tian, Fang; Yourek, Gregory; Shi, Xiaolei; Yang, Yili

    2014-08-01

    Wilms tumor recapitulates the development of the kidney and represents a unique opportunity to understand the relationship between normal and tumor development. This has been illustrated by the findings that mutations of Wnt/β-catenin pathway-related WT1, β-catenin, and WTX together account for about one-third of Wilms tumor cases. While intense efforts are being made to explore the genetic basis of the other two-thirds of tumor cases, it is worth noting that, epigenetic changes, particularly the loss of imprinting of the DNA region encoding the major fetal growth factor IGF2, which results in its biallelic over-expression, are closely associated with the development of many Wilms tumors. Recent investigations also revealed that mutations of Drosha and Dicer, the RNases required for miRNA generation, and Dis3L2, the 3'-5' exonuclease that normally degrades miRNAs and mRNAs, could cause predisposition to Wilms tumors, demonstrating that miRNA can play a pivotal role in Wilms tumor development. Interestingly, Lin28, a direct target of miRNA let-7 and potent regulator of stem cell self-renewal and differentiation, is significantly elevated in some Wilms tumors, and enforced expression of Lin28 during kidney development could induce Wilms tumor. With the success in establishing mice nephroblastoma models through over-expressing IGF2 and deleting WT1, and advances in understanding the ENU-induced rat model, we are now able to explore the molecular and cellular mechanisms induced by these genetic, epigenetic, and miRNA alterations in animal models to understand the development of Wilms tumor. These animal models may also serve as valuable systems to assess new treatment targets and strategies for Wilms tumor. Copyright © 2014 Elsevier B.V. All rights reserved.

  5. Frequent silencing of the candidate tumor suppressor TRIM58 by promoter methylation in early-stage lung adenocarcinoma

    PubMed Central

    Naruto, Takuya; Kohmoto, Tomohiro; Watabnabe, Miki; Tsuboi, Mitsuhiro; Takizawa, Hiromitsu; Kondo, Kazuya; Tangoku, Akira; Imoto, Issei

    2017-01-01

    In this study, we aimed to identify novel drivers that would be epigenetically altered through aberrant methylation in early-stage lung adenocarcinoma (LADC), regardless of the presence or absence of tobacco smoking-induced epigenetic field defects. Through genome-wide screening for aberrantly methylated CpG islands (CGIs) in 12 clinically uniform, stage-I LADC cases affecting six non-smokers and six smokers, we identified candidate tumor-suppressor genes (TSGs) inactivated by hypermethylation. Through systematic expression analyses of those candidates in panels of additional tumor samples and cell lines treated or not treated with 5-aza-deoxycitidine followed by validation analyses of cancer-specific silencing by CGI hypermethylation using a public database, we identified TRIM58 as the most prominent candidate for TSG. TRIM58 was robustly silenced by hypermethylation even in early-stage primary LADC, and the restoration of TRIM58 expression in LADC cell lines inhibited cell growth in vitro and in vivo in anchorage-dependent and -independent manners. Our findings suggest that aberrant inactivation of TRIM58 consequent to CGI hypermethylation might stimulate the early carcinogenesis of LADC regardless of smoking status; furthermore, TRIM58 methylation might be a possible early diagnostic and epigenetic therapeutic target in LADC. PMID:27926516

  6. Frequent silencing of the candidate tumor suppressor TRIM58 by promoter methylation in early-stage lung adenocarcinoma.

    PubMed

    Kajiura, Koichiro; Masuda, Kiyoshi; Naruto, Takuya; Kohmoto, Tomohiro; Watabnabe, Miki; Tsuboi, Mitsuhiro; Takizawa, Hiromitsu; Kondo, Kazuya; Tangoku, Akira; Imoto, Issei

    2017-01-10

    In this study, we aimed to identify novel drivers that would be epigenetically altered through aberrant methylation in early-stage lung adenocarcinoma (LADC), regardless of the presence or absence of tobacco smoking-induced epigenetic field defects. Through genome-wide screening for aberrantly methylated CpG islands (CGIs) in 12 clinically uniform, stage-I LADC cases affecting six non-smokers and six smokers, we identified candidate tumor-suppressor genes (TSGs) inactivated by hypermethylation. Through systematic expression analyses of those candidates in panels of additional tumor samples and cell lines treated or not treated with 5-aza-deoxycitidine followed by validation analyses of cancer-specific silencing by CGI hypermethylation using a public database, we identified TRIM58 as the most prominent candidate for TSG. TRIM58 was robustly silenced by hypermethylation even in early-stage primary LADC, and the restoration of TRIM58 expression in LADC cell lines inhibited cell growth in vitro and in vivo in anchorage-dependent and -independent manners. Our findings suggest that aberrant inactivation of TRIM58 consequent to CGI hypermethylation might stimulate the early carcinogenesis of LADC regardless of smoking status; furthermore, TRIM58 methylation might be a possible early diagnostic and epigenetic therapeutic target in LADC.

  7. Functional insulin receptors are overexpressed in thyroid tumors: is this an early event in thyroid tumorigenesis?

    PubMed

    Frittitta, L; Sciacca, L; Catalfamo, R; Ippolito, A; Gangemi, P; Pezzino, V; Filetti, S; Vigneri, R

    1999-01-15

    Insulin receptor (IR), a member of the receptor tyrosine kinase family, is expressed in normal thyroid cells and affects thyroid cell proliferation and differentiation. The authors measured IR content in benign and malignant thyroid tumors by three independent methods: a specific radioimmunoassay, 125I-insulin binding studies, and immunohistochemistry. The results obtained were compared with the IR content in paired, adjacent, normal thyroid tissue. To assess IR function in thyroid carcinoma cells, glucose uptake responsiveness to insulin was also studied in a human transformed thyroid cell line (B-CPAP) and in follicular carcinoma cells in primary culture. In 9 toxic adenomas, the average IR content was similar to that observed in the 9 paired normal thyroid tissue specimens from the same patients (2.2+/-0.3 vs. 2.1+/-0.3). In 13 benign nonfunctioning, or "cold," adenomas, the average IR content was significantly higher (P < 0.001) than in paired normal tissue specimens (4.3+/-0.5 vs. 1.8+/-0.1). In 12 papillary and 10 follicular carcinomas, IR content was significantly higher (P < 0.001) than in the adjacent normal thyroid tissue (4.0+/-0.4 vs. 1.6+/-0.2 and 5.6+/-1.0 vs. 1.8+/-0.2, respectively). The finding of a higher IR content in benign "cold" adenomas and in thyroid carcinomas was confirmed by both binding and immunostaining studies. The current studies indicate that 1) IR content is elevated in most follicular and papillary differentiated thyroid carcinomas, and 2) IR content is also elevated in most benign follicular adenomas ("cold" nodules) but not in highly differentiated, hyperfunctioning follicular adenomas ("hot" nodules), which very rarely become malignant. This observation suggests that increased IR expression is not restricted to the thyroid malignant phenotype but is already present in the premalignant "cold" adenomas. It may contribute, therefore, to thyroid tumorigenesis and/or represent an early event that gives a selective growth advantage

  8. Selenium Reduces Early Signs of Tumor Necrosis Factor Alpha-Induced Meniscal Tissue Degradation.

    PubMed

    Häfelein, Klaus; Preuße-Prange, Andrea; Behrendt, Peter; Kurz, Bodo

    2017-05-01

    Meniscal integrity is a prerequisite for sustained knee joint health and prevention of meniscal degeneration is a main research goal. Cartilage-protective effects of selenium have been described, but little is known about the impact on the meniscus. We therefore investigated the influence of sodium selenite on meniscal explants under tumor necrosis factor-alpha (TNFα)-stimulated proinflammatory conditions. Meniscal explant disks (3 mm diameter × 1 mm thickness) were isolated from 2-year-old cattle and incubated with TNFα (10 ng/ml) and sodium selenite (low dose, LoD 6.7 ng/ml as being found in Insulin-Transferrin-Selenium medium supplements, ITS; medium-dose, MeD 40 ng/ml described as physiological synovial concentration; high dose, HiD 100 ng/ml described as optimal serum concentration). After 3 days of culture glycosaminoglycan (GAG) release (DMMB assay), nitric oxide (NO) production (Griess assay), gene expression of matrix-degrading enzymes (quantitative RT-PCR), and apoptosis rate were determined. TNFα led to a significant raise of GAG release and NO production. LoD and MeD selenite significantly reduced the TNFα-induced GAG release (by 83, 55 %, respectively), NO production (by 59, 40 %, respectively), and apoptosis (by 68, 39 %, respectively). LoD and MeD selenite showed a tendency to reduce the TNFα-mediated increase of inducible NO-synthase (iNOS) levels, LoD selenite furthermore matrix metalloproteinase (MMP)-3 transcription levels and a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS)-4 levels. LoD and less pronounced MeD selenite show a substantial impact on the early meniscal inflammatory response. To our knowledge this is the first study showing the protective influence of selenium on meniscal tissue maintenance. To understand the superior potency of low-dose selenium on molecular level future studies are needed.

  9. Early Numeracy Assessment: The Development of the Preschool Early Numeracy Scales

    ERIC Educational Resources Information Center

    Purpura, David J.; Lonigan, Christopher J.

    2015-01-01

    Research Findings: The focus of this study was to construct and validate 12 brief early numeracy assessment tasks that measure the skills and concepts identified as key to early mathematics development by the National Council of Teachers of Mathematics (2006) and the National Mathematics Advisory Panel (2008)-as well as critical developmental…

  10. Parents Resourcing Children's Early Development and Learning

    ERIC Educational Resources Information Center

    Nichols, Sue; Nixon, Helen; Pudney, Valerie; Jurvansuu, Sari

    2009-01-01

    Parents deal with a complex web of choices when seeking and using knowledge and resources related to their young children's literacy development. Information concerning children's learning and development comes in many forms and is produced by an increasingly diverse range of players including governments, non-government organizations and…

  11. [Basics of tumor development and importance of human papilloma virus (HPV) for head and neck cancer].

    PubMed

    Wittekindt, C; Wagner, S; Mayer, C S; Klußmann, J P

    2012-03-01

    Head and Neck Squamous Cell Carcinoma (HNSCC) are the 6th most common cancers worldwide. While the incidence of larynx-hypopharynx carcinoma decreases, actually an increase in oropharyngeal squamous cell carcinoma (OSCC) is observed. Classical risk factors for HNSCC are smoking and alcohol. Though, it was shown recently for 25 to 60% of OSCC, to be associated with an infection by oncogenic human papilloma virus (HPV). The development of "common" head-neck-tumors is substantially enhanced by an accumulation of genetic changes, which lead to an inactivation of tumor suppressor genes or to an activation of proto-oncogenes. A more or less uniform sequence of different DNA-damages leads to genetic instability. In this context, an early and frequent event is deletion on the short arm of chromosome 9, which results in inactivation of the p16-gene. On the contrary, for HPV-induced carcinogenesis, expression of the viral proteins E6 and E7 is most important, since E6 and E7 lead to inactivation of the cellular tumor-suppressor-proteins p53 and Rb. The process of natural transoral infection is not yet clear. However, as a matter of fact peroral HPV-infection is not seldom and in most cases such an infection heals completely and uneventfully. Smoking seems to increases the probability for developing an HPV-associated tumor. The association of HNSCC with HPV can be proven with established methods in clinical diagnostics. In addition to classical prognostic factors, diagnosis of an HPV-association may become important for future therapies. Prognostic relevance of HPV probably surmounts many known risk-factors, for instance regional metastasis. Until now, no other molecular markers are established in clinical routine. Future therapy concepts may vary for the two subgroups of patients, especially patients with HPV-associated OSCC may take advantage of a less aggressive postoperative treatment. Finally an outlook will be given on possible target-aimed therapies, of which so far

  12. Comparison between the early cellular response to electron radiation and the production of tumors

    SciT

    Sinclair, Ian P.

    1972-11-01

    The aim of the study is to quantitate radiation-induced cell population changes in various epithelial components of rat skin and to correlate them, if possible with the subsequent production of tumors.

  13. FTIR spectro-imaging of collagen scaffold formation during glioma tumor development.

    PubMed

    Noreen, Razia; Chien, Chia-Chi; Chen, Hsiang-Hsin; Bobroff, Vladimir; Moenner, Michel; Javerzat, Sophie; Hwu, Yeukuang; Petibois, Cyril

    2013-11-01

    Evidence has recently emerged that solid and diffuse tumors produce a specific extracellular matrix (ECM) for division and diffusion, also developing a specific interface with microvasculature. This ECM is mainly composed of collagens and their scaffolding appears to drive tumor growth. Although collagens are not easily analyzable by UV-fluorescence means, FTIR imaging has appeared as a valuable tool to characterize collagen contents in tissues, specially the brain, where ECM is normally devoid of collagen proteins. Here, we used FTIR imaging to characterize collagen content changes in growing glioma tumors. We could determine that C6-derived solid tumors presented high content of triple helix after 8-11 days of growth (typical of collagen fibrils formation; 8/8 tumor samples; 91 % of total variance), and further turned to larger α-helix (days 12-15; 9/10 of tumors; 94 % of variance) and β-turns (day 18-21; 7/8 tumors; 97 % of variance) contents, which suggest the incorporation of non-fibrillar collagen types in ECM, a sign of more and more organized collagen scaffold along tumor progression. The growth of tumors was also associated to the level of collagen produced (P < 0.05). This study thus confirms that collagen scaffolding is a major event accompanying the angiogenic shift and faster tumor growth in solid glioma phenotypes.

  14. Ranitidine modifies myeloid cell populations and inhibits breast tumor development and spread in mice

    PubMed Central

    Vila-Leahey, Ava; Oldford, Sharon A.; Marignani, Paola A.; Wang, Jun; Haidl, Ian D.; Marshall, Jean S.

    2016-01-01

    ABSTRACT Histamine receptor 2 (H2) antagonists are widely used clinically for the control of gastrointestinal symptoms, but also impact immune function. They have been reported to reduce tumor growth in established colon and lung cancer models. Histamine has also been reported to modify populations of myeloid-derived suppressor cells (MDSCs). We have examined the impact of the widely used H2 antagonist ranitidine, on both myeloid cell populations and tumor development and spread, in three distinct models of breast cancer that highlight different stages of cancer progression. Oral ranitidine treatment significantly decreased the monocytic MDSC population in the spleen and bone marrow both alone and in the context of an orthotopic breast tumor model. H2 antagonists ranitidine and famotidine, but not H1 or H4 antagonists, significantly inhibited lung metastasis in the 4T1 model. In the E0771 model, ranitidine decreased primary tumor growth while omeprazole treatment had no impact on tumor development. Gemcitabine treatment prevented the tumor growth inhibition associated with ranitidine treatment. In keeping with ranitidine-induced changes in myeloid cell populations in non-tumor-bearing mice, ranitidine also delayed the onset of spontaneous tumor development, and decreased the number of tumors that developed in LKB1−/−/NIC mice. These results indicate that ranitidine alters monocyte populations associated with MDSC activity, and subsequently impacts breast tumor development and outcome. Ranitidine has potential as an adjuvant therapy or preventative agent in breast cancer and provides a novel and safe approach to the long-term reduction of tumor-associated immune suppression. PMID:27622015

  15. Early psychosis workforce development: Core competencies for mental health professionals working in the early psychosis field.

    PubMed

    Osman, Helen; Jorm, Anthony F; Killackey, Eoin; Francey, Shona; Mulcahy, Dianne

    2017-08-09

    The aim of this study was to identify the core competencies required of mental health professionals working in the early psychosis field, which could function as an evidence-based tool to support the early psychosis workforce and in turn assist early psychosis service implementation and strengthen early psychosis model fidelity. The Delphi method was used to establish expert consensus on the core competencies. In the first stage, a systematic literature search was conducted to generate competency items. In the second stage, a panel consisting of expert early psychosis clinicians from around the world was formed. Panel members then rated each of the competency items on how essential they are to the clinical practice of all early psychosis clinicians. In total, 1023 pieces of literature including textbooks, journal articles and grey literature were reviewed. A final 542 competency items were identified for inclusion in the questionnaire. A total of 63 early psychosis experts participated in 3 rating rounds. Of the 542 competency items, 242 were endorsed as the required core competencies. There were 29 competency items that were endorsed by 62 or more experts, and these may be considered the foundational competencies for early psychosis practice. The study generated a set of core competencies that provide a common language for early psychosis clinicians across professional disciplines and country of practice, and potentially are a useful professional resource to support early psychosis workforce development and service reform. © 2017 John Wiley & Sons Australia, Ltd.

  16. Early development of fern gametophytes in microgravity

    NASA Technical Reports Server (NTRS)

    Roux, Stanley J.; Chatterjee, Ani; Hillier, Sheila; Cannon, Tom

    2003-01-01

    Dormant spores of the fern Ceratopteris richardii were flown on Shuttle mission STS-93 to evaluate the effects of micro-g on their development and on their pattern of gene expression. Prior to flight the spores were sterilized and sown into one of two environments: (1) Microscope slides in a video-microscopy module; and (2) Petri dishes. All spores were then stored in darkness until use. Spore germination was initiated on orbit after exposure to light. For the spores on microscope slides, cell level changes were recorded through the clear spore coat of the spores by video microscopy. After their exposure to light, spores in petri dishes were frozen in orbit at four different time points during which on earth gravity fixes the polarity of their development. Spores were then stored frozen in Biological Research in Canister units until recovery on earth. The RNAs from these cells and from 1-g control cells were extracted and analyzed on earth after flight to assay changes in gene expression. Video microscopy results revealed that the germinated spores developed normally in microgravity, although the polarity of their development, which is guided by gravity on earth, was random in space. Differential Display-PCR analyses of RNA extracted from space-flown cells showed that there was about a 5% change in the pattern of gene expression between cells developing in micro-g compared to those developing on earth. c2002 Published by Elsevier Science Ltd on behalf of COSPAR.

  17. “Sentinel” Circulating Tumor Cells Allow Early Diagnosis of Lung Cancer in Patients with Chronic Obstructive Pulmonary Disease

    PubMed Central

    Ilie, Marius; Hofman, Véronique; Long-Mira, Elodie; Selva, Eric; Vignaud, Jean-Michel; Padovani, Bernard; Mouroux, Jérôme; Marquette, Charles-Hugo; Hofman, Paul

    2014-01-01

    Chronic obstructive pulmonary disease (COPD) is a risk factor for lung cancer. Migration of circulating tumor cells (CTCs) into the blood stream is an early event that occurs during carcinogenesis. We aimed to examine the presence of CTCs in complement to CT-scan in COPD patients without clinically detectable lung cancer as a first step to identify a new marker for early lung cancer diagnosis. The presence of CTCs was examined by an ISET filtration-enrichment technique, for 245 subjects without cancer, including 168 (68.6%) COPD patients, and 77 subjects without COPD (31.4%), including 42 control smokers and 35 non-smoking healthy individuals. CTCs were identified by cytomorphological analysis and characterized by studying their expression of epithelial and mesenchymal markers. COPD patients were monitored annually by low-dose spiral CT. CTCs were detected in 3% of COPD patients (5 out of 168 patients). The annual surveillance of the CTC-positive COPD patients by CT-scan screening detected lung nodules 1 to 4 years after CTC detection, leading to prompt surgical resection and histopathological diagnosis of early-stage lung cancer. Follow-up of the 5 patients by CT-scan and ISET 12 month after surgery showed no tumor recurrence. CTCs detected in COPD patients had a heterogeneous expression of epithelial and mesenchymal markers, which was similar to the corresponding lung tumor phenotype. No CTCs were detected in control smoking and non-smoking healthy individuals. CTCs can be detected in patients with COPD without clinically detectable lung cancer. Monitoring “sentinel” CTC-positive COPD patients may allow early diagnosis of lung cancer. PMID:25360587

  18. Tumor inoculation site affects the development of cancer cachexia and muscle wasting.

    PubMed

    Matsuyama, Tatsuzo; Ishikawa, Takeshi; Okayama, Tetsuya; Oka, Kaname; Adachi, Satoko; Mizushima, Katsura; Kimura, Reiko; Okajima, Manabu; Sakai, Hiromi; Sakamoto, Naoyuki; Katada, Kazuhiro; Kamada, Kazuhiro; Uchiyama, Kazuhiko; Handa, Osamu; Takagi, Tomohisa; Kokura, Satoshi; Naito, Yuji; Itoh, Yoshito

    2015-12-01

    The phenotype and severity of cancer cachexia differ among tumor types and metastatic site in individual patients. In this study, we evaluated if differences in tumor microenvironment would affect the development of cancer cachexia in a murine model, and demonstrated that body weight, adipose tissue and gastrocnemius muscle decreased in tumor-bearing mice. Interestingly, a reduction in heart weight was observed in the intraperitoneal tumor group but not in the subcutaneous group. We evaluated 23 circulating cytokines and members of the TGF-β family, and found that levels of IL-6, TNF-α and activin A increased in both groups of tumor-bearing mice. Eotaxin and G-CSF levels in the intraperitoneal tumor group were higher than in the subcutaneous group. Atrogin 1 and MuRF1 mRNA expressions in the gastrocnemius muscle increased significantly in both groups of tumor-bearing mice, however, in the myocardium, expression of these mRNAs increased in the intraperitoneal group but not in subcutaneous group. Based on these results, we believe that differences in microenvironment where tumor cells develop can affect the progression and phenotype of cancer cachexia through alterations in various circulating factors derived from the tumor microenvironment. © 2015 UICC.

  19. Chaos, Poverty, and Parenting: Predictors of Early Language Development

    ERIC Educational Resources Information Center

    Vernon-Feagans, Lynne; Garrett-Peters, Patricia; Willoughby, Michael; Mills-Koonce, Roger

    2012-01-01

    Studies have shown that distal family risk factors like poverty and maternal education are strongly related to children's early language development. Yet, few studies have examined these risk factors in combination with more proximal day-to-day experiences of children that might be critical to understanding variation in early language. Young…

  20. Childhood Immunization: A Key Component of Early Childhood Development

    ERIC Educational Resources Information Center

    Messonnier, Nancy

    2017-01-01

    Physical health is a key component of early childhood development and school readiness. By keeping children healthy and decreasing the chances of disease outbreaks, immunizations help early childhood programs create a safe environment for children. While overall vaccination rates are high nationally for most vaccines routinely recommended for…

  1. Online Professional Development: Choices for Early Childhood Educators

    ERIC Educational Resources Information Center

    Olsen, Heather; Donaldson, Ana J.; Hudson, Susan D.

    2010-01-01

    Early childhood educators are responsible for providing young children with the best possible early care and education. Research on child care workers' education has shown that professional preparation makes a significant impact on children's cognitive and emotional development (National Association for the Education of Young Children [NAEYC],…

  2. Alberta Learning: Early Development Instrument Pilot Project Evaluation.

    ERIC Educational Resources Information Center

    Meaney, Wanda; Harris-Lorenze, Elayne

    The Early Development Instrument (EDI) was designed by McMaster University to measure the outcomes of childrens early years as they influence their readiness to learn at school. The EDI was piloted in several Canadian cities in recent years through two national initiatives. Building on these initiatives, Alberta Learning piloted the EDI as a…

  3. Activities for Career Development in Early Childhood Curriculum.

    ERIC Educational Resources Information Center

    Yawkey, Thomas Daniels; Aronin, Eugene L.

    The book presents career education activities and approaches for use by teachers, administrators, counselors, and students involved in early childhood education (ages three through eight). Part One stresses the importance of and rationale for career development in the early childhood curriculum. Research support for the approach to career…

  4. Family Strategies to Support and Develop Resilience in Early Childhood

    ERIC Educational Resources Information Center

    Taket, A. R.; Nolan, A.; Stagnitti, K.

    2014-01-01

    Early childhood is an important time for the development of resilience. A recently completed study has followed three cohorts of resilient children and young people living in disadvantaged areas in Victoria, Australia, through different transitions in their educational careers. This paper focuses on the early childhood cohort, where we have…

  5. Developing Prosocial Behaviors in Early Adolescence with Reactive Aggression

    ERIC Educational Resources Information Center

    Fung, Annis L. C.

    2008-01-01

    Despite the alarming rise of early adolescence aggression in Hong Kong, it is the pioneer evidence-based outcome study on Anger Coping Training (ACT) program for early adolescence with reactive aggression to develop their prosocial behaviors. This research program involved experimental and control groups with pre- and post-comparison using a …

  6. Early Speech Motor Development: Cognitive and Linguistic Considerations

    ERIC Educational Resources Information Center

    Nip, Ignatius S. B.; Green, Jordan R.; Marx, David B.

    2009-01-01

    This longitudinal investigation examines developmental changes in orofacial movements occurring during the early stages of communication development. The goals were to identify developmental trends in early speech motor performance and to determine how these trends differ across orofacial behaviors thought to vary in cognitive and linguistic…

  7. CD34 EXPRESSION BY HAIR FOLLICLE STEM CELLS IS REQUIRED FOR SKIN TUMOR DEVELOPMENT IN MICE

    EPA Science Inventory

    We used knockout mice to show that a cell surface protein called CD34 is required for skin tumor formation in mice. Wild type mice treated with 7-12-Dimethylbenz(a)anthracene (DMBA) and a tumor promoter developed papillomas. When we treated CD34 knockout (KO) mice the same way, n...

  8. ECR-MAPK regulation in liver early development.

    PubMed

    Zhao, Xiu-Ju; Zhuo, Hexian

    2014-01-01

    Early growth is connected to a key link between embryonic development and aging. In this paper, liver gene expression profiles were assayed at postnatal day 22 and week 16 of age. Meanwhile another independent animal experiment and cell culture were carried out for validation. Significance analysis of microarrays, qPCR verification, drug induction/inhibition assays, and metabonomics indicated that alpha-2u globulin (extracellular region)-socs2 (-SH2-containing signals/receptor tyrosine kinases)-ppp2r2a/pik3c3 (MAPK signaling)-hsd3b5/cav2 (metabolism/organization) plays a vital role in early development. Taken together, early development of male rats is ECR and MAPK-mediated coordination of cancer-like growth and negative regulations. Our data represent the first comprehensive description of early individual development, which could be a valuable basis for understanding the functioning of the gene interaction network of infant development.

  9. Early detection of tumor relapse/regrowth by consecutive minimal residual disease monitoring in high-risk neuroblastoma patients

    PubMed Central

    Hirase, Satoshi; Saitoh, Atsuro; Hartomo, Tri Budi; Kozaki, Aiko; Yanai, Tomoko; Hasegawa, Daiichiro; Kawasaki, Keiichiro; Kosaka, Yoshiyuki; Matsuo, Masafumi; Yamamoto, Nobuyuki; Mori, Takeshi; Hayakawa, Akira; Iijima, Kazumoto; Nishio, Hisahide; Nishimura, Noriyuki

    2016-01-01

    Neuroblastoma is an aggressive pediatric tumor accounting for ~15% of cancer-associated mortalities in children. Despite the current intensive therapy, >50% of high-risk patients experience tumor relapse or regrowth caused by the activation of minimal residual disease (MRD). Although several MRD detection protocols using various reverse transcription-quantitative polymerase chain reaction (RT-qPCR) markers have been reported to evaluate the therapeutic response and disease status of neuroblastoma patients, their clinical significance remains elusive. The present study reports two high-risk neuroblastoma patients, whose MRD was consecutively monitored using 11 RT-qPCR markers (CHRNA3, CRMP1, DBH, DCX, DDC, GABRB3, GAP43, ISL1, KIF1A, PHOX2B and TH) during their course of treatment. The two patients initially responded to the induction therapy and reached MRD-negative status. The patients' MRD subsequently became positive with no elevation of their urinary homovanillic acid, urinary vanillylmandelic acid and serum neuron-specific enolase levels at 13 or 19 weeks prior to the clinical diagnosis of tumor relapse or regrowth. The present cases highlight the possibility of consecutive MRD monitoring using 11 markers to enable an early detection of tumor relapse or regrowth in high-risk neuroblastoma patients. PMID:27446404

  10. Reading Development Subtypes and Their Early Characteristics

    ERIC Educational Resources Information Center

    Torppa, Minna; Tolvanen, Asko; Poikkeus, Anna-Maija; Eklund, Kenneth; Lerkkanen, Marja-Kristiina; Leskinen, Esko; Lyytinen, Heikki

    2007-01-01

    The present findings are drawn from the Jyvaskyla Longitudinal Study of Dyslexia (JLD), in which approximately 100 children with familial risk of dyslexia and 100 control children have been followed from birth. In this paper we report data on the reading development of the JLD children and their classmates, a total of 1,750 children from four…

  11. Developing an Engineering Identity in Early Childhood

    ERIC Educational Resources Information Center

    Pantoya, Michelle L.; Aguirre-Munoz, Zenaida; Hunt, Emily M.

    2015-01-01

    This project describes a strategy to introduce young children to engineering in a way that develops their engineering identity. The targeted age group is 3-7 year old students because they rarely experience purposeful engineering instruction. The curriculum was designed around an engineering storybook and included interactive academic discussions…

  12. Early developments in solar cooling equipment

    NASA Technical Reports Server (NTRS)

    Price, J. M.

    1978-01-01

    A brief description of a development program to design, fabricate and field test a series of solar operated or driven cooling devices, undertaken by the Marshall Space Flight Center in the context of the Solar Heating and Cooling Demonstration Act of 1974, is presented. Attention is given to two basic design concepts: the Rankine cycle principle and the use of a dessicant for cooling.

  13. School Building in Early Development. Part 2.

    ERIC Educational Resources Information Center

    Dijkgraaf, C.; Giertz, L. M.

    1975-01-01

    Development is characterized by urbanization. New settlements grow either as enlargements of existing ones or as new population concentrations. Three periods may be distinguished in the growth of a settlement: (1) the wild period of first settling, (2) the consolidation period, and (3) the stabilized society. The number of school-aged children per…

  14. Economic Deprivation and Early Childhood Development.

    ERIC Educational Resources Information Center

    Duncan, Greg J.; And Others

    1994-01-01

    Examined the relationship between poverty and children's developmental outcomes, the effects of the timing and duration of poverty, and the effects of poverty at the family and neighborhood level, analyzing data from two longitudinal surveys. Found that poverty status was strongly related to low levels of cognitive development, even after…

  15. The Early Development of Programmable Machinery.

    ERIC Educational Resources Information Center

    Collins, Martin D.

    1985-01-01

    Programmable equipment innovations, precursors of today's technology, are examined, including the development of the binary code and feedback control systems, such as temperature sensing devices, interchangeable parts, punched cards carrying instructions, continuous flow oil refining process, assembly lines for mass production, and the…

  16. Plasticity during Early Brain Development Is Determined by Ontogenetic Potential.

    PubMed

    Krägeloh-Mann, Ingeborg; Lidzba, Karen; Pavlova, Marina A; Wilke, Marko; Staudt, Martin

    2017-04-01

    Two competing hypotheses address neuroplasticity during early brain development: the "Kennard principle" describes the compensatory capacities of the immature developing CNS as superior to those of the adult brain, whereas the "Hebb principle" argues that the young brain is especially sensitive to insults. We provide evidence that these principles are not mutually exclusive. Following early brain lesions that are unilateral, the brain can refer to homotopic areas of the healthy hemisphere. This potential for reorganization is unique to the young brain but available only when, during ontogenesis of brain development, these areas have been used for the functions addressed. With respect to motor function, ipsilateral motor tracts can be recruited, which are only available during early brain development. Language can be reorganized to the right after early left hemispheric lesions, as the representation of the language network is initially bilateral. However, even in these situations, compensatory capacities of the developing brain are found to have limitations, probably defined by early determinants. Thus, plasticity and adaptivity are seen only within ontogenetic potential; that is, axonal or cortical structures cannot be recruited beyond early developmental possibilities. The young brain is probably more sensitive and vulnerable to lesions when these are bilateral. This is shown here for bilateral periventricular white matter lesions that clearly have an impact on cortical architecture and function, thus probably interfering with early network building. Georg Thieme Verlag KG Stuttgart · New York.

  17. High cyclin A expression, but not Ki67, is associated with early recurrence in desmoid tumors.

    PubMed

    Santti, Kirsi; Ihalainen, Hanna; Rönty, Mikko; Böhling, Tom; Karlsson, Christina; Haglund, Caj; Tarkkanen, Maija; Blomqvist, Carl

    2018-06-07

    Desmoid tumors are soft-tissue tumors originating from myofibroblasts with a tendency to recur after surgery. High expression of proliferation markers is associated with shortened progression-free and/or overall survival in many neoplasms, including soft-tissue sarcomas. We investigated the prognostic role of cyclin A and Ki67 in desmoid tumors by immunohistochemistry. The study included 76 patients with desmoid tumor operated at Helsinki University Hospital between 1987 and 2011. A tissue micro array (TMA) was constructed and the TMA sections were immunostained with cyclin A and Ki67 antibodies. A computer-assisted image analysis was performed. Cyclin A expression was evaluable in 74 and Ki67 in 70 patients. Cyclin A immunopositivity varied from 0% to 9.9%, with a mean of 1.9%. Cyclin A expression correlated significantly with Ki67. Cyclin A expression was associated with recurrence-free survival (HR 1.9, 95% CI = 1.1-3.2, P = .02), as were positive margin (HR 6.0, 95% CI = 1.6-22.5, P = .008) and extremity location (HR 5.3, 95% CI = 1.7-16.8, P = 0.005). Ki67 immunopositivity varied from 0.33% to 13.8%, with a mean of 4.6%, but had no significant prognostic impact (HR 1.1, P = .2). Our study indicates that cyclin A may be a new prognostic biomarker in surgically treated desmoid tumors. © 2018 Wiley Periodicals, Inc.

  18. Transarterial chemoembolization for early stage hepatocellular carcinoma decrease local tumor control and overall survival compared to radiofrequency ablation

    PubMed Central

    Hocquelet, Arnaud; Seror, Olivier; Blanc, Jean-Frédéric; Frulio, Nora; Salut, Cécile; Nault, Jean-Charles; Hervé Trillaud

    2017-01-01

    Background & Aims To compare treatment failure and survival associated with ultrasound-guided radiofrequency ablation (RFA) and trans-arterial chemoembolization (TACE) for early-stage HCC in Child-Pugh A cirrhosis patients. Methods 122 cirrhotic patients (RFA: 61; TACE: 61) were well matched according to cirrhosis severity; tumor size and serum alpha-fetoprotein. TACE was performed in case of inconspicuous nodule on US or nodule with “at risk location”. Treatment failure was defined as local tumor progression (LTP) and primary treatment failure (failing to obtain complete response after two treatment session). Treatment failure and overall survival (OS) were compared after coarsened exact matching. Cox proportional model to assess independent predictive factors was performed. Results No significant difference was seen for baseline characteristics between the two groups. Mean tumor size was 3cm in both group with 41% HCC>3cm. Treatment failure rates after TACE was 42.6% (14 primary treatment failures and 12 LTP) and 9.8% after RFA (no primary treatment failure and 6 LTP) P < 0.001. TACE was the only predictive factor of treatment failure (Hazard ratio: 5.573). The 4-years OS after RFA and TACE were 54.1% and 31.5% (P = 0.042), respectively. Conclusion For Child-Pugh A patients with early-stage HCC, alternative treatment as supra-selective TACE to RFA regarded as too challenging using common US guidance decrease significantly the local tumor control and overall survival. Efforts to improve feasibility of RFA especially for inconspicuous target have to be made. PMID:27793027

  19. Ultraviolet B irradiation induces expansion of intraepithelial tumor cells in a tissue model of early cancer progression.

    PubMed

    Mudgil, Adarsh V; Segal, Nadav; Andriani, Frank; Wang, Youai; Fusenig, Norbert E; Garlick, Jonathan A

    2003-07-01

    Ultraviolet B irradiation is thought to enable skin cancer progression as clones of genetically damaged keratinocytes escape apoptosis and expand at the expense of adjacent normal cells. Mechanisms through which potentially malignant cells in human skin undergo clonal expansion, however, are not well understood. The goal of this study was to characterize the role of ultraviolet B irradiation on the intraepithelial expansion of early stage human tumor cells in organotypic skin cultures. To accomplish this, we have studied the effect of ultraviolet B irradiation on organotypic cultures that were fabricated by mixing normal human keratinocytes with beta-galactosidase-marked, intraepithelial tumor cells (HaCaT-ras, clone II-4), which bear mutations in both p53 alleles and harbor an activated H-ras oncogene. We found that when organotypic mixtures were exposed to an ultraviolet B dose of 50 mJ per cm2, intraepithelial tumor cells underwent a significant degree of proliferative expansion compared to nonirradiated cultures. To understand this response, organotypic cultures of nor-mal keratinocytes were exposed to ultraviolet B and showed a dose-dependent increase in numbers of sunburn cells and TUNEL-positive cells although their proliferation was suppressed. In contrast, neither the apoptotic nor the proliferative response of II-4 cells was altered by ultraviolet B in organotypic cultures. The differential response of these cell types suggested that II-4 cells were resistant to ultraviolet-B-induced alterations, which allowed these intraepithelial tumor cells to gain a selective growth and survival advantage relative to neighboring normal cells. These findings demonstrate that ultraviolet B exposure can induce the intraepithelial expansion of apoptosis-resistant, p53-mutant, and ras-activated keratinocytes, suggesting that this agent can act to promote the early stages of epithelial carcinogenesis.

  20. Development of Membrane-Bound GM-CSF and IL-18 as an Effective Tumor Vaccine

    PubMed Central

    Cheng, Ta-Chun; Chuang, Chih-Hung; Kao, Chien-Han; Hsieh, Yuan-Chin; Cheng, Kuang-Hung; Wang, Jaw-Yuan; Cheng, Chiu-Min; Chen, Chien-Shu; Cheng, Tian-Lu

    2015-01-01

    The development of effective adjuvant is the key factor to boost the immunogenicity of tumor cells as a tumor vaccine. In this study, we expressed membrane-bound granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-18 (IL-18) as adjuvants in tumor cells to stimulate immune response. B7 transmembrane domain fused GM-CSF and IL-18 was successfully expressed in the cell membrane and stimulated mouse splenocyte proliferation. Co-expression of GM-CSF and IL-18 reduced tumorigenesis (P<0.05) and enhanced tumor protective efficacy (P<0.05) significantly in comparison with GM-CSF alone. These results indicated that the combination of GM-CSF andIL-18 will enhance the immunogenicity of a cell-based anti-tumor vaccine. This membrane-bound approach can be applied to other cytokines for the development of novel vaccine strategies. PMID:26186692

  1. Early outcomes of empiric embolization of tumor-related gastrointestinal hemorrhage in patients with advanced malignancy.

    PubMed

    Tandberg, Daniel J; Smith, Tony P; Suhocki, Paul V; Pabon-Ramos, Waleska; Nelson, Rendon C; Desai, Svetang; Branch, Stanley; Kim, Charles Y

    2012-11-01

    To report short-term results of empiric transcatheter embolization for patients with advanced malignancy and gastrointestinal (GI) hemorrhage directly from a tumor invading the GI tract wall. Between 2005 and 2011, 37 mesenteric angiograms were obtained in 26 patients with advanced malignancy (20 men, six women; mean age, 56.2 y) with endoscopically confirmed symptomatic GI hemorrhage from a tumor invading the GI tract wall. Angiographic findings and clinical outcomes were retrospectively evaluated. Clinical success was defined as absence of signs and symptoms of hemorrhage for at least 30 day following embolization. Active extravasation was demonstrated in three cases. Angiographic abnormalities related to a GI tract tumor were identified on 35 of 37 angiograms, including tumor neovascularity (n = 21), tumor enhancement (n = 24), and luminal irregularity (n = 5). In the absence of active extravasation, empiric embolization with particles and/or coils was performed in 25 procedures. Cessation of hemorrhage (ie, clinical success) occurred more frequently when empiric embolization was performed (17 of 25 procedures; 68%) than when embolization was not performed (two of nine; 22%; P = .03). Empiric embolization resulted in clinical success in 10 of 11 patients with acute GI bleeding (91%), compared with seven of 14 patients (50%) with chronic GI bleeding (P = .04). No ischemic complications were encountered. In patients with advanced malignancy, in the absence of active extravasation, empiric transcatheter arterial embolization for treatment of GI hemorrhage from a direct tumor source demonstrated a 68% short-term success rate, without any ischemic complications. Copyright © 2012 SIR. Published by Elsevier Inc. All rights reserved.

  2. Resource Prospector (RP) - Early Prototyping and Development

    NASA Technical Reports Server (NTRS)

    Andrews, D.; Colaprete, A.; Quinn, J.; Bluethmann, B.; Trimble, J.

    2015-01-01

    The Resource Prospector (RP) is an In-Situ Resource Utilization (ISRU) technology demonstration mission under study by the NASA Human Exploration and Operations Mission Directorate's (HEOMD) Advanced Exploration Systems (AES) Division. The mission, currently planned to launch in 2020, will demonstrate extraction of oxygen from lunar regolith to validate ISRU capability. The mission will address key Strategic Knowledge Gaps (SKGs) for robotic and human exploration to the Moon, Near Earth Asteroids (NEAs), and ultimately Mars, as well as meet the strategic goals of the Global Exploration Roadmap (GER), offered by the International Space Exploration Coordination Group (ISECG). In this roadmap, the use of local resources is specifically addressed relating to human exploration. RP will provide knowledge to inform the selection of future mission destinations, support the development of exploration systems, and reduce the risk associated with human exploration. Expanding human presence beyond low-Earth orbit to asteroids and Mars will require the maximum possible use of local materials, so-called in-situ resources. The moon presents a unique destination to conduct robotic investigations that advance ISRU capabilities, as well as providing significant exploration and science value. Lunar regolith contains useful resources such as oxygen, water, silicon, and light metals, like aluminum and titanium. Oxygen can be separated from the regolith for life support (breathable air), or used to create rocket propellant (oxidizer). Regolith can be used to protect against radiation exposure, be processed into solar cells, or used to manufacture construction materials such as bricks and glass. RP will characterize the constituents and distribution of water and other volatiles at the poles of the Moon, enabling innovative uses of local resources, in addition to validating ISRU capabilities. This capability, as well as a deeper understanding of regolith, will be valuable in the

  3. Locoregional Tumor Extension and Preoperative Smoking are Significant Risk Factors for Early Recurrence After Esophagectomy for Cancer.

    PubMed

    Mantziari, Styliani; Allemann, Pierre; Winiker, Michael; Demartines, Nicolas; Schäfer, Markus

    2018-07-01

    Tumor recurrence during the first year after oncological esophagectomy has been reported in up to 17-66% of patients. However, little is known as to the risk factors potentially associated with this adverse outcome. The aim of this retrospective observational study was to identify clinically relevant parameters associated with early recurrence. All patients with squamous cell cancer or adenocarcinoma of the esophagus or gastroesophageal junction, operated with curative intent in our center from 2000 to 2014, were screened for this study. Univariate analysis was conducted to identify variables potentially associated with early recurrence, and clinically relevant parameters with P < 0.1 were included in multiple logistic regression. Survival analyses were conducted with the Kaplan-Meier method. Significance threshold was set at P < 0.05. Among the 164 included patients, 46 (28%) presented early recurrence. Eight patients (17.4%) had locoregional and 38 patients (82.6%) metastatic recurrence. Advanced T and N stages, lymph node capsular effraction, a high positive-to-resected lymph node ratio, positive resection margins, poor response to neoadjuvant treatment, preoperative active smoking, malnutrition and dysphagia were associated with early recurrence on a univariate level. In multivariable analysis, preoperative smoking (OR 2.76, 95% CI 1.28-6.17), pT stage (OR 1.72, 95% CI 1.18-2.58) and an increased positive-to-resected lymph node ratio (OR 6.72, 95% CI 1.08-48.51) remained independently associated with ER. Our study identified both patient- and tumor-related parameters as risk factors for early recurrence after oncological esophagectomy. Of particular interest, active smoking was significantly associated with this adverse outcome, highlighting the importance of preoperative smoking cessation.

  4. Basics of tumor development and importance of human papilloma virus (HPV) for head and neck cancer

    PubMed Central

    Wittekindt, Claus; Wagner, Steffen; Mayer, Christina Sabine; Klussmann, Jens Peter

    2012-01-01

    Head and Neck Squamous Cell Carcinomas (HNSCC) are the 6th most common cancers worldwide. While incidence rates for cancer of the hypopharynx and larynx are decreasing, a significant increase in cancer of the oropharynx (OSCC) is observed. Classical risk factors for HNSCC are smoking and alcohol. It has been shown for 25 to 60% of OSCC to be associated with an infection by oncogenic human papilloma viruses (HPV). The development of “common” cancer of the head and neck is substantially enhanced by an accumulation of genetic changes, which lead to an inactivation of tumor suppressor genes or activation of proto-oncogenes. A more or less uniform sequence of different DNA-damages leads to genetic instability. In this context, an early and frequent event is deletion on the short arm of chromosome 9, which results in inactivation of the p16-gene. In contrast, for HPV-induced carcinogenesis, expression of the viral proteins E6 and E7 is most important, since they lead to inactivation of the cellular tumor-suppressor-proteins p53 and Rb. The natural route of transoral infection is a matter of debate; peroral HPV-infections might be frequent and disappear uneventfully in most cases. Smoking seems to increase the probability for developing an HPV-associated OSCC. The association of HNSCC with HPV can be proven with established methods in clinical diagnostics. In addition to classical prognostic factors, diagnosis of HPV-association may become important for selection of future therapies. Prognostic relevance of HPV probably surmounts many known risk-factors, for example regional metastasis. Until now, no other molecular markers are established in clinical routine. Future therapy concepts may vary for the two subgroups of patients, particularly patients with HPV-associated OSCC may take advantage of less aggressive treatments. Finally, an outlook will be given on possible targeted therapies. PMID:23320061

  5. Early intestinal growth and development in poultry.

    PubMed

    Lilburn, M S; Loeffler, S

    2015-07-01

    While there are many accepted "facts" within the field of poultry science that are in truth still open for discussion, there is little debate with respect to the tremendous genetic progress that has been made with commercial broilers and turkeys (Havenstein et al., 2003, 2007). When one considers the changes in carcass development in poultry meat strains, these genetic "improvements" have not always been accompanied by correlated changes in other physiological systems and this can predispose some birds to developmental anomalies (i.e. ascites; Pavlidis et al., 2007; Wideman et al., 2013). Over the last decade, there has been increased interest in intestinal growth/health as poultry nutritionists have attempted to adopt new approaches to deal with the broader changes in the overall nutrition landscape. This landscape includes not only the aforementioned genetic changes but also a raft of governmental policies that have focused attention on the environment (phosphorus and nitrogen excretion), consumer pressure on the use of antibiotics, and renewable biofuels with its consequent effects on ingredient costs. Intestinal morphology has become a common research tool for assessing nutritional effects on the intestine but it is only one metric among many that can be used and histological results can often be interpreted in a variety of ways. This study will address the broader body of research on intestinal growth and development in commercial poultry and will attempt to integrate the topics of the intestinal: microbial interface and the role of the intestine as an immune tissue under the broad umbrella of intestinal physiology. © 2015 Poultry Science Association Inc.

  6. Advancing Early Childhood Development: from Science to Scale 1

    PubMed Central

    Black, Maureen M; Walker, Susan P; Fernald, Lia C H; Andersen, Christopher T; DiGirolamo, Ann M; Lu, Chunling; McCoy, Dana C; Fink, Günther; Shawar, Yusra R; Shiffman, Prof Jeremy; Devercelli, Amanda E; Wodon, Quentin T; Vargas-Barón, Emily; Grantham-McGregor, Sally

    2018-01-01

    Early childhood development programmes vary in coordination and quality, with inadequate and inequitable access, especially for children younger than 3 years. New estimates, based on proxy measures of stunting and poverty, indicate that 250 million children (43%) younger than 5 years in low-income and middle-income countries are at risk of not reaching their developmental potential. There is therefore an urgent need to increase multisectoral coverage of quality programming that incorporates health, nutrition, security and safety, responsive caregiving, and early learning. Equitable early childhood policies and programmes are crucial for meeting Sustainable Development Goals, and for children to develop the intellectual skills, creativity, and wellbeing required to become healthy and productive adults. In this paper, the first in a three part Series on early childhood development, we examine recent scientific progress and global commitments to early childhood development. Research, programmes, and policies have advanced substantially since 2000, with new neuroscientific evidence linking early adversity and nurturing care with brain development and function throughout the life course. PMID:27717614

  7. BRCA1-IRIS overexpression promotes and maintains the tumor initiating phenotype: implications for triple negative breast cancer early lesions

    PubMed Central

    Sullivan, Lisa M.; Sims, Hillary; Bastawisy, Ahmed El; Yousef, Hend F.; Zekri, Abdel-Rahman N.; Bahnassy, Abeer A.; ElShamy, Wael M.

    2017-01-01

    Tumor-initiating cells (TICs) are cancer cells endowed with self-renewal, multi-lineage differentiation, increased chemo-resistance, and in breast cancers the CD44+/CD24-/ALDH1+ phenotype. Triple negative breast cancers show lack of BRCA1 expression in addition to enhanced basal, epithelial-to-mesenchymal transition (EMT), and TIC phenotypes. BRCA1-IRIS (hereafter IRIS) is an oncogene produced by the alternative usage of the BRCA1 locus. IRIS is involved in induction of replication, transcription of selected oncogenes, and promoting breast cancer cells aggressiveness. Here, we demonstrate that IRIS overexpression (IRISOE) promotes TNBCs through suppressing BRCA1 expression, enhancing basal-biomarkers, EMT-inducers, and stemness-enforcers expression. IRISOE also activates the TIC phenotype in TNBC cells through elevating CD44 and ALDH1 expression/activity and preventing CD24 surface presentation by activating the internalization pathway EGFR→c-Src→cortactin. We show that the intrinsic sensitivity to an anti-CD24 cross-linking antibody-induced cell death in membranous CD24 expressing/luminal A cells could be acquired in cytoplasmic CD24 expressing IRISOE TNBC/TIC cells through IRIS silencing or inactivation. We show that fewer IRISOE TNBC/TICs cells form large tumors composed of TICs, resembling TNBCs early lesions in patients that contain metastatic precursors capable of disseminating and metastasizing at an early stage of the disease. IRIS-inhibitory peptide killed these IRISOE TNBC/TICs, in vivo and prevented their dissemination and metastasis. We propose IRIS inactivation could be pursued to prevent dissemination and metastasis from early TNBC tumor lesions in patients. PMID:28052035

  8. The development of a malignant tumor is due to a desperate asexual self-cloning process in which cancer stem cells develop the ability to mimic the genetic program of germline cells

    PubMed Central

    Vinnitsky, Vladimir

    2014-01-01

    To date there is no explanation why the development of almost all types of solid tumors occurs sharing a similar scenario: (1) creation of a cancer stem cell (CSC), (2) CSC multiplication and formation of a multicellular tumor spheroid (TS), (3) vascularization of the TS and its transformation into a vascularized primary tumor, (4) metastatic spreading of CSCs, (5) formation of a metastatic TSs and its transformation into metastatic tumors, and (6) potentially endless repetition of this cycle of events. The above gaps in our knowledge are related to the biology of cancer and specifically to tumorigenesis, which covers the process from the creation of a CSC to the formation of a malignant tumor and the development of metastases. My Oncogerminative Theory of Tumorigenesis considers tumor formation as a dynamic self-organizing process that mimics a self-organizing process of early embryo development. In the initial step in that process, gene mutations combined with epigenetic dysregulation cause somatic cells to be reprogrammed into CSCs, which are immortal pseudo-germline cells. Mimicking the behavior of fertilized germline cells, the CSC achieves immortality by passing through the stages of its life-cycle and developing into a pseudo-blastula-stage embryo, which manifests in the body as a malignant tumor. In this view, the development of a malignant tumor from a CSC is a phenomenon of developmental biology, which we named a desperate asexual self-cloning event. The theory explains seven core characteristics of malignant tumors: (1) CSC immortality, (2) multistep development of a malignant tumor from a single CSC, (3) heterogeneity of malignant tumor cell populations, (4) metastatic spread of CSCs, (5) invasive growth, (6) malignant progression, and (7) selective immune tolerance toward cancer cells. The Oncogerminative Theory of Tumorigenesis suggests new avenues for discovery of revolutionary therapies to treat, prevent, and eradicate cancer. PMID:28232878

  9. 45 CFR 1304.21 - Education and early childhood development.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... as art, music, movement, and dialogue; (iii) Promoting interaction and language use among children... DEVELOPMENT SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES THE ADMINISTRATION FOR CHILDREN, YOUTH AND... early childhood development. (a) Child development and education approach for all children. (1) In order...

  10. 45 CFR 1304.21 - Education and early childhood development.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... as art, music, movement, and dialogue; (iii) Promoting interaction and language use among children... DEVELOPMENT SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES THE ADMINISTRATION FOR CHILDREN, YOUTH AND... early childhood development. (a) Child development and education approach for all children. (1) In order...

  11. 45 CFR 1304.21 - Education and early childhood development.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... as art, music, movement, and dialogue; (iii) Promoting interaction and language use among children... DEVELOPMENT SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES THE ADMINISTRATION FOR CHILDREN, YOUTH AND... early childhood development. (a) Child development and education approach for all children. (1) In order...

  12. 45 CFR 1304.21 - Education and early childhood development.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... as art, music, movement, and dialogue; (iii) Promoting interaction and language use among children... DEVELOPMENT SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES THE ADMINISTRATION FOR CHILDREN, YOUTH AND... early childhood development. (a) Child development and education approach for all children. (1) In order...

  13. Multisession stereotactic radiosurgery for large benign brain tumors of >3cm- early clinical outcomes

    PubMed Central

    Memon, Muhammad Ali; Ahmed, Usman; Saleem, Muhammad Abid; Bhatti, Amer Iqtidar; Ahmed, Naveed; Hashim, Abdul Sattar M.

    2012-01-01

    Objective To evaluate the clinical outcome of linear accelerator based multisession stereotactic radiosurgery (SRS) for large benign brain tumors of >3cm. Methods Between June 2009 and May 2011, 35 patients having large benign brain tumors of >3cm (≥15 cm3) were treated by multisession stereotactic radiosurgery. This retrospective study was carried out at Neurospinal & Medical Institute Karachi. There were 17 (48.6 %) males and 18(51.4 %) females. Median age was 36 years (range: 13-65 years). Median target volume was 49.4 cm3 (range: 15-184 cm3). The median marginal dose was 25 Gy (range: 20–27.5Gy) prescribed to a median 75% isodose line (range: 65-100 %). Median number of 5 fractions were used ranging 3-5 fractions. Results All the patients tolerated treatment very well. 21 (58.3%) patients had remarkable clinical improvement of neurological symptoms, 14 (38.9%) patients had stable symptoms, and only one patient had transient worsening of symptoms. No permanent neurological damage or radiation injury was seen. Radiologically, 9 (25.7%) patients achieved reduction in size of the tumor, 26(74.3 %) patients were having stable disease, and overall control rate was found to be 100 %. Median follow-up time from the end of SRS was 6.4 months (range: 1-22.5months). Conclusion Linear accelerator based multisession stereotactic radiosurgery for large benign brain tumors of >3cm is effective and well tolerated. PMID:29296340

  14. Early Oral Tongue Squamous Cell Carcinoma Sampling of Margins From Tumor Bed and Worse Local Control

    PubMed Central

    Maxwell, Jessica H.; Thompson, Lester D. R.; Brandwein-Gensler, Margaret S.; Weiss, Bernhard G.; Canis, Martin; Purgina, Bibianna; Prabhu, Arpan V.; Lai, Chi; Shuai, Yongli; Carroll, William R.; Morlandt, Anthony; Duvvuri, Umamaheswar; Kim, Seungwon; Johnson, Jonas T.; Ferris, Robert L.; Seethala, Raja; Chiosea, Simion I.

    2017-01-01

    IMPORTANCE Positive margins are associated with poor prognosis among patients with oral tongue squamous cell carcinoma (SCC). However, wide variation exists in the margin sampling technique. OBJECTIVE To determine the effect of the margin sampling technique on local recurrence (LR) in patients with stage I or II oral tongue SCC. DESIGN, SETTING, AND PARTICIPANTS A retrospective study was conducted from January 1, 1986, to December 31, 2012, in 5 tertiary care centers following tumor resection and elective neck dissection in 280 patients with pathologic (p)T1-2 pN0 oral tongue SCC. Analysis was conducted from June 1, 2013, to January 20, 2015. INTERVENTIONS In group 1 (n = 119), tumor bed margins were not sampled. In group 2 (n = 61), margins were examined from the glossectomy specimen, found to be positive or suboptimal, and revised with additional tumor bed margins. In group 3 (n = 100), margins were primarily sampled from the tumor bed without preceding examination of the glossectomy specimen. The margin status (both as a binary [positive vs negative] and continuous [distance to the margin in millimeters] variable) and other clinicopathologic parameters were compared across the 3 groups and correlated with LR. MAIN OUTCOMES AND MEASURES Local recurrence. RESULTS Age, sex, pT stage, lymphovascular or perineural invasion, and adjuvant radiation treatment were similar across the 3 groups. The probability of LR-free survival at 3 years was 0.9 and 0.8 in groups 1 and 3, respectively (P = .03). The frequency of positive glossectomy margins was lowest in group 1 (9 of 117 [7.7%]) compared with groups 2 and 3 (28 of 61 [45.9%] and 23 of 95 [24.2%], respectively) (P < .001). Even after excluding cases with positive margins, the median distance to the closest margin was significantly narrower in group 3 (2 mm) compared with group 1 (3 mm) (P = .008). The status (positive vs negative) of margins obtained from the glossectomy specimen correlated with LR (P = .007), while

  15. Early Oral Tongue Squamous Cell Carcinoma: Sampling of Margins From Tumor Bed and Worse Local Control.

    PubMed

    Maxwell, Jessica H; Thompson, Lester D R; Brandwein-Gensler, Margaret S; Weiss, Bernhard G; Canis, Martin; Purgina, Bibianna; Prabhu, Arpan V; Lai, Chi; Shuai, Yongli; Carroll, William R; Morlandt, Anthony; Duvvuri, Umamaheswar; Kim, Seungwon; Johnson, Jonas T; Ferris, Robert L; Seethala, Raja; Chiosea, Simion I

    2015-12-01

    Positive margins are associated with poor prognosis among patients with oral tongue squamous cell carcinoma (SCC). However, wide variation exists in the margin sampling technique. To determine the effect of the margin sampling technique on local recurrence (LR) in patients with stage I or II oral tongue SCC. A retrospective study was conducted from January 1, 1986, to December 31, 2012, in 5 tertiary care centers following tumor resection and elective neck dissection in 280 patients with pathologic (p)T1-2 pN0 oral tongue SCC. Analysis was conducted from June 1, 2013, to January 20, 2015. In group 1 (n = 119), tumor bed margins were not sampled. In group 2 (n = 61), margins were examined from the glossectomy specimen, found to be positive or suboptimal, and revised with additional tumor bed margins. In group 3 (n = 100), margins were primarily sampled from the tumor bed without preceding examination of the glossectomy specimen. The margin status (both as a binary [positive vs negative] and continuous [distance to the margin in millimeters] variable) and other clinicopathologic parameters were compared across the 3 groups and correlated with LR. Local recurrence. Age, sex, pT stage, lymphovascular or perineural invasion, and adjuvant radiation treatment were similar across the 3 groups. The probability of LR-free survival at 3 years was 0.9 and 0.8 in groups 1 and 3, respectively (P = .03). The frequency of positive glossectomy margins was lowest in group 1 (9 of 117 [7.7%]) compared with groups 2 and 3 (28 of 61 [45.9%] and 23 of 95 [24.2%], respectively) (P < .001). Even after excluding cases with positive margins, the median distance to the closest margin was significantly narrower in group 3 (2 mm) compared with group 1 (3 mm) (P = .008). The status (positive vs negative) of margins obtained from the glossectomy specimen correlated with LR (P = .007), while the status of tumor bed margins did not. The status of the tumor bed margin was 24% sensitive (95

  16. Total enbloc spondylectomy for metastatic high grade spinal tumors: Early results

    PubMed Central

    Patil, Sanganagouda S; Nene, Abhay M

    2016-01-01

    Background: High grade metastatic spinal tumors are most common and are invasive. These patients can succumb to disease progression if not treated timely. Although considered as invasive and morbid, total enbloc spondylectomy (TES) in selected cases has better survival rates. The authors describe the results of TES for high grade metastatic spinal tumors. Materials and Methods: Five patients (four females and one male) underwent TES for solitary metastatic vertebral lesion between November 2012 and January 2014. These patients presented to us with spinal instability, unrelenting severe spinal pain and/or with severe progressive radiculopathy. Average age was 46.2 years (range 39–62 years). After complete investigations, computed tomography scan, magnetic resonance imaging scan and positron emission tomography (PET) scan, it was confirmed that these patients had high grade solitary vertebral metastatic tumor. Results: Average duration of followup was 18 months (range 16–20 months). The average preoperative visual analog scale score of 9.4 (range 9–10) improved to 2 (range 1–4) at last followup. Average blood loss was 1440 mL (range 1000–2000 mL). Average duration of surgery was 198 min (range 180–240 min). Significant pain relief was noticed in each patient in the immediate postoperative period and during followups. These patients attained complete functional activities of daily living with in a month. The imaging showed implants in situ, no recurrence of tumor, and no activity on PET scan at the final followup. Conclusion: The present series shows favorable short term results of TES for solitary, metastatic, high grade vertebral body tumors by a team approach. PMID:27512215

  17. Early development of an enterprise health data warehouse.

    PubMed

    Househ, Mowafa Said; Al-Tuwaijri, Majid

    2011-01-01

    The purpose of this study is to describe early development challenges of an enterprise data warehouse within a Saudi Arabian academic healthcare facility. An action case research method was selected for this paper. The study took place between December 2009 and February 2010. Data collection included interviews, meeting observations, and meeting minutes. Early development challenges centered on the development of clear contracts with vendors; development of a clear project plan; a need to fast-track bureaucracy; and educate clinicians and staff about the project; and lack of data standardization.

  18. Early Brain and Child Development: Connections to Early Education and Child Care

    ERIC Educational Resources Information Center

    Romano, Judith T.

    2013-01-01

    The vast majority of young children spend time in settings outside of the home, and the nature of those settings directly impacts the child's health and development. The ecobiodevelopmental framework of early brain and child development serve as the backdrop for establishing quality. This article describes the use of quality rating systems,…

  19. Integrated and Early Childhood Education: Preparation for Social Development. Theme A: Relevant Provision for Early Childhood.

    ERIC Educational Resources Information Center

    Axton, J. H. M.

    Factors which influence child development are listed and briefly discussed. These factors are (1) mother's childhood, (2) mother's age, (3) care during pregnancy and delivery, (4) early neonatal factors, (5) birth interval, (6) effect of repeated infection and malnutrition on brain growth and intellectual development, and (7) home environment. The…

  20. Getting an Early Start on Early Child Development. Education Notes. 30194

    ERIC Educational Resources Information Center

    Young, Mary Eming; Dunkelberg, Erika

    2004-01-01

    The children born this year--2004--will be eleven years old in 2015--the age of primary school completion in most countries. This is the MDG (Millennium Development Goal) generation--for whom the international community has pledged that by 2015, all children will be able to complete primary schooling. Ensuring good early child development is the…

  1. Non-invasive thermal IR detection of breast tumor development in vivo

    NASA Astrophysics Data System (ADS)

    Case, Jason R.; Young, Madison A.; Dréau, D.; Trammell, Susan R.

    2015-03-01

    Lumpectomy coupled with radiation therapy and/or chemotherapy comprises the treatment of breast cancer for many patients. We are developing an enhanced thermal IR imaging technique that can be used in real-time to guide tissue excision during a lumpectomy. This novel enhanced thermal imaging method is a combination of IR imaging (8- 10 μm) and selective heating of blood (~0.5 °C) relative to surrounding water-rich tissue using LED sources at low powers. Post-acquisition processing of these images highlights temporal changes in temperature and is sensitive to the presence of vascular structures. In this study, fluorescent and enhanced thermal imaging modalities were used to estimate breast cancer tumor volumes as a function of time in 19 murine subjects over a 30-day study period. Tumor volumes calculated from fluorescent imaging follow an exponential growth curve for the first 22 days of the study. Cell necrosis affected the tumor volume estimates based on the fluorescent images after Day 22. The tumor volumes estimated from enhanced thermal imaging show exponential growth over the entire study period. A strong correlation was found between tumor volumes estimated using fluorescent imaging and the enhanced IR images, indicating that enhanced thermal imaging is capable monitoring tumor growth. Further, the enhanced IR images reveal a corona of bright emission along the edges of the tumor masses. This novel IR technique could be used to estimate tumor margins in real-time during surgical procedures.

  2. Sipuleucel-T: Prototype for development of anti-tumor vaccines.

    PubMed

    Carballido, Estrella; Fishman, Mayer

    2011-04-01

    Prostate cancer immunotherapy officially debuted with the recent FDA approval of Sipuleucel-T. The novel trend of cancer immunotherapy relies on the identification of particular tumor-associated antigens, like prostatic acid phosphatase (PAP). Sipuleucel-T consists of autologous dendritic cells activated in vitro with recombinant fusion protein PA2024, PAP-linked to granulocyte-macrophage colony-stimulating factor. Sipuleucel-T represents a prototype for the development of cancer vaccines. Preclinical and clinical data as well as landmark studies for the existing narrow chemotherapy alternatives and early immunotherapy trials will be discussed. The pivotal trial demonstrated a 4.1-month difference of median survival, but with no effect on time to progression in asymptomatic or minimally symptomatic metastatic castrate-resistant patients. Several immunologic effects were observed in the treated population, including antibody and T cell-specific activity to P2024 and PAP. With all new therapies the extent of clinical and objective benefits versus encountered limitations should be evaluated. This review highlights the events and decisions in the process of the development of Sipuleucel-T. We discuss how this successful immunotherapy outcome challenges us to use it as a starting point for variations to or try to amplify practical anticancer progress within the antitumor vaccine paradigm.

  3. Promoting equity through integrated early child development and nutrition interventions.

    PubMed

    Black, Maureen M; Dewey, Kathryn G

    2014-01-01

    Sustainable development, a foundation of the post-2015 global agenda, depends on healthy and productive citizens. The origins of adult health begin early in life, stemming from genetic-environmental interactions that include adequate nutrition and opportunities for responsive learning. Inequities associated with inadequate nutrition and early learning opportunities can undermine children's health and development, thereby compromising their productivity and societal contributions. Transactional theory serves as a useful framework for examining the associations that link early child development and nutrition because it emphasizes the interplay that occurs between children and the environment, mediated through caregiver interactions. Although single interventions targeting early child development or nutrition can be effective, there is limited evidence on the development, implementation, evaluation, and scaling up of integrated interventions. This manuscript introduces a special edition of papers on six topics central to integrated child development/nutrition interventions: (1) review of integrated interventions; (2) methods and topics in designing integrated interventions; (3) economic considerations related to integrated interventions; (4) capacity-building considerations; (5) examples of integrated interventions; and (6) policy implications of integrated interventions. Ensuring the health and development of infants and young children through integrated child development/nutrition interventions promotes equity, a critical component of sustainable development. © 2014 New York Academy of Sciences.

  4. New Approaches for Early Detection of Breast Tumor Invasion or Progression

    DTIC Science & Technology

    2004-08-01

    had. 17p. Samples from 10 women with prolapsed uteri (elongatio coli) without any required numerous surgeries. Immediately prior to hermalignant...Sanchez-Estevez, D Hardisson, MAndujar, A Do 872 Chromosome 10 Rearrangements in Uterine Leiomyomata Involve the L Lombardia, E Bussaglia, J Prat...Vill MA; Massachusetts Institute of Technology, Cambridge, MA. Lerida, Spain. Background: Benign uterine leiomyomata (UL) are the most common tumor in

  5. Early Clinical Outcomes Using Proton Radiation for Children With Central Nervous System Atypical Teratoid Rhabdoid Tumors

    SciT

    De Amorim Bernstein, Karen; Sethi, Roshan; Trofimov, Alexei

    2013-05-01

    Purpose: Atypical teratoid/rhabdoid tumor (AT/RT) is an uncommon and aggressive tumor that often affects infants. Irradiation improves survival but has traditionally been avoided in patients under the age of 3 due to the increasing risk of neurocognitive side effects. We report the first cohort of AT/RT patients treated with proton therapy. Methods and Materials: All patients with AT/RT treated at Massachusetts General Hospital (MGH) Frances H. Burr Proton Beam Therapy Benter between July 2004 and November 2011 were included in this study. All patients were treated with 3-dimensional conformal proton therapy (3D-CPT). Results: Ten consecutive patients of a median 2.3more » years of age and with a median follow-up of 27.3 months (range, 11.3-99.4 months) were identified. Two patients suffered distant relapse; 1 patient was successfully treated with involved field irradiation and chemotherapy, while the second patient died of disease. At last follow-up, 9 patients were alive without evidence of disease. Proton radiation demonstrated increasing sparing of the cerebrum, temporal lobe, cochlea, and hypothalamus. Conclusions: Initial clinical outcomes with proton therapy are favorable. The advantages of proton therapy are particularly suited to the treatment of AT/RT, a tumor that often requires irradiation treatment at an age when avoiding irradiation to healthy tissues is most desirable.« less

  6. Early T Cell Signalling Is Reversibly Altered in PD-1+ T Lymphocytes Infiltrating Human Tumors

    PubMed Central

    Wang, Shu-Fang; Fouquet, Stéphane; Chapon, Maxime; Salmon, Hélène; Regnier, Fabienne; Labroquère, Karine; Badoual, Cécile; Damotte, Diane; Validire, Pierre; Maubec, Eve; Delongchamps, Nicolas B.; Cazes, Aurélie; Gibault, Laure; Garcette, Marylène; Dieu-Nosjean, Marie-Caroline; Zerbib, Marc; Avril, Marie-Françoise; Prévost-Blondel, Armelle; Randriamampita, Clotilde; Trautmann, Alain; Bercovici, Nadège

    2011-01-01

    To improve cancer immunotherapy, a better understanding of the weak efficiency of tumor-infiltrating T lymphocytes (TIL) is necessary. We have analyzed the functional state of human TIL immediately after resection of three types of tumors (NSCLC, melanoma and RCC). Several signalling pathways (calcium, phosphorylation of ERK and Akt) and cytokine secretion are affected to different extents in TIL, and show a partial spontaneous recovery within a few hours in culture. The global result is an anergy that is quite distinct from clonal anergy induced in vitro, and closer to adaptive tolerance in mice. PD-1 (programmed death -1) is systematically expressed by TIL and may contribute to their anergy by its mere expression, and not only when it interacts with its ligands PD-L1 or PD-L2, which are not expressed by every tumor. Indeed, the TCR-induced calcium and ERK responses were reduced in peripheral blood T cells transfected with PD-1. Inhibition by sodium stibogluconate of the SHP-1 and SHP-2 phosphatases that associate with several inhibitory receptors including PD-1, relieves part of the anergy apparent in TIL or in PD-1-transfected T cells. This work highlights some of the molecular modifications contributing to functional defects of human TIL. PMID:21408177

  7. Mammary Gland Tumor Development in Transgenic Mice Overexpressing Different Isoforms of the CDP/Cux Transcription Factor

    DTIC Science & Technology

    2009-03-01

    tumors and in uterine leiomyomas , suggesting that these proteins play a key role in tumor development and progression. My project consisted in... leiomyomas , suggesting that these proteins could play a key role in tumor development and progression (6, 7). I have also previoulsly shown that...and p110 are involved in cancer development. The p110 and p75 isoforms are overexpressed in primary human tumors, such as in uterine leiomyomas and

  8. Early childhood traumatic development and its impact on gender identity.

    PubMed

    Cohen, Y

    2001-03-01

    The author clarifies issues of gender identity typical to contemporary Western societies. Nowadays, we tend to emphasize self-autonomy as the main target of the individual's development. In adolescence this may cause many questions as to the adolescent's conception of his or her gender and sexual identity. These questions are the outcome of early development, and thus early traumas may impact the entire gender development. In this context, trauma includes not only major violations such as sexual abuse, terror attacks, and so forth, but also comprises events heretofore considered minor.

  9. Early Learning and Development: Cultural-Historical Concepts in Play

    ERIC Educational Resources Information Center

    Fleer, Marilyn

    2010-01-01

    "Early Learning and Development" provides a unique synthesis of cultural-historical theory from Vygotsky, Elkonin and Leontiev in the 20th century to the ground-breaking research of scholars such as Siraj-Blatchford, Kratsova and Hedegaard today. It demonstrates how development and learning are culturally embedded and institutionally defined, and…

  10. Child Development, Early Childhood Education and Family Life: A Bibliography.

    ERIC Educational Resources Information Center

    Reardon, Beverly, Comp.

    This bibliographical listing of approximately 2500 books on child development, early childhood education and family life was compiled as a resource for parents and students. Books are listed alphabetically by author and are grouped according to the following categories: child development; observation of children; adolescence; language…

  11. Helping Families Connect Early Literacy with Social-Emotional Development

    ERIC Educational Resources Information Center

    Santos, Rosa Milagros; Fettig, Angel; Shaffer, LaShorage

    2012-01-01

    Early childhood educators know that home is a child's first learning environment. From birth, children are comforted by hearing and listening to their caregivers' voices. The language used by families supports young children's development of oral language skills. Exposure to print materials in the home also supports literacy development. Literacy…

  12. Aesthetic Experience and Early Language and Literacy Development

    ERIC Educational Resources Information Center

    Johnson, Helen L.

    2007-01-01

    The present paper explores the connections between theory and research in language development and aesthetic education and their implications for early childhood classroom practice. The present paper posits that arts experiences make a unique and vital contribution to the child's development of language and literacy, as well as to the sense of…

  13. Professional development session for early career scientists at SITC 2012

    PubMed Central

    2013-01-01

    The Society for Immunotherapy of Cancer (SITC) 2012 Professional Development Session was held as part of the SITC 27th Annual Meeting, Washington, DC, on October 24, 2012. The session was designed as a new opportunity for early career investigators to learn about relevant career development topics in a didactic setting. PMID:25742323

  14. Promising Directions for Research and Development in Early Childhood Education.

    ERIC Educational Resources Information Center

    Elliott, David L.

    A survey of research and development studies currently needed in early childhood education stresses child development and its relation to instruction. Topics which have been discussed are perception, oral language, concept formation, learning set, motivation, and the psychology of learning. Universities and public school systems working together…

  15. Instructional Development for Early Career Academics: An Overview of Impact

    ERIC Educational Resources Information Center

    Stes, Ann; Van Petegem, Peter

    2011-01-01

    Background: Over the past decades, the issue of improving teaching in higher education has been seriously addressed. Centres for instructional development, aimed at enhancing teaching, have been set up in many countries. Instructional development for early career academics is perceived to be of particular importance. Given the considerable…

  16. Early Markers of Vulnerable Language Skill Development in Galactosaemia

    ERIC Educational Resources Information Center

    Lewis, Fiona M.; Coman, David J.; Syrmis, Maryanne

    2014-01-01

    There are no known biomedical or genetic markers to identify which infants with galactosaemia (GAL) are most at risk of poor language skill development, yet pre-linguistic communicative "red flag" behaviours are recognised as early identifiers of heightened vulnerability to impaired language development. We report on pre-linguistic…

  17. Understanding Emotional Development: Helping Early Childhood Providers Better Support Families

    ERIC Educational Resources Information Center

    Edwards, Nicole Megan

    2012-01-01

    This article is intended to provide early childhood providers with a concise overview of emerging emotional development in young children (birth-5), the important role of primary caregivers, and the link between parenting, emotional development, and behavior. Specific suggestions that have been shared with urban Head Start mothers are offered,…

  18. Culture and Early Language Development: Implications for Assessment and Intervention

    ERIC Educational Resources Information Center

    Parada, Patricia M.

    2013-01-01

    The purpose of this qualitative study--"Culture and Early Language Development: Implications for Assessment and Intervention"--was to explore and describe the perceptions and beliefs of Salvadoran mothers of low socioeconomic status regarding the language development of their young children in order to identify cultural variations in…

  19. Risk factors in past histories and familial episodes related to development of testicular germ cell tumor.

    PubMed

    Kanto, Satoru; Hiramatsu, Masayoshi; Suzuki, Kenichi; Ishidoya, Shigeto; Saito, Hideo; Yamada, Shigeyuki; Satoh, Makoto; Saito, Seiichi; Fukuzaki, Atsushi; Arai, Yoichi

    2004-08-01

    A retrospective study was conducted to examine the host factors of 240 testicular germ cell tumor patients. This study was performed to address a new theory proposed by Skakkebaek called testicular dysgenesis syndrome which claims that cryptorchism, hypospadias, poor semen quality and testicular germ cell tumors are symptoms of an underlying testicular dysgenesis in uterus. The past health histories and familial episodes of 240 testicular germ cell tumor patients were examined. The past health histories included cryptorchism, hypospadias, infertility, atrophic testis and inguinal hernia. Of the 240 patients, 13 (5.4%) had a history of cryptorchism or orchidopexy. Two (0.8%) showed existence of hypospadias or had experienced urethroplasty. Among 129 married couples, 104 (80.6%) couples were fertile. Three (1.3%) patients developed testicular tumors after they were diagnosed as infertile or came to the hospital with the complaints of infertility. Four (1.7%) had contralateral atrophic testis. 19 (7.9%) had experienced inguinal herniorrhaphy before age 15. Three (1.3%) had testicular germ cell tumor patients among their family or relatives. The testicular germ cell tumor patients showed a considerable incidence of complications such as cryptorchism, hypospadias and incomplete closure of processus vaginalis. Cryptorchism, perinatal factors and familial factors could be risks for developing testicular germ cell tumors.

  20. MicroRNA-93 inhibits tumor growth and early relapse of human colorectal cancer by affecting genes involved in the cell cycle.

    PubMed

    Yang, I-Ping; Tsai, Hsiang-Lin; Hou, Ming-Feng; Chen, Ku-Chung; Tsai, Pei-Chien; Huang, Szu-Wei; Chou, Wen-Wen; Wang, Jaw-Yuan; Juo, Suh-Hang Hank

    2012-08-01

    Colorectal cancer (CRC) is associated with high recurrence and mortality. Because deregulation of microRNAs is associated with CRC development and recurrence, the expression levels of microRNAs can be a simple and reliable biomarker to detect postoperative early relapse, thereby helping physicians to treat high-risk patients more efficiently. We used microRNA arrays and observed that microRNA-93 had substantially different expression levels in early (recurrence within 12 months after surgery) and non-early relapse CRC patients. The replication study, which included 35 early relapse and 42 non-early relapse subjects, further confirmed overexpression of microRNA-93 in non-early relapse samples. The in vitro and in vivo effects of microRNA-93 were investigated by examining cell proliferation, migration and invasion, as well as cell cycles, target-gene expression and xenograft in null mice. Cellular studies showed that the overexpression of microRNA-93 inhibited colon cancer cell proliferation and migration but not invasion. The cell cycle studies also revealed that microRNA-93 caused an accumulation of the G2 population. However, microRNA-93 could not induce cell apoptosis or necrosis. Functional studies showed that microRNA-93 could suppress CCNB1 protein expression leading to cell cycle arrest in the G2 phase. Moreover, microRNA-93 repressed expression of ERBB2, p21 and VEGF, all of which are involved in cell proliferation. MicroRNA-93 also suppressed tumor growth in null mice. This study showed that microRNA-93 can inhibit tumorigenesis and reduce the recurrence of CRC; these findings may have potential clinical applications for predicting the recurrence of CRC.

  1. Development of a novel cyclic RGD peptide for multiple targeting approaches of liposomes to tumor region.

    PubMed

    Amin, Mohamadreza; Mansourian, Mercedeh; Koning, Gerben A; Badiee, Ali; Jaafari, Mahmoud Reza; Ten Hagen, Timo L M

    2015-12-28

    Liposomes containing cytotoxic agents and targeted with Arg-Gly-Asp based peptides have frequently been used against αvβ3 integrin on tumor neovasculature. However, like many other ligand modified liposomes these preparations suffered from enhanced uptake by the reticulo endothelial system (RES) and off-targeted interaction with integrin receptors vastly expressed in normal organs causing poor biodistribution and toxic effects. Here we mainly focus on development of a RGD-modified liposomal delivery system to enhance both targeting selectivity and tumor uptake. First, sterically stabilized liposomal doxorubicin (SSLD) prepared and decorated with cRGDfK and RGDyC peptides differ in their physical properties. Stability assessments as well as in vitro and in vivo studies revealed that increasing the peptide hydrophobicity promotes the therapeutic efficacy of RGD-SSLD in a C-26 tumor model due to decreased recognition by RES and opsonization and limited off-targeted interactions. Then a novel N-methylated RGD peptide was designed and its capability in targeting integrin presenting cells was comprehensively assessed both in vitro and in vivo. RGDf[N-methyl]C promotes the liposome internalization by HUVEC via integrin mediated endocytosis. Intravital microscopy in window chamber bearing mice illustrated the capability of RGDf[N-methyl]C-liposomes in targeting both tumor vasculature and tumor cells in murine B16F0 and human BLM tumor models. Quantitative biodistribution in mice bearing B16F0 tumor revealed its high affinity to tumor with no considerable affinity to normal organs. Treatment by high dose of RGDf[N-methyl]C-SSLD was found more effective than non-targeted SSLD and no toxic side effect was observed. In conclusion, the RGDf[N-methyl]C-liposome was found promising in targeting tumor vasculature as well as other cells inside the tumor. Copyright © 2015 Elsevier B.V. All rights reserved.

  2. Development of cell-cycle checkpoint therapy for solid tumors.

    PubMed

    Tamura, Kenji

    2015-12-01

    Cellular proliferation is tightly controlled by several cell-cycle checkpoint proteins. In cancer, the genes encoding these proteins are often disrupted and cause unrestrained cancer growth. The proteins are over-expressed in many malignancies; thus, they are potential targets for anti-cancer therapies. These proteins include cyclin-dependent kinase, checkpoint kinase, WEE1 kinase, aurora kinase and polo-like kinase. Cyclin-dependent kinase inhibitors are the most advanced cell-cycle checkpoint therapeutics available. For instance, palbociclib (PD0332991) is a first-in-class, oral, highly selective inhibitor of CDK4/6 and, in combination with letrozole (Phase II; PALOMA-1) or with fulvestrant (Phase III; PALOMA-3), it has significantly prolonged progression-free survival, in patients with metastatic estrogen receptor-positive, HER2-negative breast cancer, in comparison with that observed in patients using letrozole, or fulvestrant alone, respectively. In this review, we provide an overview of the current compounds available for cell-cycle checkpoint protein-directed therapy for solid tumors. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  3. Confocal Imaging of Early Heart Development in Xenopus laevis

    PubMed Central

    Kolker, Sandra J.; Tajchman, Urszula; Weeks, Daniel L.

    2013-01-01

    Xenopus laevis provides a number of advantages for studies on cardiovascular development. The embryos are fairly large, easy to obtain, and can develop at ambient temperature in simple buffer solutions. Although classic descriptions of heart development exist, the ability to use whole mount immunohistochemical methods and confocal microscopy may enhance the ability to understand both normal and experimentally perturbed cardiovascular development. We have started to examine the early stages of cardiac development in Xenopus, seeking to identify antibodies and fixatives that allow easy examination of the developing heart. We have used monoclonal antibodies (mAbs) raised against bovine cardiac troponin T and chicken tropomyosin to visualize cardiac muscle, a goat antibody recognizing bovine type VI collagen to stain the lining of vessels, and the JB3 mAb raised against chicken fibrillin which allows the visualization of a variety of cardiovascular tissues during early development. Results from embryonic stages 24–46 are presented. PMID:10644411

  4. Challenges in early clinical development of adjuvanted vaccines.

    PubMed

    Della Cioppa, Giovanni; Jonsdottir, Ingileif; Lewis, David

    2015-06-08

    A three-step approach to the early development of adjuvanted vaccine candidates is proposed, the goal of which is to allow ample space for exploratory and hypothesis-generating human experiments and to select dose(s) and dosing schedule(s) to bring into full development. Although the proposed approach is more extensive than the traditional early development program, the authors suggest that by addressing key questions upfront the overall time, size and cost of development will be reduced and the probability of public health advancement enhanced. The immunogenicity end-points chosen for early development should be critically selected: an established immunological parameter with a well characterized assay should be selected as primary end-point for dose and schedule finding; exploratory information-rich end-points should be limited in number and based on pre-defined hypothesis generating plans, including system biology and pathway analyses. Building a pharmacodynamic profile is an important aspect of early development: to this end, multiple early (within 24h) and late (up to one year) sampling is necessary, which can be accomplished by sampling subgroups of subjects at different time points. In most cases the final target population, even if vulnerable, should be considered for inclusion in early development. In order to obtain the multiple formulations necessary for the dose and schedule finding, "bed-side mixing" of various components of the vaccine is often necessary: this is a complex and underestimated area that deserves serious research and logistical support. Copyright © 2015 Elsevier Ltd. All rights reserved.

  5. Development of Early Measures of Comprehension: Innovation in Individual Growth and Development Indicators

    ERIC Educational Resources Information Center

    Wackerle-Hollman, Alisha K.; Rodriguez, Megan I.; Bradfield, Tracy A.; Rodriguez, Michael C.; McConnell, Scott R.

    2015-01-01

    Early comprehension is an important, but not well-understood, contribution to early literacy and language development. Specifically, research regarding the nature of skills representative of early comprehension, including how they contribute to later reading success, is needed to support best practices to adequately prepare students. This article…

  6. The development of self-regulation across early childhood.

    PubMed

    Montroy, Janelle J; Bowles, Ryan P; Skibbe, Lori E; McClelland, Megan M; Morrison, Frederick J

    2016-11-01

    The development of early childhood self-regulation is often considered an early life marker for later life successes. Yet little longitudinal research has evaluated whether there are different trajectories of self-regulation development across children. This study investigates the development of behavioral self-regulation between the ages of 3 and 7 years, with a direct focus on possible heterogeneity in the developmental trajectories, and a set of potential indicators that distinguish unique behavioral self-regulation trajectories. Across 3 diverse samples, 1,386 children were assessed on behavioral self-regulation from preschool through first grade. Results indicated that majority of children develop self-regulation rapidly during early childhood, and that children follow 3 distinct developmental patterns of growth. These 3 trajectories were distinguishable based on timing of rapid gains, as well as child gender, early language skills, and maternal education levels. Findings highlight early developmental differences in how self-regulation unfolds, with implications for offering individualized support across children. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

  7. The Development of Self-Regulation across Early Childhood

    PubMed Central

    Montroy, Janelle J.; Bowles, Ryan P.; Skibbe, Lori E.; McClelland, Megan M.; Morrison, Frederick J.

    2016-01-01

    The development of early childhood self-regulation is often considered an early life marker for later life successes. Yet little longitudinal research has evaluated whether there are different trajectories of self-regulation development across children. This study investigates the development of behavioral self-regulation between the ages of three and seven, with a direct focus on possible heterogeneity in the developmental trajectories, and a set of potential indicators that distinguish unique behavioral self-regulation trajectories. Across three diverse samples, 1,386 children were assessed on behavioral self-regulation from preschool through first grade. Results indicated that majority of children develop self-regulation rapidly during early childhood, and that children follow three distinct developmental patterns of growth. These three trajectories were distinguishable based on timing of rapid gains, as well as child gender, early language skills, and maternal education levels. Findings highlight early developmental differences in how self-regulation unfolds with implications for offering individualized support across children. PMID:27709999

  8. High-b-value diffusion-weighted MR imaging for pretreatment prediction and early monitoring of tumor response to therapy in mice.

    PubMed

    Roth, Yiftach; Tichler, Thomas; Kostenich, Genady; Ruiz-Cabello, Jesus; Maier, Stephan E; Cohen, Jack S; Orenstein, Arie; Mardor, Yael

    2004-09-01

    To evaluate the use of diffusion-weighted magnetic resonance (MR) imaging with standard and high b values for pretreatment prediction and early detection of tumor response to various antineoplastic therapies in an animal model. Mice bearing C26 colon carcinoma tumors were treated with doxorubicin (n = 25) and with aminolevulinic acid-based photodynamic therapy (n = 23). Fourteen mice served as controls. Conventional T2-weighted fast spin-echo and diffusion-weighted MR images were acquired once before therapy and at 6, 24, and 48 hours after treatment. Pretreatment and early (1-2 days) posttreatment water diffusion parameters were calculated and compared with later changes in tumor volumes measured on conventional MR images by using the Pearson correlation test. In chemotherapy-treated tumors, a significant correlation (P <.002, r = 0.6) was observed between diffusion parameters that reflected tumor viability, measured prior to treatment, and changes in tumor volumes after therapy. This correlation implies that tumors with high pretreatment viability will respond better to chemotherapy than more necrotic tumors. In tumors treated with photodynamic therapy, no such correlation was found. Changes observed in water diffusion 1-2 days after treatment significantly correlated with later tumor growth rate for both therapies (P <.002, r = 0.54 for photodynamic therapy; P <.0003, r = 0.61 for chemotherapy). High-b-value diffusion-weighted MR imaging has potential use for the early detection of response to therapy and for predicting treatment outcome prior to initiation of chemotherapy. Copyright RSNA, 2004

  9. Breast cancer instructs dendritic cells to prime interleukin 13–secreting CD4+ T cells that facilitate tumor development

    PubMed Central

    Aspord, Caroline; Pedroza-Gonzalez, Alexander; Gallegos, Mike; Tindle, Sasha; Burton, Elizabeth C.; Su, Dan; Marches, Florentina; Banchereau, Jacques; Palucka, A. Karolina

    2007-01-01

    We previously reported (Bell, D., P. Chomarat, D. Broyles, G. Netto, G.M. Harb, S. Lebecque, J. Valladeau, J. Davoust, K.A. Palucka, and J. Banchereau. 1999. J. Exp. Med. 190: 1417–1426) that breast cancer tumors are infiltrated with mature dendritic cells (DCs), which cluster with CD4+ T cells. We now show that CD4+ T cells infiltrating breast cancer tumors secrete type 1 (interferon γ) as well as high levels of type 2 (interleukin [IL] 4 and IL-13) cytokines. Immunofluorescence staining of tissue sections revealed intense IL-13 staining on breast cancer cells. The expression of phosphorylated signal transducer and activator of transcription 6 in breast cancer cells suggests that IL-13 actually delivers signals to cancer cells. To determine the link between breast cancer, DCs, and CD4+ T cells, we implanted human breast cancer cell lines in nonobese diabetic/LtSz-scid/scid β2 microglobulin–deficient mice engrafted with human CD34+ hematopoietic progenitor cells and autologous T cells. There, CD4+ T cells promote early tumor development. This is dependent on DCs and can be partially prevented by administration of IL-13 antagonists. Thus, breast cancer targets DCs to facilitate its development. PMID:17438063

  10. Development of Advanced Technologies for Complete Genomic and Proteomic Characterization of Quantized Human Tumor Cells

    DTIC Science & Technology

    2013-07-01

    AVAILABILITY STATEMENT Approved for Public Release; Distribution Unlimited 13. SUPPLEMENTARY NOTES 14. ABSTRACT With the establishment of GBM cell lines...and quantized cell populations form these GBM patients tumor samples we are able to complete some of our aims of our project. We will continue to...collect tumor samples with consent from families of GBM patients in preparation to perform the molecular analysis of these. Our efforts in the development

  11. Hypoxic Tumor Kinase Signaling Mediated by STAT5A in Development of Castration-Resistant Prostate Cancer

    PubMed Central

    Røe, Kathrine; Bratland, Åse; Vlatkovic, Ljiljana; Ragnum, Harald Bull; Saelen, Marie Grøn; Olsen, Dag Rune; Marignol, Laure; Ree, Anne Hansen

    2013-01-01

    In this study, we hypothesized that androgen-deprivation therapy (ADT) in prostate cancer, although initially efficient, induces changes in the tumor kinome, which subsequently promote development of castration-resistant (CR) disease. Recognizing the correlation between tumor hypoxia and poor prognosis in prostate cancer, we further hypothesized that such changes might be influenced by hypoxia. Microarrays with 144 kinase peptide substrates were applied to analyze CWR22 prostate carcinoma xenograft samples from ADT-naïve, androgen-deprived (AD), long-term AD (ADL), and CR disease stages. The impact of hypoxia was assessed by matching the xenograft kinase activity profiles with those acquired from hypoxic and normoxic prostate carcinoma cell cultures, whereas the clinical relevance was evaluated by analyzing prostatectomy tumor samples from patients with locally advanced disease, either in ADT-naïve or early CR disease stages. By using this novel peptide substrate microarray method we revealed high kinase activity mediated by signal transducer and activator of transcription 5A (STAT5A) in CR prostate cancer. Additionally, we uncovered high STAT5A kinase activity already in regressing ADL xenografts, before renewed CR growth was evidenced. Finally, since increased STAT5A kinase activity also was detected after exposing prostate carcinoma cells to hypoxia, we propose long-term ADT to induce tumor hypoxia and stimulate STAT5A kinase activity, subsequently leading to renewed CR tumor growth. Hence, the study detected STAT5A as a candidate to be further investigated for its potential as marker of advanced prostate cancer and as possible therapeutic target protein. PMID:23675504

  12. Development of a 3D ultrasound-guided system for thermal ablation of liver tumors

    NASA Astrophysics Data System (ADS)

    Neshat, Hamid R. S.; Cool, Derek W.; Barker, Kevin; Gardi, Lori; Kakani, Nirmal; Fenster, Aaron

    2013-03-01

    Two-dimensional ultrasound (2D US) imaging is commonly used for diagnostic and intraoperative guidance of interventional abdominal procedures including percutaneous thermal ablation of focal liver tumors with radiofrequency (RF) or microwave (MW) induced energy. However, in many situations 2D US may not provide enough anatomical detail and guidance information. Therefore, intra-procedural CT or MR imaging are used in many centers for guidance purposes. These modalities are costly and are mainly utilized to confirm tool placement rather than guiding the insertion. Three-dimensional ultrasound (3D US) has been introduced to address these issues. In this paper, we present our integrated solution to provide 3D US images using a newly developed mechanical transducer with a large field-ofview and without the need for external tracking devices to combine diagnostic and planning information of different modalities for intraoperative guidance. The system provides tools to segment the target(s), plan the treatment, and detect the ablation applicators during the procedure for guiding purposes. We present experimental results used to ensure that our system generates accurate measurements and our early clinical evaluation results. The results suggest that 3D US used for focal liver ablation can provide a more reliable planning and guidance tool compared to 2D US only, and in many cases offers comparable measurements to other alternatives at significantly lower cost, faster time and with no harmful radiation.

  13. Development of tumor-targeted near infrared probes for fluorescence guided surgery.

    PubMed

    Kelderhouse, Lindsay E; Chelvam, Venkatesh; Wayua, Charity; Mahalingam, Sakkarapalayam; Poh, Scott; Kularatne, Sumith A; Low, Philip S

    2013-06-19

    Complete surgical resection of malignant disease is the only reliable method to cure cancer. Unfortunately, quantitative tumor resection is often limited by a surgeon's ability to locate all malignant disease and distinguish it from healthy tissue. Fluorescence-guided surgery has emerged as a tool to aid surgeons in the identification and removal of malignant lesions. While nontargeted fluorescent dyes have been shown to passively accumulate in some tumors, the resulting tumor-to-background ratios are often poor, and the boundaries between malignant and healthy tissues can be difficult to define. To circumvent these problems, our laboratory has developed high affinity tumor targeting ligands that bind to receptors that are overexpressed on cancer cells and deliver attached molecules selectively into these cells. In this study, we explore the use of two tumor-specific targeting ligands (i.e., folic acid that targets the folate receptor (FR) and DUPA that targets prostate specific membrane antigen (PSMA)) to deliver near-infrared (NIR) fluorescent dyes specifically to FR and PSMA expressing cancers, thereby rendering only the malignant cells highly fluorescent. We report here that all FR- and PSMA-targeted NIR probes examined bind cultured cancer cells in the low nanomolar range. Moreover, upon intravenous injection into tumor-bearing mice with metastatic disease, these same ligand-NIR dye conjugates render receptor-expressing tumor tissues fluorescent, enabling their facile resection with minimal contamination from healthy tissues.

  14. Tumor microenvironment is multifaceted.

    PubMed

    Sautès-Fridman, Catherine; Cherfils-Vicini, Julien; Damotte, Diane; Fisson, Sylvain; Fridman, Wolf Hervé; Cremer, Isabelle; Dieu-Nosjean, Marie-Caroline

    2011-03-01

    Cancer initiation, progression, and invasion occur in a complex and dynamic microenvironment which depends on the hosts and sites where tumors develop. Tumors arising in mucosal tissues may progress in an inflammatory context linked to local viral and/or bacterial infections. At the opposite, tumors developing in immunoprivileged sites are protected from microorganisms and grow in an immunosuppressive environment. In the present review, we summarize and present our recent data on the influence of infectious context and immune cell infiltration organization in human Non-Small Cell Lung Cancers (NSCLC) progression. We show that stimulation of tumor cells by TLR for viral ssRNA, such as TLR7/8, or bacteria, such as TLR4, promotes cell survival and induces chemoresistance. On the opposite, stimulation by TLR3, receptor for double-stranded viral RNA, decreases tumor cell viability and induces chemosensitivity in some lung tumor cell lines. Since fresh lung tumor cells exhibit a gene expression profile characteristic of TLR-stimulated lung tumor cell lines, we suspect that viral and bacterial influence may not only act on the host immune system but also directly on tumor growth and sensitivity to chemotherapy. The stroma of NSCLC contains tertiary lymphoid structures (or Tumor-induced Bronchus-Associated Lymphoid Tissues (Ti-BALT)) with mature DC, follicular DC, and T and B cells. Two subsets of immature DC, Langerhans cells (LC) and interstitial DC (intDC), were detected in the tumor nests and the stroma, respectively. Here, we show that the densities of the three DC subsets, mature DC, LC, and intDC, are highly predictive of disease-specific survival in a series of 74 early-stage NSCLC patients. We hypothesize that the mature DC may derive from local activation and migration of the immature DC--and especially LC which contact the tumor cells--to the tertiary lymphoid structures, after sampling and processing of the tumor antigens. In view of the prominent role of DC in

  15. Temperament, Executive Control, and ADHD across Early Development

    PubMed Central

    Rabinovitz, Beth B.; O’Neill, Sarah; Rajendran, Khushmand; Halperin, Jeffrey M.

    2015-01-01

    Research examining factors linking early temperament and later ADHD is limited by cross-sectional approaches and having the same informant rate both temperament and psychopathology. We used multi-informant/multi-method longitudinal data to test the hypothesis that negative emotionality during preschool is positively associated with ADHD symptom severity in middle childhood, but developing executive control mediates this relation. Children (N=161) with and without ADHD were evaluated three times: Parent and teacher temperament ratings and NEPSY Visual Attention at ages 3–4 years; WISC-IV Working Memory Index and NEPSY Response Set at age 6 years; and ADHD symptoms using the Kiddie-SADS at age 7 years. Parent and teacher ratings of preschoolers’ temperament were combined to form an Anger/Frustration composite. Similarly, an Executive Functioning composite was derived from age 6 measures. Bootstrapping was used to determine whether age 6 Executive Functioning mediated the relation between early Anger/Frustration and later ADHD symptom severity, while controlling for early executive functioning. Preschoolers’ Anger/Frustration was significantly associated with later ADHD symptoms, with this relation partially mediated by age 6 Executive Functioning. Developing executive control mediates the relation between early Anger/Frustration and later ADHD symptom severity, suggesting that Anger/Frustration influences ADHD symptom severity through its impact on developing executive control. Early interventions targeting the harmful influences of negative emotionality or enhancing executive functioning may diminish later ADHD severity. PMID:26854505

  16. Embedded Professional Development and Classroom-Based Early Reading Intervention: Early Diagnostic Reading Intervention through Coaching

    ERIC Educational Resources Information Center

    Amendum, Steven J.

    2014-01-01

    The purpose of the current mixed-methods study was to investigate a model of professional development and classroom-based early reading intervention implemented by the 1st-grade teaching team in a large urban/suburban school district in the southeastern United States. The intervention provided teachers with ongoing embedded professional…

  17. New Hampshire Early Childhood Professional Development System: Guide to Early Childhood Careers.

    ERIC Educational Resources Information Center

    McDonnell, Tessa, Ed.

    The community of child care providers in New Hampshire has adopted the Early Childhood Professional Development System as an initial step toward assuring quality care and education for children. This guide describes the components of that system and is presented in eight sections. Section 1 of the guide introduces the system based on a set of two…

  18. The Australian Early Development Index: Reshaping Family-Child Relationships in Early Childhood Education

    ERIC Educational Resources Information Center

    Peers, Chris

    2011-01-01

    This article addresses the cultural significance of the Australian Early Development Index (AEDI) and discusses changes that the discourse of this instrument makes to the way in which the child is conceptualised. It analyses the technological function of the AEDI to examine how it makes the child a universal resource for human capital. The article…

  19. Early Learning Foundations. Indiana's Early Learning Development Framework Aligned to the Indiana Academic Standards, 2014

    ERIC Educational Resources Information Center

    Indiana Department of Education, 2015

    2015-01-01

    The "Foundations" (English/language arts, mathematics, social emotional skills, approaches to play and learning, science, social studies, creative arts, and physical health and growth) are Indiana's early learning development framework and are aligned to the 2014 Indiana Academic Standards. This framework provides core elements that…

  20. Early childhood obesity is associated with compromised cerebellar development.

    PubMed

    Miller, Jennifer L; Couch, Jessica; Schwenk, Krista; Long, Michelle; Towler, Stephen; Theriaque, Douglas W; He, Guojun; Liu, Yijun; Driscoll, Daniel J; Leonard, Christiana M

    2009-01-01

    As part of a study investigating commonalities between Prader-Willi syndrome (PWS-a genetic imprinting disorder) and early-onset obesity of unknown etiology (EMO) we measured total cerebral and cerebellar volume on volumetric magnetic resonance imaging (MRI) images. Individuals with PWS (N = 16) and EMO (N = 12) had smaller cerebellar volumes than a control group of 15 siblings (p = .02 control vs. EMO; p = .0005 control vs. PWS), although there was no difference among the groups in cerebral volume. Individuals with PWS and EMO also had impaired cognitive function: general intellectual ability (GIA): PWS 65 +/- 25; EMO 81 +/- 19; and Controls 112 +/- 13 (p < .0001 controls vs. PWS and controls vs. EMO). As both conditions are characterized by early-onset obesity and slowed cognitive development, these results raise the possibility that early childhood obesity retards both cerebellar and cognitive development.

  1. Activated ovarian endothelial cells promote early follicular development and survival.

    PubMed

    Kedem, Alon; Aelion-Brauer, Anate; Guo, Peipei; Wen, Duancheng; Ding, Bi-Sen; Lis, Raphael; Cheng, Du; Sandler, Vladislav M; Rafii, Shahin; Rosenwaks, Zev

    2017-09-19

    New data suggests that endothelial cells (ECs) elaborate essential "angiocrine factors". The aim of this study is to investigate the role of activated ovarian endothelial cells in early in-vitro follicular development. Mouse ovarian ECs were isolated using magnetic cell sorting or by FACS and cultured in serum free media. After a constitutive activation of the Akt pathway was initiated, early follicles (50-150 um) were mechanically isolated from 8-day-old mice and co-cultured with these activated ovarian endothelial cells (AOEC) (n = 32), gel (n = 24) or within matrigel (n = 27) in serum free media for 14 days. Follicular growth, survival and function were assessed. After 6 passages, flow cytometry showed 93% of cells grown in serum-free culture were VE-cadherin positive, CD-31 positive and CD 45 negative, matching the known EC profile. Beginning on day 4 of culture, we observed significantly higher follicular and oocyte growth rates in follicles co-cultured with AOECs compared with follicles on gel or matrigel. After 14 days of culture, 73% of primary follicles and 83% of secondary follicles co-cultured with AOEC survived, whereas the majority of follicles cultured on gel or matrigel underwent atresia. This is the first report of successful isolation and culture of ovarian ECs. We suggest that co-culture with activated ovarian ECs promotes early follicular development and survival. This model is a novel platform for the in vitro maturation of early follicles and for the future exploration of endothelial-follicular communication. In vitro development of early follicles necessitates a complex interplay of growth factors and signals required for development. Endothelial cells (ECs) may elaborate essential "angiocrine factors" involved in organ regeneration. We demonstrate that co-culture with ovarian ECs enables culture of primary and early secondary mouse ovarian follicles.

  2. Lessons for tumor biomarker trials: vicious cycles, scientific method & developing guidelines.

    PubMed

    Hayes, Daniel; Raison, Claire

    2015-02-01

    Interview with Daniel Hayes, by Claire Raison (Commissioning Editor) Daniel F Hayes, M.D. is the Stuart A Padnos Professor of Breast Cancer Research and co-Director of the Breast Oncology Program at the University of Michigan Comprehensive Cancer Center (Ann Arbor, MI, USA). Dr Hayes has extensive experience in clinical and translational breast cancer biomarker research, and in drug development and clinical trials. Around 30 years ago, he led the discovery of the circulating breast tumor biomarker, CA15-3, which started his career into further tumor biomarker work. The main thrust of his work since then has been in clinical trials, tumor biomarkers and trying to integrate the two. Dr Hayes is Chair of the Correlative Sciences Committee of the North American Breast Cancer Group (now called the Breast Cancer Steering Committee), and co-chairs the Expert Panel for Tumor Biomarker Practice Guidelines for the American Society of Clinical Oncology.

  3. In vivo preclinical photoacoustic imaging of tumor vasculature development and therapy

    NASA Astrophysics Data System (ADS)

    Laufer, Jan; Johnson, Peter; Zhang, Edward; Treeby, Bradley; Cox, Ben; Pedley, Barbara; Beard, Paul

    2012-05-01

    The use of a novel all-optical photoacoustic scanner for imaging the development of tumor vasculature and its response to a therapeutic vascular disrupting agent is described. The scanner employs a Fabry-Perot polymer film ultrasound sensor for mapping the photoacoustic waves and an image reconstruction algorithm based upon attenuation-compensated acoustic time reversal. The system was used to noninvasively image human colorectal tumor xenografts implanted subcutaneously in mice. Label-free three-dimensional in vivo images of whole tumors to depths of almost 10 mm with sub-100-micron spatial resolution were acquired in a longitudinal manner. This enabled the development of tumor-related vascular features, such as vessel tortuosity, feeding vessel recruitment, and necrosis to be visualized over time. The system was also used to study the temporal evolution of the response of the tumor vasculature following the administration of a therapeutic vascular disrupting agent (OXi4503). This revealed the well-known destruction and recovery phases associated with this agent. These studies illustrate the broader potential of this technology as an imaging tool for the preclinical and clinical study of tumors and other pathologies characterized by changes in the vasculature.

  4. WISP1 genetic variants as predictors of tumor development with urothelial cell carcinoma.

    PubMed

    Lee, Hsiang-Lin; Chiou, Hui-Ling; Wang, Shian-Shiang; Hung, Sheng-Chun; Chou, Ming-Chih; Yang, Shun-Fa; Hsieh, Ming-Ju; Chou, Ying-Erh

    2018-04-01

    Urothelial cell carcinoma (UCC) of the urinary bladder is a major malignancy of the genitourinary tract. Etiological factors, such as the environment, ethnicity, genetics, and diet, contribute to UCC carcinogenesis. WNT1-inducible signaling pathway protein 1 (WISP1), also known as CCN4, a cysteine-rich protein belonging to the Cyr61, CTGF, Nov (CCN) family of matricellular proteins, has many developmental functions and might be involved in carcinogenesis. This study investigated WISP1 single-nucleotide polymorphisms to evaluate UCC susceptibility and clinicopathological characteristics. Real-time polymerase chain reaction was used to analyze 4 single-nucleotide polymorphisms of WISP1 in 369 patients with UCC and 738 controls without cancer. The results showed that in 128 women with UCC who carried WISP1 rs2929973 (AG + GG) variants had a higher risk of developing an advanced muscle-invasive tumor stage (pT2-pT4, P = 0.007) and a large tumor (T1-T4, P = 0.030). Further analyses revealed that a correlation between the expressions of WISP1 and invasive tumor and large tumor size in urothelial carcinoma was observed in the TCGA (The Cancer Genome Atlas) dataset. Our results indicated that patients with UCC carrying rs2977530 genetic variants (AG + GG) have a higher risk of developing a more invasive tumor stage and a large tumor. WISP1 polymorphisms may serve as a marker or a therapeutic target in UCC. Copyright © 2017 Elsevier Inc. All rights reserved.

  5. Early development of synchrony in cortical activations in the human.

    PubMed

    Koolen, N; Dereymaeker, A; Räsänen, O; Jansen, K; Vervisch, J; Matic, V; Naulaers, G; De Vos, M; Van Huffel, S; Vanhatalo, S

    2016-05-13

    Early intermittent cortical activity is thought to play a crucial role in the growth of neuronal network development, and large scale brain networks are known to provide the basis for higher brain functions. Yet, the early development of the large scale synchrony in cortical activations is unknown. Here, we tested the hypothesis that the early intermittent cortical activations seen in the human scalp EEG show a clear developmental course during the last trimester of pregnancy, the period of intensive growth of cortico-cortical connections. We recorded scalp EEG from altogether 22 premature infants at post-menstrual age between 30 and 44 weeks, and the early cortical synchrony was quantified using recently introduced activation synchrony index (ASI). The developmental correlations of ASI were computed for individual EEG signals as well as anatomically and mathematically defined spatial subgroups. We report two main findings. First, we observed a robust and statistically significant increase in ASI in all cortical areas. Second, there were significant spatial gradients in the synchrony in fronto-occipital and left-to-right directions. These findings provide evidence that early cortical activity is increasingly synchronized across the neocortex. The ASI-based metrics introduced in our work allow direct translational comparison to in vivo animal models, as well as hold promise for implementation as a functional developmental biomarker in future research on human neonates. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

  6. Family Concepts in Early Learning and Development Standards

    ERIC Educational Resources Information Center

    Walsh, Bridget A.; Sanchez, Claudia; Lee, Angela M.; Casillas, Nicole; Hansen, Caitlynn

    2016-01-01

    This exploratory study investigated the use of concepts related to families, parents, and the home in 51 state-level early learning and development standards documents. Guidelines from six national family involvement, engagement, and school-partnership models were used to create the Family Involvement Models Analysis Chart (FIMAC), which served as…

  7. Regionalism and Development in Early Nineteenth Century Spanish America.

    ERIC Educational Resources Information Center

    Friedman, Douglas

    An understanding of regionalism in early 19th century Spanish America is crucial to any understanding of this region's economic development. Regionalism became the barrier to the kind of integrated national economy that some writers claim could have been implemented had it not been for the imposition of dependency by external forces. This…

  8. Starting Smart: How Early Experiences Affect Brain Development. Second Edition.

    ERIC Educational Resources Information Center

    Hawley, Theresa

    Based on recent research, it is now believed that brain growth is highly dependent upon children's early experiences. Neurons allow communication and coordinated functioning among various brain areas. Brain development after birth consists of an ongoing process of wiring and rewiring the connections among neurons. The forming and breaking of…

  9. Applying cognitive training to target executive functions during early development.

    PubMed

    Wass, Sam V

    2015-01-01

    Developmental psychopathology is increasingly recognizing the importance of distinguishing causal processes (i.e., the mechanisms that cause a disease) from developmental outcomes (i.e., the symptoms of the disorder as it is eventually diagnosed). Targeting causal processes early in disordered development may be more effective than waiting until outcomes are established and then trying to reverse the pathogenic process. In this review, I evaluate evidence suggesting that neural and behavioral plasticity may be greatest at very early stages of development. I also describe correlational evidence suggesting that, across a number of conditions, early emerging individual differences in attentional control and working memory may play a role in mediating later-developing differences in academic and other forms of learning. I review the currently small number of studies that applied direct and indirect cognitive training targeted at young individuals and discuss methodological challenges associated with targeting this age group. I also discuss a number of ways in which early, targeted cognitive training may be used to help us understand the developmental mechanisms subserving typical and atypical cognitive development.

  10. The Ecology of Early Reading Development for Children in Poverty

    ERIC Educational Resources Information Center

    Kainz, Kirsten; Vernon-Feagans, Lynne

    2007-01-01

    In this study we investigated reading development from kindergarten to third grade for 1,913 economically disadvantaged children from the Early Childhood Longitudinal Study-Kindergarten Cohort. Characteristics of the child, the family, classroom instruction, and school composition were used to model influences from multiple levels of children's…

  11. Rethinking Early Learning and Development Standards in the Ugandan Context

    ERIC Educational Resources Information Center

    Ejuu, Godfrey

    2013-01-01

    Concerns that the African child is being tailored to be a "global child," alongside other homogenizing and dominating projections, such as early learning and development standards (ELDS), have increased. African communities need to be assured that global standards and global indicators will not further homogenize nations and thereby risk…

  12. Changing the Perspective on Early Development of Rett Syndrome

    ERIC Educational Resources Information Center

    Marschik, Peter B.; Kaufmann, Walter E.; Sigafoos, Jeff; Wolin, Thomas; Zhang, Dajie; Bartl-Pokorny, Katrin D.; Pini, Giorgio; Zappella, Michele; Tager-Flusberg, Helen; Einspieler, Christa; Johnston, Michael V.

    2013-01-01

    We delineated the achievement of early speech-language milestones in 15 young children with Rett syndrome ("MECP2" positive) in the first two years of life using retrospective video analysis. By contrast to the commonly accepted concept that these children are normal in the pre-regression period, we found markedly atypical development of…

  13. Model of Early Support of Child Development in Poland

    ERIC Educational Resources Information Center

    Czyz, Anna Katarzyna

    2018-01-01

    The development of a child, especially a child with a disability, is conditional upon the initiation of rehabilitation measures immediately after the problem has been identified. The quality of the reaction is conditioned by the functioning of the therapeutic team. The main purpose of the research was the diagnosis of early support system for…

  14. Identification of the Social Development in Early Childhood in Pakistan

    ERIC Educational Resources Information Center

    Malik, Asif; Sarwar, Muhammad; Khan, Naeemullah

    2010-01-01

    This study was conducted to identify the social development in early childhood years. It was delimited to eight private schools of Lahore City from the area of Faisal Town and Shadman. Forty students (male and female) were randomly selected as the sample. Five students from Nursery, Prep and grade one were selected from each school. A checklist…

  15. The Use of Electrophysiology in the Study of Early Development

    ERIC Educational Resources Information Center

    Szucs, Denes

    2005-01-01

    Electrophysiology is a timely and important tool in the study of early cognitive development. This commentary polishes the definition of event-related potential (ERP) components; often interpreted as expressions of mental processes. Further, attention is drawn to time-frequency analysis of the electroencephalogram (EEG) which conveys much more…

  16. Development of the Life Story in Early Adolescence

    ERIC Educational Resources Information Center

    Steiner, Kristina L.; Pillemer, David B.

    2018-01-01

    Life span developmental psychology proposes that the ability to create a coherent life narrative does not develop until early adolescence. Using a novel methodology, 10-, 12-, and 14-year-old participants were asked to tell their life stories aloud to a researcher. Later, participants separated their transcribed narratives into self-identified…

  17. MAMMARY GLAND DEVELOPMENT: EARLY LIFE EFFECTS FROM THE ENVIRONMENT

    EPA Science Inventory

    Mammary Gland Development: Early Life Effects from the Environment

    S.E. Fenton. Reproductive Toxicology Division, National Health and Environmental Effects Laboratory, ORD, U.S. EPA, Research Triangle Park, NC 27711.

    As signs of precocious puberty in girls reach ...

  18. Predictors of Early versus Later Spelling Development in Danish

    ERIC Educational Resources Information Center

    Nielsen, Anne-Mette Veber; Juul, Holger

    2016-01-01

    The present study examined phoneme awareness, phonological short term memory, letter knowledge, rapid automatized naming (RAN), and visual-verbal paired associate learning (PAL) as longitudinal predictors of spelling skills in an early phase (Grade 2) and a later phase (Grade 5) of development in a sample of 140 children learning to spell in the…

  19. Career Planning and Development for Early-Career Scientists

    EPA Science Inventory

    Early career development can be looked at as being of two major phases. The first phase is the formal educational process leading to an awarded degree, postdoctoral training, and potentially formal certification in a scientific discipline. The second phase is the informal educa...

  20. Early Intervention and Its Effects on Maternal and Child Development.

    ERIC Educational Resources Information Center

    Slaughter, Diana T.

    1983-01-01

    The longitudinal study reported used an intervention strategy to test the thesis that sociocultural background, mediated by maternal attitudes and behaviors, influences Black children's early development in educationally significant ways. Two models of parent education were contrasted: the Levenstein toy demonstration program and the…

  1. Developing Early Undergraduate Research at a Two-Year College

    ERIC Educational Resources Information Center

    Sibbernsen, Kendra

    2013-01-01

    Two-year college (TYC) physics teachers are not often required to provide student research experiences as a part of their contracted duties. However, some TYC physics faculty members are interested in developing research opportunities for their freshman- and sophomore-level students, often called "early undergraduate research" (EUR).…

  2. Applying cognitive training to target executive functions during early development

    PubMed Central

    Wass, Sam V.

    2015-01-01

    Developmental psychopathology is increasingly recognizing the importance of distinguishing causal processes (i.e., the mechanisms that cause a disease) from developmental outcomes (i.e., the symptoms of the disorder as it is eventually diagnosed). Targeting causal processes early in disordered development may be more effective than waiting until outcomes are established and then trying to reverse the pathogenic process. In this review, I evaluate evidence suggesting that neural and behavioral plasticity may be greatest at very early stages of development. I also describe correlational evidence suggesting that, across a number of conditions, early emerging individual differences in attentional control and working memory may play a role in mediating later-developing differences in academic and other forms of learning. I review the currently small number of studies that applied direct and indirect cognitive training targeted at young individuals and discuss methodological challenges associated with targeting this age group. I also discuss a number of ways in which early, targeted cognitive training may be used to help us understand the developmental mechanisms subserving typical and atypical cognitive development. PMID:24511910

  3. Guidelines for Making a Video Presentation on Early Development.

    ERIC Educational Resources Information Center

    Cooper, Carolyn S.; And Others

    This paper discusses the production of videotape recordings illustrating developmental milestones of early childhood to serve as a reference point in working with parents or staff caring for young children who have disabilities. Procedures for making a video presentation include the following steps: select a topic (such as motor development,…

  4. Approaches to Developing Health in Early Years Settings

    ERIC Educational Resources Information Center

    Mooney, Ann; Boddy, Janet; Statham, June; Warwick, Ian

    2008-01-01

    Purpose: The purpose of the paper is to consider the opportunities and difficulties in developing health-promotion work in early years settings in the UK. Design/methodology/approach: As the first study of its kind conducted in the UK, a multi-method approach was adopted involving: an overview of health-related guidance and of effective…

  5. Formative Evaluation of the Early Development Instrument: Progress and Prospects

    ERIC Educational Resources Information Center

    Keating, Daniel P.

    2007-01-01

    This article is a commentary for the special issue on the Early Development Instrument (EDI), a community tool to assess children's school readiness and developmental outcomes at a group level. The EDI is administered by kindergarten teachers, who assess their kindergarten students on 5 developmental domains: physical health and well-being, social…

  6. State Guide to Developing Successful Early Childhood Data Systems

    ERIC Educational Resources Information Center

    ICF International (NJ1), 2012

    2012-01-01

    Early education leaders--inside and outside of government--are looking for new ways to improve quality, accountability, and efficiency across many different programs serving young children and their families, and they see investment in data systems as a pivotal part of that effort. However, it can be challenging to develop and implement effective…

  7. Towards Sustainable National Development through Well Managed Early Childhood Education

    ERIC Educational Resources Information Center

    Abraham, Nath M.

    2012-01-01

    This paper discusses issues relating to sustainable development and effective management of early childhood education. The child is the "owner" of the future. The problems that confront the current generation are complex and serious that cannot be addressed in the same way they were created. But they can be addressed. The concept of…

  8. More Alike than Different: Early Childhood Professional Development in Guatemala

    ERIC Educational Resources Information Center

    Hardin, Belinda J.; Vardell, Rosemarie; de Castaneda, Albertina

    2008-01-01

    This article describes an early childhood professional development project that took place in the summer of 2005 in Guatemala City. Located in Central America, Guatemala has a population of approximately 12.3 million people, including more than two million children under the age of 5 (UNESCO Institute for Statistics, 2007; UNICEF, 2004). Events…

  9. Black Female Faculty Success and Early Career Professional Development

    ERIC Educational Resources Information Center

    Jones, Tamara Bertrand; Osborne-Lampkin, La'Tara

    2013-01-01

    In recent years, a number of Black female junior scholars have participated in an early career professional development program designed to address socialization issues through individual and small group mentoring. This descriptive qualitative study investigated scholars' perceptions of the importance and effectiveness of a research…

  10. HIV Infection: Transmission, Effects on Early Development, and Interventions.

    ERIC Educational Resources Information Center

    Lowenthal, Barbara

    1997-01-01

    Describes the modes of transmission of HIV and the course of the disease in infants and toddlers. Information is provided on its effects on early development, medical screening and treatments, therapies, psychosocial assistance, and interventions, including nutritional therapy, occupational and physical therapies, and speech and language therapy.…

  11. Toward the development of intrafraction tumor deformation tracking using a dynamic multi-leaf collimator

    PubMed Central

    Ge, Yuanyuan; O’Brien, Ricky T.; Shieh, Chun-Chien; Booth, Jeremy T.; Keall, Paul J.

    2014-01-01

    Purpose: Intrafraction deformation limits targeting accuracy in radiotherapy. Studies show tumor deformation of over 10 mm for both single tumor deformation and system deformation (due to differential motion between primary tumors and involved lymph nodes). Such deformation cannot be adapted to with current radiotherapy methods. The objective of this study was to develop and experimentally investigate the ability of a dynamic multi-leaf collimator (DMLC) tracking system to account for tumor deformation. Methods: To compensate for tumor deformation, the DMLC tracking strategy is to warp the planned beam aperture directly to conform to the new tumor shape based on real time tumor deformation input. Two deformable phantoms that correspond to a single tumor and a tumor system were developed. The planar deformations derived from the phantom images in beam's eye view were used to guide the aperture warping. An in-house deformable image registration software was developed to automatically trigger the registration once new target image was acquired and send the computed deformation to the DMLC tracking software. Because the registration speed is not fast enough to implement the experiment in real-time manner, the phantom deformation only proceeded to the next position until registration of the current deformation position was completed. The deformation tracking accuracy was evaluated by a geometric target coverage metric defined as the sum of the area incorrectly outside and inside the ideal aperture. The individual contributions from the deformable registration algorithm and the finite leaf width to the tracking uncertainty were analyzed. Clinical proof-of-principle experiment of deformation tracking using previously acquired MR images of a lung cancer patient was implemented to represent the MRI-Linac environment. Intensity-modulated radiation therapy (IMRT) treatment delivered with enabled deformation tracking was simulated and demonstrated. Results: The first

  12. Toward the development of intrafraction tumor deformation tracking using a dynamic multi-leaf collimator

    SciT

    Ge, Yuanyuan; O’Brien, Ricky T.; Shieh, Chun-Chien

    Purpose: Intrafraction deformation limits targeting accuracy in radiotherapy. Studies show tumor deformation of over 10 mm for both single tumor deformation and system deformation (due to differential motion between primary tumors and involved lymph nodes). Such deformation cannot be adapted to with current radiotherapy methods. The objective of this study was to develop and experimentally investigate the ability of a dynamic multi-leaf collimator (DMLC) tracking system to account for tumor deformation. Methods: To compensate for tumor deformation, the DMLC tracking strategy is to warp the planned beam aperture directly to conform to the new tumor shape based on real timemore » tumor deformation input. Two deformable phantoms that correspond to a single tumor and a tumor system were developed. The planar deformations derived from the phantom images in beam's eye view were used to guide the aperture warping. An in-house deformable image registration software was developed to automatically trigger the registration once new target image was acquired and send the computed deformation to the DMLC tracking software. Because the registration speed is not fast enough to implement the experiment in real-time manner, the phantom deformation only proceeded to the next position until registration of the current deformation position was completed. The deformation tracking accuracy was evaluated by a geometric target coverage metric defined as the sum of the area incorrectly outside and inside the ideal aperture. The individual contributions from the deformable registration algorithm and the finite leaf width to the tracking uncertainty were analyzed. Clinical proof-of-principle experiment of deformation tracking using previously acquired MR images of a lung cancer patient was implemented to represent the MRI-Linac environment. Intensity-modulated radiation therapy (IMRT) treatment delivered with enabled deformation tracking was simulated and demonstrated. Results: The first

  13. Use of early tumor shrinkage to predict long-term outcome in metastatic colorectal cancer treated with cetuximab.

    PubMed

    Piessevaux, Hubert; Buyse, Marc; Schlichting, Michael; Van Cutsem, Eric; Bokemeyer, Carsten; Heeger, Steffen; Tejpar, Sabine

    2013-10-20

    Early tumor shrinkage (ETS) is associated with long-term outcome in patients with chemorefractory metastatic colorectal cancer (mCRC) receiving cetuximab. This association was investigated in the first-line setting in the randomized CRYSTAL and OPUS mCRC trials, after controlling for KRAS tumor mutation status. Radiologic assessments at week 8 were used to calculate the relative change in the sum of the longest diameters of the target lesions. Time-dependent receiver operating characteristics provided Cτ-indices (time-dependent c-index). Cox regression models and subpopulation treatment effect pattern plot analysis investigated associations between ETS (radiologic tumor size decrease at week 8) and survival and progression-free survival (PFS). In both trials, in patients with KRAS wild-type mCRC, Cτ values for PFS and survival were higher (P < .001) in those receiving chemotherapy plus cetuximab versus chemotherapy alone, indicating a stronger predictive value of ETS for long-term outcome in these patients. In the CRYSTAL and OPUS trials, respectively, the cutoff value of ETS ≥ 20% (v < 20%) identified patients with KRAS wild-type mCRC receiving chemotherapy plus cetuximab with longer PFS (medians 14.1 v 7.3 months, hazard ratio [HR] = 0.32; P < .001, and medians 11.9 v 5.7 months, HR = 0.22; P < .001) and survival (medians 30.0 v 18.6 months, HR = 0.53; P < .001 and medians 26.0 v 15.7 months, HR = 0.43; P = .006). ETS was significantly associated with long-term outcome in patients with KRAS wild-type mCRC treated first-line with chemotherapy plus cetuximab. Validation in prospective trials is required to assess the value of this on-treatment marker in the clinical decision-making process.

  14. Interstitial radiation therapy for early-stage nasal vestibule cancer: A continuing quest for optimal tumor control and cosmesis

    SciT

    Levendag, Peter C.; Nijdam, Wideke M.; Moolenburgh, Sanne E. van

    Introduction: This article reports on the effectiveness, cosmetic outcome, and costs of interstitial high-dose-rate (HDR) brachytherapy for early-stage cancer of the nasal vestibule (NV) proper and/or columella high-dose-rate (HDR). Methods and Materials: Tumor control, survival, cosmetic outcome, functional results, and costs were established in 64 T1/T2N0 nasal vestibule cancers treated from 1991-2005 by fractionated interstitial radiation therapy (IRT) only. Total dose is 44 Gy: 2 fractions of 3 Gy per day, 6-hour interval, first and last fraction 4 Gy. Cosmesis is noted in the chart by the medical doctor during follow-up, by the patient (visual analog scale), and by amore » panel. Finally, full hospital costs are computed. Results: A local relapse-free survival rate of 92% at 5 years was obtained. Four local failures were observed; all four patients were salvaged. The neck was not treated electively; no neck recurrence in follow-up was seen. Excellent cosmetic and functional results were observed. With 10 days admission for full treatment, hospital costs amounted to Euro 5772 ($7044). Conclusion: Excellent tumor control, cosmesis, and function of nasal airway passage can be achieved when HDR-IRT for T1/T2N0 NV cancers is used. For the more advanced cancers (Wang classification: T3 tumor stage), we elect to treat by local excision followed by a reconstructive procedure. The costs, admission to hospital inclusive, for treatment by HDR-IRT amounts to Euro 5772 ($7044 US). This contrasts substantially with the full hospital costs when NV cancers are treated by plastic reconstructive surgery, being on average threefold as expensive.« less

  15. The Impact of Tumor Size on Outcomes After Stereotactic Body Radiation Therapy for Medically Inoperable Early-Stage Non-Small Cell Lung Cancer

    SciT

    Allibhai, Zishan; Taremi, Mojgan; Bezjak, Andrea

    2013-12-01

    Purpose: Stereotactic body radiation therapy for medically inoperable early-stage non-small cell lung cancer (NSCLC) offers excellent control rates. Most published series deal mainly with small (usually <4 cm), peripheral, solitary tumors. Larger tumors are associated with poorer outcomes (ie, lower control rates, higher toxicity) when treated with conventional RT. It is unclear whether SBRT is sufficiently potent to control these larger tumors. We therefore evaluated and examined the influence of tumor size on treatment outcomes after SBRT. Methods and Materials: Between October 2004 and October 2010, 185 medically inoperable patients with early (T1-T2N0M0) NSCLC were treated on a prospective researchmore » ethics board-approved single-institution protocol. Prescription doses were risk-adapted based on tumor size and location. Follow-up included prospective assessment of toxicity (as per Common Terminology Criteria for Adverse Events, version 3.0) and serial computed tomography scans. Patterns of failure, toxicity, and survival outcomes were calculated using Kaplan-Meier method, and the significance of tumor size (diameter, volume) with respect to patient, treatment, and tumor factors was tested. Results: Median follow-up was 15.2 months. Tumor size was not associated with local failure but was associated with regional failure (P=.011) and distant failure (P=.021). Poorer overall survival (P=.001), disease-free survival (P=.001), and cause-specific survival (P=.005) were also significantly associated with tumor size (with tumor volume more significant than diameter). Gross tumor volume and planning target volume were significantly associated with grade 2 or worse radiation pneumonitis. However, overall rates of grade ≥3 pneumonitis were low and not significantly affected by tumor or target size. Conclusions: Currently employed stereotactic body radiation therapy dose regimens can provide safe effective local therapy even for larger solitary NSCLC tumors (up to

  16. Early breast tumor and late SARS detections using space-variant multispectral infrared imaging at a single pixel

    NASA Astrophysics Data System (ADS)

    Szu, Harold H.; Buss, James R.; Kopriva, Ivica

    2004-04-01

    We proposed the physics approach to solve a physical inverse problem, namely to choose the unique equilibrium solution (at the minimum free energy: H= E - ToS, including the Wiener, l.m.s E, and ICA, Max S, as special cases). The "unsupervised classification" presumes that required information must be learned and derived directly and solely from the data alone, in consistence with the classical Duda-Hart ATR definition of the "unlabelled data". Such truly unsupervised methodology is presented for space-variant imaging processing for a single pixel in the real world case of remote sensing, early tumor detections and SARS. The indeterminacy of the multiple solutions of the inverse problem is regulated or selected by means of the absolute minimum of isothermal free energy as the ground truth of local equilibrium condition at the single-pixel foot print.

  17. Cholinergic Mechanisms, Early Brain Development, and Risk for Schizophrenia

    PubMed Central

    Ross, Randal G; Stevens, Karen E; Proctor, William R; Leonard, Sherry; Kisley, Michael A; Hunter, Sharon K; Freedman, Robert; Adams, Catherine E

    2009-01-01

    Neuropsychiatric diseases are complex illnesses where the onset of diagnostic symptomology is often the end result of a decades-long process of aberrant brain development. The identification of novel treatment strategies aimed at normalizing early brain development and preventing mental illness should be a major therapeutic goal; however, there are few models for how this goal might be achieved. This report uses the attentional deficits of schizophrenia as an example and reviews data from genetic, anatomical, physiological, and pharmacologic studies to hypothesize a developmental model with translational primary prevention implications. Specifically, the model suggests that an early interaction between α7 nicotinic receptor density and choline availability may contribute to the development of schizophrenia-associated attentional deficits. Translational implications, including perinatal dietary choline supplementation, are discussed. It is hoped that presentation of this model will stimulate other efforts to develop empirically-driven primary prevention strategies. PMID:19925602

  18. Is photodynamic therapy a selective treatment? Analysis of local complications after endoscopic photodynamic therapy of early stage tumors of gastrointestinal, tracheobronchial, and urinary tracts

    NASA Astrophysics Data System (ADS)

    Spinelli, Pasquale; Dal Fante, Marco; Mancini, Andrea

    1995-03-01

    Selectivity is the most emphasized advantage of photodynamic therapy (PDT). However, at drug and light doses used for clinical applications, response from normal tissue surrounding the tumor reduces the real selectivity of the drug-light system and increases the surface of the area responding to the treatment. It is now evident that light irradiation of a sensitized patient produces damage at a various degree not only in the tumor but also in non-neoplastic tissues included in the field of irradiation. We report our experience in endoscopic PDT of early stage tumors in tracheobronchial, gastrointestinal and urinary tracts, describing early and late local complications caused by the damage of normal tissues adjacent to the tumors and included in the field of light irradiation. Among 44 patients treated, local complications, attributable to a poor selectivity of the modality, occurred in 6 patients (14%). In particular, the rate of local complications was 9% in patients treated for esophageal tumors, 14% in patients with gastric tumors, 9% in patients with tracheobronchial tumors, and 67% in bladder cancer patients. Clinical pictures as well as endoscopic findings at various intervals from treatment showed that mucositis is a common event following endoscopic PDT. It causes exudation and significant tissue inflammatory response, whose consequences are different in the various organs treated. Photoradiation must be, as much as possible, limited to the malignant area.

  19. Developing International Collaborations for Early Career Researchers in Psychology

    PubMed Central

    Flanagan, Julianne C.; Barrett, Emma L.; Crome, Erica; Forbes, Miriam

    2015-01-01

    International collaboration is becoming increasingly vital as the emphasis on unmet need for mental health across cultures and nations grows. Opportunities exist for early career researchers to engage in international collaboration. However, little information is provided about such opportunities in most current psychology training models. The authors are early career researchers in psychology from U.S. and Australia who have developed a collaborative relationship over the past two years. Our goal is to increase awareness of funding opportunities to support international research and to highlight the benefits and challenges associated with international collaboration based on our experience. PMID:27453624

  20. Early development of Xenopus embryos is affected by simulated gravity

    NASA Technical Reports Server (NTRS)

    Yokota, Hiroki; Neff, Anton W.; Malacinski, George M.

    1994-01-01

    Early amphibian (Xenopus laevis) development under clinostat-simulated weightlessness and centrifuge-simulated hypergravity was studied. The results revealed significant effects on (i) 'morphological patterning' such as the cleavage furrow pattern in the vegetal hemisphere at the eight-cell stage and the shape of the dorsal lip in early gastrulae and (ii) 'the timing of embryonic events' such as the third cleavage furrow completion and the dorsal lip appearance. Substantial variations in sensitivity to simulated force fields were observed, which should be considered in interpreting spaceflight data.

  1. Effects of early life stress on amygdala and striatal development

    PubMed Central

    Fareri, Dominic S.; Tottenham, Nim

    2016-01-01

    Species-expected caregiving early in life is critical for the normative development and regulation of emotional behavior, the ability to effectively evaluate affective stimuli in the environment, and the ability to sustain social relationships. Severe psychosocial stressors early in life (early life stress; ELS) in the form of the absence of species expected caregiving (i.e., caregiver deprivation), can drastically impact one’s social and emotional success, leading to the onset of internalizing illness later in life. Development of the amygdala and striatum, two key regions supporting affective valuation and learning, is significantly affected by ELS, and their altered developmental trajectories have important implications for cognitive, behavioral and socioemotional development. However, an understanding of the impact of ELS on the development of functional interactions between these regions and subsequent behavioral effects is lacking. In this review, we highlight the roles of the amygdala and striatum in affective valuation and learning in maturity and across development. We discuss their function separately as well as their interaction. We highlight evidence across species characterizing how ELS induced changes in the development of the amygdala and striatum mediate subsequent behavioral changes associated with internalizing illness, positing a particular import of the effect of ELS on their interaction. PMID:27174149

  2. Effects of early life stress on amygdala and striatal development.

    PubMed

    Fareri, Dominic S; Tottenham, Nim

    2016-06-01

    Species-expected caregiving early in life is critical for the normative development and regulation of emotional behavior, the ability to effectively evaluate affective stimuli in the environment, and the ability to sustain social relationships. Severe psychosocial stressors early in life (early life stress; ELS) in the form of the absence of species expected caregiving (i.e., caregiver deprivation), can drastically impact one's social and emotional success, leading to the onset of internalizing illness later in life. Development of the amygdala and striatum, two key regions supporting affective valuation and learning, is significantly affected by ELS, and their altered developmental trajectories have important implications for cognitive, behavioral and socioemotional development. However, an understanding of the impact of ELS on the development of functional interactions between these regions and subsequent behavioral effects is lacking. In this review, we highlight the roles of the amygdala and striatum in affective valuation and learning in maturity and across development. We discuss their function separately as well as their interaction. We highlight evidence across species characterizing how ELS induced changes in the development of the amygdala and striatum mediate subsequent behavioral changes associated with internalizing illness, positing a particular import of the effect of ELS on their interaction. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

  3. Mammary Tumor Development: Stromal-Epithelial Interactions in Oncogenesis.

    DTIC Science & Technology

    1996-09-01

    differentiation, prolif- erative preneoplastic lesions, or invasive adenocarcinomas , depending on the promoter con- struct used and the animal’s age when...Zn). Virgin RSV-SGF transgenic mice showed marked preneoplastic MG ductal proliferation by 6 mo. By 8 mo., 1/3 had developed adenocarcinoma . Virgin...fat pRSGF Constitutively expressed Highly abnormal. None Normal Observed at 8 1/3 of mice show months of age invasive secretory adenocarcinoma SGF

  4. Fathers' sensitive parenting and the development of early executive functioning.

    PubMed

    Towe-Goodman, Nissa R; Willoughby, Michael; Blair, Clancy; Gustafsson, Hanna C; Mills-Koonce, W Roger; Cox, Martha J

    2014-12-01

    Using data from a diverse sample of 620 families residing in rural, predominately low-income communities, this study examined longitudinal links between fathers' sensitive parenting in infancy and toddlerhood and children's early executive functioning, as well as the contribution of maternal sensitive parenting. After accounting for the quality of concurrent and prior parental care, children's early cognitive ability, and other child and family factors, fathers' and mothers' sensitive and supportive parenting during play at 24 months predicted children's executive functioning at 3 years of age. In contrast, paternal parenting quality during play at 7 months did not make an independent contribution above that of maternal care, but the links between maternal sensitive and supportive parenting and executive functioning seemed to operate in similar ways during infancy and toddlerhood. These findings add to prior work on early experience and children's executive functioning, suggesting that both fathers and mothers play a distinct and complementary role in the development of these self-regulatory skills.

  5. Enhancement of leptin receptor signaling by SOCS3 deficiency induces development of gastric tumors in mice.

    PubMed

    Inagaki-Ohara, K; Mayuzumi, H; Kato, S; Minokoshi, Y; Otsubo, T; Kawamura, Y I; Dohi, T; Matsuzaki, G; Yoshimura, A

    2014-01-02

    Leptin acts on its receptor (ObR) in the hypothalamus to inhibit food intake and energy expenditure. Leptin and ObR are also expressed in the gastrointestinal tract; however, the physiological significance of leptin signaling in the gut remains uncertain. Suppressor of cytokine signaling 3 (SOCS3) is a key negative feedback regulator of ObR-mediated signaling in the hypothalamus. We now show that gastrointestinal epithelial cell-specific SOCS3 conditional knockout (T3b-SOCS3 cKO) mice developed gastric tumors by enhancing leptin production and the ObRb/signal transducer and activator of transcription 3 (STAT3) signaling pathway. All T3b-SOCS3 cKO mice developed tumors in the stomach but not in the bowels by 2 months of age, even though the SOCS3 deletion occurred in both the epithelium of stomach and bowels. The tumors developed in the absence of the inflammatory response and all cKO mice died within 6 months. These tumors displayed pathology and molecular alterations, such as an increase in MUC2 (Mucin 2, oligomeric mucus/gel-forming) and TFF3 (trefoil factor 3), resembling human intestinal-type gastric tumors. Administration of antileptin antibody to T3b-SOCS3 cKO mice reduced hyperplasia of gastric mucosa, which is the step of the initiation of gastric tumor. These data suggest that SOCS3 is an antigastric tumor gene that suppresses leptin overexpression and ObRb/STAT3 hyperactivation, supporting the hypothesis that the leptin/ObRb/STAT3 axis accelerates tumorigenesis and that it may represent a new therapeutic target for the treatment of gastric cancer.

  6. Development of oral cancer vaccine using recombinant Bifidobacterium displaying Wilms' tumor 1 protein.

    PubMed

    Kitagawa, Koichi; Oda, Tsugumi; Saito, Hiroki; Araki, Ayame; Gonoi, Reina; Shigemura, Katsumi; Hashii, Yoshiko; Katayama, Takane; Fujisawa, Masato; Shirakawa, Toshiro

    2017-06-01

    Several types of vaccine-delivering tumor-associated antigens (TAAs) have been developed in basic and clinical research. Wilms' tumor 1 (WT1), identified as a gene responsible for pediatric renal neoplasm, is one of the most promising TAA for cancer immunotherapy. Peptide and dendritic cell-based WT1 cancer vaccines showed some therapeutic efficacy in clinical and pre-clinical studies but as yet no oral WT1 vaccine can be administrated in a simple and easy way. In the present study, we constructed a novel oral cancer vaccine using a recombinant Bifidobacterium longum displaying WT1 protein. B. longum 420 was orally administered into mice inoculated with WT1-expressing tumor cells for 4 weeks to examine anti-tumor effects. To analyze the WT1-specific cellular immune responses to oral B. longum 420, mice splenocytes were isolated and cytokine production and cytotoxic activities were determined. Oral administrations of B. longum 420 significantly inhibited WT1-expressing tumor growth and prolonged survival in mice. Immunohistochemical study and immunological assays revealed that B. longum 420 substantially induced tumor infiltration of CD4 + T and CD8 + T cells, systemic WT1-specific cytokine production, and cytotoxic activity mediated by WT1-epitope specific cytotoxic T lymphocytes, with no apparent adverse effects. Our novel oral cancer vaccine safely induced WT1-specific cellular immunity via activation of the gut mucosal immune system and achieved therapeutic efficacy with several practical advantages over existing non-oral vaccines.

  7. Flor-Essence? Herbal Tonic Promotes Mammary Tumor Development in Sprague Dawley Rats

    SciT

    Bennett, L; Montgomery, J; Steinberg, S

    Background: Women who are diagnosed with breast cancer often self-administer complementary and alternative medicines to augment their conventional treatments, improve health, or prevent recurrence. Flor-Essence{reg_sign} Tonic is a complex mixture of herbal extracts used by cancer patients because of anecdotal evidence that it can treat or prevent disease. Methods: Female Sprague Dawley rats were given water or exposed to 3% or 6% Flor-Essence{reg_sign} beginning at one day of age. Mammary tumors were induced with a single oral 40 mg/kg/bw dose of dimethylbenz(a)anthracene at 50 days of age and sacrificed at 23 weeks. Rats were maintained on AIN-76A diet. Results: Controlmore » rats had palpable mammary tumor incidence of 51.0% at 19 weeks of age compared to 65.0% and 59.4% for the 3% and 6% Flor-Essence{reg_sign} groups respectively. Overall, no significant difference in time until first palpable tumor was detected among any of the groups. At necropsy, mammary tumor incidence was 82.5% for controls compared to 90.0% and 97.3% for rats consuming 3% and 6% Flor-Essence{reg_sign}, respectively. Mean mammary tumor multiplicity ({+-}SES) for the controls was 2.8 ({+-} 0.5) and statistically different from the 3% or 6% Flor- Essence{reg_sign} groups with 5.2 ({+-} 0.7), and 4.8 ({+-} 0.6), respectively (p{<=}0.01). As expected, the majority of isolated tumors were diagnosed as adenocarcinomas. Conclusions: Flor-Essence{reg_sign} can promote mammary tumor development in the Sprague Dawley rat model. This observation is contrary to widely available anecdotal evidence as well as the desire of the consumer that this commercially available herbal tonic will suppress and/or inhibit tumor growth.« less

  8. Early development of physical aggression and early risk factors for chronic physical aggression in humans.

    PubMed

    Tremblay, Richard E

    2014-01-01

    This chapter describes the state of knowledge on the development of physical aggression from early childhood to adulthood, the long term outcomes of chronic physical aggression during childhood and the risk factors for chronic physical aggression. Unraveling the development of physical aggression is important to understand when and why humans start using physical aggression, to understand why some humans suffer from chronic physical aggression and to understand how to prevent the development of this disorder which causes much distress to the aggressors and their victims. The study of the developmental origins of aggression also sheds light on the reasons why situational prevention of aggression is important at all ages and in all cultures.

  9. Interplay between TGF-β signaling and receptor tyrosine kinases in tumor development.

    PubMed

    Shi, Qiaoni; Chen, Ye-Guang

    2017-10-01

    Transforming growth factor-β (TGF-β) signaling regulates cell proliferation, differentiation, migration and death, and plays a critical role in embryogenesis and tissue homeostasis. Its deregulation results in various diseases including tumor formation. Receptor tyrosine kinases (RTKs), such as epidermal growth factor receptor (EGFR), fibroblast growth factor receptor (FGFR), vascular endothelial growth factor receptor (VEGFR) and platelet-derived growth factor receptor (PDGFR), also play key roles in the development and progression of many types of tumors. It has been realized that TGF-β signaling and RTK pathways interact with each other and their interplay is important for cancer development. They are mutually regulated and cooperatively modulate cell survival and migration, epithelial-mesenchymal transition, and tumor microenvironment to accelerate tumorigenesis and tumor metastasis. RTKs can modulate Smad-dependent transcription or cooperate with TGF-β to potentiate its oncogenic activity, while TGF-β signaling can in turn control RTK signaling by regulating their activities or expression. This review summarizes current understandings of the interplay between TGF-β signaling and RTKs and its influence on tumor development.

  10. Development of Biologically Based Therapies for Basal-Like Tumors

    DTIC Science & Technology

    2007-04-01

    Lynda R. Sawyer5, Xiaping He2,3, Melissa A. Troester6, Carolyn I. Sartor3,7, Thais Rieger-House8, Philip S. Bernard8, Lisa A. Carey5, and Charles M...med.unc.edu Xiaping He: xiaping@med.unc.edu Melissa A.Troester: troester@schoolph.umass.edu Carolyn I. Sartor: carolyn_sartor@med.unc.edu Thais Rieger... Giordano A: Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors in breast cancer: current status and future development. Front Biosci

  11. Alternatives to the fish early life-stage test: Developing a conceptual model for early fish development

    EPA Science Inventory

    Chronic fish toxicity is a key parameter for hazard classification and environmental risk assessment of chemicals, and the OECD 210 fish early life-stage (FELS) test is the primary guideline test used for various international regulatory programs. There exists a need to develop ...

  12. Gross Motor Development, Movement Abnormalities, and Early Identification of Autism

    PubMed Central

    Young, Gregory S.; Goldring, Stacy; Greiss-Hess, Laura; Herrera, Adriana M.; Steele, Joel; Macari, Suzanne; Hepburn, Susan; Rogers, Sally J.

    2015-01-01

    Gross motor development (supine, prone, rolling, sitting, crawling, walking) and movement abnormalities were examined in the home videos of infants later diagnosed with autism (regression and no regression subgroups), developmental delays (DD), or typical development. Group differences in maturity were found for walking, prone, and supine, with the DD and Autism-No Regression groups both showing later developing motor maturity than typical children. The only statistically significant differences in movement abnormalities were in the DD group; the two autism groups did not differ from the typical group in rates of movement abnormalities or lack of protective responses. These findings do not replicate previous investigations suggesting that early motor abnormalities seen on home video can assist in early identification of autism. PMID:17805956

  13. Early stress and human behavioral development: emerging evolutionary perspectives.

    PubMed

    Del Giudice, M

    2014-08-01

    Stress experienced early in life exerts a powerful, lasting influence on development. Converging empirical findings show that stressful experiences become deeply embedded in the child's neurobiology, with an astonishing range of long-term effects on cognition, emotion, and behavior. In contrast with the prevailing view that such effects are the maladaptive outcomes of 'toxic' stress, adaptive models regard them as manifestations of evolved developmental plasticity. In this paper, I offer a brief introduction to adaptive models of early stress and human behavioral development, with emphasis on recent theoretical contributions and emerging concepts in the field. I begin by contrasting dysregulation models of early stress with their adaptive counterparts; I then introduce life history theory as a unifying framework, and review recent work on predictive adaptive responses (PARs) in human life history development. In particular, I discuss the distinction between forecasting the future state of the environment (external prediction) and forecasting the future state of the organism (internal prediction). Next, I present the adaptive calibration model, an integrative model of individual differences in stress responsivity based on life history concepts. I conclude by examining how maternal-fetal conflict may shape the physiology of prenatal stress and its adaptive and maladaptive effects on postnatal development. In total, I aim to show how theoretical work from evolutionary biology is reshaping the way we think about the role of stress in human development, and provide researchers with an up-to-date conceptual map of this fascinating and rapidly evolving field.

  14. A Model of Overall Survival Predicts Treatment Outcomes with Atezolizumab versus Chemotherapy in Non-Small Cell Lung Cancer Based on Early Tumor Kinetics.

    PubMed

    Claret, Laurent; Jin, Jin Y; Ferté, Charles; Winter, Helen; Girish, Sandhya; Stroh, Mark; He, Pei; Ballinger, Marcus; Sandler, Alan; Joshi, Amita; Rittmeyer, Achim; Gandara, David; Soria, Jean-Charles; Bruno, René

    2018-04-23

    Purpose: Standard endpoints often poorly predict overall survival (OS) with immunotherapies. We investigated the predictive performance of model-based tumor growth inhibition (TGI) metrics using data from atezolizumab clinical trials in patients with non-small cell lung cancer. Experimental Design: OS benefit with atezolizumab versus docetaxel was observed in both POPLAR (phase II) and OAK (phase III), although progression-free survival was similar between arms. A multivariate model linking baseline patient characteristics and on-treatment tumor growth rate constant (KG), estimated using time profiles of sum of longest diameters (RECIST 1.1) to OS, was developed using POPLAR data. The model was evaluated to predict OAK outcome based on estimated KG at TGI data cutoffs ranging from 10 to 122 weeks. Results: In POPLAR, TGI profiles in both arms crossed at 25 weeks, with more shrinkage with docetaxel and slower KG with atezolizumab. A log-normal OS model, with albumin and number of metastatic sites as independent prognostic factors and estimated KG, predicted OS HR in subpopulations of patients with varying baseline PD-L1 expression in both POPLAR and OAK: model-predicted OAK HR (95% prediction interval), 0.73 (0.63-0.85), versus 0.73 observed. The POPLAR OS model predicted greater than 97% chance of success of OAK (significant OS HR, P < 0.05) from the 40-week data cutoff onward with 50% of the total number of tumor assessments when a successful study was predicted from 70 weeks onward based on observed OS. Conclusions: KG has potential as a model-based early endpoint to inform decisions in cancer immunotherapy studies. Clin Cancer Res; 1-7. ©2018 AACR. ©2018 American Association for Cancer Research.

  15. Novel in vivo flow cytometry platform for early prognosis of metastatic activity of circulating tumor cells (Conference Presentation)

    NASA Astrophysics Data System (ADS)

    Nolan, Jacqueline; Cai, Chenzhoung; Nedosekin, Dmitry A.; Zharov, Vladimir P.

    2017-02-01

    Approximately 8 million people lose their lives due to cancer each year. Metastatic disease is responsible for 90% of those cancer-related deaths. Only viable circulating tumor cells (CTCs) that can survive in the blood circulation can create secondary tumors. Thus, real-time enumeration of CTCs and assessment of their viability in vivo has great biological significance. However, little progress has been made in this field. Conventional flow cytometry is the current technique being used for the assessment of cell viability, but there are many limitations to this technique: 1) cell properties may be altered during the extraction and processing method; 2) collection of cells from blood prevents the long-term study of individual cells in their natural biological environment; and 3) there are time-consuming preparation procedures. Whether it be for the assessment of antitumor drugs, where induction of apoptosis or necrosis is the preferred event, or the identification of nanoparticle-induced toxicity during nanotherapeutic treatment, it is clear that new approaches for assessment of the viability circulating blood cells and CTCs are urgently needed. We have developed a novel high speed, multicolor in vivo flow cytometry (FC) platform that integrates photoacoustic (PA) and fluorescence FC (PAFFC) and demonstrate its ability to enumerate rare circulating normal and abnormal (e.g. tumor) cells and assess their viability (e.g. apoptotic and necrotic) in a mouse model.

  16. Conditions on Early Mars Might Have Fostered Rapid and Early Development of Life

    NASA Technical Reports Server (NTRS)

    Gibson, Everett K.; McKay, David S.; Thomas-Keprta, Kathie L.; Clemett, Simon J.; Wentworth, Susan J.

    2007-01-01

    The exploration of Mars during the past decades has begun to unveil the history of the planet. The combinations of remote sensing, in situ geochemical compositional measurements and photographic observations from both above and on the surface have shown Mars to have a dynamic and active geologic evolution. Mars geologic evolution clearly had conditions that were suitable for supporting life. For a planet to be able to be habitable, it must have water, carbon sources, energy sources and a dynamic geologic past. Mars meets all of these requirements. The first 600 My of Martian history were ripe for life to develop because of the abundance of (i) Water-carved canyons and oceans or lakes with the early presence of near surface water shown by precipitated carbonates in ALH84001 well-dated at approx.3.9 Gy., (ii) Energy from the original accretional processes, a molten core which generated a strong magnetic field leaving a permanent record in the early crust, early active volcanism continuing throughout Martian history, and, and continuing impact processes, (iii) Carbon and water from possibly extensive volcanic outgassing (i.e. H2O, CO2, CH4, CO, O2, N2, H2S, SO2, etc.) and (iv) some crustal tectonics as revealed by faulting and possible plate movement reflected by the magnetic pattern in the crust. The question arises: "Why would life not evolve from these favorable conditions on early Mars in its first 600 My?" During this period, it seems likely that environmental near-surface conditions on Mars were more favorable to life than at any later time. Standing bodies of water, precipitation and flowing surface water, and possibly abundant hydrothermal energy would all favor the formation of early life. Even if life developed elsewhere (on Earth, Venus, or on other solar systems) and was transported to Mars, the surface conditions were likely very hospitable for that introduced life to multiply and evolve.

  17. Characteristics of effective professional development for early career science teachers

    NASA Astrophysics Data System (ADS)

    Simon, Shirley; Campbell, Sandra; Johnson, Sally; Stylianidou, Fani

    2011-04-01

    The research reported here set out to investigate the features in schools and science departments that were seen as effective in contributing to the continuing professional development (CPD) of early career science teachers. Ten schools took part in the study, selected on the basis of their reputation for having effective CPD practices. To gain different perspectives from within the organisations we conducted interviews with senior members of staff, heads of science departments and early career teachers. A thematic analysis of the interviews is presented, drawing on findings from across the 10 schools, and exemplified in more detail by a vignette to show specific features of effective CPD practice. The study has revealed a wealth of practice across the 10 schools, which included a focus on broadening experience beyond the classroom, having an open, sharing, non-threatening culture and systemic procedures for mentoring and support that involved ring-fenced budgets. The schools also deployed staff judiciously in critical roles that model practice and motivate early career science teachers. Early career teachers were concerned primarily with their overall development as teachers, though some science specific examples such as observing practical work and sessions to address subject knowledge were seen as important.

  18. Endosperm turgor pressure decreases during early Arabidopsis seed development.

    PubMed

    Beauzamy, Léna; Fourquin, Chloé; Dubrulle, Nelly; Boursiac, Yann; Boudaoud, Arezki; Ingram, Gwyneth

    2016-09-15

    In Arabidopsis, rapid expansion of the coenocytic endosperm after fertilisation has been proposed to drive early seed growth, which is in turn constrained by the seed coat. This hypothesis implies physical heterogeneity between the endosperm and seed coat compartments during early seed development, which to date has not been demonstrated. Here, we combine tissue indentation with modelling to show that the physical properties of the developing seed are consistent with the hypothesis that elevated endosperm-derived turgor pressure drives early seed expansion. We provide evidence that whole-seed turgor is generated by the endosperm at early developmental stages. Furthermore, we show that endosperm cellularisation and seed growth arrest are associated with a drop in endosperm turgor pressure. Finally, we demonstrate that this decrease is perturbed when the function of POLYCOMB REPRESSIVE COMPLEX 2 is lost, suggesting that turgor pressure changes could be a target of genomic imprinting. Our results indicate a developmental role for changes in endosperm turgor pressure in the Arabidopsis seed. © 2016. Published by The Company of Biologists Ltd.

  19. [Dental caries and early childhood development: a pilot study].

    PubMed

    Núñez, F Loreto; Sanz, B Javier; Mejía, L Gloria

    2015-01-01

    To investigate the association between dental caries and early childhood development in 3-year-olds from Talca, Chile. A pilot study with a convenience sample of 3-year-olds from Talca (n = 39) who attend public healthcare centers. Child development was measured by the Psychomotor Development Index (PDI), a screening tool used nationally among pre-school children to assess language development, fine motor skills and coordination areas. Dental caries prevalence was evaluated by decayed, missing, filled teeth (DFMT) and decayed, missing, filled tooth surfaces (DFMS) ceo-d and ceo-s indexes. The children were divided into two groups according to the PDIscore: those with a score of 40 or more were considered developmentally normal (n = 32), and those with a score below 40 were considered as having impaired development (n = 7). The severity of caries (DMFT) was negatively correlated with PDI (r = -0.82), and children with the lowest TEPSI score had the highest DFMT values. The average DMFT in children with normal development was 1.31, and 3.57 for those with impaired development. This pilot study indicates that the severity of dental caries is correlated with early childhood development. Copyright © 2015. Publicado por Elsevier España, S.L.U.

  20. The early Cambrian fossil embryo Pseudooides is a direct-developing cnidarian, not an early ecdysozoan

    PubMed Central

    2017-01-01

    Early Cambrian Pseudooides prima has been described from embryonic and post-embryonic stages of development, exhibiting long germ-band development. There has been some debate about the pattern of segmentation, but this interpretation, as among the earliest records of ecdysozoans, has been generally accepted. Here, we show that the ‘germ band’ of P. prima embryos separates along its mid axis during development, with the transverse furrows between the ‘somites’ unfolding into the polar aperture of the ten-sided theca of Hexaconularia sichuanensis, conventionally interpreted as a scyphozoan cnidarian; co-occurring post-embryonic remains of ecdysozoans are unrelated. We recognize H. sichuanensis as a junior synonym of P. prima as a consequence of identifying these two form-taxa as distinct developmental stages of the same organism. Direct development in P. prima parallels the co-occuring olivooids Olivooides, and Quadrapyrgites and Bayesian phylogenetic analysis of a novel phenotype dataset indicates that, despite differences in their tetra-, penta- and pseudo-hexa-radial symmetry, these hexangulaconulariids comprise a clade of scyphozoan medusozoans, with Arthrochites and conulariids, that all exhibit direct development from embryo to thecate polyp. The affinity of hexangulaconulariids and olivooids to extant scyphozoan medusozoans indicates that the prevalence of tetraradial symmetry and indirect development are a vestige of a broader spectrum of body-plan symmetries and developmental modes that was manifest in their early Phanerozoic counterparts. PMID:29237861

  1. The early Cambrian fossil embryo Pseudooides is a direct-developing cnidarian, not an early ecdysozoan.

    PubMed

    Duan, Baichuan; Dong, Xi-Ping; Porras, Luis; Vargas, Kelly; Cunningham, John A; Donoghue, Philip C J

    2017-12-20

    Early Cambrian Pseudooides prima has been described from embryonic and post-embryonic stages of development, exhibiting long germ-band development. There has been some debate about the pattern of segmentation, but this interpretation, as among the earliest records of ecdysozoans, has been generally accepted. Here, we show that the 'germ band' of P. prima embryos separates along its mid axis during development, with the transverse furrows between the 'somites' unfolding into the polar aperture of the ten-sided theca of Hexaconularia sichuanensis , conventionally interpreted as a scyphozoan cnidarian; co-occurring post-embryonic remains of ecdysozoans are unrelated. We recognize H. sichuanensis as a junior synonym of P. prima as a consequence of identifying these two form-taxa as distinct developmental stages of the same organism. Direct development in P. prima parallels the co-occuring olivooids Olivooides, and Quadrapyrgites and Bayesian phylogenetic analysis of a novel phenotype dataset indicates that, despite differences in their tetra-, penta- and pseudo-hexa-radial symmetry, these hexangulaconulariids comprise a clade of scyphozoan medusozoans, with Arthrochites and conulariids, that all exhibit direct development from embryo to thecate polyp. The affinity of hexangulaconulariids and olivooids to extant scyphozoan medusozoans indicates that the prevalence of tetraradial symmetry and indirect development are a vestige of a broader spectrum of body-plan symmetries and developmental modes that was manifest in their early Phanerozoic counterparts. © 2017 The Authors.

  2. Social conversational skills development in early implanted children.

    PubMed

    Guerzoni, Letizia; Murri, Alessandra; Fabrizi, Enrico; Nicastri, Maria; Mancini, Patrizia; Cuda, Domenico

    2016-09-01

    Social conversational skills are a salient aspect of early pragmatic development in young children. These skills include two different abilities, assertiveness and responsiveness. This study investigated the development of these abilities in early implanted children and their relationships with lexical development and some language-sensitive variables. Prospective, observational, nonrandomized study. Participants included 28 children with congenital profound sensorineural hearing loss. The mean age at device activation was 13.3 months (standard deviation [SD] ±4.2). The Social-Conversational Skills Rating Scale was used to evaluate assertiveness and responsiveness. The MacArthur-Bates Communicative Development Inventory (Words and Sentences form) was used to analyze the lexical development. The device experience was 12 months for each child, and the mean age at testing was 25.9 months (SD ±4.6). Assertiveness and responsiveness scores were within the normal range of normal-hearing age-matched peers. Age at cochlear implant activation exerted a significant impact, with the highest scores associated to the youngest patients. The residual correlations between assertiveness and responsiveness with the lexical development were positive and strongly significant (r = 0.69 and 0.73, respectively). Preoperative hearing threshold demonstrated an associated significant coefficient on the assertiveness score. Age at diagnosis and maternal education level were not correlated with the social conversational skills. Early-implanted children developed social conversational skills that are similar to normal-hearing peers matched for age 1 year after device activation. Social conversational skills and lexical development were strongly correlated, but the present study design cannot specify the direction of this relationship. Children with better preoperative residual hearing exhibited better assertive ability. 4 Laryngoscope, 126:2098-2105, 2016. © 2015 The American Laryngological

  3. Studies Toward Birth and Early Mammalian Development in Space

    NASA Technical Reports Server (NTRS)

    Ronca, April E.; Dalton, Bonnie (Technical Monitor)

    2002-01-01

    Successful reproduction is the hallmark of a species' ability to adapt to its environment and must be realized to sustain life beyond Earth. Before taking this immense step, we need to understand the effects of altered gravity on critical phases of mammalian reproduction, viz., those events surrounding pregnancy, birth and the early development of offspring. No mammal has yet undergone birth in space. however studies spanning the gravity continuum from 0 to 2-g are revealing insights into how birth and early postnatal development will proceed in space. In this presentation, I will report the results of behavioral studies of rat mothers and offspring exposed from mid- to late pregnancy to either hypogravity (0-g) or hypergravity (1.5 or 2-g).

  4. Relationship between the neighbourhood built environment and early child development.

    PubMed

    Christian, Hayley; Ball, Stephen J; Zubrick, Stephen R; Brinkman, Sally; Turrell, Gavin; Boruff, Bryan; Foster, Sarah

    2017-11-01

    The relationship between features of the neighbourhood built environment and early child development was investigated using area-level data from the Australian Early Development Census. Overall 9.0% of children were developmentally vulnerable on the Physical Health and Well-being domain, 8.1% on the Social Competence domain and 8.1% on the Emotional Maturity domain. After adjustment for socio-demographic factors, Local Communities with the highest quintile of home yard space had significantly lower odds of developmental vulnerability on the Emotional Maturity domain. Residing in a Local Community with fewer main roads was associated with a decrease in the proportion of children developmentally vulnerable on the Social Competence domain. Overall, sociodemographic factors were more important than aspects of the neighbourhood physical environment for explaining variation between Local Communities in the developmental vulnerability of children. Copyright © 2017 Elsevier Ltd. All rights reserved.

  5. Lexically-based learning and early grammatical development.

    PubMed

    Lieven, E V; Pine, J M; Baldwin, G

    1997-02-01

    Pine & Lieven (1993) suggest that a lexically-based positional analysis can account for the structure of a considerable proportion of children's early multiword corpora. The present study tests this claim on a second, larger sample of eleven children aged between 1;0 and 3;0 from a different social background, and extends the analysis to later in development. Results indicate that the positional analysis can account for a mean of 60% of all the children's multiword utterances and that the great majority of all other utterances are defined as frozen by the analysis. Alternative explanations of the data based on hypothesizing underlying syntactic or semantic relations are investigated through analyses of pronoun case marking and of verbs with prototypical agent-patient roles. Neither supports the view that the children's utterances are being produced on the basis of general underlying rules and categories. The implications of widespread distributional learning in early language development are discussed.

  6. Hazards to Early Development: The Biological Embedding of Early Life Adversity.

    PubMed

    Nelson, Charles A

    2017-10-11

    The number of children under 18 years of age has increased worldwide over the past decade. This growth spurt is due, in part, to remarkable progress in child survival. Alas, surviving early hazards, like prematurity or infectious disease, does not guarantee that children's development will not be compromised by other hazards as they grow older. Throughout the world, children continue to be confronted with a large number of biological and psychosocial challenges that greatly limit their developmental potential. The focus of this article is how such adverse experiences impact the developing brain. Copyright © 2017 Elsevier Inc. All rights reserved.

  7. Development and characterization of non-resonant multiphoton photoacoustic spectroscopy (NMPPAS) for brain tumor margining

    NASA Astrophysics Data System (ADS)

    Dahal, Sudhir

    During tumor removal surgery, due to the problems associated with obtaining high-resolution, real-time chemical images of where exactly the tumor ends and healthy tissue begins (tumor margining), it is often necessary to remove a much larger volume of tissue than the tumor itself. In the case of brain tumor surgery, however, it is extremely unsafe to remove excess tissue. Therefore, without an accurate image of the tumor margins, some of the tumor's finger-like projections are inevitably left behind in the surrounding parenchyma to grow again. For this reason, the development of techniques capable of providing high-resolution real-time images of tumor margins up to centimeters below the surface of a tissue is ideal for the diagnosis and treatment of tumors, as well as surgical guidance during brain tumor excision. A novel spectroscopic technique, non-resonant multiphoton photoacoustic spectroscopy (NMPPAS), is being developed with the capabilities of obtaining high-resolution subsurface chemical-based images of underlying tumors. This novel technique combines the strengths of multiphoton tissue spectroscopy and photoacoustic spectroscopy into a diagnostic methodology that will, ultimately, provide unparalleled chemical information and images to provide the state of sub-surface tissues. The NMPPAS technique employs near-infrared light (in the diagnostic window) to excite ultraviolet and/or visible light absorbing species deep below the tissue's surface. Once a multiphoton absorption event occurs, non-radiative relaxation processes generates a localized thermal expansion and subsequent acoustic wave that can be detected using a piezoelectric transducer. Since NMPPAS employs an acoustic detection modality, much deeper diagnoses can be performed than that is possible using current state of the art high-resolution chemical imaging techniques such as multiphoton fluorescence spectroscopy. NMPPAS was employed to differentiate between excised brain tumors (astrocytoma III

  8. Early zebrafish development: It’s in the maternal genes

    PubMed Central

    Abrams, Elliott W.; Mullins, Mary C.

    2009-01-01

    Summary The earliest stages of embryonic development in all animals examined rely on maternal gene products that are generated during oogenesis and supplied to the egg. The period of maternal control of embryonic development varies among animals according to the onset of zygotic transcription and the persistence of maternal gene products. This maternal regulation has been little studied in vertebrates, due to the difficulty in manipulating maternal gene function and lack of basic molecular information. However, recent maternal-effect screens in the zebrafish have generated more than 40 unique mutants that are providing new molecular entry points to the maternal control of early vertebrate development. Here we discuss recent studies of 12 zebrafish mutant genes that illuminate the maternal molecular controls on embryonic development, including advances in the regulation of animal-vegetal polarity, egg activation, cleavage development, body plan formation, tissue morphogenesis, microRNA function and germ cell development. PMID:19608405

  9. Reading Instruction Affects the Cognitive Skills Supporting Early Reading Development

    ERIC Educational Resources Information Center

    McGeown, Sarah P.; Johnston, Rhona S.; Medford, Emma

    2012-01-01

    This study examined the cognitive skills associated with early reading development when children were taught by different types of instruction. Seventy-nine children (mean age at pre-test 4;10 (0.22 S.D.) and post-test 5;03 (0.21 S.D.)) were taught to read either by an eclectic approach which included sight-word learning, guessing from context and…

  10. Dynamic Self-Organization and Early Lexical Development in Children

    ERIC Educational Resources Information Center

    Li, Ping; Zhao, Xiaowei; Whinney, Brian Mac

    2007-01-01

    In this study we present a self-organizing connectionist model of early lexical development. We call this model DevLex-II, based on the earlier DevLex model. DevLex-II can simulate a variety of empirical patterns in children's acquisition of words. These include a clear vocabulary spurt, effects of word frequency and length on age of acquisition,…

  11. 2015 Guidance on cancer immunotherapy development in early-phase clinical studies.

    PubMed

    2015-12-01

    The development of cancer immunotherapies is progressing rapidly with a variety of technological approaches. They consist of "cancer vaccines", which are based on the idea of vaccination, "effector cell therapy", classified as passive immunotherapy, and "inhibition of immunosuppression", which intends to break immunological tolerance to autoantigens or immunosuppressive environments characterizing antitumor immune responses. Recent reports showing clinical evidence of efficacy of immune checkpoint inhibitors and adoptive immunotherapies with tumor-infiltrating lymphocytes and tumor-specific receptor gene-modified T cells indicate the beginning of a new era for cancer immunotherapy. This guidance summarizes ideas that will be helpful to those who plan to develop cancer immunotherapy. The aims of this guidance are to discuss and offer important points in early phase clinical studies of innovative cancer immunotherapy, with future progress in this field, and to contribute to the effective development of cancer immunotherapy aligned with the scope of regulatory science. This guidance covers cancer vaccines, effector cell therapy, and inhibition of immunosuppression, including immune checkpoint inhibitors. © 2015 The Authors. Cancer Science published by Wiley Publishing Asia Pty Ltd on behalf of Japanese Cancer Association.

  12. Early Life Growth Predicts Pubertal Development in South African Adolescents.

    PubMed

    Lundeen, Elizabeth A; Norris, Shane A; Martorell, Reynaldo; Suchdev, Parminder S; Mehta, Neil K; Richter, Linda M; Stein, Aryeh D

    2016-03-01

    Given global trends toward earlier onset of puberty and the adverse psychosocial consequences of early puberty, it is important to understand the childhood predictors of pubertal timing and tempo. We examined the association between early growth and the timing and tempo of puberty in adolescents in South Africa. We analyzed prospectively collected data from 1060 boys and 1135 girls participating in the Birth-to-Twenty cohort in Soweto, South Africa. Height-for-age z scores (HAZs) and body mass index-for-age z scores (BMIZs) were calculated based on height (centimeters) and body mass index (kilograms per meter squared) at ages 5 y and 8 y. The development of genitals, breasts, and pubic hair was recorded annually from 9 to 16 y of age with the use of the Tanner sexual maturation scale (SMS). We used latent class growth analysis to identify pubertal trajectory classes and also characterized children as fast or slow developers based on the SMS score at 12 y of age. We used multinomial logistic regression to estimate associations of HAZ and BMIZ at ages 5 and 8 y with pubertal development. We identified 3 classes for pubic hair development (for both girls and boys) and 4 classes for breast (for girls) and genital (for boys) development. In girls, both HAZ and BMIZ at age 5 y were positively associated with pubic hair development [relative risk ratio (RRR): 1.57, P < 0.001 and RRR: 1.51, P < 0.01, respectively], as was BMI at age 8 y (RRR: 2.06, P = 0.03); similar findings were observed for breast development. In boys, HAZ and BMIZ at age 5 y were positively associated with pubic hair development (RRR: 1.78, P < 0.001 and RRR: 1.43, P < 0.01, respectively); HAZ at age 5 y was associated with development of genitals (RRR: 2.19, P < 0.01). In boys and girls, both height and body mass index in early childhood predicted the trajectory of pubertal development. This may provide a tool to identify children at risk of early pubertal onset.

  13. Biased gene expression in early honeybee larval development

    PubMed Central

    2013-01-01

    Background Female larvae of the honeybee (Apis mellifera) develop into either queens or workers depending on nutrition. This nutritional stimulus triggers different developmental trajectories, resulting in adults that differ from each other in physiology, behaviour and life span. Results To understand how these trajectories are established we have generated a comprehensive atlas of gene expression throughout larval development. We found substantial differences in gene expression between worker and queen-destined larvae at 6 hours after hatching. Some of these early changes in gene expression are maintained throughout larval development, indicating that caste-specific developmental trajectories are established much earlier than previously thought. Within our gene expression data we identified processes that potentially underlie caste differentiation. Queen-destined larvae have higher expression of genes involved in transcription, translation and protein folding early in development with a later switch to genes involved in energy generation. Using RNA interference, we were able to demonstrate that one of these genes, hexamerin 70b, has a role in caste differentiation. Both queen and worker developmental trajectories are associated with the expression of genes that have alternative splice variants, although only a single variant of a gene tends to be differentially expressed in a given caste. Conclusions Our data, based on the biases in gene expression early in development together with published data, supports the idea that caste development in the honeybee consists of two phases; an initial biased phase of development, where larvae can still switch to the other caste by differential feeding, followed by commitment to a particular developmental trajectory. PMID:24350621

  14. Early development and replacement of the stickleback dentition

    PubMed Central

    Ellis, Nicholas A.; Donde, Nikunj N.; Miller, Craig T.

    2017-01-01

    Teeth have long served as a model system to study basic questions about vertebrate organogenesis, morphogenesis, and evolution. In non-mammalian vertebrates, teeth typically regenerate throughout adult life. Fish have evolved a tremendous diversity in dental patterning in both their oral and pharyngeal dentitions, offering numerous opportunities to study how morphology develops, regenerates, and evolves in different lineages. Threespine stickleback fish (Gasterosteus aculeatus) have emerged as a new system to study how morphology evolves, and provide a particularly powerful system to study the development and evolution of dental morphology. Here we describe the oral and pharyngeal dentitions of stickleback fish, providing additional morphological, histological, and molecular evidence for homology of oral and pharyngeal teeth. Focusing on the ventral pharyngeal dentition in a dense developmental time course of lab-reared fish, we describe the temporal and spatial consensus sequence of early tooth formation. Early in development, this sequence is highly stereotypical and consists of seventeen primary teeth forming the early tooth field, followed by the first tooth replacement event. Comparing this detailed morphological and ontogenetic sequence to that described in other fish reveals that major changes to how dental morphology arises and regenerates have evolved across different fish lineages. PMID:27145214

  15. Developing an Early Childhood Teacher Workforce Development Strategy for Rural and Remote Communities

    ERIC Educational Resources Information Center

    Price, Anne; Jackson-Barrett, Elizabeth

    2009-01-01

    The North West Early Childhood and Primary Teacher Workforce Development Strategy offers students in the Pilbara and Kimberley the opportunity to enrol in a Western Australian University's fully accredited Bachelor of Education (Early Childhood and Primary) part time and externally--so they can continue to live and work in their communities. The…

  16. Decreasing CNPY2 Expression Diminishes Colorectal Tumor Growth and Development through Activation of p53 Pathway.

    PubMed

    Yan, Ping; Gong, Hui; Zhai, Xiaoyan; Feng, Yi; Wu, Jun; He, Sheng; Guo, Jian; Wang, Xiaoxia; Guo, Rui; Xie, Jun; Li, Ren-Ke

    2016-04-01

    Neovascularization drives tumor development, and angiogenic factors are important neovascularization initiators. We recently identified the secreted angiogenic factor CNPY2, but its involvement in cancer has not been explored. Herein, we investigate CNPY2's role in human colorectal cancer (CRC) development. Tumor samples were obtained from CRC patients undergoing surgery. Canopy 2 (CNPY2) expression was analyzed in tumor and adjacent normal tissue. Stable lines of human HCT116 cells expressing CNPY2 shRNA or control shRNA were established. To determine CNPY2's effects on tumor xenografts in vivo, human CNPY2 shRNA HCT116 cells and controls were injected into nude mice, separately. Cellular apoptosis, growth, and angiogenesis in the xenografts were evaluated. CNPY2 expression was significantly higher in CRC tissues. CNPY2 knockdown in HCT116 cells inhibited growth and migration and promoted apoptosis. In xenografts, CNPY2 knockdown prevented tumor growth and angiogenesis and promoted apoptosis. Knockdown of CNPY2 in the HCT116 CRC cell line reversibly increased p53 activity. The p53 activation increased cyclin-dependent kinase inhibitor p21 and decreased cyclin-dependent kinase 2, thereby inhibiting tumor cell growth, inducing cell apoptosis, and reducing angiogenesis both in vitro and in vivo. CNPY2 may play a critical role in CRC development by enhancing cell proliferation, migration, and angiogenesis and by inhibiting apoptosis through negative regulation of the p53 pathway. Therefore, CNPY2 may represent a novel CRC therapeutic target and prognostic indicator. Copyright © 2016 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  17. Early mathematics development and later achievement: Further evidence

    NASA Astrophysics Data System (ADS)

    Aubrey, Carol; Godfrey, Ray; Dahl, Sarah

    2006-05-01

    There is a growing international recognition of the importance of the early years of schooling as well as an interest being shown in the relationship of early education to later achievement. This article focuses on a cohort of English pupils who have been tracked through primary school during the first five years of the new National Numeracy Strategy. It reports a limited longitudinal study of young children's early mathematical development, initially within three testing cycles: at the mid-point and towards the end of their reception year (at five years-of-age) and again at the mid-point of Year 1 (at six years-ofage). These cycles were located within the broader context of progress through to the end of Key Stage 1 (at seven years) and Key Stage 2 (at eleven years) on the basis of national standardised assessment tests (SATs). Results showed that children who bring into school early mathematical knowledge do appear to be advantaged in terms of their mathematical progress through primary school. Numerical attainment increases in importance across the primary years and practical problem solving remains an important element of this. This finding is significant given the current emphasis on numerical calculation in the English curriculum. It is concluded that without active intervention, it is likely that children with little mathematical knowledge at the beginning of formal schooling will remain low achievers throughout their primary years and, probably, beyond.

  18. Early Hematopoietic Zinc Finger Protein Prevents Tumor Cell Recognition by Natural Killer Cells1

    PubMed Central

    La Rocca, Rosanna; Fulciniti, Mariateresa; Lakshmikanth, Tadepally; Mesuraca, Maria; Ali, Talib Hassan; Mazzei, Valerio; Amodio, Nicola; Catalano, Lucio; Rotoli, Bruno; Ouerfelli, Ouathek; Grieco, Michele; Gulletta, Elio; Bond, Heather M.; Morrone, Giovanni; Ferrone, Soldano; Carbone, Ennio

    2009-01-01

    Early hematopoietic zinc finger/zinc finger protein 521 (EHZF/ZNF521) is a novel zinc finger protein expressed in hematopoietic stem and progenitor cells and is down-regulated during their differentiation. Its transcript is also abundant in some hematopoietic malignancies. Analysis of the changes in the antigenic profile of cells transfected with EHZF cDNA revealed up-regulation of HLA class I cell surface expression. This phenotypic change was associated with an increased level of HLA class I H chain, in absence of detectable changes in the expression of other Ag-processing machinery components. Enhanced resistance of target cells to NK cell-mediated cytotoxicity was induced by enforced expression of EHZF in the cervical carcinoma cell line HeLa and in the B lymphoblastoid cell line IM9. Preincubation of transfected cells with HLA class I Ag-specific mAb restored target cell susceptibility to NK cell-mediated lysis, indicating a specific role for HLA class I Ag up-regulation in the NK resistance induced by EHZF. A potential clinical significance of these findings is further suggested by the inverse correlation between EHZF and MHC class I expression levels, and autologous NK susceptibility of freshly explanted multiple myeloma cells. PMID:19342626

  19. 75 FR 16490 - Prospective Grant of Exclusive License: Development of PANVAC and Tumor Associated Antigens as...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-04-01

    ... Exclusive License: Development of PANVAC and Tumor Associated Antigens as Cancer Vaccines AGENCY: National... T-cell activation. The patents and patent applications describe a vaccine technology, TRICOM, in... activate both CD4+ and CD8+ T cells. When a TRICOM based vaccine expressing TAAs is administered it greatly...

  20. Do External or Internal Factors Lead to Tumor Development? It Is Still Unknown.

    PubMed

    Manskikh, V N

    2017-01-01

    Arguments supporting the "bad luck" hypothesis presented by C. Tomasetti and B. Vogelstein ((2015) Science, 347, 78-81) and A. V. Lichtenstein ((2017) Biochemistry (Moscow), 82, 75-80) are critically discussed. Those arguments are not sufficient for recognition of the "bad luck" hypothesis and the leading role of internal factors in spontaneous tumor development.

  1. INFLUENCE OF ENDOCRINE DISRUPTING COMPOUNDS (EDCS) ON MAMMARY GLAND DEVELOPMENT AND TUMOR SUSCEPTIBILITY

    EPA Science Inventory

    Influence of Endocrine Disrupting Compounds (EDCs) on Mammary Gland Development and Tumor Susceptibility.

    Suzanne E. Fenton1, and Jennifer Rayner1,2

    1 Reproductive Toxicology Division, NHEERL/ORD, U.S. EPA, Research Triangle Park, NC, and 2 Department of Environmen...

  2. Disrupting circadian homeostatis of sympathetic signaling promotes tumor development in mice

    Cell proliferation in all rapidly renewing mammalian tissues follows a circadian rhythm that is often disrupted in advanced-stage tumors. Epidemiologic studies have revealed a clear link between disruption of circadian rhythms and cancer development in humans. Mice lacking the circadian genes Perio...

  3. Effects of diet-induced obesity on secondary tumor development and plasma cytokine expression in mice

    The present study investigated the effects of diet-induced obesity on secondary tumor development and expression of plasma cytokines in mice. Three-wk old male C57BL/6 mice were fed the AIN-93G diet or a 45% fat diet (kcal %; n=25/group) for 7 wks before they were subcutaneously injected with 2.5 x ...

  4. Genetically engineered mouse models of craniopharyngioma: an opportunity for therapy development and understanding of tumor biology

    PubMed Central

    Martinez‐Barbera, Juan Pedro

    2017-01-01

    Abstract Adamantinomatous craniopharyngioma (ACP) is the commonest tumor of the sellar region in childhood. Two genetically engineered mouse models have been developed and are giving valuable insights into ACP biology. These models have identified novel pathways activated in tumors, revealed an important function of paracrine signalling and extended conventional theories about the role of organ‐specific stem cells in tumorigenesis. In this review, we summarize these mouse models, what has been learnt, their limitations and open questions for future research. We then discussed how these mouse models may be used to test novel therapeutics against potentially targetable pathways recently identified in human ACP. PMID:28414891

  5. Development of an autofluorescent probe designed to help brain tumor removal: study on an animal model

    NASA Astrophysics Data System (ADS)

    Siebert, R.; Leh, B.; Charon, Y.; Collado-Hilly, M.; Duval, M.-A.; Menard, L.; Monnet, F. P.; Varlet, P.

    2010-02-01

    The complete resection of the brain tumour is crucial to the patient life quality and prognosis. An autofluorescence probe aiming at helping the surgeon to improve the completeness of the removal is being developed. Autofluorescence spectroscopy is a promising approach to define whether the tissue is cancerous or not. First ex vivo measurements have been realised on an animal model. After tumorous cell injection in rat brain, autofluorescence intensity is revealed from the extracted brain. These autofluorescence data are compared to results from a histological analysis of same brains. First indicators are identified that may have the ability to differentiate tumorous and healthy tissues.

  6. Towards the development of tumor necrosis factor (TNF) sensitizers: making TNF work against cancer.

    PubMed

    Mocellin, Simone; Pilati, Pierluigi; Nitti, Donato

    2007-01-01

    Although TNF antitumor activity has been demonstrated in many preclinical models and in non-comparative clinical trials, no evidence exists that TNF-based treatments increase patient survival. Moreover, due to systemic toxicity, TNF can only be administered through sophisticated locoregional drug-delivery systems in patients with some types of organ-confined solid tumors; as a corollary, the impossibility to administer TNF through the systemic route does not allow to test the effectiveness of this cytokine in other clinical settings for the treatment of a broader spectrum of tumor types. A challenge many researchers are tackling is to dissect the cascade of molecular events underlying tumor sensitivity to TNF so to fully explore the anticancer potential of this molecule. The rationale for the development of strategies aimed at sensitizing malignant cells to TNF is to exploit tumor-specific molecular derangements to modulate TNF biological activities and ultimately maximize its tumor-selective cytotoxicity. This would not only enhance the anticancer activity of current TNF-based locoregional regimens, but would also open the avenue to the systemic administration of this cytokine and thus to a much wider clinical experimentation of TNF in the oncology field. In this review we first summarize the molecular biology of TNF and its cancer-related properties; then, the available findings regarding some among the most promising and best characterized TNF sensitizers are overviewed.

  7. Cancer vaccines: the challenge of developing an ideal tumor killing system.

    PubMed

    Mocellin, Simone

    2005-09-01

    Despite the evidence that the immune system plays a significant role in controlling tumor growth in natural conditions and in response to therapeutic vaccination, cancer cells can survive their attack as the disease progresses and no vaccination regimen should be currently proposed to patients outside experimental clinical trials. Clinical results show that the immune system can be actively polarized against malignant cells by means of a variety of vaccination strategies, and that in some cases this is associated with tumor regression. This implies that under some unique circumstances, the naturally "dormant" immune effectors can actually be put at work and used as endogenous weapons against malignant cells. Consequently, the main challenge of tumor immunologists appears to lie on the ability of reproducing those conditions in a larger set of patients. The complexity of the immune network and the still enigmatic host-tumor interactions make these tasks at the same time challenging and fascinating. Recent tumor immunology findings are giving new impetus to the development of more effective vaccination strategies and might revolutionize the way of designing the next generation of cancer vaccines. In the near future, the implementation of these insights in the clinical setting and the completion/conduction of comparative randomized phase III trials will allow oncologists to define the actual role of cancer vaccines in the fight against malignancy.

  8. Reflections on the early development of poxvirus vectors.

    PubMed

    Moss, Bernard

    2013-09-06

    Poxvirus expression vectors were described in 1982 and quickly became widely used for vaccine development as well as research in numerous fields. Advantages of the vectors include simple construction, ability to accommodate large amounts of foreign DNA and high expression levels. Numerous poxvirus-based veterinary vaccines are currently in use and many others are in human clinical trials. The early reports of poxvirus vectors paved the way for and stimulated the development of other viral vectors and recombinant DNA vaccines. Published by Elsevier Ltd.

  9. Early career professional development issues for military academic psychiatrists.

    PubMed

    Warner, Christopher H; Bobo, William V; Flynn, Julianne

    2005-01-01

    Academically motivated graduates of military psychiatric residency programs confront serious challenges. In this article, the authors present a junior faculty development model organized around four overlapping domains: mentorship, scholarship, research, and career planning/development. Using these four domains as a platform for discussion, the authors focus on challenges facing academically oriented early-career military psychiatrists and provide guidance. The authors believe that a proactive stance, skillful mentoring, self-awareness through conscious planning and effort, ability to capitalize on existing opportunities for growth, and attention to detail are all vital to the junior military psychiatrist.

  10. Development of an assisting detection system for early infarct diagnosis

    SciT

    Sim, K. S.; Nia, M. E.; Ee, C. S.

    2015-04-24

    In this paper, a detection assisting system for early infarct detection is developed. This new developed method is used to assist the medical practitioners to diagnose infarct from computed tomography images of brain. Using this assisting system, the infarct could be diagnosed at earlier stages. The non-contrast computed tomography (NCCT) brain images are the data set used for this system. Detection module extracts the pixel data from NCCT brain images, and produces the colourized version of images. The proposed method showed great potential in detecting infarct, and helps medical practitioners to make earlier and better diagnoses.

  11. Early childhood development: impact of national human development, family poverty, parenting practices and access to early childhood education.

    PubMed

    Tran, T D; Luchters, S; Fisher, J

    2017-05-01

    This study was to describe and quantify the relationships among family poverty, parents' caregiving practices, access to education and the development of children living in low- and middle-income countries (LAMIC). We conducted a secondary analysis of data collected in UNICEF's Multiple Indicator Cluster Surveys (MICS). Early childhood development was assessed in four domains: language-cognitive, physical, socio-emotional and approaches to learning. Countries were classified into three groups on the basis of the Human Development Index (HDI). Overall, data from 97 731 children aged 36 to 59 months from 35 LAMIC were included in the after analyses. The mean child development scale score was 4.93 out of a maximum score of 10 (95%CI 4.90 to 4.97) in low-HDI countries and 7.08 (95%CI 7.05 to 7.12) in high-HDI countries. Family poverty was associated with lower child development scores in all countries. The total indirect effect of family poverty on child development score via attending early childhood education, care for the child at home and use of harsh punishments at home was -0.13 SD (77.8% of the total effect) in low-HDI countries, -0.09 SD (23.8% of the total effect) in medium-HDI countries and -0.02 SD (6.9% of the total effect) in high-HDI countries. Children in the most disadvantaged position in their societies and children living in low-HDI countries are at the greatest risk of failing to reach their developmental potential. Optimizing care for child development at home is essential to reduce the adverse effects of poverty on children's early development and subsequent life. © 2016 John Wiley & Sons Ltd.

  12. Early quantitative evaluation of a tumor vasculature disruptive agent AVE8062 using dynamic contrast-enhanced ultrasonography.

    PubMed

    Lavisse, Sonia; Lejeune, Pascale; Rouffiac, Valérie; Elie, Nicolas; Bribes, Estelle; Demers, Brigitte; Vrignaud, Patricia; Bissery, Marie-Christine; Brulé, Aude; Koscielny, Serge; Péronneau, Pierre; Lassau, Nathalie

    2008-02-01

    To evaluate the early tumor vasculature disrupting effects of the AVE8062 molecule and the feasibility of dynamic contrast-enhanced ultrasonography (DCE-US) in the quantitative assessment of these effects. AVE8062 was administered at a single dose (41 mg/kg) to 40 melanoma-bearing nude mice, which were all imaged before and after drug administration (5 + 15 minutes, 1, 6, and 24 hours). Using an ultrasound scanner (Aplio, Toshiba), intratumor vessels were counted in power Doppler mode and tumor microvasculature was assessed in a specific harmonic mode associated with a perfusion and quantification software for contrast-uptake quantification (Sonovue, Bracco). The peak intensity (PI), time-to-PI (T PI), and full-width at half maximum (FWHM) were extracted from the time-intensity curves expressed as linear raw data. Histologic analysis evaluated microvessel density (MVD) and necrosis at each time point studied. Statistical significance was estimated (paired sum rank and Mann-Whitney tests) to evaluate drug activity and to compare its efficacy at the different time points. In power Doppler mode, intratumoral vessels depletion started 15 minutes postinjection (32%, P = 0.004) and the decrease was maximal at 6 hours (51%, P = 0.002). PI decreased by 3.5- and 45.7-fold at 1 and 6 hours, respectively, compared with preinjection values (P = 0.016 and P = 0.008). The decrease at 6 hours was significantly different from the variation at 1 hour (P = 0.0012) and at 24 hours (P = 0.0008). T PI and FWHM showed a significant increase exclusively at 6 hours (P = 0.0034, P = 0.0039). Histology revealed significantly decreased MVD and increased necrosis at 24 hours (P < 0.01). DCE-US allowed quantitative in vivo evaluation of the functional effects of AVE8062, which was found most effective on tumoral microvasculature 6 hours after its administration. A clinical phase-1 study of AVE8062 is ongoing using the same ultrasonography methodology before and 6 and 24 hours

  13. Dynamic expression of the LAP family of genes during early development of Xenopus tropicalis.

    PubMed

    Yang, Qiutan; Lv, Xiaoyan; Kong, Qinghua; Li, Chaocui; Zhou, Qin; Mao, Bingyu

    2011-10-01

    The leucine-rich repeats and PDZ (LAP) family of genes are crucial for the maintenance of cell polarity as well as for epithelial homeostasis and tumor suppression in both vertebrates and invertebrates. Four members of this gene family are known: densin, erbin, scribble and lano. Here, we identified the four members of the LAP gene family in Xenopus tropicalis and studied their expression patterns during embryonic development. The Xenopus LAP proteins show a conserved domain structure that is similar to their homologs in other vertebrates. In Xenopus embryos, these genes were detected in animal cap cells at the early gastrula stage. At later stages of development, they were widely expressed in epithelial tissues that are highly polar in nature, including the neural epithelia, optic and otic vesicles, and in the pronephros. These data suggest that the roles of the Xenopus LAP genes in the control of cell polarity and morphogenesis are conserved during early development. Erbin and lano show similar expression patterns in the developing head, suggesting potential functional interactions between the two molecules in vivo.

  14. DNA Methylation Mediated Control of Gene Expression Is Critical for Development of Crown Gall Tumors

    PubMed Central

    Kneitz, Susanne; Weber, Dana; Fuchs, Joerg; Hedrich, Rainer; Deeken, Rosalia

    2013-01-01

    Crown gall tumors develop after integration of the T-DNA of virulent Agrobacterium tumefaciens strains into the plant genome. Expression of the T-DNA–encoded oncogenes triggers proliferation and differentiation of transformed plant cells. Crown gall development is known to be accompanied by global changes in transcription, metabolite levels, and physiological processes. High levels of abscisic acid (ABA) in crown galls regulate expression of drought stress responsive genes and mediate drought stress acclimation, which is essential for wild-type-like tumor growth. An impact of epigenetic processes such as DNA methylation on crown gall development has been suggested; however, it has not yet been investigated comprehensively. In this study, the methylation pattern of Arabidopsis thaliana crown galls was analyzed on a genome-wide scale as well as at the single gene level. Bisulfite sequencing analysis revealed that the oncogenes Ipt, IaaH, and IaaM were unmethylated in crown galls. Nevertheless, the oncogenes were susceptible to siRNA–mediated methylation, which inhibited their expression and subsequently crown gall growth. Genome arrays, hybridized with methylated DNA obtained by immunoprecipitation, revealed a globally hypermethylated crown gall genome, while promoters were rather hypomethylated. Mutants with reduced non-CG methylation developed larger tumors than the wild-type controls, indicating that hypermethylation inhibits plant tumor growth. The differential methylation pattern of crown galls and the stem tissue from which they originate correlated with transcriptional changes. Genes known to be transcriptionally inhibited by ABA and methylated in crown galls became promoter methylated upon treatment of A. thaliana with ABA. This suggests that the high ABA levels in crown galls may mediate DNA methylation and regulate expression of genes involved in drought stress protection. In summary, our studies provide evidence that epigenetic processes regulate gene

  15. DNA methylation mediated control of gene expression is critical for development of crown gall tumors.

    PubMed

    Gohlke, Jochen; Scholz, Claus-Juergen; Kneitz, Susanne; Weber, Dana; Fuchs, Joerg; Hedrich, Rainer; Deeken, Rosalia

    2013-01-01

    Crown gall tumors develop after integration of the T-DNA of virulent Agrobacterium tumefaciens strains into the plant genome. Expression of the T-DNA-encoded oncogenes triggers proliferation and differentiation of transformed plant cells. Crown gall development is known to be accompanied by global changes in transcription, metabolite levels, and physiological processes. High levels of abscisic acid (ABA) in crown galls regulate expression of drought stress responsive genes and mediate drought stress acclimation, which is essential for wild-type-like tumor growth. An impact of epigenetic processes such as DNA methylation on crown gall development has been suggested; however, it has not yet been investigated comprehensively. In this study, the methylation pattern of Arabidopsis thaliana crown galls was analyzed on a genome-wide scale as well as at the single gene level. Bisulfite sequencing analysis revealed that the oncogenes Ipt, IaaH, and IaaM were unmethylated in crown galls. Nevertheless, the oncogenes were susceptible to siRNA-mediated methylation, which inhibited their expression and subsequently crown gall growth. Genome arrays, hybridized with methylated DNA obtained by immunoprecipitation, revealed a globally hypermethylated crown gall genome, while promoters were rather hypomethylated. Mutants with reduced non-CG methylation developed larger tumors than the wild-type controls, indicating that hypermethylation inhibits plant tumor growth. The differential methylation pattern of crown galls and the stem tissue from which they originate correlated with transcriptional changes. Genes known to be transcriptionally inhibited by ABA and methylated in crown galls became promoter methylated upon treatment of A. thaliana with ABA. This suggests that the high ABA levels in crown galls may mediate DNA methylation and regulate expression of genes involved in drought stress protection. In summary, our studies provide evidence that epigenetic processes regulate gene

  16. Metformin reduces the Walker-256 tumor development in obese-MSG rats via AMPK and FOXO3a.

    PubMed

    de Queiroz, Eveline A I F; Akamine, Eliana H; de Carvalho, Maria Helena C; Sampaio, Sandra C; Fortes, Zuleica B

    2015-01-15

    Studies have associated obesity with a wide variety of cancers. Metformin, an anti-diabetic drug, has recently received attention as a potentially useful therapeutic agent for treating cancer. Therefore, the objective of this study was to analyze the mechanisms involved in the increase in tumor development and the reduction of it by metformin in obesity using an experimental breast tumor model. Newborn male Wistar rats were subcutaneously injected with 400mg/kg monosodium glutamate (MSG) (obese) or saline (control) at 2, 3, 4, 5 and 6 days of age. After 16 weeks, 1 × 10(7) Walker-256 tumor cells were subcutaneously injected in the right flank of the rats and concomitantly the treatment with metformin 300 mg/kg/15 days, via gavage, started. The rats were divided into 4 groups: control tumor (CT), control tumor metformin (CTM), obese-MSG tumor (OT) and obese-MSG tumor metformin (OTM). On the 18th week the tumor development and metformin effect were analyzed. Tumor development was higher in OT rats compared with CT rats. Activation of insulin-IR-ERK1/2 pathway and an anti-apoptotic effect might be the mechanisms involved in the higher development of tumor in obesity. The effect of metformin reducing the tumor development in obese rats might involve increased mRNA expression of pRb and p27, increased activity of AMPK and FOXO3a and decreased expression of p-ERK1/2 (Thr202/Tyr204) in Walker-256 tumor. Our data allow us to suggest that metformin, reducing the stimulatory effect of obesity on tumor development, has a potential role in the management of cancers. Copyright © 2014 Elsevier Inc. All rights reserved.

  17. Early Therapy Evaluation of Combined Anti-DR5 Antibody and Gemcitabine in Orthotopic Pancreatic Tumor Xenografts by Diffusion Weighted Magnetic Resonance Imaging

    PubMed Central

    Kim, Hyunki; Morgan, Desiree E.; Buchsbaum, Donald J.; Zeng, Huadong; Grizzle, William E.; Warram, Jason M.; Stockard, Cecil R.; McNally, Lacey R.; Long, Joshua W.; Sellers, Jeffrey C.; Forero, Andres; Zinn, Kurt R.

    2008-01-01

    Early therapeutic efficacy of anti-DR5 antibody (TRA-8) combined with gemcitabine was measured using diffusion-weighted magnetic resonance imaging (DWI) in an orthotopic pancreatic tumor model. Groups 1–4 of SCID mice (n=5–7/group) bearing orthotopically implanted, luciferase-positive human pancreatic tumors (MIA PaCa-2) were subsequently (4–5 weeks thereafter) injected with saline (control), gemcitabine (120mg/kg), TRA-8 (200μg), or TRA-8 combined with gemcitabine, respectively, on day 0. DWI, anatomical MRI, and bioluminescence imaging were performed on days 0, 1, 2, and 3 after treatment. Three tumors from each group were collected randomly on day 3 after imaging, and TUNEL staining was performed to quantify apoptotic cellularity. At just 1 day after starting therapy, the changes of apparent diffusion coefficient (ADC) in tumor regions for groups 3 (TRA-8) and 4 (TRA-8/Gem) were 21±9% (mean±SE) and 27±3%, respectively, significantly higher (p <0.05) than those of groups 1 (−1±5%) and 2 (−2±4%). There was no statistical difference in tumor volumes for the groups at this time. The mean ADC values of groups 2–4 gradually increased over 3 days, which were concurrent with tumor-volume regressions and bioluminescence-signal decreases. Apoptotic-cell densities of tumors in groups 1–4 were 0.7±0.4%, 0.6±0.2%, 3.1±0.9%, and 4.7±1.0%, respectively, linearly proportional to the ADC changes on day 1. Further, the ADC changes were highly correlated with the previously reported mean survival times of animals treated with the same agents and doses. This study supports the clinical use of DWI for pancreatic tumor patients for early assessment of drug efficacy. PMID:18922909

  18. β-HPV Infection Correlates with Early Stages of Carcinogenesis in Skin Tumors and Patient-Derived Xenografts from a Kidney Transplant Recipient Cohort.

    PubMed

    Borgogna, Cinzia; Olivero, Carlotta; Lanfredini, Simone; Calati, Federica; De Andrea, Marco; Zavattaro, Elisa; Savoia, Paola; Trisolini, Elena; Boldorini, Renzo; Patel, Girish K; Gariglio, Marisa

    2018-01-01

    Many malignancies that occur in high excess in kidney transplant recipients (KTRs) are due to viruses that thrive in the setting of immunosuppression. Keratinocyte carcinoma (KC), the most frequently occurring cancer type in KTR, has been associated with skin infection by human papillomavirus (HPV) from the beta genus. In this report, we extend our previous investigation aimed at identifying the presence of active β-HPV infection in skin tumors from KTRs through detection of viral protein expression. Using a combination of antibodies raised against the E4 and L1 proteins of the β-genotypes, we were able to visualize infection in five tumors [one keratoacanthoma (KA), three actinic keratoses (AKs), and one seborrheic keratoses (SKs)] that were all removed from two patients who had been both transplanted twice, had developed multiple KCs, and presented with a long history of immunosuppression (>30 years). These infected tissues displayed intraepidermal hyperplasia and increased expression of the ΔNp63 protein, which extended into the upper epithelial layers. In addition, using a xenograft model system in nude mice displaying a humanized stromal bed in the site of grafting, we successfully engrafted three AKs, two of which were derived from the aforementioned KTRs and displayed β-HPV infection in the original tumor. Of note, one AK-derived xenograft, along with its ensuing lymph node metastasis, was diagnosed as squamous cell carcinoma (SCC). In the latter, both β-HPV infection and ΔNp63 expression were no longer detectable. Although the overall success rate of engrafting was very low, the results of this study show for the first time that β-HPV + and ΔNp63 + intraepidermal hyperplasia can indeed progress to an aggressive SCC able to metastasize. Consistent with a series of reports attributing a causative role of β-HPV at early stages of skin carcinogenesis through ΔNp63 induction and increased keratinocytes stemness, here we provide in vivo evidence that

  19. β-HPV Infection Correlates with Early Stages of Carcinogenesis in Skin Tumors and Patient-Derived Xenografts from a Kidney Transplant Recipient Cohort

    PubMed Central

    Borgogna, Cinzia; Olivero, Carlotta; Lanfredini, Simone; Calati, Federica; De Andrea, Marco; Zavattaro, Elisa; Savoia, Paola; Trisolini, Elena; Boldorini, Renzo; Patel, Girish K.; Gariglio, Marisa

    2018-01-01

    Many malignancies that occur in high excess in kidney transplant recipients (KTRs) are due to viruses that thrive in the setting of immunosuppression. Keratinocyte carcinoma (KC), the most frequently occurring cancer type in KTR, has been associated with skin infection by human papillomavirus (HPV) from the beta genus. In this report, we extend our previous investigation aimed at identifying the presence of active β-HPV infection in skin tumors from KTRs through detection of viral protein expression. Using a combination of antibodies raised against the E4 and L1 proteins of the β-genotypes, we were able to visualize infection in five tumors [one keratoacanthoma (KA), three actinic keratoses (AKs), and one seborrheic keratoses (SKs)] that were all removed from two patients who had been both transplanted twice, had developed multiple KCs, and presented with a long history of immunosuppression (>30 years). These infected tissues displayed intraepidermal hyperplasia and increased expression of the ΔNp63 protein, which extended into the upper epithelial layers. In addition, using a xenograft model system in nude mice displaying a humanized stromal bed in the site of grafting, we successfully engrafted three AKs, two of which were derived from the aforementioned KTRs and displayed β-HPV infection in the original tumor. Of note, one AK-derived xenograft, along with its ensuing lymph node metastasis, was diagnosed as squamous cell carcinoma (SCC). In the latter, both β-HPV infection and ΔNp63 expression were no longer detectable. Although the overall success rate of engrafting was very low, the results of this study show for the first time that β-HPV+ and ΔNp63+ intraepidermal hyperplasia can indeed progress to an aggressive SCC able to metastasize. Consistent with a series of reports attributing a causative role of β-HPV at early stages of skin carcinogenesis through ΔNp63 induction and increased keratinocytes stemness, here we provide in vivo evidence that

  20. Ca2+ signalling and early embryonic patterning during zebrafish development.

    PubMed

    Webb, Sarah E; Miller, Andrew L

    2007-09-01

    1. It has been proposed that Ca2+ signalling, in the form of pulses, waves and steady gradients, may play a crucial role in key pattern-forming events during early vertebrate development. 2. With reference to the embryo of the zebrafish (Danio rerio), herein we review the Ca2+ transients reported from the cleavage to segmentation periods. This time-window includes most of the major pattern-forming events of early development, which transform a single-cell zygote into a complex multicellular embryo with established primary germ layers and body axes. 3. Data are presented to support our proposal that intracellular Ca2+ waves are an essential feature of embryonic cytokinesis and that propagating intercellular Ca2+ waves (both long and short range) may play a crucial role in: (i) the establishment of the embryonic periderm and the coordination of cell movements during epiboly, convergence and extension; (ii) the establishment of the basic embryonic axes and germ layers; and (iii) definition of the morphological boundaries of specific tissue domains and embryonic structures, including future organ anlagen. 4. The potential downstream targets of these Ca2+ transients are also discussed, as well as how they may integrate with other pattern-forming signalling pathways known to modulate early developmental events.

  1. Monitoring circulating prostate tumor cells after tumor resection by in vivo flow cytometry

    NASA Astrophysics Data System (ADS)

    Ding, Nan; Zhu, Xi; Xie, Chengying; Wei, Dan; Yang, Zhangru; Suo, Yuanzhen; Wei, Xunbin

    2018-02-01

    Prostate cancer has already become the biggest threat among all cancer types for male people and many people died because of its bone metastases. Circulating tumor cells (CTCs) can be used as early metastasis marker so that the detection of CTCs in blood is meaningful for early diagnosis and treatment. However, the relationship between these therapies and metastasis has not been fully clarified yet. Hence, we built PC3 subcutaneous tumor model and developed in vivo flow cytometer (IVFC) platform to record the dynamics of CTC before and after tumor resection. We found out that tumor resection can reduce CTC quantities instantaneously while having a good control of metastasis. CTC re-occurred 7 days after surgery, which might be correlated with early disseminated and deposited tumors. In conclusion, in vivo flow cytometry (IVFC) is capable of detecting CTC dynamics in prostate subcutaneous tumor model and this method could facilitate further research about relationship between other cancer therapies and circulating tumor cells.

  2. fDOT for in vivo follow-up of tumor development in mice lungs

    NASA Astrophysics Data System (ADS)

    Koenig, Anne; Hervé, Lionel; Da Silva, Anabela; Dinten, Jean-Marc; Boutet, Jérôme; Berger, Michel; Josserand, Véronique; Coll, Jean-Luc; Peltié, Philippe; Rizo, Philippe

    2007-07-01

    This paper presents in vivo experiments conducted on cancerous mice bearing mammary murine tumors. In order to reconstruct the fluorescence yield even in highly attenuating and heterogeneous regions like lungs, we developed a fDOT reconstruction method which at first corrects the light propagation model from optical heterogeneities by using the transmitted excitation light measurements. The same approach is also designed to enable working without immersing the mouse in adaptation liquid. The 3D fluorescence map is then reconstructed from the emitted signal of fluorescence and from the corrected propagation model by an ART (Algebraic Reconstruction Technique) algorithm. The system ability to reconstruct fluorescence distribution in presence of high attenuating objects has been validated on phantoms presenting a fluorescent absorbent inclusion. A study was conducted on mice to follow up lungs at different stages of tumor development. The mice were imaged after intravenous injection to the animal of a cancer specific fluorescent marker. A control experiment was conducted in parallel on healthy mice to ensure that the multiple injections of fluorophore did not induce parasite fluorescence distribution. These results validate our system performances for studying small animal lungs tumor evolution. Detection and localization of the fluorophore fixations expresses the tumor development.

  3. Merkel Cell Polyomavirus Small T Antigen Initiates Merkel Cell Carcinoma-like Tumor Development in Mice.

    PubMed

    Verhaegen, Monique E; Mangelberger, Doris; Harms, Paul W; Eberl, Markus; Wilbert, Dawn M; Meireles, Julia; Bichakjian, Christopher K; Saunders, Thomas L; Wong, Sunny Y; Dlugosz, Andrzej A

    2017-06-15

    Merkel cell carcinoma (MCC) tumor cells express several markers detected in normal Merkel cells, a nonproliferative population of neuroendocrine cells that arise from epidermis. MCCs frequently contain Merkel cell polyomavirus (MCPyV) DNA and express viral transforming antigens, sT and tLT, but the role of these putative oncogenes in MCC development, and this tumor's cell of origin, are unknown. Using a panel of preterm transgenic mice, we show that epidermis-targeted coexpression of sT and the cell fate-determinant atonal bHLH transcription factor 1 (ATOH1) leads to development of widespread cellular aggregates, with histology and marker expression mimicking that of human intraepidermal MCC. The MCC-like tumor phenotype was dependent on the FBXW7-binding domain of sT, but not the sT-PP2A binding domain. Coexpression of MCPyV tLT did not appreciably alter the phenotype driven by either sT or sT combined with ATOH1. MCPyV sT, when coexpressed with ATOH1, is thus sufficient to initiate development of epidermis-derived MCC-like tumors in mice. Cancer Res; 77(12); 3151-7. ©2017 AACR . ©2017 American Association for Cancer Research.

  4. Early Intravascular Events are Associated with Development of ARDS.

    PubMed

    Abdulnour, Raja-Elie E; Gunderson, Tina; Barkas, Ioanna; Timmons, Jack Y; Barnig, Cindy; Gong, Michelle; Kor, Daryl J; Gajic, Ognjen; Talmor, Daniel; Carter, Rickey E; Levy, Bruce D

    2018-05-21

    The acute respiratory distress syndrome (ARDS) is a devastating illness with limited therapeutic options. A better understanding of early biochemical and immunological events in ARDS could inform the development of new preventive and treatment strategies. To determine select peripheral blood lipid mediator and leukocyte responses in patients at-risk for ARDS. Patients at risk for ARDS were randomized as part of a multicenter, double-blind clinical trial of aspirin versus placebo (LIPS-A; NCT01504867). Plasma thromboxane B2 (TxB2), 15-epi-LXA4 (aspirin-triggered lipoxin A4, ATL), and peripheral blood leukocyte number and activation were determined upon enrollment and after treatment with either aspirin or placebo. Thirty-three of 367 subjects (9.0%) developed ARDS after randomization. Baseline ATL levels, total monocyte counts, intermediate monocyte (IntMo) counts, and Mo-PA were associated with the development of ARDS. Peripheral blood neutrophil count and monocyte-platelet aggregates significantly decreased over time. Of note, 9 subjects developed ARDS after randomization yet prior to study drug initiation, including 7 subjects assigned to aspirin treatment. Subjects without ARDS at the time of first dose demonstrated a lower incidence of ARDS with aspirin treatment. Compared with placebo, aspirin significantly decreased TxB2 and increased the ATL/TxB2 ratio. Biomarkers of intravascular monocyte activation in at-risk patients were associated with development of ARDS. The potential clinical benefit of early aspirin for prevention of ARDS remains uncertain. Together, results of the biochemical and immunological analyses provide a window into the early pathogenesis of human ARDS, and represent potential vascular biomarkers of ARDS risk.

  5. Impact of Pretreatment Tumor Growth Rate on Outcome of Early-Stage Lung Cancer Treated With Stereotactic Body Radiation Therapy

    SciT

    Atallah, Soha; Cho, B.C. John; Allibhai, Zishan

    2014-07-01

    Purpose: To determine the influence of pretreatment tumor growth rate on outcomes in patients with early-stage non-small cell lung cancer (NSCLC) treated with stereotactic body radiation therapy (SBRT). Methods and Materials: A review was conducted on 160 patients with T1-T2N0M0 NSCLC treated with SBRT at single institution. The patient's demographic and clinical data, time interval (t) between diagnostic and planning computed tomography (CT), vital status, disease status, and cause of death were extracted from a prospectively kept database. Differences in gross tumor volume between diagnostic CT (GTV1) and planning CT (GTV2) were recorded, and growth rate was calculated by usemore » of specific growth rate (SGR). Kaplan-Meier curves were constructed for overall survival (OS). Differences between groups were compared with a log-rank test. Multivariate analyses were performed by use of the Cox proportional hazard model with SGR and other relevant clinical factors. Cumulative incidence was calculated for local, regional, and distant failures by use of the competing risk approach and was compared with Gray's test. Results: The median time interval between diagnostic and planning CT was 82 days. The patients were divided into 2 groups, and the median SGR was used as a cut-off. The median survival times were 38.6 and 27.7 months for the low and high SGR groups, respectively (P=.03). Eastern Cooperative Oncology Group performance status (P=.01), sex (P=.04), SGR (P=.03), and GTV2 (P=.002) were predictive for OS in multivariable Cox regression analysis and, except sex, were similarly predictive for failure-free survival (FFS). The 3-year cumulative incidences of regional failure were 19.2% and 6.0% for the high and low SGR groups, respectively (P=.047). Conclusion: High SGR was correlated with both poorer OS and FFS in patients with early-stage NSCLC treated with SBRT. If validated, this measurement may be useful in identifying patients most likely to benefit from

  6. New Approaches for Early Detection of Breast Tumor Invasion or Progression

    DTIC Science & Technology

    2003-05-01

    IMMUNOHISTOCHEMICAL ASSESSMENT OF \\ Breast Disease PRIMARY LESIONS OF BREAST EPITHELIAL February 13-16, 2003 INVASION INTO BLOOD VESSELS Ritz - Carlton , Amelia...Programs, The Idea Award (BCOOI 187) and Career Development m ~ ~ ~ ~ ~ wr g .••• m Vol 16,’ No MEETING March 22 - 28, 2003 Marriott Wardman Park Hotel

  7. Illinois Early Learning Project Tip Sheets: Physical Development and Health.

    ERIC Educational Resources Information Center

    2003

    The Illinois Early Learning Project (IEL) is funded by the Illinois State Board of Education to provide information resources on early learning and training related to implementing the Illinois Early Learning Standards for parents and for early childhood personnel in all settings. The IEL tip sheets offer suggestions to parents and early childhood…

  8. The role of tumor microenvironment in development and progression of malignant melanomas - a systematic review.

    PubMed

    Gurzu, Simona; Beleaua, Marius Alexandru; Jung, Ioan

    2018-01-01

    To reveal the particular aspects of the tumor microenvironment of malignant melanomas, a systematic review including 34 representative papers was performed. The review took into account the aspects related the Wnt/β-catenin pathway-related epithelial-mesenchymal transition (EMT) versus mesenchymal-epithelial transition (MET) of keratinocytes, fibroblasts and melanoma cells, as possible tools for understanding genesis and evolution of malignant melanoma. The possible reversible features of EMT and the role of tumor microenvironment in the metastatic process were also analyzed. A particular issue was related on the cancer stem cells that include melanocyte stem cells (McSCs) and multipotent mesenchymal stem/stromal cells (MSCs). As the McSCs embryological development in mouse is not similar to human development, the role of stem cells in genesis and development of human melanoma should be proved in human melanoma cells only. For further development of targeted therapy, a better understanding of melanomagenesis pathways and its microenvironment particularities is necessary.

  9. Excess iron: considerations related to development and early growth.

    PubMed

    Wessling-Resnick, Marianne

    2017-12-01

    What effects might arise from early life exposures to high iron? This review considers the specific effects of high iron on the brain, stem cells, and the process of erythropoiesis and identifies gaps in our knowledge of what molecular damage may be incurred by oxidative stress that is imparted by high iron status in early life. Specific areas to enhance research on this topic include the following: longitudinal behavioral studies of children to test associations between iron exposures and mood, emotion, cognition, and memory; animal studies to determine epigenetic changes that reprogram brain development and metabolic changes in early life that could be followed through the life course; and the establishment of human epigenetic markers of iron exposures and oxidative stress that could be monitored for early origins of adult chronic diseases. In addition, efforts to understand how iron exposure influences stem cell biology could be enhanced by establishing platforms to collect biological specimens, including umbilical cord blood and amniotic fluid, to be made available to the research community. At the molecular level, there is a need to better understand stress erythropoiesis and changes in iron metabolism during pregnancy and development, especially with respect to regulatory control under high iron conditions that might promote ineffective erythropoiesis and iron-loading anemia. These investigations should focus not only on factors such as hepcidin and erythroferrone but should also include newly identified interactions between transferrin receptor-2 and the erythropoietin receptor. Finally, despite our understanding that several key micronutrients (e.g., vitamin A, copper, manganese, and zinc) support iron's function in erythropoiesis, how these nutrients interact remains, to our knowledge, unknown. It is necessary to consider many factors when formulating recommendations on iron supplementation. © 2017 American Society for Nutrition.

  10. Regulation of bone morphogenetic proteins in early embryonic development

    NASA Astrophysics Data System (ADS)

    Yamamoto, Yukiyo; Oelgeschläger, Michael

    2004-11-01

    Bone morphogenetic proteins (BMPs), a large subgroup of the TGF-β family of secreted growth factors, control fundamental events in early embryonic development, organogenesis and adult tissue homeostasis. The plethora of dose-dependent cellular processes regulated by BMP signalling demand a tight regulation of BMP activity. Over the last decade, a number of proteins have been identified that bind BMPs in the extracellular space and regulate the interaction of BMPs with their cognate receptors, including the secreted BMP antagonist Chordin. In the early vertebrate embryo, the localized secretion of BMP antagonists from the dorsal blastopore lip establishes a functional BMP signalling gradient that is required for the determination of the dorsoventral or back to belly body axis. In particular, inhibition of BMP activity is essential for the formation of neural tissue in the development of vertebrate and invertebrate embryos. Here we review recent studies that have provided new insight into the regulation of BMP signalling in the extracellular space. In particular, we discuss the recently identified Twisted gastrulation protein that modulates, in concert with metalloproteinases of the Tolloid family, the interaction of Chordin with BMP and a family of proteins that share structural similarities with Chordin in the respective BMP binding domains. In addition, genetic and functional studies in zebrafish and frog provide compelling evidence that the secreted protein Sizzled functionally interacts with the Chd BMP pathway, despite being expressed ventrally in the early gastrula-stage embryo. These intriguing discoveries may have important implications, not only for our current concept of early embryonic patterning, but also for the regulation of BMP activity at later developmental stages and tissue homeostasis in the adult.

  11. Early Detection of Ovarian Cancer by Tumor Epithelium-Targeted Molecular Ultrasound

    DTIC Science & Technology

    2014-10-01

    successful pregnancy outcome. *PIF Proprietary G-12 IL-33-responsive group 2 innate lymphoid cells are present in mouse uterine tissue and may play roles in... innate lymphoid cells (ILC2s) that are responsive to IL-33 drive helminth immunity, type 2 immune responses, and tissue pathology and homeostasis in...16 (IL-16) secreted by immune cells . Inflammation of the ovary and tubal epithelium due to frequent ovulation leads to the development of oxidative

  12. Paraneoplastic antigen Ma2 autoantibodies as specific blood biomarkers for detection of early recurrence of small intestine neuroendocrine tumors.

    PubMed

    Cui, Tao; Hurtig, Monica; Elgue, Graciela; Li, Su-Chen; Veronesi, Giulia; Essaghir, Ahmed; Demoulin, Jean-Baptiste; Pelosi, Giuseppe; Alimohammadi, Mohammad; Öberg, Kjell; Giandomenico, Valeria

    2010-12-30

    Small intestine neuroendocrine tumors (SI-NETs) belong to a rare group of cancers. Most patients have developed metastatic disease at the time of diagnosis, for which there is currently no cure. The delay in diagnosis is a major issue in the clinical management of the patients and new markers are urgently needed. We have previously identified paraneoplastic antigen Ma2 (PNMA2) as a novel SI-NET tissue biomarker. Therefore, we evaluated whether Ma2 autoantibodies detection in the blood stream is useful for the clinical diagnosis and recurrence of SI-NETs. A novel indirect ELISA was set up to detect Ma2 autoantibodies in blood samples of patients with SI-NET at different stages of disease. The analysis was extended to include typical and atypical lung carcinoids (TLC and ALC), to evaluate whether Ma2 autoantibodies in the blood stream become a general biomarker for NETs. In total, 124 blood samples of SI-NET patients at different stages of disease were included in the study. The novel Ma2 autoantibody ELISA showed high sensitivity, specificity and accuracy with ROC curve analysis underlying an area between 0.734 and 0.816. Ma2 autoantibodies in the blood from SI-NET patients were verified by western blot and sequential immunoprecipitation. Serum antibodies of patients stain Ma2 in the tumor tissue and neurons. We observed that SI-NET patients expressing Ma2 autoantibody levels below the cutoff had a longer progression and recurrence-free survival compared to those with higher titer. We also detected higher levels of Ma2 autoantibodies in blood samples from TLC and ALC patients than from healthy controls, as previously shown in small cell lung carcinoma samples. Here we show that high Ma2 autoantibody titer in the blood of SI-NET patients is a sensitive and specific biomarker, superior to chromogranin A (CgA) for the risk of recurrence after radical operation of these tumors.

  13. Early somatosensory processing in individuals at risk for developing psychoses.

    PubMed

    Hagenmuller, Florence; Heekeren, Karsten; Theodoridou, Anastasia; Walitza, Susanne; Haker, Helene; Rössler, Wulf; Kawohl, Wolfram

    2014-01-01

    Human cortical somatosensory evoked potentials (SEPs) allow an accurate investigation of thalamocortical and early cortical processing. SEPs reveal a burst of superimposed early (N20) high-frequency oscillations around 600 Hz. Previous studies reported alterations of SEPs in patients with schizophrenia. This study addresses the question whether those alterations are also observable in populations at risk for developing schizophrenia or bipolar disorders. To our knowledge to date, this is the first study investigating SEPs in a population at risk for developing psychoses. Median nerve SEPs were investigated using multichannel EEG in individuals at risk for developing bipolar disorders (n = 25), individuals with high-risk status (n = 59) and ultra-high-risk status for schizophrenia (n = 73) and a gender and age-matched control group (n = 45). Strengths and latencies of low- and high-frequency components as estimated by dipole source analysis were compared between groups. Low- and high-frequency source activity was reduced in both groups at risk for schizophrenia, in comparison to the group at risk for bipolar disorders. HFO amplitudes were also significant reduced in subjects with high-risk status for schizophrenia compared to healthy controls. These differences were accentuated among cannabis non-users. Reduced N20 source strengths were related to higher positive symptom load. These results suggest that the risk for schizophrenia, in contrast to bipolar disorders, may involve an impairment of early cerebral somatosensory processing. Neurophysiologic alterations in schizophrenia precede the onset of initial psychotic episode and may serve as indicator of vulnerability for developing schizophrenia.

  14. Early somatosensory processing in individuals at risk for developing psychoses

    PubMed Central

    Hagenmuller, Florence; Heekeren, Karsten; Theodoridou, Anastasia; Walitza, Susanne; Haker, Helene; Rössler, Wulf; Kawohl, Wolfram

    2014-01-01

    Human cortical somatosensory evoked potentials (SEPs) allow an accurate investigation of thalamocortical and early cortical processing. SEPs reveal a burst of superimposed early (N20) high-frequency oscillations around 600 Hz. Previous studies reported alterations of SEPs in patients with schizophrenia. This study addresses the question whether those alterations are also observable in populations at risk for developing schizophrenia or bipolar disorders. To our knowledge to date, this is the first study investigating SEPs in a population at risk for developing psychoses. Median nerve SEPs were investigated using multichannel EEG in individuals at risk for developing bipolar disorders (n = 25), individuals with high-risk status (n = 59) and ultra-high-risk status for schizophrenia (n = 73) and a gender and age-matched control group (n = 45). Strengths and latencies of low- and high-frequency components as estimated by dipole source analysis were compared between groups. Low- and high-frequency source activity was reduced in both groups at risk for schizophrenia, in comparison to the group at risk for bipolar disorders. HFO amplitudes were also significant reduced in subjects with high-risk status for schizophrenia compared to healthy controls. These differences were accentuated among cannabis non-users. Reduced N20 source strengths were related to higher positive symptom load. These results suggest that the risk for schizophrenia, in contrast to bipolar disorders, may involve an impairment of early cerebral somatosensory processing. Neurophysiologic alterations in schizophrenia precede the onset of initial psychotic episode and may serve as indicator of vulnerability for developing schizophrenia. PMID:25309363

  15. Dual effects of fluoxetine on mouse early embryonic development.

    PubMed

    Kim, Chang-Woon; Choe, Changyong; Kim, Eun-Jin; Lee, Jae-Ik; Yoon, Sook-Young; Cho, Young-Woo; Han, Sunkyu; Tak, Hyun-Min; Han, Jaehee; Kang, Dawon

    2012-11-15

    Fluoxetine, a selective serotonin reuptake inhibitor, regulates a variety of physiological processes, such as cell proliferation and apoptosis, in mammalian cells. Little is known about the role of fluoxetine in early embryonic development. This study was undertaken to investigate the effect of fluoxetine during mouse early embryonic development. Late two-cell stage embryos (2-cells) were cultured in the presence of various concentrations of fluoxetine (1 to 50μM) for different durations. When late 2-cells were incubated with 5μM fluoxetine for 6h, the percentage that developed into blastocysts increased compared to the control value. However, late 2-cells exposed to fluoxetine (5μM) over 24h showed a reduction in blastocyst formation. The addition of fluoxetine (5μM) together with KN93 or KN62 (calcium/calmodulin-dependent protein kinase II (CaMKII) inhibitors) failed to increase blastocyst formation. Fluoxetine treatment inhibited TREK-1 and TREK-2, members of the two-pore domain K(+) channel family expressed in mouse embryos, activities, indicating that fluoxetine-induced membrane depolarization in late 2-cells might have resulted from TREK inhibition. In addition, long-term exposure to fluoxetine altered the TREK mRNA expression levels. Furthermore, injection of siRNA targeting TREKs significantly decreased blastocyst formation by ~30% compared to injection of scrambled siRNA. Long-term exposure of fluoxetine had no effect on blastocyst formation of TREK deficient embryos. These results indicate that low-dose and short-term exposures of late 2-cells to fluoxetine probably increase blastocyst formation through activation of CaMKII-dependent signal transduction pathways, whereas long-term exposure decreases mouse early embryonic development through inhibition of TREK channel gating. Copyright © 2012 Elsevier Inc. All rights reserved.

  16. The Proteomic Signature of Aspergillus fumigatus During Early Development*

    PubMed Central

    Cagas, Steven E.; Jain, Mohit Raja; Li, Hong; Perlin, David S.

    2011-01-01

    Aspergillus fumigatus is a saprophytic fungus that causes a range of diseases in humans including invasive aspergillosis. All forms of disease begin with the inhalation of conidia, which germinate and develop. Four stages of early development were evaluated using the gel free system of isobaric tagging for relative and absolute quantitation to determine the full proteomic profile of the pathogen. A total of 461 proteins were identified at 0, 4, 8, and 16 h and fold changes for each were established. Ten proteins including the hydrophobin rodlet protein RodA and a protein involved in melanin synthesis Abr2 were found to decrease relative to conidia. To generate a more comprehensive view of early development, a whole genome microarray analysis was performed comparing conidia to 8 and 16 h of growth. A total of 1871 genes were found to change significantly at 8 h with 1001 genes up-regulated and 870 down-regulated. At 16 h, 1235 genes changed significantly with 855 up-regulated and 380 down-regulated. When a comparison between the proteomics and microarray data was performed at 8 h, a total of 22 proteins with significant changes also had corresponding genes that changed significantly. When the same comparison was performed at 16 h, 12 protein and gene combinations were found. This study, the most comprehensive to date, provides insights into early pathways activated during growth and development of A. fumigatus. It reveals a pathogen that is gearing up for rapid growth by building translation machinery, generating ATP, and is very much committed to aerobic metabolism. PMID:21825280

  17. Clinical assessment of early language development: a simplified short form of the Mandarin communicative development inventory.

    PubMed

    Soli, Sigfrid D; Zheng, Yun; Meng, Zhaoli; Li, Gang

    2012-09-01

    The purpose of this study was to develop a practical mean for clinical evaluation of early pediatric language development by establishing developmental trajectories for receptive and expressive vocabulary growth in children between 6 and 32 months of age using a simple, time-efficient assessment tool. Simplified short form versions of the Words and Gestures and Words and Sentences vocabulary inventories in the Mandarin Communicative Development Inventory [1] were developed and used to assess early language development in developmentally normal children from 6 to 32 months of age during routine health checks. Developmental trajectories characterizing the rate of receptive and expressive vocabulary growth between 6 and 32 months of age are reported. These trajectories allow the equivalent age corresponding to a score to be determined after a brief structured interview with the child's parents that can be conducted in a busy clinical setting. The simplified short forms of the Mandarin Communicative Development Inventories can serve as a clinically useful tool to assess early child language development, providing a practical mean of objectively assessing early language development following early interventions to treat young children with hearing impairment as well as speech and language delays. Objective evidence of language development is essential for achievement of effective (re)habilitation outcomes. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  18. Studies toward birth and early mammalian development in space

    NASA Astrophysics Data System (ADS)

    Ronca, April E.

    2003-10-01

    Sustaining life beyond Earth on either space stations or other planets will require a clear understanding of how the space environment affects key phases of mammalian reproduction and development. Pregnancy, parturition (birth) and the early development of offspring are complex processes essential for successful reproduction and the proliferation of mammalian species. While no mammal has yet undergone birth within the space environment, studies spanning the gravity continuum from 0- to 2-g are revealing startling insights into how reproduction and development may proceed under gravitational conditions deviating from those typically experienced on Earth. In this report, I review studies of pregnant Norway rats and their offspring flown in microgravity (μg) onboard the NASA Space Shuttle throughout the period corresponding to mid- to late gestation, and analogous studies of pregnant rats exposed to hypergravity ( ht) onboard the NASA Ames Research Center 24-ft centrifuge. Studies of postnatal rats flown in space or exposed to centrifugation are reviewed. Although many important questions remain unanswered, the available data suggest that numerous aspects of pregnancy, birth and early mammalian development can proceed under altered gravity conditions. Published by Elsevier Ltd on behalf of COSPAR.

  19. Effects of pulsed magnetic stimulation on tumor development and immune functions in mice.

    PubMed

    Yamaguchi, Sachiko; Ogiue-Ikeda, Mari; Sekino, Masaki; Ueno, Shoogo

    2006-01-01

    We investigated the effects of pulsed magnetic stimulation on tumor development processes and immune functions in mice. A circular coil (inner diameter = 15 mm, outer diameter = 75 mm) was used in the experiments. Stimulus conditions were pulse width = 238 micros, peak magnetic field = 0.25 T (at the center of the coil), frequency = 25 pulses/s, 1,000 pulses/sample/day and magnetically induced eddy currents in mice = 0.79-1.54 A/m(2). In an animal study, B16-BL6 melanoma model mice were exposed to the pulsed magnetic stimulation for 16 days from the day of injection of cancer cells. A tumor growth study revealed a significant tumor weight decrease in the stimulated group (54% of the sham group). In a cellular study, B16-BL6 cells were also exposed to the magnetic field (1,000 pulses/sample, and eddy currents at the bottom of the dish = 2.36-2.90 A/m(2)); however, the magnetically induced eddy currents had no effect on cell viabilities. Cytokine production in mouse spleens was measured to analyze the immunomodulatory effect after the pulsed magnetic stimulation. tumor necrosis factor (TNF-alpha) production in mouse spleens was significantly activated after the exposure of the stimulus condition described above. These results showed the first evidence of the anti-tumor effect and immunomodulatory effects brought about by the application of repetitive magnetic stimulation and also suggested the possible relationship between anti-tumor effects and the increase of TNF-alpha levels caused by pulsed magnetic stimulation.

  20. Development of ex vivo model for determining temperature distribution in tumor tissue during photothermal therapy

    NASA Astrophysics Data System (ADS)

    Liu, Shaojie; Doughty, Austin; Mesiya, Sana; Pettitt, Alex; Zhou, Feifan; Chen, Wei R.

    2017-02-01

    Temperature distribution in tissue is a crucial factor in determining the outcome of photothermal therapy in cancer treatment. In order to investigate the temperature distribution in tumor tissue during laser irradiation, we developed a novel ex vivo device to simulate the photothermal therapy on tumors. A 35°C, a thermostatic incubator was used to provide a simulation environment for body temperature of live animals. Different biological tissues (chicken breast and bovine liver) were buried inside a tissue-simulating gel and considered as tumor tissues. An 805-nm laser was used to irradiate the target tissue. A fiber with an interstitial cylindrical diffuser (10 mm) was directly inserted in the center of the tissue, and the needle probes of a thermocouple were inserted into the tissue paralleling the laser fiber at different distances to measure the temperature distribution. All of the procedures were performed in the incubator. Based on the results of this study, the temperature distribution in bovine liver is similar to that of tumor tissue under photothermal therapy with the same doses. Therefore, the developed model using bovine liver for determining temperature distribution can be used during interstitial photothermal therapy.

  1. Development of an autologous canine cancer vaccine system for resectable malignant tumors in dogs.

    PubMed

    Yannelli, J R; Wouda, R; Masterson, T J; Avdiushko, M G; Cohen, D A

    2016-12-01

    While conventional therapies exist for canine cancer, immunotherapies need to be further explored and applied to the canine setting. We have developed an autologous cancer vaccine (K9-ACV), which is available for all dogs with resectable disease. K9-ACV was evaluated for safety and immunogenicity for a variety of cancer types in a cohort of companion dogs under veterinary care. The autologous vaccine was prepared by enzymatic digestion of solid tumor biopsies. The resultant single cell suspensions were then UV-irradiated resulting in immunogenic cell death of the tumor cells. Following sterility and endotoxin testing, the tumor cells were admixed with CpG ODN adjuvant and shipped to the participating veterinary clinics. The treating veterinarians then vaccinated each patient with three intradermal injections (10 million cells per dose) at 30-day intervals (one prime and two boost injections). In a cohort of 20 dogs completing the study, 17 dogs (85%) developed an augmented IgG response to autologous tumor antigens as demonstrated using western blot analysis of pre- and post-peripheral blood samples. We also report several dogs have lived beyond expected survival time based on previously published data. In summary, K9-ACV is an additional option to be considered for the treatment of dogs with resectable cancer. Copyright © 2016 Elsevier B.V. All rights reserved.

  2. Kcnh1 Voltage-gated Potassium Channels Are Essential for Early Zebrafish Development*

    PubMed Central

    Stengel, Rayk; Rivera-Milla, Eric; Sahoo, Nirakar; Ebert, Christina; Bollig, Frank; Heinemann, Stefan H.; Schönherr, Roland; Englert, Christoph

    2012-01-01

    The Kcnh1 gene encodes a voltage-gated potassium channel highly expressed in neurons and involved in tumor cell proliferation, yet its physiological roles remain unclear. We have used the zebrafish as a model to analyze Kcnh1 function in vitro and in vivo. We found that the kcnh1 gene is duplicated in teleost fish (i.e. kcnh1a and kcnh1b) and that both genes are maternally expressed during early development. In adult zebrafish, kcnh1a and kcnh1b have distinct expression patterns but share expression in brain and testis. Heterologous expression of both genes in Xenopus oocytes revealed a strong conservation of characteristic functional properties between human and fish channels, including a unique sensitivity to intracellular Ca2+/calmodulin and modulation of voltage-dependent gating by extracellular Mg2+. Using a morpholino antisense approach, we demonstrate a strong kcnh1 loss-of-function phenotype in developing zebrafish, characterized by growth retardation, delayed hindbrain formation, and embryonic lethality. This late phenotype was preceded by transcriptional up-regulation of known cell-cycle inhibitors (p21, p27, cdh2) and down-regulation of pro-proliferative factors, including cyclin D1, at 70% epiboly. These results reveal an unanticipated basic activity of kcnh1 that is crucial for early embryonic development and patterning. PMID:22927438

  3. Toward an Integrated View of Early Language and Communication Development and Socioemotional Development.

    ERIC Educational Resources Information Center

    Prizant, Barry M.; Wetherby, Amy M.

    1990-01-01

    The article reviews literature on the integrated nature of early communication and socioemotional development in children. It discusses two models, one addressing the role of the development of mutual (interactive) and self-regulatory capacities in young children's socioemotional development, and a transactional model conceptualizing the complex…

  4. IMPACT OF OBESITY ON DEVELOPMENT AND PROGRESSION OF MAMMARY TUMORS IN PRECLINICAL MODELS OF BREAST CANCER

    PubMed Central

    Cleary, Margot P.

    2013-01-01

    Overweight and/or obesity are known risk factors for postmenopausal breast cancer. More recently increased body weight has also been associated with poor prognosis for both pre- and postmenopausal breast cancer. This relationship has primarily been identified through epidemiological studies. Additional information from in vitro studies has also been produced in attempts to delineate mechanisms of action for the association of obesity and body weight and breast cancer. This approach has identified potential growth factors such as insulin, leptin, estrogen and IGF-I which are reported to be modulated by body weight changes. However, in vitro studies are limited in scope and frequently use non-physiological concentrations of growth factors, while long follow-up is needed for human studies. Preclinical animal models provide an intermediary approach to investigate the impact of body weight and potential growth factors on mammary/breast tumor development and progression. Here results of a number of studies addressing this issue are presented. In the majority of the studies either genetically-obese or diet-induced obese rodent models have been used to investigate spontaneous, transgenic and carcinogen-induced mammary tumor development. To study tumor progression the major focus has been allograft studies in mice with either genetic or dietary-induced obesity. In general, obesity has been demonstrated to shorten mammary tumor latency and to impact tumor pathology. However, in rodents with defects in leptin and other growth factors the impact of obesity is not as straightforward. Future studies using more physiologically relevant obesity models and clearly distinguishing diet composition from body weight effects will be important in continuing to understand the factors associated with body weight’s impact on the mammary/breast cancer development and progression. PMID:24122258

  5. Anti-tumor activities of lipids and lipid analogues and their development as potential anticancer drugs.

    PubMed

    Murray, Michael; Hraiki, Adam; Bebawy, Mary; Pazderka, Curtis; Rawling, Tristan

    2015-06-01

    Lipids have the potential for development as anticancer agents. Endogenous membrane lipids, such as ceramides and certain saturated fatty acids, have been found to modulate the viability of tumor cells. In addition, many tumors over-express cyclooxygenase, lipoxygenase or cytochrome P450 enzymes that mediate the biotransformation of ω-6 polyunsaturated fatty acids (PUFAs) to potent eicosanoid regulators of tumor cell proliferation and cell death. In contrast, several analogous products from the biotransformation of ω-3 PUFAs impair particular tumorigenic pathways. For example, the ω-3 17,18-epoxide of eicosapentaenoic acid activates anti-proliferative and proapoptotic signaling cascades in tumor cells and the lipoxygenase-derived resolvins are effective inhibitors of inflammatory pathways that may drive tumor expansion. However, the development of potential anti-cancer drugs based on these molecules is complex, with in vivo stability a major issue. Nevertheless, recent successes with the antitumor alkyl phospholipids, which are synthetic analogues of naturally-occurring membrane phospholipid esters, have provided the impetus for development of further molecules. The alkyl phospholipids have been tested against a range of cancers and show considerable activity against skin cancers and certain leukemias. Very recently, it has been shown that combination strategies, in which alkyl phospholipids are used in conjunction with established anticancer agents, are promising new therapeutic approaches. In future, the evaluation of new lipid-based molecules in single-agent and combination treatments may also be assessed. This could provide a range of important treatment options in the management of advanced and metastatic cancer. Copyright © 2015 Elsevier Inc. All rights reserved.

  6. Notch signaling dynamics in the adult healthy prostate and in prostatic tumor development.

    PubMed

    Pedrosa, Ana-Rita; Graça, José L; Carvalho, Sandra; Peleteiro, Maria C; Duarte, António; Trindade, Alexandre

    2016-01-01

    The Notch signaling pathway has been implicated in prostate development, maintenance and tumorigenesis by its key role in cell-fate determination, differentiation and proliferation. Therefore, we proposed to analyze Notch family members transcription and expression, including ligands (Dll1, 3, 4 and Jagged1 and 2), receptors (Notch1-4) and effectors (Hes1, 2, 5 and Hey1, 2, L), in both normal and tumor bearing mouse prostates to better understand the dynamics of Notch signaling in prostate tumorigenesis. Wild type mice and transgenic adenocarcinoma of the mouse prostate model (TRAMP) mice were sacrificed at 18, 24 or 30 weeks of age and the prostates collected and processed for either whole prostate or prostate cell specific populations mRNA analysis and for protein expression analysis by immunohistochemistry and immunofluorescence. We observed that Dll1 and Dll4 are expressed in the luminal compartment of the mouse healthy prostate, whereas Jagged2 expression is restricted to the basal and stromal compartment. Additionally, Notch2 and Notch4 are normally expressed in the prostate luminal compartment while Notch2 and Notch3 are also expressed in the stromal layer of the healthy prostate. As prostate tumor development takes place, there is up-regulation of Notch components. Particularly, the prostate tumor lesions have increased expression of Jagged1 and 2, of Notch3 and of Hey1. We have also detected the presence of activated Notch3 in prostatic tumors that co-express Jagged1 and ultimately the Hey1 effector. Taken together our results point out the Notch axis Jagged1-2/Notch3/Hey1 to be important for prostate tumor development and worthy of additional functional studies and validation in human clinical disease. © 2015 Wiley Periodicals, Inc.

  7. Chaos, Poverty, and Parenting: Predictors of Early Language Development

    PubMed Central

    Vernon-Feagans, Lynne; Garrett-Peters, Patricia; Willoughby, Mike; Mills-Koonce, Roger

    2011-01-01

    Studies have shown that distal family risk factors like poverty and maternal education are strongly related to children's early language development. Yet, few studies have examined these risk factors in combination with more proximal day-to-day experiences of children that might be critical to understanding variation in early language. Young children's exposure to a chronically chaotic household may be one critical experience that is related to poorer language, beyond the contribution of SES and other demographic variables. In addition, it is not clear whether parenting might mediate the relationship between chaos and language. The purpose of this study was to understand how multiple indicators of chaos over children's first three years of life, in a representative sample of children living in low wealth rural communities, were related to child expressive and receptive language at 36 months. Factor analysis of 10 chaos indicators over five time periods suggested two factors that were named household disorganization and instability. Results suggested that after accounting for thirteen covariates like maternal education and poverty, one of two chaos composites (household disorganization) accounted for significant variance in receptive and expressive language. Parenting partially mediated this relationship although household disorganization continued to account for unique variance in predicting early language. PMID:23049162

  8. Macrosomia has its roots in early placental development

    PubMed Central

    Schwartz, Nadav; Quant, Hayley S.; Sammel, Mary D.; PARRY, Samuel

    2014-01-01

    Introduction We sought to determine if early placental size, as measured by 3-dimensional ultrasonography, is associated with an increased risk of delivering a macrosomic or large-for-gestational age (LGA) infant. Methods We prospectively collected 3-dimensional ultrasound volume sets of singleton pregnancies at 11–14 weeks and 18–24 weeks. Birth weights were collected from the medical records. After delivery, the ultrasound volume set were used to measure the placental volume (PV) and placental quotient (PQ=PV/gestational age), as well as the mean placental and chorionic diameters (MPD and MCD, respectively). Placental measures were analyzed as predictors of macrosomia (birth weight ≥4000 grams) and LGA (birth weight ≥90th percentile). Results The 578 pregnancies with first trimester volumes included 44 (7.6%) macrosomic and 43 (7.4%) LGA infants. 373 subjects also had second trimester volumes available. A higher PV and PQ were both significantly associated with macrosomia and LGA in both the first and second trimesters. Second trimester MPD was significantly associated with both outcomes as well, while second trimester MCD was only associated with LGA. The above associations remained significant after adjusting for maternal demographic variables such as race, ethnicity, age and diabetes. Adjusted models yielded moderate prediction of macrosomia and LGA (AUC: 0.71–0.77). Conclusions Sonographic measurement of the early placenta can identify pregnancies at greater risk of macrosomia and LGA. Macrosomia and LGA are already determined in part by early placental growth and development. PMID:25064071

  9. Fathers’ Sensitive Parenting and the Development of Early Executive Functioning

    PubMed Central

    Towe-Goodman, Nissa R.; Willoughby, Michael; Blair, Clancy; Gustafsson, Hanna C.; Mills-Koonce, W. Roger; Cox, Martha J.

    2014-01-01

    Using data from a diverse sample of 620 families residing in rural, predominately low-income communities, this study examined longitudinal links between fathers’ sensitive parenting in infancy and toddlerhood and children’s early executive functioning, as well as the contribution of maternal sensitive parenting. After accounting for the quality of concurrent and prior parental care, children’s early cognitive ability, and other child and family factors, fathers’ and mothers’ sensitive and supportive parenting during play at 24-months predicted children’s executive functioning at 3-years of age. In contrast, paternal parenting quality during play at 7-months did not make an independent contribution above that of maternal care, but the links between maternal sensitive and supportive parenting and executive functioning seemed to operate in similar ways during infancy and toddlerhood. These findings add to prior work on early experience and children’s executive functioning, suggesting that both fathers and mothers play a distinct and complementary role in the development of these self-regulatory skills. PMID:25347539

  10. Regional early development and eruption of permanent teeth: case report.

    PubMed

    Al Mullahi, A M; Bakathir, A; Al Jahdhami, S

    2017-02-01

    Early development and eruption of permanent teeth are rarely reported in scientific literature. Early eruption of permanent teeth has been reported to occur due to local factors such as trauma or dental abscesses in primary teeth, and in systemic conditions. Congenital diffuse infiltrating facial lipomatosis (CDIFL) is a rare condition that belongs to a group of lipomatosis tumours. In this disorder, the mature adipocytes invade adjacent soft and hard tissues in the facial region. Accelerated tooth eruption is one of the dental anomalies associated with CDIFL. A 3-year-old boy presented with a swelling of the lower lip localised early development and eruption of permanent teeth and dental caries involving many primary teeth. The planned treatment included biopsy of the swollen lower lip to confirm the diagnosis, surgical reduction and reconstruction of lip aesthetics. The management of the carious primary teeth included preventative and comprehensive dental care and extractions. These procedures were completed under general anaesthesia due to the child's young age and poor cooperation. The lip biopsy showed features of CDIFL such as the presence of infiltrating adipose tissue, prominent number of nerve bundles and thickened vessels. The high recurrence rate of CDIFL mandates long-term monitoring during the facial growth period of the child. Follow-up care by the paediatric dentist and maxillofacial surgeon has been required to manage all aspects of this congenital malformation. This rare disorder has many implications affecting child's facial aesthetics, psychological well being, developing occlusion and risk of dental caries. A multi-disciplinary approach is needed for management of this condition.

  11. Environmental estrogens alter early development in Xenopus laevis.

    PubMed

    Bevan, Cassandra L; Porter, Donna M; Prasad, Anita; Howard, Marthe J; Henderson, Leslie P

    2003-04-01

    A growing number of environmental toxicants found in pesticides, herbicides, and industrial solvents are believed to have deleterious effects on development by disrupting hormone-sensitive processes. We exposed Xenopus laevis embryos at early gastrula to the commonly encountered environmental estrogens nonylphenol, octylphenol, and methoxychlor, the antiandrogen, p,p-DDE, or the synthetic androgen, 17 alpha-methyltestosterone at concentrations ranging from 10 nM to 10 microM and examined them at tailbud stages (approximately 48 hr of treatment). Exposure to the three environmental estrogens, as well as to the natural estrogen 17 beta-estradiol, increased mortality, induced morphologic deformations, increased apoptosis, and altered the deposition and differentiation of neural crest-derived melanocytes in tailbud stage embryos. Although neural crest-derived melanocytes were markedly altered in embryos treated with estrogenic toxicants, expression of the early neural crest maker Xslug, a factor that regulates both the induction and subsequent migration of neural crest cells, was not affected, suggesting that the disruption induced by these compounds with respect to melanocyte development may occur at later stages of their differentiation. Co-incubation of embryos with the pure antiestrogen ICI 182,780 blocked the ability of nonylphenol to induce abnormalities in body shape and in melanocyte differentiation but did not block the effects of methoxychlor. Our data indicate not only that acute exposure to these environmental estrogens induces deleterious effects on early vertebrate development but also that different environmental estrogens may alter the fate of a specific cell type via different mechanisms. Finally, our data suggest that the differentiation of neural crest-derived melanocytes may be particularly sensitive to the disruptive actions of these ubiquitous chemical contaminants.

  12. Can taxanes provide benefit in patients with CNS tumors and in pediatric patients with tumors? An update on the preclinical development of cabazitaxel.

    PubMed

    Sémiond, D; Sidhu, S S; Bissery, M-C; Vrignaud, P

    2013-09-01

    While first-generation taxanes are valuable treatment options for many solid tumors, they are limited by an inability to cross the blood-brain barrier (BBB) and by limited efficacy in pediatric patients. Following promising preclinical data for the next-generation taxane cabazitaxel, including activity in tumor models fully sensitive, poorly sensitive or insensitive to docetaxel, and its ability to cross the BBB, further preclinical studies of cabazitaxel relevant to these two clinical indications were performed. Cabazitaxel brain distribution was assessed in mice, rats and dogs. Cabazitaxel antitumor activity was assessed in mice bearing intracranial human glioblastoma (SF295; U251) xenografts, and subcutaneous cell line-derived human pediatric sarcoma (rhabdomyosarcoma RH-30; Ewing's sarcoma TC-71 and SK-ES-1) or patient-derived pediatric sarcoma (osteosarcoma DM77 and DM113; Ewing's sarcoma DM101) xenografts. The activity of cabazitaxel-cisplatin combination was evaluated in BALB/C mice bearing the syngeneic murine colon adenocarcinoma, C51. Cabazitaxel penetrated rapidly in the brain, with a similar brain-blood radioactivity exposure relationship across different animal species. In intracranial human glioblastoma models, cabazitaxel demonstrated superior activity to docetaxel both at early (before BBB disruption) and at advanced stages, consistent with enhanced brain penetration. Compared with similar dose levels of docetaxel, cabazitaxel induced significantly greater tumor growth inhibition across six pediatric tumor models and more tumor regressions in five of the six models. Therapeutic synergism was observed between cisplatin and cabazitaxel, regardless of administration sequence. These preclinical data suggest that cabazitaxel could be an effective therapy in CNS and pediatric tumors, supporting ongoing clinical evaluation in these indications.

  13. Development of a GNSS-Enhanced Tsunami Early Warning System

    NASA Astrophysics Data System (ADS)

    Bawden, G. W.; Melbourne, T. I.; Bock, Y.; Song, Y. T.; Komjathy, A.

    2015-12-01

    The past decade has witnessed a terrible loss of life and economic disruption caused by large earthquakes and resultant tsunamis impacting coastal communities and infrastructure across the Indo-Pacific region. NASA has funded the early development of a prototype real-time Global Navigation Satellite System (RT-GNSS) based rapid earthquake and tsunami early warning (GNSS-TEW) system that may be used to enhance seismic tsunami early warning systems for large earthquakes. This prototype GNSS-TEW system geodetically estimates fault parameters (earthquake magnitude, location, strike, dip, and slip magnitude/direction on a gridded fault plane both along strike and at depth) and tsunami source parameters (seafloor displacement, tsunami energy scale, and 3D tsunami initials) within minutes after the mainshock based on dynamic numerical inversions/regressions of the real-time measured displacements within a spatially distributed real-time GNSS network(s) spanning the epicentral region. It is also possible to measure fluctuations in the ionosphere's total electron content (TEC) in the RT-GNSS data caused by the pressure wave from the tsunami. This TEC approach can detect if a tsunami has been triggered by an earthquake, track its waves as they propagate through the oceanic basins, and provide upwards of 45 minutes early warning. These combined real-time geodetic approaches will very quickly address a number of important questions in the immediate minutes following a major earthquake: How big was the earthquake and what are its fault parameters? Could the earthquake have produced a tsunami and was a tsunami generated?

  14. Predictive Value of Primary Tumor Site for Loco-regional Recurrence in Early Breast Cancer Patients with One to Three Positive Axillary Lymphadenophy.

    PubMed

    Niu, Shaoqing; Wen, Ge; Ren, Yufeng; Li, Yiyang; Feng, Lingling; Wang, Chengtao; Huang, Xiaobo; Wen, Bixiu; Zhang, Yujing

    2017-01-01

    Introduction: It remains controversial on high risks for early breast cancer patients with one to three axillary nodes after mastectomy who is predisposition to locoregional recurrence. The present study is to investigate the relationship between primary tumor site and loco-regional recurrence (LRR) and explore the predictive value of clinicopathological characteristics in LRR for early breast cancer patients with one to three positive axillary lymph nodes after mastectomy. Methods: We reviewed the clinical data of 656 consecutively diagnosed patients with pT 1-2 N 1 M 0 breast cancer who were treated in Sun Yat-sen University Cancer Center with radical operation without postoperative radiotherapy between March 1998 and December 2010. The primary tumor sites included outer quadrant in 455 patients (69.36%), inner quadrant in 156 patients (23.78%)and central quadrant in 45 patients (6.86%). LRR and LRR-free survival (LRFS) in combination with clinical and pathological features were analyzed to screen out patients with higher risk of LRR. Results: The median follow-up time was 64.9 months. The 5-, 10-year LRR for the cohort was 8.6% and 12.9%, respectively; the 5-, 10-year LRFS was 86.2% and 76.4%, respectively. Multivariate analyses showed that age of ≤35 years, inner quadrant tumor and non-luminal subtype were independent risk factors for LRR and LRFS. Patients with primary tumor in inner quadrant showed higher LRR and poorer LRFS when risk factors are ≥2 than those with tumors in other sites. Conclusions: Inner quadrant tumor was an independent predictor for LRR and LRFS in patients with early breast cancer and one to three positive axillary lymph nodes, which would be more accurate in combination with other prognostic indexes including patients' age, pathological T stage, Ki67 status, molecular subtypes.

  15. Gross motor development is delayed following early cardiac surgery.

    PubMed

    Long, Suzanne H; Harris, Susan R; Eldridge, Beverley J; Galea, Mary P

    2012-10-01

    To describe the gross motor development of infants who had undergone cardiac surgery in the neonatal or early infant period. Gross motor performance was assessed when infants were 4, 8, 12, and 16 months of age with the Alberta Infant Motor Scale. This scale is a discriminative gross motor outcome measure that may be used to assess infants from birth to independent walking. Infants were videotaped during the assessment and were later evaluated by a senior paediatric physiotherapist who was blinded to each infant's medical history, including previous clinical assessments. Demographic, diagnostic, surgical, critical care, and medical variables were considered with respect to gross motor outcomes. A total of 50 infants who underwent elective or emergency cardiac surgery at less than or up to 8 weeks of age, between July 2006 and January 2008, were recruited to this study and were assessed at 4 months of age. Approximately, 92%, 84%, and 94% of study participants returned for assessment at 8, 12, and 16 months of age, respectively. Study participants had delayed gross motor development across all study time points; 62% of study participants did not have typical gross motor development during the first year of life. Hospital length of stay was associated with gross motor outcome across infancy. Active gross motor surveillance of all infants undergoing early cardiac surgery is recommended. Further studies of larger congenital heart disease samples are required, as are longitudinal studies that determine the significance of these findings at school age and beyond.

  16. Early anther ablation triggers parthenocarpic fruit development in tomato.

    PubMed

    Medina, Mónica; Roque, Edelín; Pineda, Benito; Cañas, Luis; Rodriguez-Concepción, Manuel; Beltrán, José Pío; Gómez-Mena, Concepción

    2013-08-01

    Fruit set and fruit development in tomato is largely affected by changes in environmental conditions, therefore autonomous fruit set independent of fertilization is a highly desirable trait in tomato. Here, we report the production and characterization of male-sterile transgenic plants that produce parthenocarpic fruits in two tomato cultivars (Micro-Tom and Moneymaker). We generated male-sterility using the cytotoxic gene barnase targeted to the anthers with the PsEND1 anther-specific promoter. The ovaries of these plants grew in the absence of fertilization producing seedless, parthenocarpic fruits. Early anther ablation is essential to trigger the developing of the transgenic ovaries into fruits, in the absence of the signals usually generated during pollination and fertilization. Ovaries are fully functional and can be manually pollinated to obtain seeds. The transgenic plants obtained in the commercial cultivar Moneymaker show that the parthenocarpic development of the fruit does not have negative consequences in fruit quality. Throughout metabolomic analyses of the tomato fruits, we have identified two elite lines which showed increased levels of several health promoting metabolites and volatile compounds. Thus, early anther ablation can be considered a useful tool to promote fruit set and to obtain seedless and good quality fruits in tomato plants. These plants are also useful parental lines to be used in hybrid breeding approaches. © 2013 Society for Experimental Biology, Association of Applied Biologists and John Wiley & Sons Ltd.

  17. Early Numeracy Assessment: The Development of the Preschool Numeracy Scales

    PubMed Central

    Purpura, David J.; Lonigan, Christopher J.

    2015-01-01

    Research Findings The focus of this study was to construct and validate twelve brief early numeracy assessment tasks that measure the skills and concepts identified as key to early mathematics development by the National Council of Teachers of Mathematics (2006) and the National Mathematics Advisory Panel (2008)—as well as critical developmental precursors to later mathematics skill by the Common Core State Standards (CCSS; 2010). Participants were 393 preschool children ages 3 to 5 years old. Measure development and validation occurred through three analytic phases designed to ensure that the measures were brief, reliable, and valid. These measures included: one-to-one counting, cardinality, counting subsets, subitizing, number comparison, set comparison, number order, numeral identification, set-to-numerals, story problems, number combinations, and verbal counting. Practice or Policy Teachers have extensive demands on their time, yet, they are tasked with ensuring that all students’ academic needs are met. To identify individual instructional needs and measure progress, they need to be able to efficiently assess children’s numeracy skills. The measures developed in this study are not only reliable and valid, but also easy to use and can be utilized for measuring the effects of targeted instruction on individual numeracy skills. PMID:25709375

  18. APECS: A Network for Polar Early Career Scientist Professional Development

    NASA Astrophysics Data System (ADS)

    Enderlin, E. M.

    2014-12-01

    The Association of Polar Early Career Researchers (APECS) is an international and interdisciplinary organization for undergraduate and graduate students, postdoctoral researchers, early faculty members, educators and others with interests in the polar regions, alpine regions and the wider Cryosphere. APECS is a scientific, non-profit organization with free individual membership that aims to stimulate research collaborations and develop effective future leaders in polar research, education, and outreach. APECS grew out of the 4th International Polar Year (2007-08), which emphasized the need to stimulate and nurture the next generation of scientists in order to improve the understanding and communication of the polar regions and its global connections. The APECS organizational structure includes a Council and an elected Executive Committee that are supported by a Directorate. These positions are open to all individual members through a democratic process. The APECS Directorate is funded by the Norwegian Research Council, the University of Tromsø and the Norwegian Polar Institute and is hosted by the University of Tromsø. Early career scientists benefit from a range of activities hosted/organized by APECS. Every year, numerous activities are run with partner organizations and in conjunction with major polar conferences and meetings. In-person and online panels and workshops focus on a range of topics, from developing field skills to applying for a job after graduate school. Career development webinars are hosted each fall and topical research webinars are hosted throughout the year and archived online (http://www.apecs.is). The APECS website also contains abundant information on polar news, upcoming conferences and meetings, and job postings for early career scientists. To better respond to members' needs, APECS has national/regional committees that are linked to the international overarching organization. Many of these committees organize regional meetings or

  19. Tumor Control Probability Modeling for Stereotactic Body Radiation Therapy of Early-Stage Lung Cancer Using Multiple Bio-physical Models

    PubMed Central

    Liu, Feng; Tai, An; Lee, Percy; Biswas, Tithi; Ding, George X.; El Naqa, Isaam; Grimm, Jimm; Jackson, Andrew; Kong, Feng-Ming (Spring); LaCouture, Tamara; Loo, Billy; Miften, Moyed; Solberg, Timothy; Li, X Allen

    2017-01-01

    Purpose To analyze pooled clinical data using different radiobiological models and to understand the relationship between biologically effective dose (BED) and tumor control probability (TCP) for stereotactic body radiotherapy (SBRT) of early-stage non-small cell lung cancer (NSCLC). Method and Materials The clinical data of 1-, 2-, 3-, and 5-year actuarial or Kaplan-Meier TCP from 46 selected studies were collected for SBRT of NSCLC in the literature. The TCP data were separated for Stage T1 and T2 tumors if possible, otherwise collected for combined stages. BED was calculated at isocenters using six radiobiological models. For each model, the independent model parameters were determined from a fit to the TCP data using the least chi-square (χ2) method with either one set of parameters regardless of tumor stages or two sets for T1 and T2 tumors separately. Results The fits to the clinic data yield consistent results of large α/β ratios of about 20 Gy for all models investigated. The regrowth model that accounts for the tumor repopulation and heterogeneity leads to a better fit to the data, compared to other 5 models where the fits were indistinguishable between the models. The models based on the fitting parameters predict that the T2 tumors require about additional 1 Gy physical dose at isocenters per fraction (≤5 fractions) to achieve the optimal TCP when compared to the T1 tumors. Conclusion This systematic analysis of a large set of published clinical data using different radiobiological models shows that local TCP for SBRT of early-stage NSCLC has strong dependence on BED with large α/β ratios of about 20 Gy. The six models predict that a BED (calculated with α/β of 20) of 90 Gy is sufficient to achieve TCP ≥ 95%. Among the models considered, the regrowth model leads to a better fit to the clinical data. PMID:27871671

  20. A Multi-Institutional Study of Feasibility, Implementation, and Early Clinical Results With Noninvasive Breast Brachytherapy for Tumor Bed Boost

    SciT

    Hamid, Subarna, E-mail: shamid@tuftsmedicalcenter.org; Department of Radiation Oncology, Rhode Island Hospital, Alpert Medical School of Brown University, Providence, RI; Rocchio, Kathy

    2012-08-01

    Purpose: To evaluate the feasibility, implementation, and early results of noninvasive breast brachytherapy (NIBB) for tumor bed boost with whole breast radiation therapy (WBRT). Methods and Materials: NIBB is a commercially available (AccuBoost, Billerica, MA) mammography-based, brachytherapy system in which the treatment applicators are centered on the planning target volume (PTV) to direct {sup 192}Ir emissions along orthogonal axes. A privacy-encrypted online data registry collected information from 8 independent academic and community-based institutions. Data were from 146 consecutive women with early-stage breast cancer after lumpectomy and WBRT receiving boost with NIBB between July 2007 and March 2010. Toxicity and cosmesismore » were graded according to the Common Toxicity Criteria (v. 3.0) and the Harvard scale. Median follow-up was 6 months (1-39 months). Results: Grade 1-2 skin toxicity was observed in 64%, 48%, and 21% during the acute (1-3 weeks), intermediate (4-26 weeks), and late-intermediate (>26 weeks) periods. There was no Grade 4 toxicity. At 6 months, for the entire cohort, cosmesis was excellent/good in 62%/38%. The subset receiving NIBB before WBRT had cosmetic scores of 32% and 63%, whereas during WBRT, 58% and 37% were rated as excellent and good, respectively. Breast compression was scored as 'uncomfortable' in 12%, 29%, and 59% when NIBB was delivered before, during, or after WBRT. For each patient, the fraction-to-fraction variability in PTV was low. Skin flash was associated with a higher proportion of excellent cosmesis (58% vs. 42%) relative to having the applicator all within breast tissue. Conclusions: These data indicate that NIBB is feasible and can be consistently implemented in a broad array of practice settings. Preliminary evaluation suggests that NIBB is associated with acceptably mild normal tissue toxicity and favorable early cosmesis. The application of NIBB before WBRT may be associated with better patient tolerance at

  1. SOCS3 Deficiency in Myeloid Cells Promotes Tumor Development: Involvement of STAT3 Activation and Myeloid-Derived Suppressor Cells

    PubMed Central

    Yu, Hao; Liu, Yudong; McFarland, Braden C.; Deshane, Jessy S.; Hurst, Douglas R.; Ponnazhagan, Selvarangan; Benveniste, Etty N.; Qin, Hongwei

    2015-01-01

    Suppressor of cytokine signaling (SOCS) proteins are negative regulators of the JAK/STAT pathway, and generally function as tumor suppressors. The absence of SOCS3 in particular leads to heightened activation of the STAT3 transcription factor, which has a striking ability to promote tumor survival while suppressing antitumor immunity. We report for the first time that genetic deletion of SOCS3 specifically in myeloid cells significantly enhances tumor growth, which correlates with elevated levels of myeloid-derived suppressor cells (MDSC) in the tumor microenvironment, and diminished CD8+ T-cell infiltration in tumors. The importance of MDSCs in promoting tumor growth is documented by reduced tumor growth upon depletion of MDSCs. Furthermore, SOCS3-deficient bone-marrow-derived cells exhibit heightened STAT3 activation and preferentially differentiate into the Gr-1+CD11b+Ly6G+ MDSC phenotype. Importantly, we identify granulocyte colony-stimulating factor (G-CSF) as a critical factor secreted by the tumor microenvironment that promotes development of MDSCs via a STAT3-dependent pathway. Abrogation of tumor-derived G-CSF reduces the proliferation and accumulation of Gr-1+CD11b+ MDSCs and inhibits tumor growth. These findings highlight the critical function of SOCS3 as a negative regulator of MDSC development and function, via inhibition of STAT3 activation. PMID:25649351

  2. The mechanisms how heparin affects the tumor cell induced VEGF and chemokine release from platelets to attenuate the early metastatic niche formation

    PubMed Central

    Ponert, Jan Moritz; Schwarz, Svenja; Haschemi, Reza; Müller, Jens; Pötzsch, Bernd; Bendas, Gerd

    2018-01-01

    Metastasis is responsible for the majority of cancer associated fatalities. Tumor cells leaving the primary tumor and entering the blood flow immediately interact with platelets. Activated platelets contribute in different ways to cancer cell survival and proliferation, e.g. in formation of the early metastatic niche by release of different growth factors and chemokines. Here we show that a direct interaction between platelets and MV3 melanoma or MCF7 breast cancer cells induces platelet activation and a VEGF release in citrated plasma that cannot be further elevated by the coagulation cascade and generated thrombin. In contrast, the release of platelet-derived chemokines CXCL5 and CXCL7 depends on both, a thrombin-mediated platelet activation and a direct interaction between tumor cells and platelets. Preincubation of platelets with therapeutic concentrations of unfractionated heparin reduces the tumor cell initiated VEGF release from platelets. In contrast, tumor cell induced CXCL5 and CXCL7 release from platelets was not impacted by heparin pretreatment in citrated plasma. In defibrinated, recalcified plasma, on the contrary, heparin is able to reduce CXCL5 and CXCL7 release from platelets by thrombin inhibition. Our data indicate that different chemokines and growth factors in diverse platelet granules are released in tightly regulated processes by various trigger mechanisms. We show for the first time that heparin is able to reduce the mediator release induced by different tumor cells both in a contact and coagulation dependent manner. PMID:29346400

  3. Origin and Role of a Subset of Tumor-Associated Neutrophils with Antigen-Presenting Cell Features in Early-Stage Human Lung Cancer.

    PubMed

    Singhal, Sunil; Bhojnagarwala, Pratik S; O'Brien, Shaun; Moon, Edmund K; Garfall, Alfred L; Rao, Abhishek S; Quatromoni, Jon G; Stephen, Tom Li; Litzky, Leslie; Deshpande, Charuhas; Feldman, Michael D; Hancock, Wayne W; Conejo-Garcia, Jose R; Albelda, Steven M; Eruslanov, Evgeniy B

    2016-07-11

    Based on studies in mouse tumor models, granulocytes appear to play a tumor-promoting role. However, there are limited data about the phenotype and function of tumor-associated neutrophils (TANs) in humans. Here, we identify a subset of TANs that exhibited characteristics of both neutrophils and antigen-presenting cells (APCs) in early-stage human lung cancer. These APC-like "hybrid neutrophils," which originate from CD11b(+)CD15(hi)CD10(-)CD16(low) immature progenitors, are able to cross-present antigens, as well as trigger and augment anti-tumor T cell responses. Interferon-γ and granulocyte-macrophage colony-stimulating factor are requisite factors in the tumor that, working through the Ikaros transcription factor, synergistically exert their APC-promoting effects on the progenitors. Overall, these data demonstrate the existence of a specialized TAN subset with anti-tumor capabilities in human cancer. Copyright © 2016 Elsevier Inc. All rights reserved.

  4. Direct Extraction of Tumor Response Based on Ensemble Empirical Mode Decomposition for Image Reconstruction of Early Breast Cancer Detection by UWB.

    PubMed

    Li, Qinwei; Xiao, Xia; Wang, Liang; Song, Hang; Kono, Hayato; Liu, Peifang; Lu, Hong; Kikkawa, Takamaro

    2015-10-01

    A direct extraction method of tumor response based on ensemble empirical mode decomposition (EEMD) is proposed for early breast cancer detection by ultra-wide band (UWB) microwave imaging. With this approach, the image reconstruction for the tumor detection can be realized with only extracted signals from as-detected waveforms. The calibration process executed in the previous research for obtaining reference waveforms which stand for signals detected from the tumor-free model is not required. The correctness of the method is testified by successfully detecting a 4 mm tumor located inside the glandular region in one breast model and by the model located at the interface between the gland and the fat, respectively. The reliability of the method is checked by distinguishing a tumor buried in the glandular tissue whose dielectric constant is 35. The feasibility of the method is confirmed by showing the correct tumor information in both simulation results and experimental results for the realistic 3-D printed breast phantom.

  5. The Results of Surgical Treatment of Cushing Tumors in the Republic of Uzbekistan: Establishing Transsphenoidal Surgery in A Developing Nation.

    PubMed

    Powell, Michael P; Narimova, Gulshekra J; Halimova, Zamira J

    2017-01-01

    Transsphenoidal surgery (TSS) was introduced into the Republic of Uzbekistan in 2005 and has been developing since then. The principal center for the management of all pituitary disease is a single site for a nation with a population of approximately 30 million. Results in surgery for Cushing disease are a marker of surgical technical skill in TSS. All previously published series come from the developed world, where sophisticated investigations and management are available. Many of these investigations are not available in Uzbekistan. This mixed series of 154 patients from 2000 to 2013 presents the data from Uzbekistan. The management of Cushing disease before the introduction of TSS was with unilateral adrenalectomy, a procedure virtually unknown in the West. It reduces cortisol burden but is, in the long-term, only a temporary measure because it allows the tumor to continue to grow. The results of this procedure are presented and show that in the short-term, surprisingly reasonable remission is obtained. These results are contrasted with the experience with TSS, for which the impact of the input from an experienced team including an endocrinologist and neurosurgeon from the United Kingdom allowed a transformation in management and enabled outcomes to match what can be expected in the West. TSS for Cushing's Disease achieved an early remission of 68.7% (early morning cortisol of <50 nmol/L), although 4 patients relapsed. Copyright © 2016 Elsevier Inc. All rights reserved.

  6. Medical students' professional identity development in an early nursing attachment.

    PubMed

    Helmich, Esther; Derksen, Els; Prevoo, Mathieu; Laan, Roland; Bolhuis, Sanneke; Koopmans, Raymond

    2010-07-01

    The importance of early clinical experience for medical training is well documented. However, to our knowledge there are no studies that assess the influence of very early nursing attachments on the professional development and identity construction of medical students. Working as an assistant nurse while training to be a doctor may offer valuable learning experiences, but may also present the student with difficulties with respect to identity and identification issues. The aim of the present study was to describe first-year medical students' perceptions of nurses, doctors and their own future roles as doctors before and after a nursing attachment. A questionnaire containing open questions concerning students' perceptions of nurses, doctors and their own future roles as doctors was administered to all Year 1 medical students (n=347) before and directly after a 4-week nursing attachment in hospitals and nursing homes. We carried out two confirmatory focus group interviews. We analysed the data using qualitative and quantitative content analyses. The questionnaire was completed by 316 students (response rate 91%). Before starting the attachment students regarded nurses as empathic, communicative and responsible. After the attachment students reported nurses had more competencies and responsibilities than they had expected. Students' views of doctors were ambivalent. Before and after the attachment, doctors were seen as interested and reliable, but also as arrogant, detached and insensible. However, students maintained positive views of their own future roles as doctors. Students' perceptions were influenced by age, gender and place of attachment. An early nursing attachment engenders more respect for the nursing profession. The ambivalent view of doctors needs to be explored further in relation to students' professional development. It would seem relevant to attune supervision to the age and gender differences revealed in this study.

  7. Early Childhood Development and Iranian Parents' Knowledge: A Qualitative Study.

    PubMed

    Habibi, Elham; Sajedi, Firouzeh; Afzali, Hosein Malek; Hatamizadeh, Nikta; Shahshahanipour, Soheila; Glascoe, Frances Page

    2017-01-01

    Early childhood is the most important step throughout the lifespan and it is a critical period continuing to the end of 8-year-old. Mothers' knowledge is one of the important aspects of child development. The goals of this study were to determine the situation of knowledge in Iranian parents about the concept and the importance of early childhood development (ECD) and determining the sources of parental knowledge about ECD from the perspective of parents and grandparents. This qualitative study was conducted based on the directional content analysis in 2016. The purposive sampling method is utilized to select 24 participants among parents and grandparents in Tehran. The inclusion criteria consisted of speaking in Persian and having a child or grandchild <3-year-old. Data were collected through four focus group discussions and four individual interviews. Iranian parental knowledge about integrative ECD is not enough, their knowledge about motor development and speech and language are relatively better, about cognitive development is little and socialemotional is very little. They said parents and other caregivers influence the process of children's development. Parents' knowledge resources about ECD included human resources, physical resources, virtual space, and the media. According to the majority of participants, "pediatricians are the most reliable source of parents' knowledge about ECD" even though the main focus of pediatricians is on treating diseases, physical health, and growth of children. According to the results, the knowledge of Iranian parent is not enough about ECD; therefore, actions must be taken to increase their knowledge in these domains. Parents look for reliable and valid sources to enhance their knowledge and they rely the most on pediatricians in this regard. Therefore, more studies on assessing parents' knowledge in community and the practical methods for knowledge promotion in this field is recommended.

  8. Early-stage aeolian protodune development and migration

    NASA Astrophysics Data System (ADS)

    Nield, J. M.; Baddock, M. C.; Wiggs, G.

    2017-12-01

    Early-stage bedforms, or protodunes, can be observed to form on sandy beaches, desert gravels or superimposed on the surfaces of larger dunes and can develop topography of 0.1 m or more over several hours. These protodunes are the precursors to embryo and eventually mature dunes, and so it is important to understand how feedbacks between flow, transport and form contribute to this development sequence. Whilst theory and conceptual models have offered some explanation for protodune existence and development, we know surprisingly little about how these bedforms initiate and migrate because it is difficult to measure small changes in form (millimetres; seconds) on highly active surfaces of limited topographic expression. Here, we employ terrestrial laser scanning (TLS) to measure morphological change at the high frequency and spatial resolution (sub-millimetre) required to gain new insights into protodune behaviour. Along with TLS derived saltation and surface moisture, additional sediment flux and windspeed measurements help to elucidate how the protodune topography interacts with airflow and sand transport. We focus on a number of coastal bedforms in various development stages including a 0.06 m high protodune which grew vertically by 0.005 m in two hours with the switch from erosion to deposition identified to occur at a point 0.07 m upwind of the crest. This growth was associated with a reduction in time-averaged sediment flux of 18% over the crestal region. We also observed a decline in lower stoss slope steepness (by 3°) and a steepening of the lee slope, indicating a reshaping of initial protodune form towards the morphology of a more mature dune. Our findings highlight the crucial role of form-flow feedbacks, even on very small bedforms, in driving early-stage bedform growth and development, and show how the use of high resolution TLS to measure both surface topography and grains moving above the surface, can offer new insights into a long standing deficiency

  9. Therapeutics targeting tumor immune escape: towards the development of new generation anticancer vaccines.

    PubMed

    Mocellin, Simone; Nitti, Donato

    2008-05-01

    Despite the evidence that immune effectors can play a significant role in controlling tumor growth under natural conditions or in response to therapeutic manipulation, it is clear that malignant cells evade immune surveillance in most cases. Considering that anticancer vaccination has reached a plateau of results and currently no vaccination regimen is indicated as a standard anticancer therapy, the dissection of the molecular events underlying tumor immune escape is the necessary condition to make anticancer vaccines a therapeutic weapon effective enough to be implemented in the routine clinical setting. Recent years have witnessed significant advances in our understanding of the molecular mechanisms underlying tumor immune escape. These mechanistic insights are fostering the development of rationally designed therapeutics aimed at reverting the immunosuppressive circuits that undermine an effective antitumor immune response. In this review, the best characterized mechanisms that allow cancer cells to evade immune surveillance are overviewed and the most debated controversies constellating this complex field are highlighted. In addition, the latest therapeutic strategies devised to overcome tumor immune escape are described, with special regard to those entering clinical phase investigation. Copyright (c) 2007 Wiley-Periodicals, Inc.

  10. PD-1 suppresses development of humoral responses that protect against Tn-bearing tumors

    PubMed Central

    Haro, Marcela A.; Littrell, Chad A.; Yin, Zhaojun; Huang, Xuefei; Haas, Karen M.

    2017-01-01

    Tn is a carbohydrate antigen uniquely exposed on tumor mucins and thus, an ideal target for immunotherapy. However, it has been difficult to elicit protective antibody responses against Tn antigen and other tumor associated carbohydrate antigens. Our study demonstrates this can be attributed to PD-1 immuno-inhibition. Our data show a major role for PD-1 in suppressing mucin- and Tn-specific B-cell activation, expansion, and antibody production important for protection against Tn-bearing tumor cells. These Tn/mucin-specific B cells belong to the innate-like B-1b cell subset typically responsible for T cell–independent antibody responses. Interestingly, PD-1–mediated regulation is B cell–intrinsic and CD4+ cells play a key role in supporting Tn/mucin-specific B cell antibody production in the context of PD-1 deficiency. Mucin-reactive antibodies produced in the absence of PD-1 inhibition largely belong to the IgM subclass and elicit potent antitumor effects via a complement-dependent mechanism. The identification of this role for PD-1 in regulating B cell–dependent antitumor immunity to Tn antigen highlights an opportunity to develop new therapeutic strategies targeting tumor associated carbohydrate antigens. PMID:27856425

  11. Acceleration of leukocytes' epigenetic age as an early tumor and sex-specific marker of breast and colorectal cancer.

    PubMed

    Durso, Danielle Fernandes; Bacalini, Maria Giulia; Sala, Claudia; Pirazzini, Chiara; Marasco, Elena; Bonafé, Massimiliano; do Valle, Ítalo Faria; Gentilini, Davide; Castellani, Gastone; Faria, Ana Maria Caetano; Franceschi, Claudio; Garagnani, Paolo; Nardini, Christine

    2017-04-04

    Changes in blood epigenetic age have been associated with several pathological conditions and have recently been described to anticipate cancer development. In this work, we analyze a publicly available leukocytes methylation dataset to evaluate the relation between DNA methylation age and the prospective development of specific types of cancer. We calculated DNA methylation age acceleration using five state-of-the-art estimators (three multi-site: Horvath, Hannum, Weidner; and two CpG specific: ELOV2 and FHL2) in a cohort including 845 subjects from the EPIC-Italy project and we compared 424 samples that remained cancer-free over the approximately ten years of follow-up with 235 and 166 subjects who developed breast and colorectal cancer, respectively. We show that the epigenetic age estimated from blood DNA methylation data is statistically significantly associated to future breast and male colorectal cancer development. These results are corroborated by survival analysis that shows significant association between age acceleration and cancer incidence suggesting that the chance of developing age-related diseases may be predicted by circulating epigenetic markers, with a dependence upon tumor type, sex and age estimator. These are encouraging results towards the non-invasive and perspective usage of epigenetic biomarkers.

  12. Determinants of early child development in rural Tanzania.

    PubMed

    Ribe, Ingeborg G; Svensen, Erling; Lyngmo, Britt A; Mduma, Estomih; Hinderaker, Sven G

    2018-01-01

    It has been estimated that more than 200 million children under the age of five do not reach their full potential in cognitive development. Much of what we know about brain development is based on research from high-income countries. There is limited evidence on the determinants of early child development in low-income countries, especially rural sub-Saharan Africa. The present study aimed to identify the determinants of cognitive development in children living in villages surrounding Haydom, a rural area in north-central Tanzania. This cohort study is part of the MAL-ED (The Interactions of Malnutrition & Enteric Infections: Consequences for Child Health and Development) multi-country consortium studying risk factors for ill health and poor development in children. Descriptive analysis and linear regression analyses were performed. Associations between nutritional status, socio-economic status, and home environment at 6 months of age and cognitive outcomes at 15 months of age were studied. The third edition of the Bayley Scales for Infant and Toddler Development was used to assess cognitive, language and motor development. There were 262 children enrolled into the study, and this present analysis included the 137 children with data for 15-month Bayley scores. Univariate regression analysis, weight-for-age and weight-for-length z-scores at 6 months were significantly associated with 15-month Bayley gross motor score, but not with other 15-month Bayley scores. Length-for-age z-scores at 6 months were not significantly associated with 15-month Bayley scores. The socio-economic status, measured by a set of assets and monthly income was significantly associated with 15-month Bayley cognitive score, but not with language, motor, nor total 15-month Bayley scores. Other socio-economic variables were not significantly associated with 15-month Bayley scores. No significant associations were found between the home environment and 15-month Bayley scores. In multivariate

  13. Pattern of Tumor Shrinkage during Neoadjuvant Chemotherapy Is Associated with Prognosis in Low-Grade Luminal Early Breast Cancer.

    PubMed

    Fukada, Ippei; Araki, Kazuhiro; Kobayashi, Kokoro; Shibayama, Tomoko; Takahashi, Shunji; Gomi, Naoya; Kokubu, Yumi; Oikado, Katsunori; Horii, Rie; Akiyama, Futoshi; Iwase, Takuji; Ohno, Shinji; Hatake, Kiyohiko; Sata, Naohiro; Ito, Yoshinori

    2018-01-01

    Purpose To evaluate the association between tumor shrinkage patterns shown with magnetic resonance (MR) imaging during neoadjuvant chemotherapy (NAC) and prognosis in patients with low-grade luminal breast cancer. Materials and Methods This retrospective study was approved by the institutional review board and informed consent was obtained from all subjects. The low-grade luminal breast cancer was defined as hormone receptor-positive and human epidermal growth factor receptor 2-negative with nuclear grades 1 or 2. The patterns of tumor shrinkage as revealed at MR imaging were categorized into two types: concentric shrinkage (CS) and non-CS. Among 854 patients who had received NAC in a single institution from January 2000 to December 2009, 183 patients with low-grade luminal breast cancer were retrospectively evaluated for the development set. Another data set from 292 patients who had received NAC in the same institution between January 2010 and December 2012 was used for the validation set. Among these 292 patients, 121 patients with low-grade luminal breast cancer were retrospectively evaluated. Results In the development set, the median observation period was 67.9 months. Recurrence was observed in 31 patients, and 16 deaths were related to breast cancer. There were statistically significant differences in both the disease-free survival (DFS) and overall survival (OS) rates between patterns of tumor shrinkage (P < .001 and P < .001, respectively). Multivariate analysis demonstrated that the CS pattern had the only significant independent association with DFS (P = .001) and OS (P = .009) rate. In the validation set, the median follow-up period was 56.9 months. Recurrence was observed in 20 patients (16.5%) and eight (6.6%) deaths were related to breast cancer. DFS rate was significantly longer in patients with the CS pattern (72.8 months; 95% confidence interval [CI]: 69.9, 75.6 months) than in those with the non-CS pattern (56.0 months; 95% CI: 49.1, 62.9 months

  14. Downregulation of ribosome biogenesis during early forebrain development

    PubMed Central

    Chau, Kevin F; Shannon, Morgan L; Fame, Ryann M; Fonseca, Erin; Mullan, Hillary; Johnson, Matthew B; Sendamarai, Anoop K; Springel, Mark W; Laurent, Benoit

    2018-01-01

    Forebrain precursor cells are dynamic during early brain development, yet the underlying molecular changes remain elusive. We observed major differences in transcriptional signatures of precursor cells from mouse forebrain at embryonic days E8.5 vs. E10.5 (before vs. after neural tube closure). Genes encoding protein biosynthetic machinery were strongly downregulated at E10.5. This was matched by decreases in ribosome biogenesis and protein synthesis, together with age-related changes in proteomic content of the adjacent fluids. Notably, c-MYC expression and mTOR pathway signaling were also decreased at E10.5, providing potential drivers for the effects on ribosome biogenesis and protein synthesis. Interference with c-MYC at E8.5 prematurely decreased ribosome biogenesis, while persistent c-MYC expression in cortical progenitors increased transcription of protein biosynthetic machinery and enhanced ribosome biogenesis, as well as enhanced progenitor proliferation leading to subsequent macrocephaly. These findings indicate large, coordinated changes in molecular machinery of forebrain precursors during early brain development. PMID:29745900

  15. Early Development of the Gut Microbiota and Immune Health

    PubMed Central

    Francino, M. Pilar

    2014-01-01

    In recent years, the increase in human microbiome research brought about by the rapidly evolving “omic” technologies has established that the balance among the microbial groups present in the human gut, and their multipronged interactions with the host, are crucial for health. On the other hand, epidemiological and experimental support has also grown for the ‘early programming hypothesis’, according to which factors that act in utero and early in life program the risks for adverse health outcomes later on. The microbiota of the gut develops during infancy, in close interaction with immune development, and with extensive variability across individuals. It follows that the specific process of gut colonization and the microbe-host interactions established in an individual during this period have the potential to represent main determinants of life-long propensity to immune disease. Although much remains to be learnt on the progression of events by which the gut microbiota becomes established and initiates its intimate relationships with the host, and on the long-term repercussions of this process, recent works have advanced significatively in this direction. PMID:25438024

  16. Elevated aminopeptidase N affects sperm motility and early embryo development

    PubMed Central

    Ryu, Do-Yeal; Kwon, Woo-Sung

    2017-01-01

    Aminopeptidase N (APN) is a naturally occurring ectopeptidase present in mammalian semen. Previous studies have demonstrated that APN adversely affects male fertility through the alteration of sperm motility. This enzyme constitutes 0.5 to 1% of the seminal plasma proteins, which can be transferred from the prostasomes to sperms by a fusion process. In the present study, we investigated the molecular mechanism of action of APN and its role in regulating sperm functions and male fertility. In this in vitro study, epididymal mouse spermatozoa were incubated in a capacitating media (pH 7) containing 20 ng/mL of recombinant mouse APN for 90 min. Our results demonstrated that the supplementation of recombinant APN in sperm culture medium significantly increased APN activity, and subsequently altered motility, hyperactivated motility, rapid and medium swimming speeds, viability, and the acrosome reaction of mouse spermatozoa. These effects were potentially caused by increased toxicity in the spermatozoa. Further, altered APN activity in sperm culture medium affected early embryonic development. Interestingly, the effect of elevated APN activity in sperm culture medium was independent of protein tyrosine phosphorylation and protein kinase A activity. On the basis of these results, we concluded that APN plays a significant role in the regulation of several sperm functions and early embryonic development. In addition, increased APN activity could potentially lead to several adverse consequences related to male fertility. PMID:28859152

  17. Dihydroartemisinin promotes angiogenesis during the early embryonic development of zebrafish

    PubMed Central

    Ba, Qian; Duan, Juan; Tian, Jia-qiang; Wang, Zi-liang; Chen, Tao; Li, Xiao-guang; Chen, Pei-zhan; Wu, Song-jie; Xiang, Li; Li, Jing-quan; Chu, Rui-ai; Wang, Hui

    2013-01-01

    Aim: To investigate the embryotoxicity of dihydroartemisinin (DHA), the main active metabolite of artemisinin, in zebrafish, and explore the corresponding mechanisms. Methods: The embryos of wild type and TG (flk1:GFP) transgenic zebrafish were exposed to DHA. Developmental phenotypes of the embryos were observed. Development of blood vessels was directly observed in living embryos of TG (flk1:GFP) transgenic zebrafish under fluorescence microscope. The expression of angiogenesis marker genes vegfa, flk1, and flt1 in the embryos was detected using real-time PCR and RNA in situ hybridization assays. Results: Exposure to DHA (1–10 mg/L) dose-dependently caused abnormal zebrafish embryonic phenotypes in the early developmental stage. Furthermore, exposure to DHA (10 mg/L) resulted in more pronounced embryonic angiogenesis in TG (flk1:GFP) zebrafish line. Exposure to DHA (10 mg/L) significantly increased the mRNA expression of vegfa, flk1, and flt1 in the embryos. Knockdown of the flk1 protein partially blocked the effects of DHA on embryogenesis. Conclusion: DHA causes abnormal embryonic phenotypes and promotes angiogenesis in zebrafish early embryonic development, demonstrating the potential embryotoxicity of DHA. PMID:23708556

  18. Construction of a pathological risk model of occult lymph node metastases for prognostication by semi-automated image analysis of tumor budding in early-stage oral squamous cell carcinoma

    PubMed Central

    Pedersen, Nicklas Juel; Jensen, David Hebbelstrup; Lelkaitis, Giedrius; Kiss, Katalin; Charabi, Birgitte; Specht, Lena; von Buchwald, Christian

    2017-01-01

    It is challenging to identify at diagnosis those patients with early oral squamous cell carcinoma (OSCC), who have a poor prognosis and those that have a high risk of harboring occult lymph node metastases. The aim of this study was to develop a standardized and objective digital scoring method to evaluate the predictive value of tumor budding. We developed a semi-automated image-analysis algorithm, Digital Tumor Bud Count (DTBC), to evaluate tumor budding. The algorithm was tested in 222 consecutive patients with early-stage OSCC and major endpoints were overall (OS) and progression free survival (PFS). We subsequently constructed and cross-validated a binary logistic regression model and evaluated its clinical utility by decision curve analysis. A high DTBC was an independent predictor of both poor OS and PFS in a multivariate Cox regression model. The logistic regression model was able to identify patients with occult lymph node metastases with an area under the curve (AUC) of 0.83 (95% CI: 0.78–0.89, P <0.001) and a 10-fold cross-validated AUC of 0.79. Compared to other known histopathological risk factors, the DTBC had a higher diagnostic accuracy. The proposed, novel risk model could be used as a guide to identify patients who would benefit from an up-front neck dissection. PMID:28212555

  19. Five common tumor biomarkers and CEA for diagnosing early gastric cancer: A protocol for a network meta-analysis of diagnostic test accuracy.

    PubMed

    Shen, Minghui; Wang, Hui; Wei, Kongyuan; Zhang, Jianling; You, Chongge

    2018-05-01

    Although surgical resection is the recommended treatment for the patients with gastric cancer, lots of patients show advanced or metastatic gastric cancer at the time of diagnosis. Detection of gastric cancer at early stages is a huge challenge because of lack of appropriate detection tests. Unfortunately, existing clinical guidelines focusing on early diagnosis of gastric cancer do not provide consistent and prudent evidence. Serum carcinoembryonic antigen was considered as a complementary test, although it is not good enough to diagnose early gastric cancer. There are no other tumor markers recommended for diagnosing early gastric cancer. This study aims to evaluate and compare the diagnostic accuracy of 5 common tumor biomarkers (CA19-9, CA125, PG, IncRNA, and DNA methylation) and CEA and their combinations for diagnosing gastric cancer through network meta-analysis method, and to rank these tests using a superiority index. PubMed, EMBASE.com, and the Cochrane Central Register of Controlled Trials (CENTRAL) will be searched from their inception to March 2018. We will include diagnostic tests which assessed the accuracy of the above-mentioned tumor biomarkers and CEA for diagnosing gastric cancer. The risk of bias for each study will be independently assessed as low, moderate, or high using criteria adapted from Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2). Network meta-analysis will be performed using STATA 12.0 and R 3.4.1 software. The competing diagnostic tests will be ranked by a superiority index. This study is ongoing and will be submitted to a peer-reviewed journal for publication. This study will provide systematically suggestions to select different tumor biomarkers for detecting the early gastric cancer.

  20. Cysteine cathepsins: their role in tumor progression and recent trends in the development of imaging probes

    PubMed Central

    Löser, Reik; Pietzsch, Jens

    2015-01-01

    Papain-like cysteine proteases bear an enormous potential as drug discovery targets for both infectious and systemic human diseases. The considerable progress in this field over the last two decades has also raised interest in the visualization of these enzymes in their native context, especially with regard to tumor imaging. After a short introduction to structure and general functions of human cysteine cathepsins, we highlight their importance for drug discovery and development and provide a critical update on the current state of knowledge toward their involvement in tumor progression, with a special emphasis on their role in therapy response. In accordance with a radiopharmaceutical point of view, the main focus of this review article will be the discussion of recently developed fluorescence and radiotracer-based imaging agents together with related molecular probes. PMID:26157794

  1. Early lexical development in Spanish-speaking infants and toddlers.

    PubMed

    Jackson-Maldonado, D; Thal, D; Marchman, V; Bates, E; Gutierrez-Clellen, V

    1993-10-01

    This paper describes the early lexical development of a group of 328 normal Spanish-speaking children aged 0;8 to 2;7. First the development and structure of a new parent report instrument, Inventario del Desarollo de Habilidades Communicativas is described. Then five studies carried out with the instrument are presented. In the first study vocabulary development of Spanish-speaking infants and toddlers is compared to that of English-speaking infants and toddlers. The English data were gathered using a comparable parental report, the MacArthur Communicative Development Inventories. In the second study the general characteristics of Spanish language acquisition, and the effects of various demographic factors on that process, are examined. Study 3 examines the differential effects of three methods of collecting the data (mail-in, personal interview, and clinic waiting room administration). Studies 4 and 5 document the reliability and validity of the instrument. Results show that the trajectories of development are very similar for Spanish- and English-speaking children in this age range, that children from varying social groups develop similarly, and that mail-in and personal interview administration techniques produce comparable results. Inventories administered in a medical clinic waiting room, on the other hand, produced lower estimates of toddler vocabulary than the other two models.

  2. Altered Gravity and Early Heart Development in Culture

    NASA Technical Reports Server (NTRS)

    Wiens, Darrell J.; Lwigale, P.; Denning, J.

    1996-01-01

    The macromolecules comprising the cytoskeleton and extracellular matrix of cells may be sensitive to gravitation. Since early development of organs depends on dynamic interactions across cell surfaces, altered gravity may disturb development. We investigated this possibility for heart development. Previous studies showed that the extracellular matrix glycoprotein fibronectin (Fn) is necessary for normal heart development. We cultured precardiac tissue explants in a high aspect ratio bioreactor vessel (HARV) to simulate microgravity. We observed tissue morphology, contraction, and Fn distribution by immunolocalization in HARV rotated and control (lxg) explants, cultured 18 hr. We also measured Fn amount by immunoassay. Explants in HARV were rotated at 6 rpm to achieve continuous freefall. Thirty-five of 37 control, but only 1 of 37 matched rotated explants exhibited contractions. Tissue architecture was identical. Immunolocalization of Fn showed remarkable differences which may be related to the development of contractions. The Fn staining in the HARV explants was less intense in all areas. Areas of linear staining along epithelia were present but shorter, and there was less intercellular staining in both mesenchymal tissue and myocardium. Initial immunoassay results of 5 matched pairs of explants showed a 22% reduction in total tissue Fn in the HARV rotated samples. Our results indicate that altered gravity in the HARV reduced the amount and distribution of Fn, as assessed by two independent criteria. This was correlated with a reduction in the development of contractile activity.

  3. Behavioral development in embryonic and early juvenile cuttlefish (Sepia officinalis).

    PubMed

    O'Brien, Caitlin E; Mezrai, Nawel; Darmaillacq, Anne-Sophie; Dickel, Ludovic

    2017-03-01

    Though a mollusc, the cuttlefish Sepia officinalis possesses a sophisticated brain, advanced sensory systems, and a large behavioral repertoire. Cuttlefish provide a unique perspective on animal behavior due to their phylogenic distance from more traditional (vertebrate) models. S. officinalis is well-suited to addressing questions of behavioral ontogeny. As embryos, they can perceive and learn from their environment and experience no direct parental care. A marked progression in learning and behavior is observed during late embryonic and early juvenile development. This improvement is concomitant with expansion and maturation of the vertical lobe, the cephalopod analog of the mammalian hippocampus. This review synthesizes existing knowledge regarding embryonic and juvenile development in this species in an effort to better understand cuttlefish behavior and animal behavior in general. It will serve as a guide to future researchers and encourage greater awareness of the utility of this species to behavioral science. © 2016 Wiley Periodicals, Inc.

  4. Transposable elements as genetic regulatory substrates in early development.

    PubMed

    Gifford, Wesley D; Pfaff, Samuel L; Macfarlan, Todd S

    2013-05-01

    The abundance and ancient origins of transposable elements (TEs) in eukaryotic genomes has spawned research into the potential symbiotic relationship between these elements and their hosts. In this review, we introduce the diversity of TEs, discuss how distinct classes are uniquely regulated in development, and describe how they appear to have been coopted for the purposes of gene regulation and the orchestration of a number of processes during early embryonic development. Although young, active TEs play an important role in somatic tissues and evolution, we focus mostly on the contributions of the older, fixed elements in mammalian genomes. We also discuss major challenges inherent in the study of TEs and contemplate future experimental approaches to further investigate how they coordinate developmental processes. Published by Elsevier Ltd.

  5. Transposable elements as genetic regulatory substrates in early development

    PubMed Central

    Gifford, Wesley D.; Pfaff, Samuel L.; Macfarlan, Todd S.

    2014-01-01

    The abundance and ancient origins of transposable elements (TEs) in eukaryotic genomes has spawned research into the potential symbiotic relationship between these elements and their hosts. In this review, we introduce the diversity of TEs, discuss how distinct classes are uniquely regulated in development, and describe how they appear to have been coopted for the purposes of gene regulation and the orchestration of a number of processes during early embryonic development. Although young, active TEs play an important role in somatic tissues and evolution, we focus mostly on the contributions of the older, fixed elements in mammalian genomes. We also discuss major challenges inherent in the study of TEs and contemplate future experimental approaches to further investigate how they coordinate developmental processes. PMID:23411159

  6. Modeling and managing risk early in software development

    NASA Technical Reports Server (NTRS)

    Briand, Lionel C.; Thomas, William M.; Hetmanski, Christopher J.

    1993-01-01

    In order to improve the quality of the software development process, we need to be able to build empirical multivariate models based on data collectable early in the software process. These models need to be both useful for prediction and easy to interpret, so that remedial actions may be taken in order to control and optimize the development process. We present an automated modeling technique which can be used as an alternative to regression techniques. We show how it can be used to facilitate the identification and aid the interpretation of the significant trends which characterize 'high risk' components in several Ada systems. Finally, we evaluate the effectiveness of our technique based on a comparison with logistic regression based models.

  7. CD34 Expression by Hair Follicle Stem Cells Is Required for Skin Tumor Development in Mice

    PubMed Central

    Trempus, Carol S.; Morris, Rebecca J.; Ehinger, Matthew; Elmore, Amy; Bortner, Carl D.; Ito, Mayumi; Cotsarelis, George; Nijhof, Joanne G.W.; Peckham, John; Flagler, Norris; Kissling, Grace; Humble, Margaret M.; King, Leon C.; Adams, Linda D.; Desai, Dhimant; Amin, Shantu; Tennant, Raymond W.

    2007-01-01

    The cell surface marker CD34 marks mouse hair follicle bulge cells, which have attributes of stem cells, including quiescence and multipotency. Using a CD34 knockout (KO) mouse, we tested the hypothesis that CD34 may participate in tumor development in mice because hair follicle stem cells are thought to be a major target of carcinogens in the two-stage model of mouse skin carcinogenesis. Following initiation with 200 nmol 7,12-dimethylbenz(a)anthracene (DMBA), mice were promoted with 12-O-tetradecanoylphorbol-13-acetate (TPA) for 20 weeks. Under these conditions, CD34KO mice failed to develop papillomas. Increasing the initiating dose of DMBA to 400 nmol resulted in tumor development in the CD34KO mice, albeit with an increased latency and lower tumor yield compared with the wild-type (WT) strain. DNA adduct analysis of keratinocytes from DMBA-initiated CD34KO mice revealed that DMBA was metabolically activated into carcinogenic diol epoxides at both 200 and 400 nmol. Chronic exposure to TPA revealed that CD34KO skin developed and sustained epidermal hyperplasia. However, CD34KO hair follicles typically remained in telogen rather than transitioning into anagen growth, confirmed by retention of bromodeoxyuridine-labeled bulge stem cells within the hair follicle. Unique localization of the hair follicle progenitor cell marker MTS24 was found in interfollicular basal cells in TPA-treated WT mice, whereas staining remained restricted to the hair follicles of CD34KO mice, suggesting that progenitor cells migrate into epidermis differently between strains. These data show that CD34 is required for TPA-induced hair follicle stem cell activation and tumor formation in mice. PMID:17483328

  8. Development of an Automated Modality-Independent Elastographic Image Analysis System for Tumor Screening

    DTIC Science & Technology

    2006-02-01

    further develop modality-independent elastography as a system that is able to reproducibly detect regions of increased stiffness within the breast based...tested on a tissue-like polymer phantom. elastography , breast cancer screening, image processing 16. SECURITY CLASSIFICATION OF: 17. LIMITATION...is a map of the breast (or other tissue of interest) that reflects material inhomogeneity, such as in the case of a tumor mass that disrupts the

  9. A novel bioactive derivative of eicosapentaenoic acid (EPA) suppresses intestinal tumor development in ApcΔ14/+ mice.

    PubMed

    Nakanishi, Masako; Hanley, Matthew P; Zha, Ruochen; Igarashi, Yuichi; Hull, Mark A; Mathias, Gary; Sciavolino, Frank; Grady, James J; Rosenberg, Daniel W

    2018-03-08

    Familial adenomatous polyposis (FAP) is a genetic disorder characterized by the development of hundreds of polyps throughout the colon. Without prophylactic colectomy, most individuals with FAP develop colorectal cancer at an early age. Treatment with EPA in the free fatty acid form (EPA-FFA) has been shown to reduce polyp burden in FAP patients. Since high-purity EPA-FFA is subject to rapid oxidation, a stable form of EPA compound has been developed in the form of magnesium l-lysinate bis-eicosapentaenoate (TP-252). We assessed the chemopreventive efficacy of TP-252 on intestinal tumor formation using ApcΔ14/+ mice and compared it with EPA-FFA. TP-252 was supplemented in a modified AIN-93G diet at 1, 2 or 4% and EPA-FFA at 2.5% by weight and administered to mice for 11 weeks. We found that administration of TP-252 significantly reduced tumor number and size in the small intestine and colon in a dose-related manner and as effectively as EPA-FFA. To gain further insight into the cancer protection afforded to the colon, we performed a comprehensive lipidomic analysis of total fatty acid composition and eicosanoid metabolites. Treatment with TP-252 significantly decreased the levels of arachidonic acid (AA) and increased EPA concentrations within the colonic mucosa. Furthermore, a classification and regression tree (CART) analysis revealed that a subset of fatty acids, including EPA and docosahexaenoic acid (DHA), and their downstream metabolites, including PGE3 and 14-hydroxy-docosahexaenoic acid (HDoHE), were strongly associated with antineoplastic activity. These results indicate that TP-252 warrants further clinical development as a potential strategy for delaying colectomy in adolescent FAP patients.

  10. Brain Development and Early Learning: Research on Brain Development. Quality Matters. Volume 1, Winter 2007

    ERIC Educational Resources Information Center

    Edie, David; Schmid, Deborah

    2007-01-01

    For decades researchers have been aware of the extraordinary development of a child's brain during the first five years of life. Recent advances in neuroscience have helped crystallize earlier findings, bringing new clarity and understanding to the field of early childhood brain development. Children are born ready to learn. They cultivate 85…

  11. Development of a Human Neurovascular Unit Organotypic Systems Model of Early Brain Development

    EPA Science Inventory

    The inability to model human brain and blood-brain barrier development in vitro poses a major challenge in studies of how chemicals impact early neurogenic periods. During human development, disruption of thyroid hormone (TH) signaling is related to adverse morphological effects ...

  12. EFFECT OF HYPOTHYROIDISM AND THYROID GRAFTS ON LYMPHOID TUMOR DEVELOPMENT IN IRRADIATED C57BL MICE

    SciT

    Nagareda, C.S.; Kaplan, H.S.

    1959-04-01

    Studies on the effect of radiothyroidectomy and thyroid grafts on the incidence of thymic implant lymphomas in thymectomized-irradiated CS7BL mice are reported. Hypothyroidism significantly inhibited thymic implant tumor development in females. A similar reduction of lymphoma incidence in hypothyroid males was not statistically significant. When thyroid activity was restored by grafting normal thyroids to radiothyroidectomized animals, lymphoma incidence returned to the level seen in euthyroid animals. I/sup 131/ uptake measurements were made on a representative number of thyroids and thyroid grafts. There was no significant uptake by the I/sup 131/-treated thyroids. Thyroid grafts were just as active as thyroids frommore » control animals. Body weight decreased significantiy in hypothyroid animals and was restored to control euthyroid levels in radiothyroidectomized animals by thyroid grafts. The possible influence of secondary nutritional and endocrine disturbances on leukemogenesis are discussed; it seems likely that the observed inhibition is attributable to hypothyroidism per se, rather than to secondary influences on nutrition or other endocrine imbalances. Incidental observations on pituitary tumor development in lymphoma- free radiothyroldectomized animals are also reported. Pituitary tumor development was completely prevented by thyroid grafts after radiothyroidectomy. (auth)« less

  13. Merkel cell polyomavirus small T antigen initiates Merkel cell carcinoma-like tumor development in mice

    PubMed Central

    Verhaegen, Monique E.; Mangelberger, Doris; Harms, Paul W.; Eberl, Markus; Wilbert, Dawn M.; Meireles, Julia; Bichakjian, Christopher K.; Saunders, Thomas L.; Wong, Sunny Y.; Dlugosz, Andrzej A.

    2017-01-01

    Merkel cell carcinoma (MCC) tumor cells express several markers detected in normal Merkel cells, a non-proliferative population of neuroendocrine cells which arise from epidermis. MCCs frequently contain Merkel cell polyomavirus (MCPyV) DNA and express viral transforming antigens, sT and tLT, but the role of these putative oncogenes in MCC development, and this tumor’s cell of origin, are unknown. Using a panel of pre-term transgenic mice, we show that epidermis-targeted co-expression of sT and the cell fate determinant atonal bHLH transcription factor 1 (Atoh1) leads to development of widespread cellular aggregates with histology and marker expression mimicking that of human intraepidermal MCC. The MCC-like tumor phenotype was dependent on the FBXW7-binding domain of sT, but not the sT-PP2A binding domain. Co-expression of MCPyV tLT did not appreciably alter the phenotype driven by either sT or sT combined with Atoh1. MCPyV sT, when co-expressed with Atoh1, is thus sufficient to initiate development of epidermis-derived MCC-like tumors in mice. PMID:28512245

  14. Deuterostome evolution: early development in the enteropneust hemichordate, Ptychodera flava

    NASA Technical Reports Server (NTRS)

    Henry, J. Q.; Tagawa, K.; Martindale, M. Q.

    2001-01-01

    Molecular and morphological comparisons indicate that the Echinodermata and Hemichordata represent closely related sister-phyla within the Deuterostomia. Much less is known about the development of the hemichordates compared to other deuterostomes. For the first time, cell lineage analyses have been carried out for an indirect-developing representative of the enteropneust hemichordates, Ptychodera flava. Single blastomeres were iontophoretically labeled with Dil at the 2- through 16-cell stages, and their fates followed through development to the tornaria larval stage. The early cleavage pattern of P. flava is similar to that of the direct-developing hemichordate, Saccoglossus kowalevskii, as well as that displayed by indirect-developing echinoids. The 16-celled embryo contains eight animal "mesomeres," four slightly larger "macromeres," and four somewhat smaller vegetal "micromeres." The first cleavage plane was not found to bear one specific relationship relative to the larval dorsoventral axis. Although individual blastomeres generate discrete clones of cells, the appearance and exact locations of these clones are variable with respect to the embryonic dorsoventral and bilateral axes. The eight animal mesomeres generate anterior (animal) ectoderm of the larva, which includes the apical organ; however, contributions to the apical organ were found to be variable as only a subset of the animal blastomeres end up contributing to its formation and this varies from embryo to embryo. The macromeres generate posterior larval ectoderm, and the vegetal micromeres form all the internal, endomesodermal tissues. These blastomere contributions are similar to those found during development of the only other hemichordate studied, the direct-developing enteropneust, S. kowalevskii. Finally, isolated blastomeres prepared at either the two- or the four-cell stage are capable of forming normal-appearing, miniature tornaria larvae. These findings indicate that the fates of these

  15. Dual effects of fluoxetine on mouse early embryonic development

    SciT

    Kim, Chang-Woon; Department of Obstetrics and Gynecology, Samsung Changwon Hospital, Sungkyunkwan University, Changwon 630-723; Choe, Changyong

    2012-11-15

    Fluoxetine, a selective serotonin reuptake inhibitor, regulates a variety of physiological processes, such as cell proliferation and apoptosis, in mammalian cells. Little is known about the role of fluoxetine in early embryonic development. This study was undertaken to investigate the effect of fluoxetine during mouse early embryonic development. Late two-cell stage embryos (2-cells) were cultured in the presence of various concentrations of fluoxetine (1 to 50 μM) for different durations. When late 2-cells were incubated with 5 μM fluoxetine for 6 h, the percentage that developed into blastocysts increased compared to the control value. However, late 2-cells exposed to fluoxetinemore » (5 μM) over 24 h showed a reduction in blastocyst formation. The addition of fluoxetine (5 μM) together with KN93 or KN62 (calcium/calmodulin-dependent protein kinase II (CaMKII) inhibitors) failed to increase blastocyst formation. Fluoxetine treatment inhibited TREK-1 and TREK-2, members of the two-pore domain K{sup +} channel family expressed in mouse embryos, activities, indicating that fluoxetine-induced membrane depolarization in late 2-cells might have resulted from TREK inhibition. In addition, long-term exposure to fluoxetine altered the TREK mRNA expression levels. Furthermore, injection of siRNA targeting TREKs significantly decreased blastocyst formation by ∼ 30% compared to injection of scrambled siRNA. Long-term exposure of fluoxetine had no effect on blastocyst formation of TREK deficient embryos. These results indicate that low-dose and short-term exposures of late 2-cells to fluoxetine probably increase blastocyst formation through activation of CaMKII-dependent signal transduction pathways, whereas long-term exposure decreases mouse early embryonic development through inhibition of TREK channel gating. Highlights: ► Short-term exposure of 2-cells to fluoxetine enhances mouse blastocyst formation. ► The enhancive effect of fluoxetine is resulted from Ca

  16. GATA-3 is required for early T lineage progenitor development

    PubMed Central

    Hosoya, Tomonori; Kuroha, Takashi; Moriguchi, Takashi; Cummings, Dustin; Maillard, Ivan; Lim, Kim-Chew

    2009-01-01

    Most T lymphocytes appear to arise from very rare early T lineage progenitors (ETPs) in the thymus, but the transcriptional programs that specify ETP generation are not completely known. The transcription factor GATA-3 is required for the development of T lymphocytes at multiple late differentiation steps as well as for the development of thymic natural killer cells. However, a role for GATA-3 before the double-negative (DN) 3 stage of T cell development has to date been obscured both by the developmental heterogeneity of DN1 thymocytes and the paucity of ETPs. We provide multiple lines of in vivo evidence through the analysis of T cell development in Gata3 hypomorphic mutant embryos, in irradiated mice reconstituted with Gata3 mutant hematopoietic cells, and in mice conditionally ablated for the Gata3 gene to show that GATA-3 is required for ETP generation. We further show that Gata3 loss does not affect hematopoietic stem cells or multipotent hematopoietic progenitors. Finally, we demonstrate that Gata3 mutant lymphoid progenitors exhibit neither increased apoptosis nor diminished cell-cycle progression. Thus, GATA-3 is required for the cell-autonomous development of the earliest characterized thymic T cell progenitors. PMID:19934022

  17. Assessment of early response to imatinib 800 mg after 400 mg progression by ¹⁸F-fluorodeoxyglucose PET in patients with metastatic gastrointestinal stromal tumors.

    PubMed

    Chacón, Matías; Eleta, Martín; Espindola, Adriel Rodríguez; Roca, Enrique; Méndez, Guillermo; Rojo, Sandra; Pupareli, Carmen

    2015-01-01

    Imatinib is the standard first-line therapy for advanced gastrointestinal stromal tumor. (18)F-fluorodeoxyglucose PET computed tomography (FDG PET/CT) shows a faster response than computed tomography in nonpretreated patients. After disease progression on imatinib 400 mg, 16 patients were exposed to 800 mg. Tumor response was evaluated by FDG PET/CT on days 7 and 37. Primary objective was to correlate early metabolic response (EMR) with progression-free survival (PFS). EMR by FDG PET/CT scan was not predictive of PFS. Median PFS in these patients was 3 months. Overall survival was influenced by gastric primary site (p = 0.05). The assessment of EMR by FDG PET/CT in patients with advanced gastrointestinal stromal tumor exposed to imatinib 800 mg was not predictive of PFS or overall survival.

  18. Paraneoplastic Antigen Ma2 Autoantibodies as Specific Blood Biomarkers for Detection of Early Recurrence of Small Intestine Neuroendocrine Tumors

    PubMed Central

    Cui, Tao; Hurtig, Monica; Elgue, Graciela; Li, Su-Chen; Veronesi, Giulia; Essaghir, Ahmed; Demoulin, Jean-Baptiste; Pelosi, Giuseppe; Alimohammadi, Mohammad; Öberg, Kjell; Giandomenico, Valeria

    2010-01-01

    Background Small intestine neuroendocrine tumors (SI-NETs) belong to a rare group of cancers. Most patients have developed metastatic disease at the time of diagnosis, for which there is currently no cure. The delay in diagnosis is a major issue in the clinical management of the patients and new markers are urgently needed. We have previously identified paraneoplastic antigen Ma2 (PNMA2) as a novel SI-NET tissue biomarker. Therefore, we evaluated whether Ma2 autoantibodies detection in the blood stream is useful for the clinical diagnosis and recurrence of SI-NETs. Methodology/Principal Findings A novel indirect ELISA was set up to detect Ma2 autoantibodies in blood samples of patients with SI-NET at different stages of disease. The analysis was extended to include typical and atypical lung carcinoids (TLC and ALC), to evaluate whether Ma2 autoantibodies in the blood stream become a general biomarker for NETs. In total, 124 blood samples of SI-NET patients at different stages of disease were included in the study. The novel Ma2 autoantibody ELISA showed high sensitivity, specificity and accuracy with ROC curve analysis underlying an area between 0.734 and 0.816. Ma2 autoantibodies in the blood from SI-NET patients were verified by western blot and sequential immunoprecipitation. Serum antibodies of patients stain Ma2 in the tumor tissue and neurons. We observed that SI-NET patients expressing Ma2 autoantibody levels below the cutoff had a longer progression and recurrence-free survival compared to those with higher titer. We also detected higher levels of Ma2 autoantibodies in blood samples from TLC and ALC patients than from healthy controls, as previously shown in small cell lung carcinoma samples. Conclusion Here we show that high Ma2 autoantibody titer in the blood of SI-NET patients is a sensitive and specific biomarker, superior to chromogranin A (CgA) for the risk of recurrence after radical operation of these tumors. PMID:21209860

  19. Short National Early Warning Score - Developing a Modified Early Warning Score.

    PubMed

    Luís, Leandro; Nunes, Carla

    2017-12-11

    Early Warning Score (EWS) systems have been developed for detecting hospital patients clinical deterioration. Many studies show that a National Early Warning Score (NEWS) performs well in discriminating survival from death in acute medical and surgical hospital wards. NEWS is validated for Portugal and is available for use. A simpler EWS system may help to reduce the risk of error, as well as increase clinician compliance with the tool. The aim of the study was to evaluate whether a simplified NEWS model will improve use and data collection. We evaluated the ability of single and aggregated parameters from the NEWS model to detect patients' clinical deterioration in the 24h prior to an outcome. There were 2 possible outcomes: Survival vs Unanticipated intensive care unit admission or death. We used binary logistic regression models and Receiver Operating Characteristic Curves (ROC) to evaluate the parameters' performance in discriminating among the outcomes for a sample of patients from 6 Portuguese hospital wards. NEWS presented an excellent discriminating capability (Area under the Curve of ROC (AUCROC)=0.944). Temperature and systolic blood pressure (SBP) parameters did not contribute significantly to the model. We developed two different models, one without temperature, and the other by removing temperature and SBP (M2). Both models had an excellent discriminating capability (AUCROC: 0.965; 0.903, respectively) and a good predictive power in the optimum threshold of the ROC curve. The 3 models revealed similar discriminant capabilities. Although the use of SBP is not clearly evident in the identification of clinical deterioration, it is recognized as an important vital sign. We recommend the use of the first new model, as its simplicity may help to improve adherence and use by health care workers. Copyright © 2017 Australian College of Critical Care Nurses Ltd. Published by Elsevier Ltd. All rights reserved.

  20. Small heterodimer partner overexpression partially protects against liver tumor development in farnesoid X receptor knockout mice

    SciT

    Li, Guodong; Kong, Bo; Zhu, Yan

    2013-10-15

    Farnesoid X receptor (FXR, Nr1h4) and small heterodimer partner (SHP, Nr0b2) are nuclear receptors that are critical to liver homeostasis. Induction of SHP serves as a major mechanism of FXR in suppressing gene expression. Both FXR{sup −/−} and SHP{sup −/−} mice develop spontaneous hepatocellular carcinoma (HCC). SHP is one of the most strongly induced genes by FXR in the liver and is a tumor suppressor, therefore, we hypothesized that deficiency of SHP contributes to HCC development in the livers of FXR{sup −/−} mice and therefore, increased SHP expression in FXR{sup −/−} mice reduces liver tumorigenesis. To test this hypothesis, wemore » generated FXR{sup −/−} mice with overexpression of SHP in hepatocytes (FXR{sup −/−}/SHP{sup Tg}) and determined the contribution of SHP in HCC development in FXR{sup −/−} mice. Hepatocyte-specific SHP overexpression did not affect liver tumor incidence or size in FXR{sup −/−} mice. However, SHP overexpression led to a lower grade of dysplasia, reduced indicator cell proliferation and increased apoptosis. All tumor-bearing mice had increased serum bile acid levels and IL-6 levels, which was associated with activation of hepatic STAT3. In conclusion, SHP partially protects FXR{sup −/−} mice from HCC formation by reducing tumor malignancy. However, disrupted bile acid homeostasis by FXR deficiency leads to inflammation and injury, which ultimately results in uncontrolled cell proliferation and tumorigenesis in the liver. - Highlights: • SHP does not prevent HCC incidence nor size in FXR KO mice but reduces malignancy. • Increased SHP promotes apoptosis. • Bile acids and inflammation maybe critical for HCC formation with FXR deficiency.« less

  1. Early motor development and cognitive abilities among Mexican preschoolers.

    PubMed

    Osorio-Valencia, Erika; Torres-Sánchez, Luisa; López-Carrillo, Lizbeth; Rothenberg, Stephen J; Schnaas, Lourdes

    2017-07-18

    Psychomotricity plays a very important role in children's development, especially for learning involving reading-writing and mathematical calculations. Evaluate motor development in children 3 years old and its relationship with their cognitive abilities at the age of 5 years. Based on a cohort study, we analyzed the information about motor performance evaluated at 3 years old by Peabody Motor Scale and cognitive abilities at 5 years old. The association was estimated using linear regression models adjusted by mother's intelligence quotient, sex, Bayley mental development index at 18 months, and quality of the environment at home (HOME scale). 148 children whose motor performance was determined at age 3 and was evaluated later at age 5 to determine their cognitive abilities. Cognitive abilities (verbal, quantitative, and memory) measured by McCarthy Scales. Significant positive associations were observed between stationary balance at age 3 with verbal abilities (β = 0.67, p = .04) and memory (β = 0.81, p = .02) at 5 years. Grasping and visual-motor integration were significant and positively associated with quantitative abilities (β = 0.74, p = .005; β = 0.61, p = .01) and memory (β = 2.11, p = .001; β = 1.74, p = .004). The results suggest that early motor performance contributes to the establishment of cognitive abilities at 5 years. Evaluation and early motor stimulation before the child is faced with formal learning likely helps to create neuronal networks that facilitate the acquisition of academic knowledge.

  2. Combined modality treatment improves tumor control and overall survival in patients with early stage Hodgkin’s lymphoma: a systematic review

    PubMed Central

    Herbst, Christine; Rehan, Fareed A.; Brillant, Corinne; Bohlius, Julia; Skoetz, Nicole; Schulz, Holger; Monsef, Ina; Specht, Lena; Engert, Andreas

    2010-01-01

    Combined modality treatment (CMT) of chemotherapy followed by localized radiotherapy is standard treatment for patients with early stage Hodgkin’s lymphoma. However, the role of radiotherapy has been questioned recently and some clinical study groups advocate chemotherapy only for this indication. We thus performed a systematic review with meta-analysis of randomized controlled trials comparing chemotherapy alone with CMT in patients with early stage Hodgkin’s lymphoma with respect to response rate, tumor control and overall survival (OS). We searched Medline, EMBASE and the Cochrane Library as well as conference proceedings from January 1980 to February 2009 for randomized controlled trials comparing chemotherapy alone versus the same chemotherapy regimen plus radiotherapy. Progression free survival and similar outcomes were analyzed together as tumor control. Effect measures used were hazard ratios for OS and tumor control as well as relative risks for complete response (CR). Meta-analyses were performed using RevMan5. Five randomized controlled trials involving 1,245 patients were included. The hazard ratio (HR) was 0.41 (95% confidence interval (CI) 0.25 to 0.66) for tumor control and 0.40 (95% CI 0.27 to 0.59) for OS for patients receiving CMT compared to chemotherapy alone. CR rates were similar between treatment groups. In sensitivity analyses another 6 trials were included that did not fulfill the inclusion criteria of our protocol but were considered relevant to the topic. These trials underlined the results of the main analysis. In conclusion, adding radiotherapy to chemotherapy improves tumor control and OS in patients with early stage Hodgkin’s lymphoma. PMID:19951972

  3. Development of Mechanochemically Active Polymers for Early Damage Detection

    NASA Astrophysics Data System (ADS)

    Zou, Jin

    Identification of early damage in polymer composite materials is of significant importance so that preventative measures can be taken before the materials reach catastrophic failure. Scientists have been developing damage detection technologies over many years and recently, mechanophore-based polymers, in which mechanical energy is translated to activate a chemical transformation, have received increasing attention. More specifically, the damage can be made detectable by mechanochromic polymers, which provide a visible color change upon the scission of covalent bonds under stress. This dissertation focuses on the study of a novel self-sensing framework for identifying early and in-situ damage by employing unique stress-sensing mechanophores. Two types of mechanophores, cyclobutane and cyclooctane, were utilized, and the former formed from cinnamoyl moeities and the latter formed from anthracene upon photodimerization. The effects on the thermal and mechanical properties with the addition of the cyclobutane-based polymers into epoxy matrices were investigated. The emergence of cracks was detected by fluorescent signals at a strain level right after the yield point of the polymer blends, and the fluorescence intensified with the accumulation of strain. Similar to the mechanism of fluorescence emission from the cleavage of cyclobutane, the cyclooctane moiety generated fluorescent emission with a higher quantum yield upon cleavage. The experimental results also demonstrated the success of employing the cyclooctane type mechanophore as a potential force sensor, as the fluorescence intensification was correlated with the strain increase.

  4. Investigational drugs in early development for treating dengue infection.

    PubMed

    Beesetti, Hemalatha; Khanna, Navin; Swaminathan, Sathyamangalam

    2016-09-01

    Dengue has emerged as the most significant arboviral disease of the current century. A drug for dengue is an urgent unmet need. As conventional drug discovery efforts have not produced any promising clinical candidates, there is a shift toward re-positioning pre-existing drugs for dengue to fast-track dengue drug development. This article provides an update on the current status of recently completed and ongoing dengue drug trials. All dengue drug trials described in this article were identified from a list of >230 trials that were returned upon searching the World Health Organization's International Clinical Trials Registry Platform web portal using the search term 'dengue' on December 31(st), 2015. None of the handful of drugs tested so far has yielded encouraging results. Early trial experience has served to emphasize the challenge of drug testing in the short therapeutic time window available, the need for tools to predict 'high-risk' patients early on and the limitations of the existing pre-clinical model systems. Significant investment of efforts and resources is a must before the availability of a safe, effective and inexpensive dengue drug becomes a reality. Currently, supportive fluid therapy remains the only option available for dengue treatment.

  5. Measuring the implementation of early childhood development programs.

    PubMed

    Aboud, Frances E; Prado, Elizabeth L

    2018-05-01

    In this paper we describe ways to measure variables of interest when evaluating the implementation of a program to improve early childhood development (ECD). The variables apply to programs delivered to parents in group sessions and home or clinic visits, as well as in early group care for children. Measurements for four categories of variables are included: training and assessment of delivery agents and supervisors; program features such as quality of delivery, reach, and dosage; recipients' acceptance and enactment; and stakeholders' engagement. Quantitative and qualitative methods are described, along with when measures might be taken throughout the processes of planning, preparing, and implementing. A few standard measures are available, along with others that researchers can select and modify according to their goals. Descriptions of measures include who might collect the information, from whom, and when, along with how information might be analyzed and findings used. By converging on a set of common methods to measure implementation variables, investigators can work toward improving programs, identifying gaps that impede the scalability and sustainability of programs, and, over time, ascertain program features that lead to successful outcomes. © 2018 The Authors. Annals of the New York Academy of Sciences published by Wiley Periodicals, Inc. on behalf of New York Academy of Sciences.

  6. Early Miocene sequence development across the New Jersey margin

    Monteverde, D.H.; Mountain, Gregory S.; Miller, K.G.

    2008-01-01

    Sequence stratigraphy provides an understanding of the interplay between eustasy, sediment supply and accommodation in the sedimentary construction of passive margins. We used this approach to follow the early to middle Miocene growth of the New Jersey margin and analyse the connection between relative changes of sea level and variable sediment supply. Eleven candidate sequence boundaries were traced in high-resolution multi-channel seismic profiles across the inner margin and matched to geophysical log signatures and lithologic changes in ODP Leg 150X onshore coreholes. Chronologies at these drill sites were then used to assign ages to the intervening seismic sequences. We conclude that the regional and global correlation of early Miocene sequences suggests a dominant role of global sea-level change but margin progradation was controlled by localized sediment contribution and that local conditions played a large role in sequence formation and preservation. Lowstand deposits were regionally restricted and their locations point to both single and multiple sediment sources. The distribution of highstand deposits, by contrast, documents redistribution by along shelf currents. We find no evidence that sea level fell below the elevation of the clinoform rollover, and the existence of extensive lowstand deposits seaward of this inflection point indicates efficient cross-shelf sediment transport mechanisms despite the apparent lack of well-developed fluvial drainage. ?? 2008 The Authors. Journal compilation ?? 2008 Blackwell Publishing.

  7. Early Dynamic 68Ga-DOTA-D-Phe1-Tyr3-Octreotide PET/CT in Patients With Hepatic Metastases of Neuroendocrine Tumors.

    PubMed

    Sänger, Philipp Wilhelm; Freesmeyer, Martin

    2016-06-01

    Whole-body PET with Ga-DOTA-D-Phe-Tyr-octreotide (Ga-DOTATOC) and contrast-enhanced CT (ceCT) are considered a standard for the staging of neuroendocrine tumors (NETs). This study sought to verify whether early dynamic (ed) Ga-DOTATOC PET/CT can reliably detect liver metastases of NETs (hypervascular, nonhypervascular; positive or negative for somatostatin receptors) and to verify if the receptor positivity has a significant impact on the detection of tumor hypervascularization. Twenty-seven patients with NET were studied by ceCT and standard whole-body PET according to established Ga-DOTATOC protocols. In addition, edPET data were obtained by continuous scanning during the first 300 seconds after bolus injections of the radiotracer. Early dynamic PET required an additional low-dose, native CT image of the liver for the purpose of attenuation correction. Time-activity and time-contrast curves were obtained, the latter being calculated by the difference between tumor and reference regions. Early dynamic PET/CT proved comparable with ceCT in readily identifying hypervascular lesions, irrespective of the receptor status, with activities rising within 16 to 40 seconds. Early dynamic PET/CT also readily identified nonhypervascular, receptor-positive lesions. Positive image contrasts were obtained for hypervascular, receptor-positive lesions, whereas early negative contrasts were obtained for nonhypervascular, receptor-negative lesions. The high image contrast of hypervascular NET metastases in early arterial phases suggests that edPET/CT can become a useful alternative in patients with contraindications to ceCT. The high density of somatostatin receptors did not seem to interfere with the detection of the lesion's hypervascularization.

  8. Early effect of boron neutron capture therapy mediated by boronophenylalanine (BPA-BNCT) on mast cells in premalignant tissue and tumors of the hamster cheek pouch.

    PubMed

    Aromando, Romina F; Trivillin, Verónica A; Heber, Elisa M; Pozzi, Emiliano; Schwint, Amanda E; Itoiz, María E

    2010-05-01

    Mast cell (MC) activation in the hamster cheek pouch cancerization model is associated with the increase in