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Sample records for age tumor grade

  1. [The role of age and tumor grade in the choice of fractionation regimen in patients with high-grade gliomas].

    PubMed

    Izmaĭlov, T R; Pan'shin, G A; Datsenko, P V

    2012-01-01

    There are currently no conventional guidelines for radiotherapy in gliomas. The treatment program is mainly formed in accordance with tumor morphology and the "golden standard" of irradiation is still the traditional mode of fractionation with a single focal dose of 2 Gy and total focal dose (TFD) of 60 Gy. In this report the treatment results of 396 patients with morphologically verified grade 3-4 malignant brain tumors receiving conventional irradiation regimen and irradiation by medium-sized fractions were analyzed to form institutional guidelines. The standard fractionation mode with a single focal dose of 2 Gy is preferable in patients with grade 3 glioma or elderly patients (over 60 years). TFD increase to 60-62 Gy in grade 4 gliomas and 54-56 Gy in grade 3 gliomas grants a significant improve in overall survival. An increase of a single irradiation fraction to 3 Gy may be used for patients younger than 60 years. In these cases it is advisable to use the TFD of 45 Gy or more (TFD of equivalent regimen with a dose greater than 54 Gy). The mentioned fractionation regimens could be recommended for the use in clinical practice to improve the results of high-grade gliomas treatment. PMID:22888654

  2. [Grading of neuroendocrine tumors].

    PubMed

    Saeger, W; Schnabel, P A; Komminoth, P

    2016-07-01

    The current WHO classification of neuroendocrine tumors (NET) differentiates between typical carcinoids (low grade NET), atypical carcinoids (intermediate grade NET) and small cell and large cell carcinomas (high grade NET) according to the prognosis. Neuroendocrine neoplasms (NEN) of the gastrointestinal tract and the pancreas are graded in an identical way. Together with the TNM system this enables a preoperative estimation of the prognosis in biopsies and fine needle aspirates. Well-differentiated tumors are graded into G1 tumors by the number of mitoses, <2 per 10 high-power fields (HPF) and the Ki-67 (index <3 %) and G2 tumors (2-20 mitoses/10 HPF, Ki-67 3-20 %). Discrepancies between the number of mitoses and the Ki-67 index are not uncommon and in these cases the higher value of the two should be applied. The more differentiated tumors of the G3 type have to be differentiated from undifferentiated carcinomas of the small cell type and large cell type with a much poorer prognosis. Prognosis relevant grading of thyroid cancers is achieved by special subtyping so that the G1-G3 system is not applicable. The rare cancers of the parathyroid gland and of the pituitary gland are not graded. Adrenal tumors also have no grading system. The prognosis is dependent on the Ki-67 index and with some reservations on the established scoring systems. PMID:27379621

  3. [Regression grading in gastrointestinal tumors].

    PubMed

    Tischoff, I; Tannapfel, A

    2012-02-01

    Preoperative neoadjuvant chemoradiation therapy is a well-established and essential part of the interdisciplinary treatment of gastrointestinal tumors. Neoadjuvant treatment leads to regressive changes in tumors. To evaluate the histological tumor response different scoring systems describing regressive changes are used and known as tumor regression grading. Tumor regression grading is usually based on the presence of residual vital tumor cells in proportion to the total tumor size. Currently, no nationally or internationally accepted grading systems exist. In general, common guidelines should be used in the pathohistological diagnostics of tumors after neoadjuvant therapy. In particularly, the standard tumor grading will be replaced by tumor regression grading. Furthermore, tumors after neoadjuvant treatment are marked with the prefix "y" in the TNM classification. PMID:22293790

  4. [Grading of gynecological tumors : Current aspects].

    PubMed

    Horn, L-C; Mayr, D; Brambs, C E; Einenkel, J; Sändig, I; Schierle, K

    2016-07-01

    Histopathological assessment of the tumor grade and cell type is central to the management and prognosis of various gynecological malignancies. Conventional grading systems for squamous carcinomas and adenocarcinomas of the vulva, vagina and cervix are poorly defined. For endometrioid tumors of the female genital tract as well as for mucinous endometrial, ovarian and seromucinous ovarian carcinomas, the 3‑tiered FIGO grading system is recommended. For uterine neuroendocrine tumors the grading system of the gastrointestinal counterparts has been adopted. Uterine leiomyosarcomas are not graded. Endometrial stromal sarcomas are divided into low and high grades, based on cellular morphology, immunohistochemical and molecular findings. A chemotherapy response score was established for chemotherapeutically treated high-grade serous pelvic cancer. For non-epithelial ovarian malignancies, only Sertoli-Leydig cell tumors and immature teratomas are graded. At this time molecular profiling has no impact on the grading of tumors of the female genital tract. PMID:27379622

  5. AB248. Expression of EphA2 protein is positively associated with age, tumor size and Fuhrman nuclear grade in clear cell renal cell carcinomas

    PubMed Central

    Wang, Longxin; Zhou, Wenquan

    2016-01-01

    Background The receptor tyrosine kinase of EphA2 has been shown frequently overexpressed in various types of human carcinomas, but the relationship between the expression of EphA2 protein in clear cell renal cell carcinoma was not well documented. Methods In the present study, using specific anit-EphA2 polyclonal antibody and immunohistochemistry, we evaluated EphA2 protein expression levels in clear cell RCC specimens surgically resected from 90 patients. Results Our results shows that EphA2 protein was positively expressed in all normal renal tubes of 90 samples (100%, 3+), which was expressed at low levels in renal cortex but high levels in the collecting ducts of the renal medulla and papilla. EphA2 was negatively or weakly expressed in 30 out of 90 samples (33.3%, 0/1+), moderately expressed in 24 samples (26.7%, 2+) and strongly expressed in 36 samples (40%, 3+). Expression of EphA2 was positively associated with age (P=0.029), tumor diameters (P<0.001) and Fuhrman nuclear grade (P<0.001). Conclusions Our results indicate that EphA2 variably expressed in clear cell renal cell carci-nomas. High expression of EphA2 was more often found in big size and high nuclear grade tumors, which indicated EphA2 protein may be used as a new marker for the prognosis of clear cell renal cell carcinoma.

  6. Age-Grade Consciousness

    ERIC Educational Resources Information Center

    Johnstone, John W. C.

    1970-01-01

    Studies of generational phenomena have not paid sufficient attention to the distinction between cohort and kinship aspects of generations. Using empirical measures of class consciousness as a model, consciousness of kind based on age is measured and related to theoretically relevant determinants and consequences." (Author)

  7. Tumor grade and chemotherapy response in endometrioid endometrial cancer.

    PubMed

    Davidson, Brittany A; Foote, Jonathan; Clark, Leslie H; Broadwater, Gloria; Ehrisman, Jessie; Gehrig, Paola; Graybill, Whitney; Alvarez Secord, Angeles; Havrilesky, Laura J

    2016-08-01

    The objective of this study is to evaluate the association between tumor grade and response to chemotherapy in patients with endometrioid endometrial adenocarcinoma. Patients with advanced or recurrent endometrioid endometrial adenocarcinoma of known tumor grade who received at least 3 cycles of chemotherapy were retrospectively identified at three institutions. RECIST 1.1 criteria were used to assess response to neoadjuvant, postoperative or salvage chemotherapy. Chi-square testing was used to evaluate the association between tumor grade and chemotherapy response. Ninety-one patients met inclusion criteria: 13 with grade 1, 29 with grade 2 and 49 with grade 3 tumors. Eighty-four percent of patients received chemotherapy for recurrence, 12% for postoperative residual disease, and 4% in the neoadjuvant setting. The majority (85%) received carboplatin and paclitaxel. Forty-six percent (6/13) of grade 1, 72% (21/29) of grade 2 and 43% (21/49) of grade 3 tumors achieved an objective response. Grade 2 tumors were more likely to respond to chemotherapy compared to grade 3 tumors (72% vs. 43%, p = 0.02; Table 2), and specifically more likely to respond to carboplatin/paclitaxel (72% vs. 41%, p = 0.016). Median progression-free survival for patients receiving chemotherapy for recurrence or progression was 9 months for grade 1, 8 months for grade 2, and 5 months for grade 3 tumors. Similar results between grade and treatment response were apparent in the subset of 37 patients with a recently re-assigned tumor grade (G2 88% vs. G3 44%, p = 0.032). In this series of endometrioid endometrial cancers, grade 2 tumors had the best measurable response to chemotherapy. PMID:27354990

  8. Grading of complications of transurethral resection of bladder tumor using Clavien–Dindo classification system

    PubMed Central

    Bansal, Ankur; Sankhwar, Satyanarayan; Goel, Apul; Kumar, Manoj; Purkait, Bimalesh; Aeron, Ruchir

    2016-01-01

    Introduction: Clavien–Dindo classification system is used for grading complications of various oncological, renal, and endourological procedures. We applied this system for grading the severity of perioperative complications in patients undergoing transurethral resection of bladder tumor (TURBT) and identify parameters predicting these complications. Materials and Methods: Data of 984 patients who underwent TURBT from 2006 to 2014 were included in this study. All data was retrospectively collected and analyzed for complications occurring within the first postoperative month. All complications were classified according to the five grades of modified CCS (.Clavien classification system). Results: A total of 172 complications were observed in 138 patients. Majority were low grade complications (Grade 1 [77.3%] and Grade 2 [12.7%]). Higher grade complications were rare (Grade 3 [6.4%] and Grade 4 [3.0%]). There was one death (Grade 5 0.6%), with an overall mortality rate of 0.1%. The incidence of complications was significantly greater for age >60 years, baseline serum creatinine >1.4 mg/dl, size of tumor >4 cm, tumor located at dome, resection time >60 min, incomplete resection and if surgery performed by a resident urologist. Conclusions: Clavien–Dindo classification system can be easily applied to grade the complications of TURBT, and it is easily reproducible. We observed that TURBT was a safe procedure. Majority of complications were Grade 1–2 (90%) and Grade 3–5 were rare (10%). Postoperative bleeding is the most common complication. A greater rate of complications of TURBT was associated with patient age, size of tumor, location of tumor, surgeon experience, resection time, and completion of tumor resection. PMID:27555684

  9. Classification and grading of canine malignant mammary tumors

    PubMed Central

    Tavasoly, Abbas; Golshahi, Hannaneh; Rezaie, Annahita; Farhadi, Mohammad

    2013-01-01

    Histological grading is a good parameter to stratify tumors according to their biological aggressiveness. The Elston and Ellis grading method in humans, invasive ductal breast carcinomas and other invasive tumors are routinely used. The aims of this study were classification of mammary gland tumors and also application of a human grading method in canine mammary carcinoma. The samples included 37 tumors of mammary glands. Mammary tumors were carcinomas (n = 32) and sarcomas (n = 5). The carcinomas were classified as simple carcinoma 56.8% (n = 21), complex carcinoma 13.5% (n = 5), carcinoma arising from benign tumor 10.8% (n= 4) and special type of carcinoma 5.4% (n = 2). Out of 32 carcinomas studied, 37.5% (n = 12) grade I, 46.9% (n = 15) grade II and 15.6% (n = 5) grade III. This study demonstrated that the Elston and Ellis method of histological grading in canine mammary tumor is a reliable prognostic factor which is correlated with histopathological classification. PMID:25593682

  10. Morphological and Immunohistochemical Reevaluation of Tumors Initially Diagnosed as Ovarian Endometrioid Carcinoma With Emphasis on High-grade Tumors.

    PubMed

    Lim, Diana; Murali, Rajmohan; Murray, Melissa P; Veras, Emanuela; Park, Kay J; Soslow, Robert A

    2016-03-01

    Ovarian endometrioid carcinomas (OEC) of low grade have characteristic morphologic features, but high-grade tumors can mimic high-grade serous and undifferentiated carcinomas. We reviewed tumors initially diagnosed as OEC to determine whether a combination of pathologic and immunohistochemical features can improve histologic subclassification. Tumors initially diagnosed as OEC were reviewed using World Health Organization criteria. We also noted the presence of associated confirmatory endometrioid features (CEFs): (i) squamous metaplasia; (ii) endometriosis; (iii) adenofibromatous background; and (iv) borderline endometrioid or mixed Mullerian component. A tissue microarray was constructed from 27 representative tumors with CEF and 14 without CEF, and sections were stained for WT-1, p16, and p53. Of 109 tumors initially diagnosed as OEC, 76 (70%) tumors were classified as OEC. The median patient age was 55 years, and 75% of patients were younger than 60 years. Ninety-two percent presented with disease confined to the pelvis, and 87% of tumors were unilateral. The median tumor size was 11.8 cm. Only 3% of tumors were high grade (grade 3of 3). Eighty percent of cases had at least 1 CEF, and 59% had at least 2 CEFs. Eleven percent overexpressed p16, 0% overexpressed p53, and 3% expressed WT-1. Only 10% of patients died of disease at last follow-up. Thirty-three (33) tumors, or 30% of tumors originally classified as endometrioid, were reclassified as serous carcinoma (OSC). The median patient age was 54.5 years, and 59% of patients were younger than 60 years of age. Only 27% had disease confined to the pelvis at presentation, 52% of tumors were unilateral, and the median tumor size was 8 cm. Associated squamous differentiation, endometrioid adenofibroma, and endometrioid or mixed Mullerian borderline tumor (CEFs) were not present in any case, but 6% of patients had endometriosis. Approximately one half of the reclassified OSC demonstrated SET-pattern morphology

  11. Computational hepatocellular carcinoma tumor grading based on cell nuclei classification

    PubMed Central

    Atupelage, Chamidu; Nagahashi, Hiroshi; Kimura, Fumikazu; Yamaguchi, Masahiro; Tokiya, Abe; Hashiguchi, Akinori; Sakamoto, Michiie

    2014-01-01

    Abstract. Hepatocellular carcinoma (HCC) is the most common histological type of primary liver cancer. HCC is graded according to the malignancy of the tissues. It is important to diagnose low-grade HCC tumors because these tissues have good prognosis. Image interpretation-based computer-aided diagnosis (CAD) systems have been developed to automate the HCC grading process. Generally, the HCC grade is determined by the characteristics of liver cell nuclei. Therefore, it is preferable that CAD systems utilize only liver cell nuclei for HCC grading. This paper proposes an automated HCC diagnosing method. In particular, it defines a pipeline-path that excludes nonliver cell nuclei in two consequent pipeline-modules and utilizes the liver cell nuclear features for HCC grading. The significance of excluding the nonliver cell nuclei for HCC grading is experimentally evaluated. Four categories of liver cell nuclear features were utilized for classifying the HCC tumors. Results indicated that nuclear texture is the dominant feature for HCC grading and others contribute to increase the classification accuracy. The proposed method was employed to classify a set of regions of interest selected from HCC whole slide images into five classes and resulted in a 95.97% correct classification rate. PMID:26158066

  12. Health and Aging Curriculum Grade Level: Preschool-Third Grade.

    ERIC Educational Resources Information Center

    McGuire, Sandra L.

    This curriculum on aging is designed to help promote positive attitudes toward age and aging among young children. It focuses on developing the concepts of: (1) aging is a natural and lifelong process of growing and developing; (2) old and young are similar in many ways; (3) older people are valuable and contributing members of society; (4) old…

  13. Irradiation of Pediatric High-Grade Spinal Cord Tumors

    SciTech Connect

    Tendulkar, Rahul D.; Pai Panandiker, Atmaram S.; Wu Shengjie; Kun, Larry E.; Broniscer, Alberto; Sanford, Robert A.; Merchant, Thomas E.

    2010-12-01

    Purpose: To report the outcome using radiation therapy (RT) for pediatric patients with high-grade spinal cord tumors. Methods and Materials: A retrospective chart review was conducted that included 17 children with high-grade spinal cord tumors treated with RT at St. Jude Children's Research Hospital between 1981 and 2007. Three patients had gross total resection, 11 had subtotal resection, and 3 underwent biopsy. The tumor diagnosis was glioblastoma multiforme (n = 7), anaplastic astrocytoma (n = 8), or anaplastic oligodendroglioma (n = 2). Seven patients received craniospinal irradiation (34.2-48.6 Gy). The median dose to the primary site was 52.2 Gy (range, 38-66 Gy). Results: The median progression-free and overall survivals were 10.8 and 13.8 months, respectively. Local tumor progression at 12 months (79% vs. 30%, p = 0.02) and median survival (13.1 vs. 27.2 months, p = 0.09) were worse for patients with glioblastoma multiforme compared with anaplastic astrocytoma or oligodendroglioma. The median overall survival was shorter for patients when failure included neuraxis dissemination (n = 8) compared with local failure alone (n = 5), 9.6 vs. 13.8 months, p = 0.08. Three long-term survivors with World Health Organization Grade III tumors were alive with follow-up, ranging from 88-239 months. Conclusions: High-grade spinal cord primary tumors in children have a poor prognosis. The propensity for neuraxis metastases as a component of progression after RT suggests the need for more aggressive therapy.

  14. Expression of merlin, NDRG2, ERBB2, and c-MYC in meningiomas: relationship with tumor grade and recurrence

    PubMed Central

    Ongaratti, B.R.; Silva, C.B.O.; Trott, G.; Haag, T.; Leães, C.G.S.; Ferreira, N.P.; Oliveira, M.C.; Pereira-Lima, J.F.S.

    2016-01-01

    Meningiomas are common, usually benign tumors of the central nervous system that have a high rate of post-surgical recurrence or regrowth. We determined expression of the proteins merlin, NDRG2, ERBB2, and c-MYC in meningiomas using immunohistochemistry and assessed relationships between protein expression and gender, age, tumor grade, and recurrence or regrowth. The study sample comprised 60 patients, (44 women and 16 men) with a mean age of 53.2±12.7 years. Tumors were classified as grade I (n=48) or grades II and III (n=12). Expression of merlin, NDRG2, ERBB2, and c-MYC was not significantly different statistically with relation to gender, age, or meningioma recurrence or regrowth. Merlin was expressed in 100% of the cases. No statistically significant difference between tumor grade and recurrence or regrowth was identified. Statistically significant differences were identified between the mean age of patients with grade I (54.83±11.60) and grades II and III (46.58±15.08) meningiomas (P=0.043), between strong c-MYC expression and grades II and III (P<0.001), and between partial surgical resection and tumor recurrence or regrowth (P<0.001). These findings reveal the lower mean age among grades II and III meningioma patients than grade I patients, the influence of the protein merlin on tumorigenesis, the association of c-MYC with aggressive meningiomas, and that partial surgical resection is associated with tumor recurrence or regrowth. PMID:27007654

  15. The diagnostic accuracy of multiparametric MRI to determine pediatric brain tumor grades and types.

    PubMed

    Koob, Mériam; Girard, Nadine; Ghattas, Badih; Fellah, Slim; Confort-Gouny, Sylviane; Figarella-Branger, Dominique; Scavarda, Didier

    2016-04-01

    Childhood brain tumors show great histological variability. The goal of this retrospective study was to assess the diagnostic accuracy of multimodal MR imaging (diffusion, perfusion, MR spectroscopy) in the distinction of pediatric brain tumor grades and types. Seventy-six patients (range 1 month to 18 years) with brain tumors underwent multimodal MR imaging. Tumors were categorized by grade (I-IV) and by histological type (A-H). Multivariate statistical analysis was performed to evaluate the diagnostic accuracy of single and combined MR modalities, and of single imaging parameters to distinguish the different groups. The highest diagnostic accuracy for tumor grading was obtained with diffusion-perfusion (73.24 %) and for tumor typing with diffusion-perfusion-MR spectroscopy (55.76 %). The best diagnostic accuracy was obtained for tumor grading in I and IV and for tumor typing in embryonal tumor and pilocytic astrocytoma. Poor accuracy was seen in other grades and types. ADC and rADC were the best parameters for tumor grading and typing followed by choline level with an intermediate echo time, CBV for grading and Tmax for typing. Multiparametric MR imaging can be accurate in determining tumor grades (primarily grades I and IV) and types (mainly pilocytic astrocytomas and embryonal tumors) in children. PMID:26732081

  16. The End of the Reading Age: Grade and Age Effects in Early Schooling

    ERIC Educational Resources Information Center

    Alexander, James R.M.; Martin, Frances

    2004-01-01

    During the school years, psychological test norms may be indexed by age or by grade. A number of studies have shown that using age-based norms appears to produce biases associated with grade assignment. Cahan and Cohen [Child Dev. 60 (1989) 1239-1249] showed that the effect of one grade was over twice the effect of 1 year of age for most verbal…

  17. 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

  18. Evaluation of Technetium-99m glucoheptonate single photon emission computed tomography for brain tumor grading

    PubMed Central

    Alam, Syed Shafiq; Junaid, Syed; Ahmed, Syed Mushtaq

    2016-01-01

    Background: This study is designed to appraise the diagnostic value of technetium-99m glucoheptonate (Tc-99m GHA) single photon emission computed tomography (SPECT) in brain tumor grading. Subjects and Methods: The study was performed on 30 patients referred from the Department of Neurosurgery, who were from both urban and rural areas. Data were collected through interview, history taking, and clinical examination followed by recording the desired parameters and finally imaging. The study subjects were divided into five groups: Controls (n = 4), low-grade tumors (n = 8), high-grade tumors (n = 8), metastases (n = 5), and nonneoplastic lesions (n = 5). This division was based on the World Health Organization (WHO) classification postclinico-histological diagnosis. Each of the subjects underwent contrast-enhanced computed tomography/contrast-enhanced magnetic resonance and Tc-99m GHA SPECT preoperatively. All were followed up postoperatively, and histopathological reports were regarded as the gold standard for tumor grading wherever available. Results: It was found that high-grade tumors (Grades III/IV and IV/IV according to the WHO classification) showed significantly higher tumor to normal (T/N) ratios as well as Tmax/N ratios when compared with low-grade tumors (Grades I/IV and II/IV), metastases or nonneoplastic lesions. Conclusions: In summary, the results of this study suggest that in situations where a preoperative grading of tumor is required Tc-99m GHA can be used in tumor grading and its use should be encouraged. Semi-quantitative analysis using both T/N as well as Tmax/N can be used in differentiating high-grade tumors from low-grade ones. PMID:27057217

  19. Gene expression-based biomarkers for Anopheles gambiae age grading.

    PubMed

    Wang, Mei-Hui; Marinotti, Osvaldo; Zhong, Daibin; James, Anthony A; Walker, Edward; Guda, Tom; Kweka, Eliningaya J; Githure, John; Yan, Guiyun

    2013-01-01

    Information on population age structure of mosquitoes under natural conditions is fundamental to the understanding of vectorial capacity and crucial for assessing the impact of vector control measures on malaria transmission. Transcriptional profiling has been proposed as a method for predicting mosquito age for Aedes and Anopheles mosquitoes, however, whether this new method is adequate for natural conditions is unknown. This study tests the applicability of transcriptional profiling for age-grading of Anopheles gambiae, the most important malaria vector in Africa. The transcript abundance of two An. gambiae genes, AGAP009551 and AGAP011615, was measured during aging under laboratory and field conditions in three mosquito strains. Age-dependent monotonic changes in transcript levels were observed in all strains evaluated. These genes were validated as age-grading biomarkers using the mark, release and recapture (MRR) method. The MRR method determined a good correspondence between actual and predicted age, and thus demonstrated the value of age classifications derived from the transcriptional profiling of these two genes. The technique was used to establish the age structure of mosquito populations from two malaria-endemic areas in western Kenya. The population age structure determined by the transcriptional profiling method was consistent with that based on mosquito parity. This study demonstrates that the transcription profiling method based on two genes is valuable for age determination of natural mosquitoes, providing a new approach for determining a key life history trait of malaria vectors. PMID:23936017

  20. Tumor Necrosis Adds Prognostically Significant Information to Grade in Clear Cell Renal Cell Carcinoma: A Study of 842 Consecutive Cases From a Single Institution.

    PubMed

    Khor, Li-Yan; Dhakal, Hari P; Jia, Xuefei; Reynolds, Jordan P; McKenney, Jesse K; Rini, Brian I; Magi-Galluzzi, Cristina; Przybycin, Christopher G

    2016-09-01

    Tumor necrosis has been shown to be an independent predictor of adverse outcome in renal cell carcinoma. A modification of the International Society of Urological Pathology (ISUP) grading system for renal cell carcinomas has recently been proposed, which incorporates the presence of tumor necrosis into grade. The investigators proposing this system found that necrosis added significant prognostic information to ISUP grade. We attempted to describe our experience with the effect of tumor necrosis in relationship to nuclear grade by reviewing the slides from a large consecutive series of localized clear cell renal cell carcinomas from our institution and obtaining long-term clinical follow-up information (overall survival). Of the 842 clear cell renal cell carcinomas reviewed, 265 (31.5%) were ISUP grade 1 or 2, 437 (51.9%) were ISUP grade 3, and 140 (16.6%) were ISUP grade 4. Tumor necrosis was present in 177 (21%) cases. Five hundred and forty-seven (64.9%) cases were stage pT1, 83 (9.9%) were stage pT2, 193 (22.9%) were stage pT3a, and 19 (2.3%) were pT3b or higher. Median follow-up was 73.2 months (range 0.12 to 273.6), and 310 (36.8%) patients died. On univariable analysis, there was no significant difference in outcome for tumors of ISUP grades 1 to 3. After adjustment for age, tumor stage, and tumor size, ISUP grade 4 and necrosis were significant predictors of overall survival on multivariable analysis. When the recently proposed modified grading system incorporating tumor necrosis was applied to our data, there was no significant difference in overall survival between patients with modified grade 1 tumors and those with modified grade 2 tumors (P=0.31); however, there was a statistically significant difference between patients with modified grade 1 or 2 tumors and those with modified grade 3 tumors (P=0.04),and a substantial difference in outcome between those with modified grade 3 and modified grade 4 tumors (P<0.001). When a recursive partitioning approach

  1. Epigenetic silencing of the kinase tumor suppressor WNK2 is tumor-type and tumor-grade specific

    PubMed Central

    Jun, Peter; Hong, Chibo; Lal, Anita; Wong, Judith M.; McDermott, Michael W.; Bollen, Andrew W.; Plass, Christoph; Held, William A.; Smiraglia, Dominic J.; Costello, Joseph F.

    2009-01-01

    Both genetic and epigenetic mechanisms contribute to meningioma development by altering gene expression and protein function. To determine the relative contribution of each mechanism to meningioma development, we used an integrative approach measuring copy number and DNA methylation changes genomewide. We found that genetic alterations affected 1.9%, 7.4%, and 13.3% of the 691 loci studied, whereas epigenetic mechanisms affected 5.4%, 9.9%, and 10.3% of these loci in grade I, II, and III meningiomas, respectively. Genetic and epigenetic mechanisms rarely involved the same locus in any given tumor. The predilection for epigenetic rather than genetic silencing was exemplified at the 5′ CpG island of WNK2, a serine-threonine kinase gene on chromosome 9q22.31. WNK2 is known to negatively regulate epidermal growth factor receptor signaling via inhibition of MEK1 (mitogen-activated protein kinase kinase 1), and point mutations have been reported in WNK1, WNK2, WNK3, and WNK4. In meningiomas, WNK2 was aberrantly methylated in 83% and 71% of grade II and III meningiomas, respectively, but rarely in a total of 209 tumors from 13 other tumor types. Aberrant methylation of the CpG island was associated with decreased expression in primary tumors. WNK2 could be reactivated with a methylation inhibitor in IOMM-Lee, a meningioma cell line with a densely methylated WNK2 CpG island and lack of WNK2 expression. Expression of exogenous WNK2 inhibited colony formation, implicating it as a potential cell growth suppressor. These findings indicate that epigenetic mechanisms are common across meningiomas of all grades and that for specific genes such as WNK2, epigenetic alteration may be the dominant, grade-specific mechanism of gene inactivation. PMID:19001526

  2. Age and sex graded helminth infections in a Nigerian village.

    PubMed

    Arinola, O; Fawole, O

    1995-02-01

    Prevalence of helminth parasites was carried out in both male and female villagers graded into three age groups (5-14 years, 15-25 years, 26-55 years). Children between 5 and 14 years of age had the highest prevalence of Ascaris, Schistosoma haematobium and Trichuris while the villagers between 26-55 years of age had lowest prevalence of these parasites. However, hookworms were highly common among the villagers aged between 26 and 55 years and least common among the school children aged between 5 and 14 years. Female children between the ages of 5 and 14 years and males of the same age group were highly infested with Ascaris and Trichuris. This finding in a Nigerian village suggested that helminth infestation is age and sex dependent which is therefore a factor of the frequency in host-parasite contact determined by mode of life of the parasites and the hosts. PMID:7796748

  3. Computer-Aided Assessment of Tumor Grade for Breast Cancer in Ultrasound Images

    PubMed Central

    2015-01-01

    This study involved developing a computer-aided diagnosis (CAD) system for discriminating the grades of breast cancer tumors in ultrasound (US) images. Histological tumor grades of breast cancer lesions are standard prognostic indicators. Tumor grade information enables physicians to determine appropriate treatments for their patients. US imaging is a noninvasive approach to breast cancer examination. In this study, 148 3-dimensional US images of malignant breast tumors were obtained. Textural, morphological, ellipsoid fitting, and posterior acoustic features were quantified to characterize the tumor masses. A support vector machine was developed to classify breast tumor grades as either low or high. The proposed CAD system achieved an accuracy of 85.14% (126/148), a sensitivity of 79.31% (23/29), a specificity of 86.55% (103/119), and an AZ of 0.7940. PMID:25810750

  4. Canine intracranial gliomas: Relationship between magnetic resonance imaging criteria and tumor type and grade

    PubMed Central

    Bentley, R.T.; Ober, C.P.; Anderson, K.L.; Feeney, D.A.; Naughton, J.F.; Ohlfest, J.R.; O’Sullivan, M.G.; Miller, M.A.; Constable, P.D.; Pluhar, G.E.

    2013-01-01

    Limited information is available to assist in the ante-mortem prediction of tumor type and grade for dogs with primary brain tumors. The objective of the current study was to identify magnetic resonance imaging (MRI) criteria related to the histopathological type and grade of gliomas in dogs. A convenience sample utilizing client-owned dogs (n=31) with gliomas was used. Medical records of dogs with intracranial lesions admitted to two veterinary referral hospitals were reviewed and cases with a complete brain MRI and definitive histopathological diagnosis were retrieved for analysis. Each MRI was independently interpreted by five investigators who were provided with standardized grading instructions and remained blinded to the histopathological diagnosis. Mild to no contrast enhancement, an absence of cystic structures (single or multiple), and a tumor location other than the thalamo-capsular region were independently associated with grade II tumors compared to higher grade tumors. In comparison to oligodendrogliomas, astrocytomas were independently associated with the presence of moderate to extensive peri-tumoral edema, a lack of ventricular distortion, and an isointense or hyperintense T1W-signal. When clinical and MRI features indicate that a glioma is most likely, certain MRI criteria can be used to inform the level of suspicion for low tumor grade, particularly poor contrast enhancement. Information obtained from the MRI of such dogs can also assist in predicting an astrocytoma or an oligodendroglioma, but no single imaging characteristic allows for a particular tumor type to be ruled out. PMID:24051197

  5. Evaluations of mosquito age grading techniques based on morphological changes.

    PubMed

    Hugo, L E; Quick-Miles, S; Kay, B H; Ryan, P A

    2008-05-01

    Evaluations were made of the accuracy and practicality of mosquito age grading methods based on changes to mosquito morphology; including the Detinova ovarian tracheation, midgut meconium, Polovodova ovariole dilatation, ovarian injection, and daily growth line methods. Laboratory maintained Aedes vigilax (Skuse) and Culex annulirostris (Skuse) females of known chronological and physiological ages were used for these assessments. Application of the Detinova technique to laboratory reared Ae. vigilax females in a blinded trial enabled the successful identification of nulliparous and parous females in 83.7-89.8% of specimens. The success rate for identifying nulliparous females increased to 87.8-98.0% when observations of ovarian tracheation were combined with observations of the presence of midgut meconium. However, application of the Polovodova method only enabled 57.5% of nulliparous, 1-parous, 2-parous, and 3-parous Ae. vigilax females to be correctly classified, and ovarian injections were found to be unfeasible. Poor correlation was observed between the number of growth lines per phragma and the calendar age of laboratory reared Ae. vigilax females. In summary, morphological age grading methods that offer simple two-category predictions (ovarian tracheation and midgut meconium methods) were found to provide high-accuracy classifications, whereas methods that offer the separation of multiple age categories (ovariolar dilatation and growth line methods) were found to be extremely difficult and of low accuracy. The usefulness of the morphology-based methods is discussed in view of the availability of new mosquito age grading techniques based on cuticular hydrocarbon and gene transcription changes. PMID:18533427

  6. Applications of a novel tumor-grading-metastasis staging system for pancreatic neuroendocrine tumors

    PubMed Central

    Yang, Min; Tan, Chun-Lu; Zhang, Yi; Ke, Neng-Wen; Zeng, Lin; Li, Ang; Zhang, Hao; Xiong, Jun-Jie; Guo, Zi-Heng; Tian, Bo-Le; Liu, Xu-Bao

    2016-01-01

    Abstract The ability to stratify patients with pancreatic neuroendocrine tumors (p-NETs) into prognostic groups has been hindered by the absence of a commonly accepted staging system. Both the 7th tumor-node-metastasis (TNM) staging guidelines by the American Joint Committee on Cancer (AJCC) and the 2010 grading classifications by the World Health Organization (WHO) were validated to be unsatisfactory. We aim to evaluate the feasibility of combining the latest AJCC and WHO criteria to devise a novel tumor-grading-metastasis (TGM) staging system. We also sought to examine the stage-specific survival rates and the prognostic value of this new TGM system for p-NETs. Data of 120 patients with surgical resection and histopathological diagnosis of p-NETs from January 2004 to February 2014 in our institution were retrospectively collected and analyzed. Based on the AJCC and WHO criteria, we replaced the stage N0 and N1 with stage Ga (NET G1 and NET G2) and Gb (NET G3 and MANEC) respectively, without changes of the definition of T or M stage. The present novel TGM staging system was grouped as follows: stage I was defined as T1–2, Ga, M0; stage II as T3, Ga, M0 or as T1–3, Gb, M0; stage III as T4, Ga–b, M0 and stage IV as any T, M1. The new TGM staging system successfully distributed 55, 42, 12, and 11 eligible patients in stage I to IV, respectively. Differences of survival compared stage I with III and IV for patients with p-NETs were both statistically significant (P < 0.001), as well as those of stage II with III and IV (P < 0.001). Patients in stage I showed better a survival than those in stage II, whereas difference between stages III and IV was not notable (P = 0.001, P = 0.286, respectively). In multivariate models, when the TGM staging system was evaluated in place of the individual T, G, and M variables, this new criteria were proven to be an independent predictor of survival for surgically resected p-NETs (P < 0.05). Stratifying patients well

  7. The Value of 5-Aminolevulinic Acid in Low-grade Gliomas and High-grade Gliomas Lacking Glioblastoma Imaging Features: An Analysis Based on Fluorescence, Magnetic Resonance Imaging, 18F-Fluoroethyl Tyrosine Positron Emission Tomography, and Tumor Molecular Factors

    PubMed Central

    Jaber, Mohammed; Wölfer, Johannes; Ewelt, Christian; Holling, Markus; Hasselblatt, Martin; Niederstadt, Thomas; Zoubi, Tarek; Weckesser, Matthias

    2015-01-01

    BACKGROUND: Approximately 20% of grade II and most grade III gliomas fluoresce after 5-aminolevulinic acid (5-ALA) application. Conversely, approximately 30% of nonenhancing gliomas are actually high grade. OBJECTIVE: The aim of this study was to identify preoperative factors (ie, age, enhancement, 18F-fluoroethyl tyrosine positron emission tomography [18F-FET PET] uptake ratios) for predicting fluorescence in gliomas without typical glioblastomas imaging features and to determine whether fluorescence will allow prediction of tumor grade or molecular characteristics. METHODS: Patients harboring gliomas without typical glioblastoma imaging features were given 5-ALA. Fluorescence was recorded intraoperatively, and biopsy specimens collected from fluorescing tissue. World Health Organization (WHO) grade, Ki-67/MIB-1 index, IDH1 (R132H) mutation status, O6-methylguanine DNA methyltransferase (MGMT) promoter methylation status, and 1p/19q co-deletion status were assessed. Predictive factors for fluorescence were derived from preoperative magnetic resonance imaging and 18F-FET PET. Classification and regression tree analysis and receiver-operating-characteristic curves were generated for defining predictors. RESULTS: Of 166 tumors, 82 were diagnosed as WHO grade II, 76 as grade III, and 8 as glioblastomas grade IV. Contrast enhancement, tumor volume, and 18F-FET PET uptake ratio >1.85 predicted fluorescence. Fluorescence correlated with WHO grade (P < .001) and Ki-67/MIB-1 index (P < .001), but not with MGMT promoter methylation status, IDH1 mutation status, or 1p19q co-deletion status. The Ki-67/MIB-1 index in fluorescing grade III gliomas was higher than in nonfluorescing tumors, whereas in fluorescing and nonfluorescing grade II tumors, no differences were noted. CONCLUSION: Age, tumor volume, and 18F-FET PET uptake are factors predicting 5-ALA-induced fluorescence in gliomas without typical glioblastoma imaging features. Fluorescence was associated with an increased

  8. Detection of Human Herpesvirus-6 Variants in Pediatric Brain Tumors: Association of Viral Antigen in Low Grade Gliomas

    PubMed Central

    Crawford, John R.; Santi, Maria R.; Thorarinsdottir, Halldora K.; Cornelison, Robert; Rushing, Elisabeth J.; Zhang, Huizhen; Yao, Karen; Jacobson, Steven; MacDonald, Tobey J.

    2009-01-01

    Background Human Herpesvirus-6 (HHV-6) has been associated with a diverse spectrum of central nervous system (CNS) diseases and reported glial tropism. Objective To determine if HHV-6 is present in a series of pediatric brain tumors. Study Design Pediatric gliomas from 88 untreated patients represented in a tissue microarray (TMA) were screened for HHV-6 by nested polymerase chain reaction (PCR), in situ hybridization (ISH), and immunohistochemistry (IHC) and compared to non glial tumors (N=22) and control brain (N=32). Results were correlated with tumor grade and overall survival. Results HHV-6 U57 was detected by nested PCR in 68/120 (57%) tumors and 7/32 (22%) age-matched non-tumor brain (P=0.001). HHV-6 U31 was positive in 73/120 (61%) tumors and 11/32 (34%) controls (P=0.019). Seventy-two percent (43/60) of tumors were HHV-6 Variant A. HHV-6 U57 was confirmed by ISH in 83/150 (54%) tumors and 10/32 (31%) controls (P=0.021), revealing a non-lymphocytic origin of HHV-6. HHV-6A/B gp116/64/54 late antigen was detected by IHC in 50/124 (40%) tumors and 6/32 (18%) controls (P=0.013). Interestingly, 58% of low grade gliomas (N=67) were IHC positive compared to 19% of high grade gliomas (N=21, P=0.002) and 25% of non gliomas (N=36; P=0.001). HHV-6A/B gp116/64/54 antigen co-localized with glial fibrillary acidic protein, confirming the astrocytic origin of antigen. Overall, there was no primary association between HHV-6A/B gp116/64/54 antigen detection and survival (P=0.861). Conclusions We provide the first reported series of HHV-6 detection in pediatric brain tumors. The predominance of HHV-6 in glial tumors warrants further investigation into potential neurooncologic disease mechanisms. PMID:19505845

  9. Noninvasive magnetic resonance spectroscopic imaging biomarkers to predict the clinical grade of pediatric brain tumors.

    PubMed

    Astrakas, Loukas G; Zurakowski, David; Tzika, A Aria; Zarifi, Maria K; Anthony, Douglas C; De Girolami, Umberto; Tarbell, Nancy J; Black, Peter McLaren

    2004-12-15

    The diagnosis and therapy of childhood brain tumors, most of which are low grade, can be complicated because of their frequent adjacent location to crucial structures, which limits diagnostic biopsy. Also, although new prognostic biomarkers identified by molecular analysis or DNA microarray gene profiling are promising, they too depend on invasive biopsy. Here, we test the hypothesis that combining information from biologically important intracellular molecules (biomarkers), noninvasively obtained by proton magnetic resonance spectroscopic imaging, will increase the diagnostic accuracy in determining the clinical grade of pediatric brain tumors. We evaluate the proton magnetic resonance spectroscopic imaging exams for 66 children with brain tumors. The intracellular biomarkers for choline-containing compounds (Cho), N-acetylaspartate, total creatine, and lipids and/or lactate were measured at the highest Cho region and normalized to the surrounding healthy tissue total creatine. Neuropathological grading was done with WHO criteria. Normalized Cho and lipids and/or lactate were elevated in high-grade (n = 23) versus low-grade (n = 43) tumors, which multiple logistic regression confirmed are independent predictors of tumor grade (for Cho, odds ratio 24.8, P < 0.001; and for lipids and/or lactate, odds ratio 4.4, P < 0.001). A linear combination of normalized Cho and lipids and/or lactate that maximizes diagnostic accuracy was calculated by maximizing the area under the receiver operating characteristic curve. Proton magnetic resonance spectroscopic imaging, although not a proxy for histology, provides noninvasive, in vivo biomarkers for predicting clinical grades of pediatric brain tumors. PMID:15623597

  10. Inactivated autograft–prosthesis composite have a role for grade III giant cell tumor of bone around the knee

    PubMed Central

    2013-01-01

    Background Giant cell tumors (GCT) around the knee are common and pose a special problem of reconstruction after tumor excision, especially for grade III GCT. We questioned whether en bloc resection and reconstruction with alcohol inactivated autograft-prosthesis composite would provide (1) local control and long-term survival and (2) useful limb function in patients who had grade III GCT around the knee. Methods We retrospectively reviewed eight patients (5 males and 3 females) treated with this procedure with mean age of 31 years (range 20 to 43 years) from Jan 2007 to Oct 2008. 5 lesions were located in distal femur and 3 in proximal tibia. 4 patients were with primary tumor and the other 4 with recurrence. 2 patients showed pathological fracture. Results Mean Follow-up is 54 months ranging from 38 to 47 months. No recurrence, metastasis, prosthesis loosening were found. The mean healing time between autograft and host bone was 5.5 months. The mean MSTS score was 26.3 (88%) ranging from 25 to 29. The mean ISOLS composite graft score was 32.8 (88.5%) ranging from 28 to 35. Creeping substitution is possibly the main way in bony junction. The healing time in femoral lesion is faster than that in tibial lesion. Conclusions The technique of alcohol inactivated autograft-prosthesis composite could be able to achieve satisfactory oncological and functional outcomes in Grade III GCT. PMID:24209887

  11. Villous Tumor of the Urinary Bladder Resembling Low-grade Mucinous Neoplasm of the Appendix

    PubMed Central

    Ito, Ayako; Sakura, Yuma; Sugimoto, Mikio; Kakehi, Yoshiyuki; Kuroda, Naoto

    2016-01-01

    Mucinous neoplasms of the urinary tract are very rare. We present a 63-year-old-women who had a sessile papillary villous tumor in urinary bladder. Although transurethral resection of the bladder tumor (TURBT) was performed, the villous tumor repetitively recurred and gradually spread to the entire surface of bladder lumen. Histopathologic and immunohistochemical examination showed that the lesion was very similar to low-grade mucinous neoplasm arising in appendix vermiformis. There are no reports on appendiceal metaplasia of urinary bladder mucosa. In this case, we describe this unprecedented neoplasm as “villous tumor of the urinary bladder resembling low-grade mucinous neoplasm of the appendix.” PMID:27169015

  12. Distinct types of tumors exhibit differential grade of inflammation and angiogenesis in mice.

    PubMed

    Viana, C T R; Campos, P P; Carvalho, L A; Cenedezi, J M; Lavall, L; Lopes, M T P; Ferreira, M A N D; Andrade, S P

    2013-03-01

    Inflammation, angiogenesis and cytokine production are common features of almost, if not all tumors. However, the extent of these processes induced by different types of tumors has not been evaluated. We investigated the growth pattern of the experimental metastatic tumors, B16F10 melanoma, CT26.WT colon and 4T1 mammary cells inoculated in the flank of syngeneic mice and determined the degree of inflammation, angiogenesis, and production level of pro-inflammatory and pro-angiogenic cytokines within the tumors. In addition, we have analyzed vascular changes in the interface between the tumors and the adjacent cutaneous tissue and levels of relevant pro-inflammatory and pro-angiogenic cytokines systemically. The weight of tumors 15 days post-inoculation of 10(6) cells was markedly different. Melanomas were 2 and 10-fold heavier than colon and mammary tumors, respectively. Locally, CT26.WT tumor cells induced more vessels in cutaneous tissue adjacent to the tumors but systemically, the plasma levels of VEGF were higher (approximately 2-fold) in 4T1 tumor-bearing mice compared with the other two tumors. Mammary tumors presented the most prominent inflammatory content as assessed by a range of markers (inflammatory enzymes and cytokines). The vascular index, as determined by the intra-tumor amount of hemoglobin and number of vessels in hot spot areas, was also higher (approximately 2-fold) in melanomas compared with the other two tumors. These findings showing that distinct tumor types determine differential grade of inflammation, angiogenesis and host interaction in mice may provide new insights to tailor differential therapeutic approach based on the status of tumor biomarkers. PMID:23253264

  13. Toppling high-grade pulmonary neuroendocrine tumors with a DLL3-targeted trojan horse.

    PubMed

    Dylla, Scott J

    2016-03-01

    Delta-like protein 3 (DLL3) is a novel and tractable tumor-initiating cell-associated target for the antibody-drug conjugate SC16LD6.5 in high-grade pulmonary neuroendocrine tumors. Elevated expression of DLL3, an inhibitor of Notch pathway activation, marks the second recent observation that impairment of Notch receptor signaling may play a critical role in neuroendocrine tumorigenesis. PMID:27308627

  14. Grading and Reporting Student Progress in an Age of Standards.

    ERIC Educational Resources Information Center

    Trumbull, Elise, Ed.; Farr, Beverly, Ed.

    The essays in this collection offer a comprehensive analysis of the challenges of communicating effectively about student achievement. Discussions of concepts related to grading and reporting progress are mixed with practical advice. The chapters are: (1) "Grading Practices; An Overview of the Issues" (Beverly P. Farr); (2) "Why Do We Grade--and…

  15. Central nervous system tumors in chinese children under the age of 3: a population study.

    PubMed

    Liu, Anthony Pak-Yin; Shing, Matthew Ming-Kong; Yuen, Hui-Leung; Li, Chak-Ho; Ling, Siu-Cheung; Luk, Chung-Wing; Ha, Shau-Yin; Li, Chi-Kong; Chan, Godfrey Chi-Fung

    2015-03-01

    The management of central nervous system tumors in children below the age of 3 years represents a special challenge to pediatric oncologists with distinctive epidemiology, treatment considerations, and prognosis. Population-based epidemiological data on this particular patient group is lacking in Chinese. We reviewed the population-based pediatric tumor registry in Hong Kong between 1999 and 2011. Eighty-one children with primary central nervous system tumors from 0 to 3 years of age were identified (annual incidence: 4.16 cases per 100,000). Forty-one (50.6%) were male and the mean duration of follow-up was 94 months (±8.1). Primary tumors were infratentorial in 43 (53.1%). The tumor types in decreasing frequency were astrocytoma (n=17), medulloblastoma (n=16), ependymoma (n=13), choroid plexus tumor (n=7), primitive neuroectodermal tumor (n=7), atypical teratoid rhabdoid tumor (n=6), germ cell tumor (GCT, n=5), craniopharyngioma (n=4), and ganglioglioma (n=3). Three patients presented antenatally. Treatment included surgery in 82.7%, chemotherapy in 50.6%, and radiotherapy in 25.9%. There were 29 deaths (35.8%) and 19 relapses (23.5%) during the review period with the 1-year overall survival (OS), 5-year OS, 1-year event-free survival (EFS), and 5-year EFS being 79.4% (±4.6), 63.5% (±5.9), 68.9% (±5.3), and 52.5% (±5.9), respectively. Significantly better OS and EFS were observed in patients who received gross total resection, but those with high-grade tumors, antenatal diagnosis, or atypical teratoid rhabdoid tumor/primitive neuroectodermal tumor had worse outcome. Survival did not differ with age. Comparison with statistics from other studies revealed higher rates of embryonal tumor, GCT, and craniopharyngioma in Hong Kong Chinese. Disease outcome appeared to be better in our cohort comparing to previous reports probably due to the higher proportion of GCT locally. PMID:24608077

  16. Flotillin-1 protein is upregulated in human endometrial cancer and localization shifts from epithelial to stromal with increasing tumor grade.

    PubMed

    Winship, Amy Louise; Rainczuk, Kate; Dimitriadis, Evdokia

    2016-01-01

    Endometrial cancer is the most common invasive gynecological malignancy. Flotillin-1 is an integral membrane protein and estrogen responsive gene. Flotillin-1 expression and localization in human endometrial cancers grades 1-3 was investigated using real-time RT-PCR and immunohistochemistry. Flotillin-1 mRNA levels were unchanged in endometrial cancer versus benign endometrium. Flotillin-1 protein was significantly reduced in the epithelial compartment with increasing tumor grade, although levels increased in the tumor stroma across grades. We have identified a novel factor in human endometrial cancer and observed a shift in epithelial to stromal localization with increasing tumor grade in women. PMID:26682635

  17. Oncocytoma-Like Renal Tumor With Transformation Toward High-Grade Oncocytic Carcinoma

    PubMed Central

    Sirintrapun, Sahussapont J.; Geisinger, Kim R.; Cimic, Adela; Snow, Anthony; Hagenkord, Jill; Monzon, Federico; Legendre, Benjamin L.; Ghazalpour, Anatole; Bender, Ryan P.; Gatalica, Zoran

    2014-01-01

    Abstract Renal oncocytoma is a benign tumor with characteristic histologic findings. We describe an oncocytoma-like renal tumor with progression to high-grade oncocytic carcinoma and metastasis. A 74-year-old man with no family history of cancer presented with hematuria. Computed tomography showed an 11 cm heterogeneous multilobulated mass in the right kidney lower pole, enlarged aortocaval lymph nodes, and multiple lung nodules. In the nephrectomy specimen, approximately one third of the renal tumor histologically showed regions classic for benign oncocytoma transitioning to regions of high-grade carcinoma without sharp demarcation. With extensive genomic investigation using single nucleotide polymorphism-based array virtual karyotyping, multiregion sequencing, and expression array analysis, we were able to show a common lineage between the benign oncocytoma and high-grade oncocytic carcinoma regions in the tumor. We were also able to show karyotypic differences underlying this progression. The benign oncocytoma showed no chromosomal aberrations, whereas the high-grade oncocytic carcinoma showed loss of the 17p region housing FLCN (folliculin [Birt–Hogg–Dubé protein]), loss of 8p, and gain of 8q. Gene expression patterns supported dysregulation and activation of phosphoinositide 3-kinase (PI3K)/v-akt murine thymoma viral oncogene homolog (Akt), mitogen-activated protein kinase (MAPK)/extracellular-signal-regulated kinase (ERK), and mechanistic target of rapamycin (serine/threonine kinase) (mTOR) pathways in the high-grade oncocytic carcinoma regions. This was partly attributable to FLCN underexpression but further accentuated by overexpression of numerous genes on 8q. In the high-grade oncocytic carcinoma region, vascular endothelial growth factor A along with metalloproteinases matrix metallopeptidase 9 and matrix metallopeptidase 12 were overexpressed, facilitating angiogenesis and invasiveness. Genetic molecular testing provided evidence for the

  18. Diffusion-Weighted Imaging in Meningioma: Prediction of Tumor Grade and Association with Histopathological Parameters12

    PubMed Central

    Surov, Alexey; Gottschling, Sebastian; Mawrin, Christian; Prell, Julian; Spielmann, Rolf Peter; Wienke, Andreas; Fiedler, Eckhard

    2015-01-01

    OBJECTIVES: To analyze diffusion-weighted imaging (DWI) findings of meningiomas and to compare them with tumor grade, cell count, and proliferation index and to test a possibility of use of apparent diffusion coefficient (ADC) to differentiate benign from atypical/malignant tumors. METHODS: Forty-nine meningiomas were analyzed. DWI was done using a multislice single-shot echo-planar imaging sequence. A polygonal region of interest was drawn on ADC maps around the margin of the lesion. In all lesions, minimal ADC values (ADCmin) and mean ADC values (ADCmean) were estimated. Normalized ADC (NADC) was calculated in every case as a ratio ADCmean meningioma/ADCmean white matter. All meningiomas were surgically resected and analyzed histopathologically. The tumor proliferation index was estimated on Ki-67 antigen–stained specimens. Cell density was calculated. Collected data were evaluated by means of descriptive statistics. Analyses of ADC/NADC values were performed by means of two-sided t tests. RESULTS: The mean ADCmean value was higher in grade I meningiomas in comparison to grade II/III tumors (0.96 vs 0.80 × 10− 3 mm2s− 1, P = .006). Grade II/III meningiomas showed lower NADC values in comparison to grade I tumors (1.05 vs 1.26, P = .015). There was no significant difference in ADCmin values between grade I and II/III tumors (0.69 vs 0.63 × 10− 3 mm2s− 1, P = .539). The estimated cell count varied from 486 to 2091 (mean value, 1158.20 ± 333.74; median value, 1108). There were no significant differences in cell count between grade I and grade II/III tumors (1163.93 vs 1123.86 cells, P = .77). The mean level of the proliferation index was 4.78 ± 5.08%, the range was 1% to 18%, and the median value was 2%. The proliferation index was statistically significant higher in grade II/III meningiomas in comparison to grade I tumors (15.43% vs 3.00%, P = .001). Ki-67 was negatively associated with ADCmean (r = − 0.61, P < .001) and NADC (r = − 0.60, P

  19. Predominance of M2-polarized macrophages in bladder cancer affects angiogenesis, tumor grade and invasiveness

    PubMed Central

    TAKEUCHI, HISASHI; TANAKA, MICHIO; TANAKA, AYAKO; TSUNEMI, AKISA; YAMAMOTO, HIDENOBU

    2016-01-01

    Tumor-associated macrophages (TAMs) often assume an immunoregulatory M2 phenotype. Thus, the aim of the present study was to clarify the correlation of vascularity and TAMs, in particular the M2 phenotype in the stroma and tumor areas, with the clinical and pathological outcomes of patients with bladder cancer. The TAM counts and microvessel counts (MVCs) were determined immunohistochemically in 21 patients with bladder cancer. The number of infiltrating TAMs was measured using immunohistochemistry with anti-cluster of differentiation (CD)68 and anti-CD163 antibodies, to identify a macrophage lineage marker and an M2-polarized-specific cell surface receptor, respectively. CD68+ and CD163+ macrophages were evaluated in the stroma and tumor areas, and areas with a high density of infiltrating cell spots were counted. MVCs were determined using immunohistochemistry with anti-CD34 antibodies. The results revealed that the higher ratio of CD163+/CD68+ macrophages in the stroma, tumor and total tumor tissues were correlated with a higher stage and grade (P<0.05). In addition, the low ratio of CD68+/CD34+ microvessels was correlated with a higher stage (P<0.05). There was also a positive correlation between TAMs and MVC (r2=0.25; P<0.05). These results suggest that the TAM polarized M2 phenotype affects microvessels, pathological outcome, tumor grade and invasiveness. PMID:27123124

  20. TRAIL Death Receptor-4 Expression Positively Correlates With the Tumor Grade in Breast Cancer Patients With Invasive Ductal Carcinoma

    SciTech Connect

    Sanlioglu, Ahter D.; Korcum, Aylin F.; Pestereli, Elif; Erdogan, Gulgun; Karaveli, Seyda; Savas, Burhan; Griffith, Thomas S.; Sanlioglu, Salih V.

    2007-11-01

    Purpose: Tumor necrosis factor-related apoptosis inducing ligand (TRAIL) selectively induces apoptosis in cancer cells but not in normal cells, and a number of clinical trials have recently been initiated to test the safety and antitumoral potential of TRAIL in cancer patients. Four different receptors have been identified to interact with TRAIL: two are death-inducing receptors (TRAIL-R1 [DR4] and TRAIL-R2 [DR5]), whereas the other two (TRAIL-R3 [DcR1] and TRAIL-R4 [DcR2]) do not induce death upon ligation and are believed to counteract TRAIL-induced cytotoxicity. Because high levels of DcR2 expression have recently been correlated with carcinogenesis in the prostate and lung, this study investigated the importance of TRAIL and TRAIL receptor expression in breast cancer patients with invasive ductal carcinoma, taking various prognostic markers into consideration. Methods and Materials: Immunohistochemical analyses were performed on 90 breast cancer patients with invasive ductal carcinoma using TRAIL and TRAIL receptor-specific antibodies. Age, menopausal status, tumor size, lymph node status, tumor grade, lymphovascular invasion, perineural invasion, extracapsular tumor extension, presence of an extensive intraductal component, multicentricity, estrogen and progesterone receptor status, and CerbB2 expression levels were analyzed with respect to TRAIL/TRAIL receptor expression patterns. Results: The highest TRAIL receptor expressed in patients with invasive ductal carcinoma was DR4. Although progesterone receptor-positive patients exhibited lower DR5 expression, CerbB2-positive tissues displayed higher levels of both DR5 and TRAIL expressions. Conclusions: DR4 expression positively correlates with the tumor grade in breast cancer patients with invasive ductal carcinoma.

  1. Ovarian Yolk Sac Tumor With High-Grade Serous Carcinoma in a 62-Year-Old Woman.

    PubMed

    McCarthy, Whitney A; Masand, Ramya P

    2016-06-01

    Ovarian yolk sac tumors are germ cell tumors that usually present in children and young women. Rarely, these tumors can arise in older women, usually in conjunction with surface epithelial tumors, suggesting divergent differentiation from the latter. The combination of mixed ovarian yolk sac tumor and high-grade serous carcinoma is rare, with only one case documented in the literature. We present a case of mixed ovarian yolk sac tumor and high-grade serous carcinoma in a postmenopausal woman, including a brief discussion of the immunohistochemical findings and differential diagnosis. Despite the rarity of mixed ovarian yolk sac tumor and surface epithelial tumors, it is important to recognize the biphasic nature of the tumor, which should prompt a thorough immunohistochemical evaluation. The therapeutic and prognostic implications of proper diagnosis cannot be overemphasized. PMID:26782153

  2. Translationally Controlled Tumor Protein in Prostatic Adenocarcinoma: Correlation with Tumor Grading and Treatment-Related Changes

    PubMed Central

    Rocca, Bruno Jim; Ginori, Alessandro; Barone, Aurora; Calandra, Calogera; Crivelli, Filippo; De Falco, Giulia; Gazaneo, Sara; Tripodi, Sergio; Cevenini, Gabriele; del Vecchio, Maria Teresa; Ambrosio, Maria Raffaella; Tosi, Piero

    2015-01-01

    Prostate cancer is the second leading cause of cancer-related death. The androgen deprivation therapy is the standard treatment for advanced stages. Unfortunately, virtually all tumors become resistant to androgen withdrawal. The progression to castration-resistance is not fully understood, although a recent paper has suggested translationally controlled tumor protein to be implicated in the process. The present study was designed to investigate the role of this protein in prostate cancer, focusing on the correlation between its expression level with tumor differentiation and response to treatment. We retrieved 292 prostatic cancer specimens; of these 153 had been treated only by radical prostatectomy and 139 had undergone radical prostatectomy after neoadjuvant treatment with combined androgen blockade therapy. Non-neoplastic controls were represented by 102 prostatic peripheral zone specimens. In untreated patients, the expression of the protein, evaluated by RT-qPCR and immunohistochemistry, was significantly higher in tumor specimens than in non-neoplastic control, increasing as Gleason pattern and score progressed. In treated prostates, the staining was correlated with the response to treatment. An association between protein expression and the main clinicopathological factors involved in prostate cancer aggressiveness was identified. These findings suggest that the protein may be a promising prognostic factor and a target for therapy. PMID:25667934

  3. What Is the Ideal Tumor Regression Grading System in Rectal Cancer Patients after Preoperative Chemoradiotherapy?

    PubMed Central

    Kim, Soo Hee; Chang, Hee Jin; Kim, Dae Yong; Park, Ji Won; Baek, Ji Yeon; Kim, Sun Young; Park, Sung Chan; Oh, Jae Hwan; Yu, Ami; Nam, Byung-Ho

    2016-01-01

    Purpose Tumor regression grade (TRG) is predictive of therapeutic response in rectal cancer patients after chemoradiotherapy (CRT) followed by curative resection. However, various TRG systems have been suggested, with subjective categorization, resulting in interobserver variability. This study compared the prognostic validity of four different TRG systems in order to identify the most ideal TRG system. Materials and Methods This study included 933 patients who underwent preoperative CRT and curative resection. Primary tumors alone were graded according to the American Joint Committee on Cancer (AJCC), Dworak, and Ryan TRG systems, and both primary tumors and regional lymph nodes were graded according to a modified Dworak TRG system. The ability of each TRG system to predict recurrence-free survival (RFS) and overall survival (OS) was analyzed using chi-square and C statistics. Results All four TRG systems were significantly predictive of both RFS and OS (p < 0.001 each), however none was a better predictor of prognosis than ypStage. Among the four TRGs, the mDworak TRG system was a better predictor of RFS and OS than the AJCC, Dworak, and Ryan TRG systems, and both the chi-square and C statistics were higher for the former, although the differences were not statistically significant. The combination of ypStage and the modified Dworak TRG better predicted RFS and OS than ypStage alone. Conclusion The modified Dworak TRG system for evaluation of entire tumors including regional lymph nodes is a better predictor of survival than current TRG systems for evaluation of the primary tumor alone. PMID:26511803

  4. Effect of rotation age on lumber grade, yield, and strength of unthinned loblolly pine

    SciTech Connect

    Clark, A.; McAlister, R.H.; Saucier, J.R.; Reitter, K.

    1996-01-01

    This study examines the effect of rotation age on the grade, yield, and strength of lumber produced from unthinned loblolly pine stands in the coastal plain of Georgia. Six stands representing 22-, 28-, and 40-year rotations were sampled. A stratified random sample of trees with diameters at breast height ranging from 8 to 16 inches was selected from each stand and processed into limber. The strength, yield, and grade of lumber produced increased with increasing rotation age. Based on study data, equations were developed to predict total lumber volume, lumber volume by lumber grade, sawlog stem weight, and cubic volume. Because the yeild of higher grade lumber increased in older trees, the value of lumber produced per cubic foot increased significantly with increasing age. A financial analysis of a simulated plantation harvested at ages ranging from 20 to 40 years illustrates the effects of increasing lumber value and rotation age on net present value of an unthinned loblolly pine stand.

  5. Tumor Grade

    MedlinePlus

    ... Caregivers Questions to Ask about Advanced Cancer Research Managing Cancer Care Finding Health Care Services Advance Directives ... Feelings Planning for Advanced Cancer Advanced Cancer & Caregivers Managing Cancer Care Finding Health Care Services Advance Directives ...

  6. Relationship of Age for Grade and Pubertal Stage to Early Initiation of Substance Use

    PubMed Central

    Chung, Paul J.; Elliott, Marc N.; Davies, Susan L.; Tortolero, Susan; Baumler, Elizabeth; Banspach, Stephen W.; Schuster, Mark A.

    2015-01-01

    Introduction Studies suggest students who are substantially older than the average age for their grade engage in risky health behaviors, including substance use. However, most studies do not account for the distinct reasons why students are old for their grade (ie, grade retention vs delayed school entry) or for their pubertal stage. Thus, whether the association between age for grade and substance use is confounded by these factors is unknown. We sought to determine whether age, grade, or pubertal stage were associated with early substance use. Methods Cross-sectional Healthy Passages Wave I survey data from 5,147 fifth graders and their caregivers in Alabama, California, and Texas from 2004 through 2006 were analyzed in 2014. Logistic regressions examined whether older age for grade, grade retention, delayed school entry, or pubertal stage were associated with use of any substance, cigarettes, alcohol, or other drugs. Results Seventeen percent of fifth graders reported trying at least 1 substance. Among boys, advanced pubertal stage was associated with increased odds of cigarette, alcohol, or other drug use, whereas delayed school entry was associated with lower odds of any substance, alcohol, or other drug use. Among girls, advanced pubertal stage was associated only with higher odds of alcohol use, and delayed school entry was not associated with substance use. Neither older age for grade or grade retention was independently associated with substance use after controlling for potential confounders. Conclusion Advanced pubertal stage may be a more important risk factor for substance use than age for grade. Pediatricians should consider initiating substance use screening earlier for patients with advanced pubertal stage. PMID:26583575

  7. Factors Influencing Neurocognitive Outcomes in Young Patients With Benign and Low-Grade Brain Tumors Treated With Stereotactic Conformal Radiotherapy

    SciTech Connect

    Jalali, Rakesh; Mallick, Indranil; Dutta, Debnarayan

    2010-07-15

    Purpose: To present the effect of radiotherapy doses to different volumes of normal structures on neurocognitive outcomes in young patients with benign and low-grade brain tumors treated prospectively with stereotactic conformal radiotherapy (SCRT). Methods and Materials: Twenty-eight patients (median age, 13 years) with residual/progressive brain tumors (10 craniopharyngioma, 8 cerebellar astrocytoma, 6 optic pathway glioma and 4 cerebral low-grade glioma) were treated with SCRT to a dose of 54 Gy in 30 fractions over 6 weeks. Prospective neuropsychological assessments were done at baseline before RT and at subsequent follow-up examinations. The change in intelligence quotient (IQ) scores was correlated with various factors, including dose-volume to normal structures. Results: Although the overall mean full-scale IQ (FSIQ) at baseline before RT remained unchanged at 2-year follow-up after SCRT, one third of patients did show a >10% decline in FSIQ as compared with baseline. Logistic regression analysis demonstrated that patients aged <15 years had a significantly higher chance of developing a >10% drop in FSIQ than older patients (53% vs. 10%, p = 0.03). Dosimetric comparison in patients showing a >10% decline vs. patients showing a <10% decline in IQ revealed that patients receiving >43.2 Gy to >13% of volume of the left temporal lobe were the ones to show a significant drop in FSIQ (p = 0.048). Radiotherapy doses to other normal structures, including supratentorial brain, right temporal lobe, and frontal lobes, did not reveal any significant correlation. Conclusion: Our prospectively collected dosimetric data show younger age and radiotherapy doses to left temporal lobe to be predictors of neurocognitive decline, and may well be used as possible dose constraints for high-precision radiotherapy planning.

  8. Language Learning Strategies, Course Grades, and Age in EFL Secondary School Learners

    ERIC Educational Resources Information Center

    Tragant, Elsa; Victori, Mia

    2012-01-01

    In studies dealing with language learning strategies in the school context, the variables of proficiency and age are often difficult to isolate since students accumulate more hours of foreign language instruction as they move up from grade to grade. This study aimed to deal with these two variables independently by analysing learning strategy use…

  9. Teacher Views about the Starting Age of the First Grade Elementary School

    ERIC Educational Resources Information Center

    Ari, Asim

    2014-01-01

    This research critically investigated the implementation in Turkey of starting elementary-school first grade at age 5 (60 months) according to teacher feedback. While the study is designed as qualitative, a kind of single case study approach is used with a group of 50 volunteer first-grade teachers serving in 15 elementary schools in the Eskisehir…

  10. Analysis of EZH2: micro-RNA network in low and high grade astrocytic tumors.

    PubMed

    Sharma, Vikas; Purkait, Suvendu; Takkar, Sonam; Malgulwar, Prit Benny; Kumar, Anupam; Pathak, Pankaj; Suri, Vaishali; Sharma, Mehar C; Suri, Ashish; Kale, Shashank Sharad; Kulshreshtha, Ritu; Sarkar, Chitra

    2016-04-01

    Enhancer of Zeste homologue2 (EZH2) is an epigenetic regulator that functions as oncogene in astrocytic tumors, however, EZH2 regulation remains little studied. In this study, we measured EZH2 levels in low (Gr-II,DA) and high grade (Gr-IV,GBM) astrocytic tumors and found significant increased EZH2 transcript level with grade(median DA-8.5, GBM-28.9).However, a different trend was reflected in protein levels, with GBMs showing high EZH2 LI(median-26.5) compared to DA (median 0.3). This difference in correlation of EZH2 protein and RNA levels suggested post-transcriptional regulation of EZH2, likely mediated by miRNAs. We selected eleven miRNAs that strongly predicted to target EZH2 and measured their expression. Three miRNAs (miR-26a-5p,miR27a-3p and miR-498) showed significant correlation with EZH2 protein, suggesting them as regulators of EZH2, however miR-26a-5p levels decreased with grade. ChIP analyses revealed H3K27me3 modifications in miR-26a promoter suggesting feedback loop between EZH2 and miR26a. We further measured six downstream miRNA targets of EZH2 and found significant downregulation of four (miR-181a/b and 200b/c) in GBM. Interestingly, EZH2 associated miRNAs were predicted to target 25 genes in glioma-pathway, suggesting their role in tumor formation or progression. Collectively, our work suggests EZH2 and its miRNA interactors may serve as promising biomarkers for progression of astrocytic tumors and may offer novel therapeutic strategies. PMID:26746204

  11. World Health Organization grade II-III astrocytomas consist of genetically distinct tumor lineages.

    PubMed

    Hattori, Natsuki; Hirose, Yuichi; Sasaki, Hikaru; Nakae, Shunsuke; Hayashi, Saeko; Ohba, Shigeo; Adachi, Kazuhide; Hayashi, Takuro; Nishiyama, Yuya; Hasegawa, Mitsuhiro; Abe, Masato

    2016-08-01

    Recent investigations revealed genetic analysis provides important information in management of gliomas, and we previously reported grade II-III gliomas could be classified into clinically relevant subgroups based on the DNA copy number aberrations (CNAs). To develop more precise genetic subgrouping, we investigated the correlation between CNAs and mutational status of the gene encoding isocitrate dehydrogenase (IDH) of those tumors. We analyzed the IDH status and CNAs of 174 adult supratentorial gliomas of astrocytic or oligodendroglial origin by PCR-based direct sequencing and comparative genomic hybridization, respectively. We analyzed the relationship between genetic subclassification and clinical features. We found the most frequent aberrations in IDH mutant tumors were the combined whole arm-loss of 1p and 19q (1p/19q codeletion) followed by gain on chromosome arm 7q (+7q). The gain of whole chromosome 7 (+7) and loss of 10q (-10q) were detected in IDH wild-type tumors. Kaplan-Meier estimates for progression-free survival showed that the tumors with mutant IDH, -1p/19q, or +7q (in the absence of +7p) survived longer than tumors with wild-type IDH, +7, or -10q. As tumors with +7 (IDH wild-type) showed a more aggressive clinical nature, they are probably not a subtype that developed from the slowly progressive tumors with +7q (IDH mutant). Thus, tumors with a gain on chromosome 7 (mostly astrocytic) comprise multiple lineages, and such differences in their biological nature should be taken into consideration during their clinical management. PMID:27196377

  12. Site-specific tumor grading system in colorectal cancer: multicenter pathologic review of the value of quantifying poorly differentiated clusters.

    PubMed

    Ueno, Hideki; Hase, Kazuo; Hashiguchi, Yojiro; Shimazaki, Hideyuki; Tanaka, Masafumi; Miyake, Ohki; Masaki, Tadahiko; Shimada, Yoshifumi; Kinugasa, Yusuke; Mori, Yoshiyuki; Kishimoto, Mitsuo; Kameoka, Shingo; Sato, Yu; Matsuda, Keiji; Nakadoi, Koichi; Shinto, Eiji; Nakamura, Takahiro; Sugihara, Kenichi

    2014-02-01

    The study aimed to determine the value of a novel site-specific grading system based on quantifying poorly differentiated clusters (PDC; Grade(PDC)) in colorectal cancer (CRC). A multicenter pathologic review involving 12 institutions was performed on 3243 CRC cases (stage I, 583; II, 1331; III, 1329). Cancer clusters of ≥5 cancer cells and lacking a gland-like structure (PDCs) were counted under a ×20 objective lens in a field containing the maximum clusters. Tumors with <5, 5 to 9, and ≥10 PDCs were classified as grades G1, G2, and G3, respectively. According to Grade(PDC), 1594, 1005, and 644 tumors were classified as G1, G2, and G3 and had 5-year recurrence-free survival rates of 91.6%, 75.4%, and 59.6%, respectively (P<0.0001). Multivariate analysis showed that Grade exerted an influence on prognostic outcome independently of TNM staging; approximately 20% and 46% of stage I and II patients, respectively, were selected by Grade(PDC) as a population whose survival estimate was comparable to or even worse than that of stage III patients. Grade(PDC) surpassed TNM staging in the ability to stratify patients by recurrence-free survival (Akaike information criterion, 2915.6 vs. 2994.0) and had a higher prognostic value than American Joint Committee on Cancer (AJCC) grading (Grade(AJCC)) at all stages. Regarding judgment reproducibility of grading tumors, weighted κ among the 12 institutions was 0.40 for Grade(AJCC) and 0.52 for Grade(PDC). Grade(PDC) has a robust prognostic power and promises to be of sufficient clinical value to merit implementation as a site-specific grading system in CRC. PMID:24418853

  13. The Age Grading of Physical Activity among Children.

    ERIC Educational Resources Information Center

    Ostrow, Andrew C.; And Others

    1987-01-01

    Preschool children (N=102) viewed sex facial pictures of two fictitiously aged adults and then rated competence of the adults on six physical activities. Children's assessments of the competence of adult participation in physical activity were largely dictated by their perceptions of the adult's age. Adults perceived as older were rated as less…

  14. Can PPH3 be helpful to assess the discordant grade in primary and metastatic enteropancreatic neuroendocrine tumors?

    PubMed

    Dumars, Clotilde; Foubert, Fanny; Touchefeu, Yann; Regenet, Nicolas; Senellart, Hélène; Matysiak-Budnik, Tamara; Heymann, Marie-Françoise

    2016-08-01

    Therapeutic strategy in neuroendocrine tumors (NETs) is based on histological characteristics of the primary tumor (PT), even in case of metastatic disease. Our aim was to compare the tumor grade between PT and their liver metastases (LM) in patients with enteropancreatic NETs. Forty-one patients treated for sporadic NETs (10 pancreatic, 31 intestinal) were included. All presented synchronous (35) or metachronous (6) LM. Tumor grade was evaluated for PT and LM according to the WHO classification, using Ki-67 labeling and mitotic count (MC) evaluated with or without phospho-histone H3 (PPH3). Tumor grade differed between primary and metastatic tumor in 16/41 patients (39 %), with an increase of grade in 13 of them (32 %). The median Ki-67, MC, and PPH3 in metastases were statistically higher than in PT (p = 0.0002, 0.02, and 0.01). In 17 of 65 cases tested with PPH3 (26 %), this antibody was more efficient in assessing the grade compared to the usual MC, and in 2/65 cases compared to the Ki-67. A better correlation was observed between Ki-67 and PPH3 (p = 0.0001) than between Ki-67 and MC without immunohistochemistry. There is a significant difference in tumor grade between primary and metastatic NETs, underlining the necessity of a systematic biopsy on LM for patient management. Moreover, PPH3 appears to be a powerful antibody to assess the MC and the tumor grade much more accurately when associated with Ki-67. PMID:27048356

  15. Mucinous Borderline Ovarian Tumor in Very Old Aged Postmenopausal Woman

    PubMed Central

    Lee, Seung-Hee; Lee, Hae-Hyeog; Lee, Arum; Kim, Yeon-Suk; Jeon, Dong-Su; Kwak, Jeong Ja; Yang, Yo-Sep

    2015-01-01

    Mucinous borderline ovarian tumors (BOTs) occur most often in women between the ages of 20 and 30. Early-stage detection of the condition has a more favorable prognosis. In this case report, the authors present an elderly 93-year old woman who visited our hospital due to severe abdominal pain after being diagnosed with a pelvic mass 2 years ago and not undergoing any treatment since the diagnosis was made. She underwent emergency left salpingo-oophorectomy and was diagnosed with mucinous BOT according to biopsy results. PMID:26793682

  16. 1p/19q-driven prognostic molecular classification for high-grade oligodendroglial tumors.

    PubMed

    Jiang, Haihui; Zhang, Zhe; Ren, Xiaohui; Zeng, Wei; Jia, Wenqing; Wang, Junmei; Lin, Song

    2014-12-01

    The subjectivity in pathological diagnosis of anaplastic oligoastrocytoma (AOA) and uncertainty in designation of glioblastoma with oligodendroglioma component (GBMO) were two major dilemmas which puzzled neuro-pathologists and neurosurgeons. The present study was designed to project a molecular classification scheme based on the status of chromosome 1p and 19q. Patients (n = 117) with histological diagnosis of primary high-grade oligodendroglial tumors (HGOs) enrolled in the study. Fluorescence in situ hybridization (FISH) for chromosomes 1p and 19q was performed. Univariate analysis showed that higher tumor grade, 1p/19q maintenance and 1q/19p co polysomy were confirmed as risk factors in HGOs (P < 0.01). Accordingly, patients with HGOs were divided into four subtypes which conferred remarkably distinct prognosis based on the number of risk factors (0 risk factor: HGOs-1, 1 risk factor: HGOs-2, 2 risk factors: HGOs-3, 3 risk factors: HGOs-4). Cox regression model revealed that the tumor grade was no longer independently associated with survival, while the molecular classification scheme showed a marked prognostic significance (HR = 0.359, 95 % CI 0.261-0.494, P < 0.001 for progression-free survival (PFS); HR = 0.393, 95 % CI 0.283-0.546, P < 0.001 for overall survival (OS)). The classification scheme incorporating traditional pathology with molecular information can be served as a supplement of the current WHO classification system and contribute to the personalized treatment decision-making. PMID:25151507

  17. A Comparative Study of Survival Rate in High Grade Glioma Tumors Being Treated by Radiotherapy Alone Versus Chemoradiation With Nitrosourea

    PubMed Central

    Houshyari, Mohammad; Hajalikhani, Farzaneh; Rakhsha, Afshin; Hajian, Parastoo

    2015-01-01

    Background: In adults, malignant glioma (high-grade glioma) is one of the most common brain tumors. In spite of different types of treatment, the outcome is still not likely to be favorable. The aim of this study was to determine the difference between survival rate in adult patients with high grade glioma treated by radiotherapy only and those treated by a combination of radiotherapy and nitrosurea-based chemotherapy. Methods: This study was conducted using the records of 48 patients with grade 3 or 4 of glial brain tumor referred to the radiation-oncology ward of Shohada-e-Tajrish Hospital in Tehran, Iran from 2005 to 2012. The patients had undergone radiotherapy alone or adjuvant chemoradiation with nitrosourea. The median survival of patients after receiving the different types of treatment were evaluated using the Kaplan –Meier method and the log –rank exam. Data were analyzed using univariate analysis for median survival regarding to the patients’ age, gender, extent of surgery, Karnofsky performance status (KPS) with the Kaplan-Meier method, and the log-rank exam. We used the Cox-model for multivariate analysis. Results: Records of 48 patients were studied (34 men and 14 women). The mean survival were 18 months for men and 15.2 months for women (P = 0.05). Around 58% (28 patients) were more than 50 years old, and 42% (20 patients) were less than 50, and mean survival for the two age groups were 13 and 20 months, respectively (P < 0.001). Then, the patients were divided into three groups according to the extent of surgery, i.e., excisional biopsy (11 patients), stereotactic biopsy (22 patients), and resection (15 patients), and the mean survival for the three groups were 14.7, 17.3, and 18.8 months, respectively. There was no significant statistical difference for mean survival between the three groups (P = 0.23). The KPS was greater than 70% in 23 patients and less than 70% in 21 patients, and the mean survival for the former and latter groups were 17

  18. Relationship of Age, Marital Status, and Work Experience of Community College Nursing Students to Grades.

    ERIC Educational Resources Information Center

    Frerichs, Marian L.

    To investigate differences in academic success due to age (younger or older than age 23), marital status, and nursing experience, a three-way analysis of variance was performed on the grade point averages of 1,435 female nursing students enrolled in 22 Associate Degree Nursing (ADN) programs in Illinois. The sample, representing over 90 percent of…

  19. Under the Radar: The Impact of Relatively Young Age for Grade Level on Academic Achievement

    ERIC Educational Resources Information Center

    Ryken, Klazina

    2012-01-01

    The purpose of this study was to determine whether age differences affect students' academic achievement, and whether age differences affect students in low-income areas differently than those in mixed or higher-income areas. Student achievement data for grades 3, 7, and 11 in language arts and math were obtained from a variety of schools…

  20. Influence of age, sex, and balance on mature skipping by children in grades K-8.

    PubMed

    Loovis, E M; Butterfield, S A

    2000-06-01

    This study examined the contributions of age, sex, and balance on maturity of skipping by children in Grades K-8. The subjects were 379 boys and 337 girls (ages 4-14 years) enrolled in a medium-size school system in southeastern Maine. Each subject was individually assessed on skipping as well as static and dynamic balance. To assess the independent statistical contributions of age, sex, static balance, and dynamic balance within each grade, data were subjected to multiple regression analysis. Development of mature form in skipping was related to balance in two isolated but unaccountable instances. PMID:10883788

  1. Effect of Tumor Subtype on Survival and the Graded Prognostic Assessment for Patients With Breast Cancer and Brain Metastases

    SciTech Connect

    Sperduto, Paul W.; Kased, Norbert; Roberge, David; Xu Zhiyuan; Shanley, Ryan; Luo, Xianghua; Sneed, Penny K.; Chao, Samuel T.; Weil, Robert J.; Suh, John; Bhatt, Amit; Jensen, Ashley W.; Brown, Paul D.; Shih, Helen A.; Kirkpatrick, John; Gaspar, Laurie E.; Fiveash, John B.; and others

    2012-04-01

    Purpose: The diagnosis-specific Graded Prognostic Assessment (GPA) was published to clarify prognosis for patients with brain metastases. This study refines the existing Breast-GPA by analyzing a larger cohort and tumor subtype. Methods and Materials: A multi-institutional retrospective database of 400 breast cancer patients treated for newly diagnosed brain metastases was generated. Prognostic factors significant for survival were analyzed by multivariate Cox regression and recursive partitioning analysis (RPA). Factors were weighted by the magnitude of their regression coefficients to define the GPA index. Results: Significant prognostic factors by multivariate Cox regression and RPA were Karnofsky performance status (KPS), HER2, ER/PR status, and the interaction between ER/PR and HER2. RPA showed age was significant for patients with KPS 60 to 80. The median survival time (MST) overall was 13.8 months, and for GPA scores of 0 to 1.0, 1.5 to 2.0, 2.5 to 3.0, and 3.5 to 4.0 were 3.4 (n = 23), 7.7 (n = 104), 15.1 (n = 140), and 25.3 (n = 133) months, respectively (p < 0.0001). Among HER2-negative patients, being ER/PR positive improved MST from 6.4 to 9.7 months, whereas in HER2-positive patients, being ER/PR positive improved MST from 17.9 to 20.7 months. The log-rank statistic (predictive power) was 110 for the Breast-GPA vs. 55 for tumor subtype. Conclusions: The Breast-GPA documents wide variation in prognosis and shows clear separation between subgroups of patients with breast cancer and brain metastases. This tool will aid clinical decision making and stratification in clinical trials. These data confirm the effect of tumor subtype on survival and show the Breast-GPA offers significantly more predictive power than the tumor subtype alone.

  2. An Age-Graded Model for Career Development Education.

    ERIC Educational Resources Information Center

    Tuckman, Bruce W.

    This paper presents a career developmental model covering the ages of 5 to 18. Career development education includes experiences which facilitate self-awareness, career-awareness and career decision-making. Before choosing a model for career development, it is necessary to decide on a model for child development. The model developed here borrows…

  3. An Age-Graded Model for Career Development Education

    ERIC Educational Resources Information Center

    Tuckman, Bruce W.

    1974-01-01

    This paper attempts to provide a framework by which educators interested in stimulating career development can choose the learning experiences most likely to have payoffs for different age youth. Eight stages of child development are described with career development themes suggested for each stage along with sample activities. (Author)

  4. Professor Age and Gender Affect Student Perceptions and Grades

    ERIC Educational Resources Information Center

    Joye, Shauna W.; Wilson, Janie H.

    2015-01-01

    Student evaluations provide rich information about teaching performance, but a number of factors beyond teacher effectiveness influence student evaluations. In this study we examined the effects of professor gender and perceived age on ratings of effectiveness and rapport as well as academic performance. We also asked students to rate professor…

  5. Aging, tumor suppression and cancer: High-wire act!

    SciTech Connect

    Campisi, Judith

    2004-08-15

    Evolutionary theory holds that aging is a consequence of the declining force of natural selection with age. We discuss here the evidence that among the causes of aging in complex multicellular organisms, such as mammals, is the antagonistically pleiotropic effects of the cellular responses that protect the organism from cancer. Cancer is relatively rare in young mammals, owing in large measure to the activity of tumor suppressor mechanisms. These mechanisms either protect the genome from damage and/or mutations, or they elicit cellular responses--apoptosis or senescence--that eliminate or prevent the proliferation of somatic cells at risk for neoplastic transformation.We focus here on the senescence response, reviewing its causes, regulation and effects. In addition, we describe recent data that support the idea that both senescence and apoptosis may indeed be the double-edged swords predicted by the evolutionary hypothesis of antagonistic pleiotropy--protecting organisms from cancer early in life, but promoting aging phenotypes, including late life cancer, in older organisms.

  6. Frequency of MED12 mutations in phyllodes tumors: Inverse correlation with histologic grade.

    PubMed

    Yoon, Nara; Bae, Go Eun; Kang, So Young; Choi, Mi Sun; Hwang, Hye Won; Kim, Seok Won; Lee, Jeong Eon; Nam, Seok Jin; Gong, Gyungyub; Lee, Hee Jin; Bae, Young Kyung; Lee, Ahwon; Cho, Eun Yoon

    2016-06-01

    Phyllodes tumor (PT) is a rare breast biphasic tumor with a potential risk of recurrence and metastasis. In this study, the frequency of MED12 mutations in 176 PTs (49 benign, 49 borderline, and 78 malignant) was determined and the prognostic effect of these mutations in malignant type PT was evaluated. Analysis of MED12 mutations was performed by Sanger sequencing targeting the hotspot mutation region (exon 2) of MED12. Immunohistochemistry was also applied for evaluation of MED12 protein expression on tissue microarray blocks for 133 PTs including 50 benign, 50 borderline, and 33 malignant cases. A notable difference in the frequency of MED12 mutations was found according to histologic grade (71.4% of benign PTs, 51% of borderline PTs, 26.9% of malignant PTs; P < 0.001). MED12 protein expression was not correlated with MED12 mutation status. Patients with malignant PTs that harbored MED12 mutations demonstrated improved disease-free survival (DFS) compared with those without MED12 mutation (P = 0.07). MED12 mutation was a common molecular alteration in PT and the frequency of MED12 mutation decreased with increasing histologic grade. In malignant PT, MED12 exon 2 mutations showed improved DFS but without significance. © 2016 Wiley Periodicals, Inc. PMID:26856273

  7. West Virginia Adolescents' Health Risk Behaviors: Differences by Gender, Age, Grade Level, and Level of Rurality.

    ERIC Educational Resources Information Center

    Meehan, Merrill L.; And Others

    In 1990, the Youth Risk Behavior Survey (YRBS) was completed by a random sample of 1,448 West Virginia public-school students in grades 9-12. The sample was 51 percent male and 89 percent white. About 71 percent of subjects were aged 15-17; 39 percent were in the ninth grade. The YRBS covered behaviors producing vehicle-related or other injuries,…

  8. People Through the Ages. Social Studies Interim Grade Guide for Grade Eight.

    ERIC Educational Resources Information Center

    Manitoba Dept. of Education, Winnipeg. Curriculum Development Branch.

    Supplementary units of study help eighth graders in Manitoba explore the ways people lived within selected societies of the past and realize that life today is closely related to developments which have occurred through the ages. Units and subtopics are: (1) Life during Prehistoric and Early Historic Times--prehistoric times, life in early river…

  9. K Plus Education in Aging: A Literature Approach to the Teaching about Aging for Grades K-3.

    ERIC Educational Resources Information Center

    Sadoff, Eugene

    The purpose of this guide is to provide K-3 teachers with activities which will sensitize students to the needs and concerns of older adults and permit them to develop positive attitudes toward the entire aging process. There are four major sections to the guide, one for each grade level. Each activity revolves around a particular story book…

  10. Advances in Tumor Screening, Imaging, and Avatar Technologies for High-Grade Serous Ovarian Cancer

    PubMed Central

    Ohman, Anders W.; Hasan, Noor; Dinulescu, Daniela M.

    2014-01-01

    The majority of high-grade serous ovarian carcinoma cases are detected in advanced stages when treatment options are limited. Surgery is less effective at eradicating the disease when it is widespread, resulting in high rates of disease relapse and chemoresistance. Current screening techniques are ineffective for early tumor detection and consequently, BRCA mutations carriers, with an increased risk for developing high-grade serous ovarian cancer, elect to undergo risk-reducing surgery. While prophylactic surgery is associated with a significant reduction in the risk of cancer development, it also results in surgical menopause and significant adverse side effects. The development of efficient early-stage screening protocols and imaging technologies is critical to improving the outcome and quality of life for current patients and women at increased risk. In addition, more accurate animal models are necessary in order to provide relevant in vivo testing systems and advance our understanding of the disease origin and progression. Moreover, both genetically engineered and tumor xenograft animal models enable the preclinical testing of novel imaging techniques and molecularly targeted therapies as they become available. Recent advances in xenograft technologies have made possible the creation of avatar mice, personalized tumorgrafts, which can be used as therapy testing surrogates for individual patients prior to or during treatment. High-grade serous ovarian cancer may be an ideal candidate for use with avatar models based on key characteristics of the tumorgraft platform. This review explores multiple strategies, including novel imaging and screening technologies in both patients and animal models, aimed at detecting cancer in the early-stages and improving the disease prognosis. PMID:25478323

  11. International Society Of Neuropathology--Haarlem consensus guidelines for nervous system tumor classification and grading.

    PubMed

    Louis, David N; Perry, Arie; Burger, Peter; Ellison, David W; Reifenberger, Guido; von Deimling, Andreas; Aldape, Kenneth; Brat, Daniel; Collins, V Peter; Eberhart, Charles; Figarella-Branger, Dominique; Fuller, Gregory N; Giangaspero, Felice; Giannini, Caterina; Hawkins, Cynthia; Kleihues, Paul; Korshunov, Andrey; Kros, Johan M; Beatriz Lopes, M; Ng, Ho-Keung; Ohgaki, Hiroko; Paulus, Werner; Pietsch, Torsten; Rosenblum, Marc; Rushing, Elisabeth; Soylemezoglu, Figen; Wiestler, Otmar; Wesseling, Pieter

    2014-09-01

    Major discoveries in the biology of nervous system tumors have raised the question of how non-histological data such as molecular information can be incorporated into the next World Health Organization (WHO) classification of central nervous system tumors. To address this question, a meeting of neuropathologists with expertise in molecular diagnosis was held in Haarlem, the Netherlands, under the sponsorship of the International Society of Neuropathology (ISN). Prior to the meeting, participants solicited input from clinical colleagues in diverse neuro-oncological specialties. The present "white paper" catalogs the recommendations of the meeting, at which a consensus was reached that incorporation of molecular information into the next WHO classification should follow a set of provided "ISN-Haarlem" guidelines. Salient recommendations include that (i) diagnostic entities should be defined as narrowly as possible to optimize interobserver reproducibility, clinicopathological predictions and therapeutic planning; (ii) diagnoses should be "layered" with histologic classification, WHO grade and molecular information listed below an "integrated diagnosis"; (iii) determinations should be made for each tumor entity as to whether molecular information is required, suggested or not needed for its definition; (iv) some pediatric entities should be separated from their adult counterparts; (v) input for guiding decisions regarding tumor classification should be solicited from experts in complementary disciplines of neuro-oncology; and (iv) entity-specific molecular testing and reporting formats should be followed in diagnostic reports. It is hoped that these guidelines will facilitate the forthcoming update of the fourth edition of the WHO classification of central nervous system tumors. PMID:24990071

  12. Altered MicroRNA Expression Is Associated with Tumor Grade, Molecular Background and Outcome in Childhood Infratentorial Ependymoma

    PubMed Central

    Zakrzewska, Magdalena; Fendler, Wojciech; Zakrzewski, Krzysztof; Sikorska, Beata; Grajkowska, Wiesława; Dembowska-Bagińska, Bożenna; Filipek, Iwona; Stefańczyk, Łukasz; Liberski, Paweł P.

    2016-01-01

    Background Ependymal tumors are the third most common group of brain tumors in children, accounting for about 10% of all primary brain neoplasms. According to the current WHO classification, they comprise four entities with the most frequent ependymoma and anaplastic ependymoma. The most of pediatric tumors are located within the posterior fossa, with a tendency to infiltrate the vital brain structures. This limits surgical resection and poses a considerable clinical problem. Moreover, there are no appropriate outcome prognostic factors besides the extent of surgical resection. Despite definition of molecular subgroups, the majority of childhood ependymomas present a balanced genome, which makes it difficult to establish molecular prognostic factors. Methods The purpose of our study was to explore whether miRNA expression could be used as prognostic markers in pediatric infratentorial ependymomas. We also performed a mRNA expression pattern analysis of NELL2 and LAMA2 genes, with immunohistochemical illustrations of representative cases. The miRNA and mRNA expression was measured in 53 pediatric infratentorial ependymomas using a real-time quantitative PCR. Results Three miRNAs were shown to efficiently differentiate between grade II and III ependymomas: miR-17-5p, miR-19a-3p, and miR-106b-5p. Survival analysis showed that the probabilities of overall (p = 0.036) and event-free survival (p = 0.002) were reduced with higher than median miRNA expression levels of miR-17-5p. Using multivariate analysis adjusted for patient's age, sex, tumor grade and localization, we showed statistically significant associations with event-free survival (p = 0004) and borderline statistical significance with overall survival (p = 0.057) for miR-17-5p. Correlation analysis of miR-19a, miR-17-5p, miR-106b revealed that their expression levels were significantly correlated with EZH2 expression, suggested marker of PFA ependymomas. Furthermore, lower expression level of LAMA2 mRNA was

  13. PTEN loss and chromosome 8 alterations in Gleason grade 3 prostate cancer cores predicts the presence of un-sampled grade 4 tumor: implications for active surveillance.

    PubMed

    Trock, Bruce J; Fedor, Helen; Gurel, Bora; Jenkins, Robert B; Knudsen, B S; Fine, Samson W; Said, Jonathan W; Carter, H Ballentine; Lotan, Tamara L; De Marzo, Angelo M

    2016-07-01

    Men who enter active surveillance because their biopsy exhibits only Gleason grade 3 (G3) frequently have higher grade tumor missed by biopsy. Thus, biomarkers are needed that, when measured on G3 tissue, can predict the presence of higher grade tumor in the whole prostate. We evaluated whether PTEN loss, chromosome 8q gain (MYC) and/or 8p loss (LPL) measured only on G3 cores is associated with un-sampled G4 tumor. A tissue microarray was constructed of prostatectomy tissue from patients whose prostates exhibited only Gleason score 3+3, only 3+4 or only 4+3 tumor (n=50 per group). Cores sampled only from areas of G3 were evaluated for PTEN loss by immunohistochemistry, and PTEN deletion, LPL/8p loss and MYC/8q gain by fluorescence in situ hybridization. Biomarker results were compared between Gleason score 6 vs 7 tumors using conditional logistic regression. PTEN protein loss, odds ratio=4.99, P=0.033; MYC/8q gain, odds ratio=5.36, P=0.010; and LPL/8p loss, odds ratio=3.96, P=0.003 were significantly more common in G3 cores derived from Gleason 7 vs Gleason 6 tumors. PTEN gene deletion was not statistically significant. Associations were stronger comparing Gleason 4+3 vs 6 than for Gleason 3+4 vs 6. MYC/8q gain, LPL/8p loss and PTEN protein loss measured in G3 tissue microarray cores strongly differentiate whether the core comes from a Gleason 6 or Gleason 7 tumor. If validated to predict upgrading from G3 biopsy to prostatectomy these biomarkers could reduce the likelihood of enrolling high-risk men and facilitate safe patient selection for active surveillance. PMID:27080984

  14. Neurodevelopmental Outcomes of Extremely Low Gestational Age Neonates with Low Grade Periventricular-Intraventricular Hemorrhage

    PubMed Central

    Payne, Allison H.; Hintz, Susan R.; Hibbs, Anna Maria; Walsh, Michele C.; Vohr, Betty R.; Bann, Carla M.; Wilson-Costello, Deanne E.

    2014-01-01

    Objective To compare neurodevelopmental outcomes at 18–22 months corrected age for extremely low gestational age infants with low grade (Grade 1 or 2) periventricular-intraventricular hemorrhage to infants with either no hemorrhage or severe (Grade 3 or 4) hemorrhage on cranial ultrasound. Design Longitudinal observational study Setting Sixteen centers of the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network Participants 1472 infants born at <27 weeks gestational age between 2006–2008 with ultrasound results within the first 28 days of life and surviving to 18–22 months with complete follow-up assessments were eligible. Main Exposure Low grade periventricular-intraventricular hemorrhage Outcome Measures Outcomes included cerebral palsy, gross motor functional limitation, Bayley III cognitive and language scores, and composite measures of neurodevelopmental impairment. Regression modeling evaluated the association of hemorrhage severity with adverse outcomes while controlling for potentially confounding variables and center differences. Results Low grade hemorrhage was not associated with significant differences in unadjusted or adjusted risk of any adverse neurodevelopmental outcome compared to infants without hemorrhage. Compared with low grade hemorrhage, severe hemorrhage was associated with decrease in adjusted continuous cognitive (−3.91, [95% Confidence Interval [CI]: −6.41, −1.42]) and language (−3.19 [−6.19, −0.19]) scores as well as increased odds of each adjusted categorical outcome except severe cognitive impairment (OR: 1.46 [0.74, 2.88]) and mild language impairment (OR: 1.35 [0.88, 2.06]). Conclusion At 18–22 months, the neurodevelopmental outcomes of extremely low gestational age infants with low grade periventricular-intraventricular hemorrhage are not significantly different from those without hemorrhage. PMID:23460139

  15. A Phase II Trial of a Histone Deacetylase Inhibitor Panobinostat in Patients With Low-Grade Neuroendocrine Tumors

    PubMed Central

    Lubner, Sam J.; Mulkerin, Daniel L.; Rajguru, Saurabh; Carmichael, Lakeesha; Chen, Herb; Holen, Kyle D.; LoConte, Noelle K.

    2016-01-01

    Lessons Learned Pancreatic neuroendocrine tumors versus carcinoid tumors should be examined separately in clinical trials. Progression-free survival is more clinically relevant as the primary endpoint (rather than response rate) in phase II trials for low-grade neuroendocrine tumors. Background. The most common subtypes of neuroendocrine tumors (NETs) are pancreatic islet cell tumors and carcinoids, which represent only 2% of all gastrointestinal malignancies. Histone deacetylase (HDAC) inhibitors have already been shown to suppress tumor growth and induce apoptosis in various malignancies. In NET cells, HDAC inhibitors have resulted in increased Notch1 expression and subsequent inhibition of growth. We present here a phase II study of the novel HDAC inhibitor panobinostat in patients with low-grade NET. Methods. Adult patients with histologically confirmed, metastatic, low-grade NETs and an Eastern Cooperative Oncology Group (ECOG) performance status of ≤2 were treated with oral panobinostat 20 mg once daily three times per week. Treatment was continued until patients experienced unacceptable toxicities or disease progression. The study was stopped at planned interim analysis based on a Simon two-stage design. Results. Fifteen patients were accrued, and 13 were evaluable for response. No responses were seen, but the stable disease rate was 100%. The median progression-free survival (PFS) was 9.9 months, and the median overall survival was 47.3 months. Fatigue (27%), thrombocytopenia (20%), diarrhea (13%), and nausea (13%) were the most common related grade 3 toxicities. There was one grade 4 thrombocytopenia (7%). These results did not meet the prespecified criteria to open the study to full accrual. Conclusion. The HDAC inhibitor panobinostat has a high stable disease rate and reasonable PFS in low-grade NET, but has a low response rate. PMID:27261467

  16. The effects of early grade retention: Effect modification by prior achievement and age.

    PubMed

    Vandecandelaere, Machteld; Vansteelandt, Stijn; De Fraine, Bieke; Van Damme, Jan

    2016-02-01

    This study examines the effects of early grade retention and different effects according to prior achievement and age. Within a population of children at risk of early retention, we compared the development throughout primary school in mathematics achievement after kindergarten retention, first-grade retention, and continuous promotion. Analyzing data from a large-scale longitudinal study using covariate balancing propensity score weighting, the findings revealed that early grade repeaters would score higher in mathematics if they were promoted each year instead. However, the effects diminished or even disappeared in the long term. Compared to kindergarten retention, first-grade retention was found to be more harmful for the mathematics development of younger children specifically. PMID:26790704

  17. Radial expansion rates and tumor growth kinetics predict malignant transformation in contrast-enhancing low-grade diffuse astrocytoma

    PubMed Central

    Hathout, Leith; Pope, Whitney B; Lai, Albert; Nghiemphu, Phioanh L; Cloughesy, Timothy F; Ellingson, Benjamin M

    2015-01-01

    Summary Background Contrast-enhancing low-grade diffuse astrocytomas are an understudied, aggressive subtype at increased risk because of few radiographic indications of malignant transformation. In the current study, we tested whether tumor growth kinetics could identify tumors that undergo malignant transformation to higher grades. Methods Thirty patients with untreated diffuse astrocytomas (WHO II) that underwent tumor progression were enrolled. Contrast-enhancing and T2 hyperintense tumor regions were segmented and the radius of tumor at two time points leading to progression was estimated. Radial expansion rates were used to estimate proliferation and invasion rates using a biomathematical model. Results Radial expansion rates for both contrast-enhancing (p = 0.0040) and T2 hyperintense regions (p = 0.0016) were significantly higher in WHO II–IV tumors compared with nontransformers. Similarly, model estimates showed a significantly higher proliferation (p = 0.0324) and invasion rate (p = 0.0050) in WHO II–IV tumors compared with nontransformers. Conclusion Tumor growth kinetics can identify contrast-enhancing diffuse astrocytomas undergoing malignant transformation. PMID:26095141

  18. 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

  19. Asphalt Pavement Aging and Temperature Dependent Properties Using Functionally Graded Viscoelastic Model

    ERIC Educational Resources Information Center

    Dave, Eshan V.

    2009-01-01

    Asphalt concrete pavements are inherently graded viscoelastic structures. Oxidative aging of asphalt binder and temperature cycling due to climatic conditions being the major cause of non-homogeneity. Current pavement analysis and simulation procedures dwell on the use of layered approach to account for these non-homogeneities. The conventional…

  20. Content Analysis of an Intergenerational Unit on Aging in a Sixth-Grade Classroom.

    ERIC Educational Resources Information Center

    Corbin, David E.; And Others

    1987-01-01

    Evaluated seven-day program incorporating discussion, dance, and song to bring children and older adults from the community together in sixth-grade unit on aging. Survey of 21 students following the program suggests that students began to perceive older participants in active rather than passive terms and that nature of program became more…

  1. Mathematics Confidence, Grade-Level Choice, Gender, and Age in Preservice Teachers

    ERIC Educational Resources Information Center

    Pearson, Lesley Knoth

    2012-01-01

    Problem: The purpose of the study was to determine whether teachers' mathematics confidence influenced their choice of grade level. The study also examined whether there was a difference in teachers' mathematics confidence based on their age or gender. Method: A 6-item Mathematics Survey was distributed to 83 single-and multiple-subject…

  2. 42 CFR 21.28 - Age requirements, Regular Corps, senior assistant grade and below.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 42 Public Health 1 2010-10-01 2010-10-01 false Age requirements, Regular Corps, senior assistant grade and below. 21.28 Section 21.28 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN... active service in the Commissioned Corps of the Public Health Service shall be increased by the period...

  3. 42 CFR 21.28 - Age requirements, Regular Corps, senior assistant grade and below.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 42 Public Health 1 2012-10-01 2012-10-01 false Age requirements, Regular Corps, senior assistant grade and below. 21.28 Section 21.28 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN... active service in the Commissioned Corps of the Public Health Service shall be increased by the period...

  4. 42 CFR 21.28 - Age requirements, Regular Corps, senior assistant grade and below.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 42 Public Health 1 2013-10-01 2013-10-01 false Age requirements, Regular Corps, senior assistant grade and below. 21.28 Section 21.28 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN... active service in the Commissioned Corps of the Public Health Service shall be increased by the period...

  5. 42 CFR 21.28 - Age requirements, Regular Corps, senior assistant grade and below.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 42 Public Health 1 2014-10-01 2014-10-01 false Age requirements, Regular Corps, senior assistant grade and below. 21.28 Section 21.28 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN... active service in the Commissioned Corps of the Public Health Service shall be increased by the period...

  6. 42 CFR 21.28 - Age requirements, Regular Corps, senior assistant grade and below.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 42 Public Health 1 2011-10-01 2011-10-01 false Age requirements, Regular Corps, senior assistant grade and below. 21.28 Section 21.28 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN... active service in the Commissioned Corps of the Public Health Service shall be increased by the period...

  7. Nonlinear ghost waves accelerate the progression of high-grade brain tumors

    NASA Astrophysics Data System (ADS)

    Pardo, Rosa; Martínez-González, Alicia; Pérez-García, Víctor M.

    2016-10-01

    We study a reduced continuous model describing the evolution of high grade gliomas in response to hypoxic events through the interplay of different cellular phenotypes. We show that hypoxic events, even when sporadic and/or limited in space, may have a crucial role on the acceleration of high grade gliomas growth. Our modeling approach is based on two cellular phenotypes. One of them is more migratory and a second one is more proliferative. Transitions between both phenotypes are driven by the local oxygen values, assumed in this simple model to be uniform. Surprisingly, even very localized in time hypoxia events leading to transient migratory populations have the potential to accelerate the tumor's invasion speed up to speeds close to those of the migratory phenotype. The high invasion speed persists for times much longer than the lifetime of the hypoxic event. Moreover, the phenomenon is observed both when the migratory cells form a persistent wave of cells located on the invasion front and when they form a evanescent "ghost" wave disappearing after a short time by decay to the more proliferative phenotype. Our findings are obtained through numerical simulations of the model equations both in 1D and higher dimensional scenarios. We also provide a deeper mathematical analysis of some aspects of the problem such as the conditions for the existence of persistent waves of cells with a more migratory phenotype.

  8. The Differential Effects of Age and First Grade Schooling on the Development of Infralogical and Logico-Mathematical Concrete Operations

    ERIC Educational Resources Information Center

    Cahan, Sorel; Greenbaum, Charles; Artman, Lavee; Deluya, Nilly; Gappel-Gilon, Yael

    2008-01-01

    Using the ''between-grade levels'' regression discontinuity design, this study examined the hypothesized differential sensitivity of logico-mathematical (LM) and infralogical (IL) operational tasks to the effects of chronological age and first grade schooling in a sample of 580 1st and 2nd grade Israeli children. The results indicate that the…

  9. Effect of host age on the transplantation, growth, and radiation response of EMT6 tumors

    SciTech Connect

    Rockwell, S.

    1981-02-01

    The characteristics of EMT6 tumors in young adult and aged BALB/c KaRw mice were compared. The number of tumor cells implanted s.c. necessary to cause tumors in 50% of the injection sites was lower in aging than in young adult mice. The latent period of intradermally implanted tumors was shorter in aging mice than in young animals; however, the growth curves of established tumors were similar. The number and appearance of lung colonies after injection of cells i.v. and the pattern of spontaneous metastases were similar in young and aged animals. Radiation dose-response curves for the cells of tumors in young and aging mice were different and suggested that the proportion of hypoxic cells was higher in tumors on aging animals. These findings suggest that both immunological and nonimmunological tumor-host interactions differ in young and aged animals and that such factors may influence the natural history of the tumor and the response of the tumor to treatment.

  10. GE-01MOLECULAR AND PATHOLOGIC SUBSETS OF LOW GRADE GLIOMAS AND GLIONEURONAL TUMORS IDENTIFIED BY microRNA PROFILING

    PubMed Central

    Ames, Heather; Vizcaino, M. Adelita; Rodriguez, Fausto

    2014-01-01

    Low-grade (WHO I-II) gliomas represent the most frequent primary tumors of the central nervous system in children. They often have a good prognosis following total resection, however they can create many neurological complications due to mass effect, and may be difficult to resect depending on anatomic location. MicroRNAs have been identified as molecular regulators of protein expression that can repress multiple mRNAs concurrently through base pairing. Specific microRNAs are often suppressed during early cell differentiation to promote the expression of mitogenic proteins that are associated with the maintenance of specific stem cell types, a mechanism for growth and survival that is frequently exploited in cancer cells. Identification of these microRNA signatures present in low grade glioma and glioneuronal tumor sub-types could therefore lead to a wealth of candidate biomarkers. We used NanoString technology to analyze the expression levels of 800 microRNAs in nine low-grade glial and glioneuronal tumor subtypes (n = 45) using formalin-fixed paraffin-embedded tissue. We then generated hierarchical clusters following evaluation via significant analysis of microarrays (SAMs). Hierarchical clustering separated tumors from non-neoplastic brain. When looking at individual tumors, subependymal giant cell astrocytomas (SEGA) clustered sharply together, consistent with a unique microRNA expression signature in this tuberous sclerosis associated tumor subtype, compared to other low grade glial and glioneuronal tumors. Candidate microRNAs were validated using qRT-PCR. In SEGAs, microRNAs miR-219-5p, miR-129-2-3p, miR-338-3p, miR-487b, miR-885-5p, and miR-323-3p were significantly down-regulated by more than 15 fold as compared to normal brain and were also significantly down-regulated as compared to other low grade gliomas. In summary, altered microRNA expression is a feature of low grade glial and glioneuronal tumors. MicroRNA profiling may therefore be useful in

  11. Effect of host age on tumor-associated angiogenesis in mice.

    PubMed

    Kreisle, R A; Stebler, B A; Ershler, W B

    1990-01-01

    Previous reports on the slower growth of tumors in senescent mice have suggested a decrease in tumor angiogenesis in these animals, but such an observation has not yet been documented quantitatively. In this study, we report the relative amount of tumor angiogenesis and tumor volume for two different types of tumor in 11 young (8-9-wk old) versus nine older (19-mo old) male C57BL/10 mice. B16 melanoma or SP1 methylcholanthrene-induced fibrosarcoma cells were injected into the ventral skin of mice. After 3 days, the mice were killed and the injection sites were examined for angiogenesis surrounding the tumor (centrally directed tumor angiogenesis), nerve-associated angiogenesis, and tumor volume. In the older mice, there was significantly less centrally directed tumor angiogenesis for both tumors tested, and nerve-associated angiogenesis was decreased for B16 melanoma. The mean tumor volume for the B16 implants was smaller for the older animals, but the mean SP1 tumor volumes were identical for both age groups. These findings support the hypothesis that tumor growth in older animals is associated with less formation of new blood vessels, and this may explain the slower tumor growth observed in aged animals with certain experimental tumors. PMID:1688382

  12. Evaluation of molecular markers in canine mammary tumors: correlation with histological grading.

    PubMed

    Vinothini, G; Balachandran, C; Nagini, S

    2009-01-01

    The objective of this study was to evaluate molecular markers involved in mammary tumorigenesis in a canine model that mimics many essential elements of human breast cancer. Thirty mammary gland tumors and control tissues obtained from female dogs were included in the study. We analyzed changes in the expression of markers of hormone and receptor status (estradiol, estrogen receptor; ER and HER-2/neu), hormone metabolism (CYP1A1 and CYP1B1), cell proliferation and survival [proliferating cell nuclear antigen (PCNA), glutathione S-transferase-P (GST-P), nuclear factor-kappaB (NF-kappaB-p50, NF-kappaB-p65), phosphorylated-inhibitor of kappaB-alpha (p-IkappaB-alpha) and IkappaB], apoptosis (Bcl-2, Bax, caspases, Apaf-1, cytochrome-C, and PARP), invasion [matrix metalloproteinases-2 and -9 (MMP-2, MMP-9), tissue inhibitor of matrix metalloproteinase-2 (TIMP-2), and reversion-inducing cysteine-rich protein with Kazal motifs (RECK)], angiogenesis [vascular endothelial growth factor (VEGF)], and epigenetics [DNA methyltransferase (Dnmt-1), histone deacetylase (HDAC-1)] by immunohistochemical localization and Western blot analysis and correlated these with histological grade. The present study provides evidence that increased expression of ER, HER-2/neu, estradiol, and its metabolizing enzymes, as well as proteins involved in cell proliferation, apoptosis evasion, invasion, and angiogenesis may confer a selective growth advantage to canine mammary tumors. To our knowledge this is the first report on the hallmark capabilities of canine mammary tumors, which lends credence to the view that the dog is a valuable model for human breast cancer studies. PMID:20225757

  13. A DLL3-targeted antibody-drug conjugate eradicates high-grade pulmonary neuroendocrine tumor-initiating cells in vivo

    PubMed Central

    Saunders, Laura R.; Bankovich, Alexander J.; Anderson, Wade C.; Aujay, Monette A.; Bheddah, Sheila; Black, KristenAnn; Desai, Radhika; Escarpe, Paul A.; Hampl, Johannes; Laysang, Amy; Liu, David; Lopez-Molina, Javier; Milton, Milly; Park, Albert; Pysz, Marybeth A.; Shao, Hui; Slingerland, Brian; Torgov, Michael; Williams, Samuel A.; Foord, Orit; Howard, Philip; Jassem, Jacek; Badzio, Andrzej; Czapiewski, Piotr; Harpole, David H.; Dowlati, Afshin; Massion, Pierre P.; Travis, William D.; Pietanza, M. Catherine; Poirier, J. T.; Rudin, Charles M.; Stull, Robert A.; Dylla, Scott J.

    2016-01-01

    The high-grade pulmonary neuroendocrine tumors, small cell lung cancer (SCLC) and large cell neuroendocrine carcinoma (LCNEC), remain among the most deadly malignancies. Therapies that effectively target and kill tumor-initiating cells (TICs) in these cancers should translate to improved patient survival. Patient-derived xenograft (PDX) tumors serve as excellent models to study tumor biology and characterize TICs. Increased expression of delta-like 3 (DLL3) was discovered in SCLC and LCNEC PDX tumors and confirmed in primary SCLC and LCNEC tumors. DLL3 protein is expressed on the surface of tumor cells but not in normal adult tissues. A DLL3-targeted antibody-drug conjugate (ADC), SC16LD6.5, comprised of a humanized anti-DLL3 monoclonal antibody conjugated to a DNA-damaging pyrrolobenzodiazepine (PBD) dimer toxin, induced durable tumor regression in vivo across multiple PDX models. Serial transplantation experiments executed with limiting dilutions of cells provided functional evidence confirming that the lack of tumor recurrence after SC16LD6.5 exposure resulted from effective targeting of DLL3-expressing TICs. In vivo efficacy correlated with DLL3 expression, and responses were observed in PDX models initiated from patients with both limited and extensive-stage disease and were independent of their sensitivity to standard-of-care chemotherapy regimens. SC16LD6.5 effectively targets and eradicates DLL3-expressing TICs in SCLC and LCNEC PDX tumors and is a promising first-in-class ADC for the treatment of high-grade pulmonary neuroendocrine tumors. PMID:26311731

  14. Clinical significance of the plasminogen activator system in relation to grade of tumor and treatment response in colorectal carcinoma patients.

    PubMed

    Halamkova, J; Kiss, I; Pavlovsky, Z; Tomasek, J; Jarkovsky, J; Cech, Z; Tucek, S; Hanakova, L; Moulis, M; Zavrelova, J; Man, M; Benda, P; Robek, O; Kala, Z; Penka, M

    2011-01-01

    Urokinase (uPA) plays an essential role in the activation of plasminogen to plasmin, and together with its receptor (uPAR), tissue activator (tPA) and urokinase inhibitors (PAI 1, PAI 2, PAI 3 and protease nexin) forms the plasminogen activator system (PAS), a component of metastatic cascade importantly contributing to the invasive growth and angiogenesis of malignant tumours. In our project we examined the expression of uPA, uPAR, PAI 1 and PAI 2 in tumor tissue and we also studied the plasma levels of PAI 1 before and after the initiation of therapy in patients with colorectal carcinoma in relationship to grade of tumor and the treatment response. In our prospective evaluation we included 80 patients treated for adenocarcinoma of the colon and rectum. Analysis of collected data revealed statistically significant evidence of a relationship between the level of PAI 1 in plasma before treatment and grade of the tumor, which increases with tumor grade (p=0.025). We demonstrated that there exists a statistically significant relationship between the expression of PAI 2 (p<0.001) and uPAR (p=0.031) and grade of tumor. We also confirmed a statistically significant relationship between soluble levels of PAI 1 before treatment and therapeutic response (p=0.021). In our group of patients the expression of uPA, uPAR, PAI 1 and 2 in tumor tissue in relation to response to treatment was also assessed. Our results suggest that the greater expression of these parameters in tumor tissue is linked to a worse response to therapy. In conclusion, PAS factors help as a prognostic indicators and could also act as a predictive factor in colorectal carcinoma. PMID:21744990

  15. Nuclear medicine imaging of gastro-entero-pancreatic neuroendocrine tumors. The key role of cellular differentiation and tumor grade: from theory to clinical practice

    PubMed Central

    Rust, Edmond; Hubele, Fabrice; Marzano, Ettore; Goichot, Bernard; Pessaux, Patrick; Kurtz, Jean-Emmanuel

    2012-01-01

    Abstract Nuclear medicine imaging is a powerful diagnostic tool for the management of patients with gastro-entero-pancreatic neuroendocrine tumors, mainly developed considering some cellular characteristics that are specific to the neuroendocrine phenotype. Hence, overexpression of specific trans membrane receptors as well as the cellular ability to take up, accumulate, and decarboxylate amine precursors have been considered for diagnostic radiotracer development. Moreover, the glycolytic metabolism, which is not a specific energetic pathway of neuroendocrine tumors, has been proposed for radionuclide imaging of neuroendocrine tumors. The results of scintigraphic examinations reflect the pathologic features and tumor metabolic properties, allowing the in vivo characterization of the disease. In this article, the influence of both cellular differentiation and tumor grade in the scintigraphic pattern is reviewed according to the literature data. The relationship between nuclear imaging results and prognosis is also discussed. Despite the existence of a relationship between the results of scintigraphic imaging and cellular differentiation, tumor grade and patient outcome, the mechanism explaining the variability of the results needs further investigation. PMID:22743056

  16. Expression of TGF-beta signaling factors in invasive breast cancers: relationships with age at diagnosis and tumor characteristics.

    PubMed

    Figueroa, Jonine D; Flanders, Kathleen C; Garcia-Closas, Montserrat; Anderson, William F; Yang, Xiaohong R; Matsuno, Rayna K; Duggan, Máire A; Pfeiffer, Ruth M; Ooshima, Akira; Cornelison, Robert; Gierach, Gretchen L; Brinton, Louise A; Lissowska, Jolanta; Peplonska, Beata; Wakefield, Lalage M; Sherman, Mark E

    2010-06-01

    The transforming growth factor beta (TGF-beta) pathway can play either a tumor-suppressing or a tumor-promoting role in human breast carcinogenesis. In order to determine whether expression of TGF-beta signaling factors varies by age at onset and breast tumor characteristics that have prognostic significance, we undertook a study of 623 women with invasive breast carcinoma enrolled in a population-based case-control study conducted in Poland from 2000 to 2003. TGF-beta signaling factors were analyzed by immunohistochemistry in tumor tissue microarrays. We found that most tumors expressed extracellular-TGF-beta1 (78%), TGF-beta2 (91%), TGF-beta3 (93%), TGF-betaR2 (72%), and phospho-SMAD2 (61%), whereas intracellular-TGF-beta1 was expressed in 32% of tumors. Expression of TGF-beta ligands (beta1, beta2, and beta3) was associated with prognostically favorable pathological features including small size, and low grade, and these associations were similar for ER-positive and negative tumors. On the contrary, expression of the receptor TGF-betaR2 was primarily associated with small tumor size among ER-negative tumors, while expression of the transcription factor phospho-SMAD2 was associated with positive nodal status among ER-negative tumors. The greater frequency of expression of phospho-SMAD2 in cancers associated with lymph node metastases is consistent with a pro-progression role for TGF-beta. In addition, expression of extracellular-TGF-beta1 (P = 0.005), TGF-betaR2 (P = 8.2E-11), and phospho-SMAD2 (P = 1.3E-8) was strongly associated with earlier age at onset, independent of ER status. Our data provide evidence that TGF-beta signaling patterns vary by age and pathologic features of prognostic significance including ER expression. These results warrant analysis in studies of clinical outcomes accounting for age, ER status and treatment. PMID:19937272

  17. Expression of TGF-β signaling factors in invasive breast cancers: relationships with age at diagnosis and tumor characteristics

    PubMed Central

    Flanders, Kathleen C.; Garcia-Closas, Montserrat; Anderson, William F.; Yang, Xiaohong R.; Matsuno, Rayna K.; Duggan, Máire A.; Pfeiffer, Ruth M.; Ooshima, Akira; Cornelison, Robert; Gierach, Gretchen L.; Brinton, Louise A.; Lissowska, Jolanta; Peplonska, Beata; Wakefield, Lalage M.; Sherman, Mark E.

    2014-01-01

    The transforming growth factor beta (TGF-β) pathway can play either a tumor-suppressing or a tumor-promoting role in human breast carcinogenesis. In order to determine whether expression of TGF-β signaling factors varies by age at onset and breast tumor characteristics that have prognostic significance, we undertook a study of 623 women with invasive breast carcinoma enrolled in a population-based case–control study conducted in Poland from 2000 to 2003. TGF-β signaling factors were analyzed by immunohistochemistry in tumor tissue microarrays. We found that most tumors expressed extracellular-TGF-β1 (78%), TGF-β2 (91%), TGF-β3 (93%), TGF-βR2 (72%), and phospho-SMAD2 (61%), whereas intracellular-TGF-β1 was expressed in 32% of tumors. Expression of TGF-β ligands (β1, β2, and β3) was associated with prognostically favorable pathological features including small size, and low grade, and these associations were similar for ER-positive and negative tumors. On the contrary, expression of the receptor TGF-βR2 was primarily associated with small tumor size among ER-negative tumors, while expression of the transcription factor phospho-SMAD2 was associated with positive nodal status among ER-negative tumors. The greater frequency of expression of phospho-SMAD2 in cancers associated with lymph node metastases is consistent with a pro-progression role for TGF-β. In addition, expression of extracellular-TGF-β1 (P = 0.005), TGF-βR2 (P = 8.2E-11), and phospho-SMAD2 (P = 1.3E-8) was strongly associated with earlier age at onset, independent of ER status. Our data provide evidence that TGF-β signaling patterns vary by age and pathologic features of prognostic significance including ER expression. These results warrant analysis in studies of clinical outcomes accounting for age, ER status and treatment. PMID:19937272

  18. Well Differentiated Neuroendocrine Tumors with a Morphologically Apparent High Grade Component: A Pathway Distinct from Poorly Differentiated Neuroendocrine Carcinomas

    PubMed Central

    Tang, Laura H.; Untch, Brian R.; Reidy, Diane L.; O'Reilly, Eileen; Dhall, Deepti; Jih, Lily; Basturk, Olca; Allen, Peter J.; Klimstra, David S.

    2016-01-01

    Purpose Most well-differentiated neuroendocrine tumors (WD-NETs) of the enteropancreatic system are low-intermediate grade (G1,G2). Elevated proliferation demonstrated by either a brisk mitotic rate (>20/10 high power fields) or high Ki67 index (>20%) defines a group of aggressive neoplasms designated as high grade (G3) neuroendocrine carcinoma (NEC). High grade NEC is equated with poorly-differentiated NEC (PD-NEC) and is associated with a dismal outcome. Progression of WD-NETs to a high grade neuroendocrine neoplasm very rarely occurs and their clinicopathologic and molecular features need to be characterized. Methods We investigated the 31 cases of WD-NETs with evidence of component of a high grade neoplasm. The primary sites included pancreas, small bowel, bile duct, and rectum. Histopathology of the cases was retrospectively reviewed and selected immunohistochemistry and gene mutation analyses performed. Results The high grade component occurred either within the primary tumor (48%) or at metastatic sites (52%). The clinical presentation, radiographic features, biomarkers, and the genotype of these WD-NETs with high grade component remained akin to those of G1-G2 WD-NETs. The median disease specific survival (DSS) was 55 months (16-119 months), and 2-year and 5-year DSS was 88% and 49%, respectively – significantly better than that of a comparison group of true PD-NEC (DSS 11 months). Conclusion Mixed grades can occur in WD-NETs, which are distinguished from PDNECs by their unique phenotype, proliferative indices, and the genotype. This phenomenon of mixed grade in WD-NET provides additional evidence to the growing recognition that the current WHO G3 category contains both WD-NETs as well as PDNECs. PMID:26482044

  19. Hepatocarcinogenesis tumor grading correlated with in vivo image-guided {sup 1}H-NMR spectroscopy in a rat model

    SciTech Connect

    Towner, Rheal A. . E-mail: Rheal-Towner@omrf.ouhsc.edu; Foley, Lesley M.; Painter, Dorothy M.

    2005-09-01

    Hepatocellular carcinoma (HCC) is a common malignancy worldwide, the occurrence of which is unevenly distributed. Most hepatocellular carcinoma cases present late and have a poor prognosis; therefore, early diagnosis is essential to prolong survival. Differential diagnosis with magnetic resonance imaging (MRI) is difficult. We studied the feasibility of using magnetic resonance spectroscopy (MRS) at 7.0 T for the diagnosis and grading of liver tumors. An animal model of hepatocarcinogenesis was used, which allowed tumor progression from precancerous lesions to hepatocellular carcinomas. This study was focused primarily on the grading of the tumors and its correlation with the ratio between the MRS peaks arising from MRS-detected lipid hydrogens (0.9, 1.3 and 5.3 ppm) and compared to the {gamma}-methylene hydrogens of glutamate (Glu) and glutamine (Gln) which was used as an internal reference (2.4 ppm). The lipid methylene hydrogen (1.3 ppm) to (Glu + Gln) ratio was found to correlate with the formation of differentiated small foci and (precancerous) hepatic nodules, whereas the unsaturated olefinic lipid hydrogen (5.3 ppm) to (Glu + Gln) ratio was able to correlate with the formation of late stage tumors such as adenomas and hepatocellular carcinomas. The results of our study suggest that MRS-detected alterations in lipid metabolism can be correlated with the grading of liver tumor tissue at different stages during the carcinogenesis process.

  20. Do smoking and polymorphisms in xenobiotic metabolizing enzymes affect the histological stage and grade of bladder tumors?

    PubMed

    Ouerhani, S; Rouissi, K; Marrakchi, R; Riadh Ben Slama, M; Sfaxi, M; Ayed, M; Chebil, M; Elgaaied, Ab

    2009-05-01

    Cigarette smoking and genetic susceptibility are the two factors most closely associated with bladder cancer development. This study sought to determine the effect of smoking and genetic polymorphisms in xenobiotic metabolizing enzymes on the histological stage and grade of bladder tumors in Tunisian patients. A total of 97 patients with urothelial cell carcinomas were examined with respect to smoking status, NAT2 (N-acetyltransferase 2), GSTM1 and GSTT1 (glutathione S-transferase Mu 1 and teta 1) genotypes distribution. Our data have reported that tobacco; NAT2, GSTM1 and GSTT1 genotypes were not associated with bladder tumor stage. When we studied the superficial bladder tumor group, we have shown that in smokers tobacco was associated with the development of low-grade tumors. Conversely, non-smoker patients carrying altered NAT2 genotypes were with a 3.67-fold increased risk of developing superficial high-grade tumors (P = 0.02; RR = 3.67; 95% CI: [1.40-9.62]). PMID:19467981

  1. Are preoperative sex-related differences of affective symptoms in primary brain tumor patients associated with postoperative histopathological grading?

    PubMed

    Richter, Andre; Jenewein, J; Krayenbühl, N; Woernle, C; Bellut, D

    2016-01-01

    Our objective was to explore the impact of the histopathological tumor type on affective symptoms before surgery among male and female patients with supratentorial primary brain tumors. A total of 44 adult patients were included in the study. Depression and anxiety were measured using the Beck Depression Inventory (BDI) and the State-Trait Anxiety Inventory. Additionally, clinical interviews, including the Hamilton Depression Rating Scale (HDRS), were conducted. The general function of patients was measured with the Karnofsky Performance Status scale (KPS). All measures were obtained before surgery and therefore before the final histopathological diagnosis. All self-rating questionnaires but not the HDRS, showed significantly higher scores in female patients. The functional status assessed with the KPS was lower in female patients and correlated to the somatic part of the BDI. We further found a tendency for higher HDRS scores in male patients with a WHO grade 4 tumor stage compared to female patients. This finding was supported by positive correlations between HDRS scores and WHO grade in male and negative correlations between HDRS scores and WHO grade in female patients. In conclusion the preoperative evaluation of affective symptoms with self-rating questionnaires in patients with brain tumors may be invalidated by the patient’s functional status. Depression should be explored with clinical interviews in these patients. Sex differences of affective symptoms in this patient group may also be related to the malignancy of the tumor, but further studies are needed to disentangle this relationship. PMID:26468140

  2. Expression of PRMT5 correlates with malignant grade in gliomas and plays a pivotal role in tumor growth in vitro

    PubMed Central

    Li, Rong; Zhang, Wenbin; Yang, Xiuhua; Wheeler, Crystal G.; Friedman, Gregory K.; Province, Paula; Ding, Qiang; You, Zhiying; Fathallah-Shaykh, Hassan M.; Gillespie, G. Yancey; Zhao, Xinyang; King, Peter H.; Nabors, L. Burt

    2014-01-01

    Protein arginine methyltransferase 5 (PRMT5) catalyzes the formation of ω-NG,N'G-symmetric dimethylarginine residues on histones as well as other proteins. These modifications play an important role in cell differentiation and tumor cell growth. However, the role of PRMT5 in human glioma cells has not been characterized. In this study, we assessed protein expression profiles of PRMT5 in control brain, WHO grade II astrocytomas, anaplastic astrocytomas, and glioblastoma multiforme (GBM) by immunohistochemistry. PRMT5 was low in glial cells in control brain tissues and low grade astrocytomas. Its expression increased in parallel with malignant progression, and was highly expressed in GBM. Knockdown of PRMT5 by small hairpin RNA caused alterations of p-ERK1/2 and significantly repressed the clonogenic potential and viability of glioma cells. These findings indicate that PRMT5 is a marker of malignant progression in glioma tumors and plays a pivotal role in tumor growth. PMID:24664369

  3. Aggressive Locoregional Treatment Improves the Outcome of Liver Metastases from Grade 3 Gastroenteropancreatic Neuroendocrine Tumors.

    PubMed

    Du, Shunda; Ni, Jianjiao; Weng, Linqian; Ma, Fei; Li, Shaohua; Wang, Wenze; Sang, Xinting; Lu, Xin; Zhong, Shouxian; Mao, Yilei

    2015-08-01

    Grade 3 (G3) gastroenteropancreatic (GEP) neuroendocrine tumors (NETs) are rare, and there is no report specifically dealing with patients of liver metastases from G3 GEP NETs.From January 2004 to January 2014, 36 conservative patients with G3 GEP NET liver metastases were retrospectively identified from 3 hepatobiliary centers in China. The clinical features and treatment outcomes were analyzed.Aggressive locoregional treatments (LT, including cytoreductive surgery, radiofrequency ablation, and liver-directed intra-arterial intervention) and systemic therapy (ST) were introduced separately or combined, with 26 (72%) patients receiving resection of primary tumor and/or hepatic metastases, 12 patients receiving non-surgical locoregional interventions (NSLRIs), and 22 patients receiving certain kind of STs. Median overall survival (OS) was 20.0 months (95% confidence interval [CI]: 8.9-31.1 months) and survival rates were 62.6%, 30.1%, and 19.8%, at 1, 3, and 5 years, respectively. The median OS was 9.0 months (95%CI: 3.3-14.7 months) for patients receiving only STs (n = 6), 19 months (95%CI: 1.3-36.8 months) for patients receiving LT followed by STs (n = 16), and 101 months (95%CI: 0.0-210.2 months) for patients receiving only LT (n = 12). Moreover, compared with those receiving only ST or best supportive care, patients given certain types of LTs had higher rates of symptom alleviation (3/8 versus 20/23). On univariate analysis, positive prognostic factors of survival were pancreatic primary tumor (P = 0.013), normal total bilirubin level (P = 0.035), receiving surgery (P = 0.034), receiving NSLRI (P = 0.014), and sum of diameters of remnant tumor < 5 cm (P = 0.008). On multivariate analyses, pancreatic primary tumor (P = 0.015), normal total bilirubin level (P = 0.002), and sum of diameters of remnant tumor < 5 cm (P = 0.001) remained to be independent prognostic factors.For patients with G3 GEP NET liver

  4. Characterization of Aging Behavior in M250 Grade Maraging Steel Using Ultrasonic Measurements

    NASA Astrophysics Data System (ADS)

    Rajkumar, K. V.; Kumar, Anish; Jayakumar, T.; Raj, Baldev; Ray, K. K.

    2007-02-01

    Ultrasonic measurements have been carried out in M250 grade maraging steel specimens subjected to solution annealing at 1093 K for 1 hour followed by aging at 755 K for various durations in the range of 0.25 to 100 hours. The influence of aging on microstructure, room temperature hardness, and ultrasonic parameters (longitudinal and shear wave velocities and Poisson’s ratio) has been studied in order to derive correlations among these parameters in aged M250 maraging steel. Both hardness and ultrasonic velocities exhibit almost similar behaviors with aging time. They increase with the precipitation of intermetallic phases, Ni3Ti and Fe2Mo, and decrease with the reversion of martensite to austenite. Ultrasonic shear wave velocity is found to be more influenced by the precipitation of intermetallic phases, whereas longitudinal wave velocity is influenced more by the reversion of martensite to austenite. Unlike hardness and ultrasonic velocities, the Poisson’s ratio exhibits a monotonous decrease with aging time and, hence, can be used for unambiguous monitoring of the aging process in M250 maraging steel. Further, none of the parameters, i.e., hardness, ultrasonic velocity, or Poisson’s ratio, alone could identify the initiation of the reversion of austenite at early stage; however, the same could be identified from the correlation between ultrasonic velocity and Poisson’s ratio, indicating the advantage of using the multiparametric approach for comprehensive characterization of complex aging behavior in M250 grade maraging steel.

  5. Ciliated muconodular papillary tumor of the lung: a newly defined low-grade malignant tumor with CT findings reminiscent of adenocarcinoma.

    PubMed

    Hata, Yoshinobu; Yuasa, Rena; Sato, Fumitomo; Otsuka, Hajime; Goto, Hidenori; Isobe, Kazutoshi; Mitsuda, Aki; Wakayama, Megumi; Shibuya, Kazutoshi; Takagi, Keigo; Watanabe, Yoshiyuki

    2013-02-01

    A ciliated muconodular papillary tumor has been reported to be a peripheral low-grade malignant tumor, consisting of ciliated columnar cells and goblet cells with basaloid cell proliferation. Although ciliated muconodular papillary tumors have not yet been classified according to the World Health Organization classification, they can pose diagnostic and therapeutic problems. Here we report a resected case of ciliated muconodular papillary tumor with computed tomography findings reminiscent of adenocarcinoma, showing a small irregular nodule adjacent to the intersegment pulmonary vein. There was no uptake of F-18 fluorodeoxyglucose positron emission tomography. The patient underwent surgical resection, and a lobectomy was performed because intraoperative needle biopsy suggested neoplastic proliferation. No EGFR mutations were detected. No recurrence was noted during 24-month follow-up after lobectomy. PMID:23275641

  6. Asphalt pavement aging and temperature dependent properties using functionally graded viscoelastic model

    NASA Astrophysics Data System (ADS)

    Dave, Eshan V.

    Asphalt concrete pavements are inherently graded viscoelastic structures. Oxidative aging of asphalt binder and temperature cycling due to climatic conditions being the major cause of non-homogeneity. Current pavement analysis and simulation procedures dwell on the use of layered approach to account for these non-homogeneities. The conventional finite-element modeling (FEM) technique discretizes the problem domain into smaller elements, each with a unique constitutive property. However the assignment of unique material property description to an element in the FEM approach makes it an unattractive choice for simulation of problems with material non-homogeneities. Specialized elements such as "graded elements" allow for non-homogenous material property definitions within an element. This dissertation describes the development of graded viscoelastic finite element analysis method and its application for analysis of asphalt concrete pavements. Results show that the present research improves efficiency and accuracy of simulations for asphalt pavement systems. Some of the practical implications of this work include the new technique's capability for accurate analysis and design of asphalt pavements and overlay systems and for the determination of pavement performance with varying climatic conditions and amount of in-service age. Other application areas include simulation of functionally graded fiber-reinforced concrete, geotechnical materials, metal and metal composites at high temperatures, polymers, and several other naturally existing and engineered materials.

  7. Differentially Expressed MicroRNAs in Meningiomas Grades I and II Suggest Shared Biomarkers with Malignant Tumors

    PubMed Central

    El-Gewely, Mohamed Raafat; Andreassen, Morten; Walquist, Mari; Ursvik, Anita; Knutsen, Erik; Nystad, Mona; Coucheron, Dag H.; Myrmel, Kristin Smistad; Hennig, Rune; Johansen, Steinar D.

    2016-01-01

    Meningiomas represent the most common primary tumors of the central nervous system, but few microRNA (miRNA) profiling studies have been reported so far. Deep sequencing of small RNA libraries generated from two human meningioma biopsies WHO grades I (benign) and II (atypical) were compared to excess dura controls. Nineteen differentially expressed miRNAs were validated by RT-qPCR using tumor RNA from 15 patients and 5 meninges controls. Tumor suppressor miR-218 and miR-34a were upregulated relative to normal controls, however, miR-143, miR-193b, miR-451 and oncogenic miR-21 were all downregulated. From 10 selected putative mRNA targets tested by RT-qPCR only four were differentially expressed relative to normal controls. PTEN and E-cadherin (CDH1) were upregulated, but RUNX1T1 was downregulated. Proliferation biomarker p63 was upregulated with nuclear localization, but not detected in most normal arachnoid tissues. Immunoreactivity of E-cadherin was detected in the outermost layer of normal arachnoids, but was expressed throughout the tumors. Nuclear Cyclin D1 expression was positive in all studied meningiomas, while its expression in arachnoid was limited to a few trabecular cells. Meningiomas of grades I and II appear to share biomarkers with malignant tumors, but with some additional tumor suppressor biomarkers expression. Validation in more patients is of importance. PMID:26950155

  8. Cognitive outcomes among survivors of focal low-grade brainstem tumors diagnosed in childhood.

    PubMed

    Clark, Kellie N; Ashford, Jason M; Pai Panandiker, Atmaram S; Klimo, Paul; Merchant, Thomas E; Billups, Catherine A; Conklin, Heather M

    2016-09-01

    Pediatric focal low-grade brainstem tumors are associated with excellent prognosis. Surgical resection and conformal radiation therapy are front-line treatment options; radiation therapy (RT) serves as an excellent treatment for disease progression. Given high survival rates and limited research regarding functional outcomes, the current study examined neurocognitive outcomes in a group of low-grade brainstem glioma survivors. Forty-three survivors of focal low-grade brainstem gliomas underwent neurocognitive assessment (58 % male; median = 6.9 years at diagnosis; median = 14.9 years at latest assessment). Treatment included combinations of surgery, chemotherapy, and RT with 70 % ultimately receiving RT. Neurocognitive outcomes were evaluated through retrospective chart review. Intellectual and academic performance were significantly different from normative expectations (full scale IQ = 86.5 ± 16.8; reading comprehension = 91.3 ± 16.4; math reasoning = 88.2 ± 18.9; reference group = 100 ± 15). Further, the percentage performing below average exceeded the expected 16 % in the normative sample (full scale IQ = 43 %; reading comprehension = 37 %; math reasoning = 50 %). Mean parent ratings did not reflect concerns regarding internalizing and externalizing behaviors or executive functioning (internalizing = 54.9 ± 12.7; externalizing = 51.6 ± 14.6, global executive composite = 57.1 ± 16.0; reference group = 50 ± 10); however, the proportion with clinically elevated scores was higher than the expected 16 % (internalizing = 42 %; externalizing = 26 %; global executive composite = 38 %). Mean performance fell below average for visual-motor coordination (81.8 ± 13.2) and parent ratings of adaptive functioning (73.4 ± 24.2), with 65 and 62 % falling outside the average range, respectively. There were no significant differences between

  9. Does Relative Age Influence Motor Test Performance of Fourth Grade Pupils?

    ERIC Educational Resources Information Center

    Wattie, Nick; Tietjens, Maike; Schorer, Jörg; Ghanbari, Marie-Christine; Strauss, Bernd; Seidel, Ilka; Baker, Joseph

    2014-01-01

    The aim of the current study was to explore relative age's influence on physical and motor tests among fourth grade children (9 to 10 years) from Germany. Data from 1218 children (49% female) who had performed the German Motor Ability Test (Bös et al., 2009) were analysed. The test battery, which was comprised of physical and motor tests,…

  10. The effects of graded levels of calorie restriction: VII. Topological rearrangement of hypothalamic aging networks.

    PubMed

    Derous, Davina; Mitchell, Sharon E; Green, Cara L; Wang, Yingchun; Han, Jing Dong J; Chen, Luonan; Promislow, Daniel E L; Lusseau, David; Speakman, John R; Douglas, Alex

    2016-05-01

    Connectivity in a gene-gene network declines with age, typically within gene clusters. We explored the effect of short-term (3 months) graded calorie restriction (CR) (up to 40 %) on network structure of aging-associated genes in the murine hypothalamus by using conditional mutual information. The networks showed a topological rearrangement when exposed to graded CR with a higher relative within cluster connectivity at 40CR. We observed changes in gene centrality concordant with changes in CR level, with Ppargc1a, and Ppt1 having increased centrality and Etfdh, Traf3 and Abcc1 decreased centrality as CR increased. This change in gene centrality in a graded manner with CR, occurred in the absence of parallel changes in gene expression levels. This study emphasizes the importance of augmenting traditional differential gene expression analyses to better understand structural changes in the transcriptome. Overall our results suggested that CR induced changes in centrality of biological relevant genes that play an important role in preventing the age-associated loss of network integrity irrespective of their gene expression levels. PMID:27115072

  11. The effects of graded levels of calorie restriction: VII. Topological rearrangement of hypothalamic aging networks

    PubMed Central

    Derous, Davina; Mitchell, Sharon E.; Green, Cara L.; Wang, Yingchun; Han, Jing Dong J.; Chen, Luonan; Promislow, Daniel E.L.; Lusseau, David; Speakman, John R.; Douglas, Alex

    2016-01-01

    Connectivity in a gene-gene network declines with age, typically within gene clusters. We explored the effect of short-term (3 months) graded calorie restriction (CR) (up to 40 %) on network structure of aging-associated genes in the murine hypothalamus by using conditional mutual information. The networks showed a topological rearrangement when exposed to graded CR with a higher relative within cluster connectivity at 40CR. We observed changes in gene centrality concordant with changes in CR level, with Ppargc1a, and Ppt1 having increased centrality and Etfdh, Traf3 and Abcc1 decreased centrality as CR increased. This change in gene centrality in a graded manner with CR, occurred in the absence of parallel changes in gene expression levels. This study emphasizes the importance of augmenting traditional differential gene expression analyses to better understand structural changes in the transcriptome. Overall our results suggested that CR induced changes in centrality of biological relevant genes that play an important role in preventing the age-associated loss of network integrity irrespective of their gene expression levels. PMID:27115072

  12. Candidate tumor-suppressor genes on chromosome arm 8p in early-onset and high-grade breast cancers.

    PubMed

    Armes, Jane E; Hammet, Fleur; de Silva, Melanie; Ciciulla, John; Ramus, Susan J; Soo, Wee-Kheng; Mahoney, Alexis; Yarovaya, Natalia; Henderson, Michael A; Gish, Kurt; Hutchins, Anne-Marie; Price, Gareth R; Venter, Deon J

    2004-07-22

    Loss of genetic material from chromosome arm 8p occurs commonly in breast carcinomas, suggesting that this region is the site of one or more tumor-suppressor genes (TSGs). Comparative genomic hybridization analysis showed that 8p loss is more common in breast cancers from pre-menopausal compared with post-menopausal patients, as well as in high-grade breast cancers, regardless of the menopausal status. Subsequent high-resolution gene expression profiling of genes mapped to chromosome arm 8p, on an extended cohort of clinical tumor samples, indicated a similar dichotomy of breast cancer clinicopathologic types. Some of these genes showed differential downregulation in early-onset and later-onset, high-grade cancers compared with lower-grade, later-onset cancers. Three such genes were analysed further by in situ technologies, performed on tissue microarrays representing breast tumor and normal tissue samples. PCM1, which encodes a centrosomal protein, and DUSP4/MKP-2, which encodes a MAP kinase phosphatase, both showed frequent gene and protein loss in carcinomas. In contrast, there was an excess of cases showing loss of expression in the absence of reduced gene copy number of SFRP1, which encodes a dominant-negative receptor for Wnt-family ligands. These candidate TSGs may constitute some of the molecular drivers of chromosome arm 8p loss in breast carcinogenesis. PMID:15184884

  13. Effects of Age of English Exposure, Current Input/Output, and grade on bilingual language performance.

    PubMed

    Bedore, Lisa M; Peña, Elizabeth D; Griffin, Zenzi M; Hixon, J Gregory

    2016-05-01

    This study evaluates the effects of Age of Exposure to English (AoEE) and Current Input/Output on language performance in a cross-sectional sample of Spanish-English bilingual children. First- (N = 586) and third-graders (N = 298) who spanned a wide range of bilingual language experience participated. Parents and teachers provided information about English and Spanish language use. Short tests of semantic and morphosyntactic development in Spanish and English were used to quantify children's knowledge of each language. There were significant interactions between AoEE and Current Input/Output for children at third grade in English and in both grades for Spanish. In English, the relationship between AoEE and language scores were linear for first- and third-graders. In Spanish a nonlinear relationship was observed. We discuss how much of the variance was accounted for by AoEE and Current Input/Output. PMID:26916066

  14. Strategies to Achieve Congruence between Student Chronological Age and Grade Placement in the Compulsory Phase of Education in Botswana

    ERIC Educational Resources Information Center

    Brown, Byron; Forcheh, Ntonghanwah

    2014-01-01

    In many developing countries, researchers and policy makers have downplayed issues of age in grade intentionally. This is done partly to avoid the pedagogical issues that over-age or under-age children in schools raise. It is also done to avoid putting extra pressure on government especially in developing nations that is still working hard to…

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

    SciTech Connect

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

    2014-05-15

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

  16. Generation and Cryopreservation of Clinical Grade Wilms' Tumor 1 mRNA-Loaded Dendritic Cell Vaccines for Cancer Immunotherapy.

    PubMed

    Smits, Evelien L J M; Stein, Barbara; Nijs, Griet; Lion, Eva; Van Tendeloo, Viggo F; Willemen, Yannick; Anguille, Sébastien; Berneman, Zwi N

    2016-01-01

    First described in the 1970s, dendritic cells (DC) are currently subjects of intense investigation to exploit their unique antigen-presenting and immunoregulatory capacities. In cancer, DC show promise to elicit or amplify immune responses directed against cancer cells by activating natural killer (NK) cells and tumor antigen-specific T cells. Wilms' tumor 1 (WT1) protein is a tumor-associated antigen that is expressed in a majority of cancer types and has been designated as an antigen of major interest to be targeted in clinical cancer immunotherapy trials. In this chapter, we describe the generation, cryopreservation, and thawing of clinical grade autologous monocyte-derived DC vaccines that are loaded with WT1 by messenger RNA (mRNA) electroporation. This in-house-developed transfection method gives rise to presentation of multiple antigen epitopes and can be used for all patients without restriction of human leukocyte antigen (HLA) type. PMID:27033213

  17. Multiple direct and indirect mechanisms drive estrogen-induced tumor growth in high grade serous ovarian cancers

    PubMed Central

    Ciucci, Alessandra; Zannoni, Gian Franco; Buttarelli, Marianna; Lisi, Lucia; Travaglia, Daniele; Martinelli, Enrica; Scambia, Giovanni; Gallo, Daniela

    2016-01-01

    The notion that menopausal estrogen replacement therapy increases ovarian cancer risk, but only for the two more common types (i.e. serous and endometrioid), while possibly decreasing risk for clear cell tumors, is strongly suggestive of causality. However, whether estradiol (E2) is tumorigenic or promotes development of occult preexisting disease is unknown. The present study investigated molecular and cellular mechanisms by which E2 modulates the growth of high grade serous ovarian cancer (HGSOC). Results showed that ERα expression was necessary and sufficient to induce the growth of HGSOC cells in in vitro models. Conversely, in vivo experimental studies demonstrated that increasing the levels of circulating estrogens resulted in a significant growth acceleration of ERα-negative HGSOC xenografts, as well. Tumors from E2-treated mice had significantly higher proliferation rate, angiogenesis, and density of tumor-associated macrophage (TAM) compared to ovariectomized females. Accordingly, immunohistochemical analysis of ERα-negative tissue specimens from HGSOC patients showed a significantly greater TAM infiltration in premenopausal compared to postmenopausal women. This study describes novel insights into the impact of E2 on tumor microenvironment, independently of its direct effect on tumor cell growth, thus supporting the idea that multiple direct and indirect mechanisms drive estrogen-induced tumor growth in HGSOC. PMID:26797759

  18. ADAM9 Expression Is Associate with Glioma Tumor Grade and Histological Type, and Acts as a Prognostic Factor in Lower-Grade Gliomas.

    PubMed

    Fan, Xing; Wang, Yongheng; Zhang, Chuanbao; Liu, Li; Yang, Sen; Wang, Yinyan; Liu, Xing; Qian, Zenghui; Fang, Shengyu; Qiao, Hui; Jiang, Tao

    2016-01-01

    The A disintegrin and metalloproteinase 9 (ADAM9) protein has been suggested to promote carcinoma invasion and appears to be overexpressed in various human cancers. However, its role has rarely been investigated in gliomas and, thus, in the current study we have evaluated ADAM9 expression in gliomas and examined the relevance of its expression in the prognosis of glioma patients. Clinical characteristics, RNA sequence data, and the case follow-ups were reviewed for 303 patients who had histological, confirmed gliomas. The ADAM9 expression between lower-grade glioma (LGG) and glioblastoma (GBM) patients was compared and its association with progression-free survival (PFS) and overall survival (OS) was assessed to evaluate its prognostic value. Our data suggested that GBM patients had significantly higher expression of ADAM9 in comparison to LGG patients (p < 0.001, t-test). In addition, among the LGG patients, aggressive astrocytic tumors displayed significantly higher ADAM9 expression than oligodendroglial tumors (p < 0.001, t-test). Moreover, high ADAM9 expression also correlated with poor clinical outcome (p < 0.001 and p < 0.001, log-rank test, for PFS and OS, respectively) in LGG patients. Further, multivariate analysis suggested ADAM9 expression to be an independent marker of poor survival (p = 0.002 and p = 0.003, for PFS and OS, respectively). These results suggest that ADAM9 mRNA expression is associated with tumor grade and histological type in gliomas and can serve as an independent prognostic factor, specifically in LGG patients. PMID:27571068

  19. Tipifarnib in Treating Young Patients With Recurrent or Progressive High-Grade Glioma, Medulloblastoma, Primitive Neuroectodermal Tumor, or Brain Stem Glioma

    ClinicalTrials.gov

    2013-10-07

    Childhood High-grade Cerebral Astrocytoma; Childhood Oligodendroglioma; Recurrent Childhood Brain Stem Glioma; Recurrent Childhood Cerebellar Astrocytoma; Recurrent Childhood Cerebral Astrocytoma; Recurrent Childhood Medulloblastoma; Recurrent Childhood Supratentorial Primitive Neuroectodermal Tumor; Recurrent Childhood Visual Pathway and Hypothalamic Glioma

  20. Effects of subprimal type, quality grade, and aging time on display color of ground beef patties.

    PubMed

    Garner, C M; Unruh, J A; Hunt, M C; Boyle, E A E; Houser, T A

    2014-10-01

    A factorial design was used to evaluate the effects of two subprimal types (chuck roll and knuckle), two quality grades (Premium Choice and Select), and three vacuum-storage aging times before processing (7, 21, and 42d) ground beef patty display color attributes. Patties from chuck roll and Premium Choice subprimals had brighter red visual color scores, less discoloration, and higher L*, a*, b*, and chroma values than those from knuckle and Select subprimals, respectively. With an increased display time, patties became darker red, more discolored, and had decreased L*, a*, b*, and chroma values. Therefore, aging Premium Choice chuck rolls for less time (fewer than 21d) could maximize display color life. PMID:24880976

  1. Residual Tumor Volume as Best Outcome Predictor in Low Grade Glioma - A Nine-Years Near-Randomized Survey of Surgery vs. Biopsy.

    PubMed

    Roelz, Roland; Strohmaier, David; Jabbarli, Ramazan; Kraeutle, Rainer; Egger, Karl; Coenen, Volker A; Weyerbrock, Astrid; Reinacher, Peter C

    2016-01-01

    Diffuse low grade gliomas (DLGG) are continuously progressive primary brain neoplasms that lead to neurological deficits and death. Treatment strategies are controversial. Randomized trials establishing the prognostic value of surgery do not exist. Here, we report the results of a nine-year near-randomized patient distribution between resection and biopsy. Until 2012, the Department of Neurosurgery and the Department of Stereotactic Neurosurgery at the University Medical Center Freiburg were organized as separate administrative units both coordinating DLGG patient treatment independently. All consecutive adult patients with a new diagnosis of DLGG by either stereotactic biopsy or resection were included. Pre- and post-operative tumor volumetry was performed. 126 patients, 87 men (69%), 39 women (31%), median age 41 years, were included. 77 (61%) were initially managed by biopsy, 49 (39%) by resection. A significant survival benefit was found for patients with an initial management by resection (5-year OS 82% vs. 54%). The survival benefit of patients with initial resection was reserved to patients with a residual tumor volume of less than 15 cm(3). Maximum safe resection is the first therapy of choice in DLGG patients if a near-complete tumor removal can be achieved. Accurate prediction of the extent-of-resection is required for selection of surgical candidates. PMID:27574036

  2. Residual Tumor Volume as Best Outcome Predictor in Low Grade Glioma – A Nine-Years Near-Randomized Survey of Surgery vs. Biopsy

    PubMed Central

    Roelz, Roland; Strohmaier, David; Jabbarli, Ramazan; Kraeutle, Rainer; Egger, Karl; Coenen, Volker A.; Weyerbrock, Astrid; Reinacher, Peter C.

    2016-01-01

    Diffuse low grade gliomas (DLGG) are continuously progressive primary brain neoplasms that lead to neurological deficits and death. Treatment strategies are controversial. Randomized trials establishing the prognostic value of surgery do not exist. Here, we report the results of a nine-year near-randomized patient distribution between resection and biopsy. Until 2012, the Department of Neurosurgery and the Department of Stereotactic Neurosurgery at the University Medical Center Freiburg were organized as separate administrative units both coordinating DLGG patient treatment independently. All consecutive adult patients with a new diagnosis of DLGG by either stereotactic biopsy or resection were included. Pre- and post-operative tumor volumetry was performed. 126 patients, 87 men (69%), 39 women (31%), median age 41 years, were included. 77 (61%) were initially managed by biopsy, 49 (39%) by resection. A significant survival benefit was found for patients with an initial management by resection (5-year OS 82% vs. 54%). The survival benefit of patients with initial resection was reserved to patients with a residual tumor volume of less than 15 cm3. Maximum safe resection is the first therapy of choice in DLGG patients if a near-complete tumor removal can be achieved. Accurate prediction of the extent-of-resection is required for selection of surgical candidates. PMID:27574036

  3. Influence of age, sex, balance, and sport participation on development of sidearm striking by children grades K-8.

    PubMed

    Loovis, E M; Butterfield, S A

    1995-10-01

    The purpose of this study was to examine the contributions of age, sex, balance, and sport participation on development of sidearm-striking by children in Grades K through 8. Each of 380 boys and 337 girls (ages 4-14 years), enrolled in a medium-size school system in southeastern Maine, was individually assessed on side-arm-striking and on static and dynamic balance. All subjects completed a survey relative to their participation in school or community-sponsored sports. To assess the independent effects of age, sex, static balance, dynamic balance, and sport participation within each grade, data were subjected to multiple-regression analysis. Development of mature striking was associated with sex; boys performed better at all grades except in Grade 5 where the percentage of girls showing a mature sidearm-striking pattern approximated that of boys. PMID:8570363

  4. A comprehensive analysis of CDC20 overexpression in common malignant tumors from multiple organs: its correlation with tumor grade and stage.

    PubMed

    Gayyed, Mariana F; El-Maqsoud, Nehad M R Abd; Tawfiek, Ehab Rifat; El Gelany, Saad Abdelnaby A; Rahman, Mohamed Fathy Abdel

    2016-01-01

    High expression of cell division cycle 20 homolog (CDC20), a key component of the spindle assembly checkpoint (SAC), has been reported in various malignancies and plays a vital role in tumorigenesis and progression. The goal of this study was to evaluate the utility of CDC20 immunostaining in a wide range of malignant tumors. CDC20 immunohistochemistry was evaluated in normal tissues and compared to the most frequently occurring malignant tumors in these tissues (bladder, breast, cervical, colonic, endometrial, gastric, head and neck, liver, lung, ovarian, pancreatic, prostatic, renal, thyroid carcinomas, and testicular seminoma). Normal/non-neoplastic tissues showed positive CDC20 expression in 19.44 % of all examined cases. CDC20 staining was negative in normal and non-neoplastic tissues from the bladder, cervix, liver, stomach, and thyroid. From the all malignant tumors examined 55.7 % showed high CDC20 expression while low expression was found in 44.3 %. High expression of CDC20 was associated with high tumor grade in the bladder (p = 0.027), cervical (p = 0.032), colonic (p = 0.026), endometrial (p = 0.016), gastric (p = 0.033), liver (p = 0.028), ovarian (p = 0.044), prostatic (p = 0.040), and renal (p = 0.048) carcinomas. There was a significant correlation between high CDC20 expression and advanced tumor stage in carcinoma of the breast, colon, endometrium, and prostate (p = 0.021, p = 0.040, p = 0.047, p = 0.031, respectively). CDC20 expression may be useful as a biomarker of tumor prognosis and as a therapeutic target of human cancer. PMID:26245990

  5. Digital Mammography Screening: Does Age Influence the Detection Rates of Low-, Intermediate-, and High-Grade Ductal Carcinoma in Situ?

    PubMed

    Weigel, Stefanie; Hense, Hans W; Heidrich, Jan; Berkemeyer, Shoma; Heindel, Walter; Heidinger, Oliver

    2016-03-01

    Purpose To investigate the association between age at screening and detection rates for ductal carcinoma in situ (DCIS) separately for different nuclear grades after introduction of a population-based digital mammography screening program. Materials and Methods The retrospective study was approved by the ethics board and did not require informed consent. In 733 905 women aged 50-69 years who participated in a screening program for the first time in 2005-2008 (baseline examinations were performed with digital mammography), DCIS detection rates were determined for 5-year age groups (detection rates per 1000 women screened) to distinguish high-, intermediate-, and low-grade DCIS. Multivariable logistic regression was used to compare detection rates between age groups by adjusting for screening units (P < .05). Results There were 989 graded DCIS diagnoses among 733 905 women (detection rate, 1.35‰): 419 diagnoses of high-grade DCIS (detection rate, 0.57‰), 388 diagnoses of intermediate-grade DCIS (detection rate, 0.53‰), and 182 diagnoses of low-grade DCIS (detection rate, 0.25‰). Detection rate for types of DCIS combined increased significantly across age groups (50-54 years, detection rate of 1.15‰ [254 of 220 985 women]; 55-59 years, detection rate of 1.23‰ [218 of 177 782 women]; 60-64 years, detection rate of 1.34‰ [201 of 150 415 women]; and 65-69 years, detection rate of 1.71‰ [316 of 184 723 women]; P < .001). Of note, the detection rate for high-grade DCIS showed a significant increase with age (odds ratio, 1.18 per 5-year age group; P < .0001). The increase was lower for intermediate-grade DCIS (odds ratio, 1.11; P = .016) and not significant for low-grade DCIS (P = .10). Conclusion Total DCIS detection rates increase with age, mostly because of an increase in high- and intermediate-grade DCIS, which are precursor lesions that carry a higher risk for transition to more aggressive invasive breast cancer than low-grade DCIS. (©) RSNA, 2015

  6. Advanced age negatively impacts survival in an experimental brain tumor model.

    PubMed

    Ladomersky, Erik; Zhai, Lijie; Gritsina, Galina; Genet, Matthew; Lauing, Kristen L; Wu, Meijing; James, C David; Wainwright, Derek A

    2016-09-01

    Glioblastoma (GBM) is the most common primary malignant brain tumor in adults, with an average age of 64 years at the time of diagnosis. To study GBM, a number of mouse brain tumor models have been utilized. In these animal models, subjects tend to range from 6 to 12 weeks of age, which is analogous to that of a human teenager. Here, we examined the impact of age on host immunity and the gene expression associated with immune evasion in immunocompetent mice engrafted with syngeneic intracranial GL261. The data indicate that, in mice with brain tumors, youth conveys an advantage to survival. While age did not affect the tumor-infiltrating T cell phenotype or quantity, we discovered that old mice express higher levels of the immunoevasion enzyme, IDO1, which was decreased by the presence of brain tumor. Interestingly, other genes associated with promoting immunosuppression including CTLA-4, PD-L1 and FoxP3, were unaffected by age. These data highlight the possibility that IDO1 contributes to faster GBM outgrowth with advanced age, providing rationale for future investigation into immunotherapeutic targeting in the future. PMID:27493076

  7. Resetting of RbSr ages of volcanic rocks by low-grade burial metamorphism

    USGS Publications Warehouse

    Asmeroma, Y.; Damon, P.; Shafiqullah, M.; Dickinson, W.R.; Zartman, R.E.

    1991-01-01

    We report a nine-point RbSr whole-rock isochron age of 70??3 Ma (MSWD 3.97) for Mid-Jurassic volcanic rocks. The same rocks have also been dated by the UThPb method on zircon, giving a crystallization age of 166 ?? 11 Ma, over twice as old as the RbSr age. The data demonstrate that whole-rock RbSr ages of volcanic rocks, even lava flows with SiO2 content as low as 57 wt.%, are susceptible to complete resetting. The rocks range in composition from rhyodacite tuffs to andesite lavas. The complete breakdown of all major minerals that contain Rb and Sr resulted in an alteration mineral assemblage consisting of phengite, albite, secondary quartz, and minor amounts of chlorite and epidote. Phengite is the K-bearing product of the breakdown of biotite and K-feldspar. Pressure during low-grade metamorphism of the volcanic rocks, estimated from phengite composition to have been in the range of 4 to 6 kbar, points to thrust-related burial as the main cause of resetting. Consequently, such reset isochrons may date large-scale events such as regional thrusting and metamorphism. The coherent resetting of the RbSr isochron suggests large-scale pervasive fluid movement during thrust-related burial metamorphism. ?? 1991.

  8. Correlation between aging grade of T91 steel and spectral characteristics of the laser-induced plasma

    NASA Astrophysics Data System (ADS)

    Li, Jun; Lu, Jidong; Dai, Yuan; Dong, Meirong; Zhong, Wanli; Yao, Shunchun

    2015-08-01

    T91 steel with favorable mechanical performance has become the representative heat-resistant steel used as heat exchange surfaces in supercritical and ultra-supercritical boilers. The organizational structure and mechanical properties change during the service period, called material aging, which affects the service life and the equipment safety. To develop a fast and easy aging predictive technique of heat exchange metal surfaces, laser-induced breakdown spectroscopy (LIBS) was applied to investigate the plasma characteristics of T91 steel specimens with different aging grades. The metallographic structure, mechanical properties and spectral characteristics of the specimens were analyzed. Then, the correlations between the spectral characteristics and the aging grade were established. The analysis results show that the martensite substructure disappears, and the dimension of the carbide particles among the crystal lattices increases with aging. At the same time, the hardness of the samples gradually decreases. The peak intensities of both the matrix and the alloying element increases then decreases with aging, owing to the change of the metallography structure and mechanical properties. Furthermore, good unique value correlations between the intensity ratio of CrI/FeI, MoI/FeI and the aging grade are found. This demonstrates that LIBS is a possible new way to estimate the aging grade of metal materials.

  9. Molecular classification of non-muscle-invasive bladder cancer (pTa low-grade, pT1 low-grade, and pT1 high-grade subgroups) using methylation of tumor-suppressor genes.

    PubMed

    Sacristan, Raquel; Gonzalez, Carolina; Fernández-Gómez, Jesus M; Fresno, Florentino; Escaf, Safwan; Sánchez-Carbayo, Marta

    2014-09-01

    The role of epigenetics in distinguishing pathological and clinical subgroups in bladder cancer is not fully characterized. We evaluated whether methylation of tumor-suppressor genes (TSGs) would classify non-muscle-invasive (NMI) bladder cancer subgroups and predict outcome. A retrospective design included the following paraffin-embedded primary NMI tumor types (n = 251): pTa low grade (LG) (n = 79), pT1LG (n = 81), and pT1 high grade (HG) (n = 91). Methylation of 25 TSGs was measured using methylation-specific, multiplex, ligation-dependent probe amplification. The TSGs most frequently methylated in the overall series were STK11 (96.8%), MGMT2 (64.5%), RARB (63.0%), and GATA5 (63.0%). TSG methylation correlated to clinicopathological variables in each subgroup and in the overall NMI series. Methylation of RARB, CD44, PAX5A, GSTP1, IGSF4 (CADM1), PYCARD, CDH13, TP53, and GATA5 classified pTa versus pT1 tumors whereas RARB, CD44, GSTP1, IGSF4, CHFR, PYCARD, TP53, STK11, and GATA5 distinguished LG versus HG tumors. Multivariate analyses indicated that PAX5A, WT1, and BRCA1 methylation independently predicted recurrence in pTaLG, PAX6, ATM, CHFR, and RB1 in pT1LG disease; PYCARD, in pT1HG disease; and PAX5A and RB1, in the overall series. Methylation of TSGs provided a molecular classification of NMI disease according to clinicopathological factors. Furthermore, TSG methylation predicted recurrence in NMI subgroups. PMID:24998186

  10. Treatment of locally advanced, high-grade, malignant tumors of major salivary glands

    SciTech Connect

    Reddy, S.P.; Marks, J.E.

    1988-04-01

    A retrospective review of 45 patients with Stage III and IV malignant tumors of the major salivary glands was undertaken to determine tumor control and patient survival after treatment with surgery and conventional ionizing-radiation therapy. Eight of the 23 patients received early postoperative radiotherapy after initial surgical resection, with a local control rate of 75%. Twelve of 23 patients had surgery as definitive treatment and the tumor recurred locally in all; seven of these 12 patients were subsequently salvaged by further surgery plus postoperative radiotherapy or by radiotherapy alone, with 58% ultimate local control. The remaining three patients had unresectable tumors at diagnosis and received radiation alone, with a local tumor control rate of 33%. Patients were also analyzed according to the extent of surgical resection prior to radiation therapy and according to radiation dose. Eighty-eight percent of completely resected, 50% of partially resected, and 44% of unresected tumors were locally controlled for an overall local control rate of 61%. The 5-year survival rate was significantly higher for patients with local tumor control than for patients who failed locally (31% vs. 0%).

  11. Genetic variation in mitotic regulatory pathway genes is associated with breast tumor grade.

    PubMed

    Purrington, Kristen S; Slettedahl, Seth; Bolla, Manjeet K; Michailidou, Kyriaki; Czene, Kamila; Nevanlinna, Heli; Bojesen, Stig E; Andrulis, Irene L; Cox, Angela; Hall, Per; Carpenter, Jane; Yannoukakos, Drakoulis; Haiman, Christopher A; Fasching, Peter A; Mannermaa, Arto; Winqvist, Robert; Brenner, Hermann; Lindblom, Annika; Chenevix-Trench, Georgia; Benitez, Javier; Swerdlow, Anthony; Kristensen, Vessela; Guénel, Pascal; Meindl, Alfons; Darabi, Hatef; Eriksson, Mikael; Fagerholm, Rainer; Aittomäki, Kristiina; Blomqvist, Carl; Nordestgaard, Børge G; Nielsen, Sune F; Flyger, Henrik; Wang, Xianshu; Olswold, Curtis; Olson, Janet E; Mulligan, Anna Marie; Knight, Julia A; Tchatchou, Sandrine; Reed, Malcolm W R; Cross, Simon S; Liu, Jianjun; Li, Jingmei; Humphreys, Keith; Clarke, Christine; Scott, Rodney; Fostira, Florentia; Fountzilas, George; Konstantopoulou, Irene; Henderson, Brian E; Schumacher, Fredrick; Le Marchand, Loic; Ekici, Arif B; Hartmann, Arndt; Beckmann, Matthias W; Hartikainen, Jaana M; Kosma, Veli-Matti; Kataja, Vesa; Jukkola-Vuorinen, Arja; Pylkäs, Katri; Kauppila, Saila; Dieffenbach, Aida Karina; Stegmaier, Christa; Arndt, Volker; Margolin, Sara; Balleine, Rosemary; Arias Perez, Jose Ignacio; Pilar Zamora, M; Menéndez, Primitiva; Ashworth, Alan; Jones, Michael; Orr, Nick; Arveux, Patrick; Kerbrat, Pierre; Truong, Thérèse; Bugert, Peter; Toland, Amanda E; Ambrosone, Christine B; Labrèche, France; Goldberg, Mark S; Dumont, Martine; Ziogas, Argyrios; Lee, Eunjung; Dite, Gillian S; Apicella, Carmel; Southey, Melissa C; Long, Jirong; Shrubsole, Martha; Deming-Halverson, Sandra; Ficarazzi, Filomena; Barile, Monica; Peterlongo, Paolo; Durda, Katarzyna; Jaworska-Bieniek, Katarzyna; Tollenaar, Robert A E M; Seynaeve, Caroline; Brüning, Thomas; Ko, Yon-Dschun; Van Deurzen, Carolien H M; Martens, John W M; Kriege, Mieke; Figueroa, Jonine D; Chanock, Stephen J; Lissowska, Jolanta; Tomlinson, Ian; Kerin, Michael J; Miller, Nicola; Schneeweiss, Andreas; Tapper, William J; Gerty, Susan M; Durcan, Lorraine; Mclean, Catriona; Milne, Roger L; Baglietto, Laura; dos Santos Silva, Isabel; Fletcher, Olivia; Johnson, Nichola; Van'T Veer, Laura J; Cornelissen, Sten; Försti, Asta; Torres, Diana; Rüdiger, Thomas; Rudolph, Anja; Flesch-Janys, Dieter; Nickels, Stefan; Weltens, Caroline; Floris, Giuseppe; Moisse, Matthieu; Dennis, Joe; Wang, Qin; Dunning, Alison M; Shah, Mitul; Brown, Judith; Simard, Jacques; Anton-Culver, Hoda; Neuhausen, Susan L; Hopper, John L; Bogdanova, Natalia; Dörk, Thilo; Zheng, Wei; Radice, Paolo; Jakubowska, Anna; Lubinski, Jan; Devillee, Peter; Brauch, Hiltrud; Hooning, Maartje; García-Closas, Montserrat; Sawyer, Elinor; Burwinkel, Barbara; Marmee, Frederick; Eccles, Diana M; Giles, Graham G; Peto, Julian; Schmidt, Marjanka; Broeks, Annegien; Hamann, Ute; Chang-Claude, Jenny; Lambrechts, Diether; Pharoah, Paul D P; Easton, Douglas; Pankratz, V Shane; Slager, Susan; Vachon, Celine M; Couch, Fergus J

    2014-11-15

    Mitotic index is an important component of histologic grade and has an etiologic role in breast tumorigenesis. Several small candidate gene studies have reported associations between variation in mitotic genes and breast cancer risk. We measured associations between 2156 single nucleotide polymorphisms (SNPs) from 194 mitotic genes and breast cancer risk, overall and by histologic grade, in the Breast Cancer Association Consortium (BCAC) iCOGS study (n = 39 067 cases; n = 42 106 controls). SNPs in TACC2 [rs17550038: odds ratio (OR) = 1.24, 95% confidence interval (CI) 1.16-1.33, P = 4.2 × 10(-10)) and EIF3H (rs799890: OR = 1.07, 95% CI 1.04-1.11, P = 8.7 × 10(-6)) were significantly associated with risk of low-grade breast cancer. The TACC2 signal was retained (rs17550038: OR = 1.15, 95% CI 1.07-1.23, P = 7.9 × 10(-5)) after adjustment for breast cancer risk SNPs in the nearby FGFR2 gene, suggesting that TACC2 is a novel, independent genome-wide significant genetic risk locus for low-grade breast cancer. While no SNPs were individually associated with high-grade disease, a pathway-level gene set analysis showed that variation across the 194 mitotic genes was associated with high-grade breast cancer risk (P = 2.1 × 10(-3)). These observations will provide insight into the contribution of mitotic defects to histological grade and the etiology of breast cancer. PMID:24927736

  12. Genetic variation in mitotic regulatory pathway genes is associated with breast tumor grade

    PubMed Central

    Purrington, Kristen S.; Slettedahl, Seth; Bolla, Manjeet K.; Michailidou, Kyriaki; Czene, Kamila; Nevanlinna, Heli; Bojesen, Stig E.; Andrulis, Irene L.; Cox, Angela; Hall, Per; Carpenter, Jane; Yannoukakos, Drakoulis; Haiman, Christopher A.; Fasching, Peter A.; Mannermaa, Arto; Winqvist, Robert; Brenner, Hermann; Lindblom, Annika; Chenevix-Trench, Georgia; Benitez, Javier; Swerdlow, Anthony; Kristensen, Vessela; Guénel, Pascal; Meindl, Alfons; Darabi, Hatef; Eriksson, Mikael; Fagerholm, Rainer; Aittomäki, Kristiina; Blomqvist, Carl; Nordestgaard, Børge G.; Nielsen, Sune F.; Flyger, Henrik; Wang, Xianshu; Olswold, Curtis; Olson, Janet E.; Mulligan, Anna Marie; Knight, Julia A.; Tchatchou, Sandrine; Reed, Malcolm W.R.; Cross, Simon S.; Liu, Jianjun; Li, Jingmei; Humphreys, Keith; Clarke, Christine; Scott, Rodney; Fostira, Florentia; Fountzilas, George; Konstantopoulou, Irene; Henderson, Brian E.; Schumacher, Fredrick; Le Marchand, Loic; Ekici, Arif B.; Hartmann, Arndt; Beckmann, Matthias W.; Hartikainen, Jaana M.; Kosma, Veli-Matti; Kataja, Vesa; Jukkola-Vuorinen, Arja; Pylkäs, Katri; Kauppila, Saila; Dieffenbach, Aida Karina; Stegmaier, Christa; Arndt, Volker; Margolin, Sara; Balleine, Rosemary; Arias Perez, Jose Ignacio; Pilar Zamora, M.; Menéndez, Primitiva; Ashworth, Alan; Jones, Michael; Orr, Nick; Arveux, Patrick; Kerbrat, Pierre; Truong, Thérèse; Bugert, Peter; Toland, Amanda E.; Ambrosone, Christine B.; Labrèche, France; Goldberg, Mark S.; Dumont, Martine; Ziogas, Argyrios; Lee, Eunjung; Dite, Gillian S.; Apicella, Carmel; Southey, Melissa C.; Long, Jirong; Shrubsole, Martha; Deming-Halverson, Sandra; Ficarazzi, Filomena; Barile, Monica; Peterlongo, Paolo; Durda, Katarzyna; Jaworska-Bieniek, Katarzyna; Tollenaar, Robert A.E.M.; Seynaeve, Caroline; Brüning, Thomas; Ko, Yon-Dschun; Van Deurzen, Carolien H.M.; Martens, John W.M.; Kriege, Mieke; Figueroa, Jonine D.; Chanock, Stephen J.; Lissowska, Jolanta; Tomlinson, Ian; Kerin, Michael J.; Miller, Nicola; Schneeweiss, Andreas; Tapper, William J.; Gerty, Susan M.; Durcan, Lorraine; Mclean, Catriona; Milne, Roger L.; Baglietto, Laura; dos Santos Silva, Isabel; Fletcher, Olivia; Johnson, Nichola; Van'T Veer, Laura J.; Cornelissen, Sten; Försti, Asta; Torres, Diana; Rüdiger, Thomas; Rudolph, Anja; Flesch-Janys, Dieter; Nickels, Stefan; Weltens, Caroline; Floris, Giuseppe; Moisse, Matthieu; Dennis, Joe; Wang, Qin; Dunning, Alison M.; Shah, Mitul; Brown, Judith; Simard, Jacques; Anton-Culver, Hoda; Neuhausen, Susan L.; Hopper, John L.; Bogdanova, Natalia; Dörk, Thilo; Zheng, Wei; Radice, Paolo; Jakubowska, Anna; Lubinski, Jan; Devillee, Peter; Brauch, Hiltrud; Hooning, Maartje; García-Closas, Montserrat; Sawyer, Elinor; Burwinkel, Barbara; Marmee, Frederick; Eccles, Diana M.; Giles, Graham G.; Peto, Julian; Schmidt, Marjanka; Broeks, Annegien; Hamann, Ute; Chang-Claude, Jenny; Lambrechts, Diether; Pharoah, Paul D.P.; Easton, Douglas; Pankratz, V. Shane; Slager, Susan; Vachon, Celine M.; Couch, Fergus J.

    2014-01-01

    Mitotic index is an important component of histologic grade and has an etiologic role in breast tumorigenesis. Several small candidate gene studies have reported associations between variation in mitotic genes and breast cancer risk. We measured associations between 2156 single nucleotide polymorphisms (SNPs) from 194 mitotic genes and breast cancer risk, overall and by histologic grade, in the Breast Cancer Association Consortium (BCAC) iCOGS study (n = 39 067 cases; n = 42 106 controls). SNPs in TACC2 [rs17550038: odds ratio (OR) = 1.24, 95% confidence interval (CI) 1.16–1.33, P = 4.2 × 10−10) and EIF3H (rs799890: OR = 1.07, 95% CI 1.04–1.11, P = 8.7 × 10−6) were significantly associated with risk of low-grade breast cancer. The TACC2 signal was retained (rs17550038: OR = 1.15, 95% CI 1.07–1.23, P = 7.9 × 10−5) after adjustment for breast cancer risk SNPs in the nearby FGFR2 gene, suggesting that TACC2 is a novel, independent genome-wide significant genetic risk locus for low-grade breast cancer. While no SNPs were individually associated with high-grade disease, a pathway-level gene set analysis showed that variation across the 194 mitotic genes was associated with high-grade breast cancer risk (P = 2.1 × 10−3). These observations will provide insight into the contribution of mitotic defects to histological grade and the etiology of breast cancer. PMID:24927736

  13. Resonant Raman spectra of grades of human brain glioma tumors reveal the content of tryptophan by the 1588 cm-1 mode

    NASA Astrophysics Data System (ADS)

    Zhou, Yan; Liu, Cheng-hui; Zhou, Lixin; Zhu, Ke; Liu, Yulong; Zhang, Lin; Boydston-White, Susie; Cheng, Gangge; Pu, Yang; Bidyut, Das; Alfano, Robert R.

    2015-03-01

    RR spectra of brain normal tissue, gliomas in low grade I and II, and malignant glioma tumors in grade III and IV were measured using a confocal micro Raman spectrometer. This report focus on the relative contents of tryptophan (W) in various grades of brain glioma tumors by the intrinsic molecular resonance Raman (RR) spectroscopy method using the 1588cm-1 of tryptophan mode by 532 nm excitation. The RR spectra of key fingerprints of tryptophan, with a main vibrational mode at 1588cm-1 (W8b), were observed. It was found that tryptophan contribution was accumulated in grade I to IV gliomas and the mode of 1588cm-1 in grade III and IV malignant gliomas were enhanced by resonance.

  14. Concurrent hypermethylation of multiple genes is associated with grade of oligodendroglial tumors.

    PubMed

    Dong, S M; Pang, J C; Poon, W S; Hu, J; To, K F; Chang, A R; Ng, H K

    2001-08-01

    Current evidence suggests that epigenetic changes play an important role in the evolution of human cancers. In this study, we evaluated whether hypermethylation of CpG islands at the gene promotor regions of several tumor-related genes is involved in the carcinogenesis of oligodendroglial tumors. We examined the methylation status of 11 genes in a series of 43 oligodendroglial tumors (19 oligodendrogliomas, 13 anaplastic oligodendrogliomas, 9 oligoastrocytomas, and 2 anaplastic oligoastrocytomas) by methylation-specific polymerase chain reaction. Our results showed that hypermethylation of CpG islands was detectable in 8 of 11 genes studied and 74% of tumors were hypermethylated in at least 1 gene. Promotor hypermethylations were detected in O6-methylguanine-DNA methyltransferase (MGMT), RB1, estrogen receptor, p73, p16INK4a, death-associated protein kinase, p15INK4b, and p14ARF at 60%, 34%, 30%, 16%, 12%, 10%, 7%, and 2%, respectively. No hypermethylation was detected in the promotors of glutathione-S-transferase P1, von Hippel-Lindau or the DNA mismatch repair (hMLH1) genes. Statistical analysis revealed that concordant hypermethylation of at least 2 genes, p16INK4a and p15INK4b were significantly associated with anaplastic oligodendroglial tumors, and hypermethylation of MGMT was significantly associated with loss of chromosome 19q and with combined loss of chromosomes 1p and 19q. More importantly, several candidate tumor suppressor genes such as p16INK4a, p15INK4b, and p73 that were previously reported as unmutated in oligodendroglial tumors were found to be hypermethylated in their CpG islands. Taken together, we conclude that hypermethylation of CpG islands is a common epigenetic event that is associated with the development of oligodendroglial tumors. PMID:11487055

  15. Clinically occult tubal and ovarian high-grade serous carcinomas presenting in uterine samples: diagnostic pitfalls and clues to improve recognition of tumor origin.

    PubMed

    Bagby, Christina; Ronnett, Brigitte M; Yemelyanova, Anna; Maleki, Zahra; Kuhn, Elisabetta; Vang, Russell

    2013-09-01

    We report the clinicopathologic and immunohistochemical features in 8 patients with tubal or ovarian high-grade serous carcinoma that was present in uterine samples, in which there was the potential for clinical and morphologic misinterpretation as a primary uterine lesion before hysterectomy/bilateral salpingo-oophorectomy. Patients ranged in age from 45 to 70 yr (mean, 57 yr). The initial presentation was variable, ranging from incidental findings on routine Pap smears to pleural effusion. During the preoperative clinical investigation, 7 of 8 patients did not have evidence of an adnexal tumor based on physical examination and radiologic imaging, and serum CA-125 levels were normal to low in 4 of 5 patients. Six patients required multiple rounds of uterine samples, and the preoperative uterine specimens that contained lesional tissue and were available for rereview in all 8 patients included endometrial biopsies/curettages (n=6), endocervical curettages (n=3), Pap smears (n=2), and a hysteroscopic myomectomy specimen (n=1). The amount of carcinoma in these specimens was typically scanty. The lesions in most cases were characterized by detached and minute epithelial clusters, small papillae, and/or individual cells. The constituent glandular cells exhibited notable atypia. Psammoma bodies were identified in only 2 cases. Immunostains for WT-1 were positive in 3 of 4 preoperative specimens. All patients ultimately underwent a hysterectomy/bilateral salpingo-oophorectomy, which revealed an invasive high-grade serous carcinoma of tubal (n=6) or ovarian (n=2) origin. The mean/median tumor size was 3.2/1.7 cm. Transtubal spread was considered the most likely mechanism resulting in tubal/ovarian carcinoma being found in the preoperative uterine samples. These findings highlight the deceptive clinical features of some tubal/ovarian high-grade serous carcinomas, and demonstrate that small and clinically undetectable adnexal high-grade serous carcinomas can initially

  16. Neuropsychological status in children and young adults with benign and low-grade brain tumors treated prospectively with focal stereotactic conformal radiotherapy

    SciTech Connect

    Jalali, Rakesh . E-mail: rjalali@medscape.com; Goswami, Savita; Sarin, Rajiv; More, Niteen; Siddha, Manish; Kamble, Rashmi

    2006-11-15

    Purpose: To present prospective neuropsychological data at baseline and follow-up in children and young adults with benign and low-grade gliomas treated with focal stereotactic conformal radiotherapy (SCRT). Methods and Materials: A total of 22 patients (age 4-25 years) with residual/progressive benign and low-grade brain tumors considered suitable for SCRT underwent detailed and in-depth neuropsychological and cognitive testing at baseline before SCRT. The test battery included measurement of age-adjusted intelligence quotients (IQs) and cognitive parameters of visual, spatial, visuomotor, and attention concentrations. Anxiety was measured using the State-Trait Anxiety Inventory for Children and Hamilton Anxiety Rating Scale for patients >16 years old. Patients were treated with high-precision conformal radiotherapy under stereotactic guidance to a dose of 54 Gy in 30 fractions. All neuropsychological assessments were repeated at 6 and 24 months after SCRT completion and compared with the baseline values. Results: The baseline mean full-scale IQ before starting RT for patients <16 years was 82 (range, 33-105). For those >16 years, the corresponding value was 72 (range, 64-129). Of 20 evaluable patients, 14 (70%) had less than average IQs at baseline, even before starting radiotherapy. The verbal IQ, performance IQ, and full-scale IQ, as well as other cognitive scores, did not change significantly at the 6- and 24-month follow-up assessments for all patients. The memory quotient in older children and young adults was maintained at 6 and 24 months after SCRT, with a mean value of 93 and 100, respectively, compared with a mean baseline value of 81 before RT. The mean anxiety score in children measured by the C1 and C2 components of the State-Trait Anxiety Inventory for Children (STAIC) was 48 and 40, respectively, which improved significantly to mean values of 30 and 26, respectively, at the 24-month follow-up assessment (p = 0.005). The mean depression score in

  17. KRAS (but not BRAF) mutations in ovarian serous borderline tumor are associated with recurrent low-grade serous carcinoma

    PubMed Central

    Tsang, Yvonne T.; Deavers, Michael T.; Sun, Charlotte C.; Kwan, Suet-Yan; Kuo, Eric; Malpica, Anais; Mok, Samuel C.; Gershenson, David M.; Wong, Kwong-Kwok

    2014-01-01

    BRAF and KRAS mutations in ovarian serous borderline tumors (OSBTs) and ovarian low-grade serous carcinomas (LGSCs) have been previously described. However, whether those OSBTs would progress to LGSCs or those LGSCs were developed from OSBT precursors in previous studies is unknown. Therefore, we assessed KRAS and BRAF mutations in tumor samples from 23 recurrent LGSC patients with known initial diagnosis of OSBT. Paraffin blocks from both OSBT and LGSC samples were available for 5 patients, and either OSBT or LGSC were available for another 18 patients. Tumor cells from paraffin-embedded tissues were dissected out for mutation analysis by conventional polymerase chain reaction (PCR) and Sanger sequencing. Tumors that appeared to have wild-type KRAS by conventional PCR–Sanger sequencing were further analyzed by full COLD (coamplification at lower denaturation temperature)-PCR and deep sequencing. Full COLD-PCR was able to enrich the amplification of mutated alleles. Deep sequencing was performed with the Ion Torrent personal genome machine (PGM). By conventional PCR–Sanger sequencing, BRAF mutation was detected only in one patient and KRAS mutations were detected in 10 patients. Full COLD-PCR deep sequencing detected low-abundance KRAS mutations in eight additional patients. Three of the five patients with both OSBT and LGSC samples available had the same KRAS mutations detected in both OSBT and LGSC samples. The remaining two patients had only KRAS mutations detected in their LGSC samples. For patients with either OSBT or LGSC samples available, KRAS mutations were detected in 7 OSBT samples and 6 LGSC samples. To our surprise, patients with the KRAS G12V mutation appeared to have shorter survival times. In summary, KRAS mutations are very common in recurrent LGSC, while BRAF mutations are rare. The findings indicate that recurrent LGSC can arise from proliferation of OSBT tumor cells with or without detectable KRAS mutations. PMID:24549645

  18. Food-grade titanium dioxide exposure exacerbates tumor formation in colitis associated cancer model.

    PubMed

    Urrutia-Ortega, Ismael M; Garduño-Balderas, Luis G; Delgado-Buenrostro, Norma L; Freyre-Fonseca, Verónica; Flores-Flores, José O; González-Robles, Arturo; Pedraza-Chaverri, José; Hernández-Pando, Rogelio; Rodríguez-Sosa, Miriam; León-Cabrera, Sonia; Terrazas, Luis I; van Loveren, Henk; Chirino, Yolanda I

    2016-07-01

    Colorectal cancer is the fourth worldwide cause of death and even if some dietary habits are consider risk factors, the contribution of food additives including foodgrade titanium dioxide (TiO2), designated as E171, has been poorly investigated. We hypothesized that oral E171 intake could have impact on the enhancement of colorectal tumor formation and we aimed to investigate if E171 administration could enhance tumor formation in a colitis associated cancer (CAC) model. BALB/c male mice were grouped as follows: a) control, b) E171, c) CAC and d) CAC + E171 group (n = 6). E171 used in this study formed agglomerates of 300 nm in water. E171 intragastric administration (5 mg/kg body weight/5 days/10 weeks) was unable to induce tumor formation but dysplastic alterations were observed in the distal colon but enhanced the tumor formation in distal colon (CAC + E171 group) measured by tumor progression markers. Some E171 particles were internalized in colonic cells of the E171 and CAC + E171 groups and both groups showed a decrease in goblet cells in the distal colon. However the CAC + E171 group showed a higher decrease of these cells that act as protection barrier in colon. These results suggest that E171 could worsen pre-existent intestinal diseases. PMID:27117919

  19. Effect of Relative Age in the First Grade of Primary School on Long-Term Scholastic Results: International Comparative Evidence Using PISA 2003

    ERIC Educational Resources Information Center

    Sprietsma, Maresa

    2010-01-01

    In this paper, we estimate the effect of pupil's relative age within the first grade of primary school on mathematics and reading test scores at age 15. The main objective is to evaluate the long-term causal effect of relative age in the first grades of primary school on pupil's test in 16 different countries. We use the national rule for…

  20. Adhesive capsulitis: An age related symptom of metabolic syndrome and chronic low-grade inflammation?

    PubMed

    Pietrzak, Max

    2016-03-01

    Adhesive capsulitis (AC) is very poorly understood, particularly it's underlying etiology. Obesity and metabolic syndrome, which are strongly associated with chronic low grade inflammation, are becoming increasingly understood to underlie a raft of morbid states including upper limb pain syndromes, diabetes (DM), cardiovascular disease (CVD), cancer and central nervous system dysfunction and degeneration. Notwithstanding age, two of the strongest established risk factors for AC are DM and CVD. The hypothesis argues that similar to DM and CVD, the inflammation and capsular fibrosis seen in AC is precipitated by metabolic syndrome and chronic low grade inflammation. These pathophysiological mechanisms are highly likely to be perpetuated by upregulation of pro-inflammatory cytokine production, sympathetic dominance of autonomic balance, and neuro-immune activation. The hypothesis predicts and describes how these processes may etiologically underpin and induce each sub-classification of AC. An improved understanding of the etiology of AC may lead to more accurate diagnosis, improved management, treatment outcomes, and reduce or prevent pain, disability and suffering associated with the disease. The paper follows on with a discussion of similarities between the pathophysiology of AC to general systemic inflammatory control mechanisms whereby connective tissue (CT) fibrosis is induced as a storage depot for leukocytes and chronic inflammatory cells. The potential role of hyaluronic acid (HA), the primary component of the extracellular matrix (ECM) and CT, in the pathophysiology of AC is also discussed with potential treatment implications. Lastly, a biochemical link between physical and mental health through the ECM is described and the concept of a periventricular-limbic central driver of CT dysfunction is introduced. PMID:26880627

  1. Aging and insulin signaling differentially control normal and tumorous germline stem cells

    PubMed Central

    Kao, Shih-Han; Tseng, Chen-Yuan; Wan, Chih-Ling; Su, Yu-Han; Hsieh, Chang-Che; Pi, Haiwei; Hsu, Hwei-Jan

    2015-01-01

    Aging influences stem cells, but the processes involved remain unclear. Insulin signaling, which controls cellular nutrient sensing and organismal aging, regulates the G2 phase of Drosophila female germ line stem cell (GSC) division cycle in response to diet; furthermore, this signaling pathway is attenuated with age. The role of insulin signaling in GSCs as organisms age, however, is also unclear. Here, we report that aging results in the accumulation of tumorous GSCs, accompanied by a decline in GSC number and proliferation rate. Intriguingly, GSC loss with age is hastened by either accelerating (through eliminating expression of Myt1, a cell cycle inhibitory regulator) or delaying (through mutation of insulin receptor (dinR) GSC division, implying that disrupted cell cycle progression and insulin signaling contribute to age-dependent GSC loss. As flies age, DNA damage accumulates in GSCs, and the S phase of the GSC cell cycle is prolonged. In addition, GSC tumors (which escape the normal stem cell regulatory microenvironment, known as the niche) still respond to aging in a similar manner to normal GSCs, suggesting that niche signals are not required for GSCs to sense or respond to aging. Finally, we show that GSCs from mated and unmated females behave similarly, indicating that female GSC–male communication does not affect GSCs with age. Our results indicate the differential effects of aging and diet mediated by insulin signaling on the stem cell division cycle, highlight the complexity of the regulation of stem cell aging, and describe a link between ovarian cancer and aging. PMID:25470527

  2. Hippocampal Dosimetry Predicts Neurocognitive Function Impairment After Fractionated Stereotactic Radiotherapy for Benign or Low-Grade Adult Brain Tumors

    SciTech Connect

    Gondi, Vinai; Hermann, Bruce P.; Mehta, Minesh P.; Tome, Wolfgang A.

    2012-07-15

    Purpose: To prospectively evaluate the association between hippocampal dose and long-term neurocognitive function (NCF) impairment for benign or low-grade adult brain tumors treated with fractionated stereotactic radiotherapy (FSRT). Methods and Materials: Adult patients with benign or low-grade adult brain tumors were treated with FSRT per institutional practice. No attempt was made to spare the hippocampus. NCF testing was conducted at baseline and 18 months follow-up, on a prospective clinical trial. Regression-based standardized z scores were calculated by using similar healthy control individuals evaluated at the same test-retest interval. NCF impairment was defined as a z score {<=}-1.5. After delineation of the bilateral hippocampi according to the Radiation Therapy Oncology Group contouring atlas, dose-volume histograms were generated for the left and right hippocampi and for the composite pair. Biologically equivalent doses in 2-Gy fractions (EQD{sub 2}) assuming an {alpha}/{beta} ratio of 2 Gy were computed. Fisher's exact test and binary logistic regression were used for univariate and multivariate analyses, respectively. Dose-response data were fit to a nonlinear model. Results: Of 29 patients enrolled in this trial, 18 completed both baseline and 18-month NCF testing. An EQD{sub 2} to 40% of the bilateral hippocampi >7.3 Gy was associated with impairment in Wechsler Memory Scale-III Word List (WMS-WL) delayed recall (odds ratio [OR] 19.3; p = 0.043). The association between WMS-WL delayed recall and EQD{sub 2} to 100% of the bilateral hippocampi >0.0 Gy trended to significance (OR 14.8; p = 0.068). Conclusion: EQD{sub 2} to 40% of the bilateral hippocampi greater than 7.3 Gy is associated with long-term impairment in list-learning delayed recall after FSRT for benign or low-grade adult brain tumors. Given that modern intensity-modulated radiotherapy techniques can reduce the dose to the bilateral hippocampi below this dosimetric threshold, patients

  3. Hippocampal Dosimetry Predicts Neurocognitive Function Impairment After Fractionated Stereotactic Radiotherapy for Benign or Low-Grade Adult Brain Tumors

    SciTech Connect

    Gondi, Vinai; Hermann, Bruce P.; Mehta, Minesh P.; Tome, Wolfgang A.

    2013-02-01

    Purpose: To prospectively evaluate the association between hippocampal dose and long-term neurocognitive function (NCF) impairment for benign or low-grade adult brain tumors treated with fractionated stereotactic radiotherapy (FSRT). Methods and Materials: Adult patients with benign or low-grade adult brain tumors were treated with FSRT per institutional practice. No attempt was made to spare the hippocampus. NCF testing was conducted at baseline and 18 months follow-up, on a prospective clinical trial. Regression-based standardized z scores were calculated by using similar healthy control individuals evaluated at the same test-retest interval. NCF impairment was defined as a z score {<=}-1.5. After delineation of the bilateral hippocampi according to the Radiation Therapy Oncology Group contouring atlas, dose-volume histograms were generated for the left and right hippocampi and for the composite pair. Biologically equivalent doses in 2-Gy fractions (EQD{sub 2}) assuming an {alpha}/{beta} ratio of 2 Gy were computed. Fisher's exact test and binary logistic regression were used for univariate and multivariate analyses, respectively. Dose-response data were fit to a nonlinear model. Results: Of 29 patients enrolled in this trial, 18 completed both baseline and 18-month NCF testing. An EQD{sub 2} to 40% of the bilateral hippocampi >7.3 Gy was associated with impairment in Wechsler Memory Scale-III Word List (WMS-WL) delayed recall (odds ratio [OR] 19.3; p = 0.043). The association between WMS-WL delayed recall and EQD{sub 2} to 100% of the bilateral hippocampi >0.0 Gy trended to significance (OR 14.8; p = 0.068). Conclusion: EQD{sub 2} to 40% of the bilateral hippocampi greater than 7.3 Gy is associated with long-term impairment in list-learning delayed recall after FSRT for benign or low-grade adult brain tumors. Given that modern intensity-modulated radiotherapy techniques can reduce the dose to the bilateral hippocampi below this dosimetric threshold, patients

  4. Applications of a novel tumor-grading-metastasis staging system for pancreatic neuroendocrine tumors: An analysis of surgical patients from a Chinese institution.

    PubMed

    Yang, Min; Tan, Chun-Lu; Zhang, Yi; Ke, Neng-Wen; Zeng, Lin; Li, Ang; Zhang, Hao; Xiong, Jun-Jie; Guo, Zi-Heng; Tian, Bo-Le; Liu, Xu-Bao

    2016-07-01

    The ability to stratify patients with pancreatic neuroendocrine tumors (p-NETs) into prognostic groups has been hindered by the absence of a commonly accepted staging system. Both the 7th tumor-node-metastasis (TNM) staging guidelines by the American Joint Committee on Cancer (AJCC) and the 2010 grading classifications by the World Health Organization (WHO) were validated to be unsatisfactory.We aim to evaluate the feasibility of combining the latest AJCC and WHO criteria to devise a novel tumor-grading-metastasis (TGM) staging system. We also sought to examine the stage-specific survival rates and the prognostic value of this new TGM system for p-NETs.Data of 120 patients with surgical resection and histopathological diagnosis of p-NETs from January 2004 to February 2014 in our institution were retrospectively collected and analyzed. Based on the AJCC and WHO criteria, we replaced the stage N0 and N1 with stage Ga (NET G1 and NET G2) and Gb (NET G3 and MANEC) respectively, without changes of the definition of T or M stage. The present novel TGM staging system was grouped as follows: stage I was defined as T1-2, Ga, M0; stage II as T3, Ga, M0 or as T1-3, Gb, M0; stage III as T4, Ga-b, M0 and stage IV as any T, M1.The new TGM staging system successfully distributed 55, 42, 12, and 11 eligible patients in stage I to IV, respectively. Differences of survival compared stage I with III and IV for patients with p-NETs were both statistically significant (P < 0.001), as well as those of stage II with III and IV (P < 0.001). Patients in stage I showed better a survival than those in stage II, whereas difference between stages III and IV was not notable (P = 0.001, P = 0.286, respectively). In multivariate models, when the TGM staging system was evaluated in place of the individual T, G, and M variables, this new criteria were proven to be an independent predictor of survival for surgically resected p-NETs (P < 0.05).Stratifying patients well, the current

  5. Near-infrared spectroscopy as a complementary age grading and species identification tool for African malaria vectors

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Near-infrared spectroscopy (NIRS) was recently applied to age-grade and differentiate laboratory reared Anopheles gambiae sensu strico and Anopheles arabiensis sibling species of Anopheles gambiae sensu lato. In this study, we report further on the accuracy of this tool in simultaneously estimating ...

  6. Age in Grade Congruence and Progression in Basic Education in Bangladesh. CREATE Pathways to Access. Research Monograph No. 48

    ERIC Educational Resources Information Center

    Hossain, Altaf

    2010-01-01

    In Bangladesh gross and net enrolment rates are used to measure overage and underage enrolment in the education system. However, due to the limits of these methods in exploring the issue of age in grade, the paper uses the CREATE Community and School Survey (COMSS) data from Bangladesh. COMSS was a longitudinal survey of 6,696 households with…

  7. Can Inhibition at Preschool Age Predict Attention-Deficit/Hyperactivity Disorder Symptoms and Social Difficulties in Third Grade?

    ERIC Educational Resources Information Center

    Gewirtz, Shawn; Stanton-Chapman, Tina L.; Reeve, Ronald E.

    2009-01-01

    The present study examined whether deficits in inhibitory control in preschool-aged children are predictive of attention-deficit/hyperactivity disorder (ADHD) symptoms and certain social difficulties in middle childhood, specifically third grade. Although many studies have examined the concurrent relationships among disinhibition, ADHD and social…

  8. Genetic alterations in uncommon low-grade neuroepithelial tumors: BRAF, FGFR1, and MYB mutations occur at high frequency and align with morphology.

    PubMed

    Qaddoumi, Ibrahim; Orisme, Wilda; Wen, Ji; Santiago, Teresa; Gupta, Kirti; Dalton, James D; Tang, Bo; Haupfear, Kelly; Punchihewa, Chandanamali; Easton, John; Mulder, Heather; Boggs, Kristy; Shao, Ying; Rusch, Michael; Becksfort, Jared; Gupta, Pankaj; Wang, Shuoguo; Lee, Ryan P; Brat, Daniel; Peter Collins, V; Dahiya, Sonika; George, David; Konomos, William; Kurian, Kathreena M; McFadden, Kathryn; Serafini, Luciano Neder; Nickols, Hilary; Perry, Arie; Shurtleff, Sheila; Gajjar, Amar; Boop, Fredrick A; Klimo, Paul D; Mardis, Elaine R; Wilson, Richard K; Baker, Suzanne J; Zhang, Jinghui; Wu, Gang; Downing, James R; Tatevossian, Ruth G; Ellison, David W

    2016-06-01

    Low-grade neuroepithelial tumors (LGNTs) are diverse CNS tumors presenting in children and young adults, often with a history of epilepsy. While the genetic profiles of common LGNTs, such as the pilocytic astrocytoma and 'adult-type' diffuse gliomas, are largely established, those of uncommon LGNTs remain to be defined. In this study, we have used massively parallel sequencing and various targeted molecular genetic approaches to study alterations in 91 LGNTs, mostly from children but including young adult patients. These tumors comprise dysembryoplastic neuroepithelial tumors (DNETs; n = 22), diffuse oligodendroglial tumors (d-OTs; n = 20), diffuse astrocytomas (DAs; n = 17), angiocentric gliomas (n = 15), and gangliogliomas (n = 17). Most LGNTs (84 %) analyzed by whole-genome sequencing (WGS) were characterized by a single driver genetic alteration. Alterations of FGFR1 occurred frequently in LGNTs composed of oligodendrocyte-like cells, being present in 82 % of DNETs and 40 % of d-OTs. In contrast, a MYB-QKI fusion characterized almost all angiocentric gliomas (87 %), and MYB fusion genes were the most common genetic alteration in DAs (41 %). A BRAF:p.V600E mutation was present in 35 % of gangliogliomas and 18 % of DAs. Pathogenic alterations in FGFR1/2/3, BRAF, or MYB/MYBL1 occurred in 78 % of the series. Adult-type d-OTs with an IDH1/2 mutation occurred in four adolescents, the youngest aged 15 years at biopsy. Despite a detailed analysis, novel genetic alterations were limited to two fusion genes, EWSR1-PATZ1 and SLMAP-NTRK2, both in gangliogliomas. Alterations in BRAF, FGFR1, or MYB account for most pathogenic alterations in LGNTs, including pilocytic astrocytomas, and alignment of these genetic alterations and cytologic features across LGNTs has diagnostic implications. Additionally, therapeutic options based upon targeting the effects of these alterations are already in clinical trials. PMID:26810070

  9. Automatic Screening and Grading of Age-Related Macular Degeneration from Texture Analysis of Fundus Images.

    PubMed

    Phan, Thanh Vân; Seoud, Lama; Chakor, Hadi; Cheriet, Farida

    2016-01-01

    Age-related macular degeneration (AMD) is a disease which causes visual deficiency and irreversible blindness to the elderly. In this paper, an automatic classification method for AMD is proposed to perform robust and reproducible assessments in a telemedicine context. First, a study was carried out to highlight the most relevant features for AMD characterization based on texture, color, and visual context in fundus images. A support vector machine and a random forest were used to classify images according to the different AMD stages following the AREDS protocol and to evaluate the features' relevance. Experiments were conducted on a database of 279 fundus images coming from a telemedicine platform. The results demonstrate that local binary patterns in multiresolution are the most relevant for AMD classification, regardless of the classifier used. Depending on the classification task, our method achieves promising performances with areas under the ROC curve between 0.739 and 0.874 for screening and between 0.469 and 0.685 for grading. Moreover, the proposed automatic AMD classification system is robust with respect to image quality. PMID:27190636

  10. Automatic Screening and Grading of Age-Related Macular Degeneration from Texture Analysis of Fundus Images

    PubMed Central

    Phan, Thanh Vân; Seoud, Lama; Chakor, Hadi; Cheriet, Farida

    2016-01-01

    Age-related macular degeneration (AMD) is a disease which causes visual deficiency and irreversible blindness to the elderly. In this paper, an automatic classification method for AMD is proposed to perform robust and reproducible assessments in a telemedicine context. First, a study was carried out to highlight the most relevant features for AMD characterization based on texture, color, and visual context in fundus images. A support vector machine and a random forest were used to classify images according to the different AMD stages following the AREDS protocol and to evaluate the features' relevance. Experiments were conducted on a database of 279 fundus images coming from a telemedicine platform. The results demonstrate that local binary patterns in multiresolution are the most relevant for AMD classification, regardless of the classifier used. Depending on the classification task, our method achieves promising performances with areas under the ROC curve between 0.739 and 0.874 for screening and between 0.469 and 0.685 for grading. Moreover, the proposed automatic AMD classification system is robust with respect to image quality. PMID:27190636

  11. BIOSOCIAL CORRELATES OF AGE AT FIRST SEXUAL INTERCOURSE: THE CASE OF GRADE 9 AND GRADE 11 PUPILS IN THE NORTH WEST PROVINCE OF SOUTH AFRICA.

    PubMed

    Amoateng, Acheampong Yaw; Kalule-Sabiti, Ishmael

    2016-01-01

    Survival analysis - specifically the actuarial life-table method and the Cox Proportional Hazards model - was used to assess Bronfenbrenner's bio-ecological model with regards to the onset of sexual intercourse in a random sample of 1697 grade 9 and grade 11 pupils in the North West Province of South Africa. Data were collected in July and August 2007. Of the contextual factors examined, only academic performance and community disorganization were found to be statistically significantly associated with age at first sexual intercourse amongst girls. High academic performance by girls is positively associated with age at first sexual intercourse, while girls who live in disorganized communities initiate sexual intercourse earlier than their counterparts in other communities. Age is negatively associated with the timing of first sexual debut among both girls and boys. Males initiate sexual intercourse earlier than females, while youths with at least one sexual partner are much more likely to initiate sexual intercourse earlier than those without sexual partners. PMID:25488144

  12. Some Renal Masses Did Not "Read the Book": A Case of a High Grade Hybrid Renal Tumor Masquerading as a Renal Cyst on Non-contrast Imaging.

    PubMed

    Kominsky, Hal D; Parker, Daniel C; Gohil, Dharam; Musial, Rachel; Edwards, Kristin; Kutikov, Alexander

    2015-11-01

    Hybrid renal tumors (HRT) are rare neoplasms that contain both benign and malignant components. Sporadic solitary HRT that contain high-grade malignant pathology appear to be extremely rare [1]. We describe a case at our institution of a tumor that was characterized as a type-2 papillary RCC and atypical oncocytoma hybrid that mimicked a simple cyst on non-contrast computed tomography. PMID:26793558

  13. Does Age of Entry Into First Grade Affect Students' Achievement in School? (Technical Report).

    ERIC Educational Resources Information Center

    Davis, B. Glen; Trimble, C. Scott

    This paper reports on research conducted to determine whether there is a statistically significant difference between the achievement test scores of students who enter first grade as 5-year-olds, and those who enter first grade as 6-year-olds. Ex post facto research was conducted on 3 samples of students (17,000 from 1st grades, 17,500 from 4th…

  14. Evaluating changes in tumor volume using magnetic resonance imaging during the course of radiotherapy treatment of high-grade gliomas: Implications for conformal dose-escalation studies

    SciTech Connect

    Tsien, Christina . E-mail: ctsien@umich.edu; Gomez-Hassan, Diana; Haken, Randall K. ten; Tatro, Daniel C.; Junck, L.; Chenevert, T.L.; Lawrence, T.

    2005-06-01

    Objective: To determine whether changes in tumor volume occur during the course of conformal 3D radiotherapy of high-grade gliomas by use of magnetic resonance imaging (MRI) during treatment and whether these changes had an impact on tumor coverage. Methods and Materials: Between December 2000 and January 2004, 21 patients with WHO Grades 3 to 4 supratentorial malignant gliomas treated with 3D conformal radiotherapy (median dose, 70 Gy) were enrolled in a prospective clinical study. All patients underwent T1-weighted contrast-enhancing and T2-weighted and fluid-attenuated inversion recovery (FLAIR) imaging at approximately 1 to 2 weeks before radiotherapy, during radiotherapy (Weeks 1 and 3), and at routine intervals thereafter. All MRI scans were coregistered to the treatment-planning CT. Gross tumor volume (GTV Pre-Rx) was defined from a postoperative T1-weighted contrast-enhancing MRI performed 1 to 2 weeks before start of radiotherapy. A second GTV (GTV Week 3) was defined by use of an MRI performed during Week 3 of radiotherapy. A uniform 0.5 cm expansion of the respective GTV, PTV (Pre-Rx), and PTV (Week 3) was applied to the final boost plan. Dose-volume histograms (DVH) were used to analyze any potential adverse changes in tumor coverage based on Week 3 MRI. Results: All MRI scans were reviewed independently by a neuroradiologist (DGH). Two patients were noted to have multifocal disease at presentation and were excluded from analysis. In 19 cases, changes in the GTV based on MRI at Week 3 during radiotherapy were as follows: 2 cases had an objective decrease in GTV ({>=}50%); 12 cases revealed a slight decrease in the rim enhancement or changes in cystic appearance of the GTV; 2 cases showed no change in GTV; and 3 cases demonstrated an increase in tumor volume. Both cases with objective decreases in GTV during treatment were Grade 3 tumors. No cases of tumor progression were noted in Grade 3 tumors during treatment. In comparison, three of 12 Grade 4

  15. Different patterns in the prognostic value of age for bladder cancer-specific survival depending on tumor stages

    PubMed Central

    Feng, Huan; Zhang, Wei; Li, Jiajun; Lu, Xiaozhe

    2015-01-01

    To compare the pathological features and long-term survival of bladder cancer (BCa) in young patients with elderly counterparts. Using the U.S. National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER) population-based data, we identified 93115 patients with non-metastatic bladder cancer diagnosed between 1988 and 2003. Patients were categorized into young (50 years and under) and elderly groups (over 50 years of age). The overall and five-year bladder cancer specific survival (BCSS) data were obtained using Kaplan-Meier plots. Multivariable Cox regression models were built for the analysis of long-term survival outcomes and risk factors. There were significant differences between the two groups in primary site, pathologic grading, histologic type, AJCC stage (p<0.001). The overall and 5-year cancer specific survival rates were 88.1% and 90.8% in young group, 64.8% and 81.3% in elderly group, which had significant difference in both univariate and multivariate analysis (p<0.001). Further analysis showed this significant difference existed across all the AJCC stage patients. The study findings show different patterns in the prognostic value of age for determining BCSS, depending on the tumor stages. Compared with elderly patients, young patients with bladder cancer surgery appear to have unique characteristics and a higher overall and cancer specific survival rate. PMID:26269768

  16. TMPRSS2-ERG fusions are strongly linked to young patient age in low-grade prostate cancer.

    PubMed

    Steurer, Stefan; Mayer, Pascale Sophia; Adam, Meike; Krohn, Antje; Koop, Christina; Ospina-Klinck, Daniel; Tehrani, Ali Attarchi; Simon, Ronald; Tennstedt, Pierre; Graefen, Markus; Wittmer, Corinna; Brors, Benedikt; Plass, Christoph; Korbel, Jan; Weischenfeldt, Joachim; Sauter, Guido; Huland, Hartwig; Tsourlakis, Maria Christina; Minner, Sarah; Schlomm, Thorsten

    2014-12-01

    Based on next-generation sequencing of early-onset prostate cancer (PCa), we earlier demonstrated that PCa in young patients is prone to rearrangements involving androgen-regulated genes-such as transmembrane protease, serine 2 (TMPRSS2)-v-ets avian erythroblastosis virus E26 oncogene homolog (ERG) fusion-and provided data suggesting that this situation might be caused by increased androgen signaling in younger men. In the same study, an accumulation of chromosomal deletions was found in cancers of elderly patients. To determine how age-dependent molecular features relate to cancer phenotype, an existing data set of 11,152 PCas was expanded by additional fluorescence in situ hybridization analyses of phosphatase and tensin homolog (PTEN), 6q15 and 5q21. The results demonstrate that the decrease in TMPRSS2-ERG fusions with increasing patient age is limited to low-grade cancers (Gleason ≤3+4) and that the significant increase in the deletion frequency with age was strictly limited to ERG-negative cancers for 6q15 and 5q21 but to ERG-positive cancers for PTEN. These data suggest that the accumulation of non-androgen-linked genomic alterations with advanced patient age may require an appropriate microenvironment, such as a positive or negative ERG status. The strong link of ERG activation to young patient age and low-grade cancers may help to explain a slight predominance of low-grade cancers in young patients. PMID:25015038

  17. The impact of graded levels of daylength on turkey productivity to eighteen weeks of age.

    PubMed

    Vermette, C; Schwean-Lardner, K; Gomis, S; Crowe, T G; Classen, H L

    2016-05-01

    The impact of graded levels of day-length on the productivity of hens and toms was studied in two trials. Daylength treatments (trts) were 14 (14L), 17 (17L), 20 (20L), and 23 (23L) h and were started at 10 d of age. Turkeys (720 hens and 480 toms) were randomly allocated to 8 rooms (2 rooms per lighting trt) with six pens (3 hen--30 per pen and 3 tom--20 per pen) per room in each trial. Body weight (BW) was assessed at 0, 10, 21, 42, 63, 84, and 126 d of age; feed consumption (FC) was measured for the time periods between body weight determinations and feed efficiency (G:F; g of gain/g of feed) was calculated from BW and FC values. Birds were checked daily for mortality and culls, and affected birds were sent for necropsy. Data were analyzed according to a completely randomized block design with trial as the block and rooms nested within lighting trts. Regression analysis was used to study the relationship between dependent variables and daylength. Significance was declared at P≤ 0.05 and trends at P≤ 0.10. At both 21 and 42 d, body weight increased linearly with increasing daylength. At 84 d weights of toms decreased in a quadratic fashion and hen weights were unaffected. At 126 d, both tom and hen weights decreased linearly as daylength increased, with the magnitude of response gender dependent. Feed consumption corresponded with body weight changes, increasing for d 10 to 21, and 21 to 42 and decreasing for d 63 to 84, 84 to 105, and 105 to 126 with increasing daylength. Feed efficiency (G:F) was not affected by daylength for 10 to 84, 10 to 105 and 10 to 126 d periods. The incidence of mortality and culling was not affected by daylength for the 10 to 84 d period, but increased in a quadratic manner with increasing daylength for the 10 to 105 and 10 to 126 d periods. To conclude, daylength affects the growth and feed intake of turkeys in an age and gender-specific manner, and mortality and culling increase with longer daylength. PMID:26976908

  18. In vivo Tumor Grading of Prostate Cancer using Quantitative 111In-Capromab Pendetide SPECT/CT

    PubMed Central

    Seo, Youngho; Aparici, Carina Mari; Cooperberg, Matthew R.; Konety, Badrinath R.; Hawkins, Randall A.

    2010-01-01

    We have developed an in vivo antibody uptake quantification method using 111In-capromab pendetide single photon emission computed tomography combined with computed tomography (SPECT/CT) technology. Our goal is to evaluate this noninvasive antibody quantification method for potential prostate tumor grading. Methods Our phantom experiments focused on the robustness of an advanced iterative reconstruction algorithm that involves corrections for photon attenuation, scatter, and geometric blurring caused by radionuclide collimators. The conversion factors between image values and tracer concentrations (in Bq/ml) were calculated from uniform phantom filled with aqueous solution of 111InCl3 using the same acquisition protocol and reconstruction parameters as for patient studies. In addition, the spatial resolution of the reconstructed images was measured from a point source phantom. The measured spatial resolution was modeled into a point spread function (PSF), and the PSF was implemented in a deconvolution-based partial volume error (PVE) correction algorithm. The recovery capability to correctly estimate true tracer concentration values was tested using prostate-like and bladder-like lesion phantoms fitted in the modified NEMA/IEC body phantom. Patients with biopsy-proven prostate cancer (n=10) who underwent prostatectomy were prospectively enrolled in the preoperative SPECT/CT studies at the San Francisco VA Medical Center. The CT portion of SPECT/CT was used for CT-based attenuation map generation as well as an anatomical localization tool for clinical interpretation. Pathologic Gleason grades were compared with in vivo “antibody uptake value” (AUV) normalized by injected dose, effective half-life, and injection-scan time difference. AUVs were calculated in each lobe of prostate gland with cylindrical volumes of interest (VOIs) having dimensions of 1.5 cm both in diameter and height. Results Reconstructed SPECT images further corrected by the deconvolution

  19. Occurrence of colon tumors in a 16-year-old Japanese boy after hematopoietic stem cell transplantation for Diamond Blackfan anemia at age of 4: a case report

    PubMed Central

    Matsuda, Ikuo; Tsuchida, Yasu-aki; Toyoshima, Fumihiko; Tozawa, Katsuyuki; Ikehara, Hisatomo; Ohda, Yoshio; Hori, Kazutoshi; Ohtsuka, Yoshitoshi; Watari, Jiro; Miwa, Hiroto; Hirota, Seiichi

    2015-01-01

    Diamond Blackfan anemia (DBA) is a congenital pure red cell aplasia mainly caused by a mutation in ribosomal protein genes. One of the proposed mechanisms for red cell aplasia in DBA is apoptosis caused by constitutive activation of tumor suppressor TP53 protein following defective ribosome biogenesis. Because of this close relationship between ribosome biogenesis and TP53 activation, patients with DBA are considered to be cancer-prone. The association between bone marrow failure and tumor susceptibility in DBA appears paradoxical. Also, the detailed information is lacking on malignancy occurring in patients with DBA. Here, we report a case of a 16-year-old Japanese boy suffering from multiple colon tumors during the follow-up after hematopoietic stem cell transplantation for DBA at the age of 4. Well differentiated tubular adenocarcinoma was detected at the rectum 12 years after the transplantation, followed by multiple tubular adenomas of low to high grade throughout the colon. Endoscopic submucosal dissection was performed for these tumors and the lesions were completely resected. These tumors did not show diffuse and strong TP53 positivity by immunohistochemistry, suggesting that TP53 mutation was not involved in the tumorigenesis as observed in conventional colorectal cancers. Microsatellite instability test and immunohistochemical examination of β-catenin and MLH1 proteins of these tumors showed that WNT signaling or microsatellite instability was less likely to be involved in the present tumors as observed in conventional left-sided or right-sided colon cancers, respectively. To our knowledge, this is the first case report of colon tumors associated with DBA. PMID:26191323

  20. Occurrence of colon tumors in a 16-year-old Japanese boy after hematopoietic stem cell transplantation for Diamond Blackfan anemia at age of 4: a case report.

    PubMed

    Matsuda, Ikuo; Tsuchida, Yasu-aki; Toyoshima, Fumihiko; Tozawa, Katsuyuki; Ikehara, Hisatomo; Ohda, Yoshio; Hori, Kazutoshi; Ohtsuka, Yoshitoshi; Watari, Jiro; Miwa, Hiroto; Hirota, Seiichi

    2015-01-01

    Diamond Blackfan anemia (DBA) is a congenital pure red cell aplasia mainly caused by a mutation in ribosomal protein genes. One of the proposed mechanisms for red cell aplasia in DBA is apoptosis caused by constitutive activation of tumor suppressor TP53 protein following defective ribosome biogenesis. Because of this close relationship between ribosome biogenesis and TP53 activation, patients with DBA are considered to be cancer-prone. The association between bone marrow failure and tumor susceptibility in DBA appears paradoxical. Also, the detailed information is lacking on malignancy occurring in patients with DBA. Here, we report a case of a 16-year-old Japanese boy suffering from multiple colon tumors during the follow-up after hematopoietic stem cell transplantation for DBA at the age of 4. Well differentiated tubular adenocarcinoma was detected at the rectum 12 years after the transplantation, followed by multiple tubular adenomas of low to high grade throughout the colon. Endoscopic submucosal dissection was performed for these tumors and the lesions were completely resected. These tumors did not show diffuse and strong TP53 positivity by immunohistochemistry, suggesting that TP53 mutation was not involved in the tumorigenesis as observed in conventional colorectal cancers. Microsatellite instability test and immunohistochemical examination of β-catenin and MLH1 proteins of these tumors showed that WNT signaling or microsatellite instability was less likely to be involved in the present tumors as observed in conventional left-sided or right-sided colon cancers, respectively. To our knowledge, this is the first case report of colon tumors associated with DBA. PMID:26191323

  1. Handbook for Instruction on Aging in California Public Schools. Kindergarten Through Grade Twelve.

    ERIC Educational Resources Information Center

    California State Dept. of Education, Sacramento.

    This handbook is designed to assist teachers at the elementary and secondary level in the development of curricula on aging which can integrate the concepts of aging into ongoing lesson plans. The five content areas of instruction include chronological aging, physiological and biological aging, sociocultural aspects of aging, psychological aging,…

  2. Cytogenetic characterization of three cell lines derived from primary cervical tumors of different histologic grade

    SciTech Connect

    Hann, E.; Beauregard, L.; Mikumo, R.

    1994-09-01

    Braum et al.(1993) established three cell lines from keratinizing and nonkeratinizing cervical carcinomas. These cell lines were subsequently analyzed for growth properties and the physical state of the human papillomavirus type 16 genome. TC140, derived from a keratinizing cervical tumor, contains human papillomavirus type 16 in the episomal state. TC-146A and TC-146B, derived from a nonkeratinizing large-cell cervical carcinoma, contain human papillomavirus type 16 in the integrated state. The goal of the present study was to cytogenetically characterize these cell lines, developed from cervical carcinoma with a defined histopathology, in order to shed additional light on the biological basis of the histological and clinical heterogeneity of cervical cancers. Information on solid tumors has been limited because they are often difficult to culture and the karyotypes on the available metaphases are often complex with unidentifiable markers. The chromosomes of these three cell lines were characterized in the present study using GTG-banding. For cell line 140, the most striking chromosomal abnormalities noted were the presence of an i(5p) or i(12p) marker, an isochromosome 8q marker and multiple copies of chromosome 9. For cell line 146A, the most notable chromosomal abnormalities noted were the presence of a marker chromosome 7 with additional materials present on the long arms, an isochomosome of the long arms of chromosome 8 and a question of chromosome 19 markers. For cell line 146B, the most notable chromosomal abnormalities were found to be a deleted X chromosome, a marker chromosome 7 with additional material on the long arm, an isochromosome 8q marker, and isochromosome 16q marker and one or more copies of an isochromosome 17q marker. Fluorescent in situ hybridization experiments performed using select probes further corroborate the results of the above-mentioned conventional cytogenetic studies.

  3. IDH1 mutations at residue p.R132 (IDH1(R132)) occur frequently in high-grade gliomas but not in other solid tumors.

    PubMed

    Bleeker, Fonnet E; Lamba, Simona; Leenstra, Sieger; Troost, Dirk; Hulsebos, Theo; Vandertop, W Peter; Frattini, Milo; Molinari, Francesca; Knowles, Margaret; Cerrato, Aniello; Rodolfo, Monica; Scarpa, Aldo; Felicioni, Lara; Buttitta, Fiamma; Malatesta, Sara; Marchetti, Antonio; Bardelli, Alberto

    2009-01-01

    Systematic sequence profiling of the Glioblastoma Multiforme (GBM) genome has recently led to the identification of somatic mutations in the isocitrate dehydrogenase 1 (IDH1) gene. Interestingly, only the evolutionarily conserved residue R132 located in the substrate binding site of IDH1 was found mutated in GBM. At present, the occurrence and the relevance of p.R132 (IDH1(R132)) variants in tumors other than GBMs is largely unknown. We searched for mutations at position R132 of the IDH1 gene in a panel of 672 tumor samples. These included high-grade glioma, gastrointestinal stromal tumors (GIST), melanoma, bladder, breast, colorectal, lung, ovarian, pancreas, prostate, and thyroid carcinoma specimens. In addition, we assessed a panel of 84 cell lines from different tumor lineages. Somatic mutations affecting the IDH1(R132) residue were detected in 20% (23 of 113) high-grade glioma samples. In addition to the previously reported p.R132H and p.R132S alleles, we identified three novel somatic mutations (p.R132C, p.R132G, and p.R132L) affecting residue IDH1(R132) in GBM. Strikingly, no IDH1 mutations were detected in the other tumor types. These data indicate that cancer mutations affecting IDH1(R132) are tissue-specific, and suggest that it plays a unique role in the development of high-grade gliomas. PMID:19117336

  4. H3F3A K27M mutation in pediatric CNS tumors: a marker for diffuse high-grade astrocytomas.

    PubMed

    Gielen, Gerrit H; Gessi, Marco; Hammes, Jennifer; Kramm, Christof M; Waha, Andreas; Pietsch, Torsten

    2013-03-01

    Brain tumors are one of the most common childhood malignancies. Diffuse high-grade gliomas represent approximately 10% of pediatric brain tumors. Exon sequencing has identified a mutation in K27M of the histone H3.3 gene (H3F3A K27M and G34R/V) in about 20% of pediatric glioblastomas, but it remains to be seen whether these mutations can be considered specific for pediatric diffuse high-grade astrocytomas or also occur in other pediatric brain tumors. We performed a pyrosequencing-based analysis for the identification of H3F3A codon 27 and codon 34 mutations in 338 pediatric brain tumors. The K27M mutation occurred in 35 of 129 glioblastomas (27.1%) and in 5 of 28 (17.9%) anaplastic astrocytomas. None of the other tumor entities showed H3F3A K27M mutation. Because H3F3A K27M mutations occur exclusively in pediatric diffuse high-grade astrocytomas, analysis of codon 27 mutational status could be useful in the differential diagnosis of these neoplasms. PMID:23429371

  5. A neurogenic tumor containing a low-grade malignant peripheral nerve sheath tumor (MPNST) component with loss of p16 expression and homozygous deletion of CDKN2A/p16: a case report showing progression from a neurofibroma to a high-grade MPNST.

    PubMed

    Tajima, Shogo; Koda, Kenji

    2015-01-01

    Development of malignant peripheral nerve sheath tumors (MPNSTs) is a stepwise process that involves the alteration of many cell cycle regulators and the double inactivation of the NF1 gene. Inactivation of the TP53 gene and deletion of the CDKN2A/p16 gene are known to play an important role in the process. Herein, we present a 19-year-old man with a familial history of neurofibromatosis type 1, in whom the tumor arose from the intercostal nerve and showed 3 components: a neurofibroma, a low-grade MPNST, and a high-grade MPNST. Loss of p16 expression and homozygous deletion of the CDKN2A/p16 gene were observed in both the low-grade and the high-grade MPNST. In contrast to low-grade MPNSTs, high-grade MPNSTs generally tend to lose expression of p16 and harbor homozygous deletion of the CDKN2A/p16 gene. Loss of p16 expression and homozygous deletion of the CDKN2A/p16 gene in low-grade MPNST in our case might be related to its progression to high-grade MPNST. To the best of our knowledge, this is the first study correlating the p16 expression status and CDKN2A/p16 gene alteration in low-grade MPNSTs. PMID:26191206

  6. Oncocytoma-like renal tumor with transformation toward high-grade oncocytic carcinoma: a unique case with morphologic, immunohistochemical, and genomic characterization.

    PubMed

    Sirintrapun, Sahussapont J; Geisinger, Kim R; Cimic, Adela; Snow, Anthony; Hagenkord, Jill; Monzon, Federico; Legendre, Benjamin L; Ghazalpour, Anatole; Bender, Ryan P; Gatalica, Zoran

    2014-10-01

    Renal oncocytoma is a benign tumor with characteristic histologic findings. We describe an oncocytoma-like renal tumor with progression to high-grade oncocytic carcinoma and metastasis. A 74-year-old man with no family history of cancer presented with hematuria. Computed tomography showed an 11 cm heterogeneous multilobulated mass in the right kidney lower pole, enlarged aortocaval lymph nodes, and multiple lung nodules. In the nephrectomy specimen, approximately one third of the renal tumor histologically showed regions classic for benign oncocytoma transitioning to regions of high-grade carcinoma without sharp demarcation. With extensive genomic investigation using single nucleotide polymorphism-based array virtual karyotyping, multiregion sequencing, and expression array analysis, we were able to show a common lineage between the benign oncocytoma and high-grade oncocytic carcinoma regions in the tumor. We were also able to show karyotypic differences underlying this progression. The benign oncocytoma showed no chromosomal aberrations, whereas the high-grade oncocytic carcinoma showed loss of the 17p region housing FLCN (folliculin [Birt-Hogg-Dubé protein]), loss of 8p, and gain of 8q. Gene expression patterns supported dysregulation and activation of phosphoinositide 3-kinase (PI3K)/v-akt murine thymoma viral oncogene homolog (Akt), mitogen-activated protein kinase (MAPK)/extracellular-signal-regulated kinase (ERK), and mechanistic target of rapamycin (serine/threonine kinase) (mTOR) pathways in the high-grade oncocytic carcinoma regions. This was partly attributable to FLCN underexpression but further accentuated by overexpression of numerous genes on 8q. In the high-grade oncocytic carcinoma region, vascular endothelial growth factor A along with metalloproteinases matrix metallopeptidase 9 and matrix metallopeptidase 12 were overexpressed, facilitating angiogenesis and invasiveness. Genetic molecular testing provided evidence for the development of an

  7. BAFF, APRIL, TWEAK, BCMA, TACI and Fn14 Proteins Are Related to Human Glioma Tumor Grade: Immunohistochemistry and Public Microarray Data Meta-Analysis

    PubMed Central

    Pelekanou, Vassiliki; Notas, George; Kampa, Marilena; Tsentelierou, Eleftheria; Stathopoulos, Efstathios N.; Tsapis, Andreas; Castanas, Elias

    2013-01-01

    Gliomas are common and lethal tumors of the central nervous system (CNS). Genetic alterations, inflammatory and angiogenic processes have been identified throughout tumor progression; however, treatment still remains palliative for most cases. Biological research on parameters influencing cell survival, invasion and tumor heterogeneity identified several cytokines interfering in CNS inflammation, oxidative stress and malignant transformation, including TNF-superfamily (TNFSF) members. In this report we performed a meta-analysis of public gene-array data on the expression of a group of TNFSF ligands (BAFF, APRIL, TWEAK) and their receptors (BAFF-R, TACI, BCMA, Fn14) in gliomas. In addition, we investigated by immunohistochemistry (IHC) the tumor cells' expression of these ligands and receptors in a series of 56 gliomas of different grade. We show that in IHC, BAFF and APRIL as well as their cognate receptors (BCMA, TACI) and Fn14 expression correlate with tumor grade. This result was not evidenced in micro-arrays meta-analysis. Finally, we detected for the first time Fn14, BAFF, BCMA and TACI in glioma-related vascular endothelium. Our data, combined with our previous report in glioma cell lines, suggest a role for these receptors and ligands in glioma biology and advance these molecules as potential markers for the classification of these tumors to the proliferative, angiogenic or stem-like molecular subtype. PMID:24376672

  8. Patients with Old Age or Proximal Tumors Benefit from Metabolic Syndrome in Early Stage Gastric Cancer

    PubMed Central

    Zhang, Ying; Liu, Jian-xin; Yu, Hong-mei; Liang, Wei-ping; Jin, Ying; Ren, Chao; He, Ming-ming; Chen, Wei-wei; Luo, Hui-yan; Wang, Zhi-qiang; Zhang, Dong-sheng; Wang, Feng-hua; Li, Yu-hong; Xu, Rui-hua

    2014-01-01

    Background Metabolic syndrome and/or its components have been demonstrated to be risk factors for several cancers. They are also found to influence survival in breast, colon and prostate cancer, but the prognostic value of metabolic syndrome in gastric cancer has not been investigated. Methods Clinical data and pre-treatment information of metabolic syndrome of 587 patients diagnosed with early stage gastric cancer were retrospectively collected. The associations of metabolic syndrome and/or its components with clinical characteristics and overall survival in early stage gastric cancer were analyzed. Results Metabolic syndrome was identified to be associated with a higher tumor cell differentiation (P = 0.036). Metabolic syndrome was also demonstrated to be a significant and independent predictor for better survival in patients aged >50 years old (P = 0.009 in multivariate analysis) or patients with proximal gastric cancer (P = 0.047 in multivariate analysis). No association was found between single metabolic syndrome component and overall survival in early stage gastric cancer. In addition, patients with hypertension might have a trend of better survival through a good control of blood pressure (P = 0.052 in univariate analysis). Conclusions Metabolic syndrome was associated with a better tumor cell differentiation in patients with early stage gastric cancer. Moreover, metabolic syndrome was a significant and independent predictor for better survival in patients with old age or proximal tumors. PMID:24599168

  9. Intravenous low-grade endometrial stromal sarcoma with intracardiac extension: A CASE OF inaccurate tumor location on contrast-enhanced computed tomography

    PubMed Central

    NOGAMI, YUYA; YAMAGAMI, WATARU; MAKI, JUNKO; BANNO, KOUJI; SUSUMU, NOBUYUKI; TOMITA, KOICHI; MATSUBARA, KENTARO; OBARA, HIDEAKI; KITAGAWA, YUKO; AOKI, DAISUKE

    2016-01-01

    We herein report a case of low-grade endometrial stromal sarcoma with intracardiac extension in a 58-year-old woman with a uterine tumor with intravascular involvement. The tumor was suspected preoperatively to be an endometrial stromal sarcoma by magnetic resonance imaging. The extent of intravascular involvement was determined to be below the level of the renal veins on preoperative contrast-enhanced computed tomography (CT). However, perioperative echography revealed that the tumor extended to the right atrium. An emergency cardiotomy with extracorporeal circulation was required. The risk of tumor embolism was reduced through transection of the inferior vena cava, but the tumor was difficult to remove completely. Postoperative hormonal therapy reduced the size of the residual tumor and no recurrence was detected for 1 year. The preoperative contrast-enhanced CT was unable to detect the free-floating intravascular tumor. This case illustrates a limitation of CT and indicates that accurate determination of the tumor extent for planning a surgical strategy in similar cases should be performed using multiple imaging methods. PMID:26893856

  10. The Effects of a Second-Grade Social Studies Curriculum Infused with Positive Aging Concepts on Children's Attitudes towards Aging

    ERIC Educational Resources Information Center

    Hembacher, Diane; Cruise, Mary J.

    2006-01-01

    As the number of elderly people in our society increases, it becomes especially important for children to develop positive attitudes towards elders and towards their own aging. The American Association for Health Education has recommended the infusion of positive aging concepts in the K-12 curriculum. This qualitative study investigated the…

  11. The impact of age on oncogenic potential: tumor-initiating cells and the brain microenvironment.

    PubMed

    Stoll, Elizabeth A; Horner, Philip J; Rostomily, Robert C

    2013-10-01

    Paradoxically, aging leads to both decreased regenerative capacity in the brain and an increased risk of tumorigenesis, particularly the most common adult-onset brain tumor, glioma. A shared factor contributing to both phenomena is thought to be age-related alterations in neural progenitor cells (NPCs), which function normally to produce new neurons and glia, but are also considered likely cells of origin for malignant glioma. Upon oncogenic transformation, cells acquire characteristics known as the hallmarks of cancer, including unlimited replication, altered responses to growth and anti-growth factors, increased capacity for angiogenesis, potential for invasion, genetic instability, apoptotic evasion, escape from immune surveillance, and an adaptive metabolic phenotype. The precise molecular pathogenesis and temporal acquisition of these malignant characteristics is largely a mystery. Recent studies characterizing NPCs during normal aging, however, have begun to elucidate mechanisms underlying the age-associated increase in their malignant potential. Aging cells are dependent upon multiple compensatory pathways to maintain cell cycle control, normal niche interactions, genetic stability, programmed cell death, and oxidative metabolism. A few multi-functional proteins act as 'critical nodes' in the coordination of these various cellular activities, although both intracellular signaling and elements within the brain environment are critical to maintaining a balance between senescence and tumorigenesis. Here, we provide an overview of recent progress in our understanding of how mechanisms underlying cellular aging inform on glioma pathogenesis and malignancy. PMID:23711239

  12. Type I collagen aging impairs discoidin domain receptor 2-mediated tumor cell growth suppression.

    PubMed

    Saby, Charles; Buache, Emilie; Brassart-Pasco, Sylvie; El Btaouri, Hassan; Courageot, Marie-Pierre; Van Gulick, Laurence; Garnotel, Roselyne; Jeannesson, Pierre; Morjani, Hamid

    2016-05-01

    Tumor cells are confronted to a type I collagen rich environment which regulates cell proliferation and invasion. Biological aging has been associated with structural changes of type I collagen. Here, we address the effect of collagen aging on cell proliferation in a three-dimensional context (3D).We provide evidence for an inhibitory effect of adult collagen, but not of the old one, on proliferation of human fibrosarcoma HT-1080 cells. This effect involves both the activation of the tyrosine kinase Discoidin Domain Receptor 2 (DDR2) and the tyrosine phosphatase SHP-2. DDR2 and SHP-2 were less activated in old collagen. DDR2 inhibition decreased SHP-2 phosphorylation in adult collagen and increased cell proliferation to a level similar to that observed in old collagen.In the presence of old collagen, a high level of JAK2 and ERK1/2 phosphorylation was observed while expression of the cell cycle negative regulator p21CIP1 was decreased. Inhibition of DDR2 kinase function also led to an increase in ERK1/2 phosphorylation and a decrease in p21CIP1 expression. Similar signaling profile was observed when DDR2 was inhibited in adult collagen. Altogether, these data suggest that biological collagen aging could increase tumor cell proliferation by reducingthe activation of the key matrix sensor DDR2. PMID:27121132

  13. Quadrivalent HPV vaccine effectiveness against high-grade cervical lesions by age at vaccination: A population-based study.

    PubMed

    Herweijer, Eva; Sundström, Karin; Ploner, Alexander; Uhnoo, Ingrid; Sparén, Pär; Arnheim-Dahlström, Lisen

    2016-06-15

    Human papillomavirus (HPV) types 16/18, included in HPV vaccines, contribute to the majority of cervical cancer, and a substantial proportion of cervical intraepithelial neoplasia (CIN) grades 2/3 or worse (CIN2+/CIN3+) including adenocarcinoma in situ or worse. The aim of this study was to quantify the effect of quadrivalent HPV (qHPV) vaccination on incidence of CIN2+ and CIN3+. A nationwide cohort of girls and young women resident in Sweden 2006-2013 and aged 13-29 (n = 1,333,691) was followed for vaccination and histologically confirmed high-grade cervical lesions. Data were collected using the Swedish nationwide healthcare registers. Poisson regression was used to calculate incidence rate ratios (IRRs) and vaccine effectiveness [(1-IRR)x100%] comparing fully vaccinated with unvaccinated individuals. IRRs were adjusted for attained age and parental education, and stratified on vaccination initiation age. Effectiveness against CIN2+ was 75% (IRR = 0.25, 95%CI = 0.18-0.35) for those initiating vaccination before age 17, and 46% (IRR = 0.54, 95%CI = 0.46-0.64) and 22% (IRR = 0.78, 95%CI = 0.65-0.93) for those initiating vaccination at ages 17-19, and at ages 20-29, respectively. Vaccine effectiveness against CIN3+ was similar to vaccine effectiveness against CIN2+. Results were robust for both women participating to the organized screening program and for women at prescreening ages. We show high effectiveness of qHPV vaccination on CIN2+ and CIN3+ lesions, with greater effectiveness observed in girls younger at vaccination initiation. Continued monitoring of impact of HPV vaccination in the population is needed in order to evaluate both long-term vaccine effectiveness and to evaluate whether the vaccination program achieves anticipated effects in prevention of invasive cervical cancer. PMID:26856527

  14. Using Simulations to Teach Middle Grades U.S. History in an Age of Accountability

    ERIC Educational Resources Information Center

    DiCamillo, Lorrei; Gradwell, Jill M.

    2012-01-01

    In this year-long qualitative study we explore the case of two eighth grade U.S. History teachers who use simulations on a regular basis to teach heterogeneously-grouped students in a high-stakes testing environment. We describe the purposes the teachers espoused for implementing simulations and provide detailed portraits of three types of…

  15. Age as a Diversity Issue in Grades K-12 and in Higher Education.

    ERIC Educational Resources Information Center

    Wircenski, Michelle; Walker, Michelle; Allen, Jeff; West, Lynda

    1999-01-01

    Aging and ageism are diversity issues and should be addressed in diversity training. A balanced understanding of aging can be developed using appropriate techniques at all levels of education. Instructors should vary teaching approaches to accommodate older adult students. (SK)

  16. Younger age-at-diagnosis for familial malignant testicular germ cell tumor.

    PubMed

    Mai, Phuong L; Chen, Bingshu E; Tucker, Kathy; Friedlander, Michael; Phillips, Kelly-Anne; Hogg, David; Jewett, Michael A S; Bodrogi, Istvan; Geczi, Lajos; Olah, Edith; Heimdal, Ketil; Fosså, Sophie D; Nathanson, Katherine L; Korde, Larissa; Easton, Douglas F; Dudakia, Darshna; Huddart, Robert; Stratton, Michael R; Bishop, D Timothy; Rapley, Elizabeth A; Greene, Mark H

    2009-01-01

    One of the clinical hallmarks of hereditary cancer susceptibility disorders is a younger-than-usual age at diagnosis. Familial aggregation of testicular germ cell tumor (TGCT) has been reported, but data on whether familial TGCT cases are diagnosed at an earlier age are inconclusive. Here we compared the age at diagnosis of familial TGCT cases with that of population cases in several countries. Familial TGCT is defined as affected individuals from families with >or=2 cases of TGCT. Age at diagnosis of familial cases from the United States, Canada, United Kingdom, Australia and New Zealand, Norway, and Hungary was compared to cases identified in population-based cancer registries from the respective country, using the generalized estimation equation method. Age at diagnosis was statistically significantly younger for familial TGCT cases from North America (P = 0.024), the United Kingdom (P < 0.0001), and Australia and New Zealand (P = 0.0033) compared with population cases. When stratified by histology, the difference in age at diagnosis distribution between familial and population cases was observed for seminoma cases from North America (P = 0.002) and the United Kingdom (P < 0.0001) and non-seminoma cases from the United Kingdom (P = 0.029) and Australia and New Zealand (P = 0.0023). In summary, we found that the age at diagnosis for familial TGCT cases is, on the average, 2-3 years younger than that for the population cases in North America, United Kingdom, and Australia and New Zealand. The younger age at diagnosis might be suggestive of a genetic basis for familial TGCT. PMID:19609727

  17. Robinson's cytological grading on aspirates of breast carcinoma: Correlation with Bloom Richardson's histological grading

    PubMed Central

    Sinha, SK; Sinha, Namita; Bandyopadhyay, Ranjana; Mondal, Santosh K

    2009-01-01

    Background: Cytological grading (CG) on aspirates of breast carcinoma is a useful tool for surgical maneuver and prognosis. Aims: An endeavor was made to use CG on aspirates of breast carcinoma using Robinson's grade and to correlate it with Bloom Richardsons’ histopathological grading. Materials and Methods: A total of 59 patients of breast carcinoma, aged 28-57 years, were aspirated and the smears were graded using Robinson's criteria. All the cases were correlated with Bloom Richardson's grade on histopathology in mastectomy specimens. Lymphadenopathy in 38 cases was aspirated and stained with Papanicolaou and Romanowsky stain. Results: Robinson's CG correlated well with Bloom Richardson's histopathological grading. For grade I and II tumors, there was substantial strength of agreement between cytology and histopathology, while in grade III, the concordance was nearly perfect. Lymph node metastasis was found in 27 of 32 axillary nodes, three of five cervical nodes and the only palpable supraclavicular node. Lymph node metastasis was observed in three with cytological grade II, 28 of grade III and none of grade I. All grade I had stage A, two of grade II had stage B, while all grade III had either stage B or stage C disease. Conclusions: Thus, CG of breast carcinoma correlates well with histopathological grading and may well be useful as a prognostic marker. PMID:21938177

  18. Prognostic impact of programmed cell death-1 (PD-1) and PD-ligand 1 (PD-L1) expression in cancer cells and tumor-infiltrating lymphocytes in ovarian high grade serous carcinoma

    PubMed Central

    Kulbe, Hagen; Sehouli, Jalid; Wienert, Stephan; Lindner, Judith; Budczies, Jan; Bockmayr, Michael; Dietel, Manfred; Denkert, Carsten; Braicu, Ioana; Jöhrens, Korinna

    2016-01-01

    Aims Antibodies targeting the checkpoint molecules programmed cell death 1 (PD-1) and its ligand PD-L1 are emerging cancer therapeutics. We systematically investigated PD-1 and PD-L1 expression patterns in the poor-prognosis tumor entity high-grade serous ovarian carcinoma. Methods PD-1 and PD-L1 protein expression was determined by immunohistochemistry on tissue microarrays from 215 primary cancers both in cancer cells and in tumor-infiltrating lymphocytes (TILs). mRNA expression was measured by quantitative reverse transcription PCR. An in silico validation of mRNA data was performed in The Cancer Genome Atlas (TCGA) dataset. Results PD-1 and PD-L1 expression in cancer cells, CD3+, PD-1+, and PD-L1+ TILs densities as well as PD-1 and PD-L1 mRNA levels were positive prognostic factors for progression-free (PFS) and overall survival (OS), with all factors being significant for PFS (p < 0.035 each), and most being significant for OS. Most factors also had prognostic value that was independent from age, stage, and residual tumor. Moreover, high PD-1+ TILs as well as PD-L1+ TILs densities added prognostic value to CD3+TILs (PD-1+: p = 0.002,; PD-L1+: p = 0.002). The significant positive prognostic impact of PD-1 and PD-L1 mRNA expression could be reproduced in the TCGA gene expression datasets (p = 0.02 and p < 0.0001, respectively). Conclusions Despite their reported immune-modulatory function, high PD-1 and PD-L1 levels are indicators of a favorable prognosis in ovarian cancer. Our data indicate that PD-1 and PD-L1 molecules are biologically relevant regulators of the immune response in high-grade serous ovarian carcinoma, which is an argument for the evaluation of immune checkpoint inhibiting drugs in this tumor entity. PMID:26625204

  19. Ultrasonic Characterization of Aging Behavior in M250 Grade Maraging Steel

    NASA Astrophysics Data System (ADS)

    Yeheskel, Ori

    2009-03-01

    The increase in sound velocities during the aging of M250 maraging steel reported by Rajkumar et al. was analyzed. The present article provides a new perspective on why and to what extent the sound velocities change during aging. The main parameter that affects the elastic moduli and the sound velocities in the early and intermediate stages of aging in maraging steel is the depletion of Ni from the martensitic matrix due to Ni3Ti and Ni3Mo formation. The issue of sound velocity increase with aging time was addressed here in a few different ways to support the validity of Ni depletion.

  20. Age-Graded Themes in White American Middle-Class Slang: A Hypothesis.

    ERIC Educational Resources Information Center

    Donahue, Thomas S.

    It is proposed that middle- and upper-middle-class slang used among white young people in modern America shows age-related themes. For youngsters between the ages of eight and early adolescence, the major theme in slang use is to establish in-group and out-group membership, with standards of judgment based on clothes, manners, and physical appeal.…

  1. The Relative Effects of Chronological Age on Hispanic Students' School Readiness and Grade 2 Academic Achievement

    ERIC Educational Resources Information Center

    Furlong, Michael; Quirk, Matthew

    2011-01-01

    This study examined the relations of age, preschool experience, and gender with children's school readiness levels at kindergarten entry. The sample included 5,512 children of predominantly Hispanic heritage and from families experiencing low socioeconomic circumstances. A series of between-subjects ANOVAs indicated that age ("Eta"[superscript 2]…

  2. Age-specific prevalence of HPV genotypes in cervical cytology samples with equivocal or low-grade lesions

    PubMed Central

    Brismar-Wendel, S; Froberg, M; Hjerpe, A; Andersson, S; Johansson, B

    2009-01-01

    Background: To define the spectrum of human papillomavirus (HPV) types and establish an age limit for triage HPV testing in atypical squamous cells of undetermined significance (ASCUS) and low-grade squamous intraepithelial lesion (LSIL). Materials and methods: 343 liquid-based cytological samples from the population-based screening programme with minor abnormalities were subjected to HPV genotyping (Linear Array, Roche, Basel, Switzerland). Results: High-risk human papillomavirus (HR-HPV) was found in 71% of LSIL and 49% of ASCUS cases (P<0.001). High-risk human papillomavirus prevalence was age-dependent in LSIL (P=0.01), with decreasing prevalence until the age of 50 years, followed by a slight increase. Human papillomavirus type 16 was the most common HR-HPV, found in 23% of HPV-positive women. Human papillomavirus type 18 was the sixth most common, found in 9.9% (P<0.001). An age-dependent quadratic trend was observed for multiple infections (P=0.01) with a trough at about 42 years. The most common HR-HPV types to show a coinfection with HPV16 (clade 9) were HPV39 (28%), 45 (38%), and 59 (46%), belonging to HPV18 clade 7. The frequency of low-risk (LR) vs probable HR and HR-HPV also followed an age-dependent quadratic trend. Conclusions: After the age of 25 years, HR-HPV prevalence is similar in LSIL and ASCUS cases, motivating a low age limit for triage HPV testing. Multiple infections and LR/HR-HPV dominance are age-dependent. Genotyping in longitudinal design is needed to elucidate the importance of multiple infections in cancer progression and in cross-protection from vaccination. PMID:19623178

  3. Tumor

    MedlinePlus

    ... be removed because of their location or harmful effect on the surrounding normal brain tissue. If a tumor is cancer , possible treatments may include: Chemotherapy Radiation Surgery Targeted cancer therapy Biologic therapy Other treatment options

  4. Diffusion and Perfusion MRI to Differentiate Treatment-Related Changes Including Pseudoprogression from Recurrent Tumors in High-Grade Gliomas with Histopathologic Evidence

    PubMed Central

    Prager, A.J.; Martinez, N.; Beal, K.; Omuro, A.; Zhang, Z.; Young, R.J.

    2016-01-01

    BACKGROUND AND PURPOSE Treatment-related changes and recurrent tumors often have overlapping features on conventional MR imaging. The purpose of this study was to assess the utility of DWI and DSC perfusion imaging alone and in combination to differentiate treatment-related effects and recurrent high-grade gliomas. MATERIALS AND METHODS We retrospectively identified 68 consecutive patients with high-grade gliomas treated by surgical resection followed by radiation therapy and temozolomide, who then developed increasing enhancing mass lesions indeterminate for treatment-related changes versus recurrent tumor. All lesions were diagnosed by histopathology at repeat surgical resection. ROI analysis was performed of the enhancing lesion on the ADC and DSC maps. Measurements made by a 2D ROI of the enhancing lesion on a single slice were recorded as ADCLesion and rCBVLesion, and measurements made by the most abnormal small fixed diameter ROI as ADCROI and rCBVROI. Statistical analysis was performed with Wilcoxon rank sum tests with P = .05. RESULTS Ten of the 68 patients (14.7%) had treatment-related changes, while 58 patients (85.3%) had recurrent tumor only (n = 19) or recurrent tumor mixed with treatment effect (n = 39). DWI analysis showed higher ADCLesion in treatment-related changes than in recurrent tumor (P = .003). DSC analysis revealed lower relative cerebral blood volume (rCBV)Lesion and rCBVROI in treatment-related changes (P=.003 andP=.011, respectively). Subanalysis of patients with suspected pseudoprogression also revealed higher ADCLesion (P = .001) and lower rCBVLesion (P = .028) and rCBVROI (P = .032) in treatment-related changes. Applying a combined ADCLesion and rCBVLesion model did not outperform either the ADC or rCBV metric alone. CONCLUSIONS Treatment-related changes showed higher diffusion and lower perfusion than recurrent tumor. Similar correlations were found for patients with suspected pseudoprogression. PMID:25593202

  5. Age-graded risks for commercial sexual exploitation of male and female youth.

    PubMed

    Reid, Joan A; Piquero, Alex R

    2014-06-01

    Emerging evidence indicates male youth are affected by commercial sexual exploitation (CSE). However, most studies investigating risk markers influencing age of onset of CSE have focused on vulnerabilities of girls and women. Using a sample of 1,354 serious youthful offenders (of whom approximately 8% of males and females reported being paid for sex), the current study assessed whether risks associated with age of onset of CSE for girls and young women operated similarly in boys and young men. Findings showed that African American male youth were at heightened risk for CSE, while female youth of all races/ethnicities were at similar risk. For all youth, maternal substance use and earlier age of first sex were associated with early age of onset of CSE. For male youth, experiencing rape and substance use dependency were associated with early age of onset. Psychotic symptoms, likely experienced as social alienation, were associated with both early and late age of onset. For all youth, lower educational attainment was associated with CSE beginning in later adolescence or young adulthood. In addition, substance use dependency was linked to late age of onset for female youth. Implications of the study findings for theory development and application to CSE are noted. PMID:24366965

  6. Krüppel-Like Factor 8 (KLF8) Is Expressed in Gliomas of Different WHO Grades and Is Essential for Tumor Cell Proliferation

    PubMed Central

    Schnell, Oliver; Romagna, Alexander; Jaehnert, Irene; Albrecht, Valerie; Eigenbrod, Sabina; Juerchott, Kathrin; Kretzschmar, Hans; Tonn, Jörg-Christian; Schichor, Christian

    2012-01-01

    Krüppel-like factor 8 (KLF8) has only recently been identified to be involved in tumor cell proliferation and invasion of several different tumor entities like renal cell carcinoma, hepatocellular carcinoma and breast cancer. In the present study, we show for the first time the expression of KLF8 in gliomas of different WHO grades and its functional impact on glioma cell proliferation. In order to get information about KLF8-mRNA regulation qPCR was performed and did not reveal any significant difference in samples (n = 10 each) of non-neoplastic brain (NNB), low-grade gliomas (LGG, WHO°II) and glioblastomas (GBM, WHO°IV). Immunohistochemistry of tissue samples (n = 7 LGG, 11 AA and 12 GBM) did not show any significant difference in the fraction of KLF8-immunopositive cells of all analyzed cells in LGG (87%), AA (80%) or GBM (89%). Tissue samples from cerebral breast cancer metastasis, meningiomas but also non-neoplastic brain demonstrated comparable relative cell counts as well. Moreover, there was no correlation between KLF8 expression and the expression pattern of the assumed proliferation marker Ki67, which showed high variability between different tumor grade (9% (LGG), 6% (AA) and 15% (GBM) of Ki67-immunopositive cells). Densitometric analysis of Western blotting revealed that the relative amount of KLF8-protein did also not differ between the highly aggressive and proliferative GBM (1.05) compared to LGG (0.93; p<0.05, studens t-test). As demonstrated for some other non-glial cancer entities, KLF8-knockdown by shRNA in U87-MG cells confirmed its functional relevance, leading to an almost complete loss of tumor cell proliferation. Selective blocking of KLF8 might represent a novel anti-proliferative treatment strategy for malignant gliomas. Yet, its simultaneous expression in non-proliferating tissues could hamper this approach. PMID:22276196

  7. Immune physiology in tissue regeneration and aging, tumor growth, and regenerative medicine

    PubMed Central

    Bukovsky, Antonin; Caudle, Michael R.; Carson, Ray J.; Gaytán, Francisco; Huleihel, Mahmoud; Kruse, Andrea; Schatten, Heide; Telleria, Carlos M.

    2009-01-01

    The immune system plays an important role in immunity (immune surveillance), but also in the regulation of tissue homeostasis (immune physiology). Lessons from the female reproductive tract indicate that immune system related cells, such as intraepithelial T cells and monocyte-derived cells (MDC) in stratified epithelium, interact amongst themselves and degenerate whereas epithelial cells proliferate and differentiate. In adult ovaries, MDC and T cells are present during oocyte renewal from ovarian stem cells. Activated MDC are also associated with follicular development and atresia, and corpus luteum differentiation. Corpus luteum demise resembles rejection of a graft since it is attended by a massive influx of MDC and T cells resulting in parenchymal and vascular regression. Vascular pericytes play important roles in immune physiology, and their activities (including secretion of the Thy-1 differentiation protein) can be regulated by vascular autonomic innervation. In tumors, MDC regulate proliferation of neoplastic cells and angiogenesis. Tumor infiltrating T cells die among malignant cells. Alterations of immune physiology can result in pathology, such as autoimmune, metabolic, and degenerative diseases, but also in infertility and intrauterine growth retardation, fetal morbidity and mortality. Animal experiments indicate that modification of tissue differentiation (retardation or acceleration) during immune adaptation can cause malfunction (persistent immaturity or premature aging) of such tissue during adulthood. Thus successful stem cell therapy will depend on immune physiology in targeted tissues. From this point of view, regenerative medicine is more likely to be successful in acute rather than chronic tissue disorders. PMID:20195382

  8. X-Ray Diffraction Profile Analysis for Characterizing Isothermal Aging Behavior of M250 Grade Maraging Steel

    NASA Astrophysics Data System (ADS)

    Mahadevan, S.; Jayakumar, T.; Rao, B. P. C.; Kumar, Anish; Rajkumar, K. V.; Raj, Baldev

    2008-08-01

    X-ray diffraction (XRD) studies were carried out to characterize aging behavior of M250 grade maraging steel samples subjected to isothermal aging at 755 K for varying durations of 0.25, 1, 3, 10, 40, 70, and 100 hours. Earlier studies had shown typical features of precipitation hardening, wherein the hardness increased to a peak value due to precipitation of intermetallics and decreased upon further aging (overaging) due to reversion of martensite to austenite. Intermetallic precipitates, while coherent, are expected to increase the microstrain in the matrix. Hence, an attempt has been made in the present study to understand the microstructural changes in these samples using XRD line profile analysis. The anisotropic broadening with diffraction angle observed in the simple Williamson Hall (WH) plot has been addressed using the modified WH (mWH) approach, which takes into account the contrast caused by dislocations on line profiles, leading to new scaling factors in the WH plot. The normalized mean square strain and crystallite size estimated from mWH have been used to infer early precipitation and to characterize aging behavior. The normalized mean square strain has been used to determine the Avrami exponent in the Johnson Mehl Avrami (JMA) equation, which deals with the kinetics of precipitation. The Avrami exponent thus determined has matched well with values found by other methods, as reported in literature.

  9. Expression of Somatostatin Receptor Type 2A and PTEN in Neuroendocrine Neoplasms Is Associated with Tumor Grade but Not with Site of Origin.

    PubMed

    Wada, Hideo; Matsuda, Katsuya; Akazawa, Yuko; Yamaguchi, Yuka; Miura, Shiro; Ueki, Nozomi; Kinoshita, Akira; Yoshiura, Koh-Ichiro; Kondo, Hisayoshi; Ito, Masahiro; Nagayasu, Takeshi; Nakashima, Masahiro

    2016-09-01

    Neuroendocrine neoplasms (NENs) are derived from endocrine cells in various organs and share common morphological features. This study aimed to clarify whether NENs of different organs are comparable at the molecular pathologic level. We retrospectively collected 99 cases of NENs from gastro-entero-pancreatic, lung, and other organs and reclassified these according to identical criteria. Grade, site, and molecular expression profile including NE markers, Ki-67, p53, somatostatin receptor type 2A (SSTR2A), and phosphatase and tensin homolog (PTEN) were compared. PTEN immunoreactivity was also compared with genomic copy number by fluorescence in situ hybridization (FISH) and droplet digital polymerase chain reaction (ddPCR). No significant differences were observed in the immunoreactivities of NE markers, p53, SSTR2A, or PTEN expression in NENs between the different organ sites. PTEN and p53 functional inactivation along with the loss of membranous SSTR2A expression appeared to be commonly involved in high-grade NEN. FISH results were significantly correlated with the level of PTEN immunoreactivity and with the findings of ddPCR analyses. The demonstration that these tumors are comparable at the molecular level will likely contribute to the broadening of therapeutic options such as the use of somatostatin analogues and mTOR inhibitors against NENs regardless of the affected organ, whereas molecular characterization of tumor grade will be useful for determining treatment strategy. PMID:27256098

  10. Identification of a novel population in high-grade oligodendroglial tumors not deleted on 1p/19q using array CGH.

    PubMed

    Talagas, Matthieu; Marcorelles, Pascale; Uguen, Arnaud; Redon, Sylvia; Quintin-Roué, Isabelle; Costa, Sebastian; Férec, Claude; Morel, Frédéric; Hieu, Phong Dam; De Braekeleer, Marc

    2012-09-01

    Oligodendroglial tumors (ODTs) are primary tumors of the central nervous system that show recurrent codeletion of whole chromosome arms 1p and 19q. Non-1p/19q-deleted high-grade ODTs can present other genetic aberrations, CDKN2A deletion (9p21.3), EGFR amplification (7p11.2) and/or chromosome 10 loss, which are associated with a poor prognosis. The identification of these abnormalities allowed drafting a histo-molecular classification. The aim of this study was to precisely identify, using array CGH, the genomic hallmarks of these tumors, particularly those that are not deleted on 1p/19q. We studied 14 formalin-fixed paraffin-embedded high-grade ODTs using pangenomic oligonucleotide array CGH with an average resolution of 22.3 kb. The 1p/19q codeletion was found in five anaplastic oligodendrogliomas. The three genomic aberrations carrying a poor prognosis were found, most often associated, in five out of nine tumors not deleted on 1p/19q. In addition, four recurrent copy number alterations, involving genes that participate to cell growth and cycle, were found to be strongly associated in five tumors not deleted on 1p/19q: gain or amplification at 1q32.1 (MDM4, PIK3C2B genes), 12q14.1 (CDK4 gene), 12q14.3-q15 (MDM2 gene) and homozygous deletion at 22q13.1 (APOBEC3B gene). MDM2, MDM4, CDK4 and PIK3C2B are known for potentially being amplified or overexpressed in high-grade gliomas. However, the involvement of APOBEC3B, coding for mRNA edition enzyme, is described here for the first time. Our results show a strong association between these four alterations. Therefore, this can open a perspective for a novel subgroup in high-grade ODTs not deleted on 1p/19q. PMID:22825724

  11. Senescence marker protein 30 (SMP30)/regucalcin (RGN) expression decreases with aging, acute liver injuries and tumors in zebrafish

    SciTech Connect

    Fujisawa, Koichi; Terai, Shuji; Hirose, Yoshikazu; Takami, Taro; Yamamoto, Naoki; Sakaida, Isao

    2011-10-22

    Highlights: {yields} Zebrafish SMP30/RGN mRNA expression decreases with aging. {yields} Decreased expression was observed in liver tumors as compared to the surrounding area. {yields} SMP30/RGN is important for liver proliferation and tumorigenesis. -- Abstract: Senescence marker protein 30 (SMP30)/regucalcin (RGN) is known to be related to aging, hepatocyte proliferation and tumorigenesis. However, expression and function of non-mammalian SMP30/RGN is poorly understood. We found that zebrafish SMP30/RGN mRNA expression decreases with aging, partial hepatectomy and thioacetamide-induced acute liver injury. SMP30/RGN expression was also greatly decreased in a zebrafish liver cell line. In addition, we induced liver tumors in adult zebrafish by administering diethylnitrosamine. Decreased expression was observed in foci, hepatocellular carcinomas, cholangiocellular carcinomas and mixed tumors as compared to the surrounding area. We thus showed the importance of SMP30/RGN in liver proliferation and tumorigenesis.

  12. Nuclear Age Issues: A Teacher's Resource Guide for Kindergarten through Grade Twelve. Publication No. X-127.

    ERIC Educational Resources Information Center

    Los Angeles Unified School District, CA. Office of Instruction.

    This teacher's resource guide is designed to facilitate the planning of science and history/social science classroom instruction concerning nuclear age issues for elementary and secondary students. The materials introduce this topic with an interdisciplinary approach to a broad range of nuclear topics. The booklet is divided into five sections.…

  13. Effects of Age of English Exposure, Current Input/Output, and Grade on Bilingual Language Performance

    ERIC Educational Resources Information Center

    Bedore, Lisa M.; Pena, Elizabeth D.; Griffin, Zenzi M.; Hixon, J. Gregory

    2016-01-01

    This study evaluates the effects of Age of Exposure to English (AoEE) and Current Input/Output on language performance in a cross-sectional sample of Spanish-English bilingual children. First- (N = 586) and third-graders (N = 298) who spanned a wide range of bilingual language experience participated. Parents and teachers provided information…

  14. Jekyll and Hyde and Me: Age-Graded Differences in Conceptions of Self-Unity

    ERIC Educational Resources Information Center

    Proulx, Travis; Chandler, Michael J.

    2009-01-01

    This research details the changing ways in which young people of different ages differently warrant the conviction that, notwithstanding evidence of good and bad behaviours, selves can be understood as unified across the various roles and contexts that they occupy. Canadian adolescents and young adults were asked to explain the apparent disunity…

  15. The Cross-Age Mentoring Program: A Developmental Intervention for Promoting Students' Connectedness across Grade Levels

    ERIC Educational Resources Information Center

    Karcher, Michael J.

    2008-01-01

    In cross-age peer mentoring programs, high school students mentor younger students. Prior research demonstrates the positive effects for mentees as well as for mentors. This context-based, strengths-promoting intervention is designed to help school counselors foster high school students' leadership and collaboration skills while simultaneously…

  16. Effects of dry, vacuum, and special bag aging; USDA quality grade; and end-point temperature on yields and eating quality of beef Longissimus lumborum steaks.

    PubMed

    Dikeman, Michael E; Obuz, Ersel; Gök, Veli; Akkaya, Levent; Stroda, Sally

    2013-06-01

    This study evaluated the effects of three aging methods: (dry (D), wet (W), and special bag (SB)); two quality grades [USDA Choice((≥Small(50) marbling) and Select); and two cooked end-point temperatures (62.8 °C and 71.1 °C) on physico-chemical traits of instrumental tenderness, color, and sensory properties of Longissimus lumborum beef muscle. Dry-aged loins had higher (P<0.0001) weight loss than W or SB aged loins. However, D and SB aged loins had similar (P>0.05) combined losses. W aged loins had higher (P<0.01) L* values than D or SB aged loins. Warner-Bratzler shear force of steaks was not affected (P>0.05) by aging method or quality grade but increased (P<0.0001) as end-point temperature increased. Sensory panel evaluation also showed no effect (P>0.05) of aging method or quality grade on myofibrillar tenderness, juiciness, connective tissue amount, overall tenderness or off flavor intensity. Steaks cooked to 62.8 °C were juicier (P<0.05) than those cooked to 71.1 °C. Neither D nor SB aging had advantages over W aging. PMID:23501255

  17. Aged garlic extract inhibits 1,2-dimethylhydrazine-induced colon tumor development by suppressing cell proliferation.

    PubMed

    Jikihara, Hiroshi; Qi, Guangying; Nozoe, Koichiro; Hirokawa, Mayumi; Sato, Hiromi; Sugihara, Yuka; Shimamoto, Fumio

    2015-03-01

    Garlic and its constituents are reported to have a preventive effect against colorectal cancer in animal models. Aged garlic extract (AGE), which is produced by natural extraction from fresh garlic for more than 10 months in aqueous ethanol, also has reputed chemopreventive effects on colon carcinogenesis, but has never been studied for its effects on colon cancer development. We investigated the antitumor effects of AGE in rats with 1,2-dimethylhydrazine (DMH)-induced carcinogenesis, and the mechanism of AGE in human colon cancer cell proliferation. F344 rats randomly divided into three groups were administered DMH (20 mg/kg weight) subcutaneously once a week for 8 weeks in a basal diet. After the last injection, one group of rats was then moved onto a basal diet containing 3% wt/wt AGE, and rats were sacrificed at 8 or 31 weeks. The number of aberrant crypt foci (ACF), histological type of tumor and proliferative activity of the tumor lesions were analyzed by macroscopic, pathological and immunohistochemical methods. DLD-1 human colon cancer cells were utilized to investigate the effect of AGE on anti-cell proliferation. AGE decreased the number of ACF but had no effect on gross tumor pathology. AGE showed a lower number of adenoma and adenocarcinoma lesions by histological analysis. Immunohistochemical staining indicated that AGE suppressed the proliferative activity in adenoma and adenocarcinoma lesions, but showed no effect on normal colon mucosa. Moreover, we demonstrated that AGE delayed cell cycle progression by downregulating cyclin B1 and cdk1 expression via inactivation of NF-κB in the human colorectal cancer cells but did not induce apoptosis. These findings suggest that AGE has an antitumor effect through suppression of cell proliferation. PMID:25573280

  18. The Minnesota Grading System Using Fundus Autofluorescence of Eye Bank Eyes: A Correlation To Age-Related Macular Degeneration (An AOS Thesis)

    PubMed Central

    Olsen, Timothy W.

    2008-01-01

    Purpose To establish a grading system of eye bank eyes using fundus autofluorescence (FAF) and identify a methodology that correlates FAF to age-related macular degeneration (AMD) with clinical correlation to the Age-Related Eye Disease Study (AREDS). Methods Two hundred sixty-two eye bank eyes were evaluated using a standardized analysis of FAF. Measurements were taken with the confocal scanning laser ophthalmoscope (cSLO). First, high-resolution, digital, stereoscopic, color images were obtained and graded according to AREDS criteria. With the neurosensory retina removed, mean FAF values were obtained from cSLO images using software analysis that excludes areas of atrophy and other artifact, generating an FAF value from a grading template. Age and AMD grade were compared to FAF values. An internal fluorescence reference standard was tested. Results Standardization of the cSLO machine demonstrated that reliable data could be acquired after a 1-hour warm-up. Images obtained prior to 1 hour had falsely elevated levels of FAF. In this initial analysis, there was no statistical correlation of age to mean FAF. There was a statistically significant decrease in FAF from AREDS grade 1, 2 to 3, 4 (P < .0001). An internal fluorescent standard may serve as a quantitative reference. Conclusions The Minnesota Grading System (MGS) of FAF (MGS-FAF) establishes a standardized methodology for grading eye bank tissue to quantify FAF compounds in the retinal pigment epithelium and correlate these findings to the AREDS. Future studies could then correlate specific FAF to the aging process, histopathology AMD phenotypes, and other maculopathies, as well as to analyze the biochemistry of autofluorescent fluorophores. PMID:19277247

  19. Impact of tumor location and pathological discordance on survival of children with midline high-grade gliomas treated on Children's Cancer Group high-grade glioma study CCG-945.

    PubMed

    Eisenstat, David D; Pollack, Ian F; Demers, Alain; Sapp, Mark V; Lambert, Pascal; Weisfeld-Adams, James D; Burger, Peter C; Gilles, Floyd; Davis, Richard L; Packer, Roger; Boyett, James M; Finlay, Jonathan L

    2015-02-01

    Children with high-grade glioma (HGG) have a poor prognosis compared to those with low-grade glioma (LGG). Adjuvant chemotherapy may be beneficial, but its optimal use remains undetermined. Histology and extent of resection are important prognostic factors. We tested the hypothesis that patients with midline HGG treated on Children's Cancer Group Study (CCG) CCG-945 have a worse prognosis compared to the entire group. Of 172 children eligible for analysis, 60 had midline tumors primarily localized to the thalamus, hypothalamus and basal ganglia. Time-to-progression and death were determined from the date of initial diagnosis, and survival curves were calculated. Univariate analyses were undertaken for extent of resection, chemotherapy regimen, anatomic location, histology, proliferation index, MGMT status and p53 over-expression. For the entire midline tumor group, 5-year PFS and OS were 18.3 ± 4.8 and 25 ± 5.4 %, respectively. Many patients only had a biopsy (43.3 %). The sub-groups with near/total resection and hypothalamic location appeared to have better PFS and OS. However, the effect of tumor histology on OS was significant for children with discordant diagnoses on central pathology review of LGG compared to HGG. Proliferative index (MIB-1 > 36 %), MGMT and p53 over-expression correlated with poor outcomes. Children treated on CCG-945 with midline HGG have a worse prognosis when compared to the entire group. The midline location may directly influence the extent of resection. Central pathology review and entry of patients on clinical trials continue to be priorities to improve outcomes for children with HGG. PMID:25431150

  20. Impact of tumor location and pathological discordance on survival of children with midline high-grade gliomas treated on Children’s Cancer Group high-grade glioma study CCG-945

    PubMed Central

    Pollack, Ian F.; Demers, Alain; Sapp, Mark V.; Lambert, Pascal; Weisfeld-Adams, James D.; Burger, Peter C.; Gilles, Floyd; Davis, Richard L.; Packer, Roger; Boyett, James M.

    2015-01-01

    Children with high-grade glioma (HGG) have a poor prognosis compared to those with low-grade glioma (LGG). Adjuvant chemotherapy may be beneficial, but its optimal use remains undetermined. Histology and extent of resection are important prognostic factors. We tested the hypothesis that patients with midline HGG treated on Children’s Cancer Group Study (CCG) CCG-945 have a worse prognosis compared to the entire group. Of 172 children eligible for analysis, 60 had midline tumors primarily localized to the thalamus, hypothalamus and basal ganglia. Time-to-progression and death were determined from the date of initial diagnosis, and survival curves were calculated. Univariate analyses were undertaken for extent of resection, chemotherapy regimen, anatomic location, histology, proliferation index, MGMT status and p53 over-expression. For the entire midline tumor group, 5-year PFS and OS were 18.3 ± 4.8 and 25 ± 5.4 %, respectively. Many patients only had a biopsy (43.3 %). The sub-groups with near/total resection and hypothalamic location appeared to have better PFS and OS. However, the effect of tumor histology on OS was significant for children with discordant diagnoses on central pathology review of LGG compared to HGG. Proliferative index (MIB-1 > 36 %), MGMT and p53 over-expression correlated with poor outcomes. Children treated on CCG-945 with midline HGG have a worse prognosis when compared to the entire group. The midline location may directly influence the extent of resection. Central pathology review and entry of patients on clinical trials continue to be priorities to improve outcomes for children with HGG. PMID:25431150

  1. Expression profile of COL2A1 and the pseudogene SLC6A10P predicts tumor recurrence in high-grade serous ovarian cancer.

    PubMed

    Ganapathi, Mahrukh K; Jones, Wendell D; Sehouli, Jalid; Michener, Chad M; Braicu, Ioana E; Norris, Eric J; Biscotti, Charles V; Vaziri, Susan A J; Ganapathi, Ram N

    2016-02-01

    Tumor recurrence, following initial response to adjuvant chemotherapy, is a major problem in women with high-grade serous ovarian cancer (HGSOC). Microarray analysis of primary tumors has identified genes that may be useful in risk stratification/overall survival, but are of limited value in predicting the >70% rate for tumor recurrence. In this study, we performed RNA-Seq analysis of primary and recurrent HGSOC to first identify unique differentially expressed genes. From this dataset, we selected 21 archetypical coding genes and one noncoding RNA, based on statistically significant differences in their expression profile between tumors, for validation by qPCR in a larger cohort of 110 ovarian tumors (71 primary and 39 recurrent) and for testing association of specific genes with time-to-recurrence (TTR). Kaplan-Meier tests revealed that high expression of collagen type II, alpha 1 (COL2A1) was associated with delayed TTR (HR = 0.47, 95% CI: 0.27-0.82, p = 0.008), whereas low expression of the pseudogene, solute carrier family 6 member 10 (SLC6A10P), was associated with longer TTR (HR = 0.53, 95% CI: 0.30-0.93, p = 0.027). Notably, TTR was significantly delayed for tumors that simultaneously highly expressed COL2A1 and lowly expressed SLC6A10P (HR = 0.21, 95% CI: 0.082-0.54, p = 0.0011), an estimated median of 95 months as compared to an estimated median of 16 months for subjects expressing other levels of COL2A1 and SLC6A10P. Thus, evaluating expression levels of COL2A1 and SLC6A10P at primary surgery could be beneficial for clinically managing recurrence of HGSOC. PMID:26311224

  2. An evaluation of the morphologic features of low-grade mucinous neoplasms of the appendix metastatic in the ovary, and comparison with primary ovarian mucinous tumors.

    PubMed

    Stewart, Colin J R; Ardakani, Nima M; Doherty, Dorota A; Young, Robert H

    2014-01-01

    It may be difficult to distinguish ovarian involvement by a low-grade appendiceal mucinous neoplasm (LAMN) from a primary gastrointestinal-type primary borderline (proliferative) ovarian tumor (IBMT) or an ovarian mucinous tumor arising within a teratoma, particularly when the latter is associated with mucinous ascites/pseudomyxoma peritonei. We noted that LAMNs involving the ovaries show 2 distinctive histologic features, "scalloped" glands and subepthelial stromal clefts, whereas IBMTs more often are associated with reactive cellular stroma and histiocyte aggregates (mucin granulomas). The frequency of these features was investigated in 18 LAMNs (16 with pseudomyxoma peritonei), 18 primary IBMTs, and 6 teratoma-associated mucinous tumors (selected on the basis of associated pseudomyxoma peritonei). Scalloped glands and subepithelial clefts were identified in 17 and 16 LAMNs, respectively, and in 3 and 7 IBMTs, respectively. Conversely, reactive stroma and histiocyte aggregates were present in 2 and 0 LAMNs, respectively, and in 11 and 10 IBMTs, respectively. LAMNs were often bilateral (12/18 cases) and they more frequently showed mucin dissection of the ovarian stroma and tall mucin-rich (hypermucinous) epithelial cells compared with IBMTs. Our findings suggest that scalloped glands, subepithelial clefts, cellular stroma, and histiocyte aggregates may be useful additional morphologic parameters to help distinguish these tumor types. However, teratoma-associated mucinous neoplasms can show identical histologic features to those of LAMNs involving the ovary, and therefore accurate diagnosis of such cases requires careful macroscopic and microscopic examinations of the ovaries together with complete histologic assessment of the appendix. PMID:24300528

  3. 1H HRMAS NMR Derived Bio-markers Related to Tumor Grade, Tumor Cell Fraction, and Cell Proliferation in Prostate Tissue Samples

    PubMed Central

    Stenman, Katarina; Stattin, Pär; Stenlund, Hans; Riklund, Katrine; Gröbner, Gerhard; Bergh, Anders

    2011-01-01

    A high-resolution magic angle spinning NMR spectroscopic approach is presented for evaluating the occurrence, amount and aggressiveness of cancer in human prostate tissue samples. Using this technique, key metabolites in malignant and non-malignant samples (n = 149) were identified, and patterns of their relative abundance were analyzed by multivariate statistical methods. Ratios of various metabolites – including (glycerophophorylcholine + phosphorylcholine)/creatine, myo-inositol/scyllo-inositol, scyllo-inositol/creatine, choline/creatine, and citrate/creatine – correlated with: i) for non-malignant tissue samples, the distance to the nearest tumor and its Gleason score and; ii) the fraction of tumor cells present in the sample; and iii) tumor cell proliferation (Ki67 labelling index). This NMR-based approach allows the extraction of information that could be useful for developing novel diagnostic methods for prostate cancer. PMID:21499438

  4. Estrogens metabolism associated with polymorphisms: influence of COMT G482a genotype on age at onset of canine mammary tumors.

    PubMed

    Dias Pereira, P; Lopes, C C; Matos, A J F; Pinto, D; Gärtner, F; Lopes, C; Medeiros, R

    2008-03-01

    Catechol-O-methyltransferase (COMT) is an important enzyme participating in inactivation of carcinogenic oestrogen metabolites. In humans there is a single nucleotide polymorphism in COMT gene (COMT val158met) that has been associated with an increased risk for developing breast cancer. In dogs, there is a single nucleotide polymorphism in COMT gene (G482A), but its relation with mammary carcinogenesis has never been investigated. The aim of this study was to focus on the evaluation of such polymorphism as a risk factor for the development of mammary tumors in bitches and on the analysis of its relationship with some clinicopathologic features (dog's age and weight, number and histologic type of the lesions, lymph node metastasis) of canine mammary neoplasms. A case-control study was conducted analyzing 90 bitches with mammary tumors and 84 bitches without evidence of neoplastic disease. The COMT G482A polymorphism was analyzed by PCR-RFLP. We found a protective effect of the polymorphism in age of onset of mammary tumors, although we could not establish a significant association between COMT genotype and other clinicopathologic parameters nor with mammary tumor risk overall. Animals carrying the variant allele have a threefold likelihood of developing mammary tumors after 9 years of age in comparison with noncarriers. The Kaplan-Meier method revealed significant differences in the waiting time for onset of malignant disease for A allele carrier (12.46 years) and noncarrier (11.13 years) animals. This investigation constitutes the first case-control study designed to assess the relationship between polymorphic genes and mammary tumor risk in dogs. Our results point to the combined effect of COMT genotype with other genetic and/or environmental risk factors as important key factors for mammary tumor etiopathogenesis. PMID:18424824

  5. Age and tectonic implications of some low-grade metamorphic rocks from the Yucatan Channel

    USGS Publications Warehouse

    Vedder, J.G.; MacLeod, N.S.; Lanphere, M.A.; Dillon, William P.

    1973-01-01

    Phyllite and marble dredged from the lower part of the continental slope between Cuba and the Yucatan Peninsula seem to support the contention that a pre-early Tertiary metamorphic belt extends from the western Greater Antilles into northern Central America. The minimum K-Ar ages derived from the samples suggest that the metamorphic event was pre-Late Cretaceous, and evaluation of the K-Ar data implies that this metamorphic event is not older than Late Jurassic. Greater antiquity, however, is inferred from structural and stratigraphic relations in British Honduras, where the latest regional metamorphic event was post-Early Permian and pre-Middle Jurassic.  Rifting and extension related to plate motions along the British Honduras Quintana Roo margin through Mesozoic and earliest Cenozoic time presumably would preclude extensive regional metamorphism, permitting only limited development of schistose rocks there during that interval. The timing of metamorphic events in western Cuba is uncertain, but a pre-Middle Jurassic episode possibly is reflected in the phyllite and marble terranes of Isla de Pinos and Sierra de Trinidad. Local incipient metamorphism of Early and Middle Jurassic strata in the Sierra de los Organos may have resulted from severe tectonism that began in Late Cretaceous time and diminished in the Eocene.

  6. Breast Cancer Survival Defined by the ER/PR/HER2 Subtypes and a Surrogate Classification according to Tumor Grade and Immunohistochemical Biomarkers

    PubMed Central

    Parise, Carol A.

    2014-01-01

    Introduction. ER, PR, and HER2 are routinely available in breast cancer specimens. The purpose of this study is to contrast breast cancer-specific survival for the eight ER/PR/HER2 subtypes with survival of an immunohistochemical surrogate for the molecular subtype based on the ER/PR/HER2 subtypes and tumor grade. Methods. We identified 123,780 cases of stages 1–3 primary female invasive breast cancer from California Cancer Registry. The surrogate classification was derived using ER/PR/HER2 and tumor grade. Kaplan-Meier survival analysis and Cox proportional hazards modeling were used to assess differences in survival and risk of mortality for the ER/PR/HER2 subtypes and surrogate classification within each stage. Results. The luminal B/HER2− surrogate classification had a higher risk of mortality than the luminal B/HER2+ for all stages of disease. There was no difference in risk of mortality between the ER+/PR+/HER2− and ER+/PR+/HER2+ in stage 3. With one exception in stage 3, the ER-negative subtypes all had an increased risk of mortality when compared with the ER-positive subtypes. Conclusions. Assessment of survival using ER/PR/HER2 illustrates the heterogeneity of HER2+ subtypes. The surrogate classification provides clear separation in survival and adjusted mortality but underestimates the wide variability within the subtypes that make up the classification. PMID:24955090

  7. Survival Analyses for Patients With Surgically Resected Pancreatic Neuroendocrine Tumors by World Health Organization 2010 Grading Classifications and American Joint Committee on Cancer 2010 Staging Systems

    PubMed Central

    Yang, Min; Ke, Neng-wen; Zeng, Lin; Zhang, Yi; Tan, Chun-lu; Zhang, Hao; Mai, Gang; Tian, Bo-le; Liu, Xu-bao

    2015-01-01

    Abstract In 2010, World Health Organization (WHO) reclassified pancreatic neuroendocrine tumors (p-NETs) into 4 main groups: neuroendocrine tumor G1 (NET G1), neuroendocrine tumor G2 (NET G2), neuroendocrine carcinoma G3 (NEC G3), mixed adeno and neuroendocrine carcinoma (MANEC). Clinical value of these newly updated WHO grading criteria has not been rigorously validated. The authors aimed to evaluate the clinical consistency of the new 2010 grading classifications by WHO and the 2010 tumor-node metastasis staging systems by American Joint Committee on Cancer (AJCC) on survivals for patients with surgically resected p-NETs. Moreover, the authors would validate the prognostic value of both criteria for p-NETs. The authors retrospectively collected the clinicopathologic data of 120 eligible patients who were all surgically treated and histopathologically diagnosed as p-NETs from January 2004 to February 2014 in our single institution. The new WHO criteria were assigned to 4 stratified groups with a respective distribution of 62, 35, 17, and 6 patients. Patients with NET G1 or NET G2 obtained a statistically better survival compared with those with NEC G3 or MANEC (P < 0.001). Survivals of NET G1 was also better than those of NET G2 (P = 0.023), whereas difference of survivals between NEC G3 and MANEC present no obvious significance (P = 0.071). The AJCC 2010 staging systems were respectively defined in 61, 36, 12, and 11 patients for each stage. Differences of survivals of stage I with stage III and IV were significant (P < 0.001), as well as those of stage II with III and IV (P < 0.001); whereas comparisons of stage I with stage II and stage III with IV were not statistically significant (P = 0.129, P = 0.286; respectively). Together with radical resection, these 2 systems were both significant in univariate and multivariate analysis (P < 0.05). The newly updated WHO 2010 grading classifications and the AJCC 2010 staging systems could

  8. Survival Analyses for Patients With Surgically Resected Pancreatic Neuroendocrine Tumors by World Health Organization 2010 Grading Classifications and American Joint Committee on Cancer 2010 Staging Systems.

    PubMed

    Yang, Min; Ke, Neng-wen; Zeng, Lin; Zhang, Yi; Tan, Chun-lu; Zhang, Hao; Mai, Gang; Tian, Bo-le; Liu, Xu-bao

    2015-12-01

    In 2010, World Health Organization (WHO) reclassified pancreatic neuroendocrine tumors (p-NETs) into 4 main groups: neuroendocrine tumor G1 (NET G1), neuroendocrine tumor G2 (NET G2), neuroendocrine carcinoma G3 (NEC G3), mixed adeno and neuroendocrine carcinoma (MANEC). Clinical value of these newly updated WHO grading criteria has not been rigorously validated. The authors aimed to evaluate the clinical consistency of the new 2010 grading classifications by WHO and the 2010 tumor-node metastasis staging systems by American Joint Committee on Cancer (AJCC) on survivals for patients with surgically resected p-NETs. Moreover, the authors would validate the prognostic value of both criteria for p-NETs.The authors retrospectively collected the clinicopathologic data of 120 eligible patients who were all surgically treated and histopathologically diagnosed as p-NETs from January 2004 to February 2014 in our single institution. The new WHO criteria were assigned to 4 stratified groups with a respective distribution of 62, 35, 17, and 6 patients. Patients with NET G1 or NET G2 obtained a statistically better survival compared with those with NEC G3 or MANEC (P < 0.001). Survivals of NET G1 was also better than those of NET G2 (P = 0.023), whereas difference of survivals between NEC G3 and MANEC present no obvious significance (P = 0.071). The AJCC 2010 staging systems were respectively defined in 61, 36, 12, and 11 patients for each stage. Differences of survivals of stage I with stage III and IV were significant (P < 0.001), as well as those of stage II with III and IV (P < 0.001); whereas comparisons of stage I with stage II and stage III with IV were not statistically significant (P = 0.129, P = 0.286; respectively). Together with radical resection, these 2 systems were both significant in univariate and multivariate analysis (P < 0.05).The newly updated WHO 2010 grading classifications and the AJCC 2010 staging systems could consistently reflect the clinical outcome

  9. Early perfusion changes in patients with recurrent high-grade brain tumor treated with Bevacizumab: preliminary results by a quantitative evaluation

    PubMed Central

    2012-01-01

    Background To determine whether early monitoring of the effects of bevacizumab in patients with recurrent high-grade gliomas, by a Perfusion Computed Tomography (PCT), may be a predictor of the response to treatment assessed through conventional MRI follow-up. Methods Sixteen patients were enrolled in the present study. For each patient, two PCT examinations, before and after the first dose of bevacizumab, were acquired. Areas of abnormal Cerebral Blood Volume (CBV) were manually defined on the CBV maps, using co-registered T1- weighted images, acquired before treatment, as a guide to the tumor location. Different perfusion metrics were derived from the histogram analysis of the normalized CBV (nCBV) maps; both hyper and hypo-perfused sub-volumes were quantified in the lesion, including tumor necrosis. A two-tailed Wilcoxon test was used to establish the significance of changes in the different perfusion metrics, observed at baseline and during treatment. The relationships between changes in perfusion and morphological MRI modifications at first follow-up were investigated. Results Significant reductions in mean and median nCBV were detected throughout the entire patient population, after only a single dose of bevacizumab. The nCBV histogram modifications indicated the normalization effect of bevacizumab on the tumor abnormal vasculature. An improvement in hypoxia after a single dose of bevacizumab was predictive of a greater reduction in T1-weighted contrast-enhanced volumes at first follow-up. Conclusions These preliminary results show that a quantification of changes in necrotic intra-tumoral regions could be proposed as a potential imaging biomarker of tumor response to anti-VEGF therapies. PMID:22494770

  10. Bone tumors in a population of 400 000 insured Swedish dogs up to 10 y of age: incidence and survival

    PubMed Central

    Egenvall, Agneta; Nødtvedt, Ane; von Euler, Henrik

    2007-01-01

    The objectives of this study were to describe the incidence of, survival until, and survival after the diagnosis of canine bone tumors by breed, sex, age, and geographic location of residence. Dogs under 10 y old and insured by a Swedish insurance company between 1995 and 2002 were studied. In total, 764 dogs had claims for bone tumors, and the incidence rate was 5.5 cases per 10 000 dog-years at risk (DYAR). At ages 6, 8, and 10 y, the proportions of dogs with bone tumors were 0.13%, 0.30%, and 0.64%. The top 3 breeds at risk were Irish wolfhound, St. Bernard, and leonberger (incidence rates 99, 78, and 53 cases per 10 000 DYAR, respectively). Median survival time after diagnosis was 56 d in the 419 dogs that survived ≥ 1 d. With a Cox regression model controlling for breed and age, females were shown to be at decreased risk of bone tumors, with a hazard ratio of 0.71 (99% confidence interval 0.58 to 0.87). PMID:17955904

  11. Calcification on CT is a simple and valuable preoperative indicator of 1p/19q loss of heterozygosity in supratentorial brain tumors that are suspected grade II and III gliomas.

    PubMed

    Saito, Taiichi; Muragaki, Yoshihiro; Maruyama, Takashi; Komori, Takashi; Tamura, Manabu; Nitta, Masayuki; Tsuzuki, Shunsuke; Kawamata, Takakazu

    2016-07-01

    Gliomas with 1p/19q loss of heterozygosity (LOH) are known to be associated with longer patient survival and higher sensitivity to treatment than tumors without 1p/19q LOH. This study was designed to clarify whether the preoperative finding of calcification on CT was correlated with 1p/19q LOH in patients with suspected WHO grade II and III gliomas. This study included 250 adult patients who underwent resection for primary supratentorial tumors at Tokyo Women's Medical University Hospital. The tumors were suspected, based on MRI findings, to be WHO grade II or III gliomas. The presence of calcification on the patients' CT images was qualitatively evaluated before treatment. After surgery, the resected tumors were examined to determine their 1p/19q status and mutations of IDH1 and p53. The presence of calcification was significantly correlated with 1p/19q LOH (P < 0.0001), with a positive predictive value of 91 %. The tumors of all the 78 patients with calcification were diagnosed as oligodendroglial tumors. Seventy of these patients showed classic oligodendroglial features, while 8 patients showed non-classic features. Calcification on CT is a simple and valuable preoperative indicator of 1p/19q LOH in supratentorial brain tumors that are suspected to be WHO grade II and III gliomas. PMID:26849373

  12. Neuroendocrine tumors involving the gastroenteropancreatic tract: a clinicopathological evaluation of 773 cases

    PubMed Central

    Estrozi, Bruna; Bacchi, Carlos E

    2011-01-01

    OBJECTIVE: Description of some of the clinical pathological characteristics of neuroendocrine tumors of the gastroenteropancreatic tract in Brazilian patients. INTRODUCTION: Neuroendocrine tumors arise in many organs and share common pathological features. In 2010, the World Health Organization published a new classification for neuroendocrine tumors using a three-tiered system that applies the terms neuroendocrine tumor Grade 1, neuroendocrine tumor Grade 2, and neuroendocrine carcinoma. The tumor grades are based on their mitotic rate and the Ki-67 index. In Brazil, information on neuroendocrine tumors of gastroenteropancreatic tract is scarce. METHODS: This study investigated clinicopathological features of 773 Brazilian gastroenteropancreatic neuroendocrine tumor cases from all the geographic regions of Brazil. All of the cases emerged from the files of a single institution (a large pathology reference laboratory) between 1997 and 2009. In addition, the gastroenteropancreatic neuroendocrine tumors were graded according to the new 2010 World Health Organization classification. RESULTS: Overall there were a higher number of neuroendocrine tumors in female over male. The lower ages were seen in patients with appendiceal tumors. The most common anatomic location involved was stomach followed by small and large intestines. All cases involving the appendix were of grade 1 and 92.1% of the neuroendocrine tumors of the esophagus were neuroendocrine carcinomas (grade 3). CONCLUSIONS: In this series, the proportion of NET cases in the total number of surgical pathology cases at our institution over the past 12 years is increasing. PMID:22012036

  13. Molecular inimitability amongst tumors: implications for precision cancer medicine in the age of personalized oncology.

    PubMed

    Patel, Sandip P; Schwaederle, Maria; Daniels, Gregory A; Fanta, Paul T; Schwab, Richard B; Shimabukuro, Kelly A; Kesari, Santosh; Piccioni, David E; Bazhenova, Lyudmila A; Helsten, Teresa L; Lippman, Scott M; Parker, Barbara A; Kurzrock, Razelle

    2015-10-20

    Tumor sequencing has revolutionized oncology, allowing for detailed interrogation of the molecular underpinnings of cancer at an individual level. With this additional insight, it is increasingly apparent that not only do tumors vary within a sample (tumor heterogeneity), but also that each patient's individual tumor is a constellation of unique molecular aberrations that will require an equally unique personalized therapeutic regimen. We report here the results of 439 patients who underwent Clinical Laboratory Improvement Amendment (CLIA)-certified next generation sequencing (NGS) across histologies. Among these patients, 98.4% had a unique molecular profile, and aside from three primary brain tumor patients with a single genetic lesion (IDH1 R132H), no two patients within a given histology were molecularly identical. Additionally, two sets of patients had identical profiles consisting of two mutations in common and no other anomalies. However, these profiles did not segregate by histology (lung adenocarcinoma-appendiceal cancer (KRAS G12D and GNAS R201C), and lung adenocarcinoma-liposarcoma (CDK4 and MDM2 amplification pairs)). These findings suggest that most advanced tumors are molecular singletons within and between histologies, and that tumors that differ in histology may still nonetheless exhibit identical molecular portraits, albeit rarely. PMID:26418953

  14. Molecular inimitability amongst tumors: implications for precision cancer medicine in the age of personalized oncology

    PubMed Central

    Patel, Sandip P.; Schwaederle, Maria; Daniels, Gregory A.; Fanta, Paul T.; Schwab, Richard B.; Shimabukuro, Kelly A.; Kesari, Santosh; Piccioni, David E.; Bazhenova, Lyudmila A.; Helsten, Teresa L.; Lippman, Scott M.; Parker, Barbara A.; Kurzrock, Razelle

    2015-01-01

    Tumor sequencing has revolutionized oncology, allowing for detailed interrogation of the molecular underpinnings of cancer at an individual level. With this additional insight, it is increasingly apparent that not only do tumors vary within a sample (tumor heterogeneity), but also that each patient's individual tumor is a constellation of unique molecular aberrations that will require an equally unique personalized therapeutic regimen. We report here the results of 439 patients who underwent Clinical Laboratory Improvement Amendment (CLIA)-certified next generation sequencing (NGS) across histologies. Among these patients, 98.4% had a unique molecular profile, and aside from three primary brain tumor patients with a single genetic lesion (IDH1 R132H), no two patients within a given histology were molecularly identical. Additionally, two sets of patients had identical profiles consisting of two mutations in common and no other anomalies. However, these profiles did not segregate by histology (lung adenocarcinoma-appendiceal cancer (KRAS G12D and GNAS R201C), and lung adenocarcinoma-liposarcoma (CDK4 and MDM2 amplification pairs)). These findings suggest that most advanced tumors are molecular singletons within and between histologies, and that tumors that differ in histology may still nonetheless exhibit identical molecular portraits, albeit rarely. PMID:26418953

  15. The impact of graded levels of day length on turkey health and behavior to 18 weeks of age.

    PubMed

    Vermette, C; Schwean-Lardner, K; Gomis, S; Grahn, B H; Crowe, T G; Classen, H L

    2016-06-01

    The impact of graded levels of day length on turkey health and behavior was determined in hens and toms raised to 18 wk of age. Birds were allocated to one of 4 lighting treatments (trt) providing 14 (14L), 17 (17L), 20 (20L), and 23 (23L) h of day length. Two time-replicated trials were completed with each, providing 2 rooms per lighting trt and each room having 3 hen (n = 720) and 3 tom (n = 480) pens. Data collection included gait score (GS), the incidence of footpad dermatitis (FPD), breast buttons and blisters, ocular size and pressure (males only), and behavioral observations (males only). Data were analyzed using SAS 9.3 based on a completely randomized design nested within 4 lighting trt. Regression analysis established relationships between response criteria and day length. Differences were considered significant at P ≤ 0.05 and trends noted at P ≤ 0.10. Gait score, FPD, and the incidence of breast buttons and blisters were assessed on 5 birds per pen at 11 and 17 wk of age. Average GS increased linearly with day length at 11 and 17 wk for both hens and toms, but the effect was larger in toms. Day length did not affect FPD, but more lesions and severe scores were found for hens than toms. The presence of breast buttons and blisters increased linearly with day length (11 wk) with the effect on blisters predominately seen in toms. Eye weight and size increased with increasing day length at 12 and 18 wk. Ocular pressure was not affected by day length. Infrared cameras recorded tom behavior over a 24 h period, and behaviors were classified over 10-min intervals using a scan sampling technique at 11 and 17 wk. Alterations in behavioral repertoire were observed with a linear increase in inactive resting and a linear decrease in standing, walking, preening, and environmental and feather pecking behaviors with increased day length. To conclude, day length affected bird mobility and incidence of breast blisters in an age- and gender-specific manner, and time

  16. The evolving molecular genetics of low-grade glioma

    PubMed Central

    Venneti, Sriram; Huse, Jason T.

    2015-01-01

    Low-grade gliomas (LGG) constitute grade I and grade II tumors of astrocytic and grade II tumors of oligodendroglial lineage. Although these tumors are typically slow growing, they may be associated with significant morbidity and mortality due to recurrence and malignant progression, even in the setting of optimal resection. LGG in pediatric and adult age groups are currently classified by morphologic criteria. Recent years have heralded a molecular revolution in understanding brain tumors, including LGG. Next generation sequencing has definitively demonstrated that pediatric and adult LGG fundamentally differ in their underlying molecular characteristics, despite being histologically similar. Pediatric LGG show alterations in FGFR1 and BRAF in pilocytic astrocytomas and FGFR1 alterations in diffuse astrocytomas, each converging on the MAP kinase-signaling pathway. Adult LGG are characterized by IDH1/2 mutations and ATRX mutations in astrocytic tumors and IDH1/2 mutations and 1p/19q codeletions in oligodendroglial tumors. TERT promoter mutations are also noted in LGG and are mainly associated with oligodendrogliomas. These findings have considerably refined approaches to classifying these tumors. Moreover, many of the molecular alterations identified in LGG directly impact on prognosis, tumor biology, and the development of novel therapies. PMID:25664944

  17. Some Renal Masses Did Not “Read the Book”: A Case of a High Grade Hybrid Renal Tumor Masquerading as a Renal Cyst on Non-contrast Imaging

    PubMed Central

    Kominsky, Hal D.; Parker, Daniel C.; Gohil, Dharam; Musial, Rachel; Edwards, Kristin; Kutikov, Alexander

    2015-01-01

    Hybrid renal tumors (HRT) are rare neoplasms that contain both benign and malignant components. Sporadic solitary HRT that contain high-grade malignant pathology appear to be extremely rare [1]. We describe a case at our institution of a tumor that was characterized as a type-2 papillary RCC and atypical oncocytoma hybrid that mimicked a simple cyst on non-contrast computed tomography. PMID:26793558

  18. Phase I Study of the Anti-IGF-1R Monoclonal Antibody, Cixutumumab in Combination with Everolimus and Octreotide LAR in Advanced Low to Intermediate Grade Neuroendocrine Tumors

    PubMed Central

    Dasari, Arvind; Phan, Alexandria; Gupta, Sanjay; Rashid, Asif; Yeung, Sai-ChingJim; Hess, Kenneth; Chen, Helen; Tarco, Emily; Chen, Huiqin; Wei, Caimiao; Anh-Do, Kim; Halperin, Daniel; Meric-Bernstam, Funda; Yao, James

    2015-01-01

    Preclinical data suggest multiple roles for the insulin like growth factor receptor 1 (IGF-1R) in neuroendocrine tumors (NET) including mediating resistance to mTOR inhibitors. Everolimus, an oral mTOR inhibitor and octreotide LAR are approved for subgroups of well differentiated NET. The primary objective was to establish the safety and recommended phase II dose (RP2D) of cixutumumab, a monoclonal antibody against IGF-1R with everolimus and octreotide LAR. Patients with well differentiated NET were treated with everolimus 10 mg po daily, octreotide LAR 20 mg IM every 21 days and escalating doses of cixutumumab. An expansion cohort was enrolled at RP2D. Correlative studies included evaluation of mTOR pathway inhibition in paired tumor biopsies and effects of this combination on metabolism per indirect calorimetry. 19 patients with progressive disease, including 9 to the expansion portion were enrolled. 2 patients had dose limiting toxicities of grade 3 mucositis at cixutumumab 15 mg/kg. Long term tolerance at RP2D was problematic, the most common ≥ grade 3 adverse event (AE) being fatigue. One patient with metastatic insulinoma had a confirmed partial response while seventeen had stable disease. Median progression free survival was 43.6 weeks and median overall survival was 25.5 months. Conclusions The RP2D of this combination per predefined study protocol cixutumumab iv 10 mg/kg, octreotide LAR 20 mg IM every 21 days plus everolimus 10 mg po daily is associated with non-DLT toxicities limiting long term tolerance. Although a signal of activity was noted in this study, this will need to be reconciled with limited tolerance of the combination and data from larger studies of anti-IGF-1R monoclonal antibodies in NET that have been disappointing. PMID:25900182

  19. Potential clinical relevance of uPA and PAI-1 levels in node-negative, postmenopausal breast cancer patients bearing histological grade II tumors with ER/PR expression, during an early follow-up.

    PubMed

    Buta, Marko; Džodić, Radan; Đurišić, Igor; Marković, Ivan; Vujasinović, Tijana; Markićević, Milan; Nikolić-Vukosavljević, Dragica

    2015-09-01

    We evaluated urokinase-type plasminogen activator (uPA) and plasminogen activator inhibitor-1 (PAI-1) prognostic value in postmenopausal, node-negative breast cancer patients bearing tumors with estrogen receptor (ER)/progesterone receptor (PR) expression, treated with locoregional therapy alone, within an early follow-up. We focused our analysis on tumors of histological grade II in order to improve its prognostic value and, consequently, to improve a decision-making process. The cytosol extracts of 73 tumor samples were used for assessing several biomarkers. ER and PR levels were measured by classical biochemical method. Cathepsin D was assayed by a radiometric immunoassay while both uPA and PAI-1 level determinations were performed by enzyme-linked immunosorbent assays. HER-2 gene amplification was determined by chromogenic in situ hybridization (CISH) in primary tumor tissue. Patients bearing tumors smaller than or equal to 2 cm (pT1) or those with low PAI-1 levels (PAI-1 < 6.35 pg/mg) showed favorable outcome compared to patients bearing tumors greater than 2 cm (pT2,3) or those with high PAI-1 levels, respectively. Analyses of 4 phenotypes, defined by tumor size and PAI-1 status, revealed that patients bearing either pT1 tumors, irrespective of PAI-1 levels, or pT2,3 tumors with low PAI-1 levels, had similar disease-free interval probabilities and showed favorable outcome compared to those bearing pT2,3 tumors with high PAI-1 levels. Our findings suggest that tumor size and PAI-1, used in combination as phenotypes are not only prognostic but might also be predictive in node-negative, postmenopausal breast cancer patients bearing histological grade II tumors with ER/PR expression, during an early follow-up period. PMID:25994573

  20. Relation of surgery, tumor site, and age group to the loss of reality testing in Japanese patients with malignant tumors: a study of a hospital-based sample with a consultation-liaison service.

    PubMed

    Yoshimasu, Kouichi; Tanaka, Kazuhiro; Kiyohara, Chikako

    2005-06-01

    The relation between surgery and the loss of reality testing (LRT) in Japanese patients with malignant tumors were examined, taking into account the influence of the tumor sites and age groups. The patients were comprised of 277 men and 225 women with malignant tumors in Kyushu University Hospital, Fukuoka, Japan, who underwent a check-up at the Department of Neuropsychiatry for the first time using the consultation-liaison system. Those with known schizophrenia, dementia, mental retardation, and paranoid or schizoid (schizotypal) personality disorder were excluded. Surgery was statistically significantly associated with LRT in elderly men (> or =65 years of age), and in men with malignant tumors of the digestive organs (odds ratio [OR], 9.7; 95% confidence interval [95% CI], 3.2-29.3). Even after adjusting for tumor site and age, surgery was statistically significantly associated with LRT in men (OR, 2.6; 95% CI, 1.4-4.6) and nearly significantly associated in women (OR, 1.8; 95% CI, 0.9-3.6). There were no material associations between surgery and LRT in patients with malignant tumors of sex-specific organs or the head and neck area. The present study showed a positive relationship between surgery and LRT in Japanese men and women with malignant tumors. The association was stronger in elderly patients. As for tumor site, surgery was most strongly associated with an increased risk of LRT in patients with malignant tumors of the digestive organs. PMID:15896218

  1. The Project MACULA Retinal Pigment Epithelium Grading System for Histology and Optical Coherence Tomography in Age-Related Macular Degeneration

    PubMed Central

    Zanzottera, Emma C.; Messinger, Jeffrey D.; Ach, Thomas; Smith, R. Theodore; Freund, K. Bailey; Curcio, Christine A.

    2015-01-01

    Purpose. To seek pathways of retinal pigment epithelium (RPE) fate in age-related macular degeneration via a morphology grading system; provide nomenclature, visualization targets, and metrics for clinical imaging and model systems. Methods. Donor eyes with geographic atrophy (GA) or choroidal neovascularization (CNV) and one GA eye with previous clinical spectral-domain optical coherence tomography (SDOCT) imaging were processed for histology, photodocumented, and annotated at predefined locations. Retinal pigment epithelial cells contained spindle-shaped melanosomes, apposed a basal lamina or basal laminar deposit (BLamD), and exhibited recognizable morphologies. Thicknesses and unbiased estimates of frequencies were obtained. Results. In 13 GA eyes (449 locations), ‘Shedding,’ ‘Sloughed,’ and ‘Dissociated’ morphologies were abundant; 22.2% of atrophic locations had ‘Dissociated’ RPE. In 39 CNV eyes (1363 locations), 37.3% of locations with fibrovascular/fibrocellular scar had ‘Entombed’ RPE; ‘Sloughed,’ ‘Dissociated,’ and ‘Bilaminar’ morphologies were abundant. Of abnormal RPE, CNV and GA both had ∼35% ‘Sloughed’/‘Intraretinal,’ with more Intraretinal in CNV (9.5% vs. 1.8%). ‘Shedding’ cells associated with granule aggregations in BLamD. The RPE layer did not thin, and BLamD remained thick, with progression. Granule-containing material consistent with three morphologies correlated to SDOCT hyperreflective foci in the previously examined GA patient. Conclusions. Retinal pigment epithelium morphology indicates multiple pathways in GA and CNV. Atrophic/scarred areas have numerous cells capable of transcribing genes and generating imaging signals. Shed granule aggregates, possibly apoptotic, are visible in SDOCT, as are ‘Dissociated’ and ‘Sloughed’ cells. The significance of RPE phenotypes is addressable in longitudinal, high-resolution imaging in clinic populations. Data can motivate future molecular phenotyping

  2. Three-Dimensional Turbo-Spin-Echo Amide Proton Transfer MR Imaging at 3 Tesla and Its Application to High-Grade Human Brain Tumors

    PubMed Central

    Zhao, Xuna; Wen, Zhibo; Zhang, Ge; Huang, Fanheng; Lu, Shilong; Wang, Xianlong; Hu, Shuguang; Chen, Min; Zhou, Jinyuan

    2012-01-01

    Purpose Amide proton transfer (APT) imaging is able to extend the achievable MRI contrast to the protein level. In this study, we demonstrate the feasibility of applying a turbo spin echo (TSE)-based, three-dimensional (3D) APT sequence into routine clinical practice for patients with brain tumors. Procedures Experiments were performed on a Philips 3T MRI scanner using an eight-channel phased-array coil for reception. A fast 3D APT sequence with a TSE acquisition was proposed (saturation power, 2 μT; saturation time, 500 ms; 8 slices). The gradient echo (GRE)-based field-mapping technique or water-saturation-shift-referencing (WASSR) technique was used to acquire B0 maps to correct for B0-induced artifacts in APT images. The test was performed on a box of homogenous protein solution, four healthy volunteers, and eight patients with high-grade gliomas. Results The experimental data from a homogenous, protein-containing phantom and healthy volunteers show that the sequence produced a uniform contrast across all slices. The average MTRasym(3.5ppm) values with GRE B0-corrected 3D APT imaging and WASSR-corrected 3D APT imaging were both comparable to the values obtained using the undemanding single-slice acquisition. The average APT image intensity was consistently higher in the tumor core than in the peripheral edema and in the contralateral normal-appearing white matter (both P < 0.001). Conclusion 3D APT imaging of brain tumors can be performed in about five minutes at 3T using a routine, commercial eight-channel SENSE coil. PMID:22644987

  3. Students' perceptions of being graded as a group in the college classroom: relations among students' age, employment, and perceived group satisfaction.

    PubMed

    Barfield, Rufus L

    2002-12-01

    This investigation compared and measured for different age groups of students, hours of employment, and previous grading experiences of one student cohort in relation to their perceived overall satisfaction with being graded as a group. A cohort of 230 students from a large southern metropolitan university enrolled in sections of two undergraduate classes. Group Interaction and Decision Making and Conflict Management, participated. Analysis indicated that (a) older students (28-47 years) were more likely to be dissatisfied with a group grade experience than middle (23-27 years) and younger (18-22 years) students. (b) Older students working part time were significantly more dissatisfied with the overall group experience than the younger part-time working students. (c) Older part-time working students were significantly more dissatisfied with the overall experience of working and being graded as a group than the middle part-time and middle full-time working students. Differences were noted between the older and younger students, which supported older students' overall dissatisfaction with their experience of being graded as a group. Common complaints by older students were that younger students were immature, irresponsible, lacked "real-life" experience, and had misplaced priorities. Common complaints by younger students were that older students were too serious and rigid. It is recommended that this work be extended to include other comparison groups, graduate students, and other disciplines. PMID:12578270

  4. Mice deficient in Rbm38, a target of the p53 family, are susceptible to accelerated aging and spontaneous tumors

    PubMed Central

    Zhang, Jin; Xu, Enshun; Ren, Cong; Yan, Wensheng; Zhang, Min; Chen, Mingyi; Cardiff, Robert D.; Imai, Denise M.; Wisner, Erik; Chen, Xinbin

    2014-01-01

    RNA-binding motif protein 38 (Rbm38), also called RNPC1 [RNA-binding region (RNP1, RRM) containing 1], is a target of the p53 family and modulates p53 expression via mRNA translation. To investigate the biological function of Rbm38 in vivo, we generated an Rbm38-null mouse model. We showed that mice deficient in Rbm38 exhibit signs of accelerated aging and are prone to hematopoietic defects and spontaneous tumors. To determine the biological significance of the p53-Rbm38 loop, we showed that Rbm38 deficiency enhances accumulation of p53 induced by ionizing radiation (IR) and sensitizes mice to IR-induced lethality in a p53-dependent manner. Most importantly, Rbm38 deficiency markedly decreases the tumor penetrance in mice heterozygous for p53 via enhanced p53 expression. Interestingly, we found that Rbm38 deficiency shortens the life span of, and promotes lymphomagenesis in, mice deficient in p53. These results provide genetic evidence that Rbm38 is necessary for normal hematopoiesis and for suppressing accelerated aging and tumorigenesis. Thus, the p53-Rbm38 axis might be explored for extending longevity and for tumor suppression. PMID:25512531

  5. Enhanced Intestinal Tumor Multiplicity and Grade in vivo after HZE Exposure: Mouse Models for Space Radiation Risk Estimates

    PubMed Central

    Trani, Daniela; Datta, Kamal; Doiron, Kathryn; Kallakury, Bhaskar; Fornace, Albert J.

    2013-01-01

    Carcinogenesis induced by space radiation is considered a major risk factor in manned interplanetary and other extended missions. The models presently used to estimate the risk for cancer induction following deep space radiation exposure are based on data from A-bomb survivor cohorts and do not account for important biological differences existing between high-linear energy transfer (LET) and low-LET-induced DNA damage. High-energy and charge (HZE) radiation, the main component of galactic cosmic rays (CGR), causes highly complex DNA damage compared to low-LET radiation, which may lead to increased frequency of chromosomal rearrangements, and contribute to carcinogenic risk in astronauts. Gastrointestinal (GI) tumors are frequent in the United States, and colorectal cancer (CRC) is the third most common cancer accounting for 10% of all cancer deaths. On the basis of the aforementioned epidemiological observations and the frequency of spontaneous precancerous GI lesions in the general population, even a modest increase in incidence by space radiation exposure could have a significant effect on health risk estimates for future manned space flights. Ground-based research is necessary to reduce the uncertainties associated with projected cancer risk estimates and to gain insights into molecular mechanisms involved in space radiation-induced carcinogenesis. We investigated in vivo differential effects of γ-rays and HZE ions on intestinal tumorigenesis using two different murine models, ApcMin/+ and Apc1638 N/+. We showed that γ- and/or HZE exposure significantly enhances development and progression of intestinal tumors in a mutant-line-specific manner, and identified suitable models for in vivo studies of space radiation–induced intestinal tumorigenesis. PMID:20490531

  6. Clinical and cytopathological aspects in phyllodes tumors of the breast.

    PubMed

    Pătraşcu, Anca; Popescu, Carmen Florina; Pleşea, I E; Bădulescu, Adriana; Tănase, Florentina; Mateescu, Garofiţa

    2009-01-01

    The frequency of mesenchymal breast tumors is very low, being represented mostly by tumors with biphasic proliferation (phyllodes tumors) and less by other types of non-epithelial tumors. From clinical point of view, phyllodes tumors (PT) can mimic a breast carcinoma. Therefore, the preoperative diagnosis by cytological examination on material obtained by fine needle aspiration (FNA) is very important for adequate treatment of these tumors. In current study, we assessed clinical aspects of 79 phyllodes tumors regarding patient's age and localization of the tumors. In 17 out of 79 cases, it has been performed FNA within the tumors with further cytological examination on the smears obtained. The median age of the patients was 46.07-year-old, being progressively higher with grade of the tumors with significant values between benign and borderline tumors (p=0.04954) and between benign and malignant ones (p=0.02890). The distinguish on the smears of stromal fragments and naked stromal nuclei with variable grade of atypia regarding the tumoral type, in detriment of epithelial elements have been conclusive for fibroepithelial lesion as cytopathological diagnosis. The preoperative differentiation between a breast phyllodes tumor and a breast carcinoma is extremely important for avoiding of a useless radical surgery for the patient. If the fine needle aspiration was correctly performed, the accuracy of the cytodiagnosis has been 82% in current study. PMID:19942954

  7. Epilepsy and brain tumors.

    PubMed

    Englot, Dario J; Chang, Edward F; Vecht, Charles J

    2016-01-01

    Seizures are common in patients with brain tumors, and epilepsy can significantly impact patient quality of life. Therefore, a thorough understanding of rates and predictors of seizures, and the likelihood of seizure freedom after resection, is critical in the treatment of brain tumors. Among all tumor types, seizures are most common with glioneuronal tumors (70-80%), particularly in patients with frontotemporal or insular lesions. Seizures are also common in individuals with glioma, with the highest rates of epilepsy (60-75%) observed in patients with low-grade gliomas located in superficial cortical or insular regions. Approximately 20-50% of patients with meningioma and 20-35% of those with brain metastases also suffer from seizures. After tumor resection, approximately 60-90% are rendered seizure-free, with most favorable seizure outcomes seen in individuals with glioneuronal tumors. Gross total resection, earlier surgical therapy, and a lack of generalized seizures are common predictors of a favorable seizure outcome. With regard to anticonvulsant medication selection, evidence-based guidelines for the treatment of focal epilepsy should be followed, and individual patient factors should also be considered, including patient age, sex, organ dysfunction, comorbidity, or cotherapy. As concomitant chemotherapy commonly forms an essential part of glioma treatment, enzyme-inducing anticonvulsants should be avoided when possible. Seizure freedom is the ultimate goal in the treatment of brain tumor patients with epilepsy, given the adverse effects of seizures on quality of life. PMID:26948360

  8. A Randomized Trial Investigating the Efficacy and Safety of Water Soluble Micellar Paclitaxel (Paccal Vet) for Treatment of Nonresectable Grade 2 or 3 Mast Cell Tumors in Dogs

    PubMed Central

    Vail, D.M.; von Euler, H.; Rusk, A.W.; Barber, L.; Clifford, C.; Elmslie, R.; Fulton, L.; Hirschberger, J.; Klein, M.; London, C.; Martano, M.; McNiel, E.A.; Morris, J.S.; Northrup, N.; Phillips, B.; Polton, G.; Post, G.; Rosenberg, M.; Ruslander, D.; Sahora, A.; Siegel, S.; Thamm, D.; Westberg, S.; Winter, J.; Khanna, C.

    2013-01-01

    Background Effective treatments for dogs with advanced stage mast cell tumors (MCT) remain a pressing need. A micellar formulation of paclitaxel (paclitaxel [micellar]) has shown promise in early-phase studies. Hypothesis/Objectives The objective was to demonstrate greater activity for paclitaxel (micellar) compared with lomustine. The null hypothesis was μp = μL (ie, proportion of responders for the paclitaxel [micellar] and lomustine groups, respectively). Animals Two hundred and fifty-two dogs with advanced stage nonresectable grade 2 or 3 MCT. Methods Prospective multicenter randomized double-blind positive-controlled clinical trial. The primary endpoint was confirmed overall response rate (CORR) at 14 weeks. A secondary endpoint, biologic observed response rate (BORR), also was calculated. Safety was assessed by the characterization and grading of adverse events (AE). Results Overall CORR (7% versus 1%; P = .048) and BORR (23% versus 10%; P = .012) were greater for paclitaxel (micellar) compared with lomustine. Paclitaxel (micellar)-treated dogs were 6.5 times more likely to have a confirmed response and 3.1 times more likely to experience a biologic observed response. The majority of AE with paclitaxel (micellar) were transient and clinically manageable. Twenty-seven dogs (33%) receiving lomustine were discontinued because of hepatopathy compared with 3 dogs (2%) receiving paclitaxel (micellar) (P < .0001; odds ratio 26.7). Conclusions and Clinical Importance Paclitaxel (micellar)’s activity and safety profile are superior to lomustine. The addition of an active and novel taxane to the veterinary armamentarium could fill a substantial need and, as its mechanism of action and AE profile do not overlap with currently available TKI, its availability could lead to effective combination protocols. PMID:22390318

  9. Is adoptive T-cell therapy for solid tumors coming of age?

    PubMed

    Pedrazzoli, P; Comoli, P; Montagna, D; Demirer, T; Bregni, M

    2012-08-01

    Among the novel biological therapeutics that will increase our ability to cure human cancer in years to come, adoptive cellular therapy is one of the most promising approaches. Although this is a complex and challenging field, there have been major advances in basic and translational research resulting in clinical trial activity that is now beginning to confirm this promise. The results obtained with tumor-infiltrating lymphocytes therapy for melanoma, and virus-specific CTLs for EBV-associated malignancies are encouraging in terms of both ability to obtain clinical benefit and limited toxicity profile. In both settings, objective responses were obtained in at least 50% of treated patients. However, improvements to the clinical protocols, in terms of better patient selection and timing of administration, as well as cell product quality and availability, are clearly necessary to further ameliorate outcome, and logistical solutions are warranted to extend T-cell therapy beyond academic centers. In particular, there is a need to simplify cell production, in order to decrease costs and ease preparation. Promising implementations are underway, including harnessing the therapeutic potential of T cells transduced with TCRs directed against shared tumor antigens, and delineating strategies aimed at targeting immune evasion mechanisms exerted by tumor cells. PMID:21804611

  10. Teaching the Age of the City: The Gilded Age and After (1865-1914). A Guide for Seventh Grade Social Studies.

    ERIC Educational Resources Information Center

    New York State Education Dept., Albany. Bureau of Secondary Curriculum Development.

    Resource materials which lead to concept understandings of social change in New York City are presented in this seventh grade curriculum guide. By focusing on historical and social conditions, problems, and values in an objective manner, it is hoped that students learn through an inductive approach how to better deal with today's urbanization…

  11. SCC INITIATION AND GROWTH RATE STUDIES ON TITANIUM GRADE 7 AND BASE METAL, WELDED, AND AGED ALLOY 22 IN CONCENTRATED GROUNDWATER

    SciTech Connect

    J.H. Payer

    2005-08-01

    The stress corrosion crack initiation and growth rate response was evaluated on as-received, as-welded, cold worked and aged Alloy 22 (UNS N06022) and titanium Grades 7 (UNS R52400), 28 (UNS R55323) and 29 (UNS R56404) at 105-165 C in various aerated, concentrated groundwater environments. Time-to-failure experiments on actively-loaded tensile specimens at 105 C evaluated the effects of applied stress, welding, surface finish, shot peening, cold work, crevicing, and aging treatments in Alloy 22 (UNS N06022), and found these materials to be highly resistant to SCC (none observed). Long-term U-bend data at 165 C corroborated these findings. Titanium Grade 7 and stainless steels were also included in the 105 C test matrix. Long term crack growth rate data showed stable crack growth in titanium Grade 7. Recent creep tests in air confirm literature data that these alloys are quite susceptible to creep failure, even below the yield stress, and it is unclear whether cracking in SCC tests is only accelerated by the creep response, or whether creep is responsible for cracking. Alloy 22 exhibited stable growth rates under ''gentle'' cyclic loading, but was prone to crack arrest at fully static loading. No effect of Pb additions was observed.

  12. Piaget: A Handbook for Parents and Teachers of Children in the Age of Discovery--Preschool Through Third Grade.

    ERIC Educational Resources Information Center

    Felton, Victoria; Peterson, Rosemary

    This handbook, primarily for parents and teachers of preschool through third grade children, provides some insights into Piaget's theories about how children think and learn and presents ideas for using Piagetian-type activities and games in the home or classroom. (The handbook does not attempt to give a comprehensive analysis of Piaget's theory…

  13. Physical Access to Schooling in South Africa: Mapping Dropout, Repetition and Age-Grade Progression in Two Districts

    ERIC Educational Resources Information Center

    Motala, Shireen; Dieltiens, Veerle; Sayed, Yusuf

    2009-01-01

    The Education for All and Millennium Development Goals commit national governments, international agencies and civil society to ensure that all children are provided with basic education. In South Africa this would mean full attendance in Grades (1-9). The achievement of universal primary education and gender equity across low-income countries are…

  14. Expression of long noncoding RNA lncRNA-n336928 is correlated with tumor stage and grade and overall survival in bladder cancer.

    PubMed

    Chen, Tao; Xie, Wanqin; Xie, Linguo; Sun, Yan; Zhang, Yu; Shen, Zhonghua; Sha, Nan; Xu, Hao; Wu, Zhouliang; Hu, Hailong; Wu, Changli

    2015-12-25

    Long noncoding RNAs (lncRNAs) have been implicated playing important roles in human urologic cancers. In the present study, microarray analysis was initially performed to screen the differentially expressed lncRNAs between bladder cancer tissues and paired adjacent non-cancerous tissues (n = 3). Subsequent qRT-PCR validation was conducted using tissue samples from 95 patients with bladder cancer. Results showed that the expression level of lncRNA-n336928 (noncode database ID: n336928) was significantly higher in bladder cancer tissues compared to that in adjacent noncancerous tissues (P < 0.001). Chi-square test showed that expression of lncRNA-n336928 was positively correlated with bladder tumor stage and histological grade (P < 0.001). Kaplan-Meier survival analysis revealed that patients with bladder cancer with high expression of lncRNA-n336928 had shorter overall survival time compared to the patients with low expression of lncRNA-n336928. Multivariate analysis indicated that lncRNA-n336928 was an independent prognostic factor for overall survival for bladder cancer patients. Collectively, our study shows that high expression of lncRNA-n336928 is associated with the progression of bladder cancer, and that lncRNA-n336928 might serve as a biomarker for prognosis of bladder cancer. PMID:26551459

  15. U-Pb garnet, sphene, monazite, and rutile ages: Implications for the duration of high-grade metamorphism and cooling histories, Adirondack Mts. , New York

    SciTech Connect

    Mezger, K.; Rawnsley, C.M.; Hanson, G.N. ); Bohlen, S.R. )

    1991-05-01

    Garnet ages for the Lowlands range from 1,168-1,127 Ma, those from the central and southern Highlands from 1,154-1,013 Ma. Metamorphism in the Highlands may not have occurred as a single event but rather in several discrete thermal pulses. An age of 1,153 {plus minus} 3 Ma was determined for garnets in the syn-regional metamorphic contact aureole of the Diana syenite, consistent with that of the syenite intrusion, 1 155 {plus minus} 4 Ma. Garnets just outside the contact aureole give an age of 1,168 {plus minus} 6 Ma. In the Lowlands, monazite yielded an age of 1,161 {plus minus} 1 Ma, rutiles yielded ages of 1,005 {plus minus} 2 Ma and 953 {plus minus} 4 Ma, and sphene ages range from 1,156 to 1,103 Ma. In the Highlands, monazite yielded an age of 1,033 {plus minus} 1 Ma, rutiles yielded ages of 911 {plus minus} 2 Ma and 885 {plus minus} 2 and sphenes from 1,033 Ma to 991 Ma. The rutile and monazite ages indicate that both terranes cooled at time-integrated rates of ca. 1.5C/Ma for at least 150 Ma following the last phase of high-grade metamorphism. The Lowlands cooled to ca. 400C by ca. 1,000 Ma and the Highlands by ca. 900 Ma. The mineral ages indicate that metamorphic pressures and temperatures recorded by thermobarometry correspond to conditions attained polychronically over 150 Ma or more. Mineral ages combined with temperature estimates for peak metamorphism indicate that the closure temperature for the U-Pb system is >800C in garnet, 640-730C in monazite, and 500-670C in sphene.

  16. Astrocytoma grade IV (glioblastoma multiforme) displays 3 subtypes with unique expression profiles of intermediate filament proteins.

    PubMed

    Skalli, Omar; Wilhelmsson, Ulrika; Orndahl, Charlotte; Fekete, Boglarka; Malmgren, Kristina; Rydenhag, Bertil; Pekny, Milos

    2013-10-01

    Astrocytoma grade IV (glioblastoma multiforme) is the most common and most malignant tumor of the central nervous system and is currently noncurable. Here, we have examined a population-based cohort of 47 patients with grade IV astrocytoma, who underwent tumor surgery at Sahlgrenska University Hospital in Sweden and who survived after surgery for less than 200 days (short survivors, 28 patients) and more than 500 days (long survivors, 19 patients). For each tumor, we ascertained information on patient age, sex, tumor location, oncological treatment, and survival after surgery. The analysis of the tumor volume and the extent of tumor resection (incomplete versus complete resection of the macroscopic tumor) was made retrospectively from the preoperative radiological investigations and, when available, also from postoperative radiology. We performed semiquantitative immunohistochemical evaluation of the presence of intermediate filament (nanofilament) proteins glial fibrillary acidic protein, vimentin, nestin, and synemin in tumor cells. The intermediate filament system helps cells and tissues to cope with various types of stress, and thus, it might affect the malignant potential of grade IV astrocytoma. We propose a subclassification of astrocytomas grade IV with respect to the expression of the intermediate filament proteins glial fibrillary acidic protein, vimentin, nestin, and synemin, namely, type A, B, and C. Our results suggest that the expression of the intermediate filament proteins glial fibrillary acidic protein, vimentin, nestin, and synemin is coregulated in grade IV astrocytomas. The expression patterns of the intermediate filament proteins in astrocytoma type A, B, and C might have biological and clinical significance. PMID:23791210

  17. [Grading of lung cancer].

    PubMed

    Bohle, R M; Schnabel, P A

    2016-07-01

    In comparison with other tumor entities there is no common generally accepted grading system for lung cancer with clearly defined criteria and clinical relevance. In the recent fourth edition of the World Health Organization (WHO) classification from 2015 of tumors of the lungs, pleura, thymus and heart, there is no generally applicable grading for pulmonary adenocarcinomas, squamous cell carcinomas or rarer forms of carcinoma. Since the new IASLC/ATS/ERS classification of adenocarcinomas published in 2011, 5 different subtypes with significantly different prognosis are proposed. This results in an architectural (histologic) grading, which is usually applied to resection specimens. For squamous cell carcinoma the number of different histological subtypes in the new WHO classification was reduced compared to earlier versions but without a common grading system. In recent publications nesting and budding were proposed as the main (histologic) criteria for a grading of squamous cell carcinomas. The grading of neuroendocrine tumors (NET) of the lungs in comparison with NET in other organs is presented in a separate article in this issue. Certain rare tumor types are high grade per definition: small cell, large cell and pleomorphic carcinomas, carcinosarcomas and pulmonary blastomas. In the future it is to be expected that these developments will be further refined, e. g. by adding further subtypes for adenocarcinomas and cytologic and/or nuclear criteria for adenocarcinoma and/or squamous cell carcinomas. PMID:27356985

  18. Combination genetic signature stratifies lower-grade gliomas better than histological grade

    PubMed Central

    Zhang, Zhenyu; Shi, Zhifeng; Chen, Liang; Chung, Nellie Yuk-Fei; Liu, Joseph Shu-Ming; Li, Kay Ka-Wai; Chan, Danny Tat-Ming; Poon, Wai Sang; Wang, Ying; Zhou, Liangfu; Ng, Ho-Keung

    2015-01-01

    We studied if combination genetic signature potentially stratifies lower-grade gliomas better than histology by investigating 214 lower-grade gliomas for IDH1/2 and TERTp mutations, 1p/19q codeletion and EGFR amplification as to their impact on prognostication. Prognostic association of grading was independent of other prognostic variables including age, histological type, IDH1/2, 1p/19q and TERTp status. No single marker, including IDH1/2, superseded grading in prognostication, indicating grading was still a very important tool. Prognosis was most favorable in 31.7% of patients with IDH1/2 mutation and either 1p/19q codeletion or TERTp mutation (IDHmut-OT), intermediate in 45.8% of patients with IDH1/2 mutation only (IDHmut) and 16.9% of patients without any of the alterations (IDHwt), and poorest in 5.6% of patients with wild-type IDH1/2 and either TERTp mutation or EGFR amplification (IDHwt-ET). Our results suggested not all IDH1/2 wild-type lower-grade gliomas are aggressive and additional biomarkers are required to identify glioblastoma-equivalent tumors. Multivariate analysis revealed independent prognostic values of grading and genetic signature. Grade II IDHwt-ET gliomas exhibited shorter survival than IDH1/2 mutated grade III gliomas, suggesting combination genetic signature potentially superseded grading in prognostication. In summary, biomarker-based stratification is useful in the diagnosis and prognostication of lower-grade gliomas, and should be used together with grading. PMID:26369702

  19. [Presumed benign ovarian tumors during pregnancy].

    PubMed

    Tariel, O; Huissoud, C; Rudigoz, R C; Dubernard, G

    2013-12-01

    The incidence of ovarian tumors diagnosed during pregnancy is between 0.3 and 5.4% (LE2). The most common ovarian tumors diagnosed during pregnancy are functional cysts diagnosed incidentally during the first trimester ultrasound (LE2) and spontaneous regression is often observed. Dermoid cysts and cystadenoma are the most frequent organic benign ovarian tumors diagnosed during pregnancy (LE2). The main complication of presumed benign ovarian tumor (PBOT) during pregnancy is adnexal torsion and is estimated at around 8% (LE2), especially at the end of the first trimester and during the second trimester (LE4). Tumor markers are not reliable during pregnancy to assess the risk of malignancy of ovarian tumor (LE2). Ultrasound remains the gold standard for characterizing an ovarian tumor during pregnancy (LE3), but with a lower specificity for the diagnosis of malignancy. Pelvic MRI is accurate in the diagnosis of ovarian tumors during pregnancy and brings additional information to ultrasound (LE4). Ultrasound-guided aspiration of ovarian tumors is not recommended during pregnancy (grade C). Expectation is recommended in cases of PBOT during pregnancy, which does not enlarge (grade C). Whatever the gestational age, surgery is recommended in patients with symptoms suggesting an adnexal torsion (grade C). Laparoscopy is possible during the first and second trimester of pregnancy for the management of symptomatic PBOT (LE3). The risk of miscarriage following surgery (laparoscopy and laparotomy) for ovarian tumor during pregnancy is estimated at 2.8% (LE3). The route of delivery should not be modified by the ovarian tumour, except in case of praevia cyst requiring a cesarean section, a complication or suspicion of malignancy (grade C). Surgical treatment of PBOT may be performed during a cesarean section indicated for another reason. The risk of torsion is increased during the postpartum period (LE4). PMID:24210242

  20. Differences in fluorescence profiles from breast cancer tissues due to changes in relative tryptophan content via energy transfer: tryptophan content correlates with histologic grade and tumor size but not with lymph node metastases

    NASA Astrophysics Data System (ADS)

    Sordillo, Laura A.; Sordillo, Peter P.; Budansky, Yury; Pu, Yang; Alfano, Robert R.

    2014-12-01

    The correlation between histologic grade, an increasingly important measure of prognosis for patients with breast cancer, and tryptophan levels from tissues of 15 breast carcinoma patients was investigated. Changes in the relative content of key native organic biomolecule tryptophan were seen from the fluorescence spectra of cancerous and paired normal tissues with excitation wavelengths of 280 and 300 nm. Due to a large spectral overlap and matching excitation-emission spectra, fluorescence resonance energy transfer from tryptophan-donor to reduced nicotinamide adenine dinucleotides-acceptor was noted. We used the ratios of fluorescence intensities at their spectral emission peaks, or spectral fingerprint peaks, at 340, 440, and 460 nm. Higher ratios correlated strongly with high histologic grade, while lower-grade tumors had low ratios. Large tumor size also correlated with high ratios, while the number of lymph node metastases, a major factor in staging, was not correlated with tryptophan levels. High histologic grade correlates strongly with increased content of tryptophan in breast cancer tissues and suggests that measurement of tryptophan content may be useful as a part of the evaluation of these patients.

  1. Age dependence of tumor genetics in unfavorable neuroblastoma: arrayCGH profiles of 34 consecutive cases, using a Swedish 25-year neuroblastoma cohort for validation

    PubMed Central

    2013-01-01

    Background Aggressive neuroblastoma remains a significant cause of childhood cancer death despite current intensive multimodal treatment protocols. The purpose of the present work was to characterize the genetic and clinical diversity of such tumors by high resolution arrayCGH profiling. Methods Based on a 32K BAC whole-genome tiling path array and using 50-250K Affymetrix SNP array platforms for verification, DNA copy number profiles were generated for 34 consecutive high-risk or lethal outcome neuroblastomas. In addition, age and MYCN amplification (MNA) status were retrieved for 112 unfavorable neuroblastomas of the Swedish Childhood Cancer Registry, representing a 25-year neuroblastoma cohort of Sweden, here used for validation of the findings. Statistical tests used were: Fisher’s exact test, Bayes moderated t-test, independent samples t-test, and correlation analysis. Results MNA or segmental 11q loss (11q-) was found in 28/34 tumors. With two exceptions, these aberrations were mutually exclusive. Children with MNA tumors were diagnosed at significantly younger ages than those with 11q- tumors (mean: 27.4 vs. 69.5 months; p=0.008; n=14/12), and MNA tumors had significantly fewer segmental chromosomal aberrations (mean: 5.5 vs. 12.0; p<0.001). Furthermore, in the 11q- tumor group a positive correlation was seen between the number of segmental aberrations and the age at diagnosis (Pearson Correlation 0.606; p=0.037). Among nonMNA/non11q- tumors (n=6), one tumor displayed amplicons on 11q and 12q and three others bore evidence of progression from low-risk tumors due to retrospective evidence of disease six years before diagnosis, or due to tumor profiles with high proportions of numerical chromosomal aberrations. An early age at diagnosis of MNA neuroblastomas was verified by registry data, with an average of 29.2 months for 43 cases that were not included in the present study. Conclusion MNA and segmental 11q loss define two major genetic variants of

  2. Music Handbook for Primary Grades.

    ERIC Educational Resources Information Center

    Bowman, Doris; And Others

    GRADES OR AGES: Primary grades (1, 2, and 3). SUBJECT MATTER: Music. ORGANIZATION AND PHYSICAL APPEARANCE: This guide contains a detailed outline of the basic music concepts for elementary grades with suggestions for activities which may develop understanding of the concepts. The pages of activities are color coded by grade level. There are three…

  3. Age-Related Macular Degeneration in the Aspect of Chronic Low-Grade Inflammation (Pathophysiological ParaInflammation)

    PubMed Central

    Nita, Małgorzata; Ascaso, Francisco J.; Huerva, Valentín

    2014-01-01

    The products of oxidative stress trigger chronic low-grade inflammation (pathophysiological parainflammation) process in AMD patients. In early AMD, soft drusen contain many mediators of chronic low-grade inflammation such as C-reactive protein, adducts of the carboxyethylpyrrole protein, immunoglobulins, and acute phase molecules, as well as the complement-related proteins C3a, C5a, C5, C5b-9, CFH, CD35, and CD46. The complement system, mainly alternative pathway, mediates chronic autologous pathophysiological parainflammation in dry and exudative AMD, especially in the Y402H gene polymorphism, which causes hypofunction/lack of the protective complement factor H (CFH) and facilitates chronic inflammation mediated by C-reactive protein (CRP). Microglial activation induces photoreceptor cells injury and leads to the development of dry AMD. Many autoantibodies (antibodies against alpha beta crystallin, alpha-actinin, amyloid, C1q, chondroitin, collagen I, collagen III, collagen IV, elastin, fibronectin, heparan sulfate, histone H2A, histone H2B, hyaluronic acid, laminin, proteoglycan, vimentin, vitronectin, and aldolase C and pyruvate kinase M2) and overexpression of Fcc receptors play role in immune-mediated inflammation in AMD patients and in animal model. Macrophages infiltration of retinal/choroidal interface acts as protective factor in early AMD (M2 phenotype macrophages); however it acts as proinflammatory and proangiogenic factor in advanced AMD (M1 and M2 phenotype macrophages). PMID:25214719

  4. Androgen-mediated development of irradiation-induced thyroid tumors in rats: dependence on animal age during interval of androgen replacement in castrated males

    SciTech Connect

    Hofmann, C.; Oslapas, R.; Nayyar, R.; Paloyan, E.

    1986-07-01

    When male Long-Evans rats at age 8 weeks were radiation treated (40 microCi Na131I), thyroid follicular adenomas and carcinomas were observed at age 24 months with a high incidence of 94%. Castration of males prior to irradiation significantly reduced this tumor incidence to 60%. When testosterone (T) was replaced in castrated, irradiated male rats, differentially increased incidences of thyroid tumors occurred. Immediate (age 2-6 mo) or early (age 6-12 mo) T replacement at approximate physiologic levels led to thyroid follicular tumor incidences of 100 and 82%, respectively, whereas intermediate (12-18 mo) or late (18-24 mo) T treatment led to only 70 and 73% incidences, respectively. Continuous T replacement (2-24 mo) in castrated irradiated male rats raised thyroid tumor incidence to 100%. Since elevated thyroid-stimulating hormone (TSH) is a reported requisite for development of radiation-associated thyroid tumors, the effects of T on serum TSH levels were examined. Mean serum TSH values in all irradiated animal groups were significantly elevated above age-matched nonirradiated animals at 6, 12, 18, and 24 months. Serum TSH levels were higher in continuous T-replaced irradiated castrates than in intact, irradiated males, whereas such intact male TSH levels were greater than those for irradiated castrates without T treatment. Interval T replacement in castrated male rats was associated with increased serum TSH levels during the treatment interval and with lowered TSH levels after discontinuation of T treatment, particularly in irradiated rats. However, when irradiated, castrated males received late T replacement (age 18-24 mo), there was no elevation of TSH at the end of the treatment interval. An indirect effect of T via early stimulation of TSH may be partly responsible for the high incidence of irradiation-induced thyroid tumors in rats.

  5. Wild-Type Reovirus in Combination With Sargramostim in Treating Younger Patients With High-Grade Recurrent or Refractory Brain Tumors

    ClinicalTrials.gov

    2016-08-03

    Childhood Astrocytoma; Childhood Atypical Teratoid/Rhabdoid Tumor; Diffuse Intrinsic Pontine Glioma; Glioma; Recurrent Childhood Anaplastic Oligodendroglioma; Recurrent Childhood Brain Neoplasm; Recurrent Childhood Glioblastoma; Recurrent Childhood Medulloblastoma; Recurrent Primitive Neuroectodermal Tumor; Refractory Brain Neoplasm

  6. Survival of children with brain tumors: SEER Program, 1973-1980.

    PubMed

    Duffner, P K; Cohen, M E; Myers, M H; Heise, H W

    1986-05-01

    Eight hundred eighty-seven children with brain tumors were identified by the SEER registries (1973-1980). Twenty-five percent were low-grade supratentorial astrocytomas, medulloblastomas were 23%, cerebellar astrocytomas 12%, high-grade supratentorial astrocytomas 11%, brainstem gliomas 9%, and ependymomas 8%. The worst survivals were in children less than 2 years of age, and the best were in those aged 10 to 14 years. Five-year survivals of children with cerebellar astrocytomas were 91%, low-grade supratentorial astrocytomas 71%, high-grade supratentorial astrocytomas 35%, medulloblastomas 39%, ependymomas 28%, and brainstem gliomas 18%. PMID:3703257

  7. Effect of HSV-IL12 Loaded Tumor Cell-Based Vaccination in a Mouse Model of High-Grade Neuroblastoma

    PubMed Central

    Pereboeva, Larisa; Gillespie, G. Yancey; Cloud, Gretchen A.; Langford, Catherine

    2016-01-01

    We designed multimodal tumor vaccine that consists of irradiated tumor cells infected with the oncolytic IL-12-expressing HSV-1 virus, M002. This vaccine was tested against the syngeneic neuroblastoma mouse model Neuro 2a injected into the right caudate nucleus of the immunocompetent A/J mice. Mice were vaccinated via intramuscular injection of multimodal vaccine or uninfected irradiated tumor cells at seven and 14 days after tumor establishment. While there was no survival difference between groups vaccinated with cell-based vaccine applied following tumor injection, a premunition prime/boost vaccination strategy produced a significant survival advantage in both groups and sustained immune response to an intracranial rechallenge of the same tumor. The syngeneic but unrelated H6 hepatocellular tumor cell line grew unrestricted in vaccinated mice, indicative of vaccine-mediated specific immunity to Neuro 2a tumors. Longitudinal analyses of tumor-infiltrating lymphocytes revealed a primary adaptive T cell response involving both CD4+ and CD8+ T cell subsets. Spleen cell mononuclear preparations from vaccinated mice were significantly more cytotoxic to Neuro 2a tumor cells than spleen cells from control mice as demonstrated in a four-hour in vitro cytotoxicity assay. These results strongly suggest that an irradiated whole cell tumor vaccine incorporating IL-12-expressing M002 HSV can produce a durable, specific immunization in a murine model of intracranial tumor. PMID:27610392

  8. Effect of HSV-IL12 Loaded Tumor Cell-Based Vaccination in a Mouse Model of High-Grade Neuroblastoma.

    PubMed

    Bauer, David F; Pereboeva, Larisa; Gillespie, G Yancey; Cloud, Gretchen A; Elzafarany, Osama; Langford, Catherine; Markert, James M; Jr, Lawrence S Lamb

    2016-01-01

    We designed multimodal tumor vaccine that consists of irradiated tumor cells infected with the oncolytic IL-12-expressing HSV-1 virus, M002. This vaccine was tested against the syngeneic neuroblastoma mouse model Neuro 2a injected into the right caudate nucleus of the immunocompetent A/J mice. Mice were vaccinated via intramuscular injection of multimodal vaccine or uninfected irradiated tumor cells at seven and 14 days after tumor establishment. While there was no survival difference between groups vaccinated with cell-based vaccine applied following tumor injection, a premunition prime/boost vaccination strategy produced a significant survival advantage in both groups and sustained immune response to an intracranial rechallenge of the same tumor. The syngeneic but unrelated H6 hepatocellular tumor cell line grew unrestricted in vaccinated mice, indicative of vaccine-mediated specific immunity to Neuro 2a tumors. Longitudinal analyses of tumor-infiltrating lymphocytes revealed a primary adaptive T cell response involving both CD4+ and CD8+ T cell subsets. Spleen cell mononuclear preparations from vaccinated mice were significantly more cytotoxic to Neuro 2a tumor cells than spleen cells from control mice as demonstrated in a four-hour in vitro cytotoxicity assay. These results strongly suggest that an irradiated whole cell tumor vaccine incorporating IL-12-expressing M002 HSV can produce a durable, specific immunization in a murine model of intracranial tumor. PMID:27610392

  9. Probing single-tumor cell interactions with different-age type I collagen networks by synchrotron-based Fourier transform infrared microspectroscopy.

    PubMed

    Guilbert, Marie; Eklouh-Molinier, Christophe; Wehbe, Katia; Sulé-Suso, Josep; Yang, Ying; Cinque, Gianfelice; Jeannesson, Pierre; Sockalingum, Ganesh D

    2014-01-01

    We report here on a first study using synchrotron radiation-based Fourier transform infrared microspectroscopy and imaging to investigate HT1080 human fibrosarcoma cells grown onto different-aged type I collagen networks. Spectral images were analyzed with k-means and fuzzy C-means (FCM) clustering algorithms. K-means delineated tumor cells from their surrounding collagen networks and the latter as a function of age mainly due to specific changes in the sugar absorption region. The FCM analysis gave a better nuance of the spectral images. A progression of the biochemical information was observed upon going from the cellular compartments to the pericellular contact regions and to the intact collagens of the different age groups. Two spectral markers based on sugar and protein bands via the intensity ratio (I1032/I1655) and band area ratio (Asugar/Aamide II), showed an increase in advanced glycation endproducts (AGEs) with age. A clear-separation of the three age groups was obtained for spectra originating from the peripheral contact areas mainly due to changes in protein band intensities. The above-described markers decreased to constant levels for the three conditions indicating a masking of the biochemical information. These results hold promises to better understand the impact of age on tumor progression processes while highlighting new markers of the tumor cell invasion front. PMID:25193972

  10. Most Patients with Colorectal Tumors at Young Age Do Not Visit a Cancer Genetics Clinic

    PubMed Central

    Overbeek, Lucia I. H.; Hoogerbrugge, Nicoline; van Krieken, Joannes H. J. M.; Nagengast, Fokko M.; Ruers, Theo J. M.; Ligtenberg, Marjolijn J. L.

    2008-01-01

    Purpose This study examined the referral process for genetic counseling at a cancer genetics clinic in patients with colorectal cancer and to search for determinants of variation in this referral process. Methods Patients who were recently diagnosed with colorectal cancer at a young age or multiple cancers associated with Lynch syndrome, hereditary nonpolyposis colorectal cancer, (N = 119) were selected from PALGA, the nationwide network and registry of histopathology and cytopathology in the Netherlands. In a retrospective analysis, we examined whether these patients visited a cancer genetics clinic and identified determinants for referral to such a clinic. Factors of patients, professional practice, and hospital setting were explored with logistic regression modeling. Results Thirty-six (30 percent) patients visited a cancer genetics clinic. Seventy percent of patients whom the surgeon referred to a cancer genetics clinic decided to visit such a clinic. Analysis of determinants showed that patients with whom the surgeon discussed referral and that were treated in a teaching hospital were more likely to visit a cancer genetics clinic. Conclusion The referral process is not optimally carried out. To deliver optimal care for patients suspected of hereditary colorectal cancer, this process must be improved with interventions focusing on patient referral by surgeons and raising awareness in nonteaching hospitals. PMID:18536968

  11. Sox4 Links Tumor Suppression to Accelerated Aging in Mice by Modulating Stem Cell Activation

    PubMed Central

    Foronda, Miguel; Martínez, Paula; Schoeftner, Stefan; Gómez-López, Gonzalo; Schneider, Ralph; Flores, Juana M.; Pisano, David G.; Blasco, Maria A.

    2016-01-01

    Summary Sox4 expression is restricted in mammals to embryonic structures and some adult tissues, such as lymphoid organs, pancreas, intestine, and skin. During embryogenesis, Sox4 regulates mesenchymal and neural progenitor survival, as well as lymphocyte and myeloid differentiation, and contributes to pancreas, bone, and heart development. Aberrant Sox4 expression is linked to malignant transformation and metastasis in several types of cancer. To understand the role of Sox4 in the adult organism, we first generated mice with reduced whole-body Sox4 expression. These mice display accelerated aging and reduced cancer incidence. To specifically address a role for Sox4 in adult stem cells, we conditionally deleted Sox4 (Sox4cKO) in stratified epithelia. Sox4cKO mice show increased skin stem cell quiescence and resistance to chemical carcinogenesis concomitantly with downregulation of cell cycle, DNA repair, and activated hair follicle stem cell pathways. Altogether, these findings highlight the importance of Sox4 in regulating adult tissue homeostasis and cancer. PMID:25043184

  12. Comparing the DN4 tool with the IASP grading system for chronic neuropathic pain screening after breast tumor resection with and without paravertebral blocks: a prospective 6-month validation study.

    PubMed

    Abdallah, Faraj W; Morgan, Pamela J; Cil, Tulin; Escallon, Jaime M; Semple, John L; Chan, Vincent W

    2015-04-01

    Investigating protective strategies against chronic neuropathic pain (CNP) after breast cancer surgery entails using valid screening tools. The DN4 (Douleur Neuropathique en 4 questions) is 1 tool that offers important research advantages. This prospective 6-month follow-up study seeks to validate the DN4 and assess its responsiveness in screening for CNP that satisfies the International Association for the Study of Pain (IASP) definition and fulfills its grading system criteria after breast tumor resection with and without paravertebral blocks (PVBs). We randomized 66 females to standardized general anesthesia and sham subcutaneous injections, or PVB and total intravenous anesthesia. The 6-month CNP risk was assessed using the IASP grading system and the DN4 screening tools. We evaluated the DN4 sensitivity, specificity, and responsiveness in capturing the impact of PVB on the CNP risk relative to the IASP grading system. Data from 64 patients showed similar demographic characteristics in both groups. Twenty patients in both groups met the grading system CNP criteria; among these, 18 patients also met the DN4 CNP criteria. Furthermore, 15 patients in both groups did not meet the grading system CNP criteria; among these, 9 patients also did not meet the DN4 CNP criteria. Therefore, the sensitivity and specificity of the DN4 were estimated at 90% and 60%, respectively. Both screening tools suggested that PVB reduced the 6-month CNP risk. Our results suggest that the DN4 can reliably identify CNP at 6 months after breast tumor resection and detect the preincisional PVB effect on the risk of developing such pain. PMID:25719620

  13. Use of Near-Infrared Spectroscopy to Age-Grade and Identify Siblings of Anopheles Gambiae Complex

    Technology Transfer Automated Retrieval System (TEKTRAN)

    We used near-infrared spectroscopy (NIRS) to rapidly and non-destructively determine species and age of Anopheles gambiae ss (G3, Mali-NIH, Kisumu, ZANU, and Ifakara strains) and An. arabiensis (Dongola, KGB, and Ifakara strains). We developed NIR calibrations using mosquitoes reared and scanned at ...

  14. The Relationship between Socioeconomic Status at Age One, Opportunities to Learn and Achievement in Mathematics in Fourth Grade in Peru

    ERIC Educational Resources Information Center

    Cueto, Santiago; Guerrero, Gabriela; Leon, Juan; Zapata, Mayli; Freire, Silvana

    2014-01-01

    Using Young Lives longitudinal data from Peru, this paper explores the relationship between socioeconomic status (SES) measured at the age of one, opportunities to learn (OTL) and achievement in mathematics ten years later. Four variables of OTL were measured: hours of class per year, curriculum coverage, quality of teachers' feedback, and…

  15. Association and prognostic significance of BRCA1/2-mutation status with neoantigen load, number of tumor-infiltrating lymphocytes and expression of PD-1/PD-L1 in high grade serous ovarian cancer

    PubMed Central

    Strickland, Kyle C.; Howitt, Brooke E.; Shukla, Sachet A.; Rodig, Scott; Ritterhouse, Lauren L.; Liu, Joyce F.; Garber, Judy E.; Chowdhury, Dipanjan; Wu, Catherine J.; D'Andrea, Alan D.; Matulonis, Ursula A.; Konstantinopoulos, Panagiotis A.

    2016-01-01

    Immune checkpoint inhibitors (e.g., anti-PD-1 and anti-PD-L1 antibodies) have demonstrated remarkable efficacy against hypermutated cancers such as melanomas and lung carcinomas. One explanation for this effect is that hypermutated lesions harbor more tumor-specific neoantigens that stimulate recruitment of an increased number of tumor-infiltrating lymphocytes (TILs), which is counterbalanced by overexpression of immune checkpoints such as PD-1 or PD-L1. Given that BRCA1/2-mutated high grade serous ovarian cancers (HGSOCs) exhibit a higher mutational load and a unique mutational signature with an elevated number of larger indels up to 50 bp, we hypothesized that they may also harbor more tumor-specific neoantigens, and, therefore, exhibit increased TILs and PD-1/PD-L1 expression. Here, we report significantly higher predicted neoantigens in BRCA1/2-mutated tumors compared to tumors without alterations in homologous recombination (HR) genes (HR-proficient tumors). Tumors with higher neoantigen load were associated with improved overall survival and higher expression of immune genes associated with tumor cytotoxicity such as genes of the TCR, the IFN-gamma and the TNFR pathways. Furthermore, immunohistochemistry studies demonstrated that BRCA1/2-mutated tumors exhibited significantly increased CD3+ and CD8+ TILs, as well as elevated expression of PD-1 and PD-L1 in tumor-associated immune cells compared to HR-proficient tumors. Survival analysis showed that both BRCA1/2-mutation status and number of TILs were independently associated with outcome. Of note, two distinct groups of HGSOCs, one with very poor prognosis (HR proficient with low number of TILs) and one with very good prognosis (BRCA1/2-mutated tumors with high number of TILs) were defined. These findings support a link between BRCA1/2-mutation status, immunogenicity and survival, and suggesting that BRCA1/2-mutated HGSOCs may be more sensitive to PD-1/PD-L1 inhibitors compared to HR-proficient HGSOCs. PMID

  16. [Cartilage tumors : Pathology and radiomorphology].

    PubMed

    Uhl, M; Herget, G; Kurz, P

    2016-06-01

    Primary cartilage-forming tumors of the bone are frequent entities in the daily work of skeletal radiologists. This article describes the correlation of pathology and radiology in cartilage-forming skeletal tumors, in particular, enchondroma, osteochondroma, periosteal chondromas, chondroblastoma and various forms of chondrosarcoma. After reading, the radiologist should be able to deduce the different patterns of cartilage tumors on radiographs, CT, and MRI from the pathological aspects. Differentiation of enchondroma and chondrosarcoma is a frequent diagnostic challenge. Some imaging parameters, e. g., deep cortical scalloping (more than two thirds of the cortical thickness), cortical destruction, or a soft-tissue mass, are features of a sarcoma. Osteochondromas are bony protrusions with a continuous extension of bone marrow from the parent bone, the host cortical bone runs continuously from the osseous surface of the tumor into the shaft of the osteochondroma and the osteochondroma has a cartilage cap. Chondromyxoid fibromas are well-defined lytic and eccentric lesions of the metaphysis of the long bones, with nonspecific MRI findings. Chondroblastomas have a strong predilection for the epiphysis of long tubular bones and develop an intense perifocal bone marrow edema. Dedifferentiated chondrosarcomas are bimorphic lesions with a low-grade chondrogenic component and a high-grade noncartilaginous component. Most chondrogenic tumors have a predilection with regard to site and age at manifestation. PMID:27233920

  17. Relative Expression of Vitamin D Hydroxylases, CYP27B1 and CYP24A1, and of Cyclooxygenase-2 and Heterogeneity of Human Colorectal Cancer in Relation to Age, Gender, Tumor Location, and Malignancy: Results from Factor and Cluster Analysis.

    PubMed

    Brozek, Wolfgang; Manhardt, Teresa; Kállay, Enikö; Peterlik, Meinrad; Cross, Heide S

    2012-01-01

    Previous studies on the significance of vitamin D insufficiency and chronic inflammation in colorectal cancer development clearly indicated that maintenance of cellular homeostasis in the large intestinal epithelium requires balanced interaction of 1,25-(OH)2D3 and prostaglandin cellular signaling networks. The present study addresses the question how colorectal cancer pathogenesis depends on alterations of activities of vitamin D hydroxylases, i.e., CYP27B1-encoded 25-hydroxyvitamin D-1a-hydroxylase and CYP24A1-encoded 25-hydroxyvitamin D-24-hydroxylase, and inflammation-induced cyclooxygenase-2 (COX-2). Data from 105 cancer patients on CYP27B1, VDR, CYP24A1, and COX-2 mRNA expression in relation to tumor grade, anatomical location, gender and age were fit into a multivariate model of exploratory factor analysis. Nearly identical results were obtained by the principal factor and the maximum likelihood method, and these were confirmed by hierarchical cluster analysis: Within the eight mutually dependent variables studied four independent constellations were found that identify different features of colorectal cancer pathogenesis: (i) Escape of COX-2 activity from restraints by the CYP27B1/VDR system can initiate cancer growth anywhere in the colorectum regardless of age and gender; (ii) variations in COX-2 expression are mainly responsible for differences in cancer incidence in relation to tumor location; (iii) advancing age has a strong gender-specific influence on cancer incidence; (iv) progression from well differentiated to undifferentiated cancer is solely associated with a rise in CYP24A1 expression. PMID:24213465

  18. Encouraging Early Clinical Outcomes With Helical Tomotherapy-Based Image-Guided Intensity-Modulated Radiation Therapy for Residual, Recurrent, and/or Progressive Benign/Low-Grade Intracranial Tumors: A Comprehensive Evaluation

    SciTech Connect

    Gupta, Tejpal

    2012-02-01

    Purpose: To report early clinical outcomes of helical tomotherapy (HT)-based image-guided intensity-modulated radiation therapy (IMRT) in brain tumors of varying shape, size, and location. Materials and Methods: Patients with residual, recurrent, and/or progressive low-grade intracranial and skull-base tumors were treated on a prospective protocol of HT-based IMRT and followed clinicoradiologically. Standardized metrics were used for plan evaluation and outcome analysis. Results: Twenty-seven patients with 30 lesions were treated to a median radiotherapy dose of 54 Gy in 30 fractions. All HT plans resulted in excellent target volume coverage with steep dose-gradients. The mean (standard deviation) dose homogeneity index and conformity index was 0.07 (0.05) and 0.71 (0.08) respectively. At first response assessment, 20 of 30 lesions were stable, whereas 9 showed partial regression. One patient with a recurrent clival chordoma though neurologically stable showed imaging-defined progression, whereas another patient with stable disease on serial imaging had sustained neurologic worsening. With a median follow-up of 19 months (interquartile range, 11-26 months), the 2-year clinicoradiological progression-free survival and overall survival was 93.3% and 100% respectively. Conclusions: Careful selection of radiotherapy technique is warranted for benign/low-grade brain tumors to achieve durable local control with minimum long-term morbidity. Large or complex-shaped tumors benefit most from IMRT. Our early clinical experience of HT-based IMRT for brain tumors has been encouraging.

  19. Immunohistochemical expression of p53 and its clinicopathological correlation with modified Anneroth's histological grading system

    PubMed Central

    Dave, Kajal V; Chalishazar, Monali; Dave, Vishal R; Panja, Pritam; Singh, Manisha; Modi, Tapan G

    2016-01-01

    Introduction and Objectives: Oral squamous cell carcinoma (OSCC) is an epithelial neoplasm generally beginning as focal overgrowth of altered stem cells near the basement membrane, moving upward and laterally, replacing the normal epithelium. Histopathological grading has been used for many decades in an attempt to predict the clinical behavior of oral squamous cell carcinoma. In the present study, Forty biopsies were studied for histological grading and p53 expression. The p53 expression was studied in relation to clinical parameters such as age, sex of patient and site of tumors. Relation between histological grade of malignancy and p53 protein expression was analysed. All cases were classified according to Anneroth's histological malignancy grading system (1987). Materials and Methods: 40 cases of OSCC were assessed for clinical parameters, Anneroth's histological grading and immunohistochemically stained with p53 protien. Statistical Analysis: The results obtained were analyzed using Spearman's Co-relation. Observations and Results: The positive expression of p53 was found in 62% of carcinomas studied. Positivity of p53 showed correlation with histological grade of malignancy and with individual parameters like degree of keratinization, nuclear polymorphism, number of mitoses and lymphoplasmacytic infiltration while showed a negative correlation with pattern of invasion. Conclusion: Our study showed a significant correlation between parameters of tumor cell population, lymphoplasmacytic infiltration and p53 expression. A significant association between high grade of malignancy and p53 overexpression and insignificant correlation of p53 with age, sex of the patient and site of the tumor was found. PMID:27194859

  20. P04.18PROGNOSIS IMPACT OF THE REGIONAL DISTRIBUTION OF MGMT GENE METHYLATION ACCORDING TO THE CPGISLAND METHYLATOR PHENOTYPE AND AGE IN HIGH-GRADE GLIOMAS

    PubMed Central

    Mur, P.; de Lope, A. Rodriguez; Hernandez-Iglesias, T.; Diaz, F.; Ribalta, T.; Fiaño, C.; Garcia, J.F.; Rey, J.A.; Mollejo, M.; Meléndez, B.

    2014-01-01

    Clinical and molecular prognostic factors in gliomas include age, IDH mutation, the glioma CpG island methylator phenotype (G-CIMP) and promoter methylation of the O6-methylguanine DNA-methyltransferase (MGMT) gene, among others. Clinical trials supported the predictive value of MGMT promoter methylation for benefit from alkylating chemotherapy in elderly GBM patients. In this study, methylation data were obtained from 46 oligodendroglial samples with the Illumina 450K platform, and were analyzed with external data to reach a total 247 glioma samples. MGMT gene methylation analysis with this platform revealed two significant survival-associated CpG regions, one within the promoter (cg12981137) and the other within the gene body (cg07933035), both significantly associated with better overall survival (OS) and strongly correlated with the G-CIMP+ status. However, although around 50% of G-CIMP- tumors were MGMT methylated on these CpG sites, their prognostic relevance were not observed in these patients. Only the gene body methylation was prognostic, but in the context of age, showing significant differences of OS in elderly patients. The absence of the MGMT promoter prognostic value in G-CIMP- tumors was validated in an independent series of 59 chemoradiated GBM patients by MSP and qMSP assays. Our study suggests that the prognostic value of MGMT methylation should be reviewed in the context of specific G-CIMP profiles and age groups. Further analysis on the impact of MGMT methylation on gene and protein expression is necessary for better clinical treatment settings. The routine use of MGMT methylation for the individual treatment of patients should be still viewed with caution.

  1. Comorbid Development of Disruptive Behaviors from age 1½ to 5 Years in a Population Birth-Cohort and Association with School Adjustment in First Grade.

    PubMed

    Carbonneau, Rene; Boivin, Michel; Brendgen, Mara; Nagin, Daniel; Tremblay, Richard E

    2016-05-01

    Comorbidity is frequent among disruptive behaviors (DB) and leads to mental health problems during adolescence and adulthood. However, the early developmental origins of this comorbidity have so far received little attention. This study investigated the developmental comorbidity of three DB categories during early childhood: hyperactivity-impulsivity, non-compliance, and physical aggression. Joint developmental trajectories of DB were identified based on annual mother interviews from age 1½ to 5 years, in a population-representative birth-cohort (N = 2045). A significant proportion of children (13 % to 21 %, depending on the type of DB) consistently displayed high levels of hyperactivity-impulsivity, non-compliance, or physical aggression from age 1½ to 5 years. Developmental comorbidity was frequent, especially for boys: 10 % of boys and 3.7 % of girls were on a stable trajectory with high levels of symptoms for the three categories of DB. Significant associations were observed between preschool joint-trajectories of DB and indicators of DB and school adjustment assessed by teachers in first grade. Preschoolers who maintained high levels of hyperactivity-impulsivity, non-compliance, and physical aggression, displayed the highest number of DB symptoms in first grade for all categories according to their teacher. They were also among the most disadvantaged of their class for school adjustment indicators. Thus, DB manifestations and developmental comorbidity of DB are highly prevalent in infancy. Early childhood appears to be a critical period to prevent persistent and comorbid DB that leads to impairment at the very beginning of school attendance and to long-term serious health and social adjustment problems. PMID:26311619

  2. Prevalence of Head and Neck Tumors in Children under 12 Years of Age Referred to the Pathology Department of Children’s Hospital in Tabriz during a 10-year Period

    PubMed Central

    Fattahi, Shirin; Vosoughhosseini, Sepideh; Moradzadeh Khiavi, Monir; Mahmoudi, Seyed Mostafa; Emamverdizadeh, Parya; Noorazar, Seyed Gholamreza; Yasamineh, Neda; Lotfi, Rana

    2015-01-01

    Background and aims. Head and neck tumors are the most common complaints of people referring to different medical sections, especially in children. The aim of this study was to evaluate the prevalence of these tumors in children less than 12 years of age to provide a better perspective for future studies. Materials and methods. All the files in Department of Pathology at Tabriz Pediatric Hospital from 2001 to 2011 were screened for head and neck tumors in children under 12 years of age. Data including age and gender as well as the type, the location, and benign/malignant characteristic of the tumor were recorded. Data were analyzed by SPSS 15 statistical software, using descriptive statistics and chi-square test. Results. A total of 160 cases were identified. Most of the tumors were benign (68%) and most of the tumors occurred in the neck region (41%). The most frequent benign and malignant tumors were lymphangioma and non-Hodgkin lymphoma, respectively. The majority of benign tumors were found in children younger than 2 years old (P=0.007), but there was no age predilection for malignant tumors. Conclusion. According to our results, benign tumors were more prevalent than malignant ones. Although a low rate of benign tumors in males shows that more attention should be paid to the early diagnosis of head and neck tumors. PMID:26236435

  3. Brain tumors in infants

    PubMed Central

    Ghodsi, Seyyed Mohammad; Habibi, Zohreh; Hanaei, Sara; Moradi, Ehsan; Nejat, Farideh

    2015-01-01

    Background: Brain tumors in infants have different clinical presentations, anatomical distribution, histopathological diagnosis, and clinical prognosis compared with older children. Materials and Methods: A retrospective analysis was done in patients <12 months old who were operated on for primary brain tumor in Children's Hospital Medical Center since 2008 to 2014. Results: Thirty-one infants, 20 males and 11 females, with the mean age of 7.13 months (0.5–12) were enrolled. There were 16 supratentorial and 15 infratentorial tumors. The presenting symptoms included increased head circumference (16); bulge fontanel (15); vomiting (15); developmental regression (11); sunset eye (7); seizure (4); loss of consciousness (4); irritability (3); nystagmus (2); visual loss (2); hemiparesis (2); torticollis (2); VI palsy (3); VII, IX, X nerve palsy (each 2); and ptosis (1). Gross total and subtotal resection were performed in 19 and 11 cases, respectively. Fourteen patients needed external ventricular drainage in the perioperative period, from whom four infants required a ventriculoperitoneal shunt. One patient underwent ventriculoperitoneal shunting without tumor resection. The most common histological diagnoses were primitive neuroectodermal tumor (7), followed by anaplastic ependymoma (6) and grade II ependymoma. The rate of 30-day mortality was 19.3%. Eighteen patients are now well-controlled with or without adjuvant therapy (overall survival; 58%), from whom 13 cases are tumor free (disease free survival; 41.9%), 3 cases have residual masses with fixed or decreased size (progression-free survival; 9.6%), and 2 cases are still on chemotherapy. Conclusion: Brain tumors in infants should be treated with surgical resection, followed by chemotherapy when necessary. PMID:26962338

  4. Induction of mammary tumors in aging rats by 7,12-dimethylbenz(a)anthracene: role of DNA synthesis during carcinogenesis

    SciTech Connect

    Sinha, D.K.; Dao, T.L.

    1980-03-01

    Two routes of administration were used to test the susceptibility of the mammary gland of the rat to 7,12-dimethylbenz(a)anthracene (DMBA) carcinogenesis in relation to age of the tissue. In one series of experiments, 60-, 70-, 90-, 120-, 150-, and 200-day-old female nonbred Sprague-Dawley rats were given DMBA iv. In parallel experiments, rats of the same ages as those above were given DMBA by local application. Mammary tumors developed in 89 to 90% of the 60- and 70-day-old rats and in 40% of the 90-day-old rats. Rats 120 days old and older were completely refractory to DMBA. In contrast, all rats, irrespective of their ages, developed tumors when DMBA was applied locally. DMBA given iv significantly inhibited DNA synthesis in mammary glands, but DMBA applied locally significantly increased the Li of the mammary glands.

  5. Hypothalamic tumor

    MedlinePlus

    ... occur at any age. They are often more aggressive in adults than in children. In adults, tumors ... The treatment depends on how aggressive the tumor is, and whether it is a glioma or another type of cancer. Treatment may involve combinations of surgery, radiation , ...

  6. Aging.

    PubMed

    Park, Dong Choon; Yeo, Seung Geun

    2013-09-01

    Aging is initiated based on genetic and environmental factors that operate from the time of birth of organisms. Aging induces physiological phenomena such as reduction of cell counts, deterioration of tissue proteins, tissue atrophy, a decrease of the metabolic rate, reduction of body fluids, and calcium metabolism abnormalities, with final progression onto pathological aging. Despite the efforts from many researchers, the progression and the mechanisms of aging are not clearly understood yet. Therefore, the authors would like to introduce several theories which have gained attentions among the published theories up to date; genetic program theory, wear-and-tear theory, telomere theory, endocrine theory, DNA damage hypothesis, error catastrophe theory, the rate of living theory, mitochondrial theory, and free radical theory. Although there have been many studies that have tried to prevent aging and prolong life, here we introduce a couple of theories which have been proven more or less; food, exercise, and diet restriction. PMID:24653904

  7. Aging

    PubMed Central

    Park, Dong Choon

    2013-01-01

    Aging is initiated based on genetic and environmental factors that operate from the time of birth of organisms. Aging induces physiological phenomena such as reduction of cell counts, deterioration of tissue proteins, tissue atrophy, a decrease of the metabolic rate, reduction of body fluids, and calcium metabolism abnormalities, with final progression onto pathological aging. Despite the efforts from many researchers, the progression and the mechanisms of aging are not clearly understood yet. Therefore, the authors would like to introduce several theories which have gained attentions among the published theories up to date; genetic program theory, wear-and-tear theory, telomere theory, endocrine theory, DNA damage hypothesis, error catastrophe theory, the rate of living theory, mitochondrial theory, and free radical theory. Although there have been many studies that have tried to prevent aging and prolong life, here we introduce a couple of theories which have been proven more or less; food, exercise, and diet restriction. PMID:24653904

  8. Grading of Age-Related Macular Degeneration: Comparison between Color Fundus Photography, Fluorescein Angiography, and Spectral Domain Optical Coherence Tomography

    PubMed Central

    Mokwa, Nils F.; Keane, Pearse A.; Kirchhof, Bernd; Sadda, Srinivas R.

    2013-01-01

    Purpose. To compare color fundus photography (FP), fluorescein angiography (FA), and spectral domain optical coherence tomography (SDOCT) for the detection of age-related macular degeneration (AMD), choroidal neovascularisation (CNV), and CNV activity. Methods. FPs, FAs, and SDOCT volume scans from 120 eyes of 66 AMD and control patients were randomly collected. Control eyes were required to show no AMD, but other retinal pathology was allowed. The presence of drusen, pigmentary changes, CNV, and signs for CNV activity was independently analyzed for all imaging modalities. Results. AMD was diagnosed based on FP in 75 eyes. SDOCT and FA showed sensitivity (specificity) of 89% (76%) and 92% (82%), respectively. CNV was present on FA in 68 eyes. Sensitivity (specificity) was 78% (100%) for FP and 94% (98%) for SDOCT. CNV activity was detected by SDOCT or FA in 60 eyes with an agreement in 46 eyes. Sensitivity was 88% for SDOCT and 88% for FA. FP showed sensitivity of 38% and specificity of 98%. Conclusions. CNV lesions and activity may be missed by FP alone, but FP may help identifying drusen and pigmentary changes. SDOCT is highly sensitive for the detection of AMD, CNV, and CNV activity; however, it cannot fully replace FA. PMID:23762528

  9. Effect of aging on impact properties of ASTM A890 Grade 1C super duplex stainless steel

    SciTech Connect

    Martins, Marcelo Forti, Leonardo Rodrigues Nogueira

    2008-02-15

    Super duplex stainless steels in the solution annealed condition are thermodynamically metastable systems which, when exposed to heat, present a strong tendency to 'seek' the most favorable thermodynamic condition. The main purpose of this study was to characterize the microstructure of a super duplex stainless steel in the as cast and solution annealed conditions, and to determine the influence of aging heat treatments on its impact strength, based on Charpy impact tests applied to V-notched test specimens. The sigma phase was found to begin precipitating at heat treatment temperatures above 760 deg. C and to dissolve completely only above 1040 deg. C, with the highest peak concentration of this phase appearing at close to 850 deg. C. Heat treatments conducted at temperatures of 580 deg. C to 740 deg. C led to a reduction of the energy absorbed in the Charpy impact test in response to the precipitation of a particulate phase with particle sizes ranging from 0.5 {mu}m to 1.0 {mu}m, with a chromium and iron-rich chemical composition.

  10. Zircon U-Pb ages, Hf isotope data, and tectonic implications of Early-Middle Triassic granitoids in the Ailaoshan high-grade metamorphic belt of Southeast Tibet

    NASA Astrophysics Data System (ADS)

    Wu, Wenbin; Liu, Junlai; Chen, Xiaoyu; Zhang, Lisheng

    2016-05-01

    The Ailaoshan tectonic belt, where the effects of the Paleo-Tethyan ocean evolution and Indian-Eurasian plate collision are superimposed, is one of the most significant geological discontinuities in western Yunnan province of southeast Tibet. An Ailaoshan micro-block within the belt is bounded by the Ailaoshan suture zone to the west and the Red River Fault to the east, and consists of low- and high-grade metamorphic belts. Late Permian-Middle Triassic granitoids that are widely distributed to the west of the Ailaoshan suture zone and within the Ailaoshan micro-block may yield significant information on the Tethyan tectonic evolution of the Ailaoshan tectonic belt. This study reports new LA-ICP-MS zircon U-Pb geochronology and Hf isotope data of four granitoids from the Ailaoshan high-grade metamorphic belt. Zircon grains from the Yinjie granitoid do not have inherited cores and yield a weighted mean U-Pb age of 247.1 ± 2.0 Ma. The zircon ɛ Hf(t) values range from 7.8 to 12.1, and Hf model ages from 775 to 546 Ma, indicating that the granitoid was derived from juvenile crust. The rims of zircons from the Majie and Yuanjiang granitoids yield weighted mean U-Pb ages of 239.5 ± 1.8 and 237.9 ± 2.6 Ma, respectively, whereas the cores yield ages of 1608-352 Ma. The ɛ Hf(t) values of zircon rims range from -20.4 to -5.3, yielding Hf model ages from 2557 to 1606 Ma and suggesting that the source magma of the Majie and Yuanjiang granitoids was derived from ancient crust. An additional granitoid located near the Majie Village yields a zircon U-Pb age of 241.2 ± 1.0 Ma. Based on our geochronological and geochemical data, combined with geological observations, we propose that the Ailaoshan micro-block was derived from the western margin of the Yangtze block, and is comparable to the Zhongzan and Nam Co micro-blocks. The presence of late Permian mafic rocks with rift-related geochemical characteristics within the Ailaoshan micro-block, together with granitoids derived

  11. Isolated third nerve palsy: A rare presentation of high grade glioma.

    PubMed

    Singh, Deepak Kumar; Singh, Neha; Singh, Ragini

    2016-01-01

    High grade gliomas account for almost one-third of primary central nervous system neoplasm, mainly in adults with a mean age of 41 years. They usually present with symptoms of raised intracranial pressure such as headache, vomiting, and seizures. We report a case of 55-year-old male presenting with right side complete third nerve palsy. Magnetic resonance imaging revealed an intraaxial tumor of the right medial temporal lobe. The tumor was removed grossly, and the histological diagnosis was anaplastic astrocytoma (WHO grade 3). We discuss clinical presentation of this case along with pertinent literature. PMID:27057228

  12. Isolated third nerve palsy: A rare presentation of high grade glioma

    PubMed Central

    Singh, Deepak Kumar; Singh, Neha; Singh, Ragini

    2016-01-01

    High grade gliomas account for almost one-third of primary central nervous system neoplasm, mainly in adults with a mean age of 41 years. They usually present with symptoms of raised intracranial pressure such as headache, vomiting, and seizures. We report a case of 55-year-old male presenting with right side complete third nerve palsy. Magnetic resonance imaging revealed an intraaxial tumor of the right medial temporal lobe. The tumor was removed grossly, and the histological diagnosis was anaplastic astrocytoma (WHO grade 3). We discuss clinical presentation of this case along with pertinent literature. PMID:27057228

  13. Imprint cytology of high-grade immature ovarian teratoma: a case report, literature review, and distinction from other ovarian small round cell tumors.

    PubMed

    Ramalingam, Preetha; Teague, Daniel; Reid-Nicholson, Michelle

    2008-08-01

    Immature ovarian teratoma (IOT) is a rare and aggressive malignant neoplasm characterized by immature neural tissue. The cytomorphologic features have only rarely been described. We herein describe an additional case and review the literature regarding this entity. To the best of our knowledge, this is the first reported case with imprint cytology. A 35-year-old woman presented with a pelvic mass which was resected and sent for frozen section evaluation. Imprint smears and frozen section of the mass were diagnostic of IOT. IOT has diagnostic cytologic features which show complete concordance with histology. Differential diagnoses include other small round cell neoplasms such as ovarian neuroblastoma, small cell carcinoma of hypercalcemic type, primitive neuroectodermal tumor, Wilm's tumor, desmoplastic small round cell tumor, and Non-Hodgkin lymphoma. Distinguishing IOT from these tumors can be challenging however if diligent morphologic study and/or ancillary studies are performed accurate diagnosis is possible. PMID:18618728

  14. Spontaneous brain tumor imaging of aged rat by crystal X-ray interferometer-based phase-contrast X-ray CT

    PubMed Central

    Yoneyama, Akio; Hara, Atsuko; Ohbu, Makoto; Maruyama, Hiroko; Taguchi, Masaya; Esashi, Shogo; Matsushima, Tsubasa; Terazaki, Kei; Hyodo, Kazuyuki; Takeda, Tohoru

    2016-01-01

    Background Crystal X-ray interferometer-based phase-contrast X-ray computed tomography (C-PCCT) enables the depiction of internal structures of biological tissue without contrast agents. Purpose To determine the advantage of this technique in visualizing detailed morphological structures of a rare spontaneous brain tumor in an aged rat. Material and Methods An aged rat’s spontaneous brain tumor was imaged by C-PCCT without contrast agent. Three-dimensional (3D) images of the tumor microvasculature were reconstructed and compared with pathological pictures. Results C-PCCT depicted the tumor’s various pathological features clearly, e.g. its cell density and vasculature, and blood clots caused by hemorrhaging and/or hematomas. The obtained images resembled pathological pictures with a magnification of ×20 and were used to reconstruct 3D images of the tumor vascularity up to approximately 26 µm in diameter. Conclusion Since C-PCCT is able to depict various pathological conditions, it might be useful for cancer research. PMID:26962462

  15. Screening Outcomes in Older US Women Undergoing Multiple Mammograms in Community Practice: Does Interval, Age, or Comorbidity Score Affect Tumor Characteristics or False Positive Rates?

    PubMed Central

    2013-01-01

    Background Uncertainty exists about the appropriate use of screening mammography among older women because comorbid illnesses may diminish the benefit of screening. We examined the risk of adverse tumor characteristics and false positive rates according to screening interval, age, and comorbidity. Methods From January 1999 to December 2006, data were collected prospectively on 2993 older women with breast cancer and 137 949 older women without breast cancer who underwent mammography at facilities that participated in a data linkage between the Breast Cancer Surveillance Consortium and Medicare claims. Women were aged 66 to 89 years at study entry to allow for measurement of 1 year of preexisting illnesses. We used logistic regression analyses to calculate the odds of advanced (IIb, III, IV) stage, large (>20 millimeters) tumors, and 10-year cumulative probability of false-positive mammography by screening frequency (1 vs 2 years), age, and comorbidity score. The comorbidity score was derived using the Klabunde approximation of the Charlson score. All statistical tests were two-sided. Results Adverse tumor characteristics did not differ statistically significantly by comorbidity, age, or interval. Cumulative probability of a false-positive mammography result was higher among annual screeners than biennial screeners irrespective of comorbidity: 48.0% (95% confidence interval [CI] = 46.1% to 49.9%) of annual screeners aged 66 to 74 years had a false-positive result compared with 29.0% (95% CI = 28.1% to 29.9%) of biennial screeners. Conclusion Women aged 66 to 89 years who undergo biennial screening mammography have similar risk of advanced-stage disease and lower cumulative risk of a false-positive recommendation than annual screeners, regardless of comorbidity. PMID:23385442

  16. Breast cancer survival disparity between African American and Caucasian women in Arkansas: A race-by-grade analysis

    PubMed Central

    Monzavi-Karbassi, Behjatolah; Siegel, Eric R.; Medarametla, Srikanth; Makhoul, Issam; Kieber-Emmons, Thomas

    2016-01-01

    Despite progress in breast cancer treatment, disparity persists in survival time between African American (AA) and Caucasian women in the US. Tumor stage and tumor grade are the major prognostic factors that define tumor aggressiveness and contribute to racial disparity between AA and Caucasian women. Studying the interaction of race with tumor grade or stage may provide further insights into the role of intrinsic biological aggressiveness in disecting the AA-Caucasian survival disparity. Therefore, the current study was performed to evaluate the interaction of race with tumor grade and stage at diagnosis regarding survival in a cohort of patients treated at the Winthrop P. Rockefeller Cancer Institute of the University of Arkansas for Medical Sciences (Little Rock, AR, USA). The cohort included 1,077 patients, 208 (19.3%) AA and 869 (80.7%) Caucasian, diagnosed with breast cancer between January 1997 and December 2005. Kaplan-Meier survival plots were generated and Cox regressions were performed to analyze the associations of race with breast cancer-specific survival time. Over a mean follow-up time of 1.5 years, AA women displayed increased mortality risk due to breast cancer-specific causes [hazard ratio (HR), 1.74; 95% confidence interval (CI), 1.23–2.46]. The magnitude of racial disparity varied strongly with tumor grade (race-x-grade interaction; P<0.001). No significant interaction was observed between race and tumor stage or race and age at diagnosis. Among women diagnosed with grade I tumors, the race disparity in survival time after controlling for tumor stage and age was strong (HR, 9.07; 95% CI, 2.11–38.95), but no significant AA-Caucasian disparity was observed among women with higher-grade tumors. The data suggest that, when diagnosed with grade I breast cancer, AA may experience poorer survival outcomes compared with Caucasian patients, regardless of tumor stage or age. The findings potentially provide significant clinical and public health

  17. Local cerebral blood flow and partition coefficients measured in cerebral astrocytomas of different grades of malignancy

    SciTech Connect

    Tachibana, H.; Meyer, J.S.; Rose, J.E.; Kandula, P.

    1984-02-01

    Local cerebral blood flow and local partition coefficients were measured in patients with different grades of malignant cerebral astrocytomas (n . 5) who inhaled 35% stable xenon during computed tomography scanning. Results were compared with those in age-matched normal subjects (n . 5. Mean values for local cerebral blood flow in the gray matter in patients with astrocytomas were decreased throughout the tumor mass and surrounding brain that was apparently free of tumor. Patients with highly malignant glioblastoma multiforme (astrocytoma grade IV; n . 2) showed more variable values for local cerebral blood flow and local partition coefficients compared to those with astrocytomas of lower grades (grades I-II; n . 3). Local partition coefficients in gray matter invaded by grade IV astrocytoma were significantly higher than those in gray matter invaded by grade I-III astrocytomas. Local cerebral blood flow and local partition coefficients in the brain tissue surrounding grade IV astrocytomas were reduced to a greater extent than those in more benign tumors.

  18. Phase I Study of Vorinostat in Combination with Temozolomide in Patients with High-Grade Gliomas: North American Brain Tumor Consortium Study 04-03

    PubMed Central

    Lee, Eudocia Q.; Puduvalli, Vinay K.; Reid, Joel M.; Kuhn, John G.; Lamborn, Kathleen R.; Cloughesy, Timothy F.; Chang, Susan M.; Drappatz, Jan; Yung, W. K. Alfred; Gilbert, Mark R.; Robins, H. Ian; Lieberman, Frank S.; Lassman, Andrew B.; McGovern, Renee M.; Xu, Jihong; Desideri, Serena; Ye, Xiabu; Ames, Matthew M.; Espinoza-Delgado, Igor; Prados, Michael D.; Wen, Patrick Y.

    2013-01-01

    Purpose A phase I, dose-finding study of vorinostat in combination with temozolomide (TMZ) was conducted to determine the maximum tolerated dose (MTD), safety, and pharmacokinetics in patients with high-grade glioma (HGG). Experimental Design This phase I, dose-finding, investigational study was conducted in two parts. Part 1 was a dose-escalation study of vorinostat in combination with TMZ 150 mg/m2/day × 5 days every 28 days. Part 2 was a dose-escalation study of vorinostat in combination with TMZ 150 mg/m2/day × 5 days of the first cycle and 200 mg/m2/day × 5 days of the subsequent 28-day cycles. Results In Part 1, the MTD of vorinostat administered on days 1-7 and 15-21 of every 28 day cycle in combination with TMZ was 500 mg daily. Dose-limiting toxicities (DLTs) included grade 3 anorexia, grade 3 ALT, and grade 5 hemorrhage in the setting of grade 4 thrombocytopenia. In Part 2, the MTD of vorinostat on days 1-7 and 15-21 of every 28 day cycle combined with TMZ was 400 mg daily. No DLTs were encountered, but vorinostat dosing could not be escalated further due to thrombocytopenia. The most common serious adverse events were fatigue, lymphopenia, thrombocytopenia, and thromboembolic events. There were no apparent pharmacokinetic interactions between vorinostat and TMZ. Vorinostat treatment resulted in hyperacetylation of histones H3 and H4 in peripheral mononuclear cells. Conclusion Vorinostat in combination with temozolomide is well-tolerated in patients with HGG. A phase I/II trial of vorinostat with radiotherapy and concomitant TMZ in newly diagnosed glioblastoma is underway. PMID:22923449

  19. Application of the total reflection X-ray fluorescence method to the elemental analysis of brain tumors of different types and grades of malignancy

    NASA Astrophysics Data System (ADS)

    Lankosz, M. W.; Grzelak, M.; Ostachowicz, B.; Wandzilak, A.; Szczerbowska-Boruchowska, M.; Wrobel, P.; Radwanska, E.; Adamek, D.

    2014-11-01

    The process of carcinogenesis may influence normal biochemical reactions leading to alterations in the elemental composition of the tissue. Total reflection X-ray fluorescence analysis (TXRF) was applied to the elemental analysis of different brain tumors. The following elements were present in all the neoplastic tissues analyzed: K, Ca, Fe, Cu, Zn and Rb. The results of the analysis showed that the elemental composition of a relatively small fragment of tissue represents satisfactorily the biochemical “signature” of a cancer. On the basis of the element concentrations determined, it was possible to differentiate between some types of brain tumors.

  20. The relationship between histologic grades of invasive carcinoma of breast ducts and mast cell infiltration

    PubMed Central

    Fakhrjou, Ashraf; Naghavi-Behzad, Mohammad; Montazeri, Vahid; Karkon-Shayan, Farid; Norouzi-Panahi, Leila; Piri, Reza

    2016-01-01

    Introduction: Breast carcinoma is the most prevalent tumors among women. Transformation of inflated cells in immune response leads to increase in inflammatory cells such as macrophages, mast cells (MC) and fibroblasts. The aim of this study was to determine the relationship between grades of invasive carcinoma of the breast ducts and MC infiltration around tumoral cells. Methods: During the present study, 75 female patients suffering from invasive ductal carcinoma who underwent surgery or diagnostic biopsy during 2010 and 2013 in Educational-Medical centers of Tabriz University of Medical Sciences, were included in the study. Based on Bloom-Richardson grading system, 25 cases were selected from each grade. To better observe of MCs, samples were stained by Toluidine blue and MCs were counted in 10 40 × 10 fields. Results: The mean age was 47.56 ± 10.84 and the number of MCs was between 6 and 96 and their overall average was 43.01. Average count of MCs in grade 1, 2 and 3 were 15.92 ± 10.07, 45.32 ± 10.47, and 67.8 ± 20.70, respectively. There was a significant relationship between the number of MCs and increase in disease grade (P < 0.001). With increasing grade of malignancy, the number of MCs had grown. No significant relationship was observed between age and grade of disease or age and number of MC. Conclusion: According to obtained results, number of MC around tumoral cells increased significantly with an increase in the grade of disease. In order to treat in the first stages of the disease, recognizing primary changes in the stroma of cells could be helpful. PMID:27169108

  1. BRAF mutations in cutaneous melanoma are independently associated with age, anatomic site of the primary tumor and the degree of solar elastosis at the primary tumor site

    PubMed Central

    Bauer, Jürgen; Büttner, Petra; Murali, Rajmohan; Okamoto, Ichiro; Kolaitis, Nicholas A; Landi, Maria Teresa; Scolyer, Richard A.; Bastian, Boris C.

    2011-01-01

    SUMMARY Oncogenic BRAF mutations are more frequent in cutaneous melanoma from sites with little or moderate sun-induced damage than from sites with severe cumulative solar ultraviolet (UV) damage. We studied cutaneous melanomas from geographic regions with different levels of ambient UV radiation to delineate the relative effects of cumulative UV damage, age and anatomic site on the frequency of BRAF mutations. We show that BRAF-mutated melanomas occur in a younger age group on skin without marked solar elastosis, and less frequently affect the head and neck area, compared to melanomas without BRAF mutations. The findings indicate that BRAF-mutated melanomas arise early in life at low cumulative UV doses, whereas melanomas without BRAF mutations require accumulation of high UV doses over time. The effect of anatomic site on the mutation spectrum further suggests regional differences among cutaneous melanocytes. PMID:21324100

  2. Severe Radiation Necrosis Successfully Treated With Bevacizumab in an Infant with Low-Grade Glioma and Tumor-Associated Intractable Trigeminal Neuralgia.

    PubMed

    Pillay Smiley, Natasha; Alden, Tord; Hartsell, William; Fangusaro, Jason

    2016-09-01

    We present a unique case of radiation necrosis in a child with brain stem low-grade glioma (LGG) presenting with trigeminal neuralgia. Despite extensive therapies, severe pain persisted. She received proton beam radiation with significant improvement. However, she developed radiation necrosis and hydrocephalus. Despite surgical correction of hydrocephalus, the patient remained critically ill. She was treated with dexamethasone and bevacizumab with rapid clinical improvement. Subsequent MRIs revealed almost complete resolution of the necrosis. This case illustrates the successful treatment of trigeminal neuralgia with radiation and a rare case of radiation necrosis in an LGG successfully treated with bevacizumab and dexamethasone. PMID:27187113

  3. Progression-free survival: an important end point in evaluating therapy for recurrent high-grade gliomas.

    PubMed

    Lamborn, Kathleen R; Yung, W K Alfred; Chang, Susan M; Wen, Patrick Y; Cloughesy, Timothy F; DeAngelis, Lisa M; Robins, H Ian; Lieberman, Frank S; Fine, Howard A; Fink, Karen L; Junck, Larry; Abrey, Lauren; Gilbert, Mark R; Mehta, Minesh; Kuhn, John G; Aldape, Kenneth D; Hibberts, Janelle; Peterson, Pamela M; Prados, Michael D

    2008-04-01

    The North American Brain Tumor Consortium (NABTC) uses 6-month progression-free survival (6moPFS) as the efficacy end point of therapy trials for adult patients with recurrent high-grade gliomas. In this study, we investigated whether progression status at 6 months predicts survival from that time, implying the potential for prolonged survival if progression could be delayed. We also evaluated earlier time points to determine whether the time of progression assessment alters the strength of the prediction. Data were from 596 patient enrollments (159 with grade III gliomas and 437 with grade IV tumors) in NABTC phase II protocols between February 1998 and December 2002. Outcome was assessed statistically using Kaplan-Meier curves and Cox proportional hazards models. Median survivals were 39 and 30 weeks for patients with grade III and grade IV tumors, respectively. Twenty-eight percent of patients with grade III and 16% of patients with grade IV tumors had progression-free survival of >26 weeks. Progression status at 9, 18, and 26 weeks predicted survival from those times for patients with grade III or grade IV tumors (p < 0.001 and hazard ratios < 0.5 in all cases). Including KPS, age, number of prior chemotherapies, and response in a multivariate model did not substantively change the results. Progression status at 6 months is a strong predictor of survival, and 6moPFS is a valid end point for trials of therapy for recurrent malignant glioma. Earlier assessments of progression status also predicted survival and may be incorporated in the design of future clinical trials. PMID:18356283

  4. Progression-free survival: An important end point in evaluating therapy for recurrent high-grade gliomas

    PubMed Central

    Lamborn, Kathleen R.; Alfred Yung, W. K.; Chang, Susan M.; Wen, Patrick Y.; Cloughesy, Timothy F.; DeAngelis, Lisa M.; Robins, H. Ian; Lieberman, Frank S.; Fine, Howard A.; Fink, Karen L.; Junck, Larry; Abrey, Lauren; Gilbert, Mark R.; Mehta, Minesh; Kuhn, John G.; Aldape, Kenneth D.; Hibberts, Janelle; Peterson, Pamela M.; Prados, Michael D.

    2008-01-01

    The North American Brain Tumor Consortium (NABTC) uses 6-month progression-free survival (6moPFS) as the efficacy end point of therapy trials for adult patients with recurrent high-grade gliomas. In this study, we investigated whether progression status at 6 months predicts survival from that time, implying the potential for prolonged survival if progression could be delayed. We also evaluated earlier time points to determine whether the time of progression assessment alters the strength of the prediction. Data were from 596 patient enrollments (159 with grade III gliomas and 437 with grade IV tumors) in NABTC phase II protocols between February 1998 and December 2002. Outcome was assessed statistically using Kaplan-Meier curves and Cox proportional hazards models. Median survivals were 39 and 30 weeks for patients with grade III and grade IV tumors, respectively. Twenty-eight percent of patients with grade III and 16% of patients with grade IV tumors had progression-free survival of >26 weeks. Progression status at 9, 18, and 26 weeks predicted survival from those times for patients with grade III or grade IV tumors (p < 0.001 and hazard ratios < 0.5 in all cases). Including KPS, age, number of prior chemotherapies, and response in a multivariate model did not substantively change the results. Progression status at 6 months is a strong predictor of survival, and 6moPFS is a valid end point for trials of therapy for recurrent malignant glioma. Earlier assessments of progression status also predicted survival and may be incorporated in the design of future clinical trials. PMID:18356283

  5. Oncogene activation and tumor suppressor gene inactivation find their sites of expression in the changes in time and space of the age-adjusted cancer incidence rate.

    PubMed

    Kodama, M; Kodama, T; Murakami, M

    2000-01-01

    The purpose of the present investigation is to elucidate the relation between the distribution pattern of the age-adjusted incidence rate (AAIR) changes in time and space of 15 tumors of bothe sexes and the locations of centers of centripetal-(oncogene type) and centrifugal-(tumoe suppressor gene type) forces. The fitness of the observed log AAIR data sets to the oncogene type- and the tumor suppressor gene type-equilibrium models and the locations of 2 force centers were calculated by applying the least square method of Gauss to log AAIR pair data series with and without topological data manipulations, which are so designed as to let log AAIR pair data series fit to 2 variant (x, y) frameworks, the Rect-coordinates and the Para-coordinates. The 2 variant (x, y) coordinates are defined each as an (x, y) framework with its X axis crossed at a right angle to the regression line of the original log AAIR data (the Rect-coordinates) and as another framework with its X axis run in parallel with the regression line of the original log AAIR pair data series (the Para-coordinates). The fitness test of log AAIR data series to either the oncogene activation type equilibrium model (r = -1.000) or the tumor suppressor gene inactivation type (r = 1.000) was conducted for each of the male-female type pair data and the female-male type data, for each of log AAIR changes in space and log AAIR changes in time, and for each of the 3 (x, y) frameworks in a given neoplasia of both sexes. The results obtained are given as follows: 1) The positivity rates of the fitness test to the oncogene type equilibrium model and the tumor suppressor gene type model were each 63.3% and 56.7% with the log AAIR changes in space, and 73.3% and 73.3% with log AAIR changes in time, as tested in 15 human neoplasias of both sexes. 2) Evidence was presented to indicate that the clearance of oncogene activation and tumor suppressor gene inactivation is the sine qua non premise of carciniogenesis. 3) The r

  6. Cilengitide in Treating Children With Refractory Primary Brain Tumors

    ClinicalTrials.gov

    2013-09-27

    Childhood Central Nervous System Germ Cell Tumor; Childhood Choroid Plexus Tumor; Childhood Craniopharyngioma; Childhood Ependymoblastoma; Childhood Grade I Meningioma; Childhood Grade II Meningioma; Childhood Grade III Meningioma; Childhood High-grade Cerebellar Astrocytoma; Childhood High-grade Cerebral Astrocytoma; Childhood Infratentorial Ependymoma; Childhood Low-grade Cerebellar Astrocytoma; Childhood Low-grade Cerebral Astrocytoma; Childhood Medulloepithelioma; Childhood Mixed Glioma; Childhood Oligodendroglioma; Childhood Supratentorial Ependymoma; Recurrent Childhood Brain Stem Glioma; Recurrent Childhood Brain Tumor; Recurrent Childhood Cerebellar Astrocytoma; Recurrent Childhood Cerebral Astrocytoma; Recurrent Childhood Ependymoma; Recurrent Childhood Medulloblastoma; Recurrent Childhood Pineoblastoma; Recurrent Childhood Subependymal Giant Cell Astrocytoma; Recurrent Childhood Supratentorial Primitive Neuroectodermal Tumor; Recurrent Childhood Visual Pathway and Hypothalamic Glioma

  7. Joint NCCTG and NABTC prognostic factors analysis for high-grade recurrent glioma.

    PubMed

    Wu, Wenting; Lamborn, Kathleen R; Buckner, Jan C; Novotny, Paul J; Chang, Susan M; O'Fallon, Judith R; Jaeckle, Kurt A; Prados, Michael D

    2010-02-01

    The purpose of this study is to determine prognostic factors in patients with high-grade recurrent glioma for 3 outcome variables (overall survival, progression-free survival [PFS], and PFS rate 6 months after study registration [PFS6]). Data from 15 North Central Cancer Treatment Group (NCCTG) trials (n = 469, 1980-2004) and 12 North American Brain Tumor Consortium (NABTC) trials (n = 596, 1998-2002) were included. Eighteen prognostic variables were considered including type of treatment center (community/academic) and initial low-grade histology (yes/no). Recursive partitioning analysis (RPA), Cox proportional hazards, and logistic regression models with bootstrap resampling were used to identify prognostic variables. Longer survival was associated with last known grade (Grade) of III, younger age, ECOG performance score (PS) of 0, shorter time from initial diagnosis (DxTime), and no baseline steroid use. Factors associated with longer PFS were Grade III and shorter DxTime. For patients without temozolomide as part of the treatment regimen, the only factor associated with better PFS6 was Grade III, although DxTime was important in RPA and PS was important in logistic regression. Grade was the most important prognostic factor for all three endpoints regardless of the statistical method used. Other important variables for one or more endpoints included age, PS, and DxTime. Neither type of treatment center nor initial low-grade histology was identified as a major predictor for any endpoint. PMID:20150383

  8. Joint NCCTG and NABTC prognostic factors analysis for high-grade recurrent glioma

    PubMed Central

    Wu, Wenting; Lamborn, Kathleen R.; Buckner, Jan C.; Novotny, Paul J.; Chang, Susan M.; O'Fallon, Judith R.; Jaeckle, Kurt A.; Prados, Michael D.

    2010-01-01

    The purpose of this study is to determine prognostic factors in patients with high-grade recurrent glioma for 3 outcome variables (overall survival, progression-free survival [PFS], and PFS rate 6 months after study registration [PFS6]). Data from 15 North Central Cancer Treatment Group (NCCTG) trials (n = 469, 1980–2004) and 12 North American Brain Tumor Consortium (NABTC) trials (n = 596, 1998–2002) were included. Eighteen prognostic variables were considered including type of treatment center (community/academic) and initial low-grade histology (yes/no). Recursive partitioning analysis (RPA), Cox proportional hazards, and logistic regression models with bootstrap resampling were used to identify prognostic variables. Longer survival was associated with last known grade (Grade) of III, younger age, ECOG performance score (PS) of 0, shorter time from initial diagnosis (DxTime), and no baseline steroid use. Factors associated with longer PFS were Grade III and shorter DxTime. For patients without temozolomide as part of the treatment regimen, the only factor associated with better PFS6 was Grade III, although DxTime was important in RPA and PS was important in logistic regression. Grade was the most important prognostic factor for all three endpoints regardless of the statistical method used. Other important variables for one or more endpoints included age, PS, and DxTime. Neither type of treatment center nor initial low-grade histology was identified as a major predictor for any endpoint. PMID:20150383

  9. Improvement in High-Grade Osteosarcoma Survival

    PubMed Central

    Hung, Giun-Yi; Yen, Hsiu-Ju; Yen, Chueh-Chuan; Wu, Po-Kuei; Chen, Cheng-Fong; Chen, Paul C-H; Wu, Hung-Ta H.; Chiou, Hong-Jen; Chen, Wei-Ming

    2016-01-01

    Abstract The aim of this study was to compare survival before and after 2004 and define the prognostic factors for high-grade osteosarcomas beyond those of typical young patients with localized extremity disease. Few studies have reported the long-term treatment outcomes of high-grade osteosarcoma in Taiwan. A total of 202 patients with primary high-grade osteosarcoma who received primary chemotherapy at Taipei Veterans General Hospital between January 1995 and December 2011 were retrospectively evaluated and compared by period (1995–2003 vs 2004–2011). Patients of all ages and tumor sites and those following or not following controlled protocols were included in analysis of demographic, tumor-related, and treatment-related variables and survival. Overall survival and progression-free survival at 5 years were, respectively, 67.7% and 48% for all patients (n = 202), 77.3% and 57.1% for patients without metastasis (n = 157), and 33.9% and 14.8% for patients with metastasis (n = 45). The survival rates of patients treated after 2004 were significantly higher (by 13%–16%) compared with those of patients treated before 2004, with an accompanying 30% increase in histological good response rate (P = .002). Factors significantly contributing to inferior survival in univariate and multivariate analyses were diagnosis before 2004, metastasis at diagnosis, and being a noncandidate for a controlled treatment protocol. By comparison with the regimens used at our institution before 2004, the current results support the effectiveness of the post-2004 regimens, which consisted of substantially reduced cycles of high-dose methotrexate and a higher dosage of ifosfamide per cycle, cisplatin, and doxorubicin, for treating high-grade osteosarcoma in Asian patients. PMID:27082623

  10. Glycemic modulation in neuro-oncology: experience and future directions using a modified Atkins diet for high-grade brain tumors

    PubMed Central

    Strowd, Roy E.; Cervenka, Mackenzie C.; Henry, Bobbie J.; Kossoff, Eric H.; Hartman, Adam L.; Blakeley, Jaishri O.

    2015-01-01

    Dietary glycemic modulation through high-fat, low-carbohydrate diets, which induce a state of systemic ketosis and alter systemic metabolic signaling, have been incorporated into the clinical management of patients with neurological disease for more than a century. Mounting preclinical evidence supports the antitumor, proapoptotic, and antiangiogenic effects of disrupting glycolytic metabolism through dietary intervention. In recent years, interest in incorporating such novel therapeutic strategies in neuro-oncology has increased. To date, 3 published studies incorporating novel dietary therapies in oncology have been reported, including one phase I study in neuro-oncology, and have set the stage for further study in this field. In this article, we review the biochemical pathways, preclinical data, and early clinical translation of dietary interventions that modulate systemic glycolytic metabolism in the management of primary malignant brain tumors. We introduce the modified Atkins diet (MAD), a novel dietary alternative to the classic ketogenic diet, and discuss the critical issues facing future study. PMID:26649186

  11. IDH mutation status and role of WHO grade and mitotic index in overall survival in grade II–III diffuse gliomas

    PubMed Central

    Olar, Adriana; Wani, Khalida M; Diefes, Kristin; Heathcock, Lindsey E.; van Thuijl, Hinke F.; Gilbert, Mark R.; Armstrong, Terri S.; Sulman, Erik P.; Cahill, Daniel P.; Vera-Bolanos, Elizabeth; Yuan, Ying; Reijneveld, Jaap C.; Ylstra, Bauke; Wesseling, Pieter; Aldape, Kenneth D.

    2015-01-01

    Diffuse gliomas are up till now graded based upon morphology. Recent findings indicate that isocitrate dehydrogenase (IDH) mutation status defines biologically distinct groups of tumors. The role of tumor grade and mitotic index in patient outcome has not been evaluated following stratification by IDH mutation status. To address this, we interrogated 558 WHO grade II–III diffuse gliomas for IDH1/2 mutations and investigated the prognostic impact of WHO grade within IDH-mutant and wild-type tumor subsets independently. The prognostic impact of grade was modest in IDH-mutant [hazard ratio (HR)=1.21, 95% confidence interval (CI)=0.91–1.61] compared to IDH-wild type tumors (HR=1.74, 95% CI=0.95–3.16). Using a dichotomized mitotic index cut-off of 4/1000 tumor cells, we found that while mitotic index was significantly associated with outcome in IDH-wild type tumors (log-rank p<0.0001, HR=4.41, 95% CI=2.55–7.63), it was not associated with outcome in IDH-mutant tumors (log-rank p=0.5157, HR=1.10, 95% CI=0.80–1.51), and could demonstrate a statistical interaction (p<0.0001) between IDH mutation and mitotic index (i.e. suggesting that the effect of mitotic index on patient outcome is dependent on IDH mutation status). Patient age, an established prognostic factor in diffuse glioma, was significantly associated with outcome only in the IDH-wild type subset, and consistent with prior data, 1p/19q co-deletion conferred improved outcome in the IDH-mutant cohort. These findings suggest that stratification of grade II–III gliomas into subsets defined by the presence or absence of IDH mutation leads to subgroups with distinct prognostic characteristics. Further evaluation of grading criteria and prognostic markers is warranted within IDH-mutant versus IDH-wild type diffuse grade II–III gliomas as independent entities. PMID:25701198

  12. Collecting and Storing Blood and Brain Tumor Tissue Samples From Children With Brain Tumors

    ClinicalTrials.gov

    2016-05-17

    Childhood Atypical Teratoid/Rhabdoid Tumor; Childhood Central Nervous System Germ Cell Tumor; Childhood Choroid Plexus Tumor; Childhood Craniopharyngioma; Childhood Grade I Meningioma; Childhood Grade II Meningioma; Childhood Grade III Meningioma; Childhood High-grade Cerebral Astrocytoma; Childhood Infratentorial Ependymoma; Childhood Low-grade Cerebral Astrocytoma; Childhood Oligodendroglioma; Childhood Supratentorial Ependymoma; Newly Diagnosed Childhood Ependymoma; Recurrent Childhood Cerebellar Astrocytoma; Recurrent Childhood Cerebral Astrocytoma; Recurrent Childhood Ependymoma; Recurrent Childhood Medulloblastoma; Recurrent Childhood Supratentorial Primitive Neuroectodermal Tumor; Recurrent Childhood Visual Pathway and Hypothalamic Glioma; Recurrent Childhood Visual Pathway Glioma

  13. Prediction of Grade of Dropout from 3rd Grade Data.

    ERIC Educational Resources Information Center

    Lloyd, Dee Norman; Bleach, Gail

    Measures of background characteristics, school performance, and test achievement were analyzed for four race-by-sex samples of third graders who were known to have later become high school dropouts. In each sample, age in the third grade, course marks, and standardized achievement scores were found to be significantly related to the grade in which…

  14. A Pilot Feasibility Study of Oral 5-Fluorocytosine and Genetically-Modified Neural Stem Cells Expressing E.Coli Cytosine Deaminase for Treatment of Recurrent High Grade Gliomas

    ClinicalTrials.gov

    2015-03-02

    Adult Anaplastic Astrocytoma; Recurrent Grade III Glioma; Recurrent Grade IV Glioma; Adult Anaplastic Oligodendroglioma; Adult Brain Tumor; Adult Giant Cell Glioblastoma; Adult Glioblastoma; Adult Gliosarcoma; Adult Mixed Glioma; Recurrent Adult Brain Tumor; Adult Anaplastic Oligoastrocytoma; Recurrent High Grade Glioma

  15. Tumor location, but not H3.3K27M, significantly influences the blood-brain-barrier permeability in a genetic mouse model of pediatric high-grade glioma.

    PubMed

    Subashi, Ergys; Cordero, Francisco J; Halvorson, Kyle G; Qi, Yi; Nouls, John C; Becher, Oren J; Johnson, G Allan

    2016-01-01

    Pediatric high-grade gliomas (pHGGs) occur with strikingly different frequencies in infratentorial and supratentorial regions. Although histologically these malignancies appear similar, they represent distinct diseases. Recent genomic studies have identified histone K27M H3.3/H3.1 mutations in the majority of brainstem pHGGs; these mutations are rarely encountered in pHGGs that arise in the cerebral cortex. Previous research in brainstem pHGGs suggests a restricted permeability of the blood-brain-barrier (BBB). In this work, we use dynamic contrast-enhanced (DCE) MRI to evaluate BBB permeability in a genetic mouse model of pHGG as a function of location (cortex vs. brainstem, n = 8 mice/group) and histone mutation (mutant H3.3K27M vs. wild-type H3.3, n = 8 mice/group). The pHGG models are induced either in the brainstem or the cerebral cortex and are driven by PDGF signaling and p53 loss with either H3.3K27M or wild-type H3.3. T2-weighted MRI was used to determine tumor location/extent followed by 4D DCE-MRI for estimating the rate constant (K (trans) ) for tracer exchange across the barrier. BBB permeability was 67 % higher in cortical pHGGs relative to brainstem pHGGs (t test, p = 0.012) but was not significantly affected by the expression of mutant H3.3K27M versus wild-type H3.3 (t-test, p = 0.78). Although mice became symptomatic at approximately the same time, the mean volume of cortical tumors was 3.6 times higher than the mean volume of brainstem tumors. The difference between the mean volume of gliomas with wild-type and mutant H3.3 was insignificant. Mean K (trans) was significantly correlated to glioma volume. These results present a possible explanation for the poor response of brainstem pHGGs to systemic therapy. Our findings illustrate a potential role played by the microenvironment in shaping tumor growth and BBB permeability. PMID:26511492

  16. A Practical Approach to the Classification of WHO Grade 3 (G3) Well-differentiated Neuroendocrine Tumor (WD-NET) and Poorly Differentiated Neuroendocrine Carcinoma (PD-NEC) of the Pancreas.

    PubMed

    Tang, Laura H; Basturk, Olca; Sue, Jillian J; Klimstra, David S

    2016-09-01

    High-grade neuroendocrine neoplasms (World Health Organization [WHO] G3) of the pancreas include both well-differentiated neuroendocrine tumor (WD-NET) and poorly differentiated neuroendocrine carcinoma (PD-NEC). According to the WHO classification scheme, the diagnosis of this group of tumors is based on both the histopathology of the tumor and the assessment of proliferation fraction. However, the former can be challenging due to the lack of well-defined histologic criteria, and the latter alone (ie, >20 mitoses/10 high-power fields or Ki67>20%) may not sufficiently distinguish WD-NETs from PD-NECs. Given the considerable differences in treatment strategies and clinical outcome, additional practical modalities are required to facilitate the accurate diagnosis of high-grade pancreatic neuroendocrine neoplasms. We examined 33 cases of WHO G3 neuroendocrine neoplasms of the pancreas and attempted to classify them into WD-NET, small cell PD-NEC (PD-NEC-SCC), and large cell PD-NEC (PD-NEC-LCC) or to designate them as "ambiguous" when an uncertain diagnosis was rendered by any of the observers or there was any disagreement in classification among the 3 observers. To simplify the interpretation, both PD-NEC-SCC and PD-NEC-LCC were considered together as PD-NECs in the final analysis. The initial approach was to assess microscopically a single morphologically challenging hematoxylin and eosin section from each case without the knowledge of Ki67 values, performed independently by 3 pathologists to assess the degree of diagnostic concordance, and then evaluate immunohistochemical staining for surrogate biomarkers of known genotypes of WD-NET and PD-NEC, respectively, and, lastly, complete a clinicopathologic review to establish a final definitive classification. Loss of DAXX or ATRX protein expression defined WD-NET, and abnormal p53, Rb, SMAD4 expression signified PD-NEC. When the chosen section displayed an element of WD histopathology, or other tumor sections contained

  17. Humanities Thematic Units: Four Example Units for Gifted Students in Grade 6 (the Greeks, the Romans, the Middle Ages and the Renaissance). Programs for Gifted Students.

    ERIC Educational Resources Information Center

    Woodbury, Virginia Garton

    One in a series of units for gifted students, the booklet focuses on humanities instruction in grade 6. Program background information stresses the values of humanities as a way of studying the connections in the student's life, particularly the connections between subject areas and how they relate to humans' feelings and thoughts. Procedures…

  18. Malignant Peripheral Nerve Sheath Tumor.

    PubMed

    James, Aaron W; Shurell, Elizabeth; Singh, Arun; Dry, Sarah M; Eilber, Fritz C

    2016-10-01

    Malignant peripheral nerve sheath tumor (MPNST) is the sixth most common type of soft tissue sarcoma. Most MPNSTs arise in association with a peripheral nerve or preexisting neurofibroma. Neurofibromatosis type is the most important risk factor for MPNST. Tumor size and fludeoxyglucose F 18 avidity are among the most helpful parameters to distinguish MPNST from a benign peripheral nerve sheath tumor. The histopathologic diagnosis is predominantly a diagnosis of light microscopy. Immunohistochemical stains are most helpful to distinguish high-grade MPNST from its histologic mimics. Current surgical management of high-grade MPNST is similar to that of other high-grade soft tissue sarcomas. PMID:27591499

  19. Reduction of novel circulating long-chain fatty acids in colorectal cancer patients is independent of tumor burden and correlates with age

    PubMed Central

    2010-01-01

    Background Serum levels of novel hydroxy polyunsaturated ultra long-chain fatty acids (hPULCFAs) have been previously shown to be reduced in pre-treatment CRC patients compared to disease-free subjects, independent of disease stage. However, whether reduced levels of hPULCFAs result from the presence of cancer is currently unknown, as is the distribution of hPULCFAs in the general population. The following studies were carried out to assess whether conventional therapy would result in restoration of systemic hPULCFAs in CRC patients, and to investigate the relationship between hPULCFA levels and age. Methods Tandem mass spectrometry was used to determine serum levels of the 28 carbon-containing hPULCFA C28H46O4 (CRC-446) in the following cohorts: two independent Japanese CRC populations following surgical tumor removal (n = 86), a North American Caucasian CRC cohort (n = 150) following post-surgery combination chemo/radiation therapy, 990 randomly selected anonymized serum samples from subjects ranging between 11 and 99 years of age, as well as longitudinally collected serum samples from healthy normals (n = 8, up to 90 weeks) and stage IV CRC subjects on combination therapy (n = 12, up to 63 weeks). Results Serum CRC-446 levels in CRC subjects were significantly lower than controls (mean of 0.297 ± 0.07 ug/ml in controls versus 0.092 ± 0.03 in CRCs, p < 0.001), and were unaffected by surgical tumor removal or by chemo/radiation treatment (p > 0.05 between pre vs post surgery). CRC-446 levels showed a strong inverse association with age (p < E-11) across the randomly-selected cohort of 990 subjects, with no correlation observed in the CRC-positive subjects. Longitudinal intra-subject results, however, showed relatively stable CRC-446 levels over the short term of up to 90 weeks in both disease-free subjects and late-stage CRC patients. Conclusions Our findings show that CRC-446 levels are not affected by conventional CRC treatment and inversely correlate with age

  20. Curettage of benign bone tumors and tumor like lesions: A retrospective analysis

    PubMed Central

    Kundu, Zile Singh; Gupta, Vinay; Sangwan, Sukhbir Singh; Rana, Parveen

    2013-01-01

    Background: Curettage is one of the most common treatment options for benign lytic bone tumors and tumor like lesions. The resultant defect is usually filled. We report our outcome curettage of benign bone tumors and tumor like lesions without filling the cavity. Materials and Methods: We retrospectively studied 42 patients (28 males and 14 females) with benign bone tumors who had undergone curettage without grafting or filling of the defect by any other bone graft substitute. The age of the patients ranged from 14 to 66 years. The most common histological diagnosis was that of giant cell tumor followed by simple bone cyst, aneurysamal bone cyst, enchondroma, fibrous dysplasia, chondromyxoid fibroma, and chondroblastoma and giant cell reparative granuloma. Of the 15 giant cell tumors, 4 were radiographic grade 1 lesions, 8 were grade 2 and 3 grade 3. The mean maximum diameter of the cysts was 5.1 (range 1.1-9 cm) cm and the mean volume of the lesions was 34.89 cm3 (range 0.94-194.52 cm3). The plain radiographs of the part before and after curettage were reviewed to establish the size of the initial defect and the rate of reconstitution, filling and remodeling of the bone defect. Patients were reviewed every 3 monthly for a minimum period of 2 years. Results: Most of the bone defects completely reconstituted to a normal appearance while the rest filled partially. Two patients had preoperative and three had postoperative fractures. All the fractures healed uneventfully. Local recurrence occurred in three patients with giant cell tumor who were then reoperated. All other patients had unrestricted activities of daily living after surgery. The rate of bone reconstitution, risk of subsequent fracture or the incidence of complications was related to the size of the cyst/tumor at diagnosis. The benign cystic bone lesions with volume greater than approximately 70 cm3 were found to have higher incidence of complications. Conclusion: This study demonstrates the natural

  1. A case of pilocytic astrocytoma requiring tumor resection during pregnancy

    PubMed Central

    UMEHARA, TORU; OKITA, YOSHIKO; NONAKA, MASAHIRO; KANEMURA, YONEHIRO; KODAMA, YOSHINORI; MANO, MASAYUKI; NAKAJIMA, SHIN; FUJINAKA, TOSHIYUKI

    2016-01-01

    Low-grade glioma (LGG) is often encountered in relatively young individuals, including women of childbearing age. Notably, case series describing pregnant women with LGG have been reported in the literature. The present study reported a case of pilocytic astrocytoma (PA) requiring tumor resection during pregnancy. The patient had a history of γ-knife radiotherapy for a brainstem tumor 17 years previously. The histological diagnosis was unclear. The tumor had remained stable following radiosurgery for 17 years, including during her first pregnancy. However, rapid tumor growth around the fourth ventricle occurred at week 25 of her second pregnancy. Therefore, an urgent tumor resection was performed despite the pregnancy. Partial resection was performed since the tumor had infiltrated the brainstem. The histological diagnosis was PA. The residual tumor volume decreased gradually following the delivery. Immunostaining of the tumor for the expression of progesterone receptor revealed focal staining. It is possible that reproductive factors, including specific hormonal changes during pregnancy, affected the tumor growth. The present study described this rare case of PA, which exhibited rapid growth and required urgent surgery during pregnancy. PMID:27073664

  2. Bednar Tumor: An Uncommon Entity

    PubMed Central

    Amonkar, Gayathri P.; Rupani, Asha; Shah, Ajay; Deshpande, Ramesh

    2016-01-01

    Bednar tumor is an uncommon variant of dermatofibrosarcoma protuberans. Also known as pigmented dermatofibrosarcoma protuberans, this tumor is of intermediate grade. It is seen in adults and has a predisposition to affect the shoulder region. We report a rare case of Bednar tumor in a 40-year-old female patient. The diagnosis of Bednar tumor must be considered while reporting pigmented subcutaneous spindle cell lesions.

  3. Spinal tumors in children.

    PubMed

    Binning, Mandy; Klimo, Paul; Gluf, Wayne; Goumnerova, Liliana

    2007-10-01

    Pediatric spine tumors encompass a diverse group of pathologic diagnoses that differ markedly based on the location and age of the child. Children can be affected by primary and metastatic tumors, making the differential diagnosis and treatment options extensive. This article discusses the features of spinal tumors in children based primarily on location: extradural, intradural-extramedullary, and intramedullary tumors. Because this article deals with such a broad topic, detailed descriptions and outcomes of surgical and nonsurgical treatments for each particular tumor are limited. Rather, the key clinical, diagnostic, and therapeutic features of each tumor are discussed. PMID:17991588

  4. Grading Breast Cancer Tissues Using Molecular Portraits*

    PubMed Central

    Olsson, Niclas; Carlsson, Petter; James, Peter; Hansson, Karin; Waldemarson, Sofia; Malmström, Per; Fernö, Mårten; Ryden, Lisa; Wingren, Christer; Borrebaeck, Carl A. K.

    2013-01-01

    Tumor progression and prognosis in breast cancer patients are difficult to assess using current clinical and laboratory parameters, where a pathological grading is indicative of tumor aggressiveness. This grading is based on assessments of nuclear grade, tubule formation, and mitotic rate. We report here the first protein signatures associated with histological grades of breast cancer, determined using a novel affinity proteomics approach. We profiled 52 breast cancer tissue samples by combining nine antibodies and label-free LC-MS/MS, which generated detailed quantified proteomic maps representing 1,388 proteins. The results showed that we could define in-depth molecular portraits of histologically graded breast cancer tumors. Consequently, a 49-plex candidate tissue protein signature was defined that discriminated between histological grades 1, 2, and 3 of breast cancer tumors with high accuracy. Highly biologically relevant proteins were identified, and the differentially expressed proteins indicated further support for the current hypothesis regarding remodeling of the tumor microenvironment during tumor progression. The protein signature was corroborated using meta-analysis of transcriptional profiling data from an independent patient cohort. In addition, the potential for using the markers to estimate the likelihood of long-term metastasis-free survival was also indicated. Taken together, these molecular portraits could pave the way for improved classification and prognostication of breast cancer. PMID:23982162

  5. [The WHO/ISUP grading system for renal carcinoma].

    PubMed

    Moch, H

    2016-07-01

    Histological tumor grading is an accepted prognostic parameter of renal cell carcinoma (RCC). In 2012, the International Society of Urologic Pathologists (ISUP) proposed a novel grading system for RCC, mainly based on the evaluation of nucleoli: gradetumors have nucleoli that are inconspicuous and basophilic at ×400 magnification; gradetumors have nucleoli that are clearly visible at ×400 magnification and eosinophilic; gradetumors have clearly visible nucleoli at ×100 magnification; and gradetumors have extreme pleomorphism or rhabdoid and/or sarcomatoid morphology. This grading system was validated for clear cell renal cell carcinoma and papillary renal cell carcinoma. At the same time, the ISUP proposed not grading chromophobe renal cell carcinomas according to this system. At a consensus conference in Zurich the World Health Organization (WHO) recommended the ISUP grading system; thus, the WHO/ISUP grading system is now going to be implemented internationally. The ISUP/WHO grading system has not been validated as a prognostic parameter for other tumor subtypes, but can be used for descriptive purposes. PMID:27271258

  6. Lenalidomide in Treating Young Patients With Recurrent, Progressive, or Refractory CNS Tumors

    ClinicalTrials.gov

    2013-09-27

    Childhood Atypical Teratoid/Rhabdoid Tumor; Childhood Central Nervous System Germ Cell Tumor; Childhood Choroid Plexus Tumor; Childhood Craniopharyngioma; Childhood Ependymoblastoma; Childhood Grade I Meningioma; Childhood Grade II Meningioma; Childhood Grade III Meningioma; Childhood High-grade Cerebellar Astrocytoma; Childhood High-grade Cerebral Astrocytoma; Childhood Infratentorial Ependymoma; Childhood Low-grade Cerebellar Astrocytoma; Childhood Low-grade Cerebral Astrocytoma; Childhood Medulloepithelioma; Childhood Mixed Glioma; Childhood Oligodendroglioma; Childhood Supratentorial Ependymoma; Recurrent Childhood Brain Tumor; Recurrent Childhood Cerebellar Astrocytoma; Recurrent Childhood Cerebral Astrocytoma; Recurrent Childhood Ependymoma; Recurrent Childhood Medulloblastoma; Recurrent Childhood Pineoblastoma; Recurrent Childhood Subependymal Giant Cell Astrocytoma; Recurrent Childhood Supratentorial Primitive Neuroectodermal Tumor; Recurrent Childhood Visual Pathway and Hypothalamic Glioma

  7. Role of morphometry and proliferative parameters in grading of urothelial neoplasms

    PubMed Central

    Singh, Sunita; Kumar, Santosh; Chabbra, Sonia; Sen, Rajeev; Rana, Praveen; Malik, Shivani; Singh, Sonia; Lamba, Ramesh

    2015-01-01

    Introduction Mean nuclear area of 10 nuclei (MNA–10), mitotic activity index (MAI) and Ki–67 are highly reproducible and can be routinely used as adjuncts to histopathological grading in classifying tumors. Assays of these biomarkers are non–invasive, rapid, easy to perform, more objective and accurate, with high sensitivity and specificity, and correlate well with tumor grade. Material and methods This study was conducted at the Department of Pathology PGIMS, Rohtak on 50 cases, of which 25 cases were high–grade, 15 low–grade, 6 Papillary Urothelial Neoplasm of Low Malignant Potentialand 4 reactive lesions as per the 2004 ISUP/WHO classification. MNA–10, MAI and Ki–67 immunoquantitation were performed on stained sections. Results The age of the patients varied from 35 to 87 years. Male: female ratio was 3.5:1. The mean MNA–10 (μm2) for High Grade Malignant Potential was 104.52 ±25.64 μm2, which was significantly higher than in PUNLMP (47.64 ±10.23) and LMP (51.57 ±15.66). MAI (/10 HPF) showed an increasing trend from reactive lesions to HMP, with a mean of (3 ±1.16)/10 HPF to (21.36 ±5.31)/10 HPF respectively. Ki–67 labelling index, a proliferative marker, revealed increasing trend lowest with reactive lesions (10 ±2.83%) and highest in high grade tumors (65.96 ±14.44). Spearman's correlation showed maximum correlation between MAI and Ki–67 and the increasing grade of tumor. Conclusions MNA–10 in combination with Ki–67 and MAI was found to be stronger than MNA–10 alone. MAI has high reproducibility in differentiating low and high grade, with simple assessment in paraffin embedded sections allowing adequate histopathological analysis and visualization of proliferating cells simultaneously. This multivariate grading model should be applied in routine grading to overcome interobserver variability and to increase reproducibility of grading. PMID:25914836

  8. Vorinostat and Temozolomide in Treating Young Patients With Relapsed or Refractory Primary Brain Tumors or Spinal Cord Tumors

    ClinicalTrials.gov

    2013-05-01

    Childhood Atypical Teratoid/Rhabdoid Tumor; Childhood Central Nervous System Choriocarcinoma; Childhood Central Nervous System Embryonal Tumor; Childhood Central Nervous System Germinoma; Childhood Central Nervous System Mixed Germ Cell Tumor; Childhood Central Nervous System Teratoma; Childhood Central Nervous System Yolk Sac Tumor; Childhood Choroid Plexus Tumor; Childhood Craniopharyngioma; Childhood Ependymoblastoma; Childhood Grade I Meningioma; Childhood Grade II Meningioma; Childhood Grade III Meningioma; Childhood High-grade Cerebellar Astrocytoma; Childhood High-grade Cerebral Astrocytoma; Childhood Infratentorial Ependymoma; Childhood Low-grade Cerebellar Astrocytoma; Childhood Low-grade Cerebral Astrocytoma; Childhood Medulloepithelioma; Childhood Mixed Glioma; Childhood Oligodendroglioma; Childhood Supratentorial Ependymoma; Extra-adrenal Paraganglioma; Recurrent Childhood Brain Stem Glioma; Recurrent Childhood Central Nervous System Embryonal Tumor; Recurrent Childhood Cerebellar Astrocytoma; Recurrent Childhood Cerebral Astrocytoma; Recurrent Childhood Ependymoma; Recurrent Childhood Medulloblastoma; Recurrent Childhood Pineoblastoma; Recurrent Childhood Spinal Cord Neoplasm; Recurrent Childhood Subependymal Giant Cell Astrocytoma; Recurrent Childhood Supratentorial Primitive Neuroectodermal Tumor; Recurrent Childhood Visual Pathway and Hypothalamic Glioma

  9. Science for Grades 6-9.

    ERIC Educational Resources Information Center

    Nederland Independent School District, TX.

    GRADES OR AGES: Grades 6-9. SUBJECT MATTER: General science, life science, earth science, and physical science. ORGANIZATION AND PHYSICAL APPEARANCE: The guide is divided into separate sections for each grade. Each section is further subdivided into units. The major portion of each unit is laid out in four columns; column headings are concepts,…

  10. Elementary Mathematics, Grades 1-6.

    ERIC Educational Resources Information Center

    Nederland Independent School District, TX.

    GRADES OR AGES: Grades 1-6. SUBJECT MATTER: Elementary math. ORGANIZATION AND PHYSICAL APPEARANCE: Introductory material focuses on the philosophy and objectives of instructional material. The guide is divided into six units covering grades 1-6. Each unit presents the general goals, materials needed, minimum program, skills to be developed,…

  11. Graded response to short photoperiod during development and early adulthood in Siberian hamsters and the effects on reproduction as females age

    PubMed Central

    Place, Ned J.; Cruickshank, Jenifer

    2009-01-01

    Short day (SD) lengths delay puberty, suppress ovulation, inhibit sexual behavior, and decelerate reproductive aging in female Siberian hamsters (Phodopus sungorus). To date, the modulation of the age-associated decline in reproductive outcomes has only been demonstrated in female hamsters experiencing different day lengths during development. To determine if developmental delay is necessary for photo-inhibition to decelerate reproductive aging, hamsters raised in LD were transferred to SD as young adults and remained there for 6 months. Females that demonstrated the most immediate and sustained photo-inhibition were found to have greater numbers of ovarian primordial follicles at advanced ages (9 and 12 months) than did females held in LD, nonresponders to SD, and females with a marginal SD-response. Similarly, for females raised in SD from conception to 6 months of age, prolonged developmental delay was associated with greater numbers of primordial follicles at later ages as compared to hamsters that became refractory to SD. A robust response to SD in juvenile and adult hamsters is associated with decelerated reproductive aging, which may result in greater reproductive success in older females as compared to age-matched individuals demonstrating a more modest response to SD. PMID:19470367

  12. Simultaneous Integrated Boost Intensity-Modulated Radiotherapy in Patients With High-Grade Gliomas

    SciTech Connect

    Cho, Kwan Ho; Kim, Joo-Young; Lee, Seung Hoon

    2010-10-01

    Purpose: We analyzed outcomes of simultaneous integrated boost (SIB) intensity-modulated radiotherapy (IMRT) in patients with high-grade gliomas, compared with a literature review. Methods and Materials: Forty consecutive patients (WHO grade III, 14 patients; grade IV, 26 patients) treated with SIB-IMRT were analyzed. A dose of 2.0 Gy was delivered to the planning target volume with a SIB of 0.4 Gy to the gross tumor volume with a total dose of 60 Gy to the gross tumor volume and 50 Gy to the planning target volume in 25 fractions during 5 weeks. Twenty patients received temozolomide chemotherapy. Results: At a median follow-up of 13.4 months (range, 3.7-55.9 months), median survival was 14.8 months. One- and 2-year survival rates were 78% and 65%, respectively, for patients with grade III tumors and 56% and 31%, respectively, for patients with grade IV tumors. Age ({<=}50 vs. >50), grade (III vs. IV), subtype (astrocytoma vs. oligodendroglioma or mixed), and a Zubrod performance score (0-1 vs. >2) were predictive of survival. Of 25 (63%) patients who had recurrences, 17 patients had local failure, 9 patients had regional failure, and 1 patient had distant metastasis. Toxicities were acceptable. Conclusions: SIB-IMRT with the dose/fractionation used in this study is feasible and safe, with a survival outcome similar to the historical control. The shortening of treatment time by using SIB-IMRT may be of value, although further investigation is warranted to prove its survival advantage.

  13. The prognostic value of histological grading of posterior fossa ependymomas in children: a Children's Oncology Group study and a review of prognostic factors.

    PubMed

    Tihan, Tarik; Zhou, Tianni; Holmes, Emi; Burger, Peter C; Ozuysal, Sema; Rushing, Elisabeth J

    2008-02-01

    We performed a retrospective analysis of 96 pediatric posterior fossa ependymomas in order to determine the prognostic value of histological grade based on the current WHO grading scheme. The patients were selected among Children's Oncology Group (previously Pediatric Oncology Group-POG) patients enrolled in clinical trials, and on the basis of central pathology review, location, and age. We excluded entities such as sub-ependymoma, myxopapillary, or clear-cell ependymoma, after a consensus diagnosis by three neuropathologists. A total of 66 males and 30 females with a median age of 48 months were identified. The group was analyzed to determine the effects of histological grade, age, gender, and extent of resection on event-free and overall survival. Our results showed that extent of resection, age, and histological grade were independent prognostic variables for event-free survival. The relative risk for extent of resection and histological grade was calculated as 3.59 (P<0.001) and 3.58 (P<0.001), respectively. Overall survival significantly correlated with extent of resection and age, but not with histological grade. We compared our results with peer-reviewed publications on pediatric intracranial ependymomas in the English language between 1990 and 2005. Selection criteria identified 32 manuscripts involving 1444 patients. Extent of resection was a significant factor in 21, age in 12, and histological grading in nine of these studies. Other factors reported to be significant by more than one study included tumor location and radiation treatment. Our findings suggest that histological grade (WHO Grade II vs III) is an independent prognostic indicator for event-free survival, but may not be so for overall survival in pediatric posterior fossa ependymomas. We believe that an accurate assessment of the prognostic value of histological grade depends on the selection of a well-characterized clinical cohort of sufficient size, and the inclusion of relevant

  14. Archaean and Palaeoproterozoic gneisses reworked during a Neoproterozoic (Pan-African) high-grade event in the Mozambique belt of East Africa: Structural relationships and zircon ages from the Kidatu area, central Tanzania

    NASA Astrophysics Data System (ADS)

    Vogt, M.; Kröner, A.; Poller, U.; Sommer, H.; Muhongo, S.; Wingate, M. T. D.

    2006-06-01

    This study presents new zircon ages and Sm-Nd whole-rock isotopic compositions for high-grade gneisses from the Udzungwa Mountain area in the central part of the Mozambique belt, Tanzania. The study area comprises a succession of layered granulite-facies para- and orthogneisses, mostly retrograded to amphibolite-facies. The original intrusive contacts became obscured or severely modified during non-coaxial ductile deformation, and extensive shearing occurred during retrogression. Structures reflecting the early deformational history were mostly obscured when the rocks were transported into the lower crust as documented by severe flattening. Only the fragmented gneisses in the eastern part of the area testify to a brittle regime. Structures in narrow low strain zones that predate the currently observed layering are preserved in rootless isoclinal folds and boudins. Magmatic and detrital zircons from tonalitic to felsic orthogneisses and a metapelite sample were dated using the U-Pb and Pb-Pb evaporation methods and SHRIMP II. Cathodoluminiscence images reveal ubiquitous xenocrystic cores, rimmed by clear, unzoned overgrowth due to high-grade metamorphism. Discordant U-Pb data therefore reflect core-rim relationships, and it was not always possible to obtain precise crystallisation ages. The analyses reveal Neoarchaean, Palaeoproterozoic and Neoproterozoic protolith ages. Nd isotopic systematics yielded strongly negative ɛNd( t) -values and Neoarchaean to Palaeoproterozoic model ages, even for gneisses emplaced in the Neoproterozoic. The trace element distribution suggests upper crustal derivation of the gneisses. Therefore, our study provides evidence that recycling of older crust played a major role during the evolution of the Kidatu area. Neoarchaean rocks are interpreted to represent fragments of the Tanzania craton. Our results, together with those of earlier workers, lead to the conclusion that the central part of the Mozambique belt mainly consists of ancient

  15. Neurodevelopmental Outcomes of Children with Low-Grade Gliomas

    ERIC Educational Resources Information Center

    Ris, M. Douglas; Beebe, Dean W.

    2008-01-01

    As a group, children with low-grade gliomas (LGGs) enjoy a high rate of long-term survival and do not require the intensity of neurotoxic treatments used with higher risk pediatric brain tumors. Because they are generally considered to have favorable neurobehavioral outcomes, they have not been studied as thoroughly as higher-grade brain tumors by…

  16. A Probabilistic Atlas of Diffuse WHO Grade II Glioma Locations in the Brain

    PubMed Central

    Baumann, Cédric; Zouaoui, Sonia; Yordanova, Yordanka; Blonski, Marie; Rigau, Valérie; Chemouny, Stéphane; Taillandier, Luc; Bauchet, Luc; Duffau, Hugues; Paragios, Nikos

    2016-01-01

    Diffuse WHO grade II gliomas are diffusively infiltrative brain tumors characterized by an unavoidable anaplastic transformation. Their management is strongly dependent on their location in the brain due to interactions with functional regions and potential differences in molecular biology. In this paper, we present the construction of a probabilistic atlas mapping the preferential locations of diffuse WHO grade II gliomas in the brain. This is carried out through a sparse graph whose nodes correspond to clusters of tumors clustered together based on their spatial proximity. The interest of such an atlas is illustrated via two applications. The first one correlates tumor location with the patient’s age via a statistical analysis, highlighting the interest of the atlas for studying the origins and behavior of the tumors. The second exploits the fact that the tumors have preferential locations for automatic segmentation. Through a coupled decomposed Markov Random Field model, the atlas guides the segmentation process, and characterizes which preferential location the tumor belongs to and consequently which behavior it could be associated to. Leave-one-out cross validation experiments on a large database highlight the robustness of the graph, and yield promising segmentation results. PMID:26751577

  17. A Probabilistic Atlas of Diffuse WHO Grade II Glioma Locations in the Brain.

    PubMed

    Parisot, Sarah; Darlix, Amélie; Baumann, Cédric; Zouaoui, Sonia; Yordanova, Yordanka; Blonski, Marie; Rigau, Valérie; Chemouny, Stéphane; Taillandier, Luc; Bauchet, Luc; Duffau, Hugues; Paragios, Nikos

    2016-01-01

    Diffuse WHO grade II gliomas are diffusively infiltrative brain tumors characterized by an unavoidable anaplastic transformation. Their management is strongly dependent on their location in the brain due to interactions with functional regions and potential differences in molecular biology. In this paper, we present the construction of a probabilistic atlas mapping the preferential locations of diffuse WHO grade II gliomas in the brain. This is carried out through a sparse graph whose nodes correspond to clusters of tumors clustered together based on their spatial proximity. The interest of such an atlas is illustrated via two applications. The first one correlates tumor location with the patient's age via a statistical analysis, highlighting the interest of the atlas for studying the origins and behavior of the tumors. The second exploits the fact that the tumors have preferential locations for automatic segmentation. Through a coupled decomposed Markov Random Field model, the atlas guides the segmentation process, and characterizes which preferential location the tumor belongs to and consequently which behavior it could be associated to. Leave-one-out cross validation experiments on a large database highlight the robustness of the graph, and yield promising segmentation results. PMID:26751577

  18. Low-grade serous carcinoma of the ovary or peritoneum.

    PubMed

    Gershenson, D M

    2016-04-01

    Over the past decade, the strategy for clinical trial design in making progress against epithelial cancers of the ovary/peritoneum/fallopian tube has changed dramatically. The NRG (GOG) Rare Tumor Committee has been a leader in this transformation. No longer does 'one size fit all'. Rather, separate clinical trials for rare subtypes have been developed and, in some cases, completed. An enhanced understanding of their pathologic diagnosis, molecular biology, and clinical behavior has galvanized this change. Low-grade serous carcinoma may occur de novo or following an initial diagnosis of serous tumor of low malignant potential. It is characterized by young age at diagnosis, relative chemoresistance, and prolonged survival compared with high-grade serous carcinoma. Historically, conventional chemotherapy has demonstrated very limited activity in this subtype. Hormonal therapy may provide benefit in this subtype. Preclinical studies have identified and elucidated genes and pathways-MAP kinase pathway, IGF1-R, the angiogenesis pathway, and possibly, the PI3K/AKT/mTOR pathway in low-grade serous carcinoma. To date, clinical evidence supports the activity of MEK and BRAF inhibitors and bevacizumab. Further pursuit of targeted therapy trials is clearly warranted. PMID:27141071

  19. Solid Variant of Adenoid Cystic Carcinoma of the Breast: A Case Series With Proposal of a New Grading System.

    PubMed

    Foschini, Maria P; Rizzo, Antonio; De Leo, Antonio; Laurino, Licia; Sironi, Maria; Rucco, Vittorio

    2016-04-01

    Adenoid cystic carcinoma (ACC) of the breast is a low-grade malignancy "triple negative" breast tumor. ACC of the breast can present a great variety of morphological features having a prognostic impact. Recently, cases of ACC having solid-basaloid features (SBACC) have been described. In the present study, 6 cases of SBACC have been reported. All the cases affected female patients aged 47 to 69 years (mean = 54 years). Two patients had metastases to the axillary lymph nodes, and 2 patients experienced local recurrences. No deaths due to the tumor were observed. A review of the literature on breast SBACC showed that local recurrences and lymph node metastases are more frequent than in the ACC conventional type; nevertheless, no deaths due to the tumor are registered at the moment. On the contrary, cases of ACC with features of malignant transformation are on record. Therefore, a new grading system on breast ACC is proposed. PMID:26378056

  20. [Grading of head and neck neoplasms].

    PubMed

    Agaimy, A; Weichert, W

    2016-07-01

    Tumors of the head and neck form a heterogeneous group of benign and malignant neoplasms with significant differences in biological behavior and therapeutic strategies. Squamous cell carcinomas (SCC) of the larynx, pharynx and oral cavity represent the most frequent and, thus, clinically most important malignant neoplasms in this anatomical region. Similar to other neoplasms, grading of head and neck malignancies is based on evaluation of the tumor histology usually including both architectural and cytological features; however, the current consensus grading for head and neck SCC is of limited prognostic and therapeutic value and the reproducibility is low. Therefore, novel grading criteria have been proposed that are based on additional parameters, such as the type of tumor growth pattern at the invasive front (so-called tumor budding). These novel algorithms, however, have not yet been officially endorsed into guidelines. Salivary gland (SG) neoplasms, although less frequent, constitute a second important pathologically and clinically complex group of tumors at this location. In contrast to SCC, grading of these tumors is of high clinical importance. Based on the large variety of carcinoma entities of the SG, both entity-specific (e. g. mucoepidermoid carcinoma) algorithms but also algorithms, which are solely based on the recognition of a specific carcinoma variant with subsequent automatic assignment of the tumor grade (e. g. acinic cell carcinoma and salivary duct carcinoma) are in use. In the sinonasal tract, grading is important for non-intestinal type adenocarcinoma and esthesioneuroblastoma. In this article the most important grading schemes and criteria for head and neck malignancies are presented and their prognostic and therapeutic implications are discussed. PMID:27342593

  1. Brachial Plexus Tumors in a Consecutive Series of Twenty One Patients

    PubMed Central

    Go, Myeong Hoon; Cho, Ki Hong

    2012-01-01

    Objective This is a retrospective review of 22 surgically treated benign and malignant tumors of brachial plexus region to describe clinical presentation, the characteristics of brachial plexus tumor and clinical outcomes with a literature review. Methods Twenty-one patients with consecutive 22 surgeries for primary brachial plexus tumors were enrolled between February 2002 and November 2011 were included in this study. The medical records of all patients were reviewed. Results Eleven male and 10 female patients were enrolled. Mean age was 39 years. Three patients had brachial plexus tumor associated with neurofibromatosis (13.6%). Presenting signs and symptoms included parenthesis and numbness (54.5%), radiating pain (22.7%), direct tenderness and pain (27.2%), palpable mass (77.3%). Twelve patients presented preoperative sensory deficit (54.5%) and 9 patients presented preoperative motor deficit (40.9%). Twenty tumors (90.9%) were benign and 2 tumors (9.1%) were malignant. Benign tumors included 15 schwannomas (68.2%), 4 neurofibromas (18.2%) and 1 granular cell tumor (4.5%). There were 1 malignant peripheral nerve sheath tumor (MPNST) and 1 malignant granular cell tumor. Gross total resection was achieved in 16 patients (72.7%), including all schwannomas, 1 neurofibroma. Subtotal resection was performed in 6 tumors (27.3%), including 3 neurofibromatosis associated with brachial plexus neurofibromas, 1 MPNST and 2 granular cell tumor in one patient. Conclusion Resection of tumor is the choice of tumor in the most of benign and malignant brachial plexus tumors. Postoperative outcomes are related to grade of resection at surgery and pathological features of tumor. PMID:23091673

  2. Does the School Performance Variable Used in the International Health Behavior in School-Aged Children (HBSC) Study Reflect Students' School Grades?

    ERIC Educational Resources Information Center

    Felder-Puig, Rosemarie; Griebler, Robert; Samdal, Oddrun; King, Matthew A.; Freeman, John; Duer, Wolfgang

    2012-01-01

    Background: Given the pressure that educators and policy makers are under to achieve academic standards for students, understanding the relationship of academic success to various aspects of health is important. The international Health Behavior in School-Aged Children (HBSC) questionnaire, being used in 41 countries with different school and…

  3. The Growth of Democratic Tradition: The Age of Enlightenment. Tenth Grade Lesson. Schools of California Online Resources for Education (SCORE): Connecting California's Classrooms to the World.

    ERIC Educational Resources Information Center

    Rosa, Marie A.

    This lesson plan begins with an overview of the age of enlightenment and those ideas that influenced the founders of the United States. The lesson plan provides information sheets about five enlightenment thinkers: John Locke (1632-1704), Mary Wolstonecraft (1759-1898), Baron de Montesquieu (1689-1755), Jean Jacques Rousseau (1712-1788), and John…

  4. Age and Its Effect on Language Arts Achievement: A Longitudinal Study of California Standards Tests (CST) for 2nd through 6th Grade

    ERIC Educational Resources Information Center

    DeBerry, Karen E.

    2011-01-01

    Entrance age in kindergarten has been a controversial issue as the range from the youngest to the oldest student spans up to 24 months. This range leaves a heterogeneous gap for teachers who are already differentiating for their English Language Learners, struggling students, and high achieving students. This is compounded by the fact that the…

  5. Ispinesib in Treating Young Patients With Relapsed or Refractory Solid Tumors or Lymphoma

    ClinicalTrials.gov

    2013-01-15

    Childhood Burkitt Lymphoma; Childhood Central Nervous System Germ Cell Tumor; Childhood Choroid Plexus Tumor; Childhood Craniopharyngioma; Childhood Grade I Meningioma; Childhood Grade II Meningioma; Childhood Grade III Meningioma; Childhood High-grade Cerebral Astrocytoma; Childhood Infratentorial Ependymoma; Childhood Low-grade Cerebral Astrocytoma; Childhood Spinal Cord Neoplasm; Childhood Supratentorial Ependymoma; Recurrent Childhood Brain Stem Glioma; Recurrent Childhood Brain Tumor; Recurrent Childhood Cerebellar Astrocytoma; Recurrent Childhood Cerebral Astrocytoma; Recurrent Childhood Ependymoma; Recurrent Childhood Grade III Lymphomatoid Granulomatosis; Recurrent Childhood Large Cell Lymphoma; Recurrent Childhood Lymphoblastic Lymphoma; Recurrent Childhood Medulloblastoma; Recurrent Childhood Small Noncleaved Cell Lymphoma; Recurrent Childhood Supratentorial Primitive Neuroectodermal Tumor; Recurrent Childhood Visual Pathway and Hypothalamic Glioma; Unspecified Childhood Solid Tumor, Protocol Specific

  6. The effects of sterilization, processing and aging on the structure and morphology of medical-grade ultrahigh molecular weight polyethylene for use in total joint replacements

    NASA Astrophysics Data System (ADS)

    Goldman, Marni

    A pilot study was performed which examined the effects of gamma radiation sterilization after five years aging in air on the structure of ultrahigh molecular weight polyethylene (UHMWPE) for total joint replacements. A sterilized tibial component and a nonsterile block of polymer which had come from the same compression molded batch of material were characterized by differential scanning calorimetry (DSC), density gradient column (DGC), small angle x-ray scattering (SAXS), transmission electron microscopy (TEM) and fourier transform infrared spectroscopy (FTIR). Increases in crystallinity and density were observed for the sterilized component after five years aging in air. A thickening of the lamellae as well as an increase in their tortuosity was seen in the sterilized material. Oxygen uptake occurred in the irradiated specimens. Results indicated that chain scission was the dominant response to gamma irradiation sterilization and aging in air for five years. Material from four different processing conditions was sterilized by: gamma irradiation, electron beam irradiation, ethylene oxide gas, plasma, or not sterilized as a control. Groups were divided into aging environments: air, hyaluronic acid and hydrogen peroxide. Characterization by DSC, DGC, TEM, SAXS and FTIR was performed periodically over a period of one and a half years. Processing conditions had the least effect on the structure and morphology of UHMWPE. Initial increases in oxygen uptake were higher for those materials with higher nascent crystallinities. Trends observed for all materials as a function of sterilization, aging environment and time were similar. Sterilization method and subsequent aging time were the most important factor in examining the structure of UHMWPE. Ethylene oxide gas and plasma did not appear to alter the polymer. Both forms of irradiation resulted in the most changes with time augmenting some effects. Results indicated chain scission dominated in response to radiation and

  7. Malignant Triton Tumors in Sisters with Clinical Neurofibromatosis Type 1

    PubMed Central

    Alina, Basnet; Sebastian, Jofre A.; Gerardo, Capo

    2015-01-01

    Malignant triton tumors (MTTs) are rare and aggressive sarcomas categorized as a subgroup of malignant peripheral nerve sheath tumors (MPNSTs). MTTs arise from Schwann cells of peripheral nerves or existing neurofibromas and have elements of rhabdomyoblastic differentiation. We report the occurrence of MTTs in two sisters. The first patient is a 36-year-old female who presented with left sided chest wall swelling. She also had clinical features consistent with neurofibromatosis type 1 (NF-1). Debulking of the mass showed high-grade malignant peripheral nerve sheath tumor with skeletal muscle differentiation (MTT). The patient was treated with ifosfamide and adriamycin along with radiation. Four years after treatment, she still has no evidence of disease recurrence. Her sister subsequently presented to us at the age of 42 with left sided lateral chest wall pain. Imaging showed a multicompartmental retroperitoneal cystic mass with left psoas involvement. The tumor was resected and, similarly to her sister, it showed high-grade malignant peripheral nerve sheath tumor with rhabdomyoblastic differentiation (MTT). The patient was started on chemotherapy and radiation as described above. PMID:26114002

  8. Differences and Similarities in the Clinicopathological Features of Pancreatic Neuroendocrine Tumors in China and the United States

    PubMed Central

    Zhu, Li-Ming; Tang, Laura; Qiao, Xin-Wei; Wolin, Edward; Nissen, Nicholas N.; Dhall, Deepti; Chen, Jie; Shen, Lin; Chi, Yihebali; Yuan, Yao-Zong; Ben, Qi-Wen; Lv, Bin; Zhou, Ya-Ru; Bai, Chun-Mei; Chen, Jie; Song, Yu-Li; Song, Tian-Tian; Lu, Chong-Mei; Yu, Run; Chen, Yuan-Jia

    2016-01-01

    Abstract The presentation, pathology, and prognosis of pancreatic neuroendocrine tumors (PNETs) in Asian patients have not been studied in large cohorts. We hypothesized that the clinicopathological features of PNETs of Chinese patients might be different from those of US patients. The objectives of this study were to address whether PNETs in Chinese patients exhibit unique clinicopathological features and natural history, and can be graded and staged using the WHO/ENETS criteria. This is a retrospective review of medical records of patients with PNETs in multiple academic medical centers in China (7) and the United States (2). Tumor grading and staging were based on WHO/ENETS criteria. The clinicopathological features of PNETs of Chinese and US patients were compared. Univariate and multivariate analyses were performed to find associations between survival and patient demographics, tumor grade and stage, and other clinicopathological characteristics. A total of 977 (527 Chinese and 450 US) patients with PNETs were studied. In general, Chinese patients were younger than US patients (median age 46 vs 56 years). In Chinese patients, insulinomas were the most common (52.2%), followed by nonfunctional tumors (39.7%), whereas the order was reversed in US patients. Tumor grade distribution was similar in the 2 countries (G1: 57.5% vs 55.0%; G2: 38.5% vs 41.3%; and G3: 4.0% vs 3.7%). However, age, primary tumor size, primary tumor location, grade, and stage of subtypes of PNETs were significantly different between the 2 countries. The Chinese nonfunctional tumors were significantly larger than US ones (median size 4 vs 3 cm) and more frequently located in the head/neck region (54.9% vs 34.8%). The Chinese and US insulinomas were similar in size (median 1.5 cm) but the Chinese insulinomas relatively more frequently located in the head/neck region (48.3% vs 26.1%). Higher grade, advanced stage, metastasis, and larger primary tumor size were significantly associated with

  9. Ependymal tumors with oligodendroglioma like clear cells: Experience from a tertiary care hospital in Pakistan

    PubMed Central

    Hashmi, Fauzan Alam; Khan, Muhammad Faheem; Khan, Saad Akhtar; Waqas, Muhammad; Bari, Muhammad Ehsan; Ahmed, Arsalan

    2015-01-01

    Background: Ependymal tumors with oligodendroglioma like clear cells have never been reported from Pakistan. We aimed to see the features and outcomes of this rare entity. Methods: It was retrospective cohort conducted at the Department of Neurosurgery, Aga Khan University from 2003 to 2013. The medical records and radiology of patients with proven histopathology were reviewed. Analysis was done on SPSS 20. Results: Eleven cases of ependymal tumors with clear cells were found, which equated to 1.5% of the total tumor burden in 11 years. The median age was 49 years. Most common presenting symptom was headache 54.5%. Out of 11 patients, 9 patients had a supratentorial tumor. Magnetic resonance imaging showed hypointense signals on T1 and hyperintense signals on T2-weighted images in all cases. Contrast enhancement was found in 9 patients (77.8%), necrosis and hemorrhage was found in 4 (36%) and 3 (27%) patients, respectively. Immunohistochemistry showed glial fibrillary acidic protein and epithelial membrane antigen positivity in all cases. Ki-67 showed high proliferative index in 6 patients. According to the World Health Organization grading of ependymal tumors, 2 patients had Grade II tumors, and 9 patients had Grade III tumors with clear cells. Gross total resection was achieved in 6 (54.5%) and subtotal resection in 5 patients (45.4%). Recurrence was observed in 9 patients. Six patients died of the disease. Median progression-free survival and overall survival was 8 months and 10 months, respectively. Conclusion: Ependymal tumors with clear cells presented more commonly in Grade III lesions and were more aggressive in behavior with poorer outcome compared to similar studies. PMID:26664928

  10. Surgical Outcome of Intradural Spinal Tumors.

    PubMed

    Ahsan, M K; Sakeb, N; Ali, M Y; Awwal, M A; Khan, S I; Goni, M M; Mia, M B; Alam, M B; Zaman, N; Jannat, S N

    2016-07-01

    Results of 63 surgically treated intradural spinal tumors between the period of October 2003 and December 2014 at Bangabandhu Sheikh Mujib Medical University (BSMMU) and in our private settings, Dhaka, were analyzed retrospectively. There were 33 males, 30 females with an average age of 52.4 years (13-70 years) and followed up for at least a year. The preoperative symptom with duration, tumors location and intradural space occupancy and the histopathological diagnosis were analyzed. Pain was evaluated by the visual analogue scale (VAS) and the neurologic function was assessed by Nurick's grade. The tumors were located as, thoracic (n=32, 50.79%), lumbar (n=16, 25.39%), cervical (n=05, 07.93%), and junctional (n=10, 15.87%, CervicoThoracic-01, Thoracolumbar-09). The histopathological diagnosis included schwannoma (n=30, 47.7%), meningiomas (n=14, 22.3%), neurofibroma, arachnoid cyst and myxopapillary ependymoma (n=03, 04.76%) each and paraganglioma (n=01, 01.59%). Among the intramedullary tumors, ependymoma (n=03, 04.76%), astrocytoma and epidermoid cyst (n=02, 03.17%), haemangioblastoma, paraganglioma and cavernous haemangioma (n=01, 01.59%) each. The VAS score was reduced in all cases from 8.0±1.2 to 1.2±0.8 (p<0.003) and the Nurick's grade was improved in all cases from 3.0±1.3 to 1.0±0.0 (p<0.005). The preoperative neurological deficit improved within 8 postoperative weeks in most cases and within 1 postoperative year in all cases. Complications included cerebrospinal fluid leakage, parasthesia and further neurological deterioration (Astrocytoma) (n=02, 03.17%) and dependant bedsore and recurrence (Ependymoma) (n=01, 01.59%). Aggressive surgical excision potentially minimizes neurologic morbidity and improved outcome except intramedullary tumors where initial treatment consists of maximum safe surgical resection or biopsy. PMID:27612900

  11. Many postchemotherapy sarcomatous tumors in patients with testicular germ cell tumors are sarcomatoid yolk sac tumors: a study of 33 cases.

    PubMed

    Howitt, Brooke E; Magers, Martin J; Rice, Kevin R; Cole, Cristina D; Ulbright, Thomas M

    2015-02-01

    Sarcomatoid neoplasms in patients with testicular germ cell tumors (TGCTs) may show diverse lineages and are usually attributed to "transformation" of teratoma, although origin from yolk sac tumor (YST) has also been suggested. We evaluated 33 sarcomatoid tumors from 23 TGCT patients that lacked specific features of a defined sarcoma subtype for a number of features, including: atypia (mild, moderate, severe), cellularity, tumor necrosis, mitotic index, stromal vascularity, cell profile (spindle or epithelioid), and stromal quality (myxoid and/or fibrous). Immunohistochemical staining analyses directed against cytokeratin (AE1/AE3), SALL4, glypican-3 (GPC3), α-fetoprotein (AFP), p63, glial fibrillary acidic protein (GFAP), CD34, MUC4, smooth muscle actin (SMA), desmin, caldesmon, and myogenin were performed. Staining intensity (0=negative, 1=weak, 2=moderate, 3=strong) and extent (0=<1%, 1=1% to 10%, 2=10% to 50%, 3=>50%) were scored. Tumor grade based on the French sarcoma grading system was assessed, with grades 2-3 considered high grade. Tumors with at least moderate intensity and >10% (+) cells for both AE1/AE3 and GPC3 were considered to be sarcomatoid YST (SYST); 22 tumors from 14 patients (ages 18 to 38 y, mean 27 y) met these criteria and were the focus of this study. All SYSTs occurred after chemotherapy (3 to 132 mo after TGCT diagnosis; mean 42.5 mo, median 30.5 mo). They had spindled (100%; 19 predominant) and epithelioid cells (77%; 3 predominant) in myxoid to fibrous stroma. Thirteen exhibited at least focally severe nuclear atypia. Distinctive tumor "ringlets" and intercellular basement membrane deposits (parietal YST differentiation) were common. In addition to positivity for AE1/AE3 and GPC3, 15/22 were SALL4 (+), 10/22 were at least focally CD34 (+), and 2/22 were focally p63 (+). Fifty percent exhibited smooth muscle differentiation as evidenced by desmin (8/19), caldesmon (2/4), and/or SMA (4/6) reactivity. AFP, MUC4, GFAP, and myogenin were

  12. Academic Achievement for Fifth-Grade Students in Elementary and Intermediate School Settings: Grade Span Configurations

    ERIC Educational Resources Information Center

    Combs, Julie P.; Clark, David; Moore, George W.; Onwuegbuzie, Anthony J.; Edmonson, Stacey L.; Slate, John R.

    2011-01-01

    Few researchers have addressed student achievement outcomes as a function of grade configurations for older elementary-aged students. Thus, this study was designed to determine differences between students' Grade 5 reading and mathematics achievement in elementary schools (K-5) as compared to intermediate schools (Grade 5, 5-6) for 5 academic…

  13. Tumor Mismatch Repair Immunohistochemistry and DNA MLH1 Methylation Testing of Patients With Endometrial Cancer Diagnosed at Age Younger Than 60 Years Optimizes Triage for Population-Level Germline Mismatch Repair Gene Mutation Testing

    PubMed Central

    Buchanan, Daniel D.; Tan, Yen Y.; Walsh, Michael D.; Clendenning, Mark; Metcalf, Alexander M.; Ferguson, Kaltin; Arnold, Sven T.; Thompson, Bryony A.; Lose, Felicity A.; Parsons, Michael T.; Walters, Rhiannon J.; Pearson, Sally-Ann; Cummings, Margaret; Oehler, Martin K.; Blomfield, Penelope B.; Quinn, Michael A.; Kirk, Judy A.; Stewart, Colin J.; Obermair, Andreas; Young, Joanne P.; Webb, Penelope M.; Spurdle, Amanda B.

    2014-01-01

    Purpose Clinicopathologic data from a population-based endometrial cancer cohort, unselected for age or family history, were analyzed to determine the optimal scheme for identification of patients with germline mismatch repair (MMR) gene mutations. Patients and Methods Endometrial cancers from 702 patients recruited into the Australian National Endometrial Cancer Study (ANECS) were tested for MMR protein expression using immunohistochemistry (IHC) and for MLH1 gene promoter methylation in MLH1-deficient cases. MMR mutation testing was performed on germline DNA of patients with MMR-protein deficient tumors. Prediction of germline mutation status was compared for combinations of tumor characteristics, age at diagnosis, and various clinical criteria (Amsterdam, Bethesda, Society of Gynecologic Oncology, ANECS). Results Tumor MMR-protein deficiency was detected in 170 (24%) of 702 cases. Germline testing of 158 MMR-deficient cases identified 22 truncating mutations (3% of all cases) and four unclassified variants. Tumor MLH1 methylation was detected in 99 (89%) of 111 cases demonstrating MLH1/PMS2 IHC loss; all were germline MLH1 mutation negative. A combination of MMR IHC plus MLH1 methylation testing in women younger than 60 years of age at diagnosis provided the highest positive predictive value for the identification of mutation carriers at 46% versus ≤ 41% for any other criteria considered. Conclusion Population-level identification of patients with MMR mutation-positive endometrial cancer is optimized by stepwise testing for tumor MMR IHC loss in patients younger than 60 years, tumor MLH1 methylation in individuals with MLH1 IHC loss, and germline mutations in patients exhibiting loss of MSH6, MSH2, or PMS2 or loss of MLH1/PMS2 with absence of MLH1 methylation. PMID:24323032

  14. Sinus Tumors

    MedlinePlus

    ... Tumors Nasal Deformities Choanal Atresia Epiphora (Excessive Tearing) Disclosure Statement Printer Friendly Sinus Tumors Abtin Tabaee, MD Introduction Tumors of the nose and paranasal sinuses are rare, accounting for fewer than 1% of all tumors. These ...

  15. Bone tumor

    MedlinePlus

    Tumor - bone; Bone cancer; Primary bone tumor; Secondary bone tumor ... The cause of bone tumors is unknown. They often occur in areas of the bone that grow rapidly. Possible causes include: Genetic defects ...

  16. Improving Grading Consistency through Grade Lift Reporting

    ERIC Educational Resources Information Center

    Millet, Ido

    2010-01-01

    We define Grade Lift as the difference between average class grade and average cumulative class GPA. This metric provides an assessment of how lenient the grading was for a given course. In 2006, we started providing faculty members individualized Grade Lift reports reflecting their position relative to an anonymously plotted school-wide…

  17. Blockade of Tumor Necrosis Factor-Alpha: A Role for Adalimumab in Neovascular Age-Related Macular Degeneration Refractory to Anti-Angiogenesis Therapy?

    PubMed Central

    Fernández-Vega, Beatriz; Fernández-Vega, Álvaro; Rangel, Carlos Mario; Nicieza, Javier; Villota-Deleu, Eva; Vega, José A.; Sanchez-Avila, Ronald M.

    2016-01-01

    Aims To report a case of wet age-related macular degeneration (wet-AMD) refractory to intravitreal anti-vascular endothelial growth factor (anti-VEGF) therapy in a patient who showed visual and anatomical improvement and stabilization after starting a subcutaneous treatment course with adalimumab, an anti-tumor necrosis factor-alpha (TNF-α) drug, for concomitant Crohn's disease. Methods Observational case report of a female patient. Ophthalmological evaluation was performed by slit lamp and ophthalmoscopy (posterior pole and anterior segment). Best-corrected visual acuity (BCVA) was determined, and imaging was performed by fluorescein angiography, indocyanine green angiography, and optical coherence tomography (OCT). Intravitreal therapies used and treatment with anti-TNF-α were recorded. Results A 64-year-old woman with wet-AMD was treated with fourteen intravitreal injections of ranibizumab (0.5 mg) for a period of 40 months with intervals of 1–6 months. She initially showed a good visual and anatomical response to periodic anti-VEGF treatment but during check visits, anatomical and functional responses deteriorated. At the 40-month follow-up, the patient had developed Crohn's disease, and her rheumatologist started treatment with adalimumab (40 mg subcutaneously every 2 weeks). During the 25 months of treatment with adalimumab, the patient did not require any additional intravitreal anti-VEGF treatments because her BCVA, clinical, and OCT findings improved and remained stable. Conclusions We described a case of a patient with wet-AMD refractory to anti-VEGF therapy, which clinically benefited from subcutaneous adalimumab therapy. Treatment with subcutaneous anti-TNF-α in combination with anti-VEGF therapy avoids the high cost and risks related to multiple intravitreal anti-VEGF injections with good functional and anatomic outcomes. PMID:27065854

  18. Protolith age and deformation history of high grade metamorphic rocks from the roots of a continental magmatic arc: the Central Gneiss Complex, British Columbia, Canada

    NASA Astrophysics Data System (ADS)

    MacLeod, D.; Pearson, D. M.

    2014-12-01

    The Central Gneiss Complex, located in western British Columbia, preserves mid and lower crustal igneous and metasedimentary rocks that yield insight into deformational and thermal processes at the roots of a continental magmatic arc. The complex primarily consists of gneiss interpreted as a volcanic sequence with calcareous interlayers and lesser clastic metasedimentary rocks. Cretaceous U-Pb zircon ages from granulite-facies equivalent rocks in the core of the complex hint at rapid burial following deposition. However, a Permian or older crinoid fossil found in one locality (Hill, 1985) requires the presence of some late Paleozoic or early Mesozoic material. A new U-Pb zircon age (313±5 Ma; LA-ICPMS) from ~10 km west of this fossil locality is interpreted to record volcanism. We also conducted focused structural and geochronological analysis at higher structural levels in the northeastern Central Gneiss Complex to positively identify sedimentary lithologies with which to document the early structural history of the complex prior to early Cenozoic rapid exhumation. In this area, a subhorizontal shear zone forms the boundary between mainly clastic metasedimentary rocks and the widespread metavolcanic and carbonate rocks where an important stretched pebble conglomerate has been previously documented. In the footwall of the shear zone, flattening fabrics transition structurally upward into E-W trending stretching lineations, lineation-parallel isoclinal fold axes, and boudinage that record E-W stretching and major shear strain near the contact. S-C fabrics and shear bands yield a top to the east sense of shear. Where observed, a shallowly dipping, ~15 m thick zone of cataclasite forms the lithologic contact and overprints the shear zone. Sills and dikes record ongoing but localized magmatism throughout deformation and steep NE striking brittle normal faults crosscut all features. Ongoing work will further constrain the protolith age of these rocks, the timing of

  19. Latexin exhibits tumor-suppressor potential in pancreatic ductal adenocarcinoma

    PubMed Central

    XUE, ZHANXIONG; ZHOU, YUHUI; WANG, CHENG; ZHENG, JIHANG; ZHANG, PU; ZHOU, LINGLING; WU, LIANG; SHAN, YUNFENG; YE, MENGSI; HE, YUN; CAI, ZHENZHAI

    2016-01-01

    Recent studies suggest that latexin (Lxn) expression is involved in stem cell regulation and that it plays significant roles in tumor cell migration and invasion. The clinicopathological significance of Lxn expression and its possible correlation with CD133 expression in pancreatic ductal adenocarcinoma (PDAC) is currently unknown. In the present study, immunohistochemical analysis was performed to determine Lxn and CD133 expression in 43 PDAC patient samples and in 32 corresponding adjacent non-cancerous samples. The results were analyzed and compared with patient age, gender, tumor site and size, histological grade, clinical stage and overall mean survival time. Lxn expression was clearly decreased in the PDAC tissues compared with that in the adjacent non-cancerous tissues, while CD133 expression was increased. Low Lxn expression in the PDAC tissues was significantly correlated with tumor size (P=0.002), histological grade (P=0.000), metastasis (P=0.007) and clinical stage (P=0.018), but not with age (P=0.451), gender (P=0.395) or tumor site (P=0.697). Kaplan-Meier survival analysis revealed that low Lxn expression was significantly correlated with reduced overall survival time (P=0.000). Furthermore, Lxn expression was found to be inversely correlated with CD133 expression (r=−0.485, P=0.001). Furthermore, CD133-positive MIA PaCa-2 pancreatic tumor cells were sorted by magnetic-activated cell sorting (MACS), and those that overexpressed Lxn exhibited a significantly higher rate of apoptosis and lower proliferative activity. Our findings suggest that Lxn may function as a tumor suppressor that targets CD133-positive pancreatic cancer cells. PMID:26530530

  20. Long-Term Survival of Children Less than Six Years of Age Enrolled on the CCG-945 Phase III Trial for Newly-Diagnosed High-Grade Glioma: A Report from the Children’s Oncology Group

    PubMed Central

    Batra, V; Sands, S; Holmes, E; Geyer, JR; Yates, A; Becker, L; Burger, P; Gilles, F; Wisoff, J; Allen, J; Pollack, IF; Finlay, JL

    2015-01-01

    Background We analyzed the long-term survival of children under six years of age (<6 yo) enrolled upon the Children’s Cancer Group (CCG)-945 high-grade glioma (HGG) study to determine the impact of intrinsic biological characteristics as well as treatment upon both survival and quality of life (QOL) in this younger age population. Procedure Analyses were undertaken on patients <6 yo with institutionally diagnosed HGG enrolled on the CCG-945 trial. Comparisons of survival were performed for patients less than three years of age (<3 yo) (treated with intent to avoid irradiation) versus those between three to six years of age (3–6 yo) (treated with irradiation and chemotherapy) at diagnosis. Discordance between the institutional diagnoses of HGG and consensus-reviewed diagnoses led us to perform further survival analyses for both groups. We compared the two groups of patients for biological markers, and evaluated the neuropsychological and QOL outcomes of long-term survivors. Results Patients <3 yo (n=49,19.5% of all enrolled patients) at diagnosis had a 10-year EFS and OS of 29± 6.5% and 37.5 ± 7% respectively while for patients 3–6 yo (n=34,13.5% of all enrolled patients) 10-year EFS and OS were 35± 8% and 36 ± 8% respectively. Molecular marker analysis showed that a smaller proportion of patients <3 yo harbored TP53 mutations (p=0.05). Analysis of QOL outcomes with a median length of follow up of 15.1 years (9.5–19.2) showed comparable results. Conclusions QOL and survival data were similar for the two groups. A larger prospective study is justified to study the efficacy of chemotherapy only regimens in younger children. PMID:24038913

  1. The Harvard Southern California Chronic Ozone Exposure Study: assessing ozone exposure of grade-school-age children in two Southern California communities.

    PubMed Central

    Geyh, A S; Xue, J; Ozkaynak, H; Spengler, J D

    2000-01-01

    The Harvard Southern California Chronic Ozone Exposure Study measured personal exposure to, and indoor and outdoor ozone concentrations of, approximately 200 elementary school children 6-12 years of age for 12 months (June 1995-May 1996). We selected two Southern California communities, Upland and several towns located in the San Bernardino mountains, because certain characteristics of those communities were believed to affect personal exposures. On 6 consecutive days during each study month, participant homes were monitored for indoor and outdoor ozone concentrations, and participating children wore a small passive ozone sampler to measure personal exposure. During each sampling period, the children recorded time-location-activity information in a diary. Ambient ozone concentration data were obtained from air quality monitoring stations in the study areas. We present ozone concentration data for the ozone season (June-September 1995 and May 1996) and the nonozone season (October 1995-April 1996). During the ozone season, outdoor and indoor concentrations and personal exposure averaged 48.2, 11.8, and 18.8 ppb in Upland and 60.1, 21.4, and 25.4 ppb in the mountain towns, respectively. During the nonozone season, outdoor and indoor concentrations and personal exposure averaged 21.1, 3.2, and 6.2 ppb in Upland, and 35.7, 2.8, and 5.7 ppb in the mountain towns, respectively. Personal exposure differed by community and sex, but not by age group. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 PMID:10706534

  2. Developmental Changes in Cognitive Persistence and Academic Achievement between Grade 4 and Grade 8

    ERIC Educational Resources Information Center

    Jozsa, Krisztian; Morgan, George A.

    2014-01-01

    This study describes changes in cognitive persistence, a key measure of mastery motivation, between the ages of 10 (grade 4) and 14 (grade 8). Prior research in the field of mastery motivation has focused mainly on early childhood. No longitudinal research findings have been published about age changes in mastery motivation during the school…

  3. Pediatric Low Grade Ganglioglioma/Gangliocytoma: epidemiology, treatments, and outcome analysis on 348 children from the SEER database

    PubMed Central

    Dudley, Roy W.R.; Torok, Michelle R.; Gallegos, Danielle R.; Mulcahy-Levy, Jean M.; Hoffman, Lindsey M.; Liu, Arthur K.; Handler, Michael H.; Hankinson, Todd C.

    2014-01-01

    Background Low-grade gangliogliomas/gangliocytomas (GG) are rare tumors of the CNS, which occur mostly in young people. Due to their rarity, large-scale, population-based studies focusing on epidemiology and outcomes are lacking. Objective To use the Surveillance, Epidemiology, and End Results (SEER) datasets of the National Cancer Institute to study demographics, tumor location, initial treatment, and outcome data on low-grade GG in children. Methods SEER-STAT v8.1.2 identified all patients aged 0-19 years in the SEER datasets with low-grade GGs. Using the Kaplan-Meier method and Cox proportional hazard regression, we examined associations between these characteristics and survival. Results There were 348 children with low-grade GG diagnosed from 2004-2010, with a median follow-up of 37 months. Tumors were more prevalent in males (n=208, 59.8%) than females (n=140, 40.2%) (p<0.001). Almost 63% percent occurred in children >10 years, while only 3.5% were found in those <1 year old. Approximately 50% were located in the temporal lobes, while only 3.7% and 3.5% were located in the brainstem and spinal cord, respectively. Surgery was performed on 91.6% of cases, with gross total resection (GTR) achieved in 68.3%. Radiation was used in 3.2%. Young age (<1yrs) and brainstem location were associated with worse overall survival (OS). Conclusion This study shows that low-grade GG occur in older children with a male preference. GTR is achieved in the majority of cases, and radiation is rarely used. While the majority of patients have an excellent prognosis, infants and patients with brainstem tumors have worse survival rates. PMID:25603107

  4. Molecular subtypes of serous borderline ovarian tumor show distinct expression patterns of benign tumor and malignant tumor-associated signatures.

    PubMed

    Curry, Edward W J; Stronach, Euan A; Rama, Nona R; Wang, Yuepeng Y P; Gabra, Hani; El-Bahrawy, Mona A

    2014-03-01

    Borderline ovarian tumors show heterogeneity in clinical behavior. Most have excellent prognosis, although a small percentage show recurrence or progressive disease, usually to low-grade serous carcinoma. The aim of this study was to understand the molecular relationship between these entities and identify potential markers of tumor progression and therapeutic targets. We studied gene expression using Affymetrix HGU133plus2 GeneChip microarrays in 3 low-grade serous carcinomas, 13 serous borderline tumors and 8 serous cystadenomas. An independent data set of 18 serous borderline tumors and 3 low-grade serous carcinomas was used for validation. Unsupervised clustering revealed clear separation of benign and malignant tumors, whereas borderline tumors showed two distinct groups, one clustering with benign and the other with malignant tumors. The segregation into benign- and malignant-like borderline molecular subtypes was reproducible on applying the same analysis to an independent publicly available data set. We identified 50 genes that separate borderline tumors into their subgroups. Functional enrichment analysis of genes that separate borderline tumors to the two subgroups highlights a cell adhesion signature for the malignant-like subset, with Claudins particularly prominent. This is the first report of molecular subtypes of borderline tumors based on gene expression profiling. Our results provide the basis for identification of biomarkers for the malignant potential of borderline ovarian tumor and potential therapeutic targets for low-grade serous carcinoma. PMID:23948749

  5. Uncommon renal tumors in children: A single center experience

    PubMed Central

    Mandal, Kartik Chandra; Mukhopadhyay, Madhumita; Barman, Shibsankar; Halder, Pankaj; Mukhopadhyay, Biswanath; Kumar, Rajarshi

    2016-01-01

    Aims: Scrutiny over the clinical behaviors, management, and the final outcome of some rare renal neoplasm in order to find out some hidden facts about these tumors which are playing an important role in the disease course and its management. Materials and Methods: Retrospective evaluation of uncommon (non-Wilms’) renal neoplasm in the pediatric population in a tertiary care center. Fifteen cases of uncommon renal tumors were treated in our institution over the last 5 years (January 2008 to December 2012). The cases were tabulated in the form of age, sex, mode of presentation, preoperative investigations, intraoperative grading, pathological type, postoperative management and the final outcome. The patients were followed up for 2 years (clinically every 3 months and ultrasonography abdomen in every 6 months for first 2 years) in order to see any evidence of recurrence and complications related to postoperative chemotherapy. Results: Out of 15 cases, four cases were clear cell sarcoma (CCS) (26.6%), three cases were rhabdoid tumor (20%), three cases were congenital mesoblastic nephroma (20%), two cases were multilocular cystic nephroma (13.3%), two cases were renal teratoma (13.3%), and one case of teratoid Wilms’ tumor (6.6%). There were two deaths (one CCS and one rhabdoid tumor) due to chemotherapy-related toxicity but no recurrence. Three patients were lost during postoperative follow-up; ten patients are doing well and getting a regular visit in the follow-up clinic. Conclusion: The clinical presentations of these uncommon renal tumors are similar to that of Wilms’ tumor. Thus, preoperative diagnosis is difficult even with modern imaging techniques. Some of these tumors (CCS, rhabdoid tumor) are rapidly progressing and have a poor outcome. Hence, early intervention in the form of complete surgical resection of the tumor (whenever possible) and postoperative chemo/radiotherapy are imperative for fruitful outcome. PMID:27046976

  6. The influence of mammographic density on breast tumor characteristics.

    PubMed

    Eriksson, Louise; Czene, Kamila; Rosenberg, Lena; Humphreys, Keith; Hall, Per

    2012-07-01

    Mammographic density (MD) is a well-established risk factor for breast cancer. Whether MD influences the tumor phenotype remains to be clarified. Previous studies are highly inconsistent and most lack important covariate information. This is a case-only study within a population-based case-control study. Cases were all postmenopausal women, aged 50-74 years, with incident breast cancer, diagnosed 1993-1995, and with no history of previous cancer (n = 2,720). 1,747 women with mammograms and information on tumor characteristics were included in analyses. MD was assessed using a computer-assisted thresholding technique. We used linear, logistic, and multinomial logistic regression, adjusting for possible confounders, to study density and tumor characteristics. PD was only statistically significantly associated with tumor size in our study (regression coefficient 0.031, p = 0.017). The effect of PD on tumor size was greater when mode of detection was excluded from the model (regression coefficient 0.043, p = 0.001). No other associations between PD and the tumor characteristics studied (lymph node metastasis, ER-status, PR-status, grade, and histopathological classification) were observed. In summary, PD was positively associated with tumor size in postmenopausal women. However, the relationship was at least partially confounded by mode of detection. Although there may be a true biological relationship between MD and more highly proliferative tumors, it also seems that part of this relationship is due to masking delaying diagnosis. In conclusion, PD does not seem to be differentially associated with tumor phenotype, except for tumor size, after taking mode of detection into consideration. PMID:22710708

  7. Prognostic Molecular Subtypes of Low-Grade Cancer of the Appendix

    PubMed Central

    Levine, Edward A; Votanopoulos, Konstantinos I; Qasem, Shadi A; Philip, John; Cummins, Kathleen A; Chou, Jeff W; Ruiz, Jimmy; D’Agostino, Ralph; Shen, Perry; Miller, Lance D

    2016-01-01

    BACKGROUND Appendiceal cancer (AC) patients treated with cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) often demonstrate an unpredictable variability in their survival outcomes. Biomarkers predictive of CRS/HIPEC efficacy could better guide treatment decisions. We hypothesized that variation in the transcriptional programming of AC tumors might distinguish molecular subtypes with differential outcomes after CRS/HIPEC. STUDY DESIGN Gene expression profiles of 2 AC cohorts were analyzed using Affymetrix whole-genome expression microarrays. Hierarchical clustering methods, Kaplan-Meier analysis, and Cox regression models were used to discover and validate prognostic molecular subtypes of AC. Gene set enrichment analysis was used to infer pathologic attributes of the molecular subtypes. RESULTS Unsupervised hierarchical clustering analysis of tumor expression profiles revealed a 139-gene cassette that distinguished 2 molecular subtypes (based on low vs high expression of the gene cassette) with statistically significant survival differences (disease-specific survival, p = 0.0075; progression-free survival, p = 0.0072). In a second AC cohort, the 139-gene cassette reproducibly partitioned tumors into subtypes with significant survival differences. Tumors showing high relative expression of the genes comprising the cassette associated with poor survival outcomes (disease-specific survival, p = 0.047; progression-free survival, p = 0.0079), and exhibited gene expression patterns enriched for oncogenic processes and pathways. The prognostic value of the molecular subtypes was specific for low-grade appendiceal tumors (disease-specific survival, p = 0.028; progression-free survival, p = 0.0016), and remained significant in the presence of conventional prognostic markers, including grade, surgical resection score, Eastern Cooperative Oncology Group status, and age. CONCLUSIONS The 139-gene cassette can have actionable clinical utility for

  8. Fatal complications after stereotactic body radiation therapy for central lung tumors abutting the proximal bronchial tree

    PubMed Central

    Haseltine, Justin M.; Rimner, Andreas; Gelblum, Daphna Y.; Modh, Ankit; Rosenzweig, Kenneth E.; Jackson, Andrew; Yorke, Ellen D.; Wu, Abraham J.

    2016-01-01

    Purpose Stereotactic body radiation therapy (SBRT) is associated with excess toxicity following treatment of central lung tumors. Risk-adapted fractionation appears to have mitigated this risk, but it remains unclear whether SBRT is safe for all tumors within the central lung zone, especially those abutting the proximal bronchial tree (PBT). We investigated the dependence of toxicity on tumor proximity to PBT and whether tumors abutting the PBT had greater toxicity than other central lung tumors after SBRT. Materials and methods A total of 108 patients receiving SBRT for central lung tumors were reviewed. Patients were classified based on closest distance from tumor to PBT. Primary endpoint was SBRT-related death. Secondary endpoints were overall survival, local control, and grade 3+ pulmonary adverse events. We compared tumors abutting the PBT to nonabutting and those ≤1 cm and >1 cm from PBT. Results Median follow-up was 22.7 months. Median distance from tumor to PBT was 1.78 cm. Eighty-eight tumors were primary lung and 20 were recurrent or metastatic; 23% of tumors were adenocarcinoma and 71% squamous cell. Median age was 77.5 years. Median dose was 4500 cGy in 5 fractions prescribed to the 100% isodose line. Eighteen patients had tumors abutting the PBT, 4 of whom experienced SBRT-related death. No other patients experienced death attributed to SBRT. Risk of SBRT-related death was significantly higher for tumors abutting the PBT compared with nonabutting tumors (P < .001). Two patients with SBRT-related death received anti-vascular endothelial growth factor therapy and experienced pulmonary hemorrhage. Patients with tumors ≤1 cm from PBT had significantly more grade 3+ events than those with tumors >1cm from PBT (P = .014). Conclusions Even with risk-adapted fractionation, tumors abutting PBT are associated with a significant and differential risk of SBRT-related toxicity and death. SBRT should be used with particular caution in central-abutting tumors

  9. Transcriptional analysis of aggressiveness and heterogeneity across grades of astrocytomas.

    PubMed

    Wang, Chunjing; Funk, Cory C; Eddy, James A; Price, Nathan D

    2013-01-01

    Astrocytoma is the most common glioma, accounting for half of all primary brain and spinal cord tumors. Late detection and the aggressive nature of high-grade astrocytomas contribute to high mortality rates. Though many studies identify candidate biomarkers using high-throughput transcriptomic profiling to stratify grades and subtypes, few have resulted in clinically actionable results. This shortcoming can be attributed, in part, to pronounced lab effects that reduce signature robustness and varied individual gene expression among patients with the same tumor. We addressed these issues by uniformly preprocessing publicly available transcriptomic data, comprising 306 tumor samples from three astrocytoma grades (Grade 2, 3, and 4) and 30 non-tumor samples (normal brain as control tissues). Utilizing Differential Rank Conservation (DIRAC), a network-based classification approach, we examined the global and individual patterns of network regulation across tumor grades. Additionally, we applied gene-based approaches to identify genes whose expression changed consistently with increasing tumor grade and evaluated their robustness across multiple studies using statistical sampling. Applying DIRAC, we observed a global trend of greater network dysregulation with increasing tumor aggressiveness. Individual networks displaying greater differences in regulation between adjacent grades play well-known roles in calcium/PKC, EGF, and transcription signaling. Interestingly, many of the 90 individual genes found to monotonically increase or decrease with astrocytoma grade are implicated in cancer-affected processes such as calcium signaling, mitochondrial metabolism, and apoptosis. The fact that specific genes monotonically increase or decrease with increasing astrocytoma grade may reflect shared oncogenic mechanisms among phenotypically similar tumors. This work presents statistically significant results that enable better characterization of different human astrocytoma grades

  10. NKG2D-NKG2D Ligand Interaction Inhibits the Outgrowth of Naturally Arising Low-Grade B Cell Lymphoma In Vivo.

    PubMed

    Raju, Saravanan; Kretzmer, Lena Z; Koues, Olivia I; Payton, Jacqueline E; Oltz, Eugene M; Cashen, Amanda; Polic, Bojan; Schreiber, Robert D; Shaw, Andrey S; Markiewicz, Mary A

    2016-06-01

    It is now clear that recognition of nascent tumors by the immune system is critical for survival of the host against cancer. During cancer immunoediting, the ability of the tumor to escape immune recognition is important for tumor development. The immune system recognizes tumors via the presence of classical Ags and also by conserved innate mechanisms. One of these mechanisms is the NKG2D receptor that recognizes ligands whose expression is induced by cell transformation. In this study, we show that in NKG2D receptor-deficient mice, increasing numbers of B cells begin to express NKG2D ligands as they age. Their absence in wild-type mice suggests that these cells are normally cleared by NKG2D-expressing cells. NKG2D-deficient mice and mice constitutively expressing NKG2D ligands had increased incidence of B cell tumors, confirming that the inability to clear NKG2D ligand-expressing cells was important in tumor suppression and that NKG2D ligand expression is a marker of nascent tumors. Supporting a role for NKG2D ligand expression in controlling the progression of early-stage B cell lymphomas in humans, we found higher expression of a microRNA that inhibits human NKG2D ligand expression in tumor cells from high-grade compared with low-grade follicular lymphoma patients. PMID:27183590

  11. Grading More Accurately

    ERIC Educational Resources Information Center

    Rom, Mark Carl

    2011-01-01

    Grades matter. College grading systems, however, are often ad hoc and prone to mistakes. This essay focuses on one factor that contributes to high-quality grading systems: grading accuracy (or "efficiency"). I proceed in several steps. First, I discuss the elements of "efficient" (i.e., accurate) grading. Next, I present analytical results…

  12. Recursive partitioning analysis of prognostic variables in newly diagnosed anaplastic oligodendroglial tumors

    PubMed Central

    Panageas, Katherine S.; Reiner, Anne S.; Iwamoto, Fabio M.; Cloughesy, Timothy F.; Aldape, Kenneth D.; Rivera, Andreana L.; Eichler, April F.; Louis, David N.; Paleologos, Nina A.; Fisher, Barbara J.; Ashby, Lynn S.; Cairncross, J. Gregory; Roldán Urgoiti, Gloria B.; Wen, Patrick Y.; Ligon, Keith L.; Schiff, David; Robins, H. Ian; Rocque, Brandon G.; Chamberlain, Marc C.; Mason, Warren P.; Weaver, Susan A.; Green, Richard M.; Kamar, Francois G.; Abrey, Lauren E.; DeAngelis, Lisa M.; Jhanwar, Suresh C.; Rosenblum, Marc K.; Lassman, Andrew B.

    2014-01-01

    Background Anaplastic oligodendroglial tumors are rare, and median survival varies widely. Analysis of 1p19q deletion is performed commonly and is an important prognostic factor. However, age and other clinical variables also carry prognostic value, and it is unclear how to incorporate them into clinical decision making or to combine them for prognostication. Methods We compiled a retrospective database of 1013 patients with newly diagnosed anaplastic oligodendrogliomas or oligoastrocytomas and performed a recursive partitioning analysis to generate independent prognostic classes among 587 patients with informative 1p19q status. Variables included for survival classification were age (continuous), history of prior low-grade glioma, 1p19q deletion status, histology (presence or absence of an astrocytic component), tumor lobe, tumor hemisphere, gender, extent of resection, postresection treatment, and performance status at diagnosis. Results Recursive partitioning analysis identified 5 prognostic groups based on hazard similarity: class I (age <60 y, 1p19q codeleted), class II (age <43 y, not codeleted), class III (age 43–59 y, not codeleted, frontal lobe tumor or age ≥60 y, codeleted), class IV (age 43–59 y, not codeleted, not frontal lobe tumor or age 60–69 y, not codeleted), and class V (age ≥70 y, not codeleted). Survival differences were highly significant (P < .0001), with medians ranging from 9.3 years (95% CI: 8.4–16.0) for class I to 0.6 years (95% CI: 0.5–0.9) for class V. Conclusions These 5 distinct classification groups were defined using prognostic factors typically obtained during routine management of patients with anaplastic oligodendroglial tumors. Validation in a prospective clinical trial may better differentiate patients with respect to treatment outcome. PMID:24997140

  13. Social Studies Curriculum: Grade Six.

    ERIC Educational Resources Information Center

    Pease, Arthur

    This document outlines the content of the grade 6 social studies curriculum of the Lebanon School District, Lebanon, New Hampshire. The program is essentially a chronological review of western civilization, which includes pre-historic man, early civilization, classical civilizations of Greece and Rome, Medieval period, and the Age of Expansion.…

  14. Research Supporting Middle Grades Practice

    ERIC Educational Resources Information Center

    Hough, David L., Ed.

    2010-01-01

    Exemplary Middle Grades Research: Evidence-Based Studies Linking Theory to Practice features research published throughout 2009 in MGRJ that has been identified by the Information Age Publishing's review board as the most useful in terms of assisting educators with making practical applications from evidence-based studies to classroom and school…

  15. Electron-microprobe Th-U-Pb monazite dating in Early-Palaeozoic high-grade gneisses as a completion of U-Pb isotopic ages (Wilson Terrane, Antarctica)

    NASA Astrophysics Data System (ADS)

    Schulz, B.; Schüssler, U.

    2013-08-01

    The electron microprobe (EMP) Th-U-Pb monazite bulk chemical dating method was applied to granulite-facies rocks of the Wilson Terrane in Antarctica. A combination of this method to isotopic U-Pb-SHRIMP ages for the evaluation of metamorphic processes required the analysis of reference monazites. These can be subdivided into three groups: a) Monazite with variable total Pb at constant Th (e.g. VK-1) is unsuitable for EMP data evaluation; b) Monazite with highly variable total Pb and Th, but with at least some Th/Pb approximating an apparent isochrone (e.g. MPN) is partly useful; and c) Monazite with constant Th/Pb at high Th (e.g. Madmon monazite) is best suitable for the combined approach and can be additionally used to improve the Th calibration for EMP. Study of monazite in grain mounts and in thin sections led to partly different but complementary results: Older monazites with EMP ages up to 680 Ma occur mainly in a grain mount from diatexite and metatexite and are interpreted as detrital relics. Some of these monazites show structures and mineral-chemical zonation trends resembling metasomatism by alkali-bearing fluids. A marked mobility of Th, P, Ce, Si and U is observed. The age of the metasomatic event can be bracketed between 510 and 450 Ma. Furthermore, in the grain mount and in numerous petrographic thin sections of migmatites and gneisses, the EMP Th-U-Pb and SHRIMP U-Pb monazite data uniformly signal a major metamorphic event with a medium-pressure granulite facies peak between 512 and 496 Ma. Subsequent isothermal uplift and then amphibolite-facies conditions between 488 and 466 Ma led to crystallisation of pristine monazite. The high-grade metamorphic event, related to the Ross Orogeny, can be uniformly traced more than 600 km along strike in the Wilson Terrane.

  16. Patient-derived xenograft (PDX) tumors increase growth rate with time

    PubMed Central

    Pearson, Alexander T.; Finkel, Kelsey A.; Warner, Kristy A.; Nör, Felipe; Tice, David; Martins, Manoela D.; Jackson, Trachette L.; Nör, Jacques E.

    2016-01-01

    Patient-derived xenograft (PDX) models are frequently used for translational cancer research, and are assumed to behave consistently as the tumor ages. However, growth rate constancy as a function of time is unclear. Notably, variable PDX growth rates over time might have implications for the interpretation of translational studies. We characterized four PDX models through several in vivo passages from primary human head and neck squamous cell carcinoma and salivary gland adenoid cystic carcinoma. We developed a mathematical approach to merge growth data from different passages into a single measure of relative tumor volume normalized to study initiation size. We analyzed log-relative tumor volume increase with linear mixed effect models. Two oral pathologists analyzed the PDX tissues to determine if histopathological feature changes occurred over in vivo passages. Tumor growth rate increased over time. This was determined by repeated measures linear regression statistical analysis in four different PDX models. A quadratic statistical model for the temporal effect predicted the log-relative tumor volume significantly better than a linear time effect model. We found a significant correlation between passage number and histopathological features of higher tumor grade. Our mathematical treatment of PDX data allows statistical analysis of tumor growth data over long periods of time, including over multiple passages. Non-linear tumor growth in our regression models revealed the exponential growth rate increased over time. The dynamic tumor growth rates correlated with quantifiable histopathological changes that related to passage number in multiple types of cancer. PMID:26783960

  17. The K-Ras 4A isoform promotes apoptosis but does not affect either lifespan or spontaneous tumor incidence in aging mice

    SciTech Connect

    Plowman, Sarah J.; Arends, Mark J.; Brownstein, David G.; Luo Feijun; Devenney, Paul S.; Rose, Lorraine; Ritchie, Ann-Marie; Berry, Rachel L.; Harrison, David J.; Hooper, Martin L.; Patek, Charles E. . E-mail: Charles.Patek@ed.ac.uk

    2006-01-01

    Ras proteins function as molecular switches in signal transduction pathways, and, here, we examined the effects of the K-ras4A and 4B splice variants on cell function by comparing wild-type embryonic stem (ES) cells with K-ras {sup tm{delta}}{sup 4A/tm{delta}}{sup 4A} (exon 4A knock-out) ES cells which express K-ras4B only and K-ras {sup -/-} (exons 1-3 knock-out) ES cells which express neither splice variant, and intestinal epithelium from wild-type and K-ras {sup tm{delta}}{sup 4A/tm{delta}}{sup 4A} mice. RT-qPCR analysis found that K-ras4B expression was reduced in K-ras {sup tm{delta}}{sup 4A/tm{delta}}{sup 4A} ES cells but unaffected in small intestine. K-Ras deficiency did not affect ES cell growth, and K-Ras4A deficiency did not affect intestinal epithelial proliferation. K-ras {sup tm{delta}}{sup 4A/tm{delta}}{sup 4A} and K-ras {sup -/-} ES cells showed a reduced capacity for differentiation following LIF withdrawal, and K-ras {sup -/-} cells were least differentiated. K-Ras4A deficiency inhibited etoposide-induced apoptosis in ES cells and intestinal epithelial cells. However, K-ras {sup tm{delta}}{sup 4A/tm{delta}}{sup 4A} ES cells were more resistant to etoposide-induced apoptosis than K-ras {sup -/-} cells. The results indicate that (1) K-Ras4A promotes apoptosis while K-Ras4B inhibits it, and (2) K-Ras4B, and possibly K-Ras4A, promotes differentiation. The findings raise the possibility that alteration of the K-Ras4A/4B isoform ratio modulates tumorigenesis by differentially affecting stem cell survival and/or differentiation. However, K-Ras4A deficiency did not affect life expectancy or spontaneous overall tumor incidence in aging mice.

  18. Tumor-derived CCL-2 and CXCL-8 as possible prognostic markers of breast cancer: correlation with estrogen and progestrone receptor phenotyping.

    PubMed

    Ghoneim, H M; Maher, Sara; Abdel-Aty, Asmaa; Saad, A; Kazem, A; Demian, S R

    2009-01-01

    Prognosis of breast cancer is believed to be a multifactorial process best achieved by complex factors including host and tumor-derived biomarkers together with traditional clinicopathological parameters and tumor histologic markers. The present study aimed at evaluating the prognostic significance of chemokine ligand-2 (CCL-2) and interleukin-8 (CXCL-8) expression in extracts of breast carcinomas through correlation with clinicopathological aspects as well as estrogen receptor (ER) and progesterone receptor (PR) phenotyping. The study was conducted on 30 Egyptian breast cancer patients diagnosed by fine needle aspiration cytology (FNAC) and subjected to modified radical mastectomy. Excised tissues were used to prepare tissue sections and extracts for histopathological and immunohistochemical studies. Expression of CCL-2 and CXCL-8 was determined by enzyme-linked immunosorbent assay (ELISA). 26 patients had invasive ductal carcinoma, grades II and III with metastasis to axillary lymph nodes and ER and PR positive phenotype. Expression of CCL-2 and CXCL-8 was significantly influenced by patient's age, menopausal status, nodal involvement, tumor grade and the ER phenotype. In contrast, it was not affected by either tumor size or PR staining pattern. Both chemokines correlated positively to each other and to tumor grade and negatively to age, menopausal status of patients and ER phenotyping. It is concluded that the angiogenic chemokine CXCL-8 and the macrophage chemoattractant CCL-2 might be useful prognostic markers where their routine follow up might be of importance in assessment of tumor aggressiveness in clinical settings. PMID:22059352

  19. Music. Grade 13. Curriculum S.16.

    ERIC Educational Resources Information Center

    Ontario Dept. of Education, Toronto.

    GRADES OR AGES: Grade 13. SUBJECT MATTER: Music. ORGANIZATION AND PHYSICAL APPEARANCE: The central portion of the guide is divided into six units: voice, strings, woodwinds, brass, percussion, and theory and form. Each unit is in list form. The guide is offset printed and staple-bound with a paper cover. OBJECTIVES AND ACTIVITIES: A list of…

  20. American History and Government. Grade 11.

    ERIC Educational Resources Information Center

    Teeney, Abe D.; Nupen, Walter A.

    GRADES OR AGES: Grade 11. SUBJECT MATTER: American history and government. ORGANIZATION AND PHYSICAL APPEARANCE: The introductory material outlines the philosophy and the scope and sequence for the whole social studies program. The main body of the guide has seven sections (colonial years, federalism and expanding democracy, civil war and…

  1. Spinal tumor

    MedlinePlus

    Tumor - spinal cord ... spinal tumors occur in the nerves of the spinal cord itself. Most often these are ependymomas and other ... gene mutations. Spinal tumors can occur: Inside the spinal cord (intramedullary) In the membranes (meninges) covering the spinal ...

  2. Temozolomide and O6-Benzylguanine in Treating Children With Recurrent Brain Tumors

    ClinicalTrials.gov

    2013-09-27

    Childhood Central Nervous System Germ Cell Tumor; Childhood Choroid Plexus Tumor; Childhood Craniopharyngioma; Childhood Ependymoblastoma; Childhood Grade I Meningioma; Childhood Grade II Meningioma; Childhood Grade III Meningioma; Childhood High-grade Cerebellar Astrocytoma; Childhood High-grade Cerebral Astrocytoma; Childhood Infratentorial Ependymoma; Childhood Low-grade Cerebellar Astrocytoma; Childhood Low-grade Cerebral Astrocytoma; Childhood Medulloepithelioma; Childhood Mixed Glioma; Childhood Oligodendroglioma; Childhood Supratentorial Ependymoma; Recurrent Childhood Brain Stem Glioma; Recurrent Childhood Cerebellar Astrocytoma; Recurrent Childhood Cerebral Astrocytoma; Recurrent Childhood Ependymoma; Recurrent Childhood Medulloblastoma; Recurrent Childhood Pineoblastoma; Recurrent Childhood Subependymal Giant Cell Astrocytoma; Recurrent Childhood Supratentorial Primitive Neuroectodermal Tumor; Recurrent Childhood Visual Pathway and Hypothalamic Glioma

  3. The life and times of low-grade serous carcinoma of the ovary.

    PubMed

    Gershenson, David M

    2013-01-01

    For the past several years, all women with epithelial ovarian cancer have been treated identically, whether in a clinical trial or off protocol. Over the past decade, we have come to appreciate the magnitude of the heterogeneity of ovarian cancer. The development of the binary grading system for serous carcinoma was a major advance, leading to separate clinical trials for patients with this subtype, originating from the Gynecologic Oncology Group's Rare Tumor Committee. The mitogen-activated protein kinase (MAPK) pathway appears to play a prominent role in the pathogenesis of this subtype. Approximately 20% to 40% of low-grade serous carcinomas have a KRAS mutation, while BRAF mutations are rare-approximately 5%. In genomic profiling studies, these tumors appear to cluster with serous tumors of low malignant potential. Compared with high-grade serous carcinomas, low-grade serous carcinomas are also characterized by a low frequency of p53 mutations, greater expression of ER and PR, and greater expression of PAX2 and IGF-1. Primary treatment of low-grade serous carcinoma includes surgery plus platinum-based chemotherapy (either adjuvant or neoadjuvant). Clinical behavior is characterized by young age at diagnosis, relative chemoresistance, and prolonged overall survival. Current options for treatment of relapsed disease include secondary cytoreduction in selected patients, salvage chemotherapy, or hormone therapy. A recently completed trial of a MEK inhibitor for women with recurrent disease demonstrated promising activity. Future directions will include further investigations of the molecular biology and biomarker-driven clinical trials with targeted agent monotherapy and combinations. PMID:23714500

  4. Tumor markers of bladder cancer: the schistosomal bladder tumors versus non-schistosomal bladder tumors

    PubMed Central

    Abdulamir, Ahmed S; Hafidh, Rand R; Kadhim, Haider S; Abubakar, Fatimah

    2009-01-01

    Background The aim of this study is to comparatively elucidate the underlying molecular pathways and clinicopathological criteria in schistosomal bladder tumor (SBT) versus non-schistosomal bladder tumor (NSBT). Methods This study explored the role of p53, p16, bcl-2, ki-67, c-myc, Rb and EGFR, by using Immunohistochemistry assay, in 45 SBT and 39 NSBT patients in comparison with 16 schistosomal chronic cystitis (SC), 28 non-schistosomal chronic cystitis (NSC), and 20 normal control (CTL) subjects. The studied markers in SBT and NSBT were correlated with different clinicopathological criteria namely, tumor histopathology, grading, invasiveness, stage, and presentation of the disease. Results SBT was associated with high grade invasive squamous cell carcinoma (SCC) while NSBT was associated with lower grade less invasive transitional cell carcinoma (TCC). The expression of p53, bcl-2, c-myc, and EGFR was higher in SBT than in NSBT while Rb was higher in NSBT than in SBT. However, p16 and ki-67 were not different between SBT and NSBT. The profile of molecular markers in SC was similar to NSC except for EGFR which was higher in SC than in NSC. Both SC and NSC showed higher level of p53, bcl-2, ki-67, and EGFR than in CTL group while p16, Rb, and c-myc were not different. p53 was associated with high grade SCC in both SBT and NSBT. Bcl-2 was associated with high grade invasive tumors in SBT and NSBT. P16 was associated with low grade, late stage, and recurrent SBT and high grade, invasive, late stage, and recurrent NSBT. Rb was associated with SCC in SBT, invasive tumors in NSBT, and late stage and recurrent presentation in both SBT and NSBT. C-myc was associated with high grade, invasive, and late stage SBT and SCC, high grade, invasive, and late stage NSBT. EGFR was associated with invasive SCC in SBT and invasive, high grade, and late stage TCC in NSBT. ki-67 was associated with invasive SBT and high grade late stage NSBT. Conclusion SBT and NSBT showed distinct

  5. Proton Beam Radiation Therapy in Treating Patients With Low Grade Gliomas

    ClinicalTrials.gov

    2015-12-14

    Adult Brain Tumor; Adult Brain Stem Glioma; Adult Diffuse Astrocytoma; Adult Ependymoma; Adult Grade II Meningioma; Adult Melanocytic Lesion; Adult Meningeal Hemangiopericytoma; Adult Mixed Glioma; Adult Oligodendroglioma; Adult Pineal Gland Astrocytoma; Adult Pineocytoma; Recurrent Adult Brain Tumor

  6. Proinflammatory cytokines, aging, and age-related diseases.

    PubMed

    Michaud, Martin; Balardy, Laurent; Moulis, Guillaume; Gaudin, Clement; Peyrot, Caroline; Vellas, Bruno; Cesari, Matteo; Nourhashemi, Fati

    2013-12-01

    Inflammation is a physiological process that repairs tissues in response to endogenous or exogenous aggressions. Nevertheless, a chronic state of inflammation may have detrimental consequences. Aging is associated with increased levels of circulating cytokines and proinflammatory markers. Aged-related changes in the immune system, known as immunosenescence, and increased secretion of cytokines by adipose tissue, represent the major causes of chronic inflammation. This phenomenon is known as "inflamm-aging." High levels of interleukin (IL)-6, IL-1, tumor necrosis factor-α, and C-reactive protein are associated in the older subject with increased risk of morbidity and mortality. In particular, cohort studies have indicated TNF-α and IL-6 levels as markers of frailty. The low-grade inflammation characterizing the aging process notably concurs at the pathophysiological mechanisms underlying sarcopenia. In addition, proinflammatory cytokines (through a variety of mechanisms, such as platelet activation and endothelial activation) may play a major role in the risk of cardiovascular events. Dysregulation of the inflammatory pathway may also affect the central nervous system and be involved in the pathophysiological mechanisms of neurodegenerative disorders (eg, Alzheimer disease).The aim of the present review was to summarize different targets of the activity of proinflammatory cytokines implicated in the risk of pathological aging. PMID:23792036

  7. [Classification and natural history of bladder tumors].

    PubMed

    Allory, Yves

    2014-12-01

    Urinary bladder tumors are mainly of urothelial type. Classifications include stage and grade to provide with the required prognostic factors and help to select the most adequate treatment. Though somatic mutations in bladder tumors are known, their used for targeted therapy are restricted to clinical trials. Upper urinary tract tumors are classified as urinary bladder tumor at histological level, but tumor staging is specified according to calyx, renal pelvis or ureter location; in young patients with upper urinary tract tumor, a Lynch syndrome should be eliminated. PMID:25668829

  8. Astroblastoma: beside being a tumor entity, an occasional phenotype of astrocytic gliomas?

    PubMed Central

    Mellai, Marta; Piazzi, Angela; Casalone, Cristina; Grifoni, Silvia; Melcarne, Antonio; Annovazzi, Laura; Cassoni, Paola; Denysenko, Tetyana; Valentini, Maria Consuelo; Cistaro, Angelina; Schiffer, Davide

    2015-01-01

    The diagnosis of astroblastoma is based on a typical histological aspect with perivascular distribution of cells sending cytoplasmic extensions to the vessels and vascular hyalinization. These criteria are useful for standardizing the identification of the tumor, but, in spite of this, there are discrepancies in the literature concerning the age distribution and the benign or malignant nature of the tumor. Three cases are discussed in this study: Case 1 was a typical high-grade astroblastoma; Case 2 was an oligodendroglioma at the first intervention and an oligoastrocytoma at the second intervention with typical perivascular arrangements in the astrocytic component; Case 3 was a gemistocytic glioma with malignant features and typical perivascular arrangements. Genetic analysis showed genetic alterations that are typical of gliomas of all malignancy grades. Using the neurosphere assay, neurospheres and adherent cells were found to have developed in Case 1, while adherent cells only developed in Case 2, in line with the stemness potential of the tumors. The cases are discussed in relation to their diagnostic assessment as astroblastoma, and it is hypothesized that the typical perivascular distribution of cells may not indicate a separate and unique tumor entity, but may be a peculiarity that can be acquired by astrocytic gliomas when an unknown cause from the tumor microenvironment influences the relationship between vessels and tumor cells. PMID:25737639

  9. Neural precursor cells induce cell death of high-grade astrocytomas through stimulation of TRPV1.

    PubMed

    Stock, Kristin; Kumar, Jitender; Synowitz, Michael; Petrosino, Stefania; Imperatore, Roberta; Smith, Ewan St J; Wend, Peter; Purfürst, Bettina; Nuber, Ulrike A; Gurok, Ulf; Matyash, Vitali; Wälzlein, Joo-Hee; Chirasani, Sridhar R; Dittmar, Gunnar; Cravatt, Benjamin F; Momma, Stefan; Lewin, Gary R; Ligresti, Alessia; De Petrocellis, Luciano; Cristino, Luigia; Di Marzo, Vincenzo; Kettenmann, Helmut; Glass, Rainer

    2012-08-01

    Primary astrocytomas of grade 3 or 4 according to the classification system of the World Health Organization (high-grade astrocytomas or HGAs) are preponderant among adults and are almost invariably fatal despite the use of multimodal therapy. Here we show that the juvenile brain has an endogenous defense mechanism against HGAs. Neural precursor cells (NPCs) migrate to HGAs, reduce glioma expansion and prolong survival time by releasing endovanilloids that activate the vanilloid receptor (transient receptor potential vanilloid subfamily member-1 or TRPV1) on HGA cells. TRPV1 is highly expressed in tumor and weakly expressed in tumor-free brain. TRPV1 stimulation triggers tumor cell death through the branch of the endoplasmic reticulum stress pathway that is controlled by activating transcription factor-3 (ATF3). The antitumorigenic response of NPCs is lost with aging. NPC-mediated tumor suppression can be mimicked in the adult brain by systemic administration of the synthetic vanilloid arvanil, suggesting that TRPV1 agonists have potential as new HGA therapeutics. PMID:22820645

  10. Extragastrointestinal stromal tumors: Computed tomography and magnetic resonance imaging findings

    PubMed Central

    ZHU, JINGQI; YANG, ZHANGWEI; TANG, GUANGYU; WANG, ZHONGQIU

    2015-01-01

    Extragastrointestinal stromal tumors (EGISTs) are rare mesenchymal tumors that originate outside the gastrointestinal tract. The aim of the present study was to investigate the computed tomography (CT) and magnetic resonance imaging (MRI) features of EGISTs and analyze the correlations between radiological findings and pathological features. CT and MRI images of 24 patients with EGISTs were reviewed retrospectively. Patient demographics and tumor characteristics, including localization, size, contours, borders, cystic-necrotic components, calcification, hemorrhage, tumor vessels, attenuation and intensity, degree and pattern of enhancement, ascites, tumor invasion, lymphadenopathy and distant metastasis were recorded. Statistical analyses to compare the radiological characteristics of low- and high-grade EGISTs were performed with χ2 or Fisher’s exact tests. The mean patient age at the time of presentation was 53 years. A total of 24 EGISTs were detected, originating in the omentum (n=4), mesentery (n=19) and retroperitoneum (n=1), respectively. The EGISTs displayed a predominantly spindle cell subtype (87.5%; 21/24). The majority of the EGISTs appeared as large (>10 cm; 70.8%; 17/24), round or oval (66.7%; 16/24), cystic-solid (87.5%; 21/24) and ill-defined (66.7%; 16/24) soft-tissue masses. The EGISTs were hypodense (69.6%; 16/23) or isodense (30.4%; 7/23) on CT images, hypointense (50%; 3/6), isointense (33.3%; 2/6) or hyperintense (16.7%; 1/6) on T1-weighted imaging (T1WI), and hyperintense on T2WI (100%; 6/6) and diffusion-WI (DWI; 100%; 6/6). A total of 54.2% (13/24) of the EGISTs displayed tumor vessels. Overall, 95.8% (23/24) of the masses showed marked enhancement and 87.5% (21/24) demonstrated heterogeneous enhancement. Calcification, hemorrhage, ascites and lymphadenopathy were rare characteristics in the EGISTs. Distant metastases were present in 10 patients (41.7%). The size, borders, tumor vessels and distant metastasis correlated with high-grade

  11. Mutations in chromatin machinery and pediatric high-grade glioma

    PubMed Central

    Lulla, Rishi R.; Saratsis, Amanda Muhs; Hashizume, Rintaro

    2016-01-01

    Pediatric central nervous system tumors are the most common solid tumor of childhood. Of these, approximately one-third are gliomas that exhibit diverse biological behaviors in the unique context of the developing nervous system. Although low-grade gliomas predominate and have favorable outcomes, up to 20% of pediatric gliomas are high-grade. These tumors are a major contributor to cancer-related morbidity and mortality in infants, children, and adolescents, with long-term survival rates of only 10 to 15%. The recent discovery of somatic oncogenic mutations affecting chromatin regulation in pediatric high-grade glioma has markedly improved our understanding of disease pathogenesis, and these findings have stimulated the development of novel therapeutic approaches targeting epigenetic regulators for disease treatment. We review the current perspective on pediatric high-grade glioma genetics and epigenetics, and discuss the emerging and experimental therapeutics targeting the unique molecular abnormalities present in these deadly childhood brain tumors. PMID:27034984

  12. Mutations in chromatin machinery and pediatric high-grade glioma.

    PubMed

    Lulla, Rishi R; Saratsis, Amanda Muhs; Hashizume, Rintaro

    2016-03-01

    Pediatric central nervous system tumors are the most common solid tumor of childhood. Of these, approximately one-third are gliomas that exhibit diverse biological behaviors in the unique context of the developing nervous system. Although low-grade gliomas predominate and have favorable outcomes, up to 20% of pediatric gliomas are high-grade. These tumors are a major contributor to cancer-related morbidity and mortality in infants, children, and adolescents, with long-term survival rates of only 10 to 15%. The recent discovery of somatic oncogenic mutations affecting chromatin regulation in pediatric high-grade glioma has markedly improved our understanding of disease pathogenesis, and these findings have stimulated the development of novel therapeutic approaches targeting epigenetic regulators for disease treatment. We review the current perspective on pediatric high-grade glioma genetics and epigenetics, and discuss the emerging and experimental therapeutics targeting the unique molecular abnormalities present in these deadly childhood brain tumors. PMID:27034984

  13. Visual analysis of longitudinal brain tumor perfusion

    NASA Astrophysics Data System (ADS)

    Glaßer, Sylvia; Oeltze, Steffen; Preim, Uta; Bjørnerud, Atle; Hauser, Helwig; Preim, Bernhard

    2013-02-01

    In clinical research on diagnosis and evaluation of brain tumors, longitudinal perfusion MRI studies are acquired for tumor grading as well as to monitor and assess treatment response and patient prognosis. Within this work, we demonstrate how visual analysis techniques can be adapted to multidimensional datasets from such studies within a framework to support the computer-aided diagnosis of brain tumors. Our solution builds on two innovations: First, we introduce a pipeline yielding comparative, co-registered quantitative perfusion parameter maps over all time steps of the longitudinal study. Second, based on these time-dependent parameter maps, visual analysis methods were developed and adapted to reveal valuable insight into tumor progression, especially regarding the clinical research area of low grade glioma transformation into high grade gliomas. Our examination of four longitudinal brain studies demonstrates the suitability of the presented visual analysis methods and comprises new possibilities for the clinical researcher to characterize the development of low grade gliomas.

  14. The relationship of p53 protein in meninigioma grading and their various influencing factors amongst neurosurgical patients in Hospital Kuala Lumpur.

    PubMed

    Kantha, R; Saffari, H M; Suryati, M Y

    2007-08-01

    Meningioma, is the second most frequent intracranial tumor in Malaysia and are classified according to the World Health Organization classification. The relationship of p53 protein in the determination of meningioma grading and their influencing factors were studied via immunohistochemistry studies on 77 intracranial meningiomas (67 benign, 10 atypical). The higher the p53 reaction was correlated to the poorer the histological grade (19.4% in benign and 90% in atypical meningioma) (p < 0.001). Other variables like age, sex, ethnicity, demographic location, surgical clearance, midline shift and contrast enhancement of CT Scan Brain and clinical features were found not to be significant. PMID:18246905

  15. Quantitative Evaluation of Diffusion and Dynamic Contrast-Enhanced MR in Tumor Parenchyma and Peritumoral Area for Distinction of Brain Tumors

    PubMed Central

    Zhao, Jing; Yang, Zhi-yun; Luo, Bo-ning; Yang, Jian-yong; Chu, Jian-ping

    2015-01-01

    Purpose To quantitatively evaluate the diagnostic efficiency of parameters from diffusion and dynamic contrast-enhanced MR which based on tumor parenchyma (TP) and peritumoral (PT) area in classification of brain tumors. Methods 45 patients (male: 23, female: 22; mean age: 46 y) were prospectively recruited and they underwent conventional, DCE-MR and DWI examination. With each tumor, 10–15 regions of interest (ROIs) were manually placed on TP and PT area. ADC and permeability parameters (Ktrans, Ve, Kep and iAUC) were calculated and their diagnostic efficiency was assessed. Results In TP, all permeability parameters and ADC value could significantly discriminate Low- from High grade gliomas (HGG) (p<0.001); among theses parameters, Ve demonstrated the highest diagnostic power (iAUC: 0.79, cut-off point: 0.15); the most sensitive and specific index for gliomas grading were Ktrans (84%) and Kep (89%). While, in PT area, only Ktrans could help in gliomas grading (P = 0.009, cut-off point: 0.03 min-1). Moreover, in TP, mean Ve and iAUC of primary central nervous system lymphoma (PCNSL) and metastases were significantly higher than that in HGG (p<0.003). Further, in PT area, mean Ktrans (p≤0.004) could discriminate PCNSL from HGG and ADC (p≤0.003) could differentiate metastases with HGG. Conclusions Quantitative ADC and permeability parameters from Diffusion and DCE-MR in TP and PT area, especially DCE-MR, can aid in gliomas grading and brain tumors discrimination. Their combined application is strongly recommended in the differential diagnosis of these tumor entities. PMID:26384329

  16. [A new WHO classification of prostate tumors].

    PubMed

    Frank, G A; Andreeva, Yu Yu; Moskvina, L V; Efremov, G D; Samoilova, S I

    2016-01-01

    The paper reviews the 2016 WHO classification of prostate tumors, notes the alterations made, and describes approaches to the diagnosis of cancer types and grades. It also gives original photomicrographs from the authors' collection. The main alterations were as follows: - The types of prostate adenocarcinoma were added by pleomorphic giant-cell carcinoma; oncocytic (8290/3) and lymphoepithelial (8082/3) carcinomas were excluded. - Grade III prostatic intraepithelial neoplasia (PIN) was substituted for high grade PIN (8148/2). - Intraductal carcinoma (8500/2) was added. - Basal cell adenoma (8147/0) was excluded. - Carcinoids were referred to as low-grade neuroendocrine tumors according to the current terminology; large cell neuroendocrine cancer (8013/3) was added. - Paraganglioma (8613/3) and neuroblastoma (9500/3) were excluded. Stromal tumors were grouped with mesenchymal neoplasms. -Malignant fibrous histiocytoma, malignant peripheral nerve sheath tumor, chondroma, and hemangiopericytoma were excluded. - Synovial sarcoma (9040/3), inflammatory myofibroblastic tumor (8825/1), osteosarcoma (9180/3), undifferentiated pleomorphic sarcoma (8802/3), solitary fibrous tumor (8815/1), and malignant solitary fibrous tumor (8815/3) were added. The section of lymphoproliferative diseases was extended. The tumors of unknown origin included paraganglioma and neuroblastoma from a group of neuroendocrine tumors. The TNM staging was completely consistent with the 2010 AJCC version. PMID:27600780

  17. Prognostic Implication of Preoperative Behavior Changes in Patients with Primary High-Grade Meningiomas

    PubMed Central

    2014-01-01

    High-grade meningiomas are rare extra-axial tumors, frequently causing brain invasion and prominent brain edema. Patients harboring high-grade meningiomas occasionally present with behavior changes. Data about frequency and prognostic importance of preoperative behavior changes in patients with high-grade meningiomas is missing. 86 patients with primary high-grade meningiomas were analyzed. Statistical analysis was performed to determine correlation of preoperative behavior changes with tumor location, preoperative brain edema, tumor cleavability, tumor grade, Ki67 proliferation index, and microscopic brain invasion. Survival analysis was performed. 30 (34.9%) patients presented with preoperative behavior changes. These changes were more frequent with male patients (P = 0.066) and patients older than 55 years (P = 0.018). They correlated with frontal location (P = 0.013), tumor size (P = 0.023), microscopic brain invasion (P = 0.015), and brain edema (P = 0.006). Preoperative behavior changes did not correlate with duration of symptoms, tumor cleavability, tumor malignancy grade, and Ki67 proliferation index. They were not significantly related to overall survival or recurrence-free survival of patients with primary high-grade meningiomas. Preoperative behavior changes are frequent in patients harboring primary high-grade meningiomas. They correlate with tumor size, microscopic brain invasion, and brain edema. Preoperative behavior changes do not predict prognosis in patients with primary high-grade meningiomas. PMID:24578632

  18. Asterisk Grade Study Report.

    ERIC Educational Resources Information Center

    Kokorsky, Eileen A.

    A study was conducted at Passaic County Community College (PCCC) to investigate the operation of a grading system which utilized an asterisk (*) grade to indicate progress in a course until a letter grade was assigned. The study sought to determine the persistence of students receiving the "*" grade, the incidence of cases of students receiving…

  19. Grading. Research Brief

    ERIC Educational Resources Information Center

    Walker, Karen

    2006-01-01

    What do grades mean? Is there a commonly understood and acceptable definition for what a grade stands? The current grading system is approximately 100 years old. In the 1700s, students were given feedback but not grades. In 1780, Yale University began using a 4.0 system that is similar to the current system. In the 1830s, Harvard University…

  20. Plus and Minus Grading.

    ERIC Educational Resources Information Center

    Farland, Ronnald; Cepeda, Rita

    The current official policy of the California community colleges on grading prohibits the use of plus and minus symbols to modify a standard letter grade. Plus and minus grades may influence a student's grade point average (GPA) either through statistical effects or psychological effects on teachers and students. At its fall 1985 session, and…

  1. Overexpression of Eg5 correlates with high grade astrocytic neoplasm.

    PubMed

    Liu, Liqiong; Liu, Xichun; Mare, Marcus; Dumont, Aaron S; Zhang, Haitao; Yan, Dong; Xiong, Zhenggang

    2016-01-01

    To investigate the relationship between Eg5 and histopathological grade of astrocytoma, Eg5 expression was evaluated by immunohistochemical examination on 88 specimens including 25 cases of glioblastoma (WHO grade IV), 22 cases of anaplastic astrocytoma (WHO grade III), 20 cases of diffuse astrocytoma (WHO grade II), and 21 cases of pilocytic astrocytoma (WHO grade I). The histopathological characteristics and Eg5 expression level of each tumor were assessed and statistically analyzed. Astrocytic tumors exhibited significant correlation of expression of Eg5 with higher WHO histopathological grades (p < 0.001). Eg5 is expressed in 51-98% (mean 76.88%) of neoplastic cells in glioblastoma, 34-57% (mean 43.59%) of neoplastic cells in anaplastic astrocytoma, 6-36% (mean 18.60%) of neoplastic cells in diffuse astrocytoma, and 2-28% (mean 13.48%) of neoplastic cells in pilocytic astrocytoma. In conclusion, overexpression of Eg5 associates with high-grade astrocytic neoplasm, and it may represent an independent diagnostic and prognostic factor in grading astrocytic tumors and predicting prognosis of astrocytic tumor patients. PMID:26456023

  2. A clinicopathologic study of diencephalic pediatric low-grade gliomas with BRAF V600 mutation.

    PubMed

    Ho, Cheng-Ying; Mobley, Bret C; Gordish-Dressman, Heather; VandenBussche, Christopher J; Mason, Gary E; Bornhorst, Miriam; Esbenshade, Adam J; Tehrani, Mahtab; Orr, Brent A; LaFrance, Delecia R; Devaney, Joseph M; Meltzer, Beatrix W; Hofherr, Sean E; Burger, Peter C; Packer, Roger J; Rodriguez, Fausto J

    2015-10-01

    Among brain tumors, the BRAF (V600E) mutation is frequently associated with pleomorphic xanthoastrocytomas (PXAs) and gangliogliomas (GGs). This oncogenic mutation is also detected in ~5 % of other pediatric low-grade gliomas (LGGs) including pilocytic astrocytomas (PAs) and diffuse astrocytomas. In the current multi-institutional study of 56 non-PXA/non-GG diencephalic pediatric LGGs, the BRAF (V600) mutation rate is 36 %. V600-mutant tumors demonstrate a predilection for infants and young children (<age 3) and have a higher tendency for multicentricity. On neuroimaging, BRAF (V600)-mutant tumors appear as nodular, yet infiltrative contrast-enhancing masses. Morphologic examination reveals a monophasic, predominantly compact and partially infiltrative architecture. Due to the lack of classic morphologic features associated with PAs, pilomyxoid astrocytomas (PMAs), or diffuse astrocytomas, 75 % of the BRAF (V600)-mutant tumors could not be definitively classified on initial histopathologic evaluation. At a median follow-up of 55 months, the 5-year progression-free survival (PFS) rate for BRAF (V600)-mutant diencephalic low-grade astrocytomas (LGAs) was 22 ± 12 %, shorter than BRAF (V600)-WT PAs (52 ± 13 %) but higher than PMAs (10 ± 6 %). Of note, long-term PFS was observed in several adolescent patients with BRAF (V600)-mutant tumors. In children aged 0-12 years, 5-year PFS rate and median PFS in BRAF (V600)-mutant LGAs are 9 ± 9 % and 19 months (95 % CI 3-37 months), respectively. The PFS is comparable to that in BRAF (V600)-WT PMAs (5-year PFS rate: 10 ± 9 %; median PFS: 15 months, 95 % CI 3-32 months; p = 0.96) and significantly shorter than BRAF (V600)-WT PAs (5-year PFS rate: 46 ± 13 %; median PFS: 51 months, 95 % CI 20-∞ months; p < 0.05). In summary, diencephalic BRAF (V600)-mutant pediatric LGAs are associated with unique clinicopathologic features and have a more aggressive clinical course, especially in children

  3. Evolutionary etiology of high-grade astrocytomas

    PubMed Central

    Song, Yurong; Zhang, Qian; Kutlu, Burak; Difilippantonio, Simone; Bash, Ryan; Gilbert, Debra; Yin, Chaoying; O’Sullivan, T. Norene; Yang, Chunyu; Kozlov, Serguei; Bullitt, Elizabeth; McCarthy, Ken D.; Kafri, Tal; Louis, David N.; Miller, C. Ryan; Hood, Leroy; Van Dyke, Terry

    2013-01-01

    Glioblastoma (GBM), the most common brain malignancy, remains fatal with no effective treatment. Analyses of common aberrations in GBM suggest major regulatory pathways associated with disease etiology. However, 90% of GBMs are diagnosed at an advanced stage (primary GBMs), providing no access to early disease stages for assessing disease progression events. As such, both understanding of disease mechanisms and the development of biomarkers and therapeutics for effective disease management are limited. Here, we describe an adult-inducible astrocyte-specific system in genetically engineered mice that queries causation in disease evolution of regulatory networks perturbed in human GBM. Events yielding disease, both engineered and spontaneous, indicate ordered grade-specific perturbations that yield high-grade astrocytomas (anaplastic astrocytomas and GBMs). Impaired retinoblastoma protein RB tumor suppression yields grade II histopathology. Additional activation of v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS) network drives progression to grade III disease, and further inactivation of phosphatase and tensin homolog (PTEN) yields GBM. Spontaneous missense mutation of tumor suppressor Trp53 arises subsequent to KRAS activation, but before grade III progression. The stochastic appearance of mutations identical to those observed in humans, particularly the same spectrum of p53 amino acid changes, supports the validity of engineered lesions and the ensuing interpretations of etiology. Absence of isocitrate dehydrogenase 1 (IDH1) mutation, asymptomatic low grade disease, and rapid emergence of GBM combined with a mesenchymal transcriptome signature reflect characteristics of primary GBM and provide insight into causal relationships. PMID:24114272

  4. Brain tumors.

    PubMed Central

    Black, K. L.; Mazziotta, J. C.; Becker, D. P.

    1991-01-01

    Recent advances in experimental tumor biology are being applied to critical clinical problems of primary brain tumors. The expression of peripheral benzodiazepine receptors, which are sparse in normal brain, is increased as much as 20-fold in brain tumors. Experimental studies show promise in using labeled ligands to these receptors to identify the outer margins of malignant brain tumors. Whereas positron emission tomography has improved the dynamic understanding of tumors, the labeled selective tumor receptors with positron emitters will enhance the ability to specifically diagnose and greatly aid in the pretreatment planning for tumors. Modulation of these receptors will also affect tumor growth and metabolism. Novel methods to deliver antitumor agents to the brain and new approaches using biologic response modifiers also hold promise to further improve the management of brain tumors. Images PMID:1848735

  5. FR901228 in Treating Children With Refractory or Recurrent Solid Tumors or Leukemia

    ClinicalTrials.gov

    2013-01-15

    Blastic Phase Chronic Myelogenous Leukemia; Childhood Central Nervous System Germ Cell Tumor; Childhood Choroid Plexus Tumor; Childhood Chronic Myelogenous Leukemia; Childhood Craniopharyngioma; Childhood Grade I Meningioma; Childhood Grade II Meningioma; Childhood Grade III Meningioma; Childhood High-grade Cerebral Astrocytoma; Childhood Infratentorial Ependymoma; Childhood Low-grade Cerebral Astrocytoma; Childhood Spinal Cord Neoplasm; Childhood Supratentorial Ependymoma; Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Recurrent Childhood Brain Stem Glioma; Recurrent Childhood Cerebellar Astrocytoma; Recurrent Childhood Cerebral Astrocytoma; Recurrent Childhood Ependymoma; Recurrent Childhood Medulloblastoma; Recurrent Childhood Supratentorial Primitive Neuroectodermal Tumor; Recurrent Childhood Visual Pathway and Hypothalamic Glioma; Refractory Chronic Lymphocytic Leukemia; Relapsing Chronic Myelogenous Leukemia; Unspecified Childhood Solid Tumor, Protocol Specific

  6. ADC texture—An imaging biomarker for high-grade glioma?

    SciTech Connect

    Brynolfsson, Patrik; Hauksson, Jón; Karlsson, Mikael; Garpebring, Anders; Nyholm, Tufve; Nilsson, David; Trygg, Johan; Henriksson, Roger; Birgander, Richard; Asklund, Thomas

    2014-10-15

    Purpose: Survival for high-grade gliomas is poor, at least partly explained by intratumoral heterogeneity contributing to treatment resistance. Radiological evaluation of treatment response is in most cases limited to assessment of tumor size months after the initiation of therapy. Diffusion-weighted magnetic resonance imaging (MRI) and its estimate of the apparent diffusion coefficient (ADC) has been widely investigated, as it reflects tumor cellularity and proliferation. The aim of this study was to investigate texture analysis of ADC images in conjunction with multivariate image analysis as a means for identification of pretreatment imaging biomarkers. Methods: Twenty-three consecutive high-grade glioma patients were treated with radiotherapy (2 Gy/60 Gy) with concomitant and adjuvant temozolomide. ADC maps and T1-weighted anatomical images with and without contrast enhancement were collected prior to treatment, and (residual) tumor contrast enhancement was delineated. A gray-level co-occurrence matrix analysis was performed on the ADC maps in a cuboid encapsulating the tumor in coronal, sagittal, and transversal planes, giving a total of 60 textural descriptors for each tumor. In addition, similar examinations and analyses were performed at day 1, week 2, and week 6 into treatment. Principal component analysis (PCA) was applied to reduce dimensionality of the data, and the five largest components (scores) were used in subsequent analyses. MRI assessment three months after completion of radiochemotherapy was used for classifying tumor progression or regression. Results: The score scatter plots revealed that the first, third, and fifth components of the pretreatment examinations exhibited a pattern that strongly correlated to survival. Two groups could be identified: one with a median survival after diagnosis of 1099 days and one with 345 days, p = 0.0001. Conclusions: By combining PCA and texture analysis, ADC texture characteristics were identified, which seems

  7. Denosumab-treated Giant Cell Tumor of Bone Exhibits Morphologic Overlap With Malignant Giant Cell Tumor of Bone.

    PubMed

    Wojcik, John; Rosenberg, Andrew E; Bredella, Miriam A; Choy, Edwin; Hornicek, Francis J; Nielsen, G Petur; Deshpande, Vikram

    2016-01-01

    Giant cell tumor (GCT) of bone is a locally aggressive benign neoplasm characterized by an abundance of osteoclastic giant cells that are induced by the neoplastic mononuclear cells; the latter express high levels of receptor activator of nuclear factor κ-B ligand (RANKL). Denosumab, a RANKL inhibitor, which is clinically used to treat GCT, leads to a marked alteration in the histologic appearance of the tumor with giant cell depletion and new bone deposition, leading to substantial histologic overlap with other primary tumors of bone. Most significantly, denosumab-treated GCT (tGCT) with abundant bone deposition may mimic de novo osteosarcoma, or GCT that has undergone malignant transformation. To histologically characterize tGCT, we identified 9 cases of GCT biopsied or resected after denosumab treatment. tGCT cases included 16 specimens from 9 patients including 6 female and 3 male individuals aged 16 to 47 (median 32) years. Duration of treatment varied from 2 to 55 months. We compared these tumors with malignant neoplasms arising in GCTs (n=9). The histology of tGCT was variable but appeared to relate to the length of therapy. All tGCTs showed marked giant cell depletion. Early lesions were highly cellular, and the combination of cellularity, atypia, and haphazard bone deposition caused the lesion to resemble high-grade osteosarcoma. Unlike de novo high-grade osteosarcoma or malignancies arising in GCT, however, tGCT showed less severe atypia, reduced mitotic activity, and lack of infiltrative growth pattern. Tumor in patients on prolonged therapy showed decreased cellularity and abundant new bone, deposited as broad, rounded cords or long, curvilinear arrays. The latter morphology was reminiscent of low-grade central osteosarcoma, but, unlike low-grade central osteosarcoma, tGCT was negative for MDM2 and again lacked an infiltrative growth pattern. Overall, tGCT may have a wide range of morphologic appearances. Because the treated tumors bear little

  8. Proton Beam Therapy for Aged Patients With Hepatocellular Carcinoma

    SciTech Connect

    Hata, Masaharu Tokuuye, Koichi; Sugahara, Shinji; Tohno, Eriko; Nakayama, Hidetsugu; Fukumitsu, Nobuyoshi; Mizumoto, Masashi; Abei, Masato; Shoda, Junichi; Minami, Manabu; Akine, Yasuyuki

    2007-11-01

    Purpose: To investigate the safety and efficacy of proton beam therapy for aged patients with hepatocellular carcinoma (HCC). Methods and Materials: Twenty-one patients aged {>=}80 years with HCC underwent proton beam therapy. At the time of irradiation, patient age ranged from 80 to 85 years (median, 81 years). Hepatic tumors were solitary in 17 patients and multiple in 4. Tumor size ranged from 10 to 135 mm (median, 40 mm) in maximum diameter. Ten, 5, and 6 patients received proton beam irradiation with total doses of 60 Gy in 10 fractions, 66 Gy in 22 fractions, and 70 Gy in 35 fractions, respectively, according to tumor location. Results: All irradiated tumors were controlled during the follow-up period of 6-49 months (median, 16 months). Five patients showed new hepatic tumors outside the irradiated volume, 2-13 months after treatment, and 1 of them also had lung metastasis. The local progression-free and disease-free rates were 100% and 72% at 3 years, respectively. Of 21 patients, 7 died 6-49 months after treatment; 2 patients each died of trauma and old age, and 1 patient each died of HCC, pneumonia, and arrhythmia. The 3-year overall, cause-specific, and disease-free survival rates were 62%, 88%, and 51%, respectively. No therapy-related toxicity of Grade {>=} 3 but thrombocytopenia in 2 patients was observed. Conclusions: Proton beam therapy seems to be tolerable, effective, and safe for aged patients with HCC. It may contribute to prolonged survival due to tumor control.

  9. The number of tumor-free axillary lymph nodes removed as a prognostic parameter for node-negative breast cancer

    PubMed Central

    Gao, Fei; He, Ni; Wu, Pei-Hong

    2014-01-01

    Recently, there has been controversy about the relationship between the number of lymph nodes removed and survival of patients diagnosed with lymph node-negative breast cancer. To assess this relationship, 603 cases of lymph node-negative breast cancer with a median of 126 months of follow-up data were studied. Patients were stratified into two groups (Group A, 10 or fewer tumor-free lymph nodes removed; Group B, more than 10 tumor-free lymph nodes removed). The number of tumor-free lymph nodes in ipsilateral axillary resections as well as 5 other disease parameters were analyzed for prognostic value. Our results revealed that the risk of death from breast cancer was significantly associated with patient age, marital status, histologic grade, tumor size, and adjuvant therapy. The 5- and 10-year survival rates for patients with 10 or fewer tumor-free lymph nodes removed was 88.0% and 66.4%, respectively, compared with 69.2% and 51.1%, respectively, for patients with more than 10 tumor-free lymph nodes removed. For patients with 10 or fewer tumor-free lymph nodes removed, the adjusted hazard ratio (HR) for risk of death from breast cancer was 0.579 (95% confidence interval, 0.492-0.687, P < 0.001), independent of patient age, marital status, histologic grade, tumor size, and adjuvant therapy. Our study suggests that the number of tumor-free lymph nodes removed is an independent predictor in cases of lymph node-negative breast cancer. PMID:25322865

  10. Evaluating the Role of Interdigitated Neoadjuvant Chemotherapy and Radiation in the Management of High-Grade Soft-Tissue Sarcoma

    PubMed Central

    Raval, Raju R.; Frassica, Deborah; Thornton, Katherine; Meyer, Christian; Ettinger, David S.; Frassica, Frank; Weber, Kristin; Terezakis, Stephanie A.

    2016-01-01

    Objectives High-grade soft-tissue sarcoma (STS) has a poor prognosis. The goal of this study was to review treatment outcomes of patients with high-grade STS treated with interdigitated neoadjuvant chemotherapy (CT) and radiation at our institution. Materials and Methods Patients with high-grade STS (1997 to 2010) were planned for treatment with 3 cycles of neoadjuvant CT, interdigitated preoperative radiation therapy (44 Gy administered in split courses with a potential 16 Gy postoperative boost), and 3 cycles of postoperative CT. Cancer control outcomes at 3 years were analyzed. Results Sixteen patients with high-grade STS were evaluated. Median age was 53 years, the median longest tumor diameter was 14.6 cm, and median follow-up was 33 months. All 16 patients received 2 or 3 cycles of neoadjuvant CT and all patients completed neoadjuvant RT. The estimated 3-year rate for local control was 100%, disease-free survival 62.5%, and overall survival 73.4%. Conclusions Patients with high-grade STS treated with interdigitated neoadjuvant CT and radiation before surgical resection had excellent rates of local control, along with disease-free survival and overall survival similar to previously published reports. This combined-modality approach continues to have a role in the treatment of patients with high-grade STS. PMID:25268069

  11. Irinotecan in Treating Children With Refractory Solid Tumors

    ClinicalTrials.gov

    2013-06-13

    Childhood Central Nervous System Germ Cell Tumor; Childhood Choroid Plexus Tumor; Childhood Craniopharyngioma; Childhood Grade I Meningioma; Childhood Grade II Meningioma; Childhood Grade III Meningioma; Childhood Infratentorial Ependymoma; Childhood Oligodendroglioma; Childhood Supratentorial Ependymoma; Previously Treated Childhood Rhabdomyosarcoma; Recurrent Childhood Cerebellar Astrocytoma; Recurrent Childhood Cerebral Astrocytoma; Recurrent Childhood Ependymoma; Recurrent Childhood Medulloblastoma; Recurrent Childhood Rhabdomyosarcoma; Recurrent Childhood Visual Pathway and Hypothalamic Glioma; Recurrent Childhood Visual Pathway Glioma; Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor; Recurrent Neuroblastoma; Recurrent Osteosarcoma; Unspecified Childhood Solid Tumor, Protocol Specific

  12. Glioma Groups Based on 1p/19q, IDH, and TERT Promoter Mutations in Tumors

    PubMed Central

    Eckel-Passow, Jeanette E.; Lachance, Daniel H.; Molinaro, Annette M.; Walsh, Kyle M.; Decker, Paul A.; Sicotte, Hugues; Pekmezci, Melike; Rice, Terri; Kosel, Matt L.; Smirnov, Ivan V.; Sarkar, Gobinda; Caron, Alissa A.; Kollmeyer, Thomas M.; Praska, Corinne E.; Chada, Anisha R.; Halder, Chandralekha; Hansen, Helen M.; McCoy, Lucie S.; Bracci, Paige M.; Marshall, Roxanne; Zheng, Shichun; Reis, Gerald F.; Pico, Alexander R.; O’Neill, Brian P.; Buckner, Jan C.; Giannini, Caterina; Huse, Jason T.; Perry, Arie; Tihan, Tarik; Berger, Mitchell S.; Chang, Susan M.; Prados, Michael D.; Wiemels, Joseph; Wiencke, John K.; Wrensch, Margaret R.; Jenkins, Robert B.

    2015-01-01

    BACKGROUND The prediction of clinical behavior, response to therapy, and outcome of infiltrative glioma is challenging. On the basis of previous studies of tumor biology, we defined five glioma molecular groups with the use of three alterations: mutations in the TERT promoter, mutations in IDH, and codeletion of chromosome arms 1p and 19q (1p/19q codeletion). We tested the hypothesis that within groups based on these features, tumors would have similar clinical variables, acquired somatic alterations, and germline variants. METHODS We scored tumors as negative or positive for each of these markers in 1087 gliomas and compared acquired alterations and patient characteristics among the five primary molecular groups. Using 11,590 controls, we assessed associations between these groups and known glioma germline variants. RESULTS Among 615 grade II or III gliomas, 29% had all three alterations (i.e., were triplepositive), 5% had TERT and IDH mutations, 45% had only IDH mutations, 7% were triple-negative, and 10% had only TERT mutations; 5% had other combinations. Among 472 grade IV gliomas, less than 1% were triple-positive, 2% had TERT and IDH mutations, 7% had only IDH mutations, 17% were triple-negative, and 74% had only TERT mutations. The mean age at diagnosis was lowest (37 years) among patients who had gliomas with only IDH mutations and was highest (59 years) among patients who had gliomas with only TERT mutations. The molecular groups were independently associated with overall survival among patients with grade II or III gliomas but not among patients with grade IV gliomas. The molecular groups were associated with specific germline variants. CONCLUSIONS Gliomas were classified into five principal groups on the basis of three tumor markers. The groups had different ages at onset, overall survival, and associations with germline variants, which implies that they are characterized by distinct mechanisms of pathogenesis. PMID:26061753

  13. Analysis of IDH mutation, 1p/19q deletion, and PTEN loss delineates prognosis in clinical low-grade diffuse gliomas

    PubMed Central

    Sabha, Nesrin; Knobbe, Christiane B.; Maganti, Majula; Al Omar, Soha; Bernstein, Mark; Cairns, Rob; Çako, Besmira; von Deimling, Andreas; Capper, David; Mak, Tak W.; Kiehl, Tim-Rasmus; Carvalho, Philippe; Garrett, Evelyn; Perry, Arie; Zadeh, Gelareh; Guha, Abhijit; Croul, Sidney

    2014-01-01

    Background Grades II and III gliomas have unpredictable rates of progression, making management decisions difficult. Currently, several clinical and radiological characteristics are utilized to predict progression and survival but collectively are suboptimal. Methods In this study, we analyzed a set of 108 nonenhancing hemispheric grade II–III gliomas. Demographic variables, including patient age, tumor diameter, extent of resection, and performance status, were combined with molecular data (IDH mutation status [mIDH], 1p/19q codeletion, PTEN deletion, and EGFR amplification). A complete dataset for all variables was compiled for 70 of the 108 patients. Both univariable and multivariable analyses were performed to determine whether the molecular data singly or in combination offer advantages over tumor type and grade for prediction of overall survival (OS) and/or progression-free rate (PFR). Results Patient age, clinical variables (tumor diameter, extent of resection, performance status), and pathology (tumor type and grade) were not predictive of OS or PFR. IDH mutation status alone was predictive of longer OS and PFR for the entire group of tumors; 1p/19q deletion alone was predictive of OS but not PFR. In the multivariable analysis, none of the clinical or demographic factors were predictive of OS or PFR. IDH mutation status, 1p/19q codeletion, and PTEN deletion were predictive of OS (P = .003, P = .005, P = .02, respectively). Both mIDH (P < .001) and the interaction term of 1p/19q and PTEN (P < .001) were found to be predictive of PFR. Conclusions We conclude that the combination of mIDH, 1p/19q codeletion, and PTEN deletion may be particularly effective in discriminating good prognosis from poor prognosis hemispheric gliomas. We propose that such a scheme merits testing on larger prospective cohorts. Should our findings be confirmed, routine clinical analysis of hemispheric gliomas for mIDH, 1p/19q codeletion, and PTEN deletion would be justified. PMID

  14. Tumor Types

    MedlinePlus

    ... acoustic neuroma is also known as a schwannoma, vestibular schwannoma, or neurilemmoma. Characteristics Arises from cells that ... multiple CNS tumors, including neurofibromas, multiple meningiomas, bilateral vestibular schwannomas, optic nerve gliomas, and spinal cord tumors. ...

  15. Silver Threads: Writing about Old Age.

    ERIC Educational Resources Information Center

    Garrison, Peggy

    1995-01-01

    Describes an experiment conducted with students in grades two through six and grade nine. States that the focus was on writing about old age. Reveals stereotypes about the elderly. Discusses how students were encouraged to write about the aging process and their feelings about aging. Concludes that aging is thought of as a major human concern, but…

  16. Brain Tumors

    MedlinePlus

    A brain tumor is a growth of abnormal cells in the tissues of the brain. Brain tumors can be benign, with no cancer cells, ... cancer cells that grow quickly. Some are primary brain tumors, which start in the brain. Others are ...

  17. Urogenital tumors

    SciTech Connect

    Weller, R.E.

    1994-03-01

    An overview is provided for veterinary care of urogenital tumors in companion animals, especially the dog. Neoplasms discussed include tumors of the kidney, urinary bladder, prostate, testis, ovary, vagina, vulva and the canine transmissible venereal tumor. Topics addressed include description, diagnosis and treatment.

  18. Dysembryoplastic Neuroepithelial Tumor of the Septum Pellucidum and the Supratentorial Midline: Histopathologic, Neuroradiologic, and Molecular Features of 7 Cases.

    PubMed

    Gessi, Marco; Hattingen, Elke; Dörner, Evelyn; Goschzik, Tobias; Dreschmann, Verena; Waha, Andreas; Pietsch, Torsten

    2016-06-01

    Dysembryoplastic neuroepithelial tumors (DNTs) are one of the most common epilepsy-associated low-grade glioneuronal tumors of the central nervous system. Although most DNTs occur in the cerebral cortex, DNT-like tumors with unusual intraventricular or periventricular localizations have been reported. Most of them involve the septum pellucidum and the foramen of Monro. In this study, we have described the neuroradiologic, histopathologic, and molecular features of 7 cases (4 female and 3 male; patient age range, 3 to 34 y; mean age, 16.7 y). The tumors, all localized near the supratentorial midline structures in proximity to the foramen of Monro and septum pellucidum, appeared in magnetic resonance imaging as well-delimited cystic lesions with cerebrospinal fluid-like signal on T1-weighted and T2-weighted images, some of them with typical fluid-attenuated inversion recovery ring sign. Histologically, they shared features with classic cortical DNTs but did not display aspects of multinodularity. From a molecular point of view the cases investigated did not show KIAA1549-BRAF fusions or FGFR1 mutations, alterations otherwise observed in pilocytic astrocytomas, or MYB and MYBL1 alterations that have been identified in a large group of pediatric low-grade gliomas. Moreover, BRAF mutations, which so far represent the most common molecular alteration found in cortical DNTs, were absent in this group of rare periventricular tumors. PMID:26796505

  19. Positron Emission Tomography Using Fluorine F 18 EF5 to Find Oxygen in Tumor Cells of Patients Who Are Undergoing Surgery or Biopsy for Newly Diagnosed Brain Tumors

    ClinicalTrials.gov

    2013-01-15

    Adult Anaplastic Astrocytoma; Adult Anaplastic Ependymoma; Adult Anaplastic Oligodendroglioma; Adult Brain Stem Glioma; Adult Central Nervous System Germ Cell Tumor; Adult Choroid Plexus Tumor; Adult Craniopharyngioma; Adult Diffuse Astrocytoma; Adult Ependymoblastoma; Adult Ependymoma; Adult Giant Cell Glioblastoma; Adult Glioblastoma; Adult Gliosarcoma; Adult Grade I Meningioma; Adult Grade II Meningioma; Adult Grade III Meningioma; Adult Medulloblastoma; Adult Meningeal Hemangiopericytoma; Adult Mixed Glioma; Adult Myxopapillary Ependymoma; Adult Oligodendroglioma; Adult Pilocytic Astrocytoma; Adult Pineoblastoma; Adult Pineocytoma; Adult Subependymoma; Adult Supratentorial Primitive Neuroectodermal Tumor (PNET); Meningeal Melanocytoma

  20. Adenomatoid odontogenic tumor, an uncommon tumor

    PubMed Central

    Vasudevan, K.; Kumar, Senthil; Vijayasamundeeswari; Vigneswari, Srivel

    2012-01-01

    Here we report a case of adenomatoid odontogenic tumor (AOT) in the maxilla in a young girl aged 14 years and its surgical management. We also review the literature and variations in the nomenclature and classifications of this interesting tumor. The review of literature gives an interesting picture regarding terminologies in the past and dilemma in classifying this tumor. The introduction of the name adenomatoid odontogenic tumour has resulted in the simpler and fruitful surgical management like enucleation and curettage with no reports of recurrences. In the past, similar lesion with the terminology like adeno ameloblastoma has resulted in unnecessary mutilating surgery. The conflicting views whether the lesion is being neoplasm or an anomalous hamartomatous growth is also being discussed. PMID:22919236

  1. Spinal and Paraspinal Ewing Tumors

    SciTech Connect

    Indelicato, Daniel J.; Keole, Sameer R.; Shahlaee, Amir H.; Morris, Christopher G.; Gibbs, C. Parker; Scarborough, Mark T.; Pincus, David W.; Marcus, Robert B.

    2010-04-15

    Purpose: To perform a review of the 40-year University of Florida experience treating spinal and paraspinal Ewing tumors. Patients and Methods: A total of 27 patients were treated between 1965 and 2007. For local management, 21 patients were treated with radiotherapy (RT) alone and 6 with surgery plus RT. All patients with metastatic disease were treated with RT alone. The risk profiles of each group were otherwise similar. The median age was 17 years, and the most frequent subsite was the sacral spine (n = 9). The median potential follow-up was 16 years. Results: The 5-year actuarial overall survival, cause-specific survival, and local control rate was 62%, 62%, and 90%, respectively. For the nonmetastatic subset (n = 22), the 5-year overall survival, cause-specific survival, and local control rate was 71%, 71%, and 89%, respectively. The local control rate was 84% for patients treated with RT alone vs. 100% for those treated with surgery plus RT. Patients who were >14 years old and those who were treated with intensive therapy demonstrated superior local control. Of 9 patients in our series with Frankel C or greater neurologic deficits at presentation, 7 experienced a full recovery with treatment. Of the 27 patients, 37% experienced Common Toxicity Criteria Grade 3 or greater toxicity, including 2 deaths from sepsis. Conclusion: Aggressive management of spinal and paraspinal Ewing tumors with RT with or without surgery results in high toxicity but excellent local control and neurologic outcomes. Efforts should be focused on identifying disease amenable to combined modality local therapy and improving RT techniques.

  2. [Preserving ovarian function in the treatment of epithelial and special (other) malignant ovarian tumors].

    PubMed

    Kolstad, P

    1987-10-01

    About 90% of malignant tumors of the ovary in Scandinavia develop from the germinal epithelium. There are great differences in the incidence rates between countries in the Western world and in Africa and Asia. The WHO classification of ovarian malignancies is generally used. The epithelial tumors comprise the serous, mucinous, endometrioid, clear cell, undifferentiated and mixed true carcinomas. In addition, borderline lesions of especially the serous and mucinous types are of interest when the question of preservation of ovarian function comes into notice. Conservative surgery, which means removal of only the afflicted ovary should be restricted to young women of the childbearing age who want to preserve the possibility of becoming pregnant. However, certain prerequisites must be fulfilled. The tumor must be located to one ovary only (Stage Ia) and must be either a borderline lesion or a Grade 1 true carcinoma of either the serous, mucinous or endometrioid type. There must be no ascites and peritoneal washings must be negative for cancer cells. Germ cell tumors are usually found in young women. Only the dysgerminomas are regularly bilateral in 10-15% of the cases. All other germ cell tumors are rarely bilateral. But both in borderline lesions, Grade 1 true carcinomas, and in germ cell tumors, a biopsy of the normal looking contralateral ovary should always be performed. Endodermal sinus tumors and immature teratomas may well be treated conservatively by surgery, but modern triple chemotherapy (VAC, PVB) must be added. Granulosa theca cell tumors are bilateral in only about 5% of the cases.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:2824278

  3. Clinical Experience With Radiation Therapy in the Management of Neurofibromatosis-Associated Central Nervous System Tumors

    SciTech Connect

    Wentworth, Stacy; Pinn, Melva; Bourland, J. Daniel; Guzman, Allan F. de; Ekstrand, Kenneth; Ellis, Thomas L.; Glazier, Steven S.; McMullen, Kevin P.; Munley, Michael; Stieber, Volker W.; Tatter, Stephen B.; Shaw, Edward G.

    2009-01-01

    Purpose: Patients with neurofibromatosis (NF) develop tumors of the central nervous system (CNS). Radiation therapy (RT) is used to treat these lesions. To better define the efficacy of RT in these patients, we reviewed our 20-year experience. Methods and Materials: Eighteen patients with NF with CNS tumors were treated from 1986 to 2007. Median follow-up was 48 months. Progression was defined as growth or recurrence of an irradiated tumor on serial imaging. Progression-free survival (PFS) was measured from the date of RT completion to the date of last follow-up imaging study. Actuarial rates of overall survival (OS) and PFS were calculated according to the Kaplan-Meier method. Results: Eighty-two tumors in 18 patients were irradiated, with an average of five tumors/patient. Median age at treatment was 25 years (range, 4.3-64 years). Tumor types included acoustic neuroma (16%), ependymoma (6%), low-grade glioma (11%), meningioma (60%), and schwanomma/neurofibroma (7%). The most common indication for treatment was growth on serial imaging. Most patients (67%) received stereotactic radiosurgery (median dose, 1,200 cGy; range, 1,000-2,400 cGy). The OS rate at 5 years was 94%. Five-year PFS rates were 75% (acoustic neuroma), 100% (ependymoma), 75% (low-grade glioma), 86% (meningioma), and 100% (schwanomma/neurofibroma). Thirteen acoustic neuromas had a local control rate of 94% with a 50% hearing preservation rate. Conclusions: RT provided local control, OS, and PFS rates similar to or better than published data for tumors in non-NF patients. Radiation therapy should be considered in NF patients with imaging progression of CNS tumors.

  4. Children's Images of Scientists: Does Grade Level Make a Difference?

    ERIC Educational Resources Information Center

    Ozel, Murat

    2012-01-01

    The purpose of this study was to assess children's images of scientists by using the Draw-A-Scientist Test (DAST) and to determine if differences in these images exist between grade levels. The DAST was administered to 243 children who were enrolled in kindergarten (aged 6) and grade 3 and 5 (aged 9 and 11). Findings obtained from the study…

  5. Genome-wide CpG island methylation and intergenic demethylation propensities vary among different tumor sites.

    PubMed

    Lee, Seung-Tae; Wiemels, Joseph L

    2016-02-18

    The epigenetic landscape of cancer includes both focal hypermethylation and broader hypomethylation in a genome-wide manner. By means of a comprehensive genomic analysis on 6637 tissues of 21 tumor types, we here show that the degrees of overall methylation in CpG island (CGI) and demethylation in intergenic regions, defined as 'backbone', largely vary among different tumors. Depending on tumor type, both CGI methylation and backbone demethylation are often associated with clinical, epidemiological and biological features such as age, sex, smoking history, anatomic location, histological type and grade, stage, molecular subtype and biological pathways. We found connections between CGI methylation and hypermutability, microsatellite instability, IDH1 mutation, 19p gain and polycomb features, and backbone demethylation with chromosomal instability, NSD1 and TP53 mutations, 5q and 19p loss and long repressive domains. These broad epigenetic patterns add a new dimension to our understanding of tumor biology and its clinical implications. PMID:26464434

  6. Genome-wide CpG island methylation and intergenic demethylation propensities vary among different tumor sites

    PubMed Central

    Lee, Seung-Tae; Wiemels, Joseph L.

    2016-01-01

    The epigenetic landscape of cancer includes both focal hypermethylation and broader hypomethylation in a genome-wide manner. By means of a comprehensive genomic analysis on 6637 tissues of 21 tumor types, we here show that the degrees of overall methylation in CpG island (CGI) and demethylation in intergenic regions, defined as ‘backbone’, largely vary among different tumors. Depending on tumor type, both CGI methylation and backbone demethylation are often associated with clinical, epidemiological and biological features such as age, sex, smoking history, anatomic location, histological type and grade, stage, molecular subtype and biological pathways. We found connections between CGI methylation and hypermutability, microsatellite instability, IDH1 mutation, 19p gain and polycomb features, and backbone demethylation with chromosomal instability, NSD1 and TP53 mutations, 5q and 19p loss and long repressive domains. These broad epigenetic patterns add a new dimension to our understanding of tumor biology and its clinical implications. PMID:26464434

  7. Gleason grading system

    MedlinePlus

    ... medlineplus.gov/ency/patientinstructions/000920.htm Gleason grading system To use the sharing features on this page, ... score of between 5 and 7. Gleason Grading System Sometimes, it can be hard to predict how ...

  8. Neural precursor cells induce cell death of high-grade astrocytomas via stimulation of TRPV1

    PubMed Central

    Stock, Kristin; Kumar, Jitender; Synowitz, Michael; Petrosino, Stefania; Imperatore, Roberta; Smith, Ewan St. J.; Wend, Peter; Purfürst, Bettina; Nuber, Ulrike A.; Gurok, Ulf; Matyash, Vitali; Wälzlein, Joo-Hee; Chirasani, Sridhar R.; Dittmar, Gunnar; Cravatt, Benjamin F.; Momma, Stefan; Lewin, Gary R.; Ligresti, Alessia; De Petrocellis, Luciano; Cristino, Luigia; Di Marzo, Vincenzo; Kettenmann, Helmut; Glass, Rainer

    2012-01-01

    Primary astrocytomas of World Health Organization grade 3 and grade 4 (HG-astrocytomas) are preponderant among adults and are almost invariably fatal despite multimodal therapy. Here, we show that the juvenile brain has an endogenous defense mechanism against HG-astrocytomas. Neural precursor cells (NPCs) migrate to HG-astrocytomas, reduce glioma expansion and prolong survival by releasing a group of fatty acid ethanolamides that have agonistic activity on the vanilloid receptor (transient receptor potential vanilloid subfamily member-1; TRPV1). TRPV1 expression is higher in HG-astrocytomas than in tumor-free brain and TRPV1 stimulation triggers tumor cell death via the activating transcription factor-3 (ATF3) controlled branch of the ER stress pathway. The anti-tumorigenic response of NPCs is lost with aging. NPC-mediated tumor suppression can be mimicked in the adult brain by systemic administration of the synthetic vanilloid Arvanil, suggesting that TRPV1 agonists hold potential as new HG-astrocytoma therapeutics. PMID:22820645

  9. Grade-A Perfect

    ERIC Educational Resources Information Center

    Brown, Joseph

    2004-01-01

    Despite the wealth of information available, there is no consensus on best practices for grading. In this article, the author identifies four key philosophical questions that should guide the development of a teacher's grading system and provides tips that can help principals guide teachers in developing a grading system. (Contains 1 figure.)

  10. General Graded Response Model.

    ERIC Educational Resources Information Center

    Samejima, Fumiko

    This paper describes the graded response model. The graded response model represents a family of mathematical models that deal with ordered polytomous categories, such as: (1) letter grading; (2) an attitude survey with "strongly disagree, disagree, agree, and strongly agree" choices; (3) partial credit given in accord with an individual's degree…

  11. [Grading of prostate cancer].

    PubMed

    Kristiansen, G; Roth, W; Helpap, B

    2016-07-01

    The current grading of prostate cancer is based on the classification system of the International Society of Urological Pathology (ISUP) following a consensus conference in Chicago in 2014. The foundations are based on the frequently modified grading system of Gleason. This article presents a brief description of the development to the current ISUP grading system. PMID:27393141

  12. Bias in Grading

    ERIC Educational Resources Information Center

    Malouff, John

    2008-01-01

    Bias in grading can be conscious or unconscious. The author describes different types of bias, such as those based on student attractiveness or performance in prior courses, and a variety of methods of reducing bias, including keeping students anonymous during grading and using detailed criteria for subjective grading.

  13. Redesigning Grading--Districtwide

    ERIC Educational Resources Information Center

    Townsley, Matt

    2014-01-01

    In the first years of his career as a high school math teacher, Matt Townsley was bothered by the fact that his grades penalized students for not learning content quickly. A student could master every standard, but low quiz grades and homework assignments they didn't complete because they didn't understand would lower their final grade,…

  14. ABT-888 and Temozolomide in Treating Young Patients With Recurrent or Refractory CNS Tumors

    ClinicalTrials.gov

    2014-07-07

    Childhood Atypical Teratoid/Rhabdoid Tumor; Childhood Central Nervous System Germ Cell Tumor; Childhood Choroid Plexus Tumor; Childhood Craniopharyngioma; Childhood Ependymoblastoma; Childhood Grade I Meningioma; Childhood Grade II Meningioma; Childhood Grade III Meningioma; Childhood High-grade Cerebellar Astrocytoma; Childhood High-grade Cerebral Astrocytoma; Childhood Infratentorial Ependymoma; Childhood Low-grade Cerebellar Astrocytoma; Childhood Low-grade Cerebral Astrocytoma; Childhood Medulloepithelioma; Childhood Mixed Glioma; Childhood Oligodendroglioma; Childhood Supratentorial Ependymoma; Recurrent Childhood Brain Stem Glioma; Recurrent Childhood Brain Tumor; Recurrent Childhood Cerebellar Astrocytoma; Recurrent Childhood Cerebral Astrocytoma; Recurrent Childhood Ependymoma; Recurrent Childhood Medulloblastoma; Recurrent Childhood Pineoblastoma; Recurrent Childhood Spinal Cord Neoplasm; Recurrent Childhood Subependymal Giant Cell Astrocytoma; Recurrent Childhood Supratentorial Primitive Neuroectodermal Tumor; Recurrent Childhood Visual Pathway and Hypothalamic Glioma

  15. SALL4 and SF-1 are sensitive and specific markers for distinguishing granulosa cell tumors from yolk sac tumors.

    PubMed

    Bai, Shuting; Wei, Shi; Ziober, Amy; Yao, Yuan; Bing, Zhanyong

    2013-04-01

    Granulosa cell tumors are classified as juvenile and adult types. They may be misinterpreted as a yolk sac tumor when they exhibit a "reticular" growth pattern and contain prominent mitotic activity. In this study, the authors performed immunohistochemical stains for SALL4 and steroidogenic factor-1 (SF-1) on 27 cases of yolk sac tumors and 24 granulosa cell tumors. Nuclear stains for both antibodies were considered as positive and the intensity of staining was graded as negative, weak, moderate, and strong. All the yolk sac tumors were positive for SALL4 (100%) with moderate to strong grade staining and negative for SF-1 (100%). In contrast, all the granulosa cell tumors were positive for SF-1 (85% moderate to strong grade staining and 15% weak staining) and negative for SALL4 (100%). The difference was significant (P < .01, Student's t test). This result indicates that these 2 markers could be used to distinguish these 2 tumors in a difficult situation. PMID:22832114

  16. Pleuropulmonary Blastoma: Evolution of an Entity as an Entry into a Familial Tumor Predisposition Syndrome.

    PubMed

    Dehner, Louis P; Messinger, Yoav H; Schultz, Kris Ann P; Williams, Gretchen M; Wikenheiser-Brokamp, Kathryn; Hill, D Ashley

    2015-01-01

    Pleuropulmonary blastoma (PPB) is the most common primary malignant neoplasm of the lung in children. Like other solid dysontogenic neoplasms, this tumor typically presents before 7 years of age. The earliest manifestation is the presence of a lung cyst(s), which is usually recognized in the first year of life and is difficult to differentiate on the basis of imaging studies from non-neoplastic cysts of early childhood. From a multilocular cyst, PPB has the potential to progress to a high-grade multipatterned primitive sarcoma. More than 65% of all affected children have a heterozygous germline mutation in DICER1. The DICER1 PPB familial tumor predisposition syndrome is initially recognized in most cases on the basis of PPB alone but also by several other unique and characteristic extrapulmonary tumors, including pediatric cystic nephroma, nasal chondromesenchymal hamartoma, nodular lesions of the thyroid, embryonal rhabdomyosarcoma of the cervix, and ciliary body medulloepithelioma. PMID:26698637

  17. Relative radiosensitivity of bone tumor induction among beagles as a function of age at injection of {sup 239}Pu or {sup 226}Ra

    SciTech Connect

    Lloyd, R.D.; Taylor, G.N.; Jee, W.S.S.; Miller, S.C.

    1999-01-01

    A comparison was made of the response to induction of skeletal malignancy from exposure of beagles to monomeric {sup 239}Pu or to {sup 226}Ra as juveniles (3 mo of age), young adults (1.5 y of age), or mature adults (5 y of age). This indicated that of these age groups, animals injected as young adults are most sensitive per Gy of average skeletal dose evaluated at 1 y before death. Dogs exposed either as juveniles or as mature adults appeared to be less sensitive. Relative radiosensitivities (RRS) of juvenile and mature beagles ranged between about 0.3 and 0.7 that of dogs injected as young adults. Mean values of RRS for both radionuclides were about 0.5, but RRS values derived from dogs given monomeric {sup 239}Pu appeared to be most reliable and were 0.27 {+-} 0.09 for dogs injected as juveniles and 0.41 {+-} 0.13 for animals exposed as mature adults.

  18. Young T Cells Age During a Redirected Anti-Tumor Attack: Chimeric Antigen Receptor-Provided Dual Costimulation is Half the Battle

    PubMed Central

    Hombach, Andreas A.; Abken, Hinrich

    2013-01-01

    Adoptive therapy with chimeric antigen receptor (CAR)-redirected T cells showed spectacular efficacy in the treatment of leukemia in recent early phase trials. Patient’s T cells were ex vivo genetically engineered with a CAR, amplified and re-administered to the patient. While T cells mediating the primary response were predominantly of young effector and central memory phenotype, repetitive antigen engagement irreversible triggers T cell maturation leaving late memory cells with the KLRG1+ CD57+ CD7− CCR7− phenotype in the long-term. These cells preferentially accumulate in the periphery, are hypo-responsive upon TCR engagement and prone to activation-induced cell death. A recent report indicates that those T cells can be rescued by CAR provided CD28 and OX40 (CD134) stimulation. We discuss the strategy with respect to prolong the anti-tumor response and to improve the over-all efficacy of adoptive cell therapy. PMID:23761793

  19. Young T Cells Age During a Redirected Anti-Tumor Attack: Chimeric Antigen Receptor-Provided Dual Costimulation is Half the Battle.

    PubMed

    Hombach, Andreas A; Abken, Hinrich

    2013-01-01

    Adoptive therapy with chimeric antigen receptor (CAR)-redirected T cells showed spectacular efficacy in the treatment of leukemia in recent early phase trials. Patient's T cells were ex vivo genetically engineered with a CAR, amplified and re-administered to the patient. While T cells mediating the primary response were predominantly of young effector and central memory phenotype, repetitive antigen engagement irreversible triggers T cell maturation leaving late memory cells with the KLRG1(+) CD57(+) CD7(-) CCR7(-) phenotype in the long-term. These cells preferentially accumulate in the periphery, are hypo-responsive upon TCR engagement and prone to activation-induced cell death. A recent report indicates that those T cells can be rescued by CAR provided CD28 and OX40 (CD134) stimulation. We discuss the strategy with respect to prolong the anti-tumor response and to improve the over-all efficacy of adoptive cell therapy. PMID:23761793

  20. Use of thallium-201 SPECT to quantitate malignancy grade of gliomas

    SciTech Connect

    Black, K.L.; Hawkins, R.A.; Kim, K.T.; Becker, D.P.; Lerner, C.; Marciano, D. )

    1989-09-01

    A quantitative preoperative technique using thallium-201 single-photon emission computerized tomography is described which predicts whether specific gliomas are of high- or low-grade malignancy. An index, based on the ratio of thallium uptake in the tumor versus the homologous contralateral brain, was calculated and compared with tumor histology. The index in 14 patients with low-grade malignant gliomas was 1.27 {plus minus} 0.40 in contrast to an index of 2.40 {plus minus} 0.61 in 11 patients with high-grade malignant gliomas (p less than 0.0005). Whether gliomas were of low- or high-grade malignancy could be predicted with 89% accuracy using a threshold of 1.5. Low-grade gliomas with an index higher than 1.5 acted biologically more like high-grade tumors, and no tumor histologically classified as being of high-grade malignancy had an index lower than 1.7. This technique could help to reduce unrecognized sampling errors during needle biopsies of brain tumors, particularly of high-grade lesions classified in error as low-grade tumors due to inadequate biopsy material.

  1. Outcomes of Multidisciplinary Management in Pediatric Low-Grade Gliomas

    SciTech Connect

    Oh, Kevin S.; Hung, Jonathan; Robertson, Patricia L.; Garton, Hugh J.; Muraszko, Karin M.; Sandler, Howard M.; Hamstra, Daniel A.

    2011-11-15

    Purpose: To evaluate the outcomes in pediatric low-grade gliomas managed in a multidisciplinary setting. Methods and Materials: We conducted a single-institution retrospective study of 181 children with Grade I-II gliomas. Log-rank and stepwise Cox proportional hazards models were used to analyze freedom from progression (FFP) and overall survival (OS). Results: Median follow-up was 6.4 years. Thirty-four (19%) of patients had neurofibromatosis Type 1 (NF1) and because of their favorable prognosis were evaluated separately. In the 147 (81%) of patients without NF1, actuarial 7-year FFP and OS were 67 {+-} 4% (standard error) and 94 {+-} 2%, respectively. In this population, tumor location in the optic pathway/hypothalamus was associated with worse FFP (39% vs. 76%, p < 0.0003), but there was no difference in OS. Age {<=}5 years was associated with worse FFP (52% vs. 75%, p < 0.02) but improved OS (97% vs. 92%, p < 0.05). In those with tissue diagnosis, gross total resection (GTR) was associated with improved 7-year FFP (81% vs. 56%, p < 0.02) and OS (100% vs. 90%, p < 0.03). In a multivariate model, only location in the optic pathway/hypothalamus predicted worse FFP (p < 0.01). Fifty patients received radiation therapy (RT). For those with less than GTR, adjuvant RT improved FFP (89% vs. 49%, p < 0.003) but not OS. There was no difference in OS between patient groups given RT as adjuvant vs. salvage therapy. In NF1 patients, 94% of tumors were located in the optic pathway/hypothalamus. With a conservative treatment strategy in this population, actuarial 7-year FFP and OS were 73 {+-} 9% and 100%, respectively. Conclusions: Low-grade gliomas in children {<=}5 years old with tumors in the optic pathway/hypothalamus are more likely to progress, but this does not confer worse OS because of the success of salvage therapy. When GTR is not achieved, adjuvant RT improves FFP but not OS. Routine adjuvant RT can be avoided and instead reserved as salvage.

  2. The USDA quality grades may mislead consumers.

    PubMed

    DeVuyst, E A; Lusk, J L; DeVuyst, M A

    2014-07-01

    This study was designed to explore consumers' perceptions about and knowledge of USDA beef quality grades. Data were collected from over 1,000 consumers in online surveys in November and December 2013, and estimates were weighted to force the sample to mirror the U.S. population in terms of age, gender, education, and region of residence. When asked to rank Prime, Choice, and Select grades in terms of leanness, only 14.4% provided the correct ranking with 57.1% of respondents incorrectly indicating steaks grading Prime were the leanest. Despite perceptions that the Prime name indicated the leanest product, in a subsequent question, 55.6% of respondents thought Prime grade to be the juiciest of the 3 grades. In addition to inquiring about perceptions of the grade names, respondents also indicated perceptions of pictures of steaks. Only 14.5% of respondents correctly matched the steak pictures with their corresponding USDA quality grade name, an outcome that is statistically worse than would have occurred through pure random matching (P = 0.03). When asked to match pictures of steaks with expected prices, 54.8% of respondents incorrectly matched the picture of the Prime steak with the lowest price level. More highly educated consumers with greater preferences for steak consumption were more likely to provide correct answers. Results reveal substantial confusion over quality grading nomenclature and suggest the need for more education or for a transition toward more descriptive terminology at the retail level. PMID:24802037

  3. Rhabdoid tumor predisposition syndrome.

    PubMed

    Sredni, Simone T; Tomita, Tadanori

    2015-01-01

    Rhabdoid tumors (RT), or malignant rhabdoid tumors, are among the most aggressive and lethal forms of human cancer. They can arise in any location in the body but are most commonly observed in the brain, where they are called atypical teratoid/rhabdoid tumors (AT/RT), and in the kidneys, where they are called rhabdoid tumors of the kidney. The vast majority of rhabdoid tumors present with a loss of function in the SMARCB1 gene, also known as INI1, BAF47, and hSNF5, a core member of the SWI/SNF chromatin-remodeling complex. Recently, mutations in a 2nd locus of the SWI/SNF complex, the SMARCA4 gene, also known as BRG1, were found in rhabdoid tumors with retention of SMARCB1 expression. Familial cases may occur in a condition known as rhabdoid tumor predisposition syndrome (RTPS). In RTPS, germline inactivation of 1 allele of a gene occurs. When the mutation occurs in the SMARCB1 gene, the syndrome is called RTPS1, and when the mutation occurs in the SMARCA4 gene it is called RTPS2. Children presenting with RTPS tend to develop tumors at a younger age, but the impact that germline mutation has on survival remains unclear. Adults who carry the mutation tend to develop multiple schwannomas. The diagnosis of RTPS should be considered in patients with RT, especially if they have multiple primary tumors, and/or in individuals with a family history of RT. Because germline mutations result in an increased risk of carriers developing RT, genetic counseling for families with this condition is recommended. PMID:25494491

  4. Absence of human cytomegalovirus infection in childhood brain tumors.

    PubMed

    Sardi, Iacopo; Lucchesi, Maurizio; Becciani, Sabrina; Facchini, Ludovica; Guidi, Milena; Buccoliero, Anna Maria; Moriondo, Maria; Baroni, Gianna; Stival, Alessia; Farina, Silvia; Genitori, Lorenzo; de Martino, Maurizio

    2015-01-01

    Human cytomegalovirus (HCMV) is a common human pathogen which induces different clinical manifestations related to the age and the immune conditions of the host. HCMV infection seems to be involved in the pathogenesis of adult glioblastomas. The aim of our study was to detect the presence of HCMV in high grade gliomas and other pediatric brain tumors. This hypothesis might have important therapeutic implications, offering a new target for adjuvant therapies. Among 106 pediatric patients affected by CNS tumors we selected 27 patients with a positive HCMV serology. The serological analysis revealed 7 patients with positive HCMV IGG (≥14 U/mL), whom had also a high HCMV IgG avidity, suggesting a more than 6 months-dated infection. Furthermore, HCMV IGM were positive (≥22 U/mL) in 20 patients. Molecular and immunohistochemical analyses were performed in all the 27 samples. Despite a positive HCMV serology, confirmed by ELISA, no viral DNA was shown at the PCR analysis in the patients' neoplastic cells. At immunohistochemistry, no expression of HCMV antigens was observed in tumoral cells. Our results are in agreement with recent results in adults which did not evidence the presence of HCMV genome in glioblastoma lesions. We did not find any correlation between HCMV infection and pediatric CNS tumors. PMID:26396923

  5. Absence of human cytomegalovirus infection in childhood brain tumors

    PubMed Central

    Sardi, Iacopo; Lucchesi, Maurizio; Becciani, Sabrina; Facchini, Ludovica; Guidi, Milena; Buccoliero, Anna Maria; Moriondo, Maria; Baroni, Gianna; Stival, Alessia; Farina, Silvia; Genitori, Lorenzo; de Martino, Maurizio

    2015-01-01

    Human cytomegalovirus (HCMV) is a common human pathogen which induces different clinical manifestations related to the age and the immune conditions of the host. HCMV infection seems to be involved in the pathogenesis of adult glioblastomas. The aim of our study was to detect the presence of HCMV in high grade gliomas and other pediatric brain tumors. This hypothesis might have important therapeutic implications, offering a new target for adjuvant therapies. Among 106 pediatric patients affected by CNS tumors we selected 27 patients with a positive HCMV serology. The serological analysis revealed 7 patients with positive HCMV IGG (≥14 U/mL), whom had also a high HCMV IgG avidity, suggesting a more than 6 months-dated infection. Furthermore, HCMV IGM were positive (≥22 U/mL) in 20 patients. Molecular and immunohistochemical analyses were performed in all the 27 samples. Despite a positive HCMV serology, confirmed by ELISA, no viral DNA was shown at the PCR analysis in the patients’ neoplastic cells. At immunohistochemistry, no expression of HCMV antigens was observed in tumoral cells. Our results are in agreement with recent results in adults which did not evidence the presence of HCMV genome in glioblastoma lesions. We did not find any correlation between HCMV infection and pediatric CNS tumors. PMID:26396923

  6. Autonomy and Task Performance: Explaining the Impact of Grades on Intrinsic Motivation

    ERIC Educational Resources Information Center

    Pulfrey, Caroline; Darnon, Celine; Butera, Fabrizio

    2013-01-01

    The use of grades to motivate constitutes an unresolved theoretical controversy. In 2 experiments carried out with different age groups and academic tracks, a standard-grade condition was compared with a condition in which differential scoring engendered higher grades and with a no-grade condition. The relative power of task performance and task…

  7. Clinical, Biologic, and Prognostic Differences on the Basis of Primary Tumor Site in Neuroblastoma: A Report From the International Neuroblastoma Risk Group Project

    PubMed Central

    Vo, Kieuhoa T.; Matthay, Katherine K.; Neuhaus, John; London, Wendy B.; Hero, Barbara; Ambros, Peter F.; Nakagawara, Akira; Miniati, Doug; Wheeler, Kate; Pearson, Andrew D.J.; Cohn, Susan L.; DuBois, Steven G.

    2014-01-01

    Purpose Neuroblastoma (NB) is a heterogeneous tumor arising from sympathetic tissues. The impact of primary tumor site in influencing the heterogeneity of NB remains unclear. Patients and Methods Children younger than age 21 years diagnosed with NB or ganglioneuroblastoma between 1990 and 2002 and with known primary site were identified from the International Neuroblastoma Risk Group database. Data were compared between sites with respect to clinical and biologic features, as well as event-free survival (EFS) and overall survival (OS). Results Among 8,369 children, 47% had adrenal tumors. All evaluated clinical and biologic variables differed statistically between primary sites. The features that were > 10% discrepant between sites were stage 4 disease, MYCN amplification, elevated ferritin, elevated lactate dehydrogenase, and segmental chromosomal aberrations, all of which were more frequent in adrenal versus nonadrenal tumors (P < .001). Adrenal tumors were more likely than nonadrenal tumors (adjusted odds ratio, 2.09; 95% CI, 1.67 to 2.63; P < .001) and thoracic tumors were less likely than nonthoracic tumors (adjusted odds ratio, 0.20; 95% CI, 0.11 to 0.39; P < .001) to have MYCN amplification after controlling for age, stage, and histologic grade. EFS and OS differed significantly according to the primary site (P < .001 for both comparisons). After controlling for age, MYCN status, and stage, patients with adrenal tumors had higher risk for events (hazard ratio, 1.13 compared with nonadrenal tumors; 95% CI, 1.03 to 1.23; P = .008), and patients with thoracic tumors had lower risk for events (HR, 0.79 compared with nonthoracic; 95% CI, 0.67 to 0.92; P = .003). Conclusion Clinical and biologic features show important differences by NB primary site, with adrenal and thoracic sites associated with inferior and superior survival, respectively. Future studies will need to investigate the biologic origin of these differences. PMID:25154816

  8. Entrance Age Policies.

    ERIC Educational Resources Information Center

    Stemnock, Suzanne K.

    1968-01-01

    This survey sought information regarding the policies of school districts across the nation on entrance requirements to kindergarten and the first grade. The school systems were classified under four strata according to total enrollment size. The most frequently reported minimum entrance age for kindergarten was 5 years of age by December 1. For…

  9. A Simple Alternative to Grading

    ERIC Educational Resources Information Center

    Potts, Glenda

    2010-01-01

    In this article, the author investigates whether an alternative grading system (contract grading) would yield the same final grades as traditional grading (letter grading), and whether or not it would be accepted by students. The author states that this study demonstrated that contract grading was widely, and for the most part, enthusiastically…

  10. Meningeal Solitary Fibrous Tumors with Delayed Extracranial Metastasis

    PubMed Central

    Han, Nayoung; Kim, Hannah; Min, Soo Kee; Paek, Sun-Ha; Park, Chul-Kee; Choi, Seung-Hong; Chae, U-Ri; Park, Sung-Hye

    2016-01-01

    Background: The term solitary fibrous tumor (SFT) is preferred over meningeal hemangiopericytoma (HPC), because NAB2-STAT6 gene fusion has been observed in both intracranial and extracranial HPCs. HPCs are now considered cellular variants of SFTs. Methods: This study analyzes 19 patients with STAT6-confirmed SFTs, who were followed for over 11 years in a single institution. Ten patients (10/19, 56.2%) had extracranial metastases (metastatic group), while the remainder (9/19) did not (non-metastatic group). These two groups were compared clinicopathologically. Results: In the metastatic group, the primary metastatic sites were the lungs (n = 6), bone (n = 4), and liver (n = 3). There was a mean lag time of 14.2 years between the diagnosis of the initial meningeal tumor to that of systemic metastasis. The median age at initial tumor onset was 37.1 years in the metastatic group and 52.5 in the non-metastatic group. The 10-year survival rates of the metastatic- and non-metastatic groups were 100% and 33%, respectively. The significant prognostic factors for poor outcomes on univariate analysis included advanced age (≥45 years) and large initial tumor size (≥5 cm). In contrast, the patients with higher tumor grade, high mitotic rate (≥5/10 high-power fields), high Ki-67 index (≥5%), and the presence of necrosis or CD34 positivity showed tendency of poor prognosis but these parameters were not statistically significant poor prognostic markers. Conclusions: Among patients with SFTs, younger patients (<45 years) experienced longer survival times and paradoxically had more frequent extracranial metastases after long latent periods than did older patients. Therefore, young patients with SFTs require careful surveillance and follow-up for early detection of systemic metastases. PMID:26657311

  11. [Imaging of childhood brain tumors].

    PubMed

    Couanet, D; Adamsbaum, C

    2006-06-01

    Brain tumors represent around a quarter of all solid tumors observed in the pediatric population. Infratentorial tumors are the most frequent, mostly encountered between 4 and 11 years of age. Early imaging is important because initial symptoms can be misinterpreted as statural and pubertal disorders or pseudoabdominal symptoms with apathy and vomiting in infants. Because signal abnormalities on MRI are most often not specific, it is essential to take into account the clinical and topographic characteristics of the lesion to establish an appropriate differential diagnosis. The main patterns of brain tumors observed in pediatrics are presented. Brain metastases are very unusual in children, in contrast to lepto-meningeal metastasis. PMID:16778744

  12. A prospective Phase II clinical trial of 5-aminolevulinic acid to assess the correlation of intraoperative fluorescence intensity and degree of histologic cellularity during resection of high-grade gliomas.

    PubMed

    Lau, Darryl; Hervey-Jumper, Shawn L; Chang, Susan; Molinaro, Annette M; McDermott, Michael W; Phillips, Joanna J; Berger, Mitchel S

    2016-05-01

    OBJECT There is evidence that 5-aminolevulinic acid (ALA) facilitates greater extent of resection and improves 6-month progression-free survival in patients with high-grade gliomas. But there remains a paucity of studies that have examined whether the intensity of ALA fluorescence correlates with tumor cellularity. Therefore, a Phase II clinical trial was undertaken to examine the correlation of intensity of ALA fluorescence with the degree of tumor cellularity. METHODS A single-center, prospective, single-arm, open-label Phase II clinical trial of ALA fluorescence-guided resection of high-grade gliomas (Grade III and IV) was held over a 43-month period (August 2010 to February 2014). ALA was administered at a dose of 20 mg/kg body weight. Intraoperative biopsies from resection cavities were collected. The biopsies were graded on a 4-point scale (0 to 3) based on ALA fluorescence intensity by the surgeon and independently based on tumor cellularity by a neuropathologist. The primary outcome of interest was the correlation of ALA fluorescence intensity to tumor cellularity. The secondary outcome of interest was ALA adverse events. Sensitivities, specificities, positive predictive values (PPVs), negative predictive values (NPVs), and Spearman correlation coefficients were calculated. RESULTS A total of 211 biopsies from 59 patients were included. Mean age was 53.3 years and 59.5% were male. The majority of biopsies were glioblastoma (GBM) (79.7%). Slightly more than half (52.5%) of all tumors were recurrent. ALA intensity of 3 correlated with presence of tumor 97.4% (PPV) of the time. However, absence of ALA fluorescence (intensity 0) correlated with the absence of tumor only 37.7% (NPV) of the time. For all tumor types, GBM, Grade III gliomas, and recurrent tumors, ALA intensity 3 correlated strongly with cellularity Grade 3; Spearman correlation coefficients (r) were 0.65, 0.66, 0.65, and 0.62, respectively. The specificity and PPV of ALA intensity 3 correlating

  13. Ovarian serous cystadenofibromas associated with a low-grade serous carcinoma of the peritoneum.

    PubMed

    Hinson, Stacy A; Silva, Elvio G; Pinto, K

    2013-06-01

    Ovarian serous cystadenofibromas are benign neoplasms that sometimes have focal areas of borderline serous tumor and rarely have been associated with epithelial proliferations in the peritoneum, resembling implants. We are reporting 2 cases of ovarian serous cystadenofibromas with serous peritoneal lesions of higher grade than the ovarian tumor: 1 case had a serous carcinoma and another 1 a serous borderline tumor. PMID:22921726

  14. Correlation of leptin receptor expression with BMI in differential grades of human meningiomas

    PubMed Central

    RUTKOWSKI, ROBERT; RESZEC, JOANNA; HERMANOWICZ, ADAM; CHRZANOWSKI, ROBERT; LYSON, TOMASZ; MARIAK, ZENON; CHYCZEWSKI, LECH

    2016-01-01

    Meningioma is one of the most common primary brain tumor, especially in postmenopausal women. The most important risk factors include radiation, primary head injury or genetic alterations, however it is currently unclear why postmenopausal women are predominantly affected. The aim of the present study was to evaluate leptin receptor (LEPR) expression and body mass index (BMI) in patients with meningiomas of differential grades. Specimens of 158 meningiomas were classified as either G1 (low-grade meningiomas, n=114) or G2/G3 (high-grade meningiomas, n=44). Immunohistochemistry was performed to assess LEPR expression. The mean BMIs of the female and male patient groups were 28.43±5.29 and 23.93±4.66, respectively. Mean BMI was significantly higher in the female group, by ~4.50 kg/m2. Patient age significantly correlated with LEPR expression, with the highly positive (++) and positive (+) groups having mean ages of 62.3±12.07 and 52.3±13.04, respectively. A strong positive correlation (r=0.73) was observed between leptin receptor expression and BMI, with the LEPR (++) group having a mean BMI of 30.11±4.49, compared to 22.12±2.48 for the LEPR (+) group. Furthermore, in the low-grade meningioma group, mean BMI was higher in female patients than male patients (28.13±5.54 and 25.38±4.57, respectively; P=0.01). Additionally, there was strong positive correlation between BMI and leptin receptor expression in the low-grade meningioma group (r=0.69). For the high-grade meningioma group, mean BMI was 29.49±4.26 and 21.76±3.98 in female and male patients, respectively, and LEPR expression strongly correlated with BMI in this group (r=0.80). The present study demonstrates a correlation between patient BMI, age, and LEPR expression status in low- and high-grade meningiomas. Our results indicate that in addition to endogenous hormones, such as estrogen or progesterone, or fatty tissue-associated proinflammatory cytokines, LEPR expression status may be a risk factor for

  15. Signal transduction molecules in gliomas of all grades

    PubMed Central

    Ermoian, Ralph P.; Kaprealian, Tania; Lamborn, Kathleen R.; Yang, Xiaodong; Jelluma, Nannette; Arvold, Nils D.; Zeidman, Ruth; Berger, Mitchel S.; Stokoe, David

    2010-01-01

    Purpose To interrogate grade II, III, and IV gliomas and characterize the critical effectors within the PI3-kinase pathway upstream and downstream of mTOR. Experimental design Tissues from 87 patients who were treated at UCSF between 1990 and 2004 were analyzed. Twenty-eight grade II, 17 grade III glioma, 26 grade IV gliomas, and 16 non-tumor brain specimens were analyzed. Protein levels were assessed by immunoblots; RNA levels were determined by polymerase chain reaction amplification. To address the multiple comparisons, first an overall analysis was done comparing the four groups using Spearman’s Correlation Coefficient. Only if this analysis was statistically significant were individual pairwise comparisons done. Results Multiple comparison analyses revealed a significant correlation with grade for all variables examined, except phosphorylated-S6. Expression of phosphorylated-4E-BP1, phosphorylated-PKB/Akt, PTEN, TSC1, and TSC2 correlated with grade (P < 0.01 for all). We extended our analyses to ask whether decreases in TSC proteins levels were due to changes in mRNA levels, or due to changes in post-transcriptional alterations. We found significantly lower levels of TSC1 and TSC2 mRNA in GBMs than in grade II gliomas or non-tumor brain (P < 0.01). Conclusions Expression levels of critical signaling molecules upstream and downstream of mTOR differ between non-tumor brain and gliomas of any grade. The single variable whose expression did not differ between non-tumor brain and gliomas was phosphorylated-S6, suggesting that other protein kinases, in addition to mTOR, contribute significantly to S6 phosphorylation. mTOR provides a rational therapeutic target in gliomas of all grades, and clinical benefit may emerge as mTOR inhibitors are combined with additional agents. PMID:18759130

  16. Calcifying Fibrous Tumor

    PubMed Central

    Chorti, Angeliki; Papavramidis, Theodossis S.; Michalopoulos, Antonios

    2016-01-01

    Abstract Calcifying fibrous tumor (CFT) is a benign lesion characterized by its specific histological findings and is found as solitary or multiple lesions in several locations of the human body. The aim of the present systematic review is to give a detailed account of all reported cases of CFT in the literature and to analyze the available data, to completely characterize the entity from epidemiological, medical, and surgical aspects. A bibliographic research was performed from 1988 until 2015. A database with the patients’ characteristics was made, including sex, age, location of the tumor, symptoms, symptoms duration, size of the tumor, diagnostic methods, treatment, metastasis, and follow-up. A total of 104 articles were identified, reporting 157 cases of CFT. Mean age of patients was 33.58 years and the ratio between men and women was 1:1.27. The most common locations of CFT were stomach (18%), small intestine (8.7%), pleura (9.9%), mesentery (5%), and peritoneum (6.8%). Mean diameter of the tumor was estimated 4.6 cm. The correlations proceeded showed that as age increases, size decreases (P = 0.001) and that the tumor is larger in females (P = 0.027). Kruskal-Wallis test showed that the larger tumors appear in the neck and adrenal gland (P = 0.001). The percentage of asymptomatic patients was 30.57%. Computed tomography and biopsy were the most common tests for the diagnosis of CFT. Open surgical procedure was performed in the majority of cases. The median hospitalization was 6.06 days and the mean follow-up period was 29.97 months. Recurrences were mentioned in 10 of 96 patients with available data. No deaths owing to CFT were mentioned in the literature. CFT should be included in the differential diagnosis of enlarging mass revealed by clinical or imaging examination either incidentally or after specific acute or chronic symptomatology. PMID:27196478

  17. Properties of textile grade ceramic fibers

    NASA Technical Reports Server (NTRS)

    Pudnos, Eric

    1992-01-01

    The availability of textile grade ceramic fibers has sparked great interest for applications in composite reinforcement and high temperature insulation. This paper summarizes the properties of various small diameter textile grade ceramic fibers currently available. Room temperature mechanical and electrical properties of the fibers are discussed for three cases: ambient conditions, after heat aging in argon, and after heat aging in wet air. Dow Corning (R) HPZ Ceramic Fiber, a silicon nitride type fiber, is shown to have improved retention of mechanical and electrical properties above 1200 C.

  18. Neurovascular Invasion and Histological Grade Serve as the Risk Factors of Cervical Lymph Node Metastases in Early Tongue Squamous Cell Carcinoma.

    PubMed

    Wu, Kailiu; Yang, Xi; Li, Liwen; Ruan, Min; Liu, Wei; Lu, Wei; Zhang, Chenping; Li, Siyi

    2016-07-01

    The objectives of this study were to analyze the regional characteristics of the cervical lymph node metastasis and to investigate the factors associated with the risk of lymph node involvement. One hundred seventy-one patients suffering from early primary squamous cell carcinoma (SCC) of the tongue (cT1-2N0) were enrolled. Gender, age, growth site, T stage, histological grade, and neurovascular invasion were statistically analyzed by K-M survival analysis and Cox multivariate analysis to evaluate the relationship between the factors and the neck lymph node metastasis. Of the 171 cases divided into the neck dissection group and observation group, 40 ended up with lymph node metastasis, of which 17 were metastasized to level I, 27 to level II, 10 to level III, 2 to level IV, and 1 to level V. Histological grade and neurovascular invasion were significantly associated with lymph node involvement in univariate and multivariate analyses. Age distribution was found to be significantly associated with the lymph node metastasis in multivariate analysis. The metastasis of early tongue SCC has a certain regularity at different sites. Age was not a critical risk factor for cervical lymph node metastasis after surgery. Tumor size was suspected to exert a negative effect on metastasis by influencing tumor invasion. Histological grade and neurovascular invasion were significantly associated with the risk of cervical lymph node metastasis of early tongue SCC. PMID:25911199

  19. Pindborg tumor

    PubMed Central

    Caliaperoumal, Santhosh Kumar; Gowri, S.; Dinakar, J.

    2016-01-01

    Calcifying epithelial odontogenic tumor (CEOT), also known as Pindborg tumor, is a rare odontogenic epithelial neoplasm. So far, nearly 200 cases have been reported in the literature. We are reporting a case of CEOT in a 42-year-old male patient with painless bony swelling in the mandible. The clinical, radiographic, and histopathologic features are discussed with relevant references. PMID:27041911

  20. [Grading of soft tissue and bone sarcomas].

    PubMed

    Petersen, I; Wardelmann, E

    2016-07-01

    Malignancy grading is an essential element in the classification of sarcomas. It correlates with the prognosis of the disease and the risk of metastasis. This article presents the grading schemes for soft tissue, bone and pediatric sarcomas. It summarizes the histological criteria of the Federation Nationale des Centres de Lutte Contre le Cancer (FNCLCC) system and the Pediatric Oncology Group as well as the grading of bone tumors by the College of American Pathologists (CAP). Furthermore, the potential relevance of gene expression signatures, the complexity index in sarcoma (CINSARC) and single genetic alterations (p53, MDM2, p16, SWI/SNF, EWSR1 fusions and PAX3/PAX7-FOXO1 fusions) for the prognosis of sarcomas are discussed. PMID:27384333

  1. A Study in Predicting English Grades for First-Time-in-College Students Using the Career Planning Program (CPP) and Multiple Assessment and Program Services (MAPS) Reading and Language Scores, Age, Gender, and Race.

    ERIC Educational Resources Information Center

    Johnson, Randell G.

    To identify a set of predictor variables for student grades in a first-quarter English course, a study was undertaken of students' reading and language scores on the Career Planning Program (CPP) and the Multiple Assessment and Program Services (MAPS) placement tests. In addition, the relationship was examined between the first-quarter English…

  2. Coming of Age in the 1990s: The Eighth-Grade Class of 1988 12 Years Later. Initial Results from the Fourth Follow-Up to the National Educational Longitudinal Study of 1988. Statistical Analysis Report.

    ERIC Educational Resources Information Center

    Ingels, Steven J.; Curtin, Thomas R.; Kaufman, Phillip; Alt, Martha Naomi; Chen, Xianglei; Owings, Jeffrey A.

    This report examines the eighth grade cohort of 1888 in the year 2000. It presents findings from the fourth followup survey of the National Education Longitudinal Study of 1988 (NELS:88), from the year in which most cohort members turned 26. The period in which this cohort attended school saw major initiatives in educational reform in the United…

  3. Intra-operative brain tumor detection using elastic light single-scattering spectroscopy: a feasibility study

    NASA Astrophysics Data System (ADS)

    Canpolat, Murat; Akyüz, Mahmut; Gökhan, Güzide Ayşe; Gürer, Elif Inanç; Tuncer, Recai

    2009-09-01

    We have investigated the potential application of elastic light single-scattering spectroscopy (ELSSS) as an adjunctive tool for intraoperative rapid detection of brain tumors and demarcation of the tumor from the surrounding normal tissue. Measurements were performed on 29 excised tumor specimens from 29 patients. There were 21 instances of low-grade tumors and eight instances of high-grade tumors. Normal gray matter and white matter brain tissue specimens of four epilepsy patients were used as a control group. One low-grade and one high-grade tumor were misclassified as normal brain tissue. Of the low- and high-grade tumors, 20 out of 21 and 7 out of 8 were correctly classified by the ELSSS system, respectively. One normal white matter tissue margin was detected in a high-grade tumor, and three normal tissue margins were detected in three low-grade tumors using spectroscopic data analysis and confirmed by histopathology. The spectral slopes were shown to be positive for normal white matter brain tissue and negative for normal gray matter and tumor tissues. Our results indicate that signs of spectral slopes may enable the discrimination of brain tumors from surrounding normal white matter brain tissue with a sensitivity of 93% and specificity of 100%.

  4. Aquaporins and Brain Tumors.

    PubMed

    Maugeri, Rosario; Schiera, Gabriella; Di Liegro, Carlo Maria; Fricano, Anna; Iacopino, Domenico Gerardo; Di Liegro, Italia

    2016-01-01

    Brain primary tumors are among the most diverse and complex human cancers, and they are normally classified on the basis of the cell-type and/or the grade of malignancy (the most malignant being glioblastoma multiforme (GBM), grade IV). Glioma cells are able to migrate throughout the brain and to stimulate angiogenesis, by inducing brain capillary endothelial cell proliferation. This in turn causes loss of tight junctions and fragility of the blood-brain barrier, which becomes leaky. As a consequence, the most serious clinical complication of glioblastoma is the vasogenic brain edema. Both glioma cell migration and edema have been correlated with modification of the expression/localization of different isoforms of aquaporins (AQPs), a family of water channels, some of which are also involved in the transport of other small molecules, such as glycerol and urea. In this review, we discuss relationships among expression/localization of AQPs and brain tumors/edema, also focusing on the possible role of these molecules as both diagnostic biomarkers of cancer progression, and therapeutic targets. Finally, we will discuss the possibility that AQPs, together with other cancer promoting factors, can be exchanged among brain cells via extracellular vesicles (EVs). PMID:27367682

  5. Aquaporins and Brain Tumors

    PubMed Central

    Maugeri, Rosario; Schiera, Gabriella; Di Liegro, Carlo Maria; Fricano, Anna; Iacopino, Domenico Gerardo; Di Liegro, Italia

    2016-01-01

    Brain primary tumors are among the most diverse and complex human cancers, and they are normally classified on the basis of the cell-type and/or the grade of malignancy (the most malignant being glioblastoma multiforme (GBM), grade IV). Glioma cells are able to migrate throughout the brain and to stimulate angiogenesis, by inducing brain capillary endothelial cell proliferation. This in turn causes loss of tight junctions and fragility of the blood–brain barrier, which becomes leaky. As a consequence, the most serious clinical complication of glioblastoma is the vasogenic brain edema. Both glioma cell migration and edema have been correlated with modification of the expression/localization of different isoforms of aquaporins (AQPs), a family of water channels, some of which are also involved in the transport of other small molecules, such as glycerol and urea. In this review, we discuss relationships among expression/localization of AQPs and brain tumors/edema, also focusing on the possible role of these molecules as both diagnostic biomarkers of cancer progression, and therapeutic targets. Finally, we will discuss the possibility that AQPs, together with other cancer promoting factors, can be exchanged among brain cells via extracellular vesicles (EVs). PMID:27367682

  6. [Tumors and tumor-like diseases of the carpal bones].

    PubMed

    Baron, J; Scharizer, E

    1987-07-01

    This presentation concerns the findings in 105 tumors or tumor-like lesions in the bones of the carpus. These tumors generally produce complaints which are uncharacteristic and they are quite difficult to recognize on X-ray. Due to this difficulty, there may be many different therapies before the correct final diagnosis is confirmed. These tumors are usually found in the scaphoid, capitate, lunate, or hamate. Of the 105 tumors, 45.7% were osteoid osteoma, which has an incidence of only 11.33% of all bone tumors in the body as a whole. Of the remaining tumors, 15.24% were diagnoses to be intraosseous ganglia (= tumorlike lesions). Lesser percentages were giant-cell tumors, osteochondromas, chondromas. One intraosseous lipoma was found and this had never before been reported. The majority of the patients were between twenty and thirty years of age. With surgical removal, complaints are generally reduced. Dramatic relief from pain is reported by patients when an osteoid osteoma is removed. The most important deduction from these findings is that tumors in the carpus are not as rare as once assumed. The possibility of bone tumors should be considered in patients with intractable pain in the carpus. PMID:3623270

  7. [Gross tumor volume (GTV) and clinical target volume (CTV) in adult gliomas].

    PubMed

    Kantor, G; Loiseau, H; Vital, A; Mazeron, J J

    2001-10-01

    Glioblastoma multiform and astrocytoma are the most frequent primary cancer of the central nervous system of adult. Definitions of gross tumor volume (GTV) and clinical target volume (CTV) are based on the confrontation of clinical presentation (age, performance status, neurologic symptoms...), histological type and imaging aspects. For glioblastoma multiform, the GTV can be defined by the area of contrast enhancement observed on the CT scan or MRI. Definition of the CTV can be more difficult and have to take into account the risk of presence of isolated malignant cells in the oedema surrounding the tumor or in the adjacent brain structures. The classical concept of GTV plus a safety margin of 2 cm around is discussed with a CTV containing at least all the oedematous area and eventually adjacent brain structures (nuclei, corpus callosum or other long associative fibers...). For low grade astrocytoma, the definition of GTV can be difficult if the tumoral infiltration is diffuse without nodular visible tumor. CTV corresponds to at least T2 MRI hypersignal area when visible. For postoperative tumor, technical considerations are important for the detection of residual tumor. A safety margin around the resected area is designed according to the risk of presence of isolated cells or involvement of adjacent brain structures. PMID:11715309

  8. Long-Term Results of Brachytherapy With Temporary Iodine-125 Seeds in Children With Low-Grade Gliomas

    SciTech Connect

    Korinthenberg, Rudolf; Neuburger, Daniela; Trippel, Michael; Ostertag, Christoph; Nikkhah, Guido

    2011-03-15

    Purpose: To retrospectively review the results of temporary I-125 brachytherapy in 94 children and adolescents with low-grade glioma. Methods and Materials: Treatment was performed in progressive tumors roughly spherical in shape with a diameter of up to 5 cm, including 79 astrocytomas, 5 oligodendrogliomas, 4 oligoastrocytomas, 1 ependymoma, and 5 other tumors. Location was suprasellar/chiasmal in 44, thalamic/basal ganglia in 18, hemispheric in 15, midbrain/pineal region in 13, and lower brainstem in 3. Initially, 8% of patients were free of symptoms, 47% were symptomatic but not disabled, and 30% were slightly, 6% moderately, and 3% severely disabled. Results: 5- and 10-year survival was 97% and 92%. The response to I-125 brachytherapy over the long term was estimated after a median observation period of 38.4 (range, 6.4-171.0) months. At that time, 4 patients were in complete, 27 in partial, and 18 in objective remission; 15 showed stable and 30 progressive tumors. Treatment results did not correlate with age, sex, histology, tumor size, location, or demarcation of the tumor. Secondary treatment became necessary in 36 patients, including 19 who underwent repeated I-125 brachytherapy. At final follow-up, the number of symptom-free patients had risen to 21%. Thirty-eight percent showed symptoms without functional impairment, 19% were slightly and 11% moderately disabled, and only 4% were severely disabled. Conclusions: Response rates similar to those of conventional radiotherapy or chemotherapy can be anticipated with I-125 brachytherapy in tumors of the appropriate size and shape. We believe it to be a useful contribution to the treatment of low-grade gliomas in children.

  9. Detection and grading of human gliomas by FTIR spectroscopy and a genetic classification algorithm

    NASA Astrophysics Data System (ADS)

    Steiner, Gerald; Shaw, R. A.; Choo-Smith, Lin-P'ing; Steller, Wolfram; Shapoval, Laryssa; Schackert, Gabriele; Sobottka, Stephan; Salzer, Reiner; Mantsch, Henry H.

    2002-03-01

    A new approach is presented to distinguish cancerous from normal brain tissue via linear discriminant analysis of Fourier transform infrared (FTIR) spectra. FTIR microspectroscopy was used to map various thin-section tumor samples with different malignancy grades (grades II-VI) and non-tumor samples obtained from various patients by surgical removal. Spectral analysis revealed features characteristic of tumors with increasing malignancy. A genetic region selection algorithm combined with linear discriminant analysis was used to derive classifiers distinguishing among spectra of control tissue, astrocytoma grade II, astrocytoma grade III and glioblastoma grade IV. Employing the World Health Organization histopathological diagnostic scheme as the gold standard, the spectra were classified with a success rate of approximately 85 percent. These results demonstrate the potential of the combination of FTIR spectroscopy and pattern recognition routines in providing a more objective method for brain tumour grading and diagnosis.

  10. Pediatric high-grade astrocytomas: a distinct neuro-oncological paradigm.

    PubMed

    Gerges, Noha; Fontebasso, Adam M; Albrecht, Steffen; Faury, Damien; Jabado, Nada

    2013-01-01

    Brain tumors are the leading cause of cancer-related death in children. High-grade astrocytomas (HGAs), in particular, are lethal in children across all ages. Integrative genome-wide analyses of the tumor's genome, transcriptome and epigenome, using next-generation sequencing technologies and genome-wide DNA methylation arrays, have provided valuable breakthroughs in our understanding of the pathogenesis of HGAs across all ages. Recent profiling studies have provided insight into the epigenetic nature of gliomas in young adults and HGAs in children, particularly with the identification of recurrent gain-of-function driver mutations in the isocitrate dehydrogenase 1 and 2 genes (IDH1/2) and the epigenetic influence of their oncometabolite 2-hydroxyglutarate, as well as mutations in the histone 3 variant 3 gene (H3F3A) and loss-of-function mutations in the histone 3 lysine 36 trimethyltransferase gene (SETD2). Mutations in H3F3A result in amino acid substitutions at residues thought to directly (K27M) or indirectly (G34R/V) affect histone post-translational modifications, suggesting they have the capacity to affect the epigenome in a profound manner. Here, we review recent genomic studies, and discuss evidence supporting the molecular characterization of pediatric HGAs to complement traditional approaches, such as histology of resected tumors. We also describe newly identified molecular mechanisms and discuss putative therapeutic approaches for HGAs specific to pediatrics, highlighting the necessity for the evolution of HGA disease management approaches. PMID:23906214

  11. Radioembolization of hepatic tumors

    PubMed Central

    2014-01-01

    Unresectable primary and metastatic liver tumors are a leading cause of cancer mortality and morbidity. This remains a challenging and key task for every oncologist despite significant advances that have been made with selective targeted systemic agents and in technology advances with radiotherapy delivery. Radioembolization (RE) is a technique of permanently implanting microspheres containing Yttrium-90 (90Y), a beta-emitting isotope with a treatment range of 2 mm, into hepatic tumors. This form of brachytherapy utilizes the unique dual vascular anatomy of the liver to preferentially deliver radioactive particles via the hepatic artery to tumor, sparing normal liver parenchyma. The main treatment inclusion criteria are patients with solid tumors, compensated liver functions, life expectancy of at least three months, and ECOG performance status 0-2. Benefit of RE has been proven in patients that have low-to-moderate extrahepatic disease burden, prior liver radiotherapy, heavy prior chemotherapy and biologic agent exposure, and history of hepatic surgery or ablation. Most of the clinical evidence is reported in metastatic colorectal, and neuroendocrine tumors (NET), and primary hepatocellular cancer. A growing body of data supports the use of RE in hepatic metastatic breast cancer, intrahepatic cholangiocarinoma, and many other metastatic tumor types. Side effects are typically mild constitutional and GI issues limited to the first 7-14 days post treatment, with only 6% grade 3 toxicity reported in large series. Potentially serious or fatal radiation induced liver disease is extremely rare, reported in only 1% or fewer in major series of both metastatic and primary tumors treated with RE. Currently, high priority prospective clinical trials are testing RE combined with chemotherapy in first line therapy for colorectal hepatic metastases, and combined with sorafenib for hepatocellular carcinomas (HCCs). Fortunately, this beneficial and now widely available therapy is

  12. Radioembolization of hepatic tumors.

    PubMed

    Kennedy, Andrew

    2014-06-01

    Unresectable primary and metastatic liver tumors are a leading cause of cancer mortality and morbidity. This remains a challenging and key task for every oncologist despite significant advances that have been made with selective targeted systemic agents and in technology advances with radiotherapy delivery. Radioembolization (RE) is a technique of permanently implanting microspheres containing Yttrium-90 ((90)Y), a beta-emitting isotope with a treatment range of 2 mm, into hepatic tumors. This form of brachytherapy utilizes the unique dual vascular anatomy of the liver to preferentially deliver radioactive particles via the hepatic artery to tumor, sparing normal liver parenchyma. The main treatment inclusion criteria are patients with solid tumors, compensated liver functions, life expectancy of at least three months, and ECOG performance status 0-2. Benefit of RE has been proven in patients that have low-to-moderate extrahepatic disease burden, prior liver radiotherapy, heavy prior chemotherapy and biologic agent exposure, and history of hepatic surgery or ablation. Most of the clinical evidence is reported in metastatic colorectal, and neuroendocrine tumors (NET), and primary hepatocellular cancer. A growing body of data supports the use of RE in hepatic metastatic breast cancer, intrahepatic cholangiocarinoma, and many other metastatic tumor types. Side effects are typically mild constitutional and GI issues limited to the first 7-14 days post treatment, with only 6% grade 3 toxicity reported in large series. Potentially serious or fatal radiation induced liver disease is extremely rare, reported in only 1% or fewer in major series of both metastatic and primary tumors treated with RE. Currently, high priority prospective clinical trials are testing RE combined with chemotherapy in first line therapy for colorectal hepatic metastases, and combined with sorafenib for hepatocellular carcinomas (HCCs). Fortunately, this beneficial and now widely available therapy

  13. Gene Expression in Oligodendroglial Tumors

    PubMed Central

    Shaw, Elisabeth J.; Haylock, Brian; Husband, David; du Plessis, Daniel; Sibson, D. Ross; Warnke, Peter C.; Walker, Carol

    2010-01-01

    Background: Oligodendroglial tumors with 1p/19q loss are more likely to be chemosensitive and have longer survival than those with intact 1p/19q, but not all respond to chemotherapy, warranting investigation of the biological basis of chemosensitivity. Methods: Gene expression profiling was performed using amplified antisense RNA from 28 oligodendroglial tumors treated with chemotherapy (26 serial stereotactic biopsy, 2 resection). Expression of differentially expressed genes was validated by real-time PCR. Results: Unsupervised hierarchical clustering showed clustering of multiple samples from the same case in 14/17 cases and identified subgroups associated with tumor grade and 1p/19q status. 176 genes were differentially expressed, 164 being associated with 1p/19q loss (86% not on 1p or 19q). 94 genes differed between responders and non-responders to chemotherapy; 12 were not associated with 1p/19q loss. Significant differential expression was confirmed in 11/13 selected genes. Novel genes associated with response to therapy included SSBP2, GFRA1, FAP and RASD1. IQGAP1, INA, TGIF1, NR2F2 and MYCBP were differentially expressed in oligodendroglial tumors with 1p/19q loss. Conclusion: Gene expression profiling using serial stereotactic biopsies indicated greater homogeneity within tumors than between tumors. Genes associated with 1p/19q status or response were identified warranting further elucidation of their role in oligodendroglial tumors. PMID:20966545

  14. Vascular Tumors

    PubMed Central

    Sepulveda, Abel; Buchanan, Edward P.

    2014-01-01

    Vascular anomalies are divided into two main groups: tumors and malformations. Vascular tumors are a large and complex group of lesions, especially for clinicians with none or little experience in this field. In the past, these lesions caused a great deal of confusion because many appear analogous to the naked eye. Thankfully, recent advances in diagnostic techniques have helped the medical community to enhance our comprehension, accurately label, diagnose, and treat these lesions. In this article, we will review the most frequent vascular tumors and provide the reader with the tools to properly label, diagnose, and manage these complex lesions. PMID:25045329

  15. Beef grading by ultrasound

    NASA Technical Reports Server (NTRS)

    Gammell, P. M.

    1981-01-01

    Reflections in ultrasonic A-scan signatures of beef carcasses indicate USDA grade. Since reflections from within muscle are determined primarily by fat/muscle interface, richness of signals is direct indication of degree of marbling and quality. Method replaces subjective sight and feel tests by individual graders and is applicable to grade analysis of live cattle.

  16. Grain Grading and Handling.

    ERIC Educational Resources Information Center

    Rendleman, Matt; Legacy, James

    This publication provides an introduction to grain grading and handling for adult students in vocational and technical education programs. Organized in five chapters, the booklet provides a brief overview of the jobs performed at a grain elevator and of the techniques used to grade grain. The first chapter introduces the grain industry and…

  17. Classroom: Efficient Grading

    ERIC Educational Resources Information Center

    Shaw, David D.; Pease, Leonard F., III.

    2014-01-01

    Grading can be accelerated to make time for more effective instruction. This article presents specific time management strategies selected to decrease administrative time required of faculty and teaching assistants, including a multiple answer multiple choice interface for exams, a three-tier grading system for open ended problem solving, and a…

  18. Controlling Grade Inflation

    ERIC Educational Resources Information Center

    Stanoyevitch, Alexander

    2008-01-01

    In this article concerning grade inflation, the author restricts his attention to the college and university level, although many of the tools and ideas developed here should be useful for high schools as well. The author considers the relationships between grades instructors assign and scores they receive on end-of-the semester student…

  19. Are Math Grades Cyclical?

    ERIC Educational Resources Information Center

    Adams, Gerald J.; Dial, Micah

    1998-01-01

    The cyclical nature of mathematics grades was studied for a cohort of elementary school students from a large metropolitan school district in Texas over six years (average cohort size of 8495). The study used an autoregressive integrated moving average (ARIMA) model. Results indicate that grades do exhibit a significant cyclical pattern. (SLD)

  20. Grading Exceptional Learners

    ERIC Educational Resources Information Center

    Jung, Lee Ann; Guskey, Thomas R.

    2010-01-01

    Teachers often grapple with the challenge of giving report card grades to students with learning disabilities and English language learners. The authors offer a five-step model that "offers a fair, accurate, and legal way to adapt the grading process for exceptional learners." The model begins with a high-quality reporting system for all students…

  1. Third Grade Reading Policies

    ERIC Educational Resources Information Center

    Rose, Stephanie

    2012-01-01

    In 2012, 14 states passed legislation geared toward improving 3rd-grade literacy through identification, intervention, and/or retention initiatives. Today, a total of 32 states and the District of Columbia have policies in statute aimed at improving 3rd-grade reading proficiency. The majority of these states require early assessment and…

  2. Making Grading Work.

    ERIC Educational Resources Information Center

    Lotto, Edward; Smith, Bruce

    Two teachers have developed a procedure for grading student compositions that seems fairer to both them and their students. The students are given a choice of which papers they wish to submit for grading, and when they do submit work, the papers are identified by a number only (chosen by the student and indexed in a class card file). Each teacher…

  3. Determining Faculty Grading Variation.

    ERIC Educational Resources Information Center

    Demerjian, Marlene D.

    A study was undertaken at the College of the Canyons, in California, to assess the variation of grades given by mathematics instructors teaching intermediate algebra. A sample was drawn from all instructors who taught Math 070 repeatedly from fall 1990 to fall 1994, resulting in the examination of the grades of at least 200 students from classes…

  4. Grades out, Badges in

    ERIC Educational Resources Information Center

    Young, Jeffrey R.

    2012-01-01

    Grades are broken. Students grub for them, pick classes where good ones come easily, and otherwise hustle to win the highest scores for the least learning. As a result, college grades are inflated to the point of meaninglessness--especially to employers who want to know which diploma-holder is best qualified for their jobs. An alternative is to…

  5. The Grades Game

    ERIC Educational Resources Information Center

    Fleenor, Andy; Lamb, Sarah; Anton, Jennifer; Stinson, Todd; Donen, Tony

    2011-01-01

    It can be quite alarming (and eye-opening) to see exactly how many of the grades students receive are based on their behaviors rather than their learning. Students should be assessed on what they know and can use rather than on their behavior. The reality, unfortunately, is that the opposite is often the case. Grades for students who work hard are…

  6. Are Grades Undermining Motivation?

    ERIC Educational Resources Information Center

    Berliner, David; Casanova, Ursula

    1988-01-01

    A study of fifth and sixth grade public school students in Israel suggests that grades and other norm-referenced methods are less effective than task-involving evaluation methods in enhancing student performance, interest, and motivation. This article consists of two commentaries on the findings, with suggestions for implementing task-involving…

  7. Phase II TPDCV protocol for pediatric low-grade hypothalamic/chiasmatic gliomas: 15-year update

    PubMed Central

    Mishra, Kavita K.; Squire, Sarah; Lamborn, Kathleen; Banerjee, Anuradha; Gupta, Nalin; Wara, William M.; Prados, Michael D.; Berger, Mitchel S.

    2010-01-01

    To report long-term results for children with low-grade hypothalamic/chiasmatic gliomas treated on a phase II chemotherapy protocol. Between 1984 and 1992, 33 children with hypothalamic/chiasmatic LGGs received TPDCV chemotherapy on a phase II prospective trial. Median age was 3.0 years (range 0.3–16.2). Twelve patients (36%) underwent STRs, 14 (42%) biopsy only, and seven (21%) no surgery. Twenty patients (61%) had pathologic JPAs, nine (27%) grade II gliomas, and four (12%) no surgical sampling. Median f/u for surviving patients was 15.2 years (range 5.3–20.7); 20 of the 23 surviving patients had 14 or more years of follow-up. Fifteen-year PFS and OS were 23.4 and 71.2%, respectively. Twenty-five patients progressed, of whom 13 are NED, two are AWD, and 10 have died. All children who died were diagnosed and first treated at age three or younger. Age at diagnosis was significantly associated with relapse and survival (P = 0.004 for PFS and P = 0.037 for OS). No PFS or OS benefit was seen with STR versus biopsy/no sampling (P = 0.58 for PFS, P = 0.59 for OS). For patients with JPAs and WHO grade II tumors, the 15-year PFS was 18.8 and 22.2% (P = 0.95) and 15-year OS was 73.7 and 55.6% (P = 0.17), respectively. Upfront TPDCV for children with hypothalamic/chiasmatic LGGs resulted in 15-year OS of 71.2% and 15-year PFS of 23.4%. No survival benefit is demonstrated for greater extent of resection. Age is a significant prognostic factor for progression and survival. PMID:20221671

  8. Phase II TPDCV protocol for pediatric low-grade hypothalamic/chiasmatic gliomas: 15-year update.

    PubMed

    Mishra, Kavita K; Squire, Sarah; Lamborn, Kathleen; Banerjee, Anuradha; Gupta, Nalin; Wara, William M; Prados, Michael D; Berger, Mitchel S; Haas-Kogan, Daphne A

    2010-10-01

    To report long-term results for children with low-grade hypothalamic/chiasmatic gliomas treated on a phase II chemotherapy protocol. Between 1984 and 1992, 33 children with hypothalamic/chiasmatic LGGs received TPDCV chemotherapy on a phase II prospective trial. Median age was 3.0 years (range 0.3-16.2). Twelve patients (36%) underwent STRs, 14 (42%) biopsy only, and seven (21%) no surgery. Twenty patients (61%) had pathologic JPAs, nine (27%) grade II gliomas, and four (12%) no surgical sampling. Median f/u for surviving patients was 15.2 years (range 5.3-20.7); 20 of the 23 surviving patients had 14 or more years of follow-up. Fifteen-year PFS and OS were 23.4 and 71.2%, respectively. Twenty-five patients progressed, of whom 13 are NED, two are AWD, and 10 have died. All children who died were diagnosed and first treated at age three or younger. Age at diagnosis was significantly associated with relapse and survival (P = 0.004 for PFS and P = 0.037 for OS). No PFS or OS benefit was seen with STR versus biopsy/no sampling (P = 0.58 for PFS, P = 0.59 for OS). For patients with JPAs and WHO grade II tumors, the 15-year PFS was 18.8 and 22.2% (P = 0.95) and 15-year OS was 73.7 and 55.6% (P = 0.17), respectively. Upfront TPDCV for children with hypothalamic/chiasmatic LGGs resulted in 15-year OS of 71.2% and 15-year PFS of 23.4%. No survival benefit is demonstrated for greater extent of resection. Age is a significant prognostic factor for progression and survival. PMID:20221671

  9. Phase I study of temozolomide in combination with thiotepa and carboplatin with autologous hematopoietic cell rescue in patients with malignant brain tumors with minimal residual disease.

    PubMed

    Egan, G; Cervone, K A; Philips, P C; Belasco, J B; Finlay, J L; Gardner, S L

    2016-04-01

    Recurrence of malignant brain tumors results in a poor prognosis with limited treatment options. High-dose chemotherapy with autologous hematopoietic cell rescue (AHCR) has been used in patients with recurrent malignant brain tumors and has shown improved outcomes compared with standard chemotherapy. Temozolomide is standard therapy for glioblastoma and has also shown activity in patients with medulloblastoma/primitive neuro-ectodermal tumor (PNET), particularly those with recurrent disease. Temozolomide was administered twice daily on days -10 to -6, followed by thiotepa 300 mg/m(2) per day and carboplatin dosed using the Calvert formula or body surface area on days -5 to -3, with AHCR day 0. Twenty-seven patients aged 3-46 years were enrolled. Diagnoses included high-grade glioma (n=12); medulloblastoma/PNET (n=9); central nervous system (CNS) germ cell tumor (n=4); ependymoma (n=1) and spinal cord PNET (n=1). Temozolomide doses ranged from 100 mg/m(2) per day to 400 mg/m(2) per day. There were no toxic deaths. Prolonged survival was noted in several patients including those with recurrent high-grade glioma, medulloblastoma and CNS germ cell tumor. Increased doses of temozolomide are feasible with AHCR. A phase II study using temozolomide, carboplatin and thiotepa with AHCR for children with recurrent malignant brain tumors is being conducted through the Pediatric Blood and Marrow Transplant Consortium. PMID:26726947

  10. Human tumor clonogenic assay for carcinoma of the lung. II. Factors that influence colony formation in soft agar.

    PubMed

    Kanzawa, F; Matsushima, Y; Hamburger, A W; Ishihara, J; Sasaki, Y; Shimizu, E; Eguchi, K; Shinkai, T; Saijo, N; Miyazawa, N

    1987-01-01

    The human tumor clonogenic assay (HTCA) has potential value for studies of both the chemosensitivity and biology of human tumors. However, many technical problems including low plating efficiencies and the preparation of sufficient numbers of viable cells remain. In this study, an improved method for disaggregation of solid tumors increased the yield of single cells. Consequently, more than 10 anticancer drugs could be tested in 94 of 168 specimens (56%). Removal of peripheral blood lymphocytes from cell suspensions derived from effusions also improved colony formation. Adequate growth for sensitivity testing (greater than 30 colonies/plate) was obtained in 122 cases (73%), inadequate growth for drug evaluation (5-29 colonies/plate) in 29 cases (17%), and no colony formation (less than 5 colonies/plate) in 17 cases (10%) of the 168 viable samples. The cloning efficiencies of cells derived from primary tumors (median 0.015%) were higher than those of cells derived from metastatic tumors (0.012%), and they varied with the location of the metastatic site. Cloning efficiencies varied markedly from specimen to specimen, and were unaffected by tumor histology, grade of differentiation, patient age, stage of disease, or prior chemotherapy. The HTCA is promising as a potential tool for studying the biology of tumors. PMID:3601316

  11. Hypothalamic tumor

    MedlinePlus

    ... in the brain to reduce spinal fluid pressure. Risks of radiation therapy include damage to healthy brain cells when tumor cells are destroyed. Common side effects from chemotherapy include loss of appetite, nausea and vomiting, and fatigue.

  12. Brain Tumors

    MedlinePlus

    ... brain. Brain tumors can be benign, with no cancer cells, or malignant, with cancer cells that grow quickly. Some are primary brain ... targeted therapy. Targeted therapy uses substances that attack cancer cells without harming normal cells. Many people get ...

  13. Wilms Tumor

    MedlinePlus

    ... diagnosis, and the condition, or histology , of the cancer cells when observed under a microscope. "Favorable" histology is associated with a good chance of a cure; tumors with "unfavorable" histology are more aggressive and ...

  14. Tumor Markers

    MedlinePlus

    ... types: Germ cell tumors, lymphoma, leukemia, melanoma, and neuroblastoma Tissue analyzed: Blood How used: To assess stage, ... NSE) Cancer types: Small cell lung cancer and neuroblastoma Tissue analyzed: Blood How used: To help in ...

  15. Wilms tumor

    MedlinePlus

    ... this tumor in most children is unknown. A missing iris of the eye (aniridia) is a birth ... Nausea Swelling in the abdomen (abdominal hernia or mass) Vomiting Exams and Tests The doctor or nurse ...

  16. Low-grade astrocytoma in a child with encephalocraniocutaneous lipomatosis.

    PubMed

    Brassesco, María Sol; Valera, Elvis Terci; Becker, Aline Paixão; Castro-Gamero, Angel Mauricio; de Aboim Machado, André; Santos, Antônio Carlos; Scrideli, Carlos Alberto; Oliveira, Ricardo Santos; Machado, Hélio Rubens; Tone, Luiz Gonzaga

    2010-02-01

    Encephalocutaneous lipomatosis (ECCL), or Haberland syndrome, is an uncommon congenital disorder with unique cutaneous, ocular and neurological features. In the present article, we describe a 3-year-old boy with ECCL who developed an extensive and recurring intraventricular low-grade glioma with atypical pathological features and elevated mitotic index. Cytogenetic analysis from tumor sample was also performed. This is the first report of a low-grade astrocytoma occurring in a child with ECCL. Whether or not the origin of the tumor is associated to the pathogenesis of the underlying syndrome is a matter for further investigation. PMID:19652916

  17. Five Obstacles to Grading Reform

    ERIC Educational Resources Information Center

    Guskey, Thomas R.

    2011-01-01

    Educators seeking to reform grading must combat five long-held traditions that stand as formidable obstacles to change: (1) Grades should provide the basis for differentiating students; (2) grade distributions should resemble a bell-shaped curve; (3) grades should be based on students' standing among classmates; (4) poor grades prompt students to…

  18. Paperless Grades and Faculty Development.

    ERIC Educational Resources Information Center

    Hardy, James C.; Jones, Dennis; Turner, Sandy

    2003-01-01

    Provides overview of process of switching from paper-based grade reporting to computer-based grading. Authors found that paperless grading decreased number of errors, made student access more immediate, and reduced costs incurred by purchasing and storing grade-scanning sheets. Authors also argue that direct entry grading encourages faculty to…

  19. Pediatric brain tumors in a low/middle income country: does it differ from that in developed world?

    PubMed

    Ezzat, Sameera; Kamal, Mohamed; El-Khateeb, Nada; El-Beltagy, Mohamed; Taha, Hala; Refaat, Amal; Awad, Madeha; Abouelnaga, Sherif; Zaghloul, Mohamed Saad

    2016-01-01

    Central nervous system (CNS) tumors are the most frequent solid tumors in children and adolescents. The epidemiology of these tumors differs in areas of the world. However, very little data is available in the low/middle income countries (LMIC). The aim of this study is to describe the characteristics of primary childhood brain tumors treated at a leading LMIC pediatric cancer hospital and its difference from that in other countries. One thousand one hundred fourteen children and adolescent having CNS tumors were treated in the largest pediatric cancer hospital in the Middle East during a period of 5½ years. They were diagnosed histopathologically in 80.2 %, through medical imaging in 19.4 % and via both tumor markers and imaging in the remaining 0.4 % of cases. Through epidemiological analysis was performed using all available patients' data revealed that 96 % of the patients had primary brain tumors, while only 4 % the primary lesion was in the spinal cord. The most common histological type was astrocytic tumor (30.0 %, pilocytic (GI) = 13.2 %, GII = 10.5 % and GIII + IV (high grade) = 6.3 %) followed by embryonal tumor (23.2 %, medulloblastoma = 18.7 %, PNET = 2.8 %, ATRT = 1.5 % and ependymoblastoma = 0.2 %) then ependymoma in 8.7 %, craniopharyngeoma in 5.3 %. The mean age at diagnosis was 7.1 ± 4.2 years which did not differ significantly by gender nor residency but it differed by the pathological subtype. The frequency of each pathological type was different among different age groups. Though the present study was a hospital-based analysis in a low/middle income country, yet it did not differ from the well-established population-based study reports in the high income countries. PMID:26514358

  20. Career Development Intervention in Fourth Grade.

    ERIC Educational Resources Information Center

    Dobson, Ruth

    This paper contains a unit of six career awareness lessons for use by elementary guidance counselors with fourth grade students. Prepared to be used with fourth graders in a middle class small community elementary school in Wisconsin, the unit is based on developmental needs that have been identified for this age group. It is intended to be both…

  1. Informational Literacy in the Middle Grades.

    ERIC Educational Resources Information Center

    Erickson, Lawrence

    1998-01-01

    Compares classical literacy (which treats reading and writing as distinct from content subjects) with informational literacy. Discusses seven key informational-literacy teaching practices and class activities that middle grade teachers can use to prepare their students for life in the information age. (SR)

  2. Physical Education, Kindergarten Through Grade Seven.

    ERIC Educational Resources Information Center

    Virginia State Dept. of Education, Richmond.

    GRADE OR AGES: K-7. SUBJECT MATTER: Physical education. ORGANIZATION AND PHYSICAL APPEARANCE: The guide is in five parts: 1) "The Place of Physical Education in the Elementary School"; 2) "Developing the Physical Education Offering"; 3) "Analysis of Skills"; 4) "Physical Education Activities"; and 5) "Related and Supplementary Materials." The…

  3. A Call to Action: Transforming Grading Practices

    ERIC Educational Resources Information Center

    Erickson, Jeffrey A.

    2011-01-01

    At a very early age, students learn the point system and how school can be about the accumulation of points, not the accumulation of knowledge and skills. Grading systems are pervasive in districts across the nation, with questionable results. For example, a southern school district was highlighted in a 2009 Associated Press story for selling test…

  4. Educational Outcomes and Indicators for Grade 8.

    ERIC Educational Resources Information Center

    Ysseldyke, James E.; And Others

    This document presents a conceptual model of educational domains and outcomes for learners in Grade 8 (or approximately 13 years of age) and possible indicators for each outcome for all students, including students with disabilities or developmental delays. In the model, educational resources (inputs and contexts) influence learning opportunity…

  5. Dysembryoplastic neuroepithelial tumor: A rare brain tumor not to be misdiagnosed

    PubMed Central

    Sukheeja, Deepti; Mehta, Jayanti

    2016-01-01

    Dysembryoplastic neuroepithelial tumor (DNET) is a recently described, morphologically unique, and surgically curable low-grade brain tumor which is included in the latest WHO classification as neuronal and mixed neuronal-glial tumor. It is usually seen in children and young adults. The importance of this particular entity is that it is a surgically curable neuroepithelial neoplasm. When recognized, the need for adjuvant radiotherapy and chemotherapy is obviated. We hereby present a case report of an 8-year-old male child who presented with intractable seizures and parieto-occipital space occupying lesion. Histologically, the tumor exhibited features of WHO grade I dysembryoplastic neuroepithelial tumor which was further confirmed by immunohistochemistry. PMID:27057233

  6. Dysembryoplastic neuroepithelial tumor: A rare brain tumor not to be misdiagnosed.