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Sample records for high grade squamous

  1. High-grade squamous intraepithelial lesion arising adjacent to vulvar lymphangioma circumscriptum: a tertiary institutional experience

    PubMed Central

    Bae, Go Eun; Yoon, Gun; Song, Yong Jung; Kim, Hyun-Soo

    2016-01-01

    Lymphangioma circumscriptum of the vulva occurs in patients who have undergone radical hysterectomy, lymph node dissection, or radiation therapy for management of advanced uterine cancer. Since vulvar lymphangioma circumscriptum typically presents as multiple, grossly verrucous vesicles of various sizes, it may be impossible to clinically distinguish vulvar lymphangioma circumscriptum from other vulvoperineal cutaneous diseases. In the present study, 16 (1.6%) out of the 1,024 vulvar biopsy or excision specimens were diagnosed as lymphangioma circumscriptum. In two (12.5%) out of the 16 cases, unusual histopathological findings were observed. Both patients had previously undergone radical hysterectomy with lymph node dissection and postoperative radiation therapy or concurrent chemoradiation therapy for advanced cervical cancer. Microscopic examination revealed high-grade squamous intraepithelial lesions, which were located immediately adjacent to the normal squamous epithelium covering the dilated subepithelial lymphatic vessels. Further, human papillomavirus genotyping confirmed that both patients were infected with high-risk human papillomavirus. High-grade squamous intraepithelial lesion cannot be grossly distinguished from vulvar lymphangioma circumscriptum because the multiple, verrucous vesicles that constitute the characteristic gross appearance of vulvar lymphangioma circumscriptum hinder its distinction. In this regard, our cases of high-grade squamous intraepithelial lesion, located adjacent to vulvar lymphangioma circumscriptum, support the notion that active surgical excision is necessary for the treatment of vulvar lymphangioma circumscriptum. PMID:27329721

  2. Revised terminology for cervical histopathology and its implications for management of high-grade squamous intraepithelial lesions of the cervix.

    PubMed

    Waxman, Alan G; Chelmow, David; Darragh, Teresa M; Lawson, Herschel; Moscicki, Anna-Barbara

    2012-12-01

    In March 2012, the College of American Pathologists and American Society for Colposcopy and Cervical Pathology, in collaboration with 35 stakeholder organizations, convened a consensus conference called the Lower Anogenital Squamous Terminology (LAST) Project. The recommendations of this project include using a uniform, two-tiered terminology to describe the histology of human papillomavirus-associated squamous disease across all anogenital tract tissues: vulva, vagina, cervix, penis, perianus, and anus. The recommended terminology is "low-grade" or "high-grade squamous intraepithelial lesion (SIL)." This terminology is familiar to clinicians, because it parallels the terminology of the Bethesda System cytologic reports. Biopsy results using SIL terminology may be further qualified using "intraepithelial neoplasia" (IN) terminology in parentheses. Laboratory p16 tissue immunostaining is recommended to better classify histopathology lesions that morphologically would earlier have been diagnosed as IN 2. p16 is also recommended for differentiating between high-grade squamous intraepithelial lesions and benign mimics. The LAST Project recommendations potentially affect the application of current guidelines for managing cervical squamous intraepithelial lesions. The authors offer interim guidance for managing cervical lesions diagnosed using this new terminology with special attention paid to managing young women with cervical high-grade squamous intraepithelial lesions on biopsy. Clinicians should be aware of the LAST Project recommendations, which include important changes from prior terminology.

  3. Cytohistological correlation of endocervical gland involvement with high-grade squamous intraepithelial lesions

    PubMed Central

    Kir, G; Karabulut, MH; Yilmaz, MS; Topal, CS; Gocmen, A

    2012-01-01

    Background: Diagnosis of endocervical glandular involvement by high-grade squamous intraepithelial lesion (HSIL-EGI) on Papanicolaou (Pap) smears can affect the clinical management of patients. Aim: The cytological criteria for the diagnosis of HSIL-EGI are described and the accuracy of this diagnosis was investigated. Materials and Methods: Seventeen patients diagnosed with HSIL-EGI and 40 patients with diagnosis of HSIL on Pap smears with follow-up cone or loop electrocautery excision procedure (LEEP) biopsies were included in the study. The following criteria were evaluated for the cytological diagnosis of HSIL-EGI: atypical cells with definite features of HSIL, three-dimensional atypical squamous cell clusters (TDCs) with attached benign endocervical epithelium, finger-like TDCs covered with intact epithelium on most sides, which represent the finger-like invaginations of the endocervical glandular area involved by HSIL, and the absence of cytological findings of in situ adenocarcinoma of the cervix. Results: On subsequent histopathological evaluation, 16 of 17 (94.1%) patients with a cytological diagnosis of HSIL-EGI and 17 of 40 (42.5%) patients with HSIL exhibited endocervical glandular involvement (P < 0.001, sensitivity: 48.5%, specificity: 95.8%, positive predictive value: 94.1%, negative predictive value: 57.5% and accuracy: 68.4%). Conclusion: Diagnosis of HSIL-EGI may be possible on Pap smears with a high positive predictive value and specificity but low sensitivity, possibly due to cytological sampling limitations. To clarify the results of the present study, more extensive studies with a particular emphasis on the sampling of the endocervical glandular area for cytological evaluation of the cervix are needed. PMID:22787292

  4. Effect of Thin Prep® imaging system on laboratory rate and relative sensitivity of atypical squamous cells, high-grade squamous intraepithelial lesion not excluded and high-grade squamous intraepithelial lesion interpretations

    PubMed Central

    Koltz, Brooke R.; Russell, Donna K.; Lu, Naiji; Bonfiglio, Thomas A.; Varghese, Sharlin

    2013-01-01

    Introduction: Automated screening of Thin Prep® Papanicolaou Tests has become increasingly common in clinical practice. Increased productivity has initiated laboratory use of the Thin Prep® Imaging System (TIS). Increased sensitivity is a potential additional benefit of TIS. Published studies have shown an increase in discovery of dysplastic cells. This study evaluates the effect of TIS on the incidence of atypical squamous cells high-grade squamous intraepithelial lesion not excluded (ASC-H) and high-grade squamous intraepithelial lesion (HGSIL) results on Thin Prep® Pap Tests by comparing TIS-assisted and manual screening findings and the diagnoses on subsequent follow-up in a screening population over a 1-year time period. Materials and Methods: A compilation of all ASC-H and HGSIL cases was prepared by conducting a computerized search over a 1-year period (7/06-6/07). The accumulated cases include Thin Prep Pap tests that were both TIS and manually screened. Follow-up results of cytologic and histologic cervical specimens were obtained for a time period extending to 2010. Interpretation utilizing TIS was in place 10 months prior to the study's initiation. Results: During the study period 70,522 Pap tests were performed in our laboratory. One third (33%) of Pap tests were screened with assistance of TIS. Manual screening was performed on 47,380 Pap tests of which 153 (0.32%) were interpreted as ASC-H and 164 (0.35%) were interpreted as HGSIL. During the same time period automated screening (TIS) was performed on 23,111 Pap tests. Interpretation of 62 (0.27%) cases provided an ASC-H result, while 71 (0.31%) were HGSIL. Follow-up cervical dysplasia by colposcopic biopsy and cone biopsy was distributed proportionally between TIS and manual screening for both ASC-H and HGSIL categories. Cervical intraepithelial neoplasia (CIN II/III) was identified on follow-up biopsy of 41% TIS cases and 45% manually screened cases for ASC-H. In the HGSIL subset 71% of TIS cases

  5. γH2Ax Expression as a Potential Biomarker Differentiating between Low and High Grade Cervical Squamous Intraepithelial Lesions (SIL) and High Risk HPV Related SIL

    PubMed Central

    Kefala, Maria; Kottaridi, Christine; Spathis, Aris; Gouloumi, Alina-Roxani; Pouliakis, Abraham; Pappas, Asimakis; Sioulas, Vasileios; Chrelias, Charalambos; Karakitsos, Petros; Panayiotides, Ioannis

    2017-01-01

    Background γH2AX is a protein biomarker for double-stranded DNA breakage; its expression was studied in cervical squamous intraepithelial lesions and carcinomas. Methods Immunostaining for phospho-γH2AX was performed in sections from histologically confirmed cervical SIL and carcinomas, as well as from normal cervices used as controls. In total, 275 cases were included in the study: 112 low grade SIL (LGSIL), 99 high grade SIL (HGSIL), 24 squamous cell carcinoma (SCC), 12 adenocarcinoma and 28 cervical specimens with no essential lesions. Correlation of histological grading, high risk vs. low risk HPV virus presence, activated vs. non-activated status (by high risk HPV mRNA expression) and γH2AX expression in both basal and surface segments of the squamous epithelium was performed. Results Gradual increase of both basal and surface γH2AX expression was noted up from normal cervices to LGSIL harboring a low risk HPV type, to LGSIL harboring a high risk virus at a non-activated state (p<0.05). Thereafter, both basal and surface γH2AX expression dropped in LGSIL harboring a high risk virus at an activated state and in HGSIL. Conclusions γH2AX could serve as a potential biomarker discriminating between LGSIL and HGSIL, as well as between LGSIL harboring high risk HPV at an activated state. PMID:28118377

  6. Regulation of PD-L1 expression in a high-grade invasive human oral squamous cell carcinoma microenvironment.

    PubMed

    Hirai, Mariko; Kitahara, Hiroko; Kobayashi, Yutaka; Kato, Koroku; Bou-Gharios, George; Nakamura, Hiroyuki; Kawashiri, Shuichi

    2017-01-01

    Blockade of the programmed-death 1 receptor (PD-1)/programmed-death ligand (PD-L1) pathway efficiently reduces tumour growth and improves survival. Durable tumour regression with blockade of the PD-1/PD-L1 checkpoint has been demonstrated in recent clinical studies. Oral squamous cell carcinoma (OSCC) is highly immunosuppressive, and PD-L1 expression has been proposed as a potential mechanism responsible for this phenotype. Despite the fact that anti-PD-1 treatment can produce durable responses, such therapy appears to benefit only a subset of patients. Thus, it is important to understand the mechanisms underlying regulation of PD-L1 expression in the OSCC microenvironment. In this study, we showed that PD-L1 expression in high-grade invasive OSCC cell lines was lower than that in a low-grade invasive OSCC line and found a close correlation between PD-L1 expression and the epithelial-mesenchymal transition (EMT). PD-L1 expression was upregulated in macrophages and dendritic cells (DCs) in high-grade invasive human OSCC tissues or co-cultured with mesenchymal-phenotype OSCC cells in vitro. TLR4-inhibitory peptide successfully suppressed PD-L1 upregulation on macrophages and DCs co-cultured with mesenchymal-phenotype OSCC cells, suggesting that some EMT-induced tumour antigen is critical for PD-L1 induction on tumour-associated macrophages and DCs. Further studies are necessary to explore the impact of EMT on the tumour immune microenvironment and to identify potential biomarkers for selecting patients who might preferentially benefit from PD-1/PD-L1 blockade or immunotherapies more broadly.

  7. Regulation of PD-L1 expression in a high-grade invasive human oral squamous cell carcinoma microenvironment

    PubMed Central

    Hirai, Mariko; Kitahara, Hiroko; Kobayashi, Yutaka; Kato, Koroku; Bou-Gharios, George; Nakamura, Hiroyuki; Kawashiri, Shuichi

    2017-01-01

    Blockade of the programmed-death 1 receptor (PD-1)/programmed-death ligand (PD-L1) pathway efficiently reduces tumour growth and improves survival. Durable tumour regression with blockade of the PD-1/PD-L1 checkpoint has been demonstrated in recent clinical studies. Oral squamous cell carcinoma (OSCC) is highly immunosuppressive, and PD-L1 expression has been proposed as a potential mechanism responsible for this phenotype. Despite the fact that anti-PD-1 treatment can produce durable responses, such therapy appears to benefit only a subset of patients. Thus, it is important to understand the mechanisms underlying regulation of PD-L1 expression in the OSCC microenvironment. In this study, we showed that PD-L1 expression in high-grade invasive OSCC cell lines was lower than that in a low-grade invasive OSCC line and found a close correlation between PD-L1 expression and the epithelial-mesenchymal transition (EMT). PD-L1 expression was upregulated in macrophages and dendritic cells (DCs) in high-grade invasive human OSCC tissues or co-cultured with mesenchymal-phenotype OSCC cells in vitro. TLR4-inhibitory peptide successfully suppressed PD-L1 upregulation on macrophages and DCs co-cultured with mesenchymal-phenotype OSCC cells, suggesting that some EMT-induced tumour antigen is critical for PD-L1 induction on tumour-associated macrophages and DCs. Further studies are necessary to explore the impact of EMT on the tumour immune microenvironment and to identify potential biomarkers for selecting patients who might preferentially benefit from PD-1/PD-L1 blockade or immunotherapies more broadly. PMID:27922697

  8. Phosphorylated mTOR expression correlates with podoplanin expression and high tumor grade in esophageal squamous cell carcinoma

    PubMed Central

    Chuang, Wen-Yu; Chang, Yu-Sun; Chao, Yin-Kai; Yeh, Chi-Ju; Ueng, Shir-Hwa; Chang, Chiu-Yueh; Liu, Yun-Hen; Tseng, Chen-Kan; Chang, Hsien-Kun; Wan, Yung-Liang; Hsueh, Chuen

    2015-01-01

    Mechanistic (or mammalian) target of rapamycin (mTOR) plays important roles in cell growth and proliferation. In esophageal squamous cell carcinoma (SCC), high expression of phosphorylated (activated) mTOR (p-mTOR) has been reported as an adverse prognostic factor in some but not all studies. The signals of mTOR pathway and mitogen-activated protein kinase (MAPK) pathway converge on 4E-binding protein 1 (4EBP1), which drives the downstream proliferative signals. We previously found that high expression of phosphorylated 4EBP1 (p-4EBP1) is an adverse prognostic factor in esophageal SCC. Podoplanin is a type-1 transmembrane glycoprotein expressed in various normal human tissues, including lymphatic endothelium. Our previous study showed that high podoplanin expression correlates with clinical nodal metastasis, which is associated with short survival in esophageal SCC. In current study, we investigated p-mTOR expression by immunohistochemistry in 75 cases of surgically resected esophageal SCC. The result was correlated with p-4EBP1 expression, podoplanin expression, clinicopathologic features and patient survival. We found that high p-mTOR expression was significantly associated with high podoplanin expression (P = 0.0030) and high tumor grade (P = 0.0014). No correlation with p-4EBP1 expression, patient survival or other clinicopathologic features was found. Recently, podoplanin expression in astrocytic brain tumors was found to be regulated by the phosphatidylinositol 3-kinase (PI3K)/AKT/activator protein-1 (AP-1) pathway. Similarly, mTOR is activated by a PI3K/AKT/mTOR pathway. The association of p-mTOR and podoplanin expression in our study could be due to a common upstream pathway. Since both mTOR and podoplanin are potential therapeutic targets, the possible benefit of combined targeted therapy warrants further investigation. PMID:26722465

  9. Anal and perianal squamous carcinomas and high-grade intraepithelial lesions exclusively associated with "low-risk" HPV genotypes 6 and 11.

    PubMed

    Cornall, Alyssa M; Roberts, Jennifer M; Garland, Suzanne M; Hillman, Richard J; Grulich, Andrew E; Tabrizi, Sepehr N

    2013-11-01

    Anal squamous cell carcinomas are predominantly associated with high-risk human papillomaviruses (HPVs), particularly HPV 16, similar to cervical, vaginal and vulvar cancers. Although the presence of "low-risk" HPVs, in particular genotypes 6 and 11, have occasionally been reported in various HPV-related anogenital cancers, the overall distribution of these genotypes in the anal canal and perianal tissue may differ to that in the cervix. In addition, although the majority of anal and perianal cancers are associated with HPV, some are not; hence, confirmation of direct association of the virus within a lesion is important. Using laser capture microdissection, anal and perianal invasive carcinomas and high-grade squamous intraepithelial lesions (HSILs) in biopsies previously associated with HPV 6 or 11 alone were isolated from tissue sections and HPV genotype tested. Of seven cases tested, four invasive carcinomas were positive for HPV 6 only, one invasive carcinoma was negative for HPV and two HSILs were positive for HPV 11 only. All samples were confirmed as HPV 16/18 negative using two different DNA targets (E6 and L1). From these results, we confirm that HPV 6 and 11 can occasionally be associated with high-grade lesion and anal cancer.

  10. Comparison of self-collected vaginal, vulvar and urine samples with physician-collected cervical samples for human papillomavirus testing to detect high-grade squamous intraepithelial lesions

    PubMed Central

    Sellors, John W.; Lorincz, Attila T.; Mahony, James B.; Mielzynska, Iwona; Lytwyn, Alice; Roth, Paula; Howard, Michelle; Chong, Sylvia; Daya, Dean; Chapman, William; Chernesky, Max

    2000-01-01

    Background Certain types of human papillomavirus (HPV) in cervical samples are strongly associated with squamous intraepithelial lesions (SIL) and invasive cervical carcinoma. We determined and compared the test characteristics of testing for HPV with samples obtained by patients and with samples obtained by their physicians. Methods In a consecutive series of women referred to a colposcopy clinic at a teaching hospital because of abnormalities on cervical cytologic screening, 200 agreed to collect vulvar, vaginal and urine samples for HPV testing. The physician then collected cervical samples for HPV testing, and colposcopy, with biopsy as indicated, was performed. Presence of HPV was evaluated using the hybrid capture II assay (Digene Corp., Silver Spring, Md.) with a probe cocktail for 13 carcinogenic types. Cervical specimens were also tested for HPV by polymerase chain reaction and hybridization with type-specific probes. Cervical smears for cytologic examination were obtained from all women. Results High-grade lesions (high-grade squamous intraepithelial lesions [HSIL], equivalent to cervical intraepithelial neoplasia [CIN] grade 2 or 3, and adenocarcinoma) were found in 58 (29.0%) of the 200 women. Carcinogenic types of HPV were detected in the self-collected vaginal samples of 50 (86.2%) of these 58 women, in the self-collected vulvar samples of 36 (62.1%) and in the self-collected urine samples of 26 (44.8%). Carcinogenic types of HPV were detected in the cervical samples collected by physicians for 57 (98.3%) of these 58 women. The remaining 142 women (71.0%) had normal findings or low-grade squamous intraepithelial lesions (LSIL, CIN grade 1). Test results were negative or noncarcinogenic types of HPV were detected in the self-collected vaginal samples of 76 (53.5%) of these 142 women, in the self-collected vulvar samples of 89 (62.7%) and in the self-collected urine samples of 99 (69.7%). The sensitivity for self-collected samples ranged from 44.8% to

  11. Immunoexpression of HPV 16/18 E6 and E7 oncoproteins in high-grade cervical squamous intraepithelial lesions in HIV-positive women.

    PubMed

    Rodrigues, L C; Speck, N M de Gois; Focchi, G R de Azevedo; Schimidt, M A; Marques, R M; Ribalta, J C Lascasas

    2016-02-19

    The aim of this study was to assess the immunoexpression of human papillomavirus genotypes 16 and 18 (E6 and E7) oncoproteins in cervical high-grade squamous intraepithelial lesions (HSIL) of human immunodeficiency virus (HIV)-positive women. These results were also compared to the persistence and/or recurrence of lesions after loop electrosurgical excision procedure. Cervical samples from 158 patients were divided into three groups according to the presence or absence of HSIL in women who were or were not HIV-positive. By using the tissue microarray technique, immunohistochemistry was performed to analyze the expression of HPV 16/18 E6 and E7 oncoproteins. Cervical samples from 95 HIV-positive women and 63 HIV-negative women were studied. A statistically significant difference was found in the immunoexpression of E6 and E7 oncoproteins in samples from HIV-positive women with HSIL and that of women with non-neoplastic tissue (P < 0.001). There was also a statistically significant correlation between the immunoexpression of E6 (P = 0.012) and E7 (P < 0.001) oncoproteins in lesion persistence among HIV-positive women. Within the limitations of this study, the immunoexpression of HPV 16/18 E6 and E7 oncoproteins may have prognostic value regarding lesion persistence in HIV-positive women.

  12. Cytological grading: An alternative to histological grading in oral squamous cell carcinoma

    PubMed Central

    Namala, Srilekha; Guduru, Vijay Srinivas; Ananthaneni, Anuradha; Devi, Sabitha; Kuberappa, Puneeth Horrati; Udayashankar, Urmila

    2016-01-01

    Background: Micronuclei (MN) in oral exfoliative cells have been shown to indicate a disparaging change in genetic information of the cell. Recent studies showed correlation between the frequency of MN and severity of this damage. Grading of lesions can be used to determine the austerity of this damage. Aims: The aim of this study is to compare the MN frequency in oral exfoliated cells of normal and oral squamous cell carcinoma (OSCC) individuals and to cytologically grade the frequency of MN in cytological smears and to correlate it with histological grading. The objective is to ascertain whether MN frequency in oral exfoliated cells can be a parameter for grading of OSCC. Settings and Design: The study group comprises of 40 subjects (20 controls and 20 OSCC patients) in the age group of 45-85 years. Materials and Methods: The cytosmear was obtained from each group and stained with Papanicolaou (PAP) stain. Twenty cells from each slide were counted for MN and cytological grade of OSCC was assigned based on the average frequency of MN. Cytological grade was correlated with histological grading and the data were recorded. Student's t-test and Spearman's correlation were used for the analysis of the data. Results: Average frequency of MN was 2.5 times higher in OSCC patients when compared to that in controls and the difference was found to be highly significant. Sixty percent correlation was found between cytological grade and histological grade of OSCC and the difference between them was not significant. Conclusions: Cytological grading can be used in grading OSCC, and MN insinuates genotoxic damage occurring in the epithelial cells. PMID:27756984

  13. Human Papillomavirus (HPV) DNA Triage of Women with Atypical Squamous Cells of Undetermined Significance with cobas 4800 HPV and Hybrid Capture 2 Tests for Detection of High-Grade Lesions of the Uterine Cervix

    PubMed Central

    Lapierre, Simon Grandjean; Sauthier, Philippe; Mayrand, Marie-Hélène; Dufresne, Simon; Petignat, Patrick; Provencher, Diane; Drouin, Pierre; Gauthier, Philippe; Dupuis, Marie-Josée; Michon, Bertrand; Ouellet, Stéphan; Hadjeres, Rachid; Ferenczy, Alex; Franco, Eduardo L.

    2012-01-01

    The triage of women with high-risk (HR) human papillomavirus (HPV)-positive smears for atypical squamous cells of undetermined significance (ASC-US) to colposcopy is now an integrated option in clinical guidelines. The performance of cobas 4800 HPV and that of Hybrid Capture 2 (HC2) for HR HPV DNA detection in cervical samples in PreservCyt were compared in 396 women referred to colposcopy for ASC-US. Of these, 316 did not have cervical intraepithelial neoplasia (CIN), 47 had CIN1, 29 had CIN2 or CIN3 (CIN2+), and 4 had CIN of unknown grade. HR HPV was detected in 129 (32.6%) and 149 (37.6%) samples with HC2 and cobas 4800 HPV, respectively (P = 0.15). The clinical sensitivities and specificities for detecting CIN2+ were 89.7% (95% confidence interval [CI], 72.8 to 97.2%) and 66.7% (95% CI, 61.7 to 71.3%) with cobas 4800 HPV and 93.1% (95% CI, 77.0 to 99.2%) and 72.2% (95% CI 67.4 to 76.5%) with HC2. The performance of cobas 4800 HPV was similar to that of HC2 for identifying women with ASC-US who would benefit the most from colposcopy. PMID:22301023

  14. Association of human papillomavirus, Neisseria gonorrhoeae and Chlamydia trachomatis co-infections on the risk of high-grade squamous intraepithelial cervical lesion

    PubMed Central

    de Abreu, André LP; Malaguti, Natália; Souza, Raquel P; Uchimura, Nelson S; Ferreira, Érika C; Pereira, Monalisa W; Carvalho, Maria DB; Pelloso, Sandra M; Bonini, Marcelo G; Gimenes, Fabrícia; Consolaro, Marcia EL

    2016-01-01

    The link between high-risk human Papillomavirus (HR-HPV) and other sexually transmitted diseases (STDs) in the risk of developing cervical cancer still unclear. Thus, in this report we investigated the rates of co-infections between HPV and other important non-HPV STDs in different cervical findings using a multiplex polymerase chain reaction (M-PCR) to simultaneously detect Chlamydia trachomatis, Neisseria gonorrhoeae, Mycoplasma genitalium, Trichomonas vaginalis, HSV-1 and -2, and Treponema pallidum. A total of 838 women aged 18 to 68 years were screened using Papanicolaou smears for cervical abnormalities, HPV and non-HPV STDs using PCR and M-PCR methods. A total of 614 (73.3%) of the women had normal cytology (NILM) and 224 (26.7%) women exhibited abnormal cytology (≥ ASC-US). HPV-DNA prevalence was 33.9%, and HPV-16 was the most prevalent genotype in women with NILM and ≥ ASC-US cytology. Non-HPV STDs were detected in 30.4% women and T. vaginalis was the most prevalent one (11.6%). A higher increased risk of ≥ ASC-US and HSIL occurred in co-infections of HR-HPV with C. trachomatis and N. gonorrhoeae. Co-infections of HPV-DNA and HR-HPV with HSV-2 exhibited a similar increased risk but only with ≥ ASC-US. Co-infections of HPV-DNA and HR-HPV with T. vaginalis demonstrated a similar increased risk of ≥ ASC-US and HSIL. We found that C. trachomatis and N. gonorrhoeae were the primary pathogens associated with HR-HPV for the increased risk for all grades of cervical abnormalities but mainly for HSIL, suggesting a possible synergistic action in cervical lesions progression. Our results reinforce the hypothesis that some non-HPV STDs might play a role as co-factors in HPV-mediated cervical carcinogenesis. These data improve our understanding of the etiology of SCC and may also be useful for disease prevention. PMID:27429850

  15. Association of human papillomavirus, Neisseria gonorrhoeae and Chlamydia trachomatis co-infections on the risk of high-grade squamous intraepithelial cervical lesion.

    PubMed

    de Abreu, André Lp; Malaguti, Natália; Souza, Raquel P; Uchimura, Nelson S; Ferreira, Érika C; Pereira, Monalisa W; Carvalho, Maria Db; Pelloso, Sandra M; Bonini, Marcelo G; Gimenes, Fabrícia; Consolaro, Marcia El

    2016-01-01

    The link between high-risk human Papillomavirus (HR-HPV) and other sexually transmitted diseases (STDs) in the risk of developing cervical cancer still unclear. Thus, in this report we investigated the rates of co-infections between HPV and other important non-HPV STDs in different cervical findings using a multiplex polymerase chain reaction (M-PCR) to simultaneously detect Chlamydia trachomatis, Neisseria gonorrhoeae, Mycoplasma genitalium, Trichomonas vaginalis, HSV-1 and -2, and Treponema pallidum. A total of 838 women aged 18 to 68 years were screened using Papanicolaou smears for cervical abnormalities, HPV and non-HPV STDs using PCR and M-PCR methods. A total of 614 (73.3%) of the women had normal cytology (NILM) and 224 (26.7%) women exhibited abnormal cytology (≥ ASC-US). HPV-DNA prevalence was 33.9%, and HPV-16 was the most prevalent genotype in women with NILM and ≥ ASC-US cytology. Non-HPV STDs were detected in 30.4% women and T. vaginalis was the most prevalent one (11.6%). A higher increased risk of ≥ ASC-US and HSIL occurred in co-infections of HR-HPV with C. trachomatis and N. gonorrhoeae. Co-infections of HPV-DNA and HR-HPV with HSV-2 exhibited a similar increased risk but only with ≥ ASC-US. Co-infections of HPV-DNA and HR-HPV with T. vaginalis demonstrated a similar increased risk of ≥ ASC-US and HSIL. We found that C. trachomatis and N. gonorrhoeae were the primary pathogens associated with HR-HPV for the increased risk for all grades of cervical abnormalities but mainly for HSIL, suggesting a possible synergistic action in cervical lesions progression. Our results reinforce the hypothesis that some non-HPV STDs might play a role as co-factors in HPV-mediated cervical carcinogenesis. These data improve our understanding of the etiology of SCC and may also be useful for disease prevention.

  16. CpG Methylation Analysis of HPV16 in Laser Capture Microdissected Archival Tissue and Whole Tissue Sections from High Grade Anal Squamous Intraepithelial Lesions: A Potential Disease Biomarker

    PubMed Central

    Molano, Monica; Tabrizi, Sepehr N.; Garland, Suzanne M.; Roberts, Jennifer M.; Machalek, Dorothy A.; Phillips, Samuel; Chandler, David; Hillman, Richard J.; Grulich, Andrew E.; Jin, Fengyi; Poynten, I. Mary; Templeton, David J.; Cornall, Alyssa M.

    2016-01-01

    Incidence and mortality rates of anal cancer are increasing globally. More than 90% of anal squamous cell carcinomas (ASCC) are associated with human papillomavirus (HPV). Studies on HPV-related anogenital lesions have shown that patterns of methylation of viral and cellular DNA targets could potentially be developed as disease biomarkers. Lesion-specific DNA isolated from formalin-fixed paraffin-embedded (FFPE) tissues from existing or prospective patient cohorts may constitute a valuable resource for methylation analysis. However, low concentrations of DNA make these samples technically challenging to analyse using existing methods. We therefore set out to develop a sensitive and reproducible nested PCR-pyrosequencing based method to accurately quantify methylation at 10 CpG sites within the E2BS1, E2BS2,3,4 and Sp1 binding sites in the viral upstream regulatory region of HPV16 genome. Methylation analyses using primary and nested PCR-pyrosequencing on 52 FFPE tissue [26 paired whole tissue sections (WTS) and laser capture microdissected (LCM) tissues] from patients with anal squamous intraepithelial lesions was performed. Using nested PCR, methylation results were obtained for the E2BS1, E2BS2,3,4 and Sp1 binding sites in 86.4% of the WTS and 81.8% of the LCM samples. Methylation patterns were strongly correlated within median values of matched pairs of WTS and LCM sections, but overall methylation was higher in LCM samples at different CpG sites. High grade lesions showed low methylation levels in the E2BS1 and E2BS2 regions, with increased methylation detected in the E2BS,3,4/Sp1 regions, showing the highest methylation at CpG site 37. The method developed is highly sensitive in samples with low amounts of DNA and demonstrated to be suitable for archival samples. Our data shows a possible role of specific methylation in the HPV16 URR for detection of HSIL. PMID:27529629

  17. CpG Methylation Analysis of HPV16 in Laser Capture Microdissected Archival Tissue and Whole Tissue Sections from High Grade Anal Squamous Intraepithelial Lesions: A Potential Disease Biomarker.

    PubMed

    Molano, Monica; Tabrizi, Sepehr N; Garland, Suzanne M; Roberts, Jennifer M; Machalek, Dorothy A; Phillips, Samuel; Chandler, David; Hillman, Richard J; Grulich, Andrew E; Jin, Fengyi; Poynten, I Mary; Templeton, David J; Cornall, Alyssa M

    2016-01-01

    Incidence and mortality rates of anal cancer are increasing globally. More than 90% of anal squamous cell carcinomas (ASCC) are associated with human papillomavirus (HPV). Studies on HPV-related anogenital lesions have shown that patterns of methylation of viral and cellular DNA targets could potentially be developed as disease biomarkers. Lesion-specific DNA isolated from formalin-fixed paraffin-embedded (FFPE) tissues from existing or prospective patient cohorts may constitute a valuable resource for methylation analysis. However, low concentrations of DNA make these samples technically challenging to analyse using existing methods. We therefore set out to develop a sensitive and reproducible nested PCR-pyrosequencing based method to accurately quantify methylation at 10 CpG sites within the E2BS1, E2BS2,3,4 and Sp1 binding sites in the viral upstream regulatory region of HPV16 genome. Methylation analyses using primary and nested PCR-pyrosequencing on 52 FFPE tissue [26 paired whole tissue sections (WTS) and laser capture microdissected (LCM) tissues] from patients with anal squamous intraepithelial lesions was performed. Using nested PCR, methylation results were obtained for the E2BS1, E2BS2,3,4 and Sp1 binding sites in 86.4% of the WTS and 81.8% of the LCM samples. Methylation patterns were strongly correlated within median values of matched pairs of WTS and LCM sections, but overall methylation was higher in LCM samples at different CpG sites. High grade lesions showed low methylation levels in the E2BS1 and E2BS2 regions, with increased methylation detected in the E2BS,3,4/Sp1 regions, showing the highest methylation at CpG site 37. The method developed is highly sensitive in samples with low amounts of DNA and demonstrated to be suitable for archival samples. Our data shows a possible role of specific methylation in the HPV16 URR for detection of HSIL.

  18. Characterization of a cluster of oncogenic mutations in E6 of a human papillomavirus 83 variant isolated from a high-grade squamous intraepithelial lesion.

    PubMed

    Cannavo, Isabelle; Benchetrit, Maxime; Loubatier, Céline; Michel, Gregory; Lemichez, Emmanuel; Giordanengo, Valérie

    2011-10-01

    We previously isolated human papillomavirus 83 (HPV83m) from a cervical smear. Sequence analysis of E6 and E7 proteins highlighted five mutations located in the second putative zinc-finger region of E6 (E6m), an important domain for protein-protein or protein-DNA interactions. Here, we show that E6m of HPV83m can trigger human primary cell proliferation and anchorage-independent growth properties, similarly to E6 of HPV16, a high-risk HPV (HR-HPV). Interestingly, we demonstrate that, in contrast to E6 of HPV16, E6m corrupts neither p53 stability nor telomerase activity, but acts as a specific modulator of the transcriptional machinery. By studying E6m reversion mutants, we confirmed the importance of the second zinc-finger domain in triggering the observed upregulation of cell growth and of the transcriptional machinery. Reversion of these mutations in E6m (to yield strain E6r) fully abolished the oncogenic potential of E6m, transforming the phenotype of E6 from a high-risk to a low-risk phenotype. Importantly, our data define the importance of a cluster of mutations in the second zinc finger of E6m in increasing the oncogenic potential of HPV83.

  19. Histologic grade in penile squamous cell carcinoma: visual estimation versus digital measurement of proportions of grades, adverse prognosis with any proportion of grade 3 and correlation of a Gleason-like system with nodal metastasis.

    PubMed

    Chaux, Alcides; Torres, José; Pfannl, Rolf; Barreto, Jose; Rodriguez, Ingrid; Velazquez, Elsa F; Cubilla, Antonio L

    2009-07-01

    Histologic grade has been reported as an important pathologic parameter predictive of nodal metastases and outcome in patients with penile squamous cell carcinoma. There is no consensus about the criteria for grading and the proportion of anaplastic cells required to classify a tumor as high grade. The incidence and management of heterogeneous tumors (tumors harboring more than 1 histologic grade) are not well established. The purposes of this study were to present a grading model for penile cancer, to test the practicality of the system by comparing a visual ("naked-eye") estimation of the proportions of grades with a digitally guided measuring system and to determine the influence on nodal metastasis of the various proportions of grades. A total of 117 penectomy and circumcision specimens with bilateral inguinal lymph node dissections were studied and 62 heterogeneous tumors were identified (53%). The following steps were taken: (1) design of a grading system model; (2) determination of proportions of histologic grades by naked-eye evaluation and by digital measurement; (3) evaluation of metastasis according to proportions of grades; (4) determination of the influence of site of grade 3 in nodal metastasis; (5) design of a Gleason-like scoring system; and (6) statistical evaluation. We designed a 3-tier grading system. Grade 1: well-differentiated cells, almost undistinguishable from normal squamous cells except for the presence of minimal basal/parabasal cell atypia. Grade 3: tumors predominantly composed of anaplastic cells. Grade 2: all tumors not fitting into criteria described for grade 1 or 3. A visual and digital-based (slides scanned and the corresponding areas measured with an image-editing software) proportions of grades were estimated and the metastatic rate between them were confronted using different proportions of grade 3. To evaluate the influence of site of grade 3 on nodal metastasis, we selected 20 heterogeneous tumors. We established 3 sites

  20. PCNA and grade in 13 canine oral squamous cell carcinomas: association with prognosis.

    PubMed

    Mestrinho, L A; Faísca, P; Peleteiro, M C; Niza, M M R E

    2017-03-01

    This study evaluated the prognosis factors of age, tumour size, anatomic location, histological grade and proliferating cell nuclear antigen (PCNA) expression in 13 dogs with oral squamous cell carcinoma (OSCC) with bone invasion and without signs of lymph node or distant metastasis. All animals were treated with radical excision performed with at least 1 cm margin, based on computed tomography images. In the 2-year follow-up, median disease-free survival was 138 days for dogs with grade 3 tumours and was not reached for those with grade 2 tumours. Grade 3 tumours and PCNA labelling index ≥65% were related with a shorter disease-free survival time and consequently poor prognosis (p = 0.003 and p = 0.034, respectively). Mean PCNA labelling index was significantly higher in recurrent cases (p = 0.011). Histological grade and PCNA expression may be important prognosis factors in canine OSCC.

  1. Concurrent primary peritoneal low-grade serous carcinoma and endometrial high-grade serous carcinoma.

    PubMed

    Lockyer, Megan G; Deavers, Michael T; Zarrin-Khameh, Neda

    2015-05-01

    A 64-yr-old postmenopausal woman with high-grade squamous intraepithelial lesion and atypical glandular cell of undetermined significance on her Pap test was found to have endometrial serous carcinoma (high grade) involving a polyp in a subsequent endometrial biopsy. She underwent hysterectomy and bilateral salpingo-oophorectomy with multiple biopsies of the peritoneum. Microscopic examination of the entirely submitted uterus showed no residual serous carcinoma. Multiple foci of low-grade serous tumor with extensive calcifications and psammoma bodies were identified on the surfaces of the left fallopian tube, ovaries, and biopsies of the peritoneum, consistent with peritoneal primary low-grade serous carcinoma. To our knowledge, this is the first reported case of low-grade serous carcinoma of the peritoneum with a concurrent (high-grade) serous carcinoma of the endometrium arising from an endometrial polyp.

  2. Synchronous high-grade squamous intraepithelial lesion and adenocarcinoma in situ of cervix in a young woman presenting with hyperchromatic crowded groups in the cervical cytology specimen: report of a case.

    PubMed

    Zafar, Nadeem; Balazs, Louisa; Benstein, Barbara D

    2008-11-01

    We report a 29-year-old woman who underwent routine gynecologic evaluation at a community clinic and had a cervical sample drawn for liquid-based cytologic evaluation. At cytology, many hyperchromatic crowded groups (HCG) were present, but a consensus could not be established whether the abnormal cells were primarily glandular or squamous with secondary endocervical glandular involvement. An interpretation of atypical endocervical cells, favor neoplastic, was rendered and biopsy advised if clinically appropriate. At biopsy, the cervix contained synchronous squamous cell carcinoma in situ, secondarily involving endocervical glands, and neighboring adenocarcinoma in situ. Immunohistochemistry for Ki-67 and p16(INK4A) crisply and precisely stained both the lesions, clearly separating them from the adjacent uninvolved mucosa. This case re-emphasizes the challenge associated with accurate evaluation of HCG at cytology, the significance of ancillary testing for surrogate markers of high-risk HPV (HR-HPV) infection, the need for adjunct testing for HPV-DNA in the setting of HCG at cervical cytology, and a recommendation to set up studies to evaluate the role of surrogate markers of HR-HPV infection in cytologic samples with HCG.

  3. Quantitative Analysis of High-Resolution Microendoscopic Images for Diagnosis of Esophageal Squamous Cell Carcinoma

    PubMed Central

    Shin, Dongsuk; Protano, Marion-Anna; Polydorides, Alexandros D.; Dawsey, Sanford M.; Pierce, Mark C.; Kim, Michelle Kang; Schwarz, Richard A.; Quang, Timothy; Parikh, Neil; Bhutani, Manoop S.; Zhang, Fan; Wang, Guiqi; Xue, Liyan; Wang, Xueshan; Xu, Hong; Anandasabapathy, Sharmila; Richards-Kortum, Rebecca R.

    2014-01-01

    Background & Aims High-resolution microendoscopy is an optical imaging technique with the potential to improve the accuracy of endoscopic screening for esophageal squamous neoplasia. Although these microscopic images can readily be interpreted by trained personnel, quantitative image analysis software could facilitate the use of this technology in low-resource settings. In this study we developed and evaluated quantitative image analysis criteria for the evaluation of neoplastic and non-neoplastic squamous esophageal mucosa. Methods We performed image analysis of 177 patients undergoing standard upper endoscopy for screening or surveillance of esophageal squamous neoplasia, using high-resolution microendoscopy, at 2 hospitals in China and 1 in the United States from May 2010 to October 2012. Biopsies were collected from imaged sites (n=375); a consensus diagnosis was provided by 2 expert gastrointestinal pathologists and used as the standard. Results Quantitative information from the high-resolution images was used to develop an algorithm to identify high-grade squamous dysplasia or invasive squamous cell cancer, based on histopathology findings. Optimal performance was obtained using mean nuclear area as the basis for classification, resulting in sensitivities and specificities of 93% and 92% in the training set, 87% and 97% in the test set, and 84% and 95% in an independent validation set, respectively. Conclusions High-resolution microendoscopy with quantitative image analysis can aid in the identification of esophageal squamous neoplasia. Use of software-based image guides may overcome issues of training and expertise in low-resource settings, allowing for widespread use of these optical biopsy technologies. PMID:25066838

  4. Histopathological grading systems analysis of oral squamous cell carcinomas of young patients

    PubMed Central

    Frare, Juliana-Cristina; Sawazaki-Calone, Iris; Ayroza-Rangel, Ana-Lucia-Carrinho; Bueno, Alexandre-Galvão; de Morais, Carlos-Floriano; Nagai, Hildebrando-Massahiro; Kunz, Reno

    2016-01-01

    Background To analyze the clinicopathological profile of young patients (≤ 40 years) with oral SCC and correlate with a control group (≥ 50 years) by means of histopathological grading systems. Material and Methods 14 young patients and 14 control patients were selected with similar clinical stage and tumor location. Demographic and clinical data were obtained from patient records and histological sections were evaluated according to four histopathological grading systems. Associations between categories of demographic and clinical data were performed through Chi-square test and Exact Fisher test. The survival analyzes were performed according to the Kaplan-Meier method. Results The comparison between groups showed a greater association of treatment modalities in younger patients (p=0.022), they had a higher incidence of local recurrence and regional metastasis (p=0.018) and lower disease-free survival in 5 years (p=0.069). There was no difference in 5-year overall survival among the studied groups. There was no difference in histological grading between studied groups according to the four used systems. Conclusions This study showed that, despite tumors had similar histological grade and more therapeutic modalities were used in the young group, tumors in young patients had a higher incidence of recurrence/metastasis, showing tendency to a more aggressive behavior. Key words:Squamous cell carcinoma, tumors histological grading, young. PMID:26946200

  5. Study of Collagen Birefringence in Different Grades of Oral Squamous Cell Carcinoma Using Picrosirius Red and Polarized Light Microscopy

    PubMed Central

    Arun Gopinathan, Pillai; Kokila, Ganganna; Jyothi, Mahadesh; Ananjan, Chatterjee; Pradeep, Linganna; Humaira Nazir, Salroo

    2015-01-01

    Objectives. The present study was done to evaluate birefringence pattern of collagen fibres in different grades of oral squamous cell carcinoma using Picrosirius red stain and polarization microscopy and to determine if there is a change in collagen fibres between different grades of oral squamous cell carcinoma. Materials and Methods. Picrosirius red stained 5 μm thick sections of previously diagnosed different grades of squamous cell carcinoma and normal oral mucosa were studied under polarization microscopy for arrangement as well as birefringence of collagen fibres around tumour islands. Results. It was found that thin collagen fibres increased and thick collagen fibres decreased with dedifferentiation of OSCC (P < 0.0001). It was observed that there was change in polarization colours of thick fibres from yellowish orange to greenish yellow with dedifferentiation of OSCC indicating loosely packed fibres (P < 0.0001). Conclusion. There was a gradual change of birefringence of collagen from yellowish orange to greenish yellow from well to poorly differentiated squamous cell carcinoma, indicating that there is a change from mature form of collagen to immature form as tumour progresses. Studying collagen fibres with Picrosirius red for stromal changes around tumour islands along with routine staining may help in predicting the prognosis of tumour. PMID:26587310

  6. Immunohistochemical expression of phosphatase and tensin homolog in histologic gradings of oral squamous cell carcinoma

    PubMed Central

    Jasphin, Shiny S. R.; Desai, Dinkar; Pandit, Siddharth; Gonsalves, Nithin M.; Nayak, Preethi B.; Iype, Amal

    2016-01-01

    Context: Phosphatase and tensin homolog (PTEN) is a tumor suppressor gene located on chromosome 10q23. PTEN has its major function in the regulation of cell adhesion, cell cycle arrest, migration, apoptosis programming, and differentiation. This genomic region suffers loss of heterozygosity in many human cancers. Aims: The aim of this study was to compare the immunohistochemical expression of PTEN in normal oral mucosa and oral squamous cell carcinoma (OSCC) and to correlate the PTEN expression in gradings of OSCC. Materials and Methods: Thirty cases of paraffin tissue sections of previously diagnosed OSCC were taken. Of thirty cases, ten were well differentiated, ten were moderately differentiated, and ten were poorly differentiated. As a control, ten paraffin sections of oral normal mucosa tissue specimens were taken from patients undergoing extractions. The sections were stained for immunohistochemical expression of PTEN. The cells stained by PTEN antibody were counted, and an immunohistochemical score was obtained. Statistical Analysis Used: Statistical analysis was done using Mann–Whitney's test and Kruskal–Wallis test. Results: Statistical analysis revealed that there was a significant difference between normal mucosa and OSCC in immunohistochemistry staining. However, there was no significant difference in PTEN expression among gradings of OSCC. Conclusions: The study concluded that there was a decrease in PTEN expression in OSCC than normal mucosa. It also concluded that PTEN is a tumor suppressor gene which has a wide role in oral carcinogenesis. PMID:27994422

  7. Histopathologic extent of cervical intraepithelial neoplasia 3 lesions in the atypical squamous cells of undetermined significance low-grade squamous intraepithelial lesion triage study: implications for subject safety and lead-time bias.

    PubMed

    Sherman, Mark E; Wang, Sophia S; Tarone, Robert; Rich, Laurie; Schiffman, Mark

    2003-04-01

    Cervical intraepithelial neoplasia 3 (CIN3) is the precursor of mostsquamous carcinomas and serves as a surrogate end point. However, small CIN3 lesions are rarely associated with concurrent invasion. We hypothesized that aggressive follow-up for cytology of atypical squamous cells of undetermined significance (ASCUS) or low-grade squamous intraepithelial lesion (LSIL) leads predominantly to detection of smaller CIN3 lesions than those usually associated with cancer. We assessed this hypothesis in a masked histopathologic review of 330 CIN3 lesions in the ASCUS LSILTriage Study, focusing on ASCUS referrals. ASCUS referrals underwent randomized management [colposcopy for repeat cytology of high-grade squamous intraepithelial lesion (HSIL), colposcopy for oncogenic human papillomavirus (HPV) detection or repeat HSIL, or immediate colposcopy]; then all were followed with repeat cytology for 2 years, followed by colposcopy and aggressive treatment. We assessed all CIN3 lesions qualitatively and measured 39 of them. CIN3 lesions were overwhelmingly small. Compared with enrollment, lesions found at follow-up or exit involved fewer tissue fragments (P < 0.01) and showed less diffuse gland involvement (P = 0.03). CIN3 lesions found postenrollment after HPV testing involved the fewest tissue fragments [versus immediate colposcopy (P = 0.04) or repeat cytology of HSIL (P = 0.02)], and none showed diffuse gland involvement. The median distal-proximal length was 6.5 mm (median replacement of total epithelium = 5%) in the 39 measured cases. We conclude that CIN3 lesions underlying ASCUS or LSIL generally lack features associated with invasion, particularly if managed using HPV testing, suggesting that aggressive management leads to early detection of CIN3 but probably prevents relatively few cancers in screened populations.

  8. Atypical squamous cells in the urine revealing endometrioid adenocarcinoma of the endometrium with squamous cell differentiation: a case report.

    PubMed

    Wang, Yinong; Otis, Christopher N; Florence, Roxanne R

    2015-01-01

    Urine cytology is mainly used to detect urothelial carcinoma (UC), especially for high-grade lesions including urothelial carcinoma in situ. Benign squamous cells are often seen in the urine specimens of women, they are either exfoliated from the trigone area of the bladder, the urethra, or the cervicovaginal region. However, abnormal squamous cells in the urine raise concerns of abnormalities of the urinary tract and cervicovaginal area which range from squamous metaplasia of the urothelium, a cervicovaginal squamous intraepithelial lesion, condyloma acuminatum of the bladder, UC with squamous differentiation, and squamous cell carcinoma. We present here a unique case of atypical squamous cells (ASCs) in the urine subsequently leading to the diagnosis of endometrioid adenocarcinoma of the endometrium with squamous differentiation. The presence of ASCs in voided urine is a rare finding that may indicate an underlying malignancy. Careful evaluation of squamous cells in the urine is an important part of our daily cytopathology practice.

  9. Correlation of c-erbB-2 and S-100 expression with the malignancy grading and anatomical site in oral squamous cell carcinoma

    PubMed Central

    Albuquerque Júnior, Ricardo L C; Miguel, Márcia C C; Costa, Antonio L L; Souza, Lélia B

    2003-01-01

    An immunohistochemical analysis of 32 cases of oral squamous cell carcinoma (eight in the inferior lip, eight in the lateral angle of the tongue, eight in the palate and eight in the mouth floor) was performed to evaluate the expression pattern of c-erbB-2 protein and S-100-positive cells in the lesions. The immunohistochemical expression was correlated with the tumour anatomical site and histological grading of malignancy. A higher frequency of c-erbB-2-positive cases was found in the tongue, even though no correlation could be detected between the protein expression and the tumour histological grading. With respect to the S-100-positive cells, it was observed that a quantitative decrease was present in the cases classified as high-grade tumours when compared to the low ones (P = 0.0007). Thus, c-erbB-2 immunohistochemical expression is correlated with anatomical localization, and the expression of the S-100 Langerhans' cell markers is decreased significantly in high-grade carcinomas. PMID:14748745

  10. Laryngeal Dysplasia, Squamous Cell Carcinoma, and Variants.

    PubMed

    Thompson, Lester D R

    2017-03-01

    Squamous cell carcinoma (SCC) is a malignant epithelial tumor showing evidence of squamous differentiation. It is the most common malignancy of the larynx, with several variants (verrucous, exophytic or papillary, spindle-cell, basaloid, acantholytic, adenosquamous) recognized, with well-established precursor lesions. Dysplasia is now separated into only low-grade and high-grade categories. Each SCC variant has unique cytomorphologic features and histologic differential diagnoses that are important to consider, as management and outcomes are different.

  11. Peripheral blood lymphocytes from low-grade squamous intraepithelial lesions patients recognize vaccine antigens in the presence of activated dendritic cells, and produced high levels of CD8 + IFNγ + T cells and low levels of IL-2 when induced to proliferate

    PubMed Central

    2012-01-01

    Background Most infections with human papillomavirus (HPV) are resolved without clinical intervention, but a minority evolves into chronic lesions of distinct grades, including cervical-uterine cancer. It is known that in most cases the immune system mediates elimination of HPV infection. However, the mechanism of immune evasion leading to HPV persistence and development of early cervical lesions is not fully understood. The aim of the present work was to evaluate the potential of peripheral blood leukocytes (PBL) from low-grade squamous intraepithelial lesions (LSIL) patients to be activated ex-vivo by vaccine antigens, the participation of cytotoxic lymphocytes and regulatory T cells, and to determine the secretion of Th1 and Th2 cytokines mediated by stimulation of T cell receptors. Results We found that PBL from LSIL patients showed a significantly lower proliferation rate to vaccine antigens as compared to that of healthy donors, even though there was not a difference in the presence of antibodies to those antigens in sera from both groups. We did not find differences in either the frequency of CD4 + CD25 + FoxP3+ in PBL, or the levels of IL-4, IL-5 and IL-10 in plasma or conditioned media from PBL incubated with TcR agonists in vitro, between the two groups. However, we detected a lower production of IL-2 and a higher proportion of CD8 + IFNγ + cells in PBL from LSIL patients as compared with PBL from normal donors. We also observed that PBL from patients infected by HPV-16 and −18 were not able to proliferate in the presence of soluble HPV antigens added to the culture; however, a high level of proliferation was attained when these antigens were presented by activated dendritic cells. Conclusions Our results suggest that the immunodeficiency reported in LSIL patients could be due to the inability of specific cytotoxic T lymphocytes that for some unknown reason are present but unable to mount a response when challenged with their antigens

  12. [Incidence and physiopathology of high-grade dysplasia in Barrett's esophagus].

    PubMed

    Coriat, Romain; Perkins, Géraldine; Brezault, Catherine

    2011-05-01

    Barrett's esophagus is a well-known precursor of esophageal adenocarcinoma. Monitoring patients with Barrett's esophagus is recommended for detecting high-grade dysplasia or cancer. Gastroesophageal reflux disease affects approximately 20% of the population in developed countries. About 10-15% of patients with gastroesophageal reflux disease develop Barrett's esophagus, which can progress to adenocarcinoma. The esophagus is normally lined by squamous mucosa. Therefore, it is clear that for an adenocarcinoma, there is a prior sequence of events that lead to normal squamous mucosa transformation.

  13. [Partial regression of Barret esophagus with high grade dysplasia and adenocarcinoma after photocoagulation and endocurietherapy under antisecretory treatment].

    PubMed

    Fremond, L; Bouché, O; Diébold, M D; Demange, L; Zeitoun, P; Thiefin, G

    1995-01-01

    Barrett's oesophagus is a premalignant condition. The possibility of eradicating at least partially the metaplastic epithelium has been reported recently. In this case report, a patient with Barrett's oesophagus complicated by high grade dysplasia and focal adenocarcinoma was treated by Nd:Yag laser then high dose rate intraluminal irradiation while on omeprazole 40 mg/day. A partial eradication of Barrett's oesophagus and a transient tumoural regression were obtained. Histologically, residual specialized-type glandular tissue was observed beneath regenerative squamous epithelium. Four months after intraluminal irradiation, a local tumoural recurrence was detected while the area of restored squamous epithelium was unchanged on omeprazole 40 mg/day. This indicates that physical destruction of Barrett's oesophagus associated with potent antisecretory treatment can induce a regression of the metaplastic epithelium, even in presence of high grade dysplasia. The persistence of specialized-type glands beneath the squamous epithelium raises important issues about its potential malignant degeneration.

  14. Multiphoton imaging of low grade, high grade intraepithelial neoplasia and intramucosal invasive cancer of esophagus

    NASA Astrophysics Data System (ADS)

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

    2017-04-01

    Esophageal squamous cell carcinoma (ESCC) is devastating because of its aggressive lymphatic spread and clinical course. It is believed to occur through low-grade intraepithelial neoplasia (LGIN), high-grade intraepithelial neoplasia (HGIN), and intramucosal invasive cancer (IMC) before transforming to submucosal cancer. In particular, these early lesions (LGIN, HGIN and IMC), which involve no lymph node nor distant metastasis, can be cured by endoscopic treatment. Therefore, early identification of these lesions is important so as to offer a curative endoscopic resection, thus slowing down the development of ESCC. In this work, spectral information and morphological features of the normal esophageal mucosa are first studied. Then, the morphological changes of LGIN, HGIN and IMC are described. Lastly, quantitative parameters are also extracted by calculating the nuclear-to-cytoplasmic ratio of epithelial cells and the pixel density of collagen in the lamina propria. These results show that multiphoton microscopy (MPM) has the ability to identify normal esophageal mucosa, LGIN, HGIN and IMC. With the development of multiphoton endoscope systems for in vivo imaging, combined with a laser ablation system, MPM has the potential to provide immediate pathologic diagnosis and curative treatment of ESCC before the transformation to submucosal cancer in the future.

  15. Analysis of CD8+ and CD4+ cells in oral squamous cell carcinoma and their association with lymph node metastasis and histologic grade of malignancy.

    PubMed

    dos antos Pereira, Joabe; da Costa Miguel, Márcia Cristina; Guedes Queiroz, Lélia Maria; da Silveira, Éricka Janine Dantas

    2014-03-01

    This study aimed to analyze CD8 and CD4 cells in oral squamous cell carcinoma and to correlate it with prognostic indicators. The sample was composed of 50 cases. Clinical data and histologic grade of malignancy were obtained. Specimens were submitted to immunohistochemistry. Cells were counted in 10 fields at the tumor invasion front and expressed as median. CD8 cells were more frequent in nonmetastatic lesions (18.5) and in low-grade specimens (18.2) (P<0.05). CD4 cells were equally distributed in nonmetastatic and metastatic lesions (4.5). In addition, they were slightly more frequent in low-grade lesions (4.7). None of these correlations were significant (P>0.05). CD8/CD4 ratio was higher in cases without metastasis (3.57) and in low-grade lesions (3.62) (P>0.05). Probably, CD8 cells are the most effective and important cells in the host immune responses against oral squamous cell carcinoma. In addition, CD4 cells could indirectly influence the host protection through regulation of CD8 recruitment and activation.

  16. Studies on high grade cerebral gliomas

    SciTech Connect

    Bleehen, N.M. )

    1990-04-01

    A brief review of attempts in the United Kingdom to improve the results of treatment of high grade (grade 3, 4) supra-tentorial astrocytomas is presented. The radiosensitizer misonidazole failed to improve the results of post-surgical radiotherapy, however, multivariate analysis of data from these patients has provided a prognostic index of use in defining good and poor prognosis patients. An overview study of adjuvant nitrosourea therapy trials has shown a small significant advantage for the chemotherapy. A study of chemosensitization by benznidazole of CCNU treatment of patients in relapse failed to demonstrate any effect. 13 references.

  17. Self-Graded and Teacher-Graded Achievement in a BSCS High School Biology Course.

    ERIC Educational Resources Information Center

    Good, Wallace Martin

    The effect of self-grading on biology students exposed to the same instruction (except grading) in an upper-middle class public school was investigated by comparing self-graded and teacher-graded populations in (1) achievement in high school biology, (2) level of aspiration behavior, (3) critical thinking skills, and (4) productivity. The…

  18. Cell membrane CD44v6 levels in squamous cell carcinoma of the lung: association with high cellular proliferation and high concentrations of EGFR and CD44v5.

    PubMed

    Ruibal, Álvaro; Aguiar, Pablo; Del Río, María Carmen; Nuñez, Matilde Isabel; Pubul, Virginia; Herranz, Michel

    2015-02-18

    Membranous CD44v6 levels in tumors and surrounding samples obtained from 94 patients with squamous cell lung carcinomas were studied and compared to clinical stage, cellular proliferation, membranous CD44v5 levels, epidermal growth factor receptor EGFR and cytoplasmatic concentrations of CYFRA 21.1. CD44v6 positive values were observed in 33/38 non-tumor samples and in 76/94 tumor samples, but there were not statistically significant differences between both subgroups. In CD44v6 positive tumor samples, CD44v6 was not associated with clinical stage, histological grade, ploidy and lymph node involvement, but significant association was found with high cellular proliferation. Likewise, CD44v6 positive tumors had significantly higher levels of EGFR and CD44v5. In patients with squamous cell lung carcinomas and clinical stage I, positive CD44v6 cases were associated with the same parameters. Furthermore, positive CD44v5 squamous tumors were associated significantly with histological grade III and lower levels of CYFRA21.1. Our findings support the value of CD44v6 as a possible indicator of poor outcome in patients with squamous lung carcinomas.

  19. 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

  20. Clinical response to glycyrrhizinic acid in genital infection due to human papillomavirus and low-grade squamous intraepithelial lesion

    PubMed Central

    Valencia, Marcelino Hernández; Pacheco, Adia Carrillo; Quijano, Tomás Hernández; Girón, Antonio Vargas; López, Carlos Vargas

    2011-01-01

    Human papilloma virus (HPV) can infect any of the mucosal areas of the body and cause cervical cancer. Until recently, no specific treatments were available for this condition; therefore, any damaged tissue had to be removed or destroyed, which may have presented obstetrical repercussions for some women. Recently, new drugs have been developed that have shown to be effective for the cure of HPV infection. Glycyrrhizinic acid (GA) has shown fewer side effects and its systemic use makes it possible to reach difficult-to-treat lesions. The purpose of this study was to evaluate the clinical outcome of GA to eliminate the epithelial lesion and HPV. We carried out a longitudinal, descriptive study that included women of reproductive age who were diagnosed with HPV associated with low-grade squamous intraepithelial lesion (LSIL). Subjects began treatment based on GA using two routes of administration - systemic (oral) and topical (spray) - with assessments every month to determine the clinical changes of the lesions through colposcopy and Papanicolaou (Pap) smear. Simple statistics were used along with two-tailed Student's t-test; P<0.05 was considered statistically significant before and after treatment. There were 70 eligible patients, of whom 62 fulfilled the inclusion criteria. Age of subjects was 27.8±9.5 years. At the time of the study, 100% of the patients had HPV infection, 40% were associated with LSIL, and only 16% used a barrier contraceptive (condom) method. Resolution was achieved in all patients from 4 weeks of treatment initiation and improvement was achieved in the majority of patients at 12 weeks (74%) (P<0.001). However, there was persistence of LSIL in 27.7% of patients and only one patient progressed to cervical intraepithelial neoplasia (CIN) II. The use of GA proved to be effective in resolving clinical HPV lesions. For cervical lesions with epithelial changes (LSIL), treatment may be required for a longer period as with other drugs used for this

  1. Clinical characteristics of high grade foveal hypoplasia.

    PubMed

    Park, Kyung-Ah; Oh, Sei Yeul

    2013-02-01

    To report clinical characteristics of high grade foveal hypoplasia. Patients with foveal hypoplasia of grade 3 or 4 on spectral domain optical coherence tomography according to a previously published scheme were enrolled. All patients underwent a full ophthalmologic assessment including visual acuity testing, slit lamp biomicroscopy, fundus examination, and evaluation of ocular alignment. The underlying causes of foveal hypoplasia were identified as albinism in five patients and aniridia in six patients. The mean logMAR visual acuity was 0.57 ± 0.24 (range 0.22-1.00) in the right eyes and 0.58 ± 0.21 (range 0.30-1.00) in the left eyes. On fundus examination in patients with albinism, two patients showed marked transparency, one patient showed moderate transparency, and two patients showed minimal transparency. Among six patients with aniridia, five patients showed normal macular pigmentation without macular reflex and one patient showed decreased macular pigmentation with no macular reflex. Patients with high grade macular hypoplasia tended to have poor visual acuities; however, the range of visual acuity was quite variable. Other factors associated with underlying disease could be the reason of this variability. Therefore, careful consideration should be given when assessing visual prognosis in foveal hypoplasia using optical coherence tomography.

  2. 40 CFR 246.200 - High-grade paper recovery.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 24 2010-07-01 2010-07-01 false High-grade paper recovery. 246.200... SEPARATION FOR MATERIALS RECOVERY GUIDELINES Requirements and Recommended Procedures § 246.200 High-grade paper recovery....

  3. 40 CFR 246.200 - High-grade paper recovery.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 25 2011-07-01 2011-07-01 false High-grade paper recovery. 246.200... SEPARATION FOR MATERIALS RECOVERY GUIDELINES Requirements and Recommended Procedures § 246.200 High-grade paper recovery....

  4. Gene therapy for high-grade glioma

    PubMed Central

    Natsume, Atsushi

    2008-01-01

    The treatment of high-grade gliomas remains difficult despite recent advances in surgery, radiotherapy and chemotherapy. True advances may emerge from the increasing understanding in molecular biology and discovery of novel mechanisms for the delivery of tumoricidal agents. In an attempt to overcome this formidable neoplasm, molecular approaches using gene therapy have been investigated clinically since 1992. The clinical trials have mainly been classified into three approaches: suicide gene therapy, immune gene therapy and oncolytic viral therapy. In this article, we review these approaches, which have been studied in previous and ongoing clinical trials. PMID:19262115

  5. High expression levels of COX-2 and P300 are associated with unfavorable survival in laryngeal squamous cell carcinoma.

    PubMed

    Chen, Yan-Feng; Luo, Rong-Zhen; Li, Yong; Cui, Bo-Kang; Song, Ming; Yang, An-Kui; Chen, Wen-Kuan

    2013-03-01

    In order to provide a basis for clinical treatment decisions, we explored whether there was a correlation between the expression of COX-2 and P300 and clinical factors in a group of patients with laryngeal squamous cell carcinoma (LSCC). A retrospective analysis of clinicopathological data was conducted in 80 patients with LSCC who presented between January 1997 and December 1998. An immunohistochemistry tissue microarray was conducted of 80 surgically resected LSCC and 20 adjacent normal tissue specimens. Survival analysis and Kaplan-Meier curves were used to compare the effects of clinicopathological factors on survival. The Cox model was applied for multivariate analysis. The expression level of COX-2/P300 in LSCC tissues and adjacent normal tissues were 47.5/50.0 versus 0.0/15.0 %. The expression of COX-2 and P300 was correlated with higher T category, N category, clinical staging, histological grade and recurrence (P < 0.05). P300 expression was correlated with COX-2 expression (P < 0.05). Univariate survival analysis showed that P300, COX-2, N category, clinical staging and recurrence factors were closely correlated with unfavorable survival (P < 0.05). Multivariate analysis showed that COX-2 expression, histological grade and recurrence were independent prognostic factors for LSCC. High expression levels of COX-2 and P300 indicated poor survival outcomes for patients with LSCC.

  6. Reduced expression of autophagy markers correlates with high-risk human papillomavirus infection in human cervical squamous cell carcinoma

    PubMed Central

    WANG, HUA-YI; YANG, GUI-FANG; HUANG, YAN-HUA; HUANG, QI-WEN; GAO, JUN; ZHAO, XIAN-DA; HUANG, LI-MING; CHEN, HONG-LEI

    2014-01-01

    Infection by an oncogenic human papillomavirus (HPV), in particular HPV16 and 18, is a high risk factor for developing cervical cancer; however, viral infection alone is not sufficient for cancer progression. Autophagy is hypothesized to be an important process during carcinogenesis. The aim of the present study was to investigate the association between autophagy and high-risk HPV (hrHPV) infection in human cervical squamous cell carcinomas (SCCs), and to analyze the clinical significance of this association. Quantum dot (QD)-based immunofluorescence histochemistry was used to detect the expression of autophagy markers, Beclin-1 and microtubule-associated proteins 1A/1B light chain 3B (LC3B) proteins, in 104 cases of cervical cancer (including 80 SCCs and 24 adenocarcinomas) and 20 normal cervical tissues. hrHPV (HPV16/18) infection was detected by QDs based fluorescence in situ hybridization in cervical cancers. The results revealed that the expression levels of Beclin-1 and LC3B were significantly lower in cervical cancer cells when compared with those of normal cervical squamous epithelial cells, and were found to negatively correlate with hrHPV infection. The expression levels of Beclin-1 and LC3B were not associated with age, tumor grade, tumor stage, tumor node metastasis stage or lymph node metastasis. However, a positive correlation was identified between Beclin-1 and LC3B protein expression. In addition, the absence of autophagy in combination with hrHPV infection may accelerate the progression of cervical SCC. In conclusion, decreased expression of Beclin-1 and LC3B may be important in cervical carcinogenesis. The hrHPV-host cell interaction may inhibit autophagy, which may aid virus duplication and infection, as well as cervical cancer development. PMID:25202355

  7. Are High School Grades Inflated? Issues in College Readiness

    ERIC Educational Resources Information Center

    ACT, Inc., 2005

    2005-01-01

    To find out whether high school grade inflation exists, data drawn from students who took the ACT in the eleventh or twelfth grades and graduated from public high schools were examined. Because grade inflation is by definition a factor that develops over time, data from a relatively long period, 1991 to 2003, or 13 years were used. The number of…

  8. Reduced expression of cytokeratin 4 and 13 is a valuable marker for histologic grading of esophageal squamous intraepithelial neoplasia.

    PubMed

    Takashima, Masaki; Kawachi, Hiroshi; Yamaguchi, Tsukasa; Nakajima, Yutaka; Kitagaki, Keisuke; Sekine, Masaki; Iida, Tadatsune; Takemura, Kosuke; Kawano, Tatsuyuki; Eishi, Yoshinobu

    2012-03-13

    Histologic evaluation of low-grade or high-grade intraepithelial neoplasia (LG-IN or HG-IN) of the esophagus is important for estimating the risk of progression to invasive carcinoma. Discrimination between LG-IN and HG-IN, or neoplasia and non-neoplastic lesion (NNL), however, is occasionally difficult. This study was designed to evaluate whether cytokeratin expression can be used for discrimination of these lesions. Esophageal Iodine-unstained lesions (n=154), less than 10 mm, were classified into HG-IN, LG-IN, and NNL. These lesions together with 154 foci of normal esophageal epithelium (NEE) were examined by immunohistochemistry for cytokeratins (CK4 and CK13), p53 overexpression, and the MIB-1 labeling index. The ratios of CK4- and CK13-positive staining were scored from 1 to 3. The CK4- and CK13-positive staining ratios were decreased in NNL (73% and 78%), LG-IN (55% and 69%), and HG-IN (33% and 48%), compared to NEE (91% and 95%). The differences between LG-IN and HG-IN, neoplasia and NNL, and among these three lesions and NEE were statistically significant (p < 0.005). The cytokeratin scores correlated with the MIB-1 labeling index (both: p < 0.0001), but not with p53 overexpression. CK4 and CK13 immunohistochemistry could be an objective method for evaluating the risk for progression to invasive carcinoma.

  9. Loss of ELF3 immunoexpression is useful for detecting oral squamous cell carcinoma but not for distinguishing between grades of epithelial dysplasia.

    PubMed

    AbdulMajeed, Ahmad A; Dalley, Andrew J; Farah, Camile S

    2013-08-01

    Early diagnosis and targeted therapy are crucial to mitigating the morbidity and mortality of oral squamous cell carcinoma. Among the potentially malignant oral disorders, epithelial dysplasia has known association with malignant transformation, but defensible gradation of dysplasia severity presents unmet challenges. Published microarray data has denoted dysregulation of CLSP, ELF3, IFI44, USP18, and CXCL13 genes in potentially malignant oral disorders. The present study investigated the diagnostic potential of these gene products to grade oral epithelial dysplasia severity. Archived biopsies from independent patient cohorts comprised "training" (n=107) and "test" (n=278) sample sets. Immunoreactivity for candidate markers was determined in the "training" set of normal oral mucosa (NOM), mild dysplasia (MD), moderate to severe dysplasia, and oral squamous cell carcinoma (OSCC). The diagnostic potential of ELF3 immunoscoring to improve detection and severity gradation of epithelial dysplasia was assessed with the "test" set. A reciprocal relationship between disease severity and immunoreactivity score for CLSP and ELF3 was observed (MD/NOM to OSCC: P<.08, Mann-Whitney U test), whereas elevated IFI44 immunostaining was present for OSCC compared to MD/NOM (P<.08, Mann-Whitney U test). Loss of ELF3 immunostaining effectively distinguished OSCC from non-malignant tissues (sensitivity=0.81; specificity=0.56; area under the curve [AUC]=0.68) but did not distinguish dysplasia from NOM (sensitivity=0.55; specificity=0.40; AUC=0.47) or moderate to severe dysplasia from MD (sensitivity=0.63; specificity=0.51; AUC=0.57). The results confirm via immunohistochemistry the relevance of published CLSP, ELF3, and IFI44 (but not USP18 or CXCL13) gene expression data to potentially malignant oral lesion severity. Loss of ELF3 immunostaining discriminated OSCC from dysplasia but was unreliable for grading dysplasia severity.

  10. Grades, Coursework, and Student Characteristics in High School Economics

    ERIC Educational Resources Information Center

    Rebeck, Ken; Walstad, William B.

    2015-01-01

    The authors use U.S. public and private high school transcripts to analyze grade distribution patterns in economics courses across student and school characteristics, and compare these grades to those earned in other selected high school courses. Results are reported for the 53 percent of 2009 high school graduates who took a basic economics…

  11. Terahertz reflectometry imaging for low and high grade gliomas

    NASA Astrophysics Data System (ADS)

    Ji, Young Bin; Oh, Seung Jae; Kang, Seok-Gu; Heo, Jung; Kim, Sang-Hoon; Choi, Yuna; Song, Seungri; Son, Hye Young; Kim, Se Hoon; Lee, Ji Hyun; Haam, Seung Joo; Huh, Yong Min; Chang, Jong Hee; Joo, Chulmin; Suh, Jin-Suck

    2016-10-01

    Gross total resection (GTR) of glioma is critical for improving the survival rate of glioma patients. One of the greatest challenges for achieving GTR is the difficulty in discriminating low grade tumor or peritumor regions that have an intact blood brain barrier (BBB) from normal brain tissues and delineating glioma margins during surgery. Here we present a highly sensitive, label-free terahertz reflectometry imaging (TRI) that overcomes current key limitations for intraoperative detection of World Health Organization (WHO) grade II (low grade), and grade III and IV (high grade) gliomas. We demonstrate that TRI provides tumor discrimination and delineation of tumor margins in brain tissues with high sensitivity on the basis of Hematoxylin and eosin (H&E) stained image. TRI may help neurosurgeons to remove gliomas completely by providing visualization of tumor margins in WHO grade II, III, and IV gliomas without contrast agents, and hence, improve patient outcomes.

  12. Terahertz reflectometry imaging for low and high grade gliomas

    PubMed Central

    Ji, Young Bin; Oh, Seung Jae; Kang, Seok-Gu; Heo, Jung; Kim, Sang-Hoon; Choi, Yuna; Song, Seungri; Son, Hye Young; Kim, Se Hoon; Lee, Ji Hyun; Haam, Seung Joo; Huh, Yong Min; Chang, Jong Hee; Joo, Chulmin; Suh, Jin-Suck

    2016-01-01

    Gross total resection (GTR) of glioma is critical for improving the survival rate of glioma patients. One of the greatest challenges for achieving GTR is the difficulty in discriminating low grade tumor or peritumor regions that have an intact blood brain barrier (BBB) from normal brain tissues and delineating glioma margins during surgery. Here we present a highly sensitive, label-free terahertz reflectometry imaging (TRI) that overcomes current key limitations for intraoperative detection of World Health Organization (WHO) grade II (low grade), and grade III and IV (high grade) gliomas. We demonstrate that TRI provides tumor discrimination and delineation of tumor margins in brain tissues with high sensitivity on the basis of Hematoxylin and eosin (H&E) stained image. TRI may help neurosurgeons to remove gliomas completely by providing visualization of tumor margins in WHO grade II, III, and IV gliomas without contrast agents, and hence, improve patient outcomes. PMID:27782153

  13. Comparison of Linear Array and Line Blot Assay for Detection of Human Papillomavirus and Diagnosis of Cervical Precancer and Cancer in the Atypical Squamous Cell of Undetermined Significance and Low-Grade Squamous Intraepithelial Lesion Triage Study▿

    PubMed Central

    Castle, Philip E.; Gravitt, Patti E.; Solomon, Diane; Wheeler, Cosette M.; Schiffman, Mark

    2008-01-01

    We evaluated Linear Array (LA), a newly commercialized PGMY09/11 L1 consensus primer PCR test that detects 37 human papillomavirus (HPV) genotypes by reverse line blot hybridization, for the detection of individual HPV genotypes and carcinogenic HPV and its clinical performance for detecting 2-year cumulative cervical precancer and cancer using archived specimens from the Atypical Squamous Cell of Undetermined Significance (ASCUS) and Low-Grade Squamous Intraepithelial Lesion Triage Study. LA testing was conducted on enrollment specimens from women referred because of an ASCUS Pap test. To gauge the performance of the new test, the results were compared to those of its prototype predecessor assay, Line Blot Assay (LBA), restricted to paired results (n = 3,335). LA testing was done masked to LBA results and clinical outcomes. The results of LA and LBA testing were compared for detection of carcinogenic HPV and clinical outcomes of cervical precancer and cancer. Overall, 50% and 55% of the women tested positive for carcinogenic HPV by LBA and LA, respectively (P < 0.0001). The percent agreement for carcinogenic HPV detection was 88%, percent positive agreement was 80%, and kappa was 0.76 for detection of carcinogenic HPV by the two assays. There was a significant increase in detection by LA for most of the 37 HPV genotypes targeted by both assays, including for 13 of 14 carcinogenic HPV genotypes. LA detected more multiple-genotype infections for all HPV genotypes among HPV-positive women (P < 0.0001) and for carcinogenic HPV genotypes among carcinogenic-HPV-positive women (P < 0.0001). LA was more sensitive (92.3% versus 87.1%; P = 0.003) and less specific (48.2% versus 54.0%; P < 0.0001) than LBA for 2-year cumulative cervical precancer and cancer as diagnosed by the Pathology Quality Control Group. In conclusion, we found LA to be a promising assay for the detection of HPV genotypes and carcinogenic HPV, and it may be clinically useful for the detection of

  14. Comparison of linear array and line blot assay for detection of human papillomavirus and diagnosis of cervical precancer and cancer in the atypical squamous cell of undetermined significance and low-grade squamous intraepithelial lesion triage study.

    PubMed

    Castle, Philip E; Gravitt, Patti E; Solomon, Diane; Wheeler, Cosette M; Schiffman, Mark

    2008-01-01

    We evaluated Linear Array (LA), a newly commercialized PGMY09/11 L1 consensus primer PCR test that detects 37 human papillomavirus (HPV) genotypes by reverse line blot hybridization, for the detection of individual HPV genotypes and carcinogenic HPV and its clinical performance for detecting 2-year cumulative cervical precancer and cancer using archived specimens from the Atypical Squamous Cell of Undetermined Significance (ASCUS) and Low-Grade Squamous Intraepithelial Lesion Triage Study. LA testing was conducted on enrollment specimens from women referred because of an ASCUS Pap test. To gauge the performance of the new test, the results were compared to those of its prototype predecessor assay, Line Blot Assay (LBA), restricted to paired results (n = 3,335). LA testing was done masked to LBA results and clinical outcomes. The results of LA and LBA testing were compared for detection of carcinogenic HPV and clinical outcomes of cervical precancer and cancer. Overall, 50% and 55% of the women tested positive for carcinogenic HPV by LBA and LA, respectively (P < 0.0001). The percent agreement for carcinogenic HPV detection was 88%, percent positive agreement was 80%, and kappa was 0.76 for detection of carcinogenic HPV by the two assays. There was a significant increase in detection by LA for most of the 37 HPV genotypes targeted by both assays, including for 13 of 14 carcinogenic HPV genotypes. LA detected more multiple-genotype infections for all HPV genotypes among HPV-positive women (P < 0.0001) and for carcinogenic HPV genotypes among carcinogenic-HPV-positive women (P < 0.0001). LA was more sensitive (92.3% versus 87.1%; P = 0.003) and less specific (48.2% versus 54.0%; P < 0.0001) than LBA for 2-year cumulative cervical precancer and cancer as diagnosed by the Pathology Quality Control Group. In conclusion, we found LA to be a promising assay for the detection of HPV genotypes and carcinogenic HPV, and it may be clinically useful for the detection of

  15. High-grade invasive urothelial carcinoma of the ureter with systematic lymph node metastasis successfully treated by nephroureterectomy followed by chemotherapy

    PubMed Central

    Liu, Zhu-Qing; Zhang, Xi; Xu, Qing

    2015-01-01

    We report a case of high-grade invasive urothelial carcinoma with squamous differentiation of the urinary tract. A 72-year-old woman was referred to our hospital because of asymptomatic gross hematuria. A right-sided laparoscopic radical nephroureterectomy with bladder cuff removal and right-sided pelvic lymphadenectomy were performed at our institution. Postoperative pathological examination showed high-grade urothelial carcinoma with squamous differentiation. Five months later, CT scan of the neck diagnosed it as lymph nodes metastasis. Following the laparoscopic radical nephroureterectomy, chemotherapy with gemcitabine and cisplatin or nedaplatin was carried out. After several cycles’ chemotherapy, nearly all the enlarged lymph node disappeared. Seven years and five years passed, urothelial carcinoma has not recurred after the surgery and all the lymph node disappeared respectively. PMID:25932275

  16. Evaluation of myeloid cells (tumor-associated tissue eosinophils and mast cells) infiltration in different grades of oral squamous cell carcinoma

    PubMed Central

    Debta, Priyanka; Debta, Fakir Mohan; Chaudhary, Minal; Bussari, Smita

    2016-01-01

    Background: The multifunctional involvement and infiltration of myeloid cells (tumor-associated tissue eosinophils [TATE] and mast cells) can provide a unique opportunity to define relevant effectors functions that may represent novel, therapeutic options for modulation of tumor onset/growth. Aim: Our study aimed to evaluate infiltration of myeloid cells (TATE and Mast cells) infiltration in different grades (WHO grading) of oral squamous cell carcinoma (OSCC). Materials and Methods: Total 30 cases of OSCC were selected for this study. Hematoxylin and eosin stain and toluidine blue special stain, to evaluate TATE and the mast cells infiltration, were used. Three-year follow-up of OSCC cases was done. Result: Among 30 cases, 63.33% cases of OSCC showed TATE-positive and 36.66% cases showed TATE-negative. Regarding mast cells infiltration, 66.66% OSCC cases showed mast cells positive and 33.33% cases did not show significant mast cells infiltration. We found significant association of TATE and mast cells infiltration in OSCC cases. These myeloid cells infiltration significantly associated with age of patients but did not show any significant association with gender, site, and habit of cases. When we compared these cells infiltration with clinical stages and different histological grades of tumor, we found their infiltration is decreasing, from Stages 1 to Stage 3 of tumor and from well to poorly differentiated carcinoma. We have also found the less infiltration of these myeloid in recurrence cases of OSCC. Conclusion: As the infiltration of TATE and mast cells are correlated, along with evaluation of TATE, we should also evaluate the presence of mast cells infiltration in OSCC. The assessment of myeloid cells could become, in the future, useful for therapeutic approaches in this subset of the patient. PMID:27688609

  17. Nuclear fractal dimension in oral squamous cell carcinoma: a novel method for the evaluation of grading, staging, and survival.

    PubMed

    Mincione, Gabriella; Di Nicola, Marta; Di Marcantonio, Maria Carmela; Muraro, Raffaella; Piattelli, Adriano; Rubini, Corrado; Penitente, Enrico; Piccirilli, Marcello; Aprile, Giuseppe; Perrotti, Vittoria; Artese, Luciano

    2015-10-01

    Fractal dimension (FD) in tissue specimens from patients with oral squamous cell carcinoma (OSCC) was evaluated. FD values in different stages of OSCC, and the correlations with clinicopathological variables and patient survival were investigated. Histological sections from OSCC and control non-neoplastic mucosa specimens were stained with hematoxylin-eosin for pathological analysis and with Feulgen for nuclear evaluation. FD in OSCC groups vs. controls revealed statistically significant differences (P < 0.001). In addition, a progressive increase of FD from stage I and II lesions and stage III and IV lesions was observed, with statistically significant differences (P = 0.003). Moreover, different degrees of tumor differentiation showed a significant difference in the average nuclear FD values (P = 0.001). A relationship between FD and patients' survival was also detected with lower FD values associated to longer survival time and higher FD values with shorter survival time (P = 0.034). These data showed that FD significantly increased during OSCC progression. Thus, FD could represent a novel prognostic tool for OSCC, as FD values significantly correlated with patient survival. Fractal geometry could give insights into tumor morphology and could become an useful tool for analyzing irregular tumor growth patterns.

  18. Photodynamic therapy of Cervical Intraepithelial Neoplasia (CIN) high grade

    NASA Astrophysics Data System (ADS)

    Carbinatto, Fernanda M.; Inada, Natalia M.; Lombardi, Welington; da Silva, Eduardo V.; Belotto, Renata; Kurachi, Cristina; Bagnato, Vanderlei S.

    2016-02-01

    Cervical intraepithelial neoplasia (CIN) is the precursor of invasive cervical cancer and associated with human papillomavirus (HPV) infection. Photodynamic therapy (PDT) is a technique that has been used for the treatment of tumors. PDT is based on the accumulation of a photosensitizer in target cells that will generate cytotoxic reactive oxygen species upon illumination, inducing the death of abnormal tissue and PDT with less damaging to normal tissues than surgery, radiation, or chemotherapy and seems to be a promising alternative procedure for CIN treatment. The CIN high grades (II and III) presents potential indications for PDT due the success of PDT for CIN low grade treatment. The patients with CIN high grade that were treated with new clinic protocol shows lesion regression to CIN low grade 60 days after the treatment. The new clinical protocol using for treatment of CIN high grade shows great potential to become a public health technique.

  19. Reliability of Grading High School Work in English

    ERIC Educational Resources Information Center

    Brimi, Hunter M.

    2011-01-01

    This research replicates the work of Starch and Elliot (1912) by examining the reliability of the grading by English teachers in a single school district. Ninety high school teachers graded the same student paper following professional development sessions in which they were trained to use NWREL's "6+1 Traits of Writing." These participants had…

  20. Do high-risk human papillomaviruses cause oral cavity squamous cell carcinoma?

    PubMed

    Mirghani, H; Amen, F; Moreau, F; Lacau St Guily, J

    2015-03-01

    High-risk human papillomaviruses (HR-HPV) are an established etiologic factor for a growing number of oropharyngeal cancers. However, their potential role in other upper aerodigestive tract locations is still a matter of debate, particularly in the oral cavity. This is of paramount importance as in the future diagnosis, treatment and follow up in head and neck squamous cell carcinoma may vary according to HPV status. This article reviews the recent published data and highlights some of the pitfalls that have hampered the accurate assessment of HR-HPV oncological role outside the oropharynx. We demonstrate that, in contrast to the oropharynx, only a small fraction of cancers located in the oral cavity seem to be HPV-related even in young non-smoking non-drinking patients. We emphasize several relevant factors to consider in assumed HPV-induced oral cavity cancers and discuss the current theories that explain why HPV-induced cancers arise preferentially in the oropharynx.

  1. Establishment of an animal model of spontaneous cervical lymph node metastasis of laryngeal squamous cell carcinoma and obtaining laryngocarcinoma cells with high metastatic potential.

    PubMed

    Chen, L W; Wang, J L; Zhang, L Y; Yang, S M; Li, C S; Yu, N; Zhao W, J D; Zhao, L D; Li, K; Liu, M B; Zhai, S Q

    2013-01-01

    To establish an animal model of spontaneous cervical lymph node metastasis of laryngeal squamous cell carcinoma and obtain laryngocarcinoma cells with high metastatic potential, laryngeal squamous cell carcinoma cell line HEP-2 in logarithmic phase were inoculated under the lingual margin mucosa of nude mice. HEP-2 cells metastasized to the cervical lymph nodes were isolated, cultured, and re-inoculated under the lingual margin mucosa of nude mice twice. The tumor formation in the tongue and in the cervical lymph nodes was confirmed by pathological examination. Carcinoma cells' ability of invasion and migration was detected by transwell assay. Human specific Alu sequences were detected by PCR, which indicated that the tumor cells originated from human laryngeal squamous cell carcinoma cell line HEP-2. Finally, an animal model of spontaneous lymph node metastasis of laryngeal squamous cell carcinoma was successfully established. Laryngeal squamous cell carcinoma cells with high metastatic potential to lymph nodes were obtained through repeated inoculations. .

  2. Endoscopic optical diagnosis provides high diagnostic accuracy of esophageal squamous cell carcinoma

    PubMed Central

    2014-01-01

    Background Recent technological advances have stimulated the development of endoscopic optical biopsy technologies. This study compared the accuracy of endoscopic diagnosis using magnifying narrow-band imaging (NBI) and histologic diagnosis of esophageal squamous lesions. Methods Patients at high risk for esophageal squamous cell carcinoma were examined with endoscopy and subsequent biopsy. The lesions diagnosed as cancer on NBI and the lesions diagnosed as cancer on biopsy were resected endoscopically or surgically. Histological diagnoses of resected specimens, the reference standards in this study, were made by a pathologist who was blind to both the endoscopic and biopsy diagnoses. The primary outcome was the accuracy of endoscopic and biopsy diagnosis. A noninferiority trial design with a noninferiority margin of −10% was chosen to investigate the accuracy of endoscopic diagnosis using magnifying NBI. Results Between November 2010 and October 2012, a total of 111 lesions in 85 patients were included in the analysis. The accuracy of endoscopic diagnosis and biopsy diagnosis for all lesions was 91.0% (101/111) and 85.6% (95/111), respectively. The difference in diagnostic accuracy was 5.4% (95% confidence interval: −2.9%–13.7%). The accuracy of endoscopic diagnosis and biopsy diagnosis of invasive cancers was 94.9% (74/78) and 84.6% (66/78), respectively. The difference was 10.3% (95% confidence interval: 1.6%–19.0%) for invasive cancers. The lower bound of the 95% confidence interval was above the prestated −10% in both cases. Conclusion Noninferiority of endoscopic diagnosis by magnifying NBI to histologic diagnosis by biopsy was established in this study (p = 0.0001). Trial registration The study was registered on 9th November 2010 in the University Hospital Medical Network Clinical Trials Registry as number: UMIN000004529. PMID:25108624

  3. 40 CFR 246.200 - High-grade paper recovery.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 26 2013-07-01 2013-07-01 false High-grade paper recovery. 246.200 Section 246.200 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) SOLID WASTES SOURCE... paper recovery....

  4. 40 CFR 246.200 - High-grade paper recovery.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 25 2014-07-01 2014-07-01 false High-grade paper recovery. 246.200 Section 246.200 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) SOLID WASTES SOURCE... paper recovery....

  5. 40 CFR 246.200 - High-grade paper recovery.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 26 2012-07-01 2011-07-01 true High-grade paper recovery. 246.200 Section 246.200 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) SOLID WASTES SOURCE... paper recovery....

  6. 1. Mill exterior, high grade chute partially restored on the ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    1. Mill exterior, high grade chute partially restored on the outside of mill building center of picture. Looking northeast from below bridge. - Kennecott Copper Corporation, Concentration Mill, On Copper River & Northwestern Railroad, Kennicott, Valdez-Cordova Census Area, AK

  7. Surgical Outcomes of High-Grade Spinal Cord Gliomas

    PubMed Central

    Hida, Kazutoshi; Yano, Syunsuke; Aoyama, Takeshi; Koyanagi, Izumi; Houkin, Kiyohiro

    2015-01-01

    Study Design A retrospective study. Purpose The purpose of this study was to obtain useful information for establishing the guidelines for treating high-grade spinal cord gliomas. Overview of Literature The optimal management of high-grade spinal cord gliomas remains controversial. We report the outcomes of the surgical management of 14 high-grade spinal glioma. Methods We analyzed the outcomes of 14 patients with high-grade spinal cord gliomas who were surgically treated between 1989 and 2012. Survival was charted with the Kaplan-Meier plots and comparisons were made with the log-rank test. Results None of the patients with high-grade spinal cord gliomas underwent total resection. Subtotal resection was performed in two patients, partial resection was performed in nine patients, and open biopsy was performed in three patients. All patients underwent postoperative radiotherapy and six patients further underwent radiation cordotomy. The median survival time for patients with high-grade spinal cord gliomas was 15 months, with a 5-year survival rate of 22.2%. The median survival time for patients with World Health Organization grade III tumors was 25.5 months, whereas the median survival time for patients with glioblastoma multiforme was 12.5 months. Both univariate and multivariate Cox proportional hazards models demonstrated a significant effect only in the group that did not include cervical cord lesion as a factor associated with survival (p=0.04 and 0.03). Conclusions The surgical outcome of patients diagnosed with high-grade spinal cord gliomas remains poor. Notably, only the model which excluded cervical cord lesions as a factor significantly predicted survival. PMID:26713128

  8. 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

  9. Management of high-risk squamous cell carcinoma of the skin.

    PubMed

    Samarasinghe, Venura; Madan, Vishal; Lear, John T

    2011-05-01

    Cutaneous squamous cell cancer (SCC) is the second most common skin cancer, accounting for one-fifth of all cutaneous malignancies. The majority arise on the head and neck skin, and cumulative UV exposure is thought to be the most likely etiological factor. The majority of deaths from SCC occur in a high-risk subgroup of patients. This high-risk subgroup of patients can be identified as those with tumors greater than 2 cm in diameter; tumor thickness over 4 mm; moderately/poorly differentiated or desmoplastic histological SCC subtype; ear, lip, hand, feet or genital tumor site; presence of perineural or lymphovascular invasion; nodal metastasis at presentation; recurrent SCC; SCC arising from scars or chronic skin disease, for example, chronic ulcers; and SCC arising in immunosuppressed patients. It is important to identify and aggressively treat these patients, as high-risk SCC are associated with a greater mortality and morbidity. This article reviews the diagnosis and management of such high-risk SCC.

  10. Middle Grades and High Schools Use Effective Strategies to Prepare Students for Challenging High School Studies. High Schools That Work

    ERIC Educational Resources Information Center

    Southern Regional Education Board (SREB), 2011

    2011-01-01

    Middle grades schools have their hands full in working with elementary schools and high schools to improve the likelihood of success for middle grades students--accelerating learning, helping elementary students move seamlessly into the middle grades, preparing middle grades students for rigorous high school courses, changing organization and…

  11. High School Extracurricular Activities & College Grades.

    ERIC Educational Resources Information Center

    Rombokas, Mary; And Others

    Many factors influence the development and socialization of American adolescents including peers, schools, family, and the community. This paper examines how the relationship of extracurricular participation influences academic growth. To determine if selected personal and academic variables during high school currently affect college academic…

  12. Risk-scoring models for individualized prediction of overall survival in low-grade and high-grade endometrial cancer

    PubMed Central

    AlHilli, Mariam M.; Mariani, Andrea; Bakkum-Gamez, Jamie N.; Dowdy, Sean C.; Weaver, Amy L.; Peethambaram, Preema P.; Keeney, Gary L.; Cliby, William A.; Podratz, Karl C.

    2015-01-01

    Objective Overall survival (OS) in endometrial cancer (EC) is dependent on patient-, disease-, and treatment-specific risk factors. Comprehensive risk-scoring models were developed to estimate OS in low-grade and high-grade EC. Methods Patients undergoing primary surgery for EC from 1999 through 2008 were stratified histologically according to the International Federation of Gynecology and Obstetrics (FIGO) as either (i) low grade: grades 1 and 2 endometrioid EC or (ii) high grade: grade 3, including non-endometrioid EC. Associations between patient-, pathological-, and treatment-specific risk factors and OS starting on postoperative day 30 were assessed using multivariable Cox regression models. Factors independently associated with OS were used to construct nomograms and risk-scoring models. Results Eligible patients (N= 1281) included 925 low-grade and 356 high-grade patients; estimated 5-year OSs were 87.0% and 51.5%, respectively. Among patients alive at last follow-up, median follow-up was 5.0 (low grade) and 4.6 years (high grade), respectively. In low-grade patients, independent factors predictive of compromised OS included age, cardiovascular disease, pulmonary dysfunction, stage, tumor diameter, pelvic lymph node status, and grade 2 or higher 30-day postoperative complications. Among high-grade patients, age, American Society of Anesthesiologists score, stage, lymphovascular space invasion, adjuvant therapy, para-aortic nodal status, and cervical stromal invasion were independent predictors of compromised OS. The two risk-scoring models/nomograms had excellent calibration and discrimination (unbiased c-indices = 0.803 and 0.759). Conclusion Patients with low-grade and high-grade EC can be counseled regarding their predicted OS using the proposed risk-scoring models. This may facilitate institution of personalized treatment algorithms, surveillance strategies, and lifestyle interventions. PMID:24690476

  13. Successful Nonoperative Management of High-Grade Blunt Renal Injuries

    PubMed Central

    Darwish, Oussama; Dang, Brian; Monda, John J.; Adsul, Prajakta; Syed, Johar; Siddiqui, Sameer A.

    2016-01-01

    Current management of high-grade blunt renal trauma favors a nonoperative approach when possible. We performed a retrospective study of high grade blunt renal injuries at our level I trauma center to determine the indications and success of nonoperative management (NOM). 47 patients with blunt grade IV or V injuries were identified between October 2004 and December 2013. Immediate operative patients (IO) were compared to nonoperatively managed (NOM). Of the 47 patients, 3 (6.4%) were IO and 44 (95.6%) NOM. IO patients had a higher heart rate on admission, 133 versus 100 in NOM (P = 0.01). IO patients had a higher rate of injury to the renal vein or artery (100%) compared to NOM group (18%) (P = 0.01). NOM failed in 3 of 44 patients (6.8%). Two required nonemergent nephrectomy and one required emergent exploration resulting in nephrectomy. Six NOM patients had kidney-related complications (13.6%). The renal salvage rate for the entire cohort was 87.2% and 93.2% for NOM. Nonoperative management for hemodynamically stable patients with high-grade blunt renal trauma is safe with a low risk of complications. Management decisions should consider hemodynamic status and visualization of active renal bleeding as well as injury grade in determining operative management. PMID:28018427

  14. High expression of prostate-specific membrane antigen in the tumor-associated neo-vasculature is associated with worse prognosis in squamous cell carcinoma of the oral cavity.

    PubMed

    Haffner, Michael C; Laimer, Johannes; Chaux, Alcides; Schäfer, Georg; Obrist, Peter; Brunner, Andrea; Kronberger, Irmgard E; Laimer, Klaus; Gurel, Bora; Koller, Johann-Benedikt; Seifarth, Christof; Zelger, Bettina; Klocker, Helmut; Rasse, Michael; Doppler, Wolfgang; Bander, Neil H

    2012-08-01

    Prostate-specific membrane antigen (PSMA) is a transmembrane protein expressed in prostate cancer as well as in the neo-vasculature of nonprostatic solid tumors. Here, we determined the expression pattern of PSMA in the vasculature of oral squamous cell carcinoma. Using a previously validated antibody, PSMA staining distribution and cyclooxygenase 2 (COX2) expression status was evaluated in a cohort of patients with squamous cell carcinoma of the oral cavity (n=96) using immunohistochemistry and was correlated with clinicopathological features as well as outcome. Twenty-four (25%) cases showed no detectable PSMA staining, 48 (50%) demonstrated positive immunoreactivity for PSMA in less than 50% of microvessels and 24 (25%) cases showed strong endothelial PSMA expression in more than 50% of tumor-associated microvessels. High endothelial PSMA expression was associated with greatly reduced survival (18.2 vs 77.3 months; P=0.0001) and maintained prognostic significance after adjusting for grade and stage in multivariate analysis (hazard ratio=2.19, P=0.007). Furthermore, we observed a strong association between endothelial PSMA and cancer cell-specific COX2 expression. In conclusion, we provide the first evidence for the prognostic significance of endothelial PSMA expression in oral squamous cell carcinoma and, suggest a potential interaction between arachidonic acid metabolites and endothelial PSMA expression in the tumor neo-vasculature.

  15. Three serum metabolite signatures for diagnosing low-grade and high-grade bladder cancer

    PubMed Central

    Tan, Guangguo; Wang, Haibo; Yuan, Jianlin; Qin, Weijun; Dong, Xin; Wu, Hong; Meng, Ping

    2017-01-01

    To address the shortcomings of cystoscopy and urine cytology for detecting and grading bladder cancer (BC), ultrahigh performance liquid chromatography (UHPLC) coupled with Q-TOF mass spectrometry in conjunction with univariate and multivariate statistical analyses was employed as an alternative method for the diagnosis of BC. A series of differential serum metabolites were further identified for low-grade(LG) and high-grade(HG) BC patients, suggesting metabolic dysfunction in malignant proliferation, immune escape, differentiation, apoptosis and invasion of cancer cells in BC patients. In total, three serum metabolites including inosine, acetyl-N-formyl-5-methoxykynurenamine and PS(O-18:0/0:0) were selected by binary logistic regression analysis, and receiver operating characteristic (ROC) test based on their combined use for HG BC showed that the area under the curve (AUC) was 0.961 in the discovery set and 0.950 in the validation set when compared to LG BC. Likewise, this composite biomarker panel can also differentiate LG BC from healthy controls with the AUC of 0.993 and 0.991 in the discovery and validation set, respectively. This finding suggested that this composite serum metabolite signature was a promising and less invasive classifier for probing and grading BC, which deserved to be further investigated in larger samples. PMID:28382976

  16. Rituximab in high-grade lymphoma.

    PubMed

    Zwick, Carsten; Murawski, Niels; Pfreundschuh, Michael

    2010-04-01

    In 1997, the approval of the anti-CD20 antibody rituximab heralded a new era of combined immunochemotherapy for the treatment of malignant lymphoma. Until then, a combination of cyclophosphamide, vincristine, doxorubicin, and prednisone (CHOP) had been the standard of treatment for aggressive B-cell lymphoma for more than 25 years. The addition of rituximab led to an impressive improvement of response rates and survival outcomes in patients with follicular and diffuse large B-cell lymphoma (DLBCL) that has been confirmed in several randomized trials. Remaining challenges in the rituximab era are the identification of the optimal chemotherapy partner with respect to synergistic effects, as well as to the lack of interference with its effector mechanisms. Finally, the question of the optimal dosage and schedule of rituximab has to be addressed in well-designed randomized trials. The outcome of patients relapsing after a rituximab-containing induction regimen is dismal even with high-dose therapy and autologous stem cell transplantation (ASCT). For these patients new modalities of second-line therapy are urgently warranted.

  17. Extremely High Tp53 Mutation Load in Esophageal Squamous Cell Carcinoma in Golestan Province, Iran

    PubMed Central

    Abedi-Ardekani, Behnoush; Kamangar, Farin; Sotoudeh, Masoud; Villar, Stephanie; Islami, Farhad; Aghcheli, Karim; Nasrollahzadeh, Dariush; Taghavi, Noushin; Dawsey, Sanford M.; Abnet, Christian C.; Hewitt, Stephen M.; Fahimi, Saman; Saidi, Farrokh; Brennan, Paul; Boffetta, Paolo; Malekzadeh, Reza; Hainaut, Pierre

    2011-01-01

    Background Golestan Province in northeastern Iran has one of the highest incidences of esophageal squamous cell carcinoma (ESCC) in the world with rates over 50 per 100,000 person-years in both sexes. We have analyzed TP53 mutation patterns in tumors from this high-risk geographic area in search of clues to the mutagenic processes involved in causing ESCC. Methodology/Principal Findings Biopsies of 119 confirmed ESCC tumor tissue from subjects enrolled in a case-control study conducted in Golestan Province were analyzed by direct sequencing of TP53 exons 2 through 11. Immunohistochemical staining for p53 was carried out using two monoclonal antibodies, DO7 and 1801. A total of 120 TP53 mutations were detected in 107/119 cases (89.9%), including 11 patients with double or triple mutations. The mutation pattern was heterogeneous with infrequent mutations at common TP53 “hotspots” but frequent transversions potentially attributable to environmental carcinogens forming bulky DNA adducts, including 40% at bases known as site of mutagenesis by polycyclic aromatic hydrocarbons (PAHs). Mutations showed different patterns according to the reported temperature of tea consumption, but no variation was observed in relation to ethnicity, tobacco or opium use, and alcoholic beverage consumption or urban versus rural residence. Conclusion/Significance ESCC tumors in people from Golestan Province show the highest rate of TP53 mutations ever reported in any cancer anywhere. The heterogeneous mutation pattern is highly suggestive of a causative role for multiple environmental carcinogens, including PAHs. The temperature and composition of tea may also influence mutagenesis. PMID:22216294

  18. Determinants of Complications and Outcome in High-Risk Squamous Cell Head-and-Neck Cancer Treated With Perioperative High-Dose Rate Brachytherapy (PHDRB)

    SciTech Connect

    Martinez-Monge, Rafael; Pagola Divasson, Maria; Cambeiro, Mauricio; Gaztanaga, Miren; Moreno, Marta; Arbea, Leire; Montesdeoca, Nestor; Alcalde, Juan

    2011-11-15

    Purpose: To determine the impact of a set of patient, tumor, and treatment factors on toxicity and outcome in patients with head-and-neck squamous cell cancer treated with surgical resection and perioperative high-dose rate brachytherapy (PHDRB) alone (single-modality [SM] group) (n = 46) or PHDRB combined with postoperative radiation or chemoradiation (combined-modality [CM] group) (n = 57). Methods and Materials: From 2000 to 2008, 103 patients received PHDRB after complete macroscopic resection. SM patients received 32 or 40 Gy of PHDRB in 8 or 10 twice-daily treatments for R0 and R1 resections. CM patients received 16 or 24 Gy of PHDRB in 4 or 6 twice-daily treatments for R0 and R1 resections, followed by external radiation of 45 Gy in 25 fractions with or without concomitant chemotherapy. Results: Grade {>=}4 complications according to the Radiation Therapy Oncology Group were more frequent in the SM group than in the CM group (p = 0.024). Grade {>=}3 and {>=}4 complications increased with the antecedent of prior irradiation (p = 0.032 and p = 0.006, respectively) and with TV{sub 150} values of 13 mL or greater (p = 0.032 and p = 0.032, respectively). After a median follow-up of 34.8 and 60.8 months for SM and CM patients, respectively, patients with high-risk margins had a 9-year local control rate of 68.0% whereas patients with wider margins had a 9-year local control of 93.7% (p = 0.045). Patients with primary and recurrent tumors had 9-year actuarial locoregional control rates of 81.8% and 54.2%, respectively (p = 0.003). Patients with lymph-vascular space invasion (LVSI)-positive and LVSI-negative tumors had 9-year distant control rates of 62.8% and 81.6%, respectively (p = 0.034). Disease-free survival rates decreased in recurrent cases (p = 0.006) as well as in LVSI-positive patients (p = 0.035). Conclusions: The complications observed are largely attributable to the antecedent of prior irradiation but can possibly be minimized by meticulous mapping and

  19. High School Grades and University Performance: A Case Study

    ERIC Educational Resources Information Center

    Cyrenne, Philippe; Chan, Alan

    2012-01-01

    A critical issue facing a number of colleges and universities is how to allocate first year places to incoming students. The decision to admit students is often based on a number of factors, but a key statistic is a student's high school grades. This paper reports on a case study of the subsequent performance at the University of Winnipeg of high…

  20. Environmental Education for Junior High Grades: A Teacher's Manual.

    ERIC Educational Resources Information Center

    Michigan State Dept. of Natural Resources, Lansing.

    Teaching suggestions for environmental education in junior high school grades are grouped under five general headings: "Geology,""Water Resources,""Soil and Land Use,""Trees, Woodlots, and Forests," and "Wild-life and Fishes." Listed under each heading are attitudes and understandings to develop, topics for discussion, and many suggested…

  1. A survival analysis comparing women with ovarian low-grade serous carcinoma to those with high-grade histology.

    PubMed

    Chen, Ming; Jin, Ying; Bi, Yalan; Yin, Jie; Wang, Yongxue; Pan, Lingya

    2014-01-01

    Ovarian low-grade serous carcinoma (LGSC) and high-grade serous carcinoma have distinct molecular profiles, clinical behaviors, and treatment responses. The survival advantage for patients with low-grade carcinoma compared with patients with high-grade histology remains controversial. We retrospectively reviewed the medical charts of 381 patients with ovarian serous carcinoma at Peking Union Medical College Hospital from 2007 to 2010. Patients were classified into two groups according to MD Anderson two-tier system: 35 (9.2%) cases with LGSC and 346 with high-grade serous carcinoma. Patients with low-grade serous ovarian cancer had a significantly younger age at diagnosis (46 versus 56 years, P=0.046), and their median progression-free survival (PFS) and overall survival values were 35.0 and 54.0 months, respectively. A multivariate analysis showed that, for serous ovarian cancer, the histological grade was a significant prognostic factor for PFS but not for overall survival (P=0.022 and P=0.0566, respectively). When stratified by the existence of a residual disease, patients with low-grade disease who underwent cytoreductive surgery without macroscopic residual disease (>1 cm) had a significantly improved median PFS time (36.0 months) compared with that of patients with high-grade carcinoma who received optimal cytoreductive surgery (16.0 months, P=0.017). Conversely, patients with low-grade and high-grade carcinoma who were left with macroscopic residue (>1 cm) experienced a similarly shorter median PFS (10.0 and 13.0 months, respectively, P=0.871). The International Federation of Gynecology and Obstetrics stage and residual disease were significant prognostic factors of low-grade carcinoma, while positive ascites was associated with a worse PFS value. Our data showed that LGSC is a different entity from high-grade carcinoma and that LGSC was associated with improved PFS after optimal cytoreductive surgery but not suboptimal operation.

  2. Comparison of subtypes of penile squamous cell carcinoma from high and low incidence geographical regions.

    PubMed

    Chaux, Alcides; Lezcano, Cecilia; Cubilla, Antonio L; Tamboli, Pheroze; Ro, Jae; Ayala, Alberto

    2010-08-01

    There is a worldwide geographical variation in the incidence of penile squamous cell carcinoma (PSCC); some subtypes are HPV-related (warty, basaloid) while others (keratinizing variants) are not. The aims of this study were to compare the distribution of different histological subtypes of PSCC from regions of low (Paraguay, 144 cases) and high (USA, 157 cases) incidence and to identify and compare tumors with and without warty and/or basaloid morphology. The distribution of subtypes in the Paraguayan and the American series was: usual, 49.3 and 46.5%; verrucous, 8.3 and 7.6%; papillary NOS, 7.6 and 5.7%; warty, 6.9 and 8.3%; basaloid, 4.2 and 7.0%; sarcomatoid, 0.7 and 0.6%; adenosquamous, 3.5 and 0.6%; and mixed, 19.4 and 23.6%, respectively. The distribution of mixed PSCC was: warty-basaloid, 50.0 and 59.5%; usual-verrucous, 21.4 and 21.6%; usual-warty, 14.3 and 8.1%; usual-basaloid, 7.1 and 0.0%; usual-papillary, 3.6 and 5.4%; and others, 3.6 and 5.4%, respectively. In conclusion, we found no geographical difference in the incidence of histological subtypes (p = 0.6501), mixed PSCC (p = 0.5937) or HPV-related tumors (p = 0.2505). Geographical variation may be the result of staging variation at clinical presentation or of pathological diagnosis. The identification of similar histological subtypes in both series validates this classification approach for penile cancer. The tendency for typical SCC to mix with verrucous and papillary carcinomas and of the basaloid to preferentially mix with benign condyloma and condylomatous (warty) carcinomas would support the hypothesis of the existence of an etiologically different dual population of penile tumors.

  3. High Intrathoracic Anastomosis with Thoracoscopy Is Safe and Feasible for Treatment of Esophageal Squamous Cell Carcinoma

    PubMed Central

    Jeon, Hyun Woo; Park, Jae Kil; Song, Kyo Young; Sung, Sook Whan

    2016-01-01

    Background Minimally invasive esophagectomy (MIE) has the potential to reduce the morbidity and mortality of esophageal cancer surgery. Esophageal squamous cell carcinoma (ESCC) has a high incidence of earlier lymphatic spread and is usually located more proximal to the incisor than esophageal adenocarcinoma; consequently, the anastomosis should be made more proximal in the thorax or in the neck. We adopted the proximal intrathoracic anastomotic technique using thoracoscopy for mid-to-lower ESCC. Methods From October 2010 to August 2014, fifty-eight consecutive patients underwent MIE for ESCC. After laparoscopic gastric tubing, thoracoscopic esophageal resection and reconstruction were performed using a 28-mm circular stapler following radical mediastinal lymph node dissection. We tried to make an anastomosis at the apex of the chest. Postoperative outcomes, including overall survival and recurrence, were assessed. Results The mean patient age was 64.3±9 years. The mean operative time was 371.8±51.6 minutes, and the duration of the thorax procedure was 254.8±38.3 minutes. The mean number of lymph nodes dissected was 31±11.7. The mean intensive care unit (ICU) stay and hospital stay were 3.5±8.2 hours and 13.6±7.4 days, respectively. The level of anastomosis was 22.3±1.8cm from the incisor. One patient died of uncontrolled sepsis due to necrosis of the gastric graft. Two patients developed small contained leakage. Nine patients exhibited distant metastasis during the follow-up period. Conclusion Thoracoscopic intrathoracic anastomosis at the proximal esophagus is feasible and safe. PMID:27011160

  4. Argon plasma coagulation for superficial esophageal squamous-cell carcinoma in high-risk patients

    PubMed Central

    Tahara, Kumiko; Tanabe, Satoshi; Ishido, Kenji; Higuchi, Katsuhiko; Sasaki, Tohru; Katada, Chikatoshi; Azuma, Mizutomo; Nakatani, Kento; Naruke, Akira; Kim, Myungchul; Koizumi, Wasaburo

    2012-01-01

    AIM: To evaluate the usefulness and safety of argon plasma coagulation (APC) for superficial esophageal squamous-cell carcinoma (SESC) in high-risk patients. METHODS: We studied 17 patients (15 men and 2 women, 21 lesions) with SESC in whom endoscopic mucosal resection (EMR), endoscopic submucosal dissection (ESD), and open surgery were contraindicated from March 1999 through February 2009. None of the patients could tolerate prolonged EMR/ESD or open surgery because of severe concomitant disease (e.g., liver cirrhosis, cerebral infarction, or ischemic heart disease) or scar formation after EMR/ESD and chemoradiotherapy. After conventional endoscopy, an iodine stain was sprayed on the esophageal mucosa to determine the lesion margins. The lesion was then ablated by APC. We retrospectively studied the treatment time, number of APC sessions per site, complications, presence or absence of recurrence, and time to recurrence. RESULTS: The median duration of follow-up was 36 mo (range: 6-120 mo). All of the tumors were macroscopically classified as superficial and slightly depressed type (0-IIc). The preoperative depth of invasion was clinical T1a (mucosal cancer) for 19 lesions and clinical T1b (submucosal cancer) for 2. The median treatment time was 15 min (range: 10-36 min). The median number of treatment sessions per site was 2 (range: 1-4). The median hospital stay was 14 d (range: 5-68 d). Among the 17 patients (21 lesions), 2 (9.5%) had recurrence and underwent additional APC with no subsequent evidence of recurrence. There were no treatment-related complications, such as bleeding or perforation. CONCLUSION: APC is considered to be safe and effective for the management of SESC that cannot be resected endoscopically because of underlying disease, as well as for the control of recurrence after EMR and local recurrence after chemoradiotherapy. PMID:23082058

  5. Multiple Human Papillomavirus Infections with High Viral Loads Are Associated with Cervical Lesions but Do Not Differentiate Grades of Cervical Abnormalities

    PubMed Central

    Depuydt, Christophe; Benoy, Ina; Bogers, Johannes; Antoine, Jerome; Arbyn, Marc; Pawlita, Michael

    2013-01-01

    Multiple human papillomavirus (HPV) genotypes often coexist within cervical epithelia and are frequently detected together in smears of different grades of cervical neoplasia. Describing the association between multiple infections and cervical disease is important in generating hypotheses regarding its pathogenesis. We analyzed the prevalence of multiple HPV infections and their attribution to cervical disease in a screening population of 999 consecutive BD SurePath liquid-based cervical cytology samples enriched with atypical squamous cells of undetermined significance (ASCUS) (n = 100), low-grade squamous intraepithelial lesions (LSIL) (n = 100), and high-grade squamous intraepithelial lesions (HSIL) (n = 97). HPV genotyping was performed only on cytology specimens using a broad-spectrum GP5+/6+-PCR/multiplex HPV genotyping (BSGP5+/6+-PCR/MPG) assay that detects and quantifies 51 HPV genotypes and 3 subtypes. Using a recently defined high viral load cutoff, the quantitative data were scored as high or low viral load. In the 36-month follow-up, 79 histologically confirmed cervical intraepithelial neoplasia grade 2 or greater (CIN2+) cases were identified. In the screening population, there was a trend of having more multiple infections at a younger age. Multiple HPV infections were common. Multiple HPV types were most prevalent in LSIL (75.9% of HPV positives), followed by HSIL (65.5%), ASCUS (64.6%), and negative for intraepithelial lesion or malignancy (NILM) (36.8%). On average, 3.2 and 2.5 HPV types were detected per LSIL and HSIL sample, respectively. Multiple HPV types with high viral loads were most prevalent in LSIL (62.6% of high viral load positives), followed by HSIL (51.9%), ASCUS (40.7%), and NILM (19.3%). Patients with multiple high viral loads showed a 4- to 6-fold-higher risk of having cervical precancerous cytological lesions than did patients with single high viral loads. Compared to NILM, multiple infections, especially with multiple high viral

  6. The Relationship of Grade Span in 9th Grade to Math Achievement in High School

    ERIC Educational Resources Information Center

    West, John; Miller, Mary Lou; Myers, Jim; Norton, Timothy

    2015-01-01

    Purpose, Scope, and Method of Study: The purpose of this study was to determine if a correlation exists between grade span for ninth grade and gains in math achievement test scores in 10th grade and 12th grade. A quantitative, longitudinal, correlational research design was employed to investigate the research questions. The population was high…

  7. Correlation of EGFR, pEGFR and p16INK4 expressions and high risk HPV infection in HIV/AIDS-related squamous cell carcinoma of conjunctiva

    PubMed Central

    2014-01-01

    Background Squamous cell carcinoma of conjunctiva has increased tenfold in the era of HIV/AIDS. The disease pattern has also changed in Africa, affecting young persons, with peak age-specific incidence of 30-39 years, similar to that of Kaposi sarcoma, a well known HIV/AIDS defining neoplasm. In addition, the disease has assumed more aggressive clinical course. The contributing role of exposure to high risk HPV in the development of SCCC is still emerging. Objective The present study aimed to investigate if immunohistochemical expressions of EGFR, pEGFR and p16, could predict infection with high risk HPV in HIV-related SCCC. Methods FFPE tissue blocks of fifty-eight cases diagnosed on hematoxylin and eosin with SCCC between 2005-2011, and subsequently confirmed from medical records to be HIV positive at the department of human pathology, UoN/KNH, were used for the study. Immunohistochemistry was performed to assess the expressions of p16INK4A, EGFR and pEGFR. This was followed with semi-nested PCR based detection and sequencing of HPV genotypes. The sequences were compared with the GenBank database, and data analyzed for significant statistical correlations using SPSS 16.0. Ethical approval to conduct the study was obtained from KNH-ERC. Results Out of the fifty-eight cases of SCCC analyzed, twenty-nine (50%) had well differentiated (grade 1), twenty one (36.2%) moderately differentiated (grade 2) while eight (13.8%) had poorly differentiated (grade 3) tumours. Immunohistochemistry assay was done in all the fifty eight studied cases, of which thirty nine cases (67.2%) were positive for p16INK4A staining, forty eight cases (82.8%) for EGFR and fifty one cases (87.9%) showed positivity for p-EGFR. HPV DNA was detected in 4 out of 40 SCCC cases (10%) in which PCR was performed, with HPV16 being the only HPV sub-type detected. Significant statistical association was found between HPV detection and p16INK4 (p=0.000, at 99% C.I) and EGFR (p=0.028, at 95% C.I) expressions

  8. OVARIAN LOW-GRADE AND HIGH-GRADE SEROUS CARCINOMA: Pathogenesis, Clinicopathologic and Molecular Biologic Features, and Diagnostic Problems

    PubMed Central

    Vang, Russell; Shih, Ie-Ming; Kurman, Robert J.

    2009-01-01

    Ovarian serous carcinomas have been graded using various systems. Recently, a 2-tier system in which tumors are subdivided into low-grade and high-grade has been proposed. This approach is simplistic, reproducible, and based on biologic evidence indicating that both tumors develop via different pathways. Low-grade serous carcinomas exhibit low-grade nuclei with infrequent mitotic figures. They evolve from adenofibromas or borderline tumors, have frequent mutations of the KRAS, BRAF, or ERBB2 genes, and lack TP53 mutations (Type I pathway). The progression to invasive carcinoma is a slow step-wise process. Low-grade tumors are indolent and have better outcome than high-grade tumors. In contrast, high-grade serous carcinomas have high-grade nuclei and numerous mitotic figures. Identification of a precursor lesion in the ovary has been elusive and therefore the origin of ovarian carcinoma has been described as de novo. More recently, studies have suggested that a proportion appear to originate from intraepithelial carcinoma in the fallopian tube. The development of these tumors is rapid (Type II pathway). The vast majority are characterized by TP53 mutations and lack mutations of KRAS, BRAF, or ERBB2. Although both types of serous carcinomas evolve along different pathways, rare high-grade serous carcinomas seem to arise through the Type I pathway. Immunohistochemical stains for p53, p16, and Ki-67 for distinction of low- from high-grade tumors are of limited value but can be helpful in selected instances. This review provides an update on the pathogenesis and clinicopathologic features of these two types of serous carcinomas and addresses some of the diagnostic problems that are encountered in routine practice. PMID:19700937

  9. 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.

  10. ?Differential Grading Standards among High Schools. ACT Research Report Series, 2004-02

    ERIC Educational Resources Information Center

    Woodruff, David J.; Ziomek, Robert L.

    2004-01-01

    The primary purpose of this study was to investigate differential grading standards among public high schools. This study focused on documenting differential grading standards between 1998 and 2002. Five years were studied to verify that the observed differences in grading standards were not transient. Differences in grading standards among high…

  11. [High-risk human papilloma virus associated oropharynx squamous cell carcinomas: clinical, biological implications and therapeutical perspectives].

    PubMed

    Guihard, S; Jung, A-C; Noël, G

    2012-02-01

    The infection of the head and neck epithelium by high-risk human papillomaviruses (HPV) is a risk factor for cancer onset and development. The incidence of HPV-related head and neck squamous cell carcinoma is currently increasing. These lesions display distinct clinical features. HPV positive patients are often younger and have a smaller history of tobacco smoking and alcohol drinking, but have a history of virus-transmitting sex practices. HPV-related tumours are mainly found in the oropharynx, are more associated to a local lymph node invasion and display a poorly differentiated morphology. Despite these more aggressive features, HPV-positive head and neck squamous cell carcinomas correlate with an improved local control, disease-free and global survival. It is thought that HPV-driven specific biologic abnormalities underlie higher tumour sensitivity to chemotherapeutic drugs and ionizing radiations. The expression of the HPV E6 and E7 oncoproteins induce cell transformation by interfering with cell signalling pathways involved in apoptosis, cell cycle, angiogenesis and induce the overexpression of the CDKN2A gene. Therefore, alternative treatments based on therapies targeting these pathways in combination with radiation dose de-escalation could be proposed to HPV-positive patients, if they are properly and reliably identified.

  12. Postoperative Chemoradiotherapy and Cetuximab for High-Risk Squamous Cell Carcinoma of the Head and Neck: Radiation Therapy Oncology Group RTOG-0234

    PubMed Central

    Harari, Paul M.; Harris, Jonathan; Kies, Merrill S.; Myers, Jeffrey N.; Jordan, Richard C.; Gillison, Maura L.; Foote, Robert L.; Machtay, Mitchell; Rotman, Marvin; Khuntia, Deepak; Straube, William; Zhang, Qiang; Ang, Kian

    2014-01-01

    Purpose To report results of a randomized phase II trial (Radiation Therapy Oncology Group RTOG-0234) examining concurrent chemoradiotherapy and cetuximab in the postoperative treatment of patients with squamous cell carcinoma of the head and neck (SCCHN) with high-risk pathologic features. Patients and Methods Eligibility required pathologic stage III to IV SCCHN with gross total resection showing positive margins and/or extracapsular nodal extension and/or two or more nodal metastases. Patients were randomly assigned to 60 Gy radiation with cetuximab once per week plus either cisplatin 30 mg/m2 or docetaxel 15 mg/m2 once per week. Results Between April 2004 and December 2006, 238 patients were enrolled. With a median follow-up of 4.4 years, 2-year overall survival (OS) was 69% for the cisplatin arm and 79% for the docetaxel arm; 2-year disease-free survival (DFS) was 57% and 66%, respectively. Patients with p16-positive oropharynx tumors showed markedly improved survival outcome relative to patients with p16-negative oropharynx tumors. Grade 3 to 4 myelosuppression was observed in 28% of patients in the cisplatin arm and 14% in the docetaxel arm; mucositis was observed in 56% and 54%, respectively. DFS in this study was compared with that in the chemoradiotherapy arm of the RTOG-9501 trial (Phase III Intergroup Trial of Surgery Followed by Radiotherapy Versus Radiochemotherapy for Resectable High Risk Squamous Cell Carcinoma of the Head and Neck), which had a hazard ratio of 0.76 for the cisplatin arm versus control (P = .05) and 0.69 for the docetaxel arm versus control (P = .01), reflecting absolute improvement in 2-year DFS of 2.5% and 11.1%, respectively. Conclusion The delivery of postoperative chemoradiotherapy and cetuximab to patients with SCCHN is feasible and tolerated with predictable toxicity. The docetaxel regimen shows favorable outcome with improved DFS and OS relative to historical controls and has commenced formal testing in a phase II/III trial

  13. Reviewing the genetic alterations in high-risk cutaneous squamous cell carcinoma: A search for prognostic markers and therapeutic targets.

    PubMed

    Ashford, Bruce G; Clark, Jonathan; Gupta, Ruta; Iyer, N Gopalakrishna; Yu, Bing; Ranson, Marie

    2017-04-03

    Cutaneous squamous cell carcinoma (SCC) is second only in incidence to basal cell carcinoma (BCC), effecting up to 500 000 people in the United States annually. Metastasis to regional lymph nodes occurs in approximately 5% of cases and imparts significant morbidity. Standard treatment in this group involves a combination of surgery and adjuvant radiation. Currently, there are no clinically useful biomarkers of metastatic potential in primary cutaneous SCC and histological predictors can be unreliable. The high level of mutational burden in normal UV-exposed skin has hampered the search for novel drivers of invasive disease, and indeed metastatic potential. This review outlines the clinical problems in high-risk and metastatic cutaneous SCCs, reviews the known genetic events and molecular mechanisms in high-risk primary cutaneous SCC and metastasis, and identifies avenues for further investigation and potential therapy.

  14. Radiosurgical boost for primary high-grade gliomas.

    PubMed

    Prisco, Flavio E; Weltman, Eduardo; de Hanriot, Rodrigo M; Brandt, Reynaldo A

    2002-04-01

    The purpose of this study was to retrospectively evaluate the survival of patients with high-grade gliomas treated with external beam radiotherapy with or without radiosurgical boost. From July 1993 to April 1998, 32 patients were selected, 15 of which received radiosurgery. Inclusion criteria were age > 18 years, histological confirmation of high-grade glioma, primary tumor treatment with curative intent, unifocal tumor and supratentorial location. All patients were found to be in classes III-VI, according to the recursive partitioning analysis proposed by the Radiation Therapy Oncology Group. The median interval between radiotherapy and radiosurgery was 5 weeks (range 1-13). Treatment volumes ranged from 2.9 to 70.3 cc (median 15.0 cc). Prescribed radiosurgery doses varied from 8.0 to 12.5 Gy (median 10.0 Gy). Radiosurgery and control groups were well balanced with respect to prognostic factor distributions. Median actuarial survival time in radiosurgery and control groups was 21.4 months and 11.6 months, respectively (p = 0.0254). Among patients with KPS > 80, median survival time was 11.0 months and 53.9 months in the control and radiosurgery groups, respectively (p = 0.0103). Radiosurgery was the single factor correlated with survival on Cox model analysis (p = 0.0362) and was associated with a 2.76 relative reduction in the risk of cancer death (95% confidence interval (CI) 1.07-7.13). Our results suggest that radiosurgery may confer a survival advantage for patients in RPA classes III-VI, especially for those with Karnofsky performance status >80. The definitive role of radiosurgical boost for patients with high-grade gliomas awaits the results of randomized trials.

  15. High-efficiency beam bending using graded photonic crystals.

    PubMed

    Oner, B B; Turduev, M; Kurt, H

    2013-05-15

    We explore beam-bending properties of graded index (GRIN) waveguide with hyperbolic secant profile. The transmission efficiency and bandwidth features are extracted for GRIN photonic crystal (PC) media composed of dielectric rods. Light guiding performance of the GRIN PC medium is analyzed for 90° and 180° waveguide bends. The finite-difference time-domain method is deployed to investigate the performance of the designed GRIN waveguides. By the help of proposed photonic configuration, bending of light is achieved with a high efficiency within a broad bandwidth, which promotes the use of GRIN PC structures for efficient light-bending purposes.

  16. Basaloid squamous cell carcinoma of oral cavity: Report of two cases

    PubMed Central

    Heera, R; Ayswarya, T; Padmakumar, SK; Ismayil, P

    2016-01-01

    Basaloid squamous cell carcinoma (BSCC) is an aggressive, high-grade, variant of squamous cell carcinoma (SCC), which is uncommon in the oral cavity but slightly more common in the oropharynx. We present two cases of BSCC, one arising in the floor of the mouth and the other arising on the lateral border of the tongue. The diagnosis of this subtype of SCC is important owing to its particular behavior, with an aggressive course, a high incidence of local recurrence, regional lymph node metastases and mortality rate. PMID:27721627

  17. Histopathologic Features of Prognostic Significance in High-Grade Osteosarcoma.

    PubMed

    Chui, Michael Herman; Kandel, Rita A; Wong, Marcus; Griffin, Anthony M; Bell, Robert S; Blackstein, Martin E; Wunder, Jay S; Dickson, Brendan C

    2016-08-23

    Context .- In osteosarcoma treated with neoadjuvant chemotherapy the extent of tumor necrosis on resection is considered an indicator of treatment response, and this has been shown to correlate with survival in most but not all studies. Objective .- To identify additional histologic variables of prognostic significance in high-grade osteosarcoma. Design .- Slides of pretreatment biopsy and primary postneoadjuvant chemotherapy resections from 165 patients with high-grade osteosarcoma were reviewed. Univariate (Kaplan-Meier) and multivariate (Cox regression) analyses were performed to identify clinical and histomorphologic attributes associated with overall survival. Results .- Univariate analyses confirmed the prognostic significance of metastatic status on presentation, primary tumor size, anatomic site, and histologic subtype. Additionally, the identification of lymphovascular invasion, 10% or more residual viable tumor, and 10 or more mitoses per 10 high-powered fields assessed in posttreatment resections were associated with poor survival, retaining significance in multivariate analyses. Based on results from multivariate analysis, we developed a prognostic index incorporating primary tumor size and site, and significant histologic features assessed on resection (ie, lymphovascular invasion status, mitotic rate, and extent of viable tumor). This scoring system segregates patients into 3 risk categories with significant differences in overall survival and retained significance in an independent validation set of 42 cases. Conclusions .- The integration of clinical and microscopic features improves prognostication of patients with osteosarcoma.

  18. Looking Forward to High School and College: Middle Grade Indicators of Readiness in Chicago Public Schools

    ERIC Educational Resources Information Center

    Allensworth, Elaine M.; Gwynne, Julia A.; Moore, Paul; de la Torre, Marisa

    2014-01-01

    There is a very large population of students who struggle with the transition from the middle grades to high school, raising concerns that high school failures are partially a function of poor middle grade preparation. As a result, middle grade practitioners are grappling with questions about what skills students need to succeed in high school,…

  19. Pre-irradiation chemotherapy for newly diagnosed high grade astrocytoma.

    PubMed

    Mathieu, N Tubiana; Genet, D; Labrousse, F; Bouillet, P; Denes, S Lavau; Martin, J; Labourey, J L; Venat, L; Clavere, P; Moreau, J J

    2004-01-01

    The purpose of this work was to determine the response rate and toxicity of a combination of Carmustine and Cisplatin administered before radiation in patients with newly diagnosed high grade astrocytoma. A good response rate has been published with this association in primary cerebral high grade tumor. This protocol was administered in a homogeneous population of 37 adult patients with measurable tumor on magnetic resonance imaging (MRI) or CT scan. After biopsy or subtotal resection, the patients received BCNU 40 mg/m2/d and CODP 40 mg/m2/d, for 3 days every 28 days for 3 cycles. Evaluation was performed before each cycle. Radiation therapy began 4 weeks after completing the chemotherapy or immediately if there was evidence of tumor progression on chemotherapy. Seven out of 37 (19%) demonstrated tumor regression with a median duration to progression of 11 months. Median survival was 6 months. Myelosuppression was the predominant but manageable toxicity. This work indicated that the first chemotherapy protocol gave poor results in a homogeneous group of patients, with bad prognosis.

  20. Social Science Instructional Guides: High School (Grades 9-12).

    ERIC Educational Resources Information Center

    Hartman, Carl; And Others

    The guide, part of a social science learning continuum from first through twelfth grades, contains outlines for two-semester social studies courses for grades 9-12. Three components comprise each section: time allocations for units, instructional objectives, and a content outline. The Grade 9 course, Cultures of the Non-Western World, contains…

  1. Yoga May Mitigate Decreases in High School Grades

    PubMed Central

    Butzer, Bethany; van Over, Max; Noggle Taylor, Jessica J.; Khalsa, Sat Bir S.

    2015-01-01

    This study involves an exploratory examination of the effects of a 12-week school-based yoga intervention on changes in grade point average (GPA) in 9th and 10th grade students. Participants included 95 high school students who had registered for physical education (PE) in spring 2010. PE class sections were group randomized to receive either a yoga intervention or a PE-as-usual control condition. The yoga intervention took place during the entire third quarter and half of the fourth quarter of the school year, and quarterly GPA was collected via school records at the end of the school year. Results revealed a significant interaction between group and quarter suggesting that GPA differed between the yoga and control groups over time. Post hoc tests revealed that while both groups exhibited a general decline in GPA over the school year, the control group exhibited a significantly greater decline in GPA from quarter 1 to quarter 3 than the yoga group. Both groups showed equivalent declines in GPA in quarter 4 after the yoga intervention had ended. The results suggest that yoga may have a protective effect on academic performance by preventing declines in GPA; however these preventive effects may not persist once yoga practice is discontinued. PMID:26347787

  2. High-Grade Leiomyosarcoma Arising in a Previously Replanted Limb

    PubMed Central

    Pan, Tiffany J.; Pantanowitz, Liron; Weiss, Kurt R.

    2015-01-01

    Sarcoma development has been associated with genetics, irradiation, viral infections, and immunodeficiency. Reports of sarcomas arising in the setting of prior trauma, as in burn scars or fracture sites, are rare. We report a case of a leiomyosarcoma arising in an arm that had previously been replanted at the level of the elbow joint following traumatic amputation when the patient was eight years old. He presented twenty-four years later with a 10.8 cm mass in the replanted arm located on the volar forearm. The tumor was completely resected and pathology examination showed a high-grade, subfascial spindle cell sarcoma diagnosed as a grade 3 leiomyosarcoma with stage pT2bNxMx. The patient underwent treatment with brachytherapy, reconstruction with a free flap, and subsequently chemotherapy. To the best of our knowledge, this is the first case report of leiomyosarcoma developing in a replanted extremity. Development of leiomyosarcoma in this case could be related to revascularization, scar formation, or chronic injury after replantation. The patient remains healthy without signs of recurrence at three-year follow-up. PMID:26366310

  3. High-grade cytomegalovirus antigenemia after hematopoietic stem cell transplantation.

    PubMed

    Asano-Mori, Y; Oshima, K; Sakata-Yanagimoto, M; Nakagawa, M; Kandabashi, K; Izutsu, K; Hangaishi, A; Motokura, T; Chiba, S; Kurokawa, M; Hirai, H; Kanda, Y

    2005-11-01

    Clinical impact of high-grade (HG) cytomegalovirus (CMV) antigenemia after hematopoietic stem cell transplantation has not been clarified. Therefore, in order to investigate the risk factors and outcome for HG-CMV antigenemia, we retrospectively analyzed the records of 154 Japanese adult patients who underwent allogeneic hematopoietic stem cell transplantation for the first time from 1995 to 2002 at the University of Tokyo Hospital. Among 107 patients who developed positive CMV antigenemia at any level, 74 received risk-adapted preemptive therapy with ganciclovir (GCV), and 17 of these developed HG-antigenemia defined as > or = 50 positive cells per two slides. The use of systemic corticosteroids at > or = 0.5 mg/kg/day at the initiation of GCV was identified as an independent significant risk factor for HG-antigenemia. Seven of the 17 HG-antigenemia patients developed CMV disease, with a cumulative incidence of 49.5%, which was significantly higher than that in the low-grade antigenemia patients (4%, P<0.001). However, overall survival was almost equivalent in the two groups. In conclusion, the development of HG-antigenemia appeared to depend on the profound immune suppression of the recipient. Although CMV disease frequently developed in HG-antigenemia patients, antiviral therapy could prevent a fatal outcome.

  4. Current views and perspectives on classification of squamous intraepithelial lesions of the head and neck.

    PubMed

    Gale, Nina; Zidar, Nina; Poljak, Mario; Cardesa, Antonio

    2014-03-01

    The current state in the field of classifying oral and laryngeal precursor lesions, as proposed in the WHO 2005 Blue Book is not ideal. The results of various inter-observer studies have shown that the currently used grading systems, with different basic concepts and different terminology, cannot continue to be reliably used in the future. The different etiology of cervical and head and neck precursor lesions requires a classification designed to cater to the specificities of the head and neck region. Trying to harmonize different classifications of the oral and laryngeal precursor lesions, we have proposed four crucial steps to set up a unified classification of squamous intraepithelial lesions (SILs): (a) the classification should contain two grades, low-grade and high-grade lesions and, specifically for the larynx, an additional grade-carcinoma in situ (CIS) which must be separated from high-grade laryngeal SILs; (b) the terminology should be unified; our preference is for the term SIL over squamous intraepithelial neoplasia; (c) all leading morphological criteria for low- and high-grade lesions, as well as for CIS, should be clearly defined; (d) agreement between clinicians and pathologists should be achieved on the most appropriate choice of treatment of different grades of SILs in separate head and neck areas.

  5. Re-irradiation alternatives for recurrent high-grade glioma

    PubMed Central

    Dong, Yuanli; Fu, Chengrui; Guan, Hui; Zhang, Tianyi; Zhang, Zicheng; Zhou, Tao; Li, Baosheng

    2016-01-01

    Despite advances in the fields of surgery, chemotherapy and radiotherapy, the prognosis for high-grade glioma (HGG) remains unsatisfactory. The majority of HGG patients experience disease recurrence. To date, no standard treatments have been established for recurrent HGG. Repeat surgery and chemotherapy demonstrate moderate efficacy. As recurrent lesions are usually located within the previously irradiated field, a second course of irradiation was once considered controversial, as it was considered to exhibit unsatisfactory efficacy and radiation-related toxicities. However, an increasing number of studies have indicated that re-irradiation may present an efficacious treatment for recurrent HGG. Re-irradiation may be delivered via conventionally fractionated stereotactic radiotherapy, hypofractionated stereotactic radiation therapy, stereotactic radiosurgery and brachytherapy techniques. In the present review, the current literature regarding re-irradiation treatment for recurrent HGG is summarized with regard to survival outcome and side effects. PMID:27703519

  6. Oral Rigosertib for Squamous Cell Carcinoma

    ClinicalTrials.gov

    2016-05-18

    Head and Neck Squamous Cell Carcinoma; Anal Squamous Cell Carcinoma; Lung Squamous Cell Carcinoma; Cervical Squamous Cell Carcinoma; Esophageal Squamous Cell Carcinoma; Skin Squamous Cell Carcinoma; Penile Squamous Cell Carcinoma

  7. Leaks in nuclear grade high efficiency aerosol filters

    SciTech Connect

    Scripsick, Ronald Clyde

    1994-07-01

    Nuclear grade high efficiency aerosol filters, also known as high efficiency particulate air (HEPA) filters, are commonly used in air cleaning systems for removal of hazardous aerosols. Performance of the filter units is important in assuring health and environmental protection. The filter units are constructed from pleated packs of fiberglass filter media sealed into rigid frames. Results of previous studies on such filter units indicate that their performance may not be completely predicted by ideal performance of the fibrous filter media. In this study, departure from ideal performance is linked to leaks existing in filter units and overall filter unit performance is derived from independent performance of the individual filter unit components. The performance of 14 nuclear grade HEPA filter units (size 1, 25 cfm) with plywood frames was evaluated with a test system that permitted independent determination of penetration as a function of particle size for the whole filter unit, the filter unit frame, and the filter media pack. Tests were performed using a polydisperse aerosol of di-2-ethylhexyl phthalate with a count median diameter of 0.2 {mu}m and geometric standard deviation of 1.6. Flow rate and differential pressure were controlled from 1% to 100% of design values. Particle counts were made upstream and downstream of the filter unit with an optical particle counter (OPC). The OPC provided count information in 28 size channels over the particle diameter range from 0.1 to 0.7 μm. Results provide evidence for a two component leak model of filler unit performance with: (1) external leaks through filter unit frames, and (2) internal leaks through defects in the media and through the seal between the media pack and frame. For the filter units evaluated, these leaks dominate overall filter unit performance over much of the flow rate and particle size ranges tested.

  8. High interstitial fluid pressure promotes tumor cell proliferation and invasion in oral squamous cell carcinoma.

    PubMed

    Yu, Tao; Liu, Kun; Wu, Yingying; Fan, Jinchuan; Chen, Jianchao; Li, Chao; Zhu, Guiquan; Wang, Zhaohui; Li, Longjiang

    2013-11-01

    It has been shown that interstitial fluid pressure (IFP) is elevated in many solid tumors. The elevated IFP in tumors is responsible, at least in part, for the poor blood supply, inadequate delivery of therapeutic agents to solid tumors and poor treatment response in patients. The present study was carried out to examine alterations in malignant phenotypes in oral squamous cell carcinoma cells subjected to conditions mimicking IFP and to identify the relevant molecular mechanisms. We investigated tumor cell proliferation and invasion using SCC-4 and SCC-9 cells subjected to an increased extracellular pressure of 0, 15 and 30 mmHg in vitro. The results revealed that the increased IFP resulted in a marked increase in cancer cell proliferation, survival and invasion in vitro and altered the expression of >1,800 genes involved in invasion and metastasis, the heat shock pathway, the p38 and JNK signaling pathway, apoptosis and the cell growth and differentiation signaling pathway. These results suggest the important potential clinical application of measuring IFP, which can be used as a generic marker of prognosis and response to therapy.

  9. Anal Squamous Intraepithelial Lesions and HPV Among Young Black Men Who Have Sex with Men

    PubMed Central

    Keglovitz, Kristin; Lancki, Nicola; Walsh, Tim; Schneider, John A.

    2017-01-01

    Abstract Purpose: Limited data are available on anal squamous intraepithelial lesions (ASILs) and anal human papillomavirus (HPV) infection in young, Black populations. The purpose of this study was to examine the prevalence of and relationships between ASILs and high-risk HPV infection in a young (<30 years of age), predominantly Black, men who have sex with men (MSM) population. Methods: Results of anal cytology and HPV DNA were gathered for 83 individuals. Results: Forty-two percent of individuals (35) had atypical squamous cells of undetermined significance and 33% (27) had low-grade squamous intraepithelial lesion by cytology. Only 9% tested positive for both high-risk HPV subtypes 16 and 18. Conclusion: Low rates of infection with both HPV types 16 and 18 may provide further evidence that we should continue to vaccinate young, Black MSM against HPV. PMID:27673362

  10. Discrimination against Students with Foreign Backgrounds: Evidence from Grading in Swedish Public High Schools

    ERIC Educational Resources Information Center

    Hinnerich, Bjorn Tyrefors; Höglin, Erik; Johannesson, Magnus

    2015-01-01

    We rigorously test for discrimination against students with foreign backgrounds in high school grading in Sweden. We analyse a random sample of national tests in the Swedish language graded both non-blindly by the student's own teacher and blindly without any identifying information. The increase in the test score due to non-blind grading is…

  11. K14-EGFP-miR-31 transgenic mice have high susceptibility to chemical-induced squamous cell tumorigenesis that is associating with Ku80 repression.

    PubMed

    Tseng, Ssu-Hsueh; Yang, Cheng-Chieh; Yu, En-Hao; Chang, Christine; Lee, Yong-Syu; Liu, Chung-Ji; Chang, Kuo-Wei; Lin, Shu-Chun

    2015-03-15

    Squamous cell carcinoma (SCC) occurring in the head and neck region and the esophagus causes tremendous cancer mortality around the world. miR-31 is among the most eminently upregulated MicroRNAs in SCC, when it occurs in the head and neck region and the esophagus. We established miR-31 transgenic mouse lines, in which miR-31 is under the control of the K14 promoter. 4-nitroquinoline 1-oxide (4NQO) is a mutagen that causes double strand breaks. The transgenic mice exhibited a higher potential for tumor induction than wild-type (Wt) mice of the tongue and esophagus after 4NQO treatment. After 4NQO treatment or irradiation, p-γH2AX expression in squamous epithelium of transgenic mice was increased more than in Wt mice. Exogenous expression of miR-31 was also found to be associated with the higher p-γH2AX expression induced by 4NQO in human oral SCC (OSCC) cell lines. The repair genes PARP1 and Ku80 were validated as new targets of miR-31 in human OSCC cell lines, and were found to be downregulated in the squamous epithelium of the tongue in transgenic mice. However, only the downregulation of Ku80 was essential for maintaining the high level of p-γH2AX induced by 4NQO in OSCC cells. Inverse expression profiles for miR-31 and Ku80 were noted in human OSCC tissue. Our study identifies the high sensitivity of K14-EGFP-miR-31 transgenic mice to chemical carcinogen-induced squamous cell tumorigenesis and shows that this seems to be associated with the downregulation of Ku80 and an impairment of repair activity in squamous cells, which are mediated by miR-31.

  12. Claspin as a biomarker of human papillomavirus-related high grade lesions of uterine cervix

    PubMed Central

    2012-01-01

    Background Claspin is a nuclear protein involved in DNA replication and damage response and is a key mediator for the S-phase checkpoint. Claspin expression is significantly high in several human solid tumors. Furthermore, high levels of claspin have been found in cervical cancer cell lines. Nevertheless, no data are available regarding claspin expression in cervical tissues. Methods In order to investigate whether claspin immunoreactivity is related to the lesion severity and High-Risk (HR) HPV infection, we analyzed claspin expression by immunohistochemistry in a series of cervical biopsies which represent the steps occurring during cervical carcinogenesis (normal tissues, Cervical Intraepithelial Neoplasias 1, 2 and 3, Squamous Cell Carcinomas). All patients also had a cervico-vaginal sample for HPV testing, collected immediately before the colposcopy-guided biopsy. The HR-HPV DNA detection was performed by the HR-HPV Hybrid Capture 2 test. HPV genotyping was performed using the Linear Array HPV Genotyping Test. Results Our results evidenced a constant and significant increase of the rate of claspin positivity from the normal tissues to carcinomas (pχ2trend < 0.0001). In fact, the normal tissues displayed either no or faint claspin immunoreactivity, whereas a moderate/high positivity was observed in 16% of the CIN1, 76% of the CIN2, 87.5% of the CIN3 and 93.3% of the cancers. Moreover, we found a statistically significant correlation between claspin expression and HR-HPV infection (pχ2 < 0.0001), irrespective of the genotype. Finally, we demonstrated the feasibility of claspin immunostaining in cervical cytology. Conclusions Our findings indicate that in vivo claspin expression is significantly related to HR-HPV infection and lesion grade both in histological and cytological samples. Therefore, the analysis of claspin expression could be clinically relevant in the diagnosis of HPV-related cervical lesions, in particular when applied to cervico

  13. Significance of a minor high-grade component in a low-grade noninvasive papillary urothelial carcinoma of bladder.

    PubMed

    Reis, Leonardo O; Taheri, Diana; Chaux, Alcides; Guner, Gunes; Mendoza Rodriguez, Maria A; Bivalacqua, Trinity J; Schoenberg, Mark P; Epstein, Jonathan I; Netto, George J

    2016-01-01

    To assess the clinicopathological features and prognostic significance of the presence of 5% or less high-grade component in otherwise low-grade noninvasive bladder urothelial carcinoma, referred to as mixed-grade (MG) urothelial carcinoma, we reviewed all archival cases with such diagnosis between 2005 and 2014. Clinicopathological and outcome parameters were compared to those in our previously reported low- and high-grade noninvasive bladder urothelial carcinoma cohorts (LGUC and HGUC, respectively). The study included 31 MG urothelial carcinomas. Mean patient age was 67.6 years, and mean follow-up was 39.7 months. Intravesical treatment was administered in 15 patients (48.4%). Recurrence occurred in 14 cases (45.2%): 10 as LGUC and 4 as HGUC; there was no stage progression. Mean time to progression was 9 months (5-17 months), and there was no death of disease. MG urothelial carcinoma stage progression and dead of disease rates were comparable to that of LGUC. MG urothelial carcinoma stage progression was significantly lower than that of HGUC, P = .002, using Pearson χ(2) test. MG urothelial carcinoma patients with no intravesical treatment had higher incidence rate of grade progression (25%) compared to LGUC patients (7.9%); however, the difference was not statistically significant. MG urothelial carcinoma had a prognosis closer to "pure" LGUC than "pure" HGUC. Untreated MG urothelial carcinoma may have a higher rate of grade progression than LGUC, although more data are needed before this issue can be definitively addressed. Until such data are available, it is reasonable to keep MG urothelial carcinoma as a distinct grade category with potential management implications.

  14. Participation and risk of high grade cytological lesions among immigrants and Italian-born women in an organized cervical cancer screening program in Central Italy.

    PubMed

    Visioli, Carmen Beatriz; Crocetti, Emanuele; Zappa, Marco; Iossa, Anna; Andersson, Karin Louise; Bulgaresi, Paolo; Alfieri, Antonia; Amunni, Gianni

    2015-06-01

    Few studies analyzed the risk for high-grade squamous intraepithelial lesions or worse (HSIL+) among immigrants and natives attending organized cervical cancer (CC) screening programs (SP). We evaluated participation and diagnosis of HSIL+ by country of birth with logistic models. Overall 540,779 invitation letters were delivered to target women of Florence SP in three screening rounds (years 2000-2002, 2003-2005, 2006-2008). The probability of attending screening was lower for immigrants than natives, but the difference decreased from 35% (1st round) to 20% (2nd-3rd round) for women born in high migration pressure (HMP) countries. The risk of HSIL+ was double than natives for HMP-born women from countries with high prevalence of human papillomavirus, even adjusting for age and previous history of Pap test. This is an important public health problem due to an increasing proportion over time of immigrant women with a lower attendance and greater risk for CC.

  15. A Highly Miniaturized Inertial Grade Gyroscope for Space Applications

    NASA Technical Reports Server (NTRS)

    Wiberg, D. V.; Challoner, A. D.; Shcheglov, K.; Hayworth, K.; Bae, S.; Yee, K.; Blaes, B.; DAgostino, S.; Stock, T.

    2001-01-01

    The evolution of inertial grade gyroscopes for space applications represents well over 50 years of technology development and an investment of hundreds of millions of dollars. The workhorse product which represents the current state-of-the art for commercially available high performance devices is the Litton-Hemishperical Resonator Gyro (HRG) Inertial Measurement Unit (IMU). This product has a performance figure of merit of 0.003 deg/hr bias drift, a volume of 567 cubic inches, weighs 19 pounds, draws about 30 watts and costs over $1 million each. Clearly devices of this magnitude are not conducive to the minimized mass, volume, power, and cost constraints of outer planet missions. An approach to breaking these potential barriers is the use of Microelectromechanical Systems (MEMS) based inertial devices. Although substantially reduced in size, mass power and cost, this approach has produced devices in the tactical performance range of greater than 1 deg/hour bias drift. This level of performance satisfies the preponderance of high market volume requirements such as automotive and tactical munitions but does not meet the limited market quantity requirements for the high precision space based market. Because of the very limited size of the space based market, there is little economic incentive for commercial fabricators of tactical grade devices to address the necessary performance improvements. The Jet Propulsion Laboratory (JPL) in conjunction with Boeing Space Systems (BSS) is addressing this void to satisfy our mutual requirements in this area. The project objective to is to achieve 0.01 deg/hr performance in an IMU which is less than 10 cubic inches in volume, weighs less than 0.5 pounds, draws less than 1 watt and is available in volume production for less than $2500. Reductions of this magnitude will be mission enabling capabilities for a variety of anticipated outer planet mission attributes such as autonomous control and docking, formation flying and robotic

  16. The significance of marked nuclear atypia in grade 1 cervical intraepithelial neoplasia.

    PubMed

    Fadare, Oluwole; Rodriguez, Rosemarie

    2009-10-01

    Approximately 10% to 15% of cases of grade 1 cervical intraepithelial neoplasia are found to have progressed to a high-grade squamous intraepithelial lesion or higher at follow-up, and there are presently no reliable morphological predictors of this subset. It has recently been reported that cases of grade 1 cervical intraepithelial neoplasia that display marked nuclear atypia (defined as cases with at least 5 epithelial cells with nuclear enlargement of at least 5 times the size of an intermediate cell, and/or multinucleation of at least 5 nuclei.) have a substantially higher rate of high-grade squamous intraepithelial lesion on short-term follow-up and may, therefore, require more aggressive initial management. We report herein our experience with a cohort of such cases. After a review of consecutive cervical biopsies, 352 cases with grade 1 cervical intraepithelial neoplasia were classified into group 1 (grade 1 cervical intraepithelial neoplasia with marked atypia, n = 31) and group 2 (grade 1 cervical intraepithelial neoplasia without marked atypia, n = 321). The average follow-up rates for groups 1 and 2 were 93.55% (29/31) and 90.65% (291/321), respectively. Average follow-up durations were 14.3 and 17.9 months, respectively. The follow-up high-grade squamous intraepithelial lesion rate of the cases with marked atypia was 10.34%, as compared with 11.68% for cases without marked atypia. The follow-up interpretive frequency (in cytologic samples) of "low-grade squamous intraepithelial lesion" was significantly higher in group 1(19/29 versus 114/291, P = .009). However, no significant differences were identified between groups 1 and 2 regarding the interpretive frequencies of either high-grade squamous intraepithelial lesion (3/29 versus 34/291, P = 1) or "negative for intraepithelial lesion or malignancy" (6/29 versus 56/291, P = .8) in follow-up cytologic samples. In subsets of both groups in which high-risk human papillomavirus testing was performed in the

  17. Squamous-cell Carcinoma of the Anus and Anal Canal: An Analysis of 55 Cases

    PubMed Central

    Gabriel, W. B.

    1941-01-01

    The analysis is of 55 cases admitted into St. Mark's Hospital from 1922 to 1940. The incidence was 3.35% of all cases of cancer of the rectum, anal canal and anus admitted during this period. Sex distribution—27 males and 28 females. The average age (61.7 years) is higher than that of columnar-cell carcinoma of the rectum (57.4 years). Histology.—The cases have been graded into three grades of malignancy—low grade, medium grade, and high grade. Low grade squamous carcinoma is twice as frequent in men as in women, and generally originates at the anal margin. Medium grade squamous carcinoma is equally distributed between men and women; it may arise at the anus or in the anal canal. High grade squamous carcinoma is much more common in the female sex and is almost entirely limited to the anal canal. Quadrant affected—about one-third of the anal margin growths and one-half of the anal canal growths were situated anteriorly. Differential diagnosis from simple papilloma, simple ulcer, chronic inflammation, tuberculous ulcer, tuberculide, primary chancre, amœbic ulcer, basal-cell carcinoma, columnar-cell carcinoma. Biopsy and grading essential before treatment is decided upon. The results of treatment in the three grades of malignancy are described. The best results were obtained in the early low-grade cases treated by interstitial radium needling. In the medium and high grades only three five-year survivals can be reported and these followed excision of the rectum. The management of the inguinal glands is discussed and the importance of a very close post-operative supervision emphasized. Squamous carcinoma of the anal canal may cause lymphatic metastases in the superior hæmorrhoidal glands; there have been four such cases in this series. Diathermy perineal excision is indicated in these cases. ImagesFig. 1Fig. 2Fig. 3Fig. 5Fig. 6aFig. 6bFig. 7Fig. 1Fig. 2Fig. 3Fig. 4 PMID:19992316

  18. HPV-related squamous neoplasia of the lower anogenital tract: an update and review of recent guidelines.

    PubMed

    Maniar, Kruti P; Nayar, Ritu

    2014-09-01

    Squamous cell carcinomas of the lower anogenital tract that are related to human papillomavirus (HPV) infection represent a significant disease burden worldwide. The diagnosis and management of their noninvasive precursors has been the subject of extensive study and debate over several decades, accompanied by an evolving understanding of HPV biology. Recent new consensus recommendations for the pathologic diagnosis of these precursor lesions were published in 2012, the result of the Lower Anogenital Squamous Terminology project cosponsored by the College of American Pathologists and the American Society for Colposcopy and Cervical Pathology. Most salient among the new guidelines are the recommendation to switch to a 2-tiered nomenclature (high-grade squamous intraepithelial lesion and low-grade squamous intraepithelial lesion) rather than the traditional 3-tiered "intraepithelial neoplasia" terminology, and the recommendation to expand use of the immunohistochemical marker p16 to distinguish between low-grade squamous intraepithelial lesion and high-grade squamous intraepithelial lesion/intraepithelial neoplasia 2. The goals of the project were to align diagnostic terminology with our knowledge of HPV biology, increase reproducibility, consolidate diverse systems of nomenclature, and ultimately better determine a patient's true cancer risk. The clinical guidelines for screening and management of cervical intraepithelial neoplasia have also been recently updated, most notably with a lengthening of screening intervals. In this review, we focus on the new guidelines put forth for pathologic diagnosis of HPV-related anogenital neoplasia, with discussion of the evidence behind them and their potential implications. We also provide an update on relevant biomarkers, clinical recommendations, and the newest developments relating to cervical neoplasia.

  19. Magnetic fabric and welding processes in high-grade tuffs

    NASA Astrophysics Data System (ADS)

    Pioli, L.; Ort, M.; Lanza, R.; Rosi, M.

    2003-04-01

    The welding fabric of tuffs is generally quantified through two main parameters: porosity and fiamme aspect ratio. However, these parameters are not useful for high-grade ignimbrites that display features indicating extensive rheomorphic flow, partial to complete obliteration of primary vitroclastic textures, and syn-depositional welding rather than load-related compaction. In this case, a 3D-microstructural characterization of the rock fabric is a fundamental proxy for the assessment of the dynamics and duration of welding processes. We have investigated the relations between magnetic fabric and welding textures in a rhyolitic, high-grade ignimbrite from the Sulcis volcanic District (SW Sardinia, Italy). The ignimbrite is characterized by dense welding throughout its preserved thickness and by regular lateral and vertical variations of welding, devitrification and vesiculation facies. Field and structural data indicate that syn-depositional welding and non-particulate (NP) flow were extensive and continuous during the emplacement of the ignimbrite. Paleomagnetic measurements of AMS, NRM, and AIRM of samples from the tuff indicate that the magnetic fabric is strain-sensitive and it is not significantly affected by post-depositional, static processes such as devitrification and vapor-phase alteration; in particular, magnetic susceptibility of the rock and the welding texture correlate well in terms of shape and orientation of the anisotropy ellipsoid. The direction of the K1 axis is indicative of the flow direction in the site of measurement. The anisotropy degree (P) increases with increasing welding and foliation (F) and lineation (L) are directly related to the strain facies. Onset of welding increased the degree of anisotropy and foliation; a non particulate, laminar flow stage further deformed the fabric stretching it along the flow direction and thus increasing L. The intensity of L is strictly related to the duration and the effect of simple shear (laminar

  20. High Vimentin Expression Associated with Lymph Node Metastasis and Predicated a Poor Prognosis in Oral Squamous Cell Carcinoma

    PubMed Central

    Liu, Shuli; Liu, Liu; Ye, Weimin; Ye, Dongxia; Wang, Tong; Guo, Wenzheng; Liao, Yueling; Xu, Dongliang; Song, Hongyong; Zhang, Ling; Zhu, Hanguang; Deng, Jiong; Zhang, Zhiyuan

    2016-01-01

    Oral squamous cell carcinoma (OSCC) is a common public health problem worldwide with poor prognosis, which is largely due to lymph node metastasis and recurrence. Identification of specific molecular markers of OSCC with lymph node metastasis would be very important for early and specific diagnosis. In this study, we screened for the potential prognosis markers via unbiased transcriptomic microarray analysis in paired two OSCC cell lines, a lymph node metastatic HN12 cell line and a low metastatic parental HN4 cell line. The results showed that vimentin, with 87-fold increase of expression, was on the top of all upregulated genes in metastatic HN12 cells compared to non-metastatic HN4 cells. Treatment of non-metastatic HN4 cells with TGF-β1 induced epithelial to mesenchymal transition (EMT), with increased vimentin expression as well as enhanced migration activity. Consistently, knockdown of vimentin via siRNA resulted in suppressed invasion and migration activities of HN12 cells, suggesting an essential role of vimentin in EMT-related functions of OSCC cells. Finally, immunohistochemical (IHC) staining analysis showed that high vimentin expression was strongly associated with high lymph node metastases (p < 0.05), and poor overall survival (p < 0.05) in OSCC patients. Thus, high vimentin expression is strongly associated with increased metastatic potential, and may serve as a prediction marker for poor prognosis in OSCC patients. PMID:27966589

  1. A novel graded bioactive high adhesion implant coating

    NASA Astrophysics Data System (ADS)

    Brohede, Ulrika; Zhao, Shuxi; Lindberg, Fredrik; Mihranyan, Albert; Forsgren, Johan; Strømme, Maria; Engqvist, Håkan

    2009-06-01

    One method to increase the clinical success rate of metal implants is to increase their bone bonding properties, i.e. to develop a bone bioactive surface leading to reduced risks of interfacial problems. Much research has been devoted to modifying the surface of metals to make them become bioactive. Many of the proposed methods include depositing a coating on the implant. However, there is a risk of coating failure due to low substrate adhesion. This paper describes a method to obtain bioactivity combined with a high coating adhesion via a gradient structure of the coating. Gradient coatings were deposited on Ti (grade 5) using reactive magnetron sputtering with increasing oxygen content. To increase the grain size in the coating, all coatings were post annealed at 385 °C. The obtained coating exhibited a gradual transition over 70 nm from crystalline titanium oxide (anatase) at the surface to metallic Ti in the substrate, as shown using cross-section transmission electron microscopy and X-ray photoelectron spectroscopy depth profiling. Using scratch testing, it could be shown that the adhesion to the substrate was well above 1 GPa. The bioactivity of the coating was verified in vitro by the spontaneous formation of hydroxylapatite upon storage in phosphate buffer solution at 37 °C for one week. The described process can be applied to implants irrespective of bulk metal in the base and should introduce the possibility to create safer permanent implants like reconstructive devices, dental, or spinal implants.

  2. Concurrent thermochemoradiotherapy for brain high-grade glioma

    NASA Astrophysics Data System (ADS)

    Ryabova, A. I.; Novikov, V. A.; Choinzonov, E. L.; Gribova, O. V.; Startseva, Zh. A.; Bober, E. E.; Frolova, I. G.; Baranova, A. V.

    2016-08-01

    Despite the achievements in the current strategies for treatment, the prognosis in malignant glioma patients remains unsatisfactory. Hyperthermia is currently considered to be the most effective and universal modifier of radiotherapy and chemotherapy. Preliminary treatment outcomes for 28 patients with newly diagnosed (23) and recurrent (5) high-grade gliomas were presented. All the patients received multimodality treatment including surgery, thermoche-moradiotherapy followed by 4 cycles of adjuvant chemotherapy. All the patients endured thermochemoradiotherapy well. A complication, limited skin burn (II stage), was diagnosed in two cases and treated conservatively without treatment interruption. A month after thermochemoradiotherapy the results were as follows: complete regression was achieved in 4 cases, partial regression in 4 cases, stable disease in 14 cases and disease progression in 6 cases (one of them is pseudo-progression). After completing the adjuvant chemotherapy 2 more patients demonstrated complete response and 1 patient had disease progression. Introduction of local hyperthermia in multimodal therapy of malignant glioma does not impair the combined modality treatment tolerability of patients with malignant gliomas. A small number of studied patients and short follow-up time do not allow making reliable conclusions about the impact of local hyperthermia on the treatment outcomes; however, there is a tendency towards the increase in disease-free survival in the patients with newly diagnosed malignant gliomas.

  3. High-Performance Slab-on-Grade Foundation Insulation Retrofits

    SciTech Connect

    Goldberg, Louise F.; Mosiman, Garrett E.

    2015-09-01

    A more accurate assessment of slab-on-grade foundation insulation energy savings than traditionally possible is now feasible. This has been enabled by advances in whole building energy simulation with 3-dimensional foundation modelling integration at each time step together with an experimental measurement of the site energy savings of SOG foundation insulation. Ten SOG insulation strategies were evaluated on a test building to identify an optimum retrofit insulation strategy in a zone 6 climate (Minneapolis, MN). The optimum insulation strategy in terms of energy savings and cost effectiveness consisted of two components: (a) R-20 XPS insulation above grade, and, (b) R-20 insulation at grade (comprising an outer layer of R-10 insulation and an interior layer of R-12 poured polyurethane insulation) tapering to R-10 XPS insulation at half the below-grade wall height (the lower half of the stem wall was uninsulated).

  4. Diffuse reflectance spectroscopy can differentiate high grade and low grade prostatic carcinoma.

    PubMed

    Werahera, Priya N; Jasion, Edward A; David Crawford, E; Lucia, M Scott; van Bokhoven, Adrie; Sullivan, Holly T; Kim, Fernando J; Maroni, Paul D; David Port, J; Daily, John W; Rosa, Francisco G La; Werahera, Priya N; Jasion, Edward A; Crawford, E David; Lucia, M Scott; van Bokhoven, Adrie; Sullivan, Holly T; Kim, Fernando J; Maroni, Paul D; Port, J David; Daily, John W; La Rosa, Francisco G; Daily, John W; Van Bokhoven, Adrie; Crawford, E David; Port, J David; Werahera, Priya N; Lucia, M Scott; Sullivan, Holly T; Maroni, Paul D; Jasion, Edward A; La Rosa, Francisco G; Kim, Fernando J

    2016-08-01

    Prostate tumors are graded by the revised Gleason Score (GS) which is the sum of the two predominant Gleason grades present ranging from 6-10. GS 6 cancer exclusively with Gleason grade 3 is designated as low grade (LG) and correlates with better clinical prognosis for patients. GS >7 cancer with at least one of the Gleason grades 4 and 5 is designated as HG indicate worse prognosis for patients. Current transrectal ultrasound guided prostate biopsies often fail to correctly diagnose HG prostate cancer due to sampling errors. Diffuse reflectance spectra (DRS) of biological tissue depend on tissue morphology and architecture. Thus, DRS could potentially differentiate between HG and LG prostatic carcinoma. A 15-gauge optical biopsy needle was prototyped to take prostate biopsies after measuring DRS with a laboratory fluorometer. This needle has an optical sensor that utilizes 8×100 μm optical fibers for tissue excitation and a single 200 μm central optical fiber to measure DRS. Tissue biopsy cores were obtained from 20 surgically excised prostates using this needle after measuring DRS at 5 nm intervals between 500-700 nm wavelengths. Tissue within a measurement window was histopathologically classified as either benign, LG, or HG and correlated with DRS. Partial least square analysis of DRS identified principal components (PC) as potential classifiers. Statistically significant PCs (p<;0.05) were tested for their ability to classify biopsy tissue using support vector machine and leave-one-out cross validation method. There were 29 HG and 49 LG cancers among 187 biopsy cores included in the study. Study results show 76% sensitivity, 80% specificity, 93% negative predictive value, and 50% positive predictive value for HG versus benign, and 76%, 73%, 84%, and 63%, for HG versus LG prostate tissue classification. DRS failed to diagnose 7/29 (24%) HG cancers. This study demonstrated that an optical biopsy needle guided by DRS has sufficient accuracy to differentiate HG

  5. Fibronectin Modulates Cell Adhesion and Signaling to Promote Single Cell Migration of Highly Invasive Oral Squamous Cell Carcinoma

    PubMed Central

    Ramos, Grasieli de Oliveira; Bernardi, Lisiane; Lauxen, Isabel; Sant’Ana Filho, Manoel; Horwitz, Alan Rick; Lamers, Marcelo Lazzaron

    2016-01-01

    Cell migration is regulated by adhesion to the extracellular matrix (ECM) through integrins and activation of small RhoGTPases, such as RhoA and Rac1, resulting in changes to actomyosin organization. During invasion, epithelial-derived tumor cells switch from laminin-enriched basal membrane to collagen and fibronectin-enriched connective tissue. How this switch affects the tumor migration is still unclear. We tested the hypothesis that ECM dictates the invasiveness of Oral Squamous Cell Carcinoma (OSCC). We analyzed the migratory properties of two OSCC lines, a low invasive cell line with high e-cadherin levels (Linv/HE-cad) or a highly invasive cell line with low e-cadherin levels (Hinv/LE-cad), plated on different ECM components. Compared to laminin, fibronectin induced non-directional collective migration and decreased RhoA activity in Linv/HE-cad OSCC. For Hinv/LE-cad OSCC, fibronectin increased Rac1 activity and induced smaller adhesions, resulting in a fast single cell migration in both 2D and 3D environments. Consistent with these observations, human OSCC biopsies exhibited similar changes in cell-ECM adhesion distribution at the invasive front of the tumor, where cells encounter fibronectin. Our results indicate that ECM composition might induce a switch from collective to single cell migration according to tumor invasiveness due to changes in cell-ECM adhesion and the resulting signaling pathways that alter actomyosin organization. PMID:26978651

  6. New Perspectives on the Correlation of SAT Scores, High School Grades, and Socioeconomic Factors

    ERIC Educational Resources Information Center

    Zwick, Rebecca; Greif Green, Jennifer

    2007-01-01

    In studies of the SAT, correlations of SAT scores, high school grades, and socioeconomic factors (SES) are usually obtained using a university as the unit of analysis. This approach obscures an important structural aspect of the data: The high school grades received by a given institution come from a large number of high schools, all of which have…

  7. DAP1 high expression increases risk of lymph node metastases in squamous cell carcinoma of the oral cavity.

    PubMed

    Santos, M; Maia, L L; Silva, C V M; Peterle, G T; Mercante, A M C; Nunes, F D; Carvalho, M B; Tajara, E H; Louro, I D; Silva-Conforti, A M A

    2015-09-08

    Death-associated protein 1 (DAP1) is a member of the DAP family. Its expression is associated with cell growth and normal death of the neoplastic cells, regulated by the mammalian target of the rapamycin protein. Activated DAP1 negatively regulates autophagy, which has been associated with the development and progression of several diseases, such as cancer, and with prognosis and survival of diverse tumor types. Therefore, in this study we analyzed DAP1 expression in 54 oral squamous cell carcinoma tumor samples and in 20 non-tumoral margins by immunohistochemistry. The results showed that DAP1 is more frequently expressed in tumor tissues compared with marginal non-tumoral cells. Additionally, high DAP1 expression is associated with a 4-fold increase in the risk of lymph node metastases. Our results suggest that the DAP1 protein can be used as a potential marker of lymph node metastases predisposition, helping define the best therapy for each patient to minimize risk of developing metastases.

  8. Opium, tobacco, and alcohol use in relation to oesophageal squamous cell carcinoma in a high-risk area of Iran.

    PubMed

    Nasrollahzadeh, D; Kamangar, F; Aghcheli, K; Sotoudeh, M; Islami, F; Abnet, C C; Shakeri, R; Pourshams, A; Marjani, H A; Nouraie, M; Khatibian, M; Semnani, S; Ye, W; Boffetta, P; Dawsey, S M; Malekzadeh, R

    2008-06-03

    The very high incidence of oesophageal squamous cell carcinoma (ESCC) in Golestan Province in northeastern Iran was suggested by studies in the 1970s as partly due to opium use, which is not uncommon in this area, but based on limited numbers. From December 2003 to June 2007, we administered a validated structured questionnaire to 300 ESCC cases and 571 controls, matched on neighbourhood of residence, age (+/-2 years), and sex. We used conditional logistic regression models to calculate odds ratios (ORs) and 95% confidence intervals (95% CIs) adjusted for potential confounders. Compared with those who used neither tobacco nor opium, risk of ESCC was increased in those who used tobacco only (OR, 95% CI: 1.70, 1.05-2.73), in those who used opium only (2.12, 1.21-3.74), and in those who used both tobacco and opium (2.35, 1.50-3.67). All forms of tobacco use (cigarettes, hookah, and nass) were associated with higher ESCC risk. Similarly, use of both crude opium and other forms of opium were associated with higher risk. Alcohol consumption was seen in only 2% of the cases and 2% of the controls, and was not associated with ESCC risk.

  9. Novel Oncogenic PDGFRA Mutations in Pediatric High-Grade Gliomas

    PubMed Central

    Paugh, Barbara S.; Zhu, Xiaoyan; Qu, Chunxu; Endersby, Raelene; Diaz, Alexander K.; Zhang, Junyuan; Bax, Dorine A.; Carvalho, Diana; Reis, Rui M.; Onar-Thomas, Arzu; Broniscer, Alberto; Wetmore, Cynthia; Zhang, Jinghui; Jones, Chris; Ellison, David W.; Baker, Suzanne J.

    2013-01-01

    The outcome for children with high-grade gliomas (HGG) remains dismal, with a two-year survival rate of only 10–30%. Diffuse intrinsic pontine glioma (DIPG) comprise a subset of HGG that arise in brainstem almost exclusively in children. Genome-wide analyses of copy number imbalances previously showed that platelet derived growth factor receptor alpha (PDGFRA) is the most frequent target of focal amplification in pediatric HGGs, including DIPGs. To determine whether PDGFRA is also targeted by more subtle mutations missed by copy number analysis, we sequenced all PDGFRA coding exons from a cohort of pediatric HGGs. Somatic activating mutations were identified in 14.4% (13/90) of non-brainstem pediatric HGGs and 4.7% (2/43) of DIPGs, including missense mutations and in-frame deletions and insertions not previously described. 40% of tumors with mutation showed concurrent amplification, while 60% carried heterozygous mutations. Six different mutations impacting different domains all resulted in ligand-independent receptor activation that was blocked by small molecule inhibitors of PDGFR. Expression of mutants in p53-null primary mouse astrocytes conferred a proliferative advantage in vitro, and generated HGGs in vivo with complete penetrance when implanted into brain. The gene expression signatures of these murine HGGs reflected the spectrum of human diffuse HGGs. PDGFRA intragenic deletion of exons 8 and 9 were previously shown in adult HGG, but were not detected in 83 non-brainstem pediatric HGG and 57 DIPGs. Thus, a distinct spectrum of mutations confers constitutive receptor activation and oncogenic activity to PDGFRα in childhood HGG. PMID:23970477

  10. Low-Cost High Resolution Microendoscopy for the Detection of Esophageal Squamous Cell Neoplasia: An International Trial

    PubMed Central

    Polydorides, Alexandros D.; Dawsey, Sanford M.; Cui, Junsheng; Xue, Liyan; Zhang, Fan; Quang, Timothy; Pierce, Mark C.; Shin, Dongsuk; Schwarz, Richard A.; Bhutani, Manoop S.; Lee, Michelle; Parikh, Neil; Hur, Chin; Xu, Weiran; Moshier, Erin; Godbold, James; Mitcham, Josephine; Hudson, Courtney

    2015-01-01

    Background and Aims Esophageal squamous cell neoplasia (ESCN) has high mortality due to late detection. In high risk regions such as China, screening is performed by Lugol's chromoendoscopy (LCE). LCE has low specificity resulting in unnecessary tissue biopsy with subsequent increase in procedure cost and risk. The purpose of this study is to evaluate the accuracy of a novel, low-cost high resolution microendoscope (HRME) as an adjunct to LCE. Methods In this prospective trial, 147 consecutive high-risk patients were enrolled from two US and two Chinese tertiary centers. Three expert and four novice endoscopists performed white light endoscopy followed by LCE and HRME. All optical images were compared to gold standard of histopathology. Results Using a per biopsy analysis, sensitivity of LCE vs. LCE + HRME was 96% vs. 91% (p=0.0832), specificity 48% vs. 88% (p<0.001), PPV 22% vs 45% (p<0.0001), NPV 98% vs. 98% (p=0.3551), and overall accuracy 57% vs. 90% (p<0.001). Using a per patient analysis, sensitivity of LCE vs. LCE + HRME was 100% vs. 95% (p=0.16), specificity 29% vs. 79% (p<0.001), PPV 32% vs. 60%, 100% vs. 98%, and accuracy 47% vs. 83% (p<0.001). With use of HRME, 136 biopsies (60%; 95% CI: 53-66%) could have been spared, and 55 patients (48%; 95% CI: 38-57%) spared any biopsy. Conclusion In this trial, HRME improved the accuracy of LCE for ESCN screening and surveillance. HRME may be a cost-effective “optical” biopsy adjunct to LCE, potentially reducing unnecessary biopsy and facilitating real-time decision-making in globally underserved regions; ClinicalTrials.gov, NCT 01384708. PMID:25980753

  11. Examining Teacher-Assigned Math Grades as Predictors for High-Stakes Testing

    ERIC Educational Resources Information Center

    Denson, Bettina Coley

    2013-01-01

    This study sought to determine whether a relationship existed between teacher-assigned classroom grades and high-stakes test scores. The study examined teacher-assigned math grades in correlation to the student scores on the Florida Comprehensive Assessment test (FCAT) in a selected Florida high school. It also sought to determine the relationship…

  12. Bilateral Basaloid Squamous Cell Carcinoma of the Parotid Gland: A Case Report and Review of the Literature

    PubMed Central

    Rivero, Alexander; Tang, Christopher G; Rasgon, Barry M

    2017-01-01

    Introduction: We describe the first known case of bilateral basaloid squamous cell carcinoma of the parotid gland, and we review existing literature. Case Presentation: A previously healthy, 70-year-old white man presented with a 2-cm enlarging mass in the tail of the right parotid gland. Magnetic resonance imaging and computed tomography showed ipsilateral pathologic adenopathy. Results of fine-needle aspiration revealed a high-grade malignancy with squamous features. The patient underwent a right total parotidectomy and modified radical neck dissection. Final pathologic findings revealed a basaloid squamous cell carcinoma. Four years after the initial resection, the patient presented with an enlarging left parotid mass. Findings of fine-needle aspiration and imaging were similar to those 4 years earlier. The patient received a left total parotidectomy and modified radical neck dissection. Postoperative radiation therapy was performed after each surgical intervention. He remains disease free at 4-year follow-up after the second mass was resected. Discussion: Squamous cell carcinoma with basaloid features is a rare and aggressive type of squamous cell carcinoma. To our knowledge, this is the first case report of bilateral parotid basaloid squamous cell carcinoma. PMID:28333602

  13. Changes in gene expression of neo-squamous mucosa after endoscopic treatment for dysplastic Barrett’s esophagus and intramucosal adenocarcinoma

    PubMed Central

    Levert-Mignon, Angelique; Bourke, Michael J; Lord, Sarah J; Taylor, Andrew C; Wettstein, Antony R; Edwards, Melanie; Botelho, Natalia K; Sonson, Rebecca; Jayasekera, Chatura; Fisher, Oliver M; Thomas, Melissa L; Macrae, Finlay; Hussey, Damian J; Watson, David I

    2016-01-01

    Background Endoscopic therapy, including by radiofrequency ablation (RFA) or endoscopic mucosal resection (EMR), is first line treatment for Barrett’s esophagus (BE) with high-grade dysplasia (HGD) or intramucosal cancer (IMC) and may be appropriate for some patients with low-grade dysplasia (LGD). Objective The purpose of this study was to investigate the molecular effects of endotherapy. Methods mRNA expression of 16 genes significantly associated with different BE stages was measured in paired pre-treatment BE tissues and post-treatment neo-squamous biopsies from 36 patients treated by RFA (19 patients, 3 IMC, 4 HGD, 12 LGD) or EMR (17 patients, 4 IMC, 13 HGD). EMR was performed prior to RFA in eight patients. Normal squamous esophageal tissues were from 20 control individuals. Results Endoscopic therapy resulted in significant change towards the normal squamous expression profile for all genes. The neo-squamous expression profile was significantly different to the normal control profile for 11 of 16 genes. Conclusion Endotherapy results in marked changes in mRNA expression, with replacement of the disordered BE dysplasia or IMC profile with a more “normal” profile. The neo-squamous mucosa was significantly different to the normal control squamous mucosa for most genes. The significance of this finding is uncertain but it may support continued endoscopic surveillance after successful endotherapy.

  14. Occupational Exploration at Ontario Junior High School: 8th Grade.

    ERIC Educational Resources Information Center

    Bates, Gene; And Others

    The document contains 47 activities for Grade 8. The contents include the following areas: questionnaires; work vocabularies; employment seeking procedures--employment ads, application forms, resumes, job interviews, and resume preparation advice; a 24-page unit presenting occupational information in relation to career choice and job application…

  15. Occupational Exploration at Ontario Junior High School: 9th Grade.

    ERIC Educational Resources Information Center

    Bates, Gene; And Others

    The document contains 56 activities for Grade 9. The contents include the following areas: questions about the future; job seeking activities and guidelines; career games; a personal interest check list; unit guides for courses in World of Work (55 pages), and Career Educational Planning (40 pages) which include objectives, activities, evaluation,…

  16. Junior High School English 1 and 2, Grade 9.

    ERIC Educational Resources Information Center

    Burbank Unified School District, CA.

    Designed for ninth grade English teachers, this curriculum guide contains (1) a course description; (2) educational goals; (3) teaching perspective; (4) a set of general principles; (5) a list of questions that teachers ask, along with answers; (6) an overview; and (7) directions for writing as a process, higher level thinking skills, how to…

  17. Histopathologic risk factors in oral and oropharyngeal squamous cell carcinoma variants: An update with special reference to HPV-related carcinomas

    PubMed Central

    2014-01-01

    Accurate identification of the microscopic risk factors of oral and oropharyngeal (OP) squamous cell carcinomas (SCC) and their morphologic variants is of at most importance, as these generally determine treatment modalities, prognosis and overall patient outcome. The great majority of oral and oropharyngeal squamous cell carcinomas are microscopically described as kerartinizing squamous cell carcinoma (KSCC). They bear certain resemblance to keratinizing stratified squamous epithelium. Tobacco habits and excessive consumption of alcoholic beverages have been considered to be the main etiologic agents in these carcinomas. The tumors occurred in older patients more commonly affected the oral tongue and floor of the mouth with well established morphologic risk factors including tumor grade, pattern of invasion and perineural involvement. Within the last 30 years however, the advent and expanding prevalence of high risk human papillomavirus (HPV) as an important etiologic agent for head and neck squamous cell carcinoma, particularly in the OP, has resulted in a significant change in the established morphologic criteria for risk assessment. The majority of HPV relate carcinomas of the OP are nonkeratinizing squamous cell carcinoma (NKSCC). These tumors are found to be more responsive to treatment with a favorable patient outcome and good prognosis. Consequently, alterations in treatment protocols aimed at de-escalation are currently being evaluated. More recently, other morphologic variants that are HPV positive are reported with increasing frequency in the OP and other head and neck sites. As a result, several clinical and pathologic questions have emerged. Importantly, whether the virus is biologically active in these tumors and involved in their pathogenesis, and second, what are the clinical implications with regard to patient management and outcome in the HPV-related variants. Examples of HPV-related squamous cell carcinoma variants that will be addressed here are

  18. High Performance Slab-on-Grade Foundation Insulation Retrofits

    SciTech Connect

    Goldberg, Louise F.; Mosiman, Garrett E.

    2015-09-01

    ?A more accurate assessment of SOG foundation insulation energy savings than traditionally possible is now feasible. This has been enabled by advances in whole building energy simulation with 3-dimensional foundation modelling integration at each time step together with an experimental measurement of the site energy savings of SOG foundation insulation. Ten SOG insulation strategies were evaluated on a test building to identify an optimum retrofit insulation strategy in a zone 6 climate (Minneapolis, MN). The optimum insulation strategy in terms of energy savings and cost effectiveness consisted of two components: (a) R-20 XPS insulation above grade, and, (b) R-20 insulation at grade (comprising an outer layer of R-10 insulation and an interior layer of R-12 poured polyurethane insulation) tapering to R-10 XPS insulation at half the below-grade wall height (the lower half of the stem wall was uninsulated). The optimum insulation strategy was applied to single and multi-family residential buildings in climate zone 4 - 7. The highest site energy savings of 5% was realized for a single family home in Duluth, MN, and the lowest savings of 1.4 % for a 4-unit townhouse in Richmond, VA. SOG foundation insulation retrofit simple paybacks ranged from 18 to 47 years. There are other benefits of SOG foundation insulation resulting from the increase in the slab surface temperatures. These include increased occupant thermal comfort, and a decrease in slab surface condensation particularly around the slab perimeter.

  19. Secondhand Smoking and the Risk of Esophageal Squamous Cell Carcinoma in a High Incidence Region, Kashmir, India

    PubMed Central

    Rafiq, Rumaisa; Shah, Idrees Ayoub; Bhat, Gulzar Ahmad; Lone, Mohd Maqbool; Islami, Farhad; Boffetta, Paolo; Dar, Nazir Ahmad

    2016-01-01

    Abstract Studies have associated secondhand smoking (SHS) with cancers of the lung, larynx, and pharynx. Only a few studies have examined the association between SHS and esophageal squamous cell carcinoma (ESCC) and the findings are inconclusive. We aimed to investigate the association between SHS and risk of ESCC in a case-control study in Kashmir, where the incidence of ESCC is high. We recruited 703 histopathologically confirmed ESCC cases and 1664 hospital-based controls individually matched to the cases for age, sex, and district of residence. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated using conditional logistic regression models. Among never-tobacco users, the ORs for the association between SHS and ESCC risk were above unity with ever exposure to SHS (OR = 1.32; 95% CI, 0.43–4.02) and exposure to SHS for >14 h/wk (median value) (OR = 2.69; 95% CI, 0.75–20.65). In the analysis of data from all participants, the OR (95% CI) for the association between SHS and ESCC was (OR = 1.02; 95% CI, 0.53–1.93) for SHS ≤14 h/wk and (OR = 1.91; 95% CI, 0.75–4.89) for SHS >14 h/wk in the models adjusted for tobacco use and several other potential confounding factors. We found an indication of increased risk of ESCC associated with exposure to SHS. Studies with larger numbers of SHS-exposed never tobacco users are required to further examine this association. PMID:26735535

  20. High expression of Naa10p associates with lymph node metastasis and predicts favorable prognosis of oral squamous cell carcinoma.

    PubMed

    Zeng, Yan; Zheng, Jun; Zhao, Juan; Jia, Pei-Rong; Yang, Yang; Yang, Guo-Jun; Ma, Jing-Feng; Gu, Yong-Qing; Xu, Jiang

    2016-05-01

    N-a-Acetyltransferase 10 protein (Naa10p) is a potential prognostic biomarker and a modulator of several types of cancer. Despite the efforts to elucidate the relationship between Naa10p expression and clinical prognosis, little is known about its expression and role in human oral squamous cell carcinoma (OSCC). In this study, we firstly detected the mRNA and protein levels of Naa10p in 10 paired OSCC tissue samples and found Naa10p was frequently overexpressed in the tumor tissues of patients with OSCC. Further detection by immunohistochemistry was used to examine Naa10p expression in 124 OSCC tumor specimens by tissue microarray (TMA), and a relative high level of Naa10p protein expression was found in 98 out of 124 cases (79.03 %). Additional analyses illustrated that Naa10p expression inversely correlated with clinical stage (p = 0.047), degree of lymph node status (p = 0.020), differentiation (p = 0.022), and recurrence (p = 0.016) of patients with OSCC. The survival analysis showed that patients with Naa10p-positive expression had a better prognosis for disease-free survival (DFS) or overall survival (OS) than those with Naa10p-negative expression (p = 0.003 for both). Furthermore, we assessed the effect of Naa10p knockdown on motility of oral cancer cells in vitro, and the results showed that Naa10p inhibit cell wound healing, migration, and invasion. In summary, our study illustrated that the expression of Naa10p had a potential value for predicting the progression of OSCC and prognosis of OSCC patients.

  1. Double Jeopardy: How Third-Grade Reading Skills and Poverty Influence High School Graduation

    ERIC Educational Resources Information Center

    Hernandez, Donald J.

    2011-01-01

    Educators and researchers have long recognized the importance of mastering reading by the end of third grade. Students who fail to reach this critical milestone often falter in the later grades and drop out before earning a high school diploma. This study relies on a unique national database of 3,975 students born between 1979 and 1989. The…

  2. High School Grade Inflation from 1991 to 2003. Research Report Series 2004-04

    ERIC Educational Resources Information Center

    Woodruff, David J.; Ziomek, Robert L.

    2004-01-01

    This report presents the results of a study investigating inflation in high school grade point average (HSGPA). Inflation was measured by comparing HSGPA to ACT Assessment (ACT) scores over the years 1991 to 2003. The results indicate the presence of grade inflation over the 13 years. That is, HSGPAs increased without a concomitant increase in…

  3. A Comparison of High School Student Interests across Three Grade and Ability Levels.

    ERIC Educational Resources Information Center

    Gill, Newell T.

    1980-01-01

    Students (Grades 9-11) in two Florida metropolitan high schools rated their interest in 28 topics, such as travel, popular music, religion, the opposite sex, war, and politics. Interests were analyzed by sex, grade, and ability track in English (Honors, Average, Basic). Findings, especially those on romantic interests, are discussed. (SJL)

  4. Perris Valley Junior High School's Language Processing for Grades 7-10.

    ERIC Educational Resources Information Center

    Zemmels, Elizabeth

    An ongoing, interdisciplinary reading program for students in grades 7-10 in Perris Union High School District (California) is described. Initiated in 1979 as a result of low reading scores, the program divides all incoming seventh grade students into homogeneous groups. In the first 6 weeks of school these new groups meet once a day for 50…

  5. Improved Middle Grades Schools for Improved High School Readiness: Ten Best Practices in the Middle Grades

    ERIC Educational Resources Information Center

    Bottoms, Gene; Timberlake, Allison

    2012-01-01

    In 2009, the Southern Regional Education Board (SREB) Committee to Improve High School Graduation Rates and Achievement, led by then-Governor Sonny Perdue of Georgia, released a report of 10 key recommendations for ensuring more students graduate from high school, and they graduate ready for college and careers. Among these 10 recommendations was…

  6. Feasibility of Transoral Robotic-Assisted High Resolution Microendoscopic Imaging of Oropharyngeal Squamous Cell Carcinoma

    PubMed Central

    Patsias, Alexis; Giraldez-Rodriguez, Laureano A.; Polydorides, Alexandros D.; Richards-Kortum, Rebecca; Anandasabapathy, Sharmila; Quang, Timothy; Sikora, Andrew G.; Miles, Brett A.

    2015-01-01

    Background Transoral robotic-assisted oncologic surgery of the head and neck offers promising functional results. Nonetheless, the efficacy of oncologic surgery remains critically dependent on obtaining negative margins. We aimed to integrate a miniaturized high resolution fiberoptic microendoscope (HRME), which provides real time histological assessment, with the da Vinci robotic system (Intuitive Surgical Inc., Sunnyvale, CA). Methods Three patients undergoing transoral robotic surgery were prospectively enrolled. Optical imaging of the oropharynx was performed intraoperatively with the robotic-assisted HRME. Results All patients underwent the procedure successfully with no complications. The HRME was successfully integrated with the Da Vinci Robotic system. Several sites of the oropharynx and associated malignancy were imaged, which correlated with the standard histopathological analysis. Conclusions Transoral robotic-assisted high resolution microendoscopic imaging of the oropharynx is a safe and technically feasible approach, providing a real time histological assessment and may serve as a valuable aid in oncologic surgery. PMID:25327825

  7. Serous versus high-grade endometrioid endometrial carcinoma: immunohistochemistry of RFP is not useful for differentiation.

    PubMed

    Ussakli, Cigdem; Usubutun, Alp; Dincer, Nazmiye; Dolgun, Anil; Bülbül, Diilek; Isikdogan, Zuhal; Haberal, Nihan; Ozen, Ozlem; Tezel, Gaye Guler

    2016-01-01

    We evaluated the immunohistochemical expression of ret finger protein (RFP) along with conventional immunohistochemical markers in endometrioid and serous carcinomas of the endometrium. A total of 124 endometrial carcinoma cases (24 grade 1 endometrioid, 60 grade 3 endometrioid, 40 serous) were retrieved from pathology archives. Tissue microarrays were constructed. The expression of RFP, WT1, ER, PR, p53 and p16 was examined immunohistochemically. Sensitivity, specificity, area under the receiver operating characteristic (ROC) curve,  statistic for interobserver reproducibility, Kruskal-Wallis test, Mann-Whitney U test and Fisher's exact tests were performed for statistical analyses. The mean RFP score was 1.54 in grade 1 endometrioid, 4.31 in grade 3 endometrioid, and 6.31 in serous carcinomas (p < 0.001). Overall, RFP scores were higher both in serous and grade 3 endometrioid carcinoma (p > 0.05), and significantly lower in grade 1 endometrioid carcinoma (p < 0.05). p16 and p53 staining patterns were able to differentiate between high-grade endometrioid and serous carcinoma (p < 0.001). ER, PR and WT-1 did not reach statistical significance for subtyping. The  values of the general agreement between the observers were 0.737 and 0.727 for endometrioid and serous carcinomas respectively (p < 0.001). Diffuse p53 and p16 staining provides the most sensitive and specific immunomarkers for differentiating high-grade endometrioid and serous carcinomas.

  8. Armodafinil in Reducing Cancer-Related Fatigue in Patients With High Grade Glioma | Division of Cancer Prevention

    Cancer.gov

    This randomized phase III trial studies armodafinil to see how well it works in reducing cancer-related fatigue in patients with high grade glioma. Armodafinil may help relieve fatigue in patients with high grade glioma. |

  9. High relative density of lymphatic vessels predicts poor survival in tongue squamous cell carcinoma.

    PubMed

    Seppälä, Miia; Pohjola, Konsta; Laranne, Jussi; Rautiainen, Markus; Huhtala, Heini; Renkonen, Risto; Lemström, Karl; Paavonen, Timo; Toppila-Salmi, Sanna

    2016-12-01

    Tongue cancer has a poor prognosis due to its early metastasis via lymphatic vessels. The present study aimed at evaluating lymphatic vessel density, relative density of lymphatic vessel, and diameter of lymphatic vessels and its predictive role in tongue cancer. Paraffin-embedded tongue and lymph node specimens (n = 113) were stained immunohistochemically with a polyclonal antibody von Willebrand factor, recognizing blood and lymphatic endothelium and with a monoclonal antibody podoplanin, recognizing lymphatic endothelium. The relative density of lymphatic vessels was counted by dividing the mean number of lymphatic vessels per microscopic field (podoplanin) by the mean number of all vessels (vWf) per microscopic field. The high relative density of lymphatic vessels (≥80 %) was associated with poor prognosis in tongue cancer. The relative density of lymphatic vessels predicted poor prognosis in the group of primary tumor size T1-T2 and in the group of non-metastatic cancer. The lymphatic vessel density and diameter of lymphatic vessels were not associated with tongue cancer survival. The relative density of lymphatic vessels might have clinically relevant prognostic impact. Further studies with increased number of patients are needed.

  10. Genomic Integration of High-Risk HPV Alters Gene Expression in Oropharyngeal Squamous Cell Carcinoma.

    PubMed

    Walline, Heather M; Komarck, Christine M; McHugh, Jonathan B; Bellile, Emily L; Brenner, J Chad; Prince, Mark E; McKean, Erin L; Chepeha, Douglas B; Wolf, Gregory T; Worden, Francis P; Bradford, Carol R; Carey, Thomas E

    2016-10-01

    High-risk HPV (hrHPV) is the leading etiologic factor in oropharyngeal cancer. HPV-positive oropharyngeal tumors generally respond well to therapy, with complete recovery in approximately 80% of patients. However, it remains unclear why some patients are nonresponsive to treatment, with 20% of patients recurring within 5 years. In this study, viral factors were examined for possible clues to differences in tumor behavior. Oropharynx tumors that responded well to therapy were compared with those that persisted and recurred. Viral oncogene alternate transcripts were assessed, and cellular sites of viral integration were mapped and sequenced. Effects of integration on gene expression were assessed by transcript analysis at the integration sites. All of the tumors demonstrated active viral oncogenesis, indicated by expression of HPV E6 and E7 oncogenes and alternate E6 splicing. In the responsive tumors, HPV integration occurred exclusively in intergenic chromosome regions, except for one tumor with viral integration into TP63. Each recurrent tumor exhibited complex HPV integration patterns into cancer-associated genes, including TNFRSF13B, SCN2A, SH2B1, UBE2V2, SMOC1, NFIA, and SEMA6D Disrupted cellular transcripts were identified in the region of integration in four of the seven affected genes.

  11. View looking northwest toward HIghGrade Ore Bin and Concentrate Bin ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    View looking northwest toward HIgh-Grade Ore Bin and Concentrate Bin - Kennecott Copper Corporation, Concentration Mill, On Copper River & Northwestern Railroad, Kennicott, Valdez-Cordova Census Area, AK

  12. High-grade ovarian cancer secreting effective exosomes in tumor angiogenesis.

    PubMed

    Yi, Huan; Ye, Jun; Yang, Xiao-Mei; Zhang, Li-Wen; Zhang, Zhi-Gang; Chen, Ya-Ping

    2015-01-01

    Ovarian cancer, the most lethal gynecological cancer, related closely to tumor stage. High-grade ovarian cancer always results in a late diagnose and high recurrence, which reduce survival within five years. Until recently, curable therapy is still under research and anti-angiogenesis proves a promising way. Tumor-derived exosomes are essential in tumor migration and metastases such as angiogenesis is enhanced by exosomes. In our study, we have made comparison between high-grade and unlikely high-grade serous ovarian cancer cells on exosomal function of endothelial cells proliferation, migration and tube formation. Exosomes derived from high-grade ovarian cancer have a profound impact on angiogenesis with comparison to unlikely high-grade ovarian cancer. Proteomic profiles revealed some potential proteins involved in exosomal function of angiogenesis such as ATF2, MTA1, ROCK1/2 and so on. Therefore, exosomes plays an influential role in angiogenesis in ovarian serous cancer and also function more effectively in high-grade ovarian cancer cells.

  13. High glucose uptake unexpectedly is accompanied by high levels of the mitochondrial β-F1-ATPase subunit in head and neck squamous cell carcinoma

    PubMed Central

    Preuss, Simon F.; Schiffer, Theresa; Schilder, Sarah; Guntinas-Lichius, Orlando; Schmidt, Matthias; Klussmann, Jens P.; Wiesner, Rudolf J.

    2015-01-01

    A hallmark of solid tumors is the consumption of large amounts of glucose and production of lactate, also known as Warburg-like metabolism. This metabolic phenotype is typical for aggressive tumor growth, and can be visualized by 18F-fluorodeoxyglucose (18F-FDG) uptake detected by positron emission tomography (PET). High 18F-FDG uptake inversely correlates with survival and goes along with reduced expression of the catalytic beta-subunit of the H+-ATP synthase (β-F1-ATPase) in several tumor entities analyzed so far. For this study we characterized a series of 15 head and neck squamous cell carcinoma (HNSCC) by (i) determining 18F-FDG-uptake; (ii) quantitative expression analysis of β-F1-ATPase (Complex V), NDUF-S1 (Complex I) and COX1 (Complex IV) of the mitochondrial electron transport chain (ETC), as well as Hsp60 (mitochondrial mass) and GAPDH (glycolysis) in tumor cells; (iii) sequencing of the mtDNA of representative tumor samples. Whereas high 18F-FDG-uptake also correlates with poor prognosis in HNSCC, it surprisingly is accompanied by high levels of β-F1-ATPase, but not by any of the other analyzed proteins. In conclusion, we here describe a completely new phenotype of metabolic adaptation possibly enabling those tumors with highest levels of β-F1-ATPase to rapidly proliferate even in hypoxic zones, which are typical for HNSCC. PMID:26452026

  14. Endoscopic Ultrasound Does Not Accurately Stage Early Adenocarcinoma or High-Grade Dysplasia of the Esophagus

    DTIC Science & Technology

    2010-01-01

    MeSH search terms: " endoscopic ultrasound," "Barrett’s esophagus ," "adeno· carcinoma," "Barrett’s esophagus and high grade dyspla.c;ia...adenocarcinoma of the esophagus ; EMR, endoscopic mucosal resection; EUS, endoscopic ul- trasound; HGD, high-grade dysplasia. <D 2010 by the AGA Institute... esophagus and early adenocarcinoma found EUS examination to have perfecr accuracy for differentiating Tl CLINICAL GASTROENTEROLOGY AND HEPATOLOGY Vol

  15. Differential proteomics analysis of low- and high-grade of astrocytoma using iTRAQ quantification

    PubMed Central

    Ren, Tong; Lin, Shide; Wang, Zhongfeng; Shang, Aijia

    2016-01-01

    Astrocytoma is one of the most common types of brain tumor, which is histologically and clinically classified into four grades (I–IV): I (pilocytic astrocytoma), II (diffuse astrocytoma), III (anaplastic astrocytoma), and IV (glioblastoma multiforme). A higher grade astrocytoma represents a worse prognosis and is more aggressive. In this study, we compared the differential proteome profile of astrocytoma from grades I to IV. The protein samples from clinical specimens of grades I, II, III, and IV astrocytoma were analyzed by two-dimensional liquid chromatography–tandem mass spectrometry and isobaric tags for relative and absolute quantitation and quantification. A total of 2,190 proteins were identified. Compared to grade I astrocytoma, 173 (12.4%), 304 (14%), and 462 (21.2%) proteins were aberrantly expressed in grades II, III, and IV, respectively. By bioinformatics analysis, the cell proliferation, invasion, and angiogenesis-related pathways increase from low- to high-grade of astrocytoma. Five differentially expressed proteins were validated by Western blot. Within them, matrix metalloproteinase-9 and metalloproteinase inhibitor 1 were upregulated in glioblastoma multiforme group; whereas fibulin-2 and -5 were downregulated in grade II/III/IV astrocytoma, and the negative expression was significantly associated with advanced clinical stage. Functional analysis showed that both fibulin-2 and -5 may exert an antitumor effect by inhibiting cell proliferation, in vitro migration/invasion in glioma cells. New molecular biomarkers are likely to be used for accurate classification of astrocytoma and likely to be the target for drug development. PMID:27713642

  16. Human Papillomavirus Genotype Distribution among Thai Women with High-Grade Cervical Intraepithelial Lesions and Invasive Cervical Cancer: a Literature Review.

    PubMed

    Kietpeerakool, Chumnan; Kleebkaow, Pilaiwan; Srisomboon, Jatupol

    2015-01-01

    Infection with high-risk human papillomavirus (HR-HPV) is an essential cause of cervical cancer. Because of substantial geographical variation in the HPV genotype distribution, data regarding HPV type-specific prevalence for a particular country are mandatory for providing baseline information to estimate effectiveness of currently implemented HPV-based cervical cancer prevention. Accordingly, this review was conducted to evaluate the HR-HPV genotype distribution among Thai women with precancerous cervical lesions i.e. cervical intraepithelial neoplasia grade 2-3 (CIN 2-3), adenocarcinoma in situ (AIS), and invasive cervical cancer by reviewing the available literature. The prevalence of HR-HPV infection among Thai women with CIN 2-3 ranged from 64.8% to 90.1% and the three most common genotypes were HPV 16 (38.5%), HPV 58 (20.0%), and HPV 18 (5.5%). There were high squamous cell carcinoma/CIN 2-3 prevalence ratios in women with CIN 2-3 infected with HPV 33 and HPV 58 (1.40 and 1.38, respectively), emphasizing the importance of these subtypes in the risk of progression to invasive cancer among Thai women. Data regarding the prevalence and genotype distribution of HR-HPV in Thai women with AIS remain unavailable. Interesting findings about the distribution of HPV genotype in cervical cancer among Thai women include: (1) a relatively high prevalence of HPV 52 and HPV 58 in invasive squamous cell carcinoma; (2) the prevalence of HPV 18-related adenocarcinoma is almost double thepreviously reported prevalence, and (3) 75% of neuroendocrine carcinomas are HPV18-positive when taking into account both single and multiple infections.

  17. Correlation of p16INK4a immunoexpression and human papillomavirus (HPV) detected by in-situ hybridization in cervical squamous neoplasia.

    PubMed

    Cheah, P L; Koh, C C; Nazarina, A R; Teoh, K H; Looi, L M

    2016-04-01

    Persistence and eventual integration of high-risk HPV (hrHPV) into the cervical cell is crucial to the progression of cervical neoplasia and it would be beneficial to morphologically identify this transformation in routine surgical pathology practice. Increased p16(INK4a) (p16) expression is a downstream event following HPV E7 binding to pRB. A study was conducted to assess the correlation between hrHPV detection using a commercial in-situ hybridization assay (Ventana INFORM HPV ISH) and p16 immunoexpression (CINtec Histology Kit) in cervical squamous intraepithelial lesions and squamous carcinoma. 27 formalin-fixed, paraffin-embedded cervical low-grade squamous intraepithelial lesions (LSIL), 21 high-grade squamous intraepithelial lesions (HSIL) and 51 squamous carcinoma (SCC) were interrogated. hrHPV was significantly more frequent in HSIL (76.2%) and SCC (88.2%) compared to LSIL(37.0%). p16 expression was similarly more frequent in HSIL (95.2%) and SCC (90.2%) compared to LSIL(3.7%). That the rates of hrHPV when compared with p16 expression were almost equivalent in HSIL and SCC while p16 was expressed in only 1 of the 10 LSIL with hrHPV, are expected considering the likelihood that transformation has occurred in HSIL and SCC but does not occur in majority of LSIL.

  18. Ninth Grade Physics: A Necessity for High School Science Programs

    ERIC Educational Resources Information Center

    Wilt, John R.

    2005-01-01

    The traditional order in which science courses are taught in U.S. high schools is biology, chemistry, physics. The physics course usually is regarded as very difficult because it requires both high-level mathematical skills and high-level thinking skills; it is taught in the final year of high school to provide time for students to develop the…

  19. Cytology and Human Papillomavirus Testing 6 to 12 Months after ASCUS or LSIL Cytology in Organized Screening To Predict High-Grade Cervical Neoplasia between Screening Rounds

    PubMed Central

    Sjøborg, Katrine D.; Nygård, Mari; Røysland, Kjetil; Campbell, Suzanne; Alfsen, G. Cecilie; Jonassen, Christine M.

    2012-01-01

    We carried out a prospective study comparing the performance of human papillomavirus (HPV) E6/E7 mRNA (PreTect HPV-Proofer; NorChip, Klokkarstua, Norway) and DNA (Amplicor HPV test; Roche Diagnostics, Basel, Switzerland) triage testing of women 6 to 12 months after atypical-squamous-cells-of-undetermined-significance (ASCUS) or low-grade-squamous-intraepithelial-lesion (LSIL) cytology in organized screening to predict high-grade cervical intraepithelial neoplasia of grade 2 or worse (CIN2+) between screening rounds. Between January 2005 and April 2008, 692 study women with screening-detected ASCUS/LSIL cytology 6 to 12 months earlier returned for HPV mRNA and DNA testing and repeat cytology. The median follow-up time was 3 years, using existing health care facilities. Follow-up test results were available for 625 women. Of the 145 CIN2+ cases detected during the study period, 95 (65.5%) were HPV mRNA positive 6 to 12 months after screening-detected ASCUS/LSIL, 44 (30.4%) were HPV mRNA negative, and 6 (4.1%) were invalid. The corresponding HPV DNA results were 139 (95.9%), 5 (3.4%), and 1 (0.7%), respectively. The cumulative incidences of CIN2+ 3 years after a negative HPV mRNA and DNA test were 10.3% (95% confidence interval [CI], 7.2 to 13.3%) and 1.8% (95% CI, 0.0 to 3.6%), respectively. The cumulative incidences of CIN2+ 3 years after positive HPV mRNA and DNA tests were 52.8% (95% CI, 40.1 to 60.1%) and 41.3% (95% CI, 35.5 to 46.6%), respectively. In conclusion, both positive HPV mRNA and DNA test results have a high enough long-term prediction of CIN2+ risk to consider referral to colposcopy as good practice when performed in delayed triage of women with ASCUS/LSIL cytology. In addition, the low CIN2+ risk among women with a negative Amplicor HPV test in our study confirms its safe use in a clinical setting. PMID:22518869

  20. Poor interobserver reproducibility in the diagnosis of high-grade endometrial carcinoma.

    PubMed

    Gilks, C Blake; Oliva, Esther; Soslow, Robert A

    2013-06-01

    Patients with high-grade subtypes of endometrial carcinoma (grade 3 endometrioid, serous, clear cell, or carcinosarcoma) have a relatively poor prognosis. The specific subtype may be used to guide patient management, but there is little information on the reproducibility of subtype diagnosis in cases of high-grade endometrial carcinoma. Fifty-six cases diagnosed as a high-grade subtype of endometrial carcinoma were identified from the pathology archives of Vancouver General Hospital. All slides for each case were reviewed independently by 3 pathologists, who diagnosed the specific tumor subtype(s) and assigned the percentage of each subtype for mixed tumors. Agreement between observers was categorized as follows: major disagreement: (A) no consensus for low-grade endometrioid versus high-grade carcinoma (any subtype), or (B) no consensus with respect to the predominant high-grade subtype present; minor disagreement: consensus was reached about the cell type of the predominant component of a mixed tumor, but there was disagreement about the subtype of the minor component. A tissue microarray was constructed from these cases and immunostained for p16, ER, PR, PTEN, and p53. In 35 of 56 (62.5%) cases, there was agreement between all 3 reviewers regarding the subtype diagnosis of the exclusive (in pure tumors) or predominant (in mixed tumors) high-grade component. Of these cases, there was a minor disagreement (ie, disagreement about the minor high-grade component subtype in a mixed tumor) in 4 cases (4/56, 7.1%). In 20 of 56 (35.8%) cases there was a major disagreement; in 17 (30.4%) of these cases there was no consensus about the major subtype diagnosis, whereas in 3 (5.4%) cases there was disagreement about whether a component of high-grade endometrial carcinoma was present. In the final case, all 3 reviewers diagnosed the case as low-grade endometrioid carcinoma, disagreeing with the original diagnosis of high-grade carcinoma. The most frequent areas of

  1. [High-grade pressure sores in frail older high-risk persons. A retrospective postmortem case-control-study].

    PubMed

    Von Renteln-Kruse, W; Krause, T; Anders, J; Kühl, M; Heinemann, A; Püschel, K

    2004-04-01

    Some old persons at risk do develop, but others, at comparable risk, do not develop high-grade pressure sores. To evaluate potentially different risk factors, we performed a post mortem case-control study in old persons who developed high-grade pressure sores within six months until 14 days before death. Consecutive cases with pressure sores grade >/=3 and potential controls at comparably high risk for pressure sores were examined before cremation. After written informed consent had been obtained by the next relatives, all available nursing and medical records of the deceased were thoroughly evaluated. Cases and controls were matched according to age, gender, immobility, and cachexia.A total of 100 cases with 71 pressure sores grade 3 and 29 pressure sores grade 4 were compared to 100 controls with 27 pressure sores grade high degree of disablement and immobility, in particular, are risk factors for high-grade pressure sores in frail older high-risk persons. Sedative drug effects and impaired patient compliance with preventive and therapeutic measures may also be associated with the development of high-grade pressure sores in old persons at high risk.

  2. An Investigation of the Relationship Between Retention in First Grade and Performance on High Stakes Tests in 3 Grade.

    PubMed

    Hughes, Jan N; Chen, Qi; Thoemmes, Felix; Kwok, Oi-Man

    2010-05-19

    The association between grade retention in first grade and passing the third grade state accountability tests, the Texas Assessment of Knowledge and Skills (TAKS) reading and math, was investigated in a sample of 769 students who were recruited into the study when they were in first grade. Of these 769 students, 165 were retained in first grade and 604 were promoted. Using propensity matching, we created five imputed datasets (average N=321) in which promoted and retained students were matched on 67 comprehensive covariates. Using GEE models, we obtained the association between retention and passing the 3(rd) grade TAKS reading and math tests. The positive association between retention and math scores was significant while the association was marginally significant for reading scores.

  3. IDH mutations as an early and consistent marker in low-grade astrocytomas WHO grade II and their consecutive secondary high-grade gliomas.

    PubMed

    Juratli, Tareq A; Kirsch, Matthias; Robel, Katja; Soucek, Silke; Geiger, Kathrin; von Kummer, Rüdiger; Schackert, Gabriele; Krex, Dietmar

    2012-07-01

    This study investigated the prognostic and predictive significance of IDH1 and IDH2 mutations in low-grade astrocytomas (LGA). The presence and consistency of IDH mutations during the progression of LGA to secondary high-grade gliomas (sHGG) were detected. Samples of patients with LGA and sHGG were investigated. The genomic regions around IDH1 codon 132 and IDH2 codon 172 were PCR amplified and directly sequenced. Furthermore, the MGMT promoter status was provided using the methylation-specific PCR. Our population comprised 71 patients with a total of 45 pairs of LGA and their consecutive sHGG. Median follow-up was 9.6 years. IDH mutations were found in 36/45 LGA (80%) and their sHGG without changes in the mutation status. A total of 71 patients with LGA were analyzed according to clinical and molecular tumor-related factors: 56/71 patients (78.8%) had an IDH mutation without significant influence on the progression-free or overall survival (OS), and 22/71 (31%) of the patients received postoperative radiotherapy (RT) after diagnosis of LGA. Patients with early RT but without IDH mutations had the shortest survival. Our study shows that IDH mutation status is stable during the progression course of LGA to sHGG. The presence of IDH mutations fails to demonstrate a significant influence on survival in the multivariate analysis of LGA patients. Early RT appears to be beneficial only LGA patients with IDH-mutations.

  4. Deubiquitinase USP9X deubiquitinates β-catenin and promotes high grade glioma cell growth

    PubMed Central

    Wang, Zhihao; Yang, Chunxu; Ouyang, Wen; Zhou, Fuxiang; Zhou, Yunfeng; Xie, Conghua

    2016-01-01

    β-catenin is a crucial signal transduction molecule in the Wnt/β-catenin signal pathway, and increased β-catenin expression has consistently been found in high grade gliomas. However, the mechanisms responsible for β-catenin overexpression have remained elusive. Here we show that the deubiquitinase USP9X stabilizes β-catenin and thereby promotes high grade glioma cell growth. USP9X binds β-catenin and removes the Lys 48-linked polyubiquitin chains that normally mark β-catenin for proteasomal degradation. Increased USP9X expression correlates with increased β-catenin protein in high grade glioma tissues. Moreover, patients with high grade glioma overexpressing USP9X have a poor prognosis. Knockdown of USP9X suppresses cell proliferation, inhibits G1/S phase conversion, and induces apoptosis in U251 and A172 cells. Interestingly, c-Myc and cyclinD1, which are important downstream target genes in the Wnt/β-catenin signal pathway, also show decreased expression in cells with siRNA-mediated down-regulation of USP9X. Down-regulation of USP9X also consistently inhibits the tumorigenicity of primary glioma cells in vivo. In summary, these results indicate that USP9X stabilizes β-catenin and activates Wnt/β-catenin signal pathway to promote glioma cell proliferation and survival. USP9X could also potentially be a novel therapeutic target for high grade gliomas. PMID:27783990

  5. Research and development of intelligent controller for high-grade sanitary ware

    NASA Astrophysics Data System (ADS)

    Bao, Kongjun; Shen, Qingping

    2013-03-01

    With the social and economic development and people's living standards improve, more and more emphasis on modern society, people improve the quality of family life, the use of intelligent controller applications in high-grade sanitary ware physiotherapy students. Analysis of high-grade sanitary ware physiotherapy common functions pointed out in the production and use of the possible risks, proposed implementation of the system hardware and matching, given the system software implementation process. High-grade sanitary ware physiotherapy intelligent controller not only to achieve elegant and beautiful, simple, physical therapy, water power, deodorant, multi-function, intelligent control, to meet the consumers, the high-end sanitary ware market, strong demand, Accelerate the enterprise product Upgrade and improve the competitiveness of enterprises.

  6. High-grade optical polydimethylsiloxane for microfluidic applications.

    PubMed

    Lovchik, Robert Dean; Wolf, Heiko; Delamarche, Emmanuel

    2011-12-01

    Commercially available polydimethylsiloxane (PDMS) elastomers, such as Sylgard 184® are widely used in soft lithography and for microfluidic applications. These PDMS elastomers contain fillers to enhance their mechanical stability. The reinforcing fillers, often sub-micrometer small SiO(2) particles, tend to aggregate, swell with water, and thereby become cognoscible in a way that can strongly interfere with the visualization of micro-scale events taking place next to PDMS structures. As PDMS microfluidics are often used for studying cells and micro-/nanoparticles and for creating/handling nanodroplets, it has become highly desirable to employ a PDMS having high optical quality and that allows microscopy observation without artifacts. Here, we present a PDMS formulation that is free of fillers and has sufficiently low viscosity to perform a filtration step of the mixed prepolymers before curing. By molding a bi-layer microfluidic network (MFN), composed of a thin filler-free PDMS layer and a thicker Sylgard 184® backing layer, PDMS MFNs featuring both high optical quality and mechanical stability, can be fabricated.

  7. Relationship between First-Grade Marks and the High School Dropout Problem.

    ERIC Educational Resources Information Center

    Simner, Marvin L.; Barnes, Michael J.

    1991-01-01

    Reviewed academic records for students who attended public school, completing secondary education between 1982 and 1986. Students who experienced most difficulty in mastering first grade reading and arithmetic had much higher probability of leaving high school without graduating and of experiencing serious academic problems while in high school…

  8. The Impact of the Non-Graded, Multi-Selective English Curriculum on High School Students.

    ERIC Educational Resources Information Center

    Gage, Thomas Evans

    Studies involving different populations were involved in this four-part evaluation of the impact of non-graded, multi-selective English on high school students. Study A involved students who consistently scored high or low in percentile gain in the four ability groups, to ascertain any pattern of courses selected, sequences of courses attended,…

  9. Closer to the Finish Line? Compulsory Attendance, Grade Attainment, and High School Graduation

    ERIC Educational Resources Information Center

    Moussa, Wael S.

    2017-01-01

    High school graduation rates are a central policy topic in the United States and have been shown to be stagnant for the past three decades. Using student-level administrative data from New York City Public Schools, I examine the impact of compulsory school attendance on high school graduation rates and grade attainment, focusing the analysis on…

  10. Small Classes in the Early Grades, Academic Achievement, and Graduating From High School

    ERIC Educational Resources Information Center

    Finn, Jeremy D.; Gerber, Susan B.; Boyd-Zaharias, Jayne

    2005-01-01

    This investigation addressed 3 questions about the long-term effects of early school experiences: (a) Is participation in small classes in the early grades (K-3) related to high school graduation? (b) Is academic achievement in K-3 related to high school graduation? (c) If class size is related to graduation, is the relationship explained by the…

  11. Oral undifferentiated high-grade pleomorphic sarcoma: report of a case.

    PubMed

    Alfredo, Edson; de Pádua, Joubert Magalhães; Vicentini, Eduardo Luis; Marchesan, Melissa Andreia; Comelli Lia, Raphael Carlos; da Cruz Perez, Danyel Elias; Silva-Sousa, Yara Teresinha Corrêa

    2008-01-01

    The current World Health Organization classification considers the existence of an undifferentiated unclassifiable category of pleomorphic sarcomas, defined as a group of pleomorphic high-grade sarcomas. Undifferentiated high-grade pleomorphic sarcoma represents about 5% of all soft tissue sarcomas in adults and occurs more commonly in the extremities. In the oral cavity, undifferentiated pleomorphic sarcoma is extremely rare. We report a case of undifferentiated high-grade pleomorphic sarcoma located in the floor of the mouth in a man 56 years old. Microscopically, spindle-shaped cells with accented pleomorphism arranged in a storiform pattern, several bizarre giant cells, and frequent atypical mitoses were observed. The tumor cells were positive only for vimentin, with focal positivity for CD68. The patient was treated by surgery and postoperative radiation therapy, and after 25 months, no recurrence was observed.

  12. The Minimum Grading Controversy: Results of a Quantitative Study of Seven Years of Grading Data from an Urban High School

    ERIC Educational Resources Information Center

    Carey, Theodore; Carifio, James

    2012-01-01

    In an effort to reduce failure and drop-out rates, schools have been implementing minimum grading. One form involves raising catastrophically low student quarter grades to a predetermined minimum--typically a 50. Proponents argue it gives struggling students a reasonable chance to recover from failure. Critics contend the practice induces grade…

  13. Detection of high-grade atypia nuclei in breast cancer imaging

    NASA Astrophysics Data System (ADS)

    Noël, Henri; Roux, Ludovic; Lu, Shijian; Boudier, Thomas

    2015-03-01

    Along with mitotic count, nuclear pleomorphism or nuclear atypia is an important criterion for the grading of breast cancer in histopathology. Though some works have been done in mitosis detection (ICPR 2012,1 MICCAI 2013,2 and ICPR 2014), not much work has been dedicated to automated nuclear atypia grading, especially the most difficult task of detection of grade 3 nuclei. We propose the use of Convolutional Neural Networks for the automated detection of cell nuclei, using images from the three grades of breast cancer for training. The images were obtained from ICPR contests. Additional manual annotation was performed to classify pixels into five classes: stroma, nuclei, lymphocytes, mitosis and fat. At total of 3,000 thumbnail images of 101 × 101 pixels were used for training. By dividing this training set in an 80/20 ratio we could obtain good training results (around 90%). We tested our CNN on images of the three grades which were not in the training set. High grades nuclei were correctly classified. We then thresholded the classification map and performed basic analysis to keep only rounded objects. Our results show that mostly all atypical nuclei were correctly detected.

  14. 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

  15. ADVANCES IN IMAGING TECHNOLOGIES IN THE EVALUATION OF HIGH-GRADE BLADDER CANCER

    PubMed Central

    Zlatev, Dimitar V.; Altobelli, Emanuela; Liao, Joseph C.

    2015-01-01

    Bladder cancer is a heterogeneous disease that ranges from low-grade variant with an indolent course, to high-grade subtype with a recurrent, progressive, and potentially lethal outcome. Accurate assessment for individualized treatment depends critically on the diagnostic accuracy of white light cystoscopy. Despite its central role, white light cystoscopy has several well-documented shortcomings including difficult flat lesion detection, imprecise tumor delineation that limits complete resection, differentiation between inflammation and malignancy, and grade and stage determination. As the limitations of white light cystoscopy contribute to the risk of cancer persistence, recurrence, and progression, there is a need for improved visualization of flat, multifocal, high-grade, and muscle-invasive lesions. Optical imaging technologies have emerged as an adjunct to white light cystoscopy with the goal to guide more effective treatment by improving cancer detection and patient stratification on the basis of grade and stage. Photodynamic diagnosis and narrow band imaging are macroscopic imaging modalities similar to white light cystoscopy, but provide additional contrast enhancement of bladder tumors and have been shown to improve detection rates. Confocal laser endomicroscopy and optical coherence tomography are microscopic imaging technologies that enable real-time high resolution, subsurface tissue characterization with spatial resolutions similar to histology. Molecular imaging offers the potential for the combination of optical imaging technologies with cancer-specific molecular agents to improve the specificity of disease detection. PMID:25882557

  16. 5α-reductase Inhibitors and Risk of High-grade or Lethal Prostate Cancer

    PubMed Central

    Preston, Mark A.; Wilson, Kathryn; Markt, Sarah C.; Ge, Rongbin; Morash, Christopher; Stampfer, Meir J.; Loda, Massimo F.; Giovannucci, Edward; Mucci, Lorelei A.; Olumi, Aria F.

    2014-01-01

    Importance 5α-reductase inhibitors (5ARIs) are widely used for benign prostatic hyperplasia despite controversy regarding potential risk of high-grade prostate cancer with use. Furthermore, the effect of 5ARIs on progression and prostate cancer death remains unclear. Objective To determine the association between 5ARI use and development of high-grade or lethal prostate cancer. Design, Setting, and Participants Prospective observational study of 38,058 men followed for prostate cancer diagnosis and outcomes between 1996–2010 in the Health Professionals Follow-up Study. Exposure Use of 5ARIs between 1996–2010. Main Outcome Measures Cox proportional hazards models were used to estimate risk of prostate cancer diagnosis or development of lethal disease with 5ARI use, adjusting for possible confounders including prostate specific antigen testing. Results During 448,803 person-years of follow-up, we ascertained 3681 incident prostate cancer cases. Of these, 289 were lethal (metastatic or fatal), 456 were high-grade (Gleason 8–10), 1238 were Gleason grade 7, and 1600 were low-grade (Gleason 2–6). A total of 2878 (7.6%) men reported use of 5ARIs between 1996 and 2010. After adjusting for confounders, men who reported ever using 5ARIs over the study period had a reduced risk of overall prostate cancer (HR 0.77; 95% CI, 0.65–0.91). 5ARI users had a reduced risk of Gleason 7 (HR 0.67; 95% CI, 0.49–0.91) and low-grade (Gleason 2–6) prostate cancer (HR 0.74; 95% CI, 0.57–0.95). 5ARI use was not associated with risk of high-grade (Gleason 8–10, HR 0.97; 95% CI, 0.64–1.46) or lethal disease (HR 0.99; 95% CI, 0.58–1.69). Increased duration of use was associated with significantly lower risk of overall prostate cancer (HR for 1 year of additional use 0.95; 95% CI, 0.92–0.99), localized (HR 0.95; 95% CI, 0.90–1.00), and low-grade disease (HR 0.92; 95% CI, 0.85–0.99). There was no association for lethal, high-grade, or grade 7 disease. Conclusions and

  17. Prospective Assessment of Patterns of Failure After High-Precision Definitive (Chemo)Radiation in Head-and-Neck Squamous Cell Carcinoma

    SciTech Connect

    Gupta, Tejpal

    2011-06-01

    Purpose: To prospectively analyze patterns of failure in patients with head-and-neck squamous cell carcinoma treated with definitive high-precision radiotherapy with a focus on location of failure relative to target volume coverage. Methods and Materials: Sixty patients treated with three-dimensional conformal radiotherapy or intensity-modulated radiation therapy were included. Locoregional failure volume was defined on the planning data set at relapse, and dose received was analyzed by use of dose-volume histograms. Results: Thirteen patients were deemed to have had locoregional failures, of which two did not have any viable tumor on salvage neck dissection, leaving eleven patients with proven persistent or recurrent locoregional disease. Of these, 9 patients had in-field failure, 1 marginal failure, and 1 both in-field and marginal failures. Overall, only 2 of 11 patients (18%) with relapse had any marginal failure. Of the 20 sites of locoregional failure, 15 (75%) were in-field and 5 (25%) marginal. Distant metastases were detected in 3 patients, whereas a second new primary developed in 3 others. With a median follow-up of 26 months (interquartile range, 18-31 months) for surviving patients, the 3-year local control, locoregional control, disease-free survival, and overall survival rates were 75.3%, 74%, 67.2%, and 60.5%, respectively. Conclusions: Locoregional relapse remains the predominant pattern of failure in head-and-neck squamous cell carcinoma treated with high-precision definitive radiotherapy with the majority of failures occurring 'in-field' within the high-dose volume. Marginal failures can occur, particularly in the vicinity of the spared parotid gland. The therapeutic index of high-precision conformal radiotherapy is largely dependent on adequate selection and delineation of target volumes and organs at risk.

  18. Utility of peripheral blood flow cytometry in differentiating low grade versus high grade myelodysplastic syndromes (MDS) and in the evaluation of cytopenias.

    PubMed

    Rashidi, Hooman H; Xu, Xiangdong; Wang, Huan-You; Shafi, Nelofar Q; Rameshkumar, Karuna; Messer, Karen; Smith, Brian R; Rose, Michal G

    2012-01-01

    The diagnostic utility of flow cytometry in the evaluation of cytopenias and in the differential diagnosis of low-grade versus high-grade myelodysplastic syndrome (MDS) is not widely appreciated. In this report, we measured granulocyte CD10/control fluorescence ratio in 29 patients with MDS & chronic myelomonocytic leukemia (CMML) using peripheral blood (PB) flow cytometry (FC). We found a lower ratio in high-grade MDS and CMML (mean ratio of 2.2 ± 0.7) vs. low-grade MDS (3.65 ± 0.9) and 16 cytopenic controls without MDS (3.67 ± 0.65; p<0.001). The sensitivity and specificity of CD10 ratio <3 for the group that included the high risk MDS and CMML patients were 87.5% and 100%, respectively. Our data suggests that FC of PB may be helpful in the work-up of patients with cytopenias and in the differential diagnosis of low-grade vs. high-grade MDS.

  19. Energy and Economics for the Senior High Grades. Unit III. Lessons and Activities for the Senior High Grades.

    ERIC Educational Resources Information Center

    Backler, Alan

    Twelve energy lessons developed for use by senior high school students are presented. These lessons are designed to help students become more aware of the energy choices that they must make in the present and for the future and to understand that the costs of maintaining a specific standard of living and thriving national economy can be controlled…

  20. Extrusion granulation and high shear granulation of different grades of lactose and highly dosed drugs: a comparative study.

    PubMed

    Keleb, E I; Vermeire, A; Vervaet, C; Remon, Jean Paul

    2004-07-01

    Formulations containing different lactose grades, paracetamol, and cimetidine were granulated by extrusion granulation and high shear granulation. Granules were evaluated for yield, friability, and compressibility. Tablets were prepared from those granules and evaluated for tensile strength, friability, disintegration time, and dissolution. The different lactose grades had an important effect on the extrusion granulation process. Particle size and morphology affected powder feeding and power consumption, but had only a minor influence on the granule and tablet properties obtained by extrusion granulation. In contrast, the lactose grades had a major influence on the granule properties obtained by high shear granulation. Addition of polyvinylpyrrolidone (PVP) was required to process pure paracetamol and cimetidine by high shear granulation, whereas it was feasible to granulate these drugs without PVP by extrusion granulation. Granules prepared by extrusion granulation exhibited a higher yield and a lower friability than those produced by high shear granulation. Paracetamol and cimetidine tablets compressed from granules prepared by extrusion granulation showed a higher tensile strength, lower friability, and lower disintegration time than those prepared from granules produced by high shear granulation. Paracetamol tablets obtained via extrusion granulation exhibited faster dissolution than those obtained via high shear granulation. For all lactose grades studied, extrusion granulation resulted in superior granule and tablet properties in comparison with those obtained by high shear granulation. These results indicate that extrusion granulation is more efficient than high shear granulation.

  1. Supporting Young Adolescents' Middle-to-High-School Transition by Creating a Ninth Grade Community of Care: Implications for Middle Grades Educators

    ERIC Educational Resources Information Center

    Ellerbrock, Cheryl R.; Kiefer, Sarah M.

    2014-01-01

    The middle-to-high-school transition and the first year of high school are critical periods in students' lives. According to the Southern Regional Education Board (SREB), "The passage of students from the middle grades to high school is the most difficult transition point in education" (2002, p. 24). Although there are many different…

  2. Separation of Nitration By-Products in Commercial-Grade Trinitro-Toluene by High Performance Liquid Chromatography.

    DTIC Science & Technology

    1982-06-01

    MRL-TN-464 SEPARATION OF NITRATION BY-PRODUCTS IN COMMERCIAL-GRADE TITR-TOLUENE BY HIGH PERFORMANCE LIQUID CHROMATOGRAPHY Peter J. Sanders ABSTRACT...UNCLASSIFIED TITLE SEPARATION OF NITRATION BY-PRODUCTS IN COMMERCIAL-GRADE TRXNITRO-TOLUENE BY HIGH PERFORMANCE LIQUID CHROMATOGRAPHY AUTHOR(S...PRODUCTS IN COMMERCIAL-GRADE TRINITRO-TOLUENE BY HIGH PERFORMANCE LIQUID CHROMATOGRAPHY 16 INTRODUCTION Fbr some time, a need has existed for the

  3. Clinical studies of combined photodynamic therapy using 5-fluorouracil and methyl-aminolevulinate in patients at high risk for squamous cell carcinoma

    NASA Astrophysics Data System (ADS)

    Maytin, Edward V.; Lohser, Sara; Tellez, Alejandra; Wene, Lauren; Ishak, Rim; Anand, Sanjay

    2013-03-01

    Photodynamic therapy (PDT) using aminolevulinic acid or its methyl ester, methyl-aminolevulinate (MAL), is an increasingly recognized approach for treating squamous neoplasia of the skin. Advantages of MAL-PDT include its ability to cover broad diseased areas (field treatment), and to do multiple sessions with little-to-no risk of scarring or mutagenesis. MAL-PDT is especially valuable in certain populations at high risk for skin cancer, including Caucasian patients with extensive solar damage, and organ transplant recipients (OTR) who take immunosuppressive drugs to prevent graft rejection. The latter group has a 65-200 fold increased risk of developing squamous cell carcinoma (SCC), a major cause of mortality. Therapeutic options for those patients, other than frequent surgeries, are very limited. Topical 5-Fluorouracil (5-FU), frequently prescribed in normal patients for pre-SCC of the skin, is only minimally effective in the OTR group. MAL-PDT, however, has ~40% efficacy for pre-SCC in OTR patients. Based upon our preclinical studies in mouse tumor models, which showed that preconditioning with 5-FU can drive higher accumulation of target protoporphyins (PpIX), we proposed a rational combination regimen of 5-FU and MAL-PDT in humans. A clinical trial was designed to test the hypothesis that a combination of 5-FU followed by MAL-PDT will elevate PpIX levels and achieve better clinical outcomes in high-risk OTR patients. Primary endpoints include PpIX levels and biochemical markers (p53) measured noninvasively and in skin biopsies. Lesion clearance and recurrence (via photographs and clinical exam) are secondary endpoints. Ongoing results of this clinical trial are presented.

  4. High Expression of KIF20A Is Associated with Poor Overall Survival and Tumor Progression in Early-Stage Cervical Squamous Cell Carcinoma

    PubMed Central

    Gu, Haifeng; Li, Min; Liu, Zhimin; Feng, Yanling; Zheng, Nianzhen; Xie, Chuanmiao; Zhang, Yanna

    2016-01-01

    Background The kinesin family member 20a (KIF20A) protein has been implicated in the development and progression of many human cancers; however, its precise function and role in cervical cancer remain largely unclear. This study aimed to investigate the expression profile and prognostic value of KIF20A in patients with early-stage cervical squamous cell carcinoma. Methods We examined the mRNA and protein levels of KIF20A in eight cervical cancer cell lines and eight paired cervical cancer samples, compared with normal cervical epithelial cells and adjacent normal cervical tissues, respectively. Immunohistochemistry was performed to detect the expression of KIF20A in paraffin-embedded specimens from 169 early-stage cervical squamous cell carcinoma patients. Statistical analyses were applied to analyze the association between KIF20A expression and clinical variables, as well with patient survival. Results The mRNA and protein expression levels of KIF20A were significantly elevated in cervical cancer cell lines and lesions compared with normal cells and corresponding normal tissues (P < 0.05). Immunohistochemistry analysis in 169 cervical cancer cases revealed that increased KIF20A expression was strongly associated with human papillomavirus (HPV) infection (P = 0.008), clinical stage (P = 0.001), tumor recurrence (P = 0.016), vital status (P < 0.001), the property of the surgical margin (P = 0.032), the lymphovascular space involvement (P = 0.014), and pelvic lymph node metastasis (P = 0.001). The overall survival and disease-free survival of patients with high levels of KIF20A expression were significantly poorer than those with low KIF20A expression. KIF20A was an independent survival prognostic factor, as evidenced by univariate and multivariate analysis. Conclusions Our results illustrate that elevated KIF20A expression correlates with HPV infection, clinical stage, tumor recurrence, lymphovascular space involvement, pelvic lymph node metastasis, and poor outcome

  5. Widespread chromosomal abnormalities in high-grade ductal carcinoma in situ of the breast. Comparative genomic hybridization study of pure high-grade DCIS.

    PubMed

    Moore, E; Magee, H; Coyne, J; Gorey, T; Dervan, P A

    1999-03-01

    For a variety of technical reasons it is rarely possible to study cytogenetic abnormalities in ductal carcinoma in situ (DCIS) using traditional techniques. However, by combining molecular biology and computerized image analysis it is possible to carry out cytogenetic analyses on formalin-fixed, paraffin-embedded tissue, using comparative genomic hybridization (CGH). The purpose of this study was to identify the prevalence of chromosomal amplifications and deletions in high-grade DCIS and to look specifically for unique or consistent abnormalities in this pre-invasive cancer. Twenty-three cases of asymptomatic, non-palpable, screen-detected, high-grade DCIS were examined using CGH on tumour cells obtained from histology slides. All cases showed chromosomal abnormalities. A wide variety of amplifications and deletions were spread across the genome. The most frequent changes were gains of chromosomes 17 (13 of 23), 16p (13 of 23), and 20q (9 of 23) and amplifications of 11q13 (22 of 23), 12q 24.1-24.2 (12 of 23), 6p21.3 (11 of 23), and 1q31-qter (6 of 23). The most frequent deletions were on 13q 21.3-q33 (7 of 23), 9p21 (4 of 23), and 6q16.1 (4 of 23). These findings indicate that high-grade DCIS is, from a cytogenetic viewpoint, an advanced lesion. There was no absolutely consistent finding in every case, but amplification of 11q13 was found in 22 of the 23 cases. The precise significance of this is unknown at present. This region of chromosome 11q harbours a number of known oncogenes, including cyclin D1 andINT2. It is likely that many of these findings are the result of accumulated chromosomal abnormalities, reflecting an unstable genome in established malignancy.

  6. Intrinsic subtypes of high-grade bladder cancer reflect the hallmarks of breast cancer biology.

    PubMed

    Damrauer, Jeffrey S; Hoadley, Katherine A; Chism, David D; Fan, Cheng; Tiganelli, Christopher J; Wobker, Sara E; Yeh, Jen Jen; Milowsky, Matthew I; Iyer, Gopa; Parker, Joel S; Kim, William Y

    2014-02-25

    We sought to define whether there are intrinsic molecular subtypes of high-grade bladder cancer. Consensus clustering performed on gene expression data from a meta-dataset of high-grade, muscle-invasive bladder tumors identified two intrinsic, molecular subsets of high-grade bladder cancer, termed "luminal" and "basal-like," which have characteristics of different stages of urothelial differentiation, reflect the luminal and basal-like molecular subtypes of breast cancer, and have clinically meaningful differences in outcome. A gene set predictor, bladder cancer analysis of subtypes by gene expression (BASE47) was defined by prediction analysis of microarrays (PAM) and accurately classifies the subtypes. Our data demonstrate that there are at least two molecularly and clinically distinct subtypes of high-grade bladder cancer and validate the BASE47 as a subtype predictor. Future studies exploring the predictive value of the BASE47 subtypes for standard of care bladder cancer therapies, as well as novel subtype-specific therapies, will be of interest.

  7. [High-grade prostatic intraepithelial neoplasia: state-of-the-art].

    PubMed

    Allina, D O; Andreeva, Iu Iu; Zavalishina, L E; Kekeeva, T V; Frank, G A

    2015-01-01

    According to current views, high-grade prostatic intraepithelial neoplasia is the most likely precursor of prostate adenocarcinoma. This review gives the latest data of genetic, proteomic, and morphological analyses of this neoplasia and touches upon the probems that might arise when searching for new markers for differential diagnosis and prognosis estimation.

  8. Connective tissue growth factor as a novel therapeutic target in high grade serous ovarian cancer

    PubMed Central

    Moran-Jones, Kim; Gloss, Brian S.; Murali, Rajmohan; Chang, David K.; Colvin, Emily K.; Jones, Marc D.; Yuen, Samuel; Howell, Viive M.; Brown, Laura M.; Wong, Carol W.; Spong, Suzanne M.; Scarlett, Christopher J.; Hacker, Neville F.; Ghosh, Sue; Mok, Samuel C.; Birrer, Michael J.; Samimi, Goli

    2015-01-01

    Ovarian cancer is the most common cause of death among women with gynecologic cancer. We examined molecular profiles of fibroblasts from normal ovary and high-grade serous ovarian tumors to identify novel therapeutic targets involved in tumor progression. We identified 2,300 genes that are significantly differentially expressed in tumor-associated fibroblasts. Fibroblast expression of one of these genes, connective tissue growth factor (CTGF), was confirmed by immunohistochemistry. CTGF protein expression in ovarian tumor fibroblasts significantly correlated with gene expression levels. CTGF is a secreted component of the tumor microenvironment and is being pursued as a therapeutic target in pancreatic cancer. We examined its effect in in vitro and ex vivo ovarian cancer models, and examined associations between CTGF expression and clinico-pathologic characteristics in patients. CTGF promotes migration and peritoneal adhesion of ovarian cancer cells. These effects are abrogated by FG-3019, a human monoclonal antibody against CTGF, currently under clinical investigation as a therapeutic agent. Immunohistochemical analyses of high-grade serous ovarian tumors reveal that the highest level of tumor stromal CTGF expression was correlated with the poorest prognosis. Our findings identify CTGF as a promoter of peritoneal adhesion, likely to mediate metastasis, and a potential therapeutic target in high-grade serous ovarian cancer. These results warrant further studies into the therapeutic efficacy of FG-3019 in high-grade serous ovarian cancer. PMID:26575166

  9. Managing the Transition to Ninth Grade in a Comprehensive Urban High School. Snapshot

    ERIC Educational Resources Information Center

    Smith, Thomas J.

    2007-01-01

    This "snapshot" illustrates how one school is managing to make a positive difference for ninth graders. It describes the Ninth Grade Success Academy, a school-within-a-school at Thomas A. Edison High School in Philadelphia, Pennsylvania, which has a number of features specifically designed to help ninth-graders make successful…

  10. "Career Education" Junior High School Style: "Semester Course" for Seventh Grade.

    ERIC Educational Resources Information Center

    Alpine School District, American Fork, UT.

    The curriculum guide is a product of the Alpine School District (American Fork, Utah) program to integrate career education concepts into the curriculum of all junior high schools in the district. The guide offers teacher-developed materials designed to help seventh grade students become aware of the dignity of work and to explore the world of…

  11. Group Art Therapy with Eighth-Grade Students Transitioning to High School

    ERIC Educational Resources Information Center

    Spier, Erin

    2010-01-01

    This study examined the effectiveness of a group art therapy intervention within a school setting to increase coping skills and decrease disruptive behaviors in a group of 6 eighth-grade students at risk for making a poor transition to high school. The mixed-method AB single-case experiment measured each individual's changes in behavior and coping…

  12. High School Grade Inflation from 2004 to 2011. ACT Research Report Series, 2013 (3)

    ERIC Educational Resources Information Center

    Zhang, Qian; Sanchez, Edgar I.

    2013-01-01

    This study explores inflation in high school grade point average (HSGPA), defined as trend over time in the conditional average of HSGPA, given ACT® Composite score. The time period considered is 2004 to 2011. Using hierarchical linear modeling, the study updates a previous analysis of Woodruff and Ziomek (2004). The study also investigates…

  13. Accelerated Mathematics and High-Ability Students' Math Achievement in Grades Three and Four

    ERIC Educational Resources Information Center

    Stanley, Ashley M.

    2011-01-01

    The purpose of this study was to explore the relationship between the use of a computer-managed integrated learning system entitled Accelerated Math (AM) as a supplement to traditional mathematics instruction on achievement as measured by TerraNova achievement tests of third and fourth grade high-ability students. Gender, socioeconomic status, and…

  14. Connective tissue growth factor as a novel therapeutic target in high grade serous ovarian cancer.

    PubMed

    Moran-Jones, Kim; Gloss, Brian S; Murali, Rajmohan; Chang, David K; Colvin, Emily K; Jones, Marc D; Yuen, Samuel; Howell, Viive M; Brown, Laura M; Wong, Carol W; Spong, Suzanne M; Scarlett, Christopher J; Hacker, Neville F; Ghosh, Sue; Mok, Samuel C; Birrer, Michael J; Samimi, Goli

    2015-12-29

    Ovarian cancer is the most common cause of death among women with gynecologic cancer. We examined molecular profiles of fibroblasts from normal ovary and high-grade serous ovarian tumors to identify novel therapeutic targets involved in tumor progression. We identified 2,300 genes that are significantly differentially expressed in tumor-associated fibroblasts. Fibroblast expression of one of these genes, connective tissue growth factor (CTGF), was confirmed by immunohistochemistry. CTGF protein expression in ovarian tumor fibroblasts significantly correlated with gene expression levels. CTGF is a secreted component of the tumor microenvironment and is being pursued as a therapeutic target in pancreatic cancer. We examined its effect in in vitro and ex vivo ovarian cancer models, and examined associations between CTGF expression and clinico-pathologic characteristics in patients. CTGF promotes migration and peritoneal adhesion of ovarian cancer cells. These effects are abrogated by FG-3019, a human monoclonal antibody against CTGF, currently under clinical investigation as a therapeutic agent. Immunohistochemical analyses of high-grade serous ovarian tumors reveal that the highest level of tumor stromal CTGF expression was correlated with the poorest prognosis. Our findings identify CTGF as a promoter of peritoneal adhesion, likely to mediate metastasis, and a potential therapeutic target in high-grade serous ovarian cancer. These results warrant further studies into the therapeutic efficacy of FG-3019 in high-grade serous ovarian cancer.

  15. 40 CFR 246.200-2 - Recommended procedures: High-grade paper recovery from smaller offices.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... offices. The recovery of high-grade paper generated by office facilities of less than 100 office workers... paper recovery from smaller offices. 246.200-2 Section 246.200-2 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) SOLID WASTES SOURCE SEPARATION FOR MATERIALS RECOVERY GUIDELINES...

  16. Life in the Fast Lane: Effects of Early Grade Acceleration on High School and College Outcomes

    ERIC Educational Resources Information Center

    McClarty, Katie Larsen

    2015-01-01

    Research has repeatedly demonstrated the positive effects of acceleration for gifted and talented students. This study expands the literature by not only evaluating the impact of early grade skipping on high school and college outcomes but also examining the role of postacceleration opportunities on subsequent performance. Using a representative…

  17. The Impact of High-Speed Internet Connectivity at Home on Eighth-Grade Student Achievement

    ERIC Educational Resources Information Center

    Kingston, Kent J.

    2013-01-01

    In the fall of 2008 Westside Community Schools - District 66, in Omaha, Nebraska implemented a one-to-one notebook computer take home model for all eighth-grade students. The purpose of this study was to determine the effect of a required yearlong one-to-one notebook computer program supported by high-speed Internet connectivity at school on (a)…

  18. Prevention of Ovarian High-Grade Serous Carcinoma by Elucidating Its Early Changes

    DTIC Science & Technology

    2014-10-01

    that i) reproductive hormone signaling is altered in HGSC, that ii) reproductive hormone receptor status (ERα/PR) may be an important indicator of...microenvironment ovulatory stresses, which may include altered reproductive hormone levels and the ovulatory inflammatory response. The...inflammatory response and altered reproductive hormone physiology. Keywords: BRCA, fallopian tube epithelium, high-grade serous carcinoma INTRODUCTION In 2013

  19. Motivating Every Student in Literacy (Including the Highly Unmotivated!), Grades 3-6

    ERIC Educational Resources Information Center

    Athans, Sandra K.; Devine, Denise Ashe

    2010-01-01

    "Motivating Every Student in Literacy (Including the Highly Unmotivated!), Grades 3-6" provides an effective model for improving reading levels and increasing motivation. Under the guidance of Athans and Devine, classroom leaders develop their own Motivation Improvement Action Plans, where small-group instruction, end-of-unit assessments, and…

  20. Prognostic impact of metallothionein on oral squamous cell carcinoma.

    PubMed

    Cardoso, Sérgio V; Barbosa, Hugo M; Candellori, Ignez M; Loyola, Adriano M; Aguiar, Maria Cássia F

    2002-08-01

    Metallothionein (MT), a low-molecular-weight protein with high cysteine content, seems to be related to neoplastic resistance to oncologic treatment and therefore has been studied as a prognostic factor for a variety of human malignant tumors. MT overexpression in neoplasms of ectodermal origin is usually associated with a poor prognosis. MT expression was evaluated in 60 samples of oral squamous cell carcinoma by immunohistochemistry to study its prognostic influence on oral cancer. Possible associations of MT immunoexpression were also investigated with respect to clinical stage (TNM), histological grading, and proliferation index (Ki-67) of the lesions. No significant statistical correlation was observed among these variables. The impact on overall survival was assessed by uni and multivariate statistical tests. Mean MT labeling index was 60%. High MT labeling indexes (over 76%) predicted shorter survival in univariate statistical analysis. In multivariate analysis, MT labeling index and clinical stage were independent prognostic factors. MT overexpression in oral squamous cell carcinoma seems to be related to a worse prognosis for patients.

  1. GLUT-1 Expression in Cutaneous Basal and Squamous Cell Carcinomas.

    PubMed

    Abdou, Asmaa Gaber; Eldien, Marwa Mohammad Serag; Elsakka, Daliah

    2015-09-01

    Glucose uptake is a key regulating step in glucose metabolism and is mediated by facilitative glucose transporters (GLUTs), and GLUT-1 is the predominant glucose transporter in many types of human cells. Cutaneous basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) represent the most common skin cancer in Egypt. The present study aimed at evaluation of the pattern and distribution of GLUT-1 in cutaneous BCC (16 cases) and SCC (16 cases) by means of immunohistochemistry. GLUT-1 was expressed in all SCC (100%) and in 62.5% of BCC. Membranous pattern of GLUT-1 was seen in 62.5% of SCC and 31.25% of BCC. Positivity (P = .02) and percentage (P = .000) of GLUT-1 expression were in favor of SCC in comparison to BCC. The high percentage of GLUT-1 expression was associated with high grade in SCC (P = .03). The immunoreactivity for GLUT-1 was more in the periphery of malignant nests of SCC while it was more in the center of BCC nests. GLUT-1 is overexpressed in cutaneous non-melanoma skin cancer. Its expression in SCC is related to differentiation status, and its expression in BCC is intimately associated with squamous metaplastic areas.

  2. Estimation of salivary sialic acid in oral premalignancy and oral squamous cell carcinoma

    PubMed Central

    Chaudhari, Vishakha; Pradeep, G. L.; Prakash, Nilima; Mahajan, Aarti M.

    2016-01-01

    Aims: Oral cancer is the most life-threatening disease of oral tissues. In societies where the incidence of oral cancer is high, clinically recognizable premalignant lesions are particularly common. Diagnosing oral cancers at an early stage is critical in improving the survival rate and reducing the morbidity associated with the disease. Alterations in the sialic acid levels in cancer patients have stimulated interest in this sugar residue as a possible tumor marker. Settings and Design: The purpose of this study was to estimate the salivary sialic acid levels in patients with oral premalignancy and squamous cell carcinoma and to correlate it with their grades to develop a cost-effective and noninvasive diagnostic parameter. Materials and Methods: Unstimulated whole saliva was collected from the groups under study and subjected to biochemical analysis for determination of sialic acid levels. Statistical Analysis Used: The salivary sialic acid levels were correlated with the clinical stage and histological grade by one-way ANOVA (SPSS software version 15). Results: Salivary sialic acid was elevated in oral squamous cell carcinoma (OSCC) compared to oral premalignancy and control group. A statistically significant correlation was observed between the grades of squamous cell carcinoma, grades of dysplasia in premalignancy, and sialic acid level. Conclusion and Clinical Significance: Evaluation of salivary sialic acid levels in premalignant and malignant lesions can serve as a screening tool. The mortality and morbidity of OSCC can be reduced if the lesions are diagnosed in early precancerous states using such noninvasive diagnostic methods for screening and monitoring of the population. PMID:27994410

  3. 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

  4. ERBB2 mutations associated with solid variant of high-grade invasive lobular breast carcinomas

    PubMed Central

    Bidard, François-Clément; Vacher, Sophie; Schnitzler, Anne; Chemlali, Walid; Trémoulet, Laurence; Fuhrmann, Laetitia; Cottu, Paul; Rouzier, Roman; Bièche, Ivan; Vincent-Salomon, Anne

    2016-01-01

    ERBB2 and ERBB3 somatic gain-of-function mutations, which may be targeted by anti-ERBB2 therapies, were reported by high-throughput sequencing studies in 1% and 2% of invasive breast cancers respectively. Our study aims to determine ERBB2 and ERBB3 mutations frequencies in grade 3 and/or ERBB2-positive invasive lobular breast carcinomas (ILC). All the 529 ILC surgically-excised registered at Institut Curie in the years 2005 to 2008 were reviewed. Thirty-nine grade 3 ERBB2-negative ILC and 16 ERBB2-positive ILC were retrieved and subjected to Sanger sequencing of the ERBB2 and ERBB3 activation mutation hotspots (ERBB2: exons 8, 17, 19, 20, 21; ERBB3: exons 3, 6, 7, 8). Among the 39 grade 3 ERBB2-negative ILC, six tumors were found to have at least one detectable ERBB2 activating mutation (incidence rate: 15%, 95%CI [4%-27%]). No ERBB2 mutation was found among the 16 ERBB2-positive ILC. No ERBB3 mutation was found in any of the 55 ILC. ERBB2 mutations were statistically associated with solid ILC features (p=0.01). Survival analyses showed no significant prognostic impact of ERBB2 mutations. Our study demonstrates that high grade ERBB2-negative ILC display a high frequency of ERBB2 mutations, and should be subjected to systematic genetic screening. PMID:27602491

  5. Declining rates of high-grade cervical lesions in young women in Connecticut, 2008-2011.

    PubMed

    Niccolai, Linda M; Julian, Pamela J; Meek, James I; McBride, Vanessa; Hadler, James L; Sosa, Lynn E

    2013-08-01

    Vaccines that prevent infection with human papillomavirus (HPV) types 16 and 18 that are known to cause cervical cancer have been available in the United States since 2006. High-grade cervical lesions are important for monitoring early vaccine impact because they are strong surrogates for cancer yet can develop within years after infection as opposed to decades. Trends in high-grade cervical lesions including cervical intraepithelial neoplasia grades 2, 2/3, and 3 and adenocarcinoma in situ among women ages 21 to 39 years old were examined using a statewide surveillance registry in Connecticut from 2008 to 2011. During this time period, HPV vaccine initiation increased among adolescent females from 45% to 61%. Analyses were stratified by age, according to census tract measures of proportion of population Black, Hispanic, living in poverty, and by urban/nonurban counties. The annual rate per 100,000 females ages 21 to 24 years declined from 834 in 2008 to 688 in 2011 (P(trend) < 0.001). No significant declines were observed among women ages 25 to 39 years. Significant declining trends also occurred in census tracts with lower proportions of the population being Black, Hispanic, or living below the federal poverty level. Declines in high-grade cervical lesions have occurred among young women during 2008 to 2011. This is the first report of declines in cervical neoplasia in the United States since HPV vaccines became available. Continued surveillance is needed to measure vaccine impact and monitor health disparities.

  6. CEUS in the differentiation between low and high-grade bladder carcinoma

    PubMed Central

    Drudi, F.M.; Di Leo, N.; Malpassini, F.; Antonini, F.; Corongiu, E.; Iori, F.

    2012-01-01

    Introduction Bladder cancer ranks 4th overall in the number of newly diagnosed cancers and 10th in causes of cancer deaths. More than 90% of all cases of bladder cancer are transitional cell carcinoma (TCC). The goal of this study is to confirm the usefulness of low mechanical index contrast-enhanced ultrasonography (CEUS), also in association with time–intensity curves, in the differentiation between high- and low-grade bladder malignant lesions. Materials and methods From February 2006 to February 2012 we recruited 144 patients. All patients underwent grayscale ultrasonography (US), color-Doppler ultrasonography (CDUS) and contrast-enhanced ultrasonography (CEUS). Subsequently all patients underwent cystoscopy and TURB. Results Histological diagnoses were: 88 high-grade carcinomas (61.1%), and 56 low-grade carcinomas (38.9%). Sensitivity and specificity of CDUS were 87.5% (126/144) and 60%, respectively. Sensitivity and specificity of CEUS were 90.9% and 85.7%, respectively. Sensitivity and specificity of TIC were 91.6% (132/144) and 85.7%, respectively. Discussion and conclusions CEUS is a reliable noninvasive method for differentiating low- and high-grade bladder carcinomas since it provides typical enhancement patterns as well as specific contrast-sonographic perfusion curves. PMID:23730389

  7. Cancer stem cell, cytokeratins and epithelial to mesenchymal transition markers expression in oral squamous cell carcinoma derived from ortothopic xenoimplantation of CD44(high) cells.

    PubMed

    de Andrade, Nathália Paiva; Rodrigues, Maria Fernanda Setúbal Destro; Rodini, Camila Oliveira; Nunes, Fabio Daumas

    2017-03-01

    Oral squamous cell carcinoma (OSCC) is the most prevalent neoplasia of oral cavity worldwide and prognosis remains unchanged in decades. Recently, different authors reported that head and neck squamous cell carcinomas have a subpopulation of tumor initiating cells that apparently correspond to cancer stem cells (CSC) and are also responsible for tumor growth and metastasis. The purpose of the present study was to investigate the microscopic and phenotypic characteristics of OSCC tumors induced after orthotopic xenoimplantation of SCC9(WT) cell line and CSC-enriched subpopulation isolated from SCC9 cell line based on high expression of the putative CSC marker CD44. Different numbers of FACS-sorted SCC9 CD44(high) and CD44(low) cells as well as SCC9(WT) (wild type) were transplanted into the tongue of BALB/C nude (NOD/SCID) mice to evaluate their tumorigenic potential. Sixty days post-induction, tumors were morphologically characterized and immunostained for CSC markers (CD44, Nanog and Bmi-1), epithelial-mesenchymal transition (Snail, Slug) and epithelial differentiating cell markers (cytokeratins 4, 13, 15, 17 and 19), as well as E-cadherin and β-catenin. The data presented here shows that SCC9 CD44(high) cells have higher ability to form tumors than SCC9 CD44(low) cells, even when significantly lower numbers of SCC9 CD44(high) cells were transplanted. Immunoassessment of tumors derived from SCC9 CD44(high) cells revealed high expression of cytokeratin CK19, β-catenin, E-cadherin and CD44, and negative or low expression of CK17, CK4, CK15, CK13, Nanog, Bmi-1, Snail and Slug. While tumors derived from SCC9(WT) showed high expression of CK17, CK19, CD44, Nanog, Bmi-1, Snail and Slug, and negative or low expression of CK4, CK15, CK13, β-catenin and E-cadherin. Thus, SCC9 CD44(high) cells were highly tumorigenic, capable of originating heterogeneous tumors and these tumors have a immunohistochemical profile different from those formed by the wild type cell line.

  8. Advances in the management of cutaneous squamous cell carcinoma

    PubMed Central

    Parikh, Sonal A.

    2014-01-01

    Cutaneous squamous cell carcinoma is one of the most common non-melanoma skin cancers worldwide. While most cutaneous squamous cell carcinomas are easily managed, there is a high-risk subset of tumors that can cause severe morbidity and mortality. Tumor characteristics as well as patient characteristics contribute to the classification of cutaneous squamous cell carcinomas as low-risk vs. high-risk. Advances in the treatment of cutaneous squamous cell carcinomas largely relate to the management of this high-risk subset. Surgical and non-surgical management options, including newer targeted molecular therapies, will be discussed here. Larger, multicenter studies are needed to determine the exact significance of individual risk factors with respect to aggressive clinical behavior and the risks of metastasis and death, as well as the role of surgical and adjuvant therapies in patients with high-risk cutaneous squamous cell carcinomas. PMID:25165569

  9. Use of the HPV MLPA assay in cervical cytology for the prediction of high grade lesions.

    PubMed

    Litjens, Rogier J N T M; Theelen, Wendy; van de Pas, Yvonne; Ossel, Jessica; Reijans, Martin; Simons, Guus; Speel, Ernst-Jan M; Slangen, Brigitte F M; Ramaekers, Frans C S; Kruitwagen, Roy F P M; Hopman, Anton H N

    2013-08-01

    Current screening methods for uterine cervical cancer such as Papanicolaou smears and/or high risk human Papillomavirus (HR-HPV) detection have a high negative predictive value but a low positive predictive value for the presence of high grade cervical lesions. Therefore, new parameters are needed to reduce the rate of unnecessary referrals for colposcopy. The predictive value of the HPV multiplex ligation-dependent probe amplification (MLPA) assay, which can assess simultaneously HPV16/18 viral load and viral integration, was evaluated. The assay was applied to 170 cervical cytological samples, and the results were correlated with the matching histological follow-up. The GP5+/6+ assay and qPCR were used as a control for HR-HPV typing. The MLPA assay classified a higher percentage of cases as high-risk (high-viral load and/or viral integration) with higher grades of dysplasia. There was a high correlation between the HPV MLPA assay and qPCR for viral load and HPV genotyping, and between the MLPA assay and the GP5+/6+ assay for HPV genotyping. The sensitivity and specificity of the HPV MLPA assay for the detection of high-grade lesions were 44% and 93%, respectively. This study demonstrates that the HPV MLPA assay can reliably detect HPV 16/18, viral load, and viral integration in cytological samples. Also, high-risk classification correlated well with the presence of high-grade dysplasia. However, for the implementation of the MLPA assay into clinical practice, additional HR-HPV types need to be included to increase the sensitivity of the assay, and thereby increase its negative predictive value.

  10. Feasibility of Using Bevacizumab With Radiation Therapy and Temozolomide in Newly Diagnosed High-Grade Glioma

    SciTech Connect

    Narayana, Ashwatha Golfinos, John G.; Fischer, Ingeborg; Raza, Shahzad; Kelly, Patrick M.D.; Parker, Erik; Knopp, Edmond A.; Medabalmi, Praveen; Zagzag, David; Eagan, Patricia; Gruber, Michael L.

    2008-10-01

    Introduction: Bevacizumab, a monoclonal antibody against vascular endothelial growth factor (VEGF), has shown promise in the treatment of patients with recurrent high-grade glioma. The purpose of this study is to test the feasibility of using bevacizumab with chemoradiation in the primary management of high-grade glioma. Methods and Materials: Fifteen patients with high-grade glioma were treated with involved field radiation therapy to a dose of 59.4 Gy at 1.8 Gy/fraction with bevacizumab 10 mg/kg on Days 14 and 28 and temozolomide 75 mg/m{sup 2}. Subsequently, bevacizumab 10 mg/kg was continued every 2 weeks with temozolomide 150 mg/m{sup 2} for 12 months. Changes in relative cerebral blood volume, perfusion-permeability index, and tumor volume measurement were measured to assess the therapeutic response. Immunohistochemistry for phosphorylated VEGF receptor 2 (pVEGFR2) was performed. Results: Thirteen patients (86.6%) completed the planned bevacizumab and chemoradiation therapy. Four Grade III/IV nonhematologic toxicities were seen. Radiographic responses were noted in 13 of 14 assessable patients (92.8%). The pVEGFR2 staining was seen in 7 of 8 patients (87.5%) at the time of initial diagnosis. Six patients have experienced relapse, 3 at the primary site and 3 as diffuse disease. One patient showed loss of pVEGFR2 expression at relapse. One-year progression-free survival and overall survival rates were 59.3% and 86.7%, respectively. Conclusion: Use of antiangiogenic therapy with radiation and temozolomide in the primary management of high-grade glioma is feasible. Perfusion imaging with relative cerebral blood volume, perfusion-permeability index, and pVEGFR2 expression may be used as a potential predictor of therapeutic response. Toxicities and patterns of relapse need to be monitored closely.

  11. Highly Transparent Compositionally Graded Buffers for New Metamorphic Multijunction Solar Cell Designs

    SciTech Connect

    Schulte, Kevin L.; France, Ryan M.; Geisz, John F.

    2017-01-01

    The development of compositionally graded buffer layers (CGBs) with enhanced transparency would enable novel five and six junction solar cells, with efficiencies approaching 50% under high concentration. We demonstrate highly transparent grades between the GaAs and InP lattice constants on both A- and B-miscut GaAs substrates, employing AlxGayIn1-x-yAs and highly Se-doped Burstein-Moss (BM) shifted GaxIn 1-xP. Transparency to >810 and >890 nm wavelengths is demonstrated with BM-shifted GaxIn1-xP on B-miscut substrates and AlxGayIn1-x-yAs/GaxIn1-xP(Se) combined grades on A-miscut substrates, respectively. 0.74 eV GaInAs solar cells grown on these transparent CGBs exhibit Woc = 0.41 V at mA/ cm2, performance comparable with the state-of-the-art GaxIn1-xP grade employed in the four-junction-inverted metamorphic multijunction (IMM) cell. A GaAs/0.74cV GaInAs tandem cell was grown with a transparent BM-shifted GaxIn1-xP CGB to verify the CGB performance in a multijunction device structure. Quantum efficiency measurements indicate that the CGB is completely transparent to photons below the GaAs bandedge, validating its use in 4-6 junction IMM devices with a single-graded buffer. This tandem represents a highly efficient two-junction band gap combination, achieving 29.6% +/- 1.2% efficiency under the AM1.5 global spectrum, demonstrating how the additional transparency enables new device structures.

  12. Early hepatocellular carcinoma with high-grade atypia in small vaguely nodular lesions.

    PubMed

    Ojima, Hidenori; Masugi, Yohei; Tsujikawa, Hanako; Emoto, Katsura; Fujii-Nishimura, Yoko; Hatano, Mami; Kawaida, Miho; Itano, Osamu; Kitagawa, Yuko; Sakamoto, Michiie

    2016-04-01

    Multistep hepatocarcinogenesis progresses from dysplastic nodules to early hepatocellular carcinoma (eHCC) and to advanced HCC. The aim of the present study was to investigate the detailed histopathological features of eHCC. We investigated 66 small vaguely nodular lesions resected from 40 patients. The degree of cellular and structural atypia and stromal invasion were assessed. The immunohistochemical expression of HCC-related markers adenylate cyclase-associated protein 2 (CAP2), heat shock protein 70 (HSP70), Bmi-1, CD34 and h-caldesmon were evaluated. Of the 66 nodules, 10 were diagnosed as low-grade dysplastic nodules (LGDN), 10 as high-grade dysplastic nodules (HGDN) and 46 as eHCC. Among the 46 eHCC, 18 nodules (39.1%) showed marked stromal invasion and/or the presence of the scirrhous component and were subclassified as high-grade eHCC (HGeHCC). The remaining 28 eHCC, which lacked these features, were subclassified as low-grade eHCC (LGeHCC) and were examined further. HGeHCC showed high levels of cellular and structural atypia and large tumor size. The immunohistochemical expression of CAP2 and the area of sinusoidal vascularization showed increases from LGDN to HGeHCC. The density of arterial tumor vessels was high in HGeHCC compared with other nodule types. Cluster analysis of these parameters subclassified 65 nodules into HGeHCC-dominant, LGeHCC and HGDN-dominant, and LGDN-dominant groups. These results indicate the increased malignant potential of HGeHCC and suggest that it is already a transitional stage to advanced HCC. We consider that our grading classification system may be valuable for considering treatment strategies for eHCC around 2 cm in diameter.

  13. Evaluating Nuclear Membrane Irregularity for the Classification of Cervical Squamous Epithelial Cells

    PubMed Central

    Tang, Jing Rui; Mat Isa, Nor Ashidi; Ch’ng, Ewe Seng

    2016-01-01

    Pap test involves searching of morphological changes in cervical squamous epithelial cells by pathologists or cytotechnologists to identify potential cancerous cells in the cervix. Nuclear membrane irregularity is one of the morphological changes of malignancy. This paper proposes two novel techniques for the evaluation of nuclear membrane irregularity. The first technique, namely, penalty-driven smoothing analysis, introduces different penalty values for nuclear membrane contour with different degrees of irregularity. The second technique, which can be subdivided into mean- or median-type residual-based analysis, computes the number of points of nuclear membrane contour that deviates from the mean or median of the nuclear membrane contour. Performance of the proposed techniques was compared to three state-of-the-art techniques, namely, radial asymmetric, shape factor, and rim difference. Friedman and post hoc tests using Holm, Shaffer, and Bergmann procedures returned significant differences for all the three classes, i.e., negative for intraepithelial lesion or malignancy (NILM) versus low grade squamous intraepithelial lesion (LSIL), NILM versus high grade squamous intraepithelial lesion (HSIL), and LSIL versus HSIL when the span value equaled 3 was employed with linear penalty function. When span values equaled 5, 7, and 9, NILM versus LSIL and HSIL showed significant differences regardless of the penalty functions. In addition, the results of penalty-driven smoothing analysis were comparable with those of other state-of-the-art techniques. Residual-based analysis returned significant differences for the comparison among the three diagnostic classes. Findings of this study proved the significance of nuclear membrane irregularity as one of the features to differentiate the different diagnostic classes of cervical squamous epithelial cells. PMID:27741266

  14. Oral Microbiota and Risk for Esophageal Squamous Cell Carcinoma in a High-Risk Area of China.

    PubMed

    Chen, Xingdong; Winckler, Björn; Lu, Ming; Cheng, Hongwei; Yuan, Ziyu; Yang, Yajun; Jin, Li; Ye, Weimin

    2015-01-01

    Poor oral health has been linked with an increased risk of esophageal squamous cell carcinoma (ESCC). We investigated whether alteration of oral microbiota is associated with ESCC risk. Fasting saliva samples were collected from 87 incident and histopathologicallly diagnosed ESCC cases, 63 subjects with dysplasia and 85 healthy controls. All subjects were also interviewed with a questionnaire. V3-V4 region of 16S rRNA was amplified and sequenced by 454-pyrosequencing platform. Carriage of each genus was compared by means of multivariate-adjusted odds ratios derived from logistic regression model. Relative abundance was compared using Metastats method. Beta diversity was estimated using Unifrac and weighted Unifrac distances. Principal coordinate analysis (PCoA) was applied to ordinate dissimilarity matrices. Multinomial logistic regression was used to compare the coordinates between different groups. ESCC subjects had an overall decreased microbial diversity compared to control and dysplasia subjects (P<0.001). Decreased carriage of genera Lautropia, Bulleidia, Catonella, Corynebacterium, Moryella, Peptococcus and Cardiobacterium were found in ESCC subjects compared to non-ESCC subjects. Multinomial logistic regression analyses on PCoA coordinates also revealed that ESCC subjects had significantly different levels for several coordinates compared to non-ESCC subjects. In conclusion, we observed a correlation between altered salivary bacterial microbiota and ESCC risk. The results of our study on the saliva microbiome are of particular interest as it reflects the shift in microbial communities. Further studies are warranted to verify this finding, and if being verified, to explore the underlying mechanisms.

  15. HER2 over-expressing high grade endometrial cancer expresses high levels of p95HER2 variant

    PubMed Central

    Growdon, Whitfield B.; Groeneweg, Jolijn; Byron, Virginia; DiGloria, Celeste; Borger, Darrell R.; Tambouret, Rosemary; Foster, Rosemary; Chenna, Ahmed; Sperinde, Jeff; Winslow, John; Rueda, Bo R.

    2015-01-01

    Background Subsets of high grade endometrial cancer (EnCa) over-express HER2 (ERBB2), yet clinical trials have failed to demonstrate any anti-tumor activity utilizing trastuzumab, an approved platform for HER2 positive breast cancer (BrCa). A truncated p95HER2 variant lacking the trastuzumab binding site may confer resistance. The objective of this investigation was to characterize the expression of the p95HER2 truncated variant in EnCa. Materials and Methods With institutional approval, 86 high grade EnCa tumors were identified with tumor specimens from surgeries performed between 2000-2011. Clinical data were collected and all specimens underwent tumor genotyping, HER2 immunohistochemistry (IHC, HercepTest®), HER2 fluorescent in situ hybridization (FISH), along with total HER2 (H2T) and p95HER2 assessment with VeraTag® testing. Regression models were used to compare a cohort of 86 breast tumors selected for equivalent HER2 protein expression. Results We identified 44 high grade endometrioid and 42 uterine serous carcinomas (USC). IHC identified high HER2 expression (2+ or 3+) in 59% of the tumors. HER2 gene amplification was observed in 16 tumors (12 USC, 4 endometrioid). Both HER2 gene amplification and protein expression correlated with H2T values. High p95HER2 expression above 2.8 RF/mm2 was observed in 53% (n = 54) with significant correlation with H2T levels. When matched to a cohort of 107 breast tumors based on HercepTest HER2 expression, high grade EnCa presented with higher p95 levels (p < 0.001). Conclusions: These data demonstrate that compared to BrCa, high grade EnCa expresses higher levels of p95HER2 possibly providing rationale for the trastuzumab resistance observed in EnCa. PMID:25602714

  16. Body mass index, serum total cholesterol, and risk of gastric high-grade dysplasia

    PubMed Central

    Huang, Ya-Kai; Kang, Wei-Ming; Ma, Zhi-Qiang; Liu, Yu-Qin; Zhou, Li; Yu, Jian-Chun

    2016-01-01

    Abstract Obesity is related to an increased risk of gastric cardia cancer. However, the influences of excess body weight and serum total cholesterol on the risk of gastric high-grade dysplasia have not been fully characterized. A case–control study was conducted to explore the relationships between body mass index (BMI), serum total cholesterol level, and the risk of gastric high-grade dysplasia in Chinese adults. A total of 893 consecutive patients with gastric high-grade dysplasia (537 men and 356 women) and 902 controls (543 men and 359 women) were enrolled from January 2000 to October 2015. Odds ratios (ORs) with 95% confidence intervals (CIs) were estimated, and a multivariate analysis was conducted. After adjusting for age, alcohol consumption, smoking status, family history of gastric cancer or esophageal cancer, and serum total cholesterol level, a BMI ranging from 27.5 to 29.9 was significantly related to an increased risk of gastric high-grade dysplasia in both men (adjusted OR = 1.87, 95% CI = 1.24–2.81) and women (adjusted OR = 2.72, 95% CI = 1.44–5.16). The 2 highest BMI categories (27.5–29.9 and ≥30.0) were identified as risk factors for gastric cardia high-grade dysplasia in both men (BMI = 27.5–29.9: adjusted OR = 1.78, 95% CI = 1.02–3.10; BMI ≥ 30.0: adjusted OR = 2.54, 95% CI = 1.27–5.08) and women (BMI = 27.5–29.9: adjusted OR = 2.88, 95% CI = 1.27–6.55; BMI ≥ 30.0: adjusted OR = 2.77, 95% CI = 1.36–5.64), whereas only a BMI ranging from 27.5 to 29.9 was a risk factor for gastric noncardia high-grade dysplasia in both men (adjusted OR = 1.98, 95% CI = 1.25–3.14) and women (adjusted OR = 2.88, 95% CI = 1.43–5.81). In addition, higher serum total cholesterol was associated with an increased risk of gastric noncardia high-grade dysplasia (adjusted OR = 1.83, 95% CI = 1.25–2.69) in women. Increased BMI was associated with an increased risk

  17. Verrucoid Variant of Invasive Squamous Cell Carcinoma in Oral Submucous Fibrosis: A Clinicopathological Challenge

    PubMed Central

    Ramani, Priya; Krithika, C.; Ananthalakshmi, R.; Jagdish, Praveena; Janardhanan, Sunitha; Jeevakarunyam, Sathiyajeeva

    2016-01-01

    Verrucous carcinoma (VC) is an exophytic, low-grade, well-differentiated variant of squamous cell carcinoma. It is described as a lesion appearing in the sixth or seventh decade of life that has minimal aggressive potential and, in long-standing cases, has been shown to transform into squamous cell carcinoma. Oral submucous fibrosis (OSMF) is a potentially malignant disorder, and about one-third of the affected population develop oral squamous cell carcinoma. The histopathological diagnosis of verrucous carcinoma is challenging, and the interpretation of early squamous cell carcinoma requires immense experience. Here we present a rare case of a 24-year-old male with OSMF transforming to verrucous carcinoma with invasive squamous cell carcinoma. Even though the case had a straightforward clinical diagnosis, the serial sectioning done for pathological diagnosis disclosed the squamous cell carcinoma.

  18. Squamous cell carcinoma of the extremities

    SciTech Connect

    Lifeso, R.M.; Bull, C.A.

    1985-06-15

    Between January 1976 and January 1983, 37 cases of squamous cell carcinoma of the extremities have been treated at the King Faisal Specialist Hospital and Research Centre by the authors. Each case has arisen in an area of preexisting scar or sinus. Twenty-nine cases were treated by definitive amputation, with 2 local recurrences and 12 nodal metastases. Seven cases had local excision, with three local recurrences and two nodal metastases. Recurrence rate was highest in Grade II and Grade III lesions, and 11 of 15 cases with Grade II disease had metastases to the regional lymph nodes an average of 5 months after surgery. With Grade I disease patients, 4 of 15 had nodal metastases an average of 5 months after surgery. Prophylactic regional nodal irradiation or node dissection was performed in seven cases. None of these cases have shown nodal metastases at an average of 24 months following definitive surgery and radiation. Routine prophylactic regional node irradiation is recommended in all cases of peripheral squamous cell carcinoma.

  19. p21WAF1/Cip1 expression is associated with cell differentiation but not with p53 mutations in squamous cell carcinomas of the larynx.

    PubMed

    Nadal, A; Jares, P; Cazorla, M; Fernández, P L; Sanjuan, X; Hernandez, L; Pinyol, M; Aldea, M; Mallofré, C; Muntané, J; Traserra, J; Campo, E; Cardesa, A

    1997-10-01

    p21WAF1/Cip1 is a recently identified gene involved in cell cycle regulation through cyclin-CDK-complex inhibition. The expression of this gene in several cell lines seems to be induced by wild-type, but not mutant, p53. p21WAF1/Cip1 expression has been studied at both mRNA and protein levels in a series of 49 normal mucosae and squamous cell carcinomas of the larynx. A significant association was found between mRNA and protein expression in tumours (P < 0.0001). p21WAF1/Cip1 expression was strongly associated with squamous cell differentiation of carcinomas, because six of seven (86 per cent) undifferentiated carcinomas (grade 4) showed very low levels of p21WAF1/Cip1 expression, whereas 41 out of 42 (98 per cent) carcinomas with squamous cell differentiation (grades 1-3) had normal or high levels of p21WAF1/Cip1 expression (P < 0.0001). In addition, p21WAF1/Cip1 expression was topologically related to the squamous differentiation of tumour cells with a distribution similar to that seen in normal squamous epithelium. No correlation was found between p21WAF1/Cip1 expression and the global S-phase of the carcinomas. p53 mutations (exons 5-9) were found in ten carcinomas with p21WAF1/Cip1 expression, but no p53 mutations were detected in three p21WAF1/Cip1-negative tumours. In conclusion, p21WAF1/Cip1 expression is frequently upregulated in squamous cell carcinomas of the larynx and is associated with tumour cell differentiation. p21WAF1/Cip1 expression in these tumours is independent of p53 gene mutations.

  20. Analysis of pulmonary nodules in patients with high-grade soft tissue sarcomas

    PubMed Central

    Matsumine, Akihiko; Matsusaka, Miki; Mizumoto, Keitaro; Mori, Mayuko; Yoshizaki, Tomoya; Matsubara, Takao; Asanuma, Kunihiro; Sudo, Akihiro

    2017-01-01

    Nowadays, small pulmonary nodules are easily detectable in patients with soft tissue sarcomas (STSs) because of highly improved computed tomography (CT) technologies. The purpose of this study was to determine the frequency and significance of the pulmonary nodules detected by CT in high-grade STS patients. 124 patients with high-grade STS were retrospectively reviewed. There were 72 males (57%) and 52 females (43%). Patients’ average age was 61 years (median (quartiles) 66 years (48–75), range 8–94 years). Pulmonary nodules were detected in 49 (39.5%) of 124 patients by CT scanning at first presentation. Of 49 patients with nodules at first presentation, 34 (69.4%) had benign lesions, and 13 (26.5%) had metastatic nodules. One patient (2%) had primary lung cancer and the remaining one with one nodule could not be definitively diagnosed due to a short follow-up time. 30 patients (24.1%) of 124 patients developed pulmonary nodules during their clinical progression. Seven (23.3%) had benign lesions, whereas 21 (70%) had metastatic lesions. Primary lung cancer was detected in two patients (6.7%). The size and timing of detection of a pulmonary nodule significantly affected the final clinical diagnosisby multivariate analysis. We conclude that pulmonary nodules can be detected highly frequently in patients with high-grade STSs because of improved CT technologies. Careful follow-up is needed if nodules are detected after initial treatment or during the clinical course of the disease. PMID:28182790

  1. Cilengitide in Treating Younger Patients With Recurrent or Progressive High-Grade Glioma That Has Not Responded to Standard Therapy

    ClinicalTrials.gov

    2014-05-05

    Childhood High-grade Cerebellar Astrocytoma; Childhood High-grade Cerebral Astrocytoma; Recurrent Childhood Anaplastic Astrocytoma; Recurrent Childhood Anaplastic Oligoastrocytoma; Recurrent Childhood Anaplastic Oligodendroglioma; Recurrent Childhood Brain Tumor; Recurrent Childhood Cerebellar Astrocytoma; Recurrent Childhood Cerebral Astrocytoma; Recurrent Childhood Glioblastoma; Recurrent Childhood Visual Pathway and Hypothalamic Glioma

  2. The Relationship of Mental Pressure with Optimism and Academic Achievement Motivation among Second Grade Male High School Students

    ERIC Educational Resources Information Center

    Sarouni, Ali Sedigh; Jenaabadi, Hossein; Pourghaz, Abdulwahab

    2016-01-01

    The present study aimed to examine the relationship of mental pressure with optimism and academic achievement motivation among second grade second period male high school students. This study followed a descriptive-correlational method. The sample included 200 second grade second period male high school students in Sooran. Data collection tools in…

  3. The Relative Predictive Validity of ACT Scores and High School Grades in Making College Admission Decisions. Issues in College Success

    ERIC Educational Resources Information Center

    ACT, Inc., 2008

    2008-01-01

    Postsecondary institutions often consider students' high school grades and ACT scores when making admission decisions. This issue brief summarizes ACT research on the relative weights of ACT scores and high school grades for predicting college persistence as well as selected indicators of academic success in college. (Contains 1 table and 3…

  4. The Effect of Conceptual Change Approach to Eliminate 9th Grade High School Students' Misconceptions about Air Pressure

    ERIC Educational Resources Information Center

    Akbas, Yavuz; Gencturk, Ebru

    2011-01-01

    The aim of this study was to determine the effectiveness of teaching based on conceptual change overcome misconceptions of 9th grade high school students about the subject of air pressure. The sampling of the study was formed with two classes of 9th grade students from a general high school in the city-center of Trabzon. A quasi-experimental…

  5. Increased SNAIL expression and low syndecan levels are associated with high Gleason grade in prostate cancer

    PubMed Central

    POBLETE, CRISTIAN E.; FULLA, JUAN; GALLARDO, MARCELA; MUÑOZ, VALENTINA; CASTELLÓN, ENRIQUE A.; GALLEGOS, IVAN; CONTRERAS, HECTOR R.

    2014-01-01

    Prostate cancer (PC) is a leading male oncologic malignancy wideworld. During malignant transformation, normal epithelial cells undergo genetic and morphological changes known as epithelial-mesenchymal transition (EMT). Several regulatory genes and specific marker proteins are involved in PC EMT. Recently, syndecans have been associated with malignancy grade and Gleason score in PC. Considering that SNAIL is mainly a gene repressor increased in PC and that syndecan promoters have putative binding sites for this repressor, we propose that SNAIL might regulate syndecan expression during PC EMT. The aim of this study was to analyze immunochemically the expression of SNAIL, syndecans 1 and 2 and other EMT markers in a tissue microarray (TMA) of PC samples and PC cell lines. The TMAs included PC samples of different Gleason grade and benign prostatic hyperplasia (BPH) samples, as non-malignant controls. PC3 and LNCaP cell lines were used as models of PC representing different tumorigenic capacities. Semi-quantitative immunohistochemistry was performed on TMAs and fluorescence immunocytochemistry and western blot analysis were conducted on cell cultures. Results show that SNAIL exhibits increased expression in high Gleason specimens compared to low histological grade and BPH samples. Accordingly, PC3 cells show higher SNAIL expression levels compared to LNCaP cells. Conversely, syndecan 1, similarly to E-cadherin (a known marker of EMT), shows a decreased expression in high Gleason grades samples and PC3 cells. Interestingly, syndecan 2 shows no changes associated to histological grade. It is concluded that increased SNAIL levels in advanced PC are associated with low expression of syndecan 1. The mechanism by which SNAIL regulates the expression of syndecan 1 remains to be investigated. PMID:24424718

  6. Oral Microbiota and Risk for Esophageal Squamous Cell Carcinoma in a High-Risk Area of China

    PubMed Central

    Chen, Xingdong; Winckler, Björn; Lu, Ming; Cheng, Hongwei; Yuan, Ziyu; Yang, Yajun; Jin, Li; Ye, Weimin

    2015-01-01

    Poor oral health has been linked with an increased risk of esophageal squamous cell carcinoma (ESCC). We investigated whether alteration of oral microbiota is associated with ESCC risk. Fasting saliva samples were collected from 87 incident and histopathologicallly diagnosed ESCC cases, 63 subjects with dysplasia and 85 healthy controls. All subjects were also interviewed with a questionnaire. V3–V4 region of 16S rRNA was amplified and sequenced by 454-pyrosequencing platform. Carriage of each genus was compared by means of multivariate-adjusted odds ratios derived from logistic regression model. Relative abundance was compared using Metastats method. Beta diversity was estimated using Unifrac and weighted Unifrac distances. Principal coordinate analysis (PCoA) was applied to ordinate dissimilarity matrices. Multinomial logistic regression was used to compare the coordinates between different groups. ESCC subjects had an overall decreased microbial diversity compared to control and dysplasia subjects (P<0.001). Decreased carriage of genera Lautropia, Bulleidia, Catonella, Corynebacterium, Moryella, Peptococcus and Cardiobacterium were found in ESCC subjects compared to non-ESCC subjects. Multinomial logistic regression analyses on PCoA coordinates also revealed that ESCC subjects had significantly different levels for several coordinates compared to non-ESCC subjects. In conclusion, we observed a correlation between altered salivary bacterial microbiota and ESCC risk. The results of our study on the saliva microbiome are of particular interest as it reflects the shift in microbial communities. Further studies are warranted to verify this finding, and if being verified, to explore the underlying mechanisms. PMID:26641451

  7. Robotic surgery compared with laparotomy for high-grade endometrial cancer.

    PubMed

    Pant, Alok; Schink, Julian; Lurain, John

    2014-06-01

    High-grade endometrial cancer often presents with occult metastatic disease and this presentation pattern can be considered a contraindication to minimally invasive surgery. We sought to compare the surgical and oncologic outcomes of patients with high-grade endometrial cancer who underwent surgical management/staging via the robotic approach versus the traditional open approach. A retrospective analysis was performed of patients with high-grade endometrial cancer who were treated at a single institution from January 2008 through December 2011. High-grade endometrial histology was defined as FIGO grade 2 or 3 endometrioid, serous, clear cell or uterine carcinosarcoma. Pre-operatively, all patients had clinical stage I disease based on a combination of physical examination and imaging studies. Baseline patient demographics, operative results, complications and oncologic outcomes were analyzed. Eighty consecutive patients were included. Forty-seven patients underwent surgical management using the robotic approach and 33 patients underwent a traditional operation via laparotomy. The groups were well matched in terms of age, body mass index, medical co-morbidities, stage and histology. The average hospital stay for patients who underwent open surgery was significantly longer than for those who underwent a robotic approach [5.6 versus 1.4 days (p = 0.0001)]. Of the patients who underwent robotic surgery, 7/47 (15 %) experienced an operative complication versus 18/33 (55 %) in the open surgery cohort (p = 0.002). The average number of pelvic lymph nodes retrieved in each cohort was 12. The average number of para-aortic lymph nodes retrieved in each group was 4. On final pathologic analysis, 20 patients in the robotic surgery arm were found to have disease that had spread beyond the uterus (43 %), compared to 14 in the traditional surgery group (42 %). There were 11/47 (23 %) recurrences in the robotic surgery group during the study period, compared to 8/33 (24

  8. Nonlinear High-Energy Pulse Propagation in Graded-Index Multimode Optical Fibers for Mode-Locked Fiber Lasers

    DTIC Science & Technology

    2014-12-23

    High-Energy Pulse Propagation in Graded -Index Multimode Optical Fibers for Mode-Locked Fiber Lasers 5a. CONTRACT NUMBER 5b. GRANT NUMBER FA9550-12-1...integration of large-core graded -index multimode fibers (GIMFs) in ultrafast mode-locked fiber lasers to dramatically increase the pulse energy...optical fibers, graded -index multimode fibers, nonlinear switching, waveguides, mode-locked fiber lasers, ultra-short pulse fiber lasers 16. SECURITY

  9. Rare earth element patterns in Archean high-grade metasediments and their tectonic significance

    NASA Technical Reports Server (NTRS)

    Taylor, Stuart Ross; Rudnick, Roberta L.; Mclennan, Scott M.; Eriksson, Kenneth A.

    1986-01-01

    REE data on metasedimentary rocks from two different types of high-grade Archean terrains are presented and analyzed. The value of REEs as indicators of crustal evolution is explained; the three geologic settings (in North America, Southern Africa, and Australia) from which the samples were obtained are described; and the data are presented in extensive tables and graphs and discussed in terms of metamorphic effects, the role of accessory phases, provenance, and tectonic implications (recycling, the previous extent of high-grade terrains, and a model of Archean crustal growth). The diversity of REE patterns in shallow-shelf metasediments is attributed to local provenance, while the Eu-depleted post-Archean patterns are associated with K-rich plutons from small, stable early Archean terrains.

  10. Variation of Mechanical Properties of High RRR And Reactor Grade Niobium With Heat Treatments

    SciTech Connect

    Ganapati Myneni; H. Umezawa

    2003-06-01

    Superconducting rf cavities used as accelerating structures in particle accelerators are made from high purity niobium with residual resistance ratios greater than 250. Reactor grade niobium is also used to make wave-guide and/or end group components for these accelerating structures. The major impurities in this type of niobium are interstitially dissolved gases such as hydrogen, nitrogen, and oxygen in addition to carbon. After fabricating the niobium accelerating structures, they are subjected to heat treatments for several hours in vacuum at temperatures of up to 900 C for degassing hydrogen or up to 1400 C for improving the thermal conductivity of niobium considerably. These heat treatments are affecting the mechanical properties of niobium drastically. In this paper the variation of the mechanical properties of high purity and reactor grade niobium with heat treatments in a vacuum of {approx} 10{sup -6} Torr and temperatures from 600 C to 1250 C for periods of 10 to 6 hours are presented.

  11. Immunotherapy for high-grade glioma: how to go beyond Phase I/II clinical trials.

    PubMed

    van Gool, Stefaan

    2013-10-01

    Evaluation of: Lasky JL 3rd, Panosyan EH, Plant A et al. Autologous tumor lysate-pulsed dendritic cell immunotherapy for pediatric patients with newly diagnosed or recurrent high-grade gliomas. Anticancer Res. 33, 2047-2056 (2013). Immunotherapy for children and adults with high-grade glioma (HGG) is an emerging innovative treatment approach, which aims at stimulating the body's own immune system against HGG by using autologous dendritic cells pulsed with autologous tumor lysate as a therapeutic vaccine. This is the third report on immunotherapy for HGG in children, bringing additional knowledge and experience to the scientific community. However, at the same time, this and other manuscripts urge for the next step in treatment development.

  12. Forming high-efficiency silicon solar cells using density-graded anti-reflection surfaces

    DOEpatents

    Yuan, Hao-Chih; Branz, Howard M.; Page, Matthew R.

    2015-07-07

    A method (50) is provided for processing a graded-density AR silicon surface (14) to provide effective surface passivation. The method (50) includes positioning a substrate or wafer (12) with a silicon surface (14) in a reaction or processing chamber (42). The silicon surface (14) has been processed (52) to be an AR surface with a density gradient or region of black silicon. The method (50) continues with heating (54) the chamber (42) to a high temperature for both doping and surface passivation. The method (50) includes forming (58), with a dopant-containing precursor in contact with the silicon surface (14) of the substrate (12), an emitter junction (16) proximate to the silicon surface (14) by doping the substrate (12). The method (50) further includes, while the chamber is maintained at the high or raised temperature, forming (62) a passivation layer (19) on the graded-density silicon anti-reflection surface (14).

  13. A spontaneous high-grade undifferentiated mammary carcinoma in a seven-week-old female rat.

    PubMed

    Faustino-Rocha, Ana I; Gama, Adelina; Oliveira, Paula A; Alvarado, Antonieta; Ferreira, Rita; Ginja, Mário

    2017-02-01

    The present work describes a rare case of a spontaneous high-grade carcinoma in a seven-week-old Sprague-Dawley female rat that had been included in the control group of an assay of mammary carcinogenesis. The mass was detected at 50days of age, it grown quickly and the animal was humanely sacrificed eight days later. The tumor was located in the left cervical region, in the vicinity of the left submandibular and sublingual glands. It was soft and reddish and had several dens with a bloody content. The tumor was PAS negative and exhibited immunostaining for ER-α. The histopathologic and immunohistochemical data are suggestive of a high-grade carcinoma from mammary gland. It was the first report of a spontaneous mammary tumor in such a young rat.

  14. Forming high efficiency silicon solar cells using density-graded anti-reflection surfaces

    DOEpatents

    Yuan, Hao-Chih; Branz, Howard M.; Page, Matthew R.

    2014-09-09

    A method (50) is provided for processing a graded-density AR silicon surface (14) to provide effective surface passivation. The method (50) includes positioning a substrate or wafer (12) with a silicon surface (14) in a reaction or processing chamber (42). The silicon surface (14) has been processed (52) to be an AR surface with a density gradient or region of black silicon. The method (50) continues with heating (54) the chamber (42) to a high temperature for both doping and surface passivation. The method (50) includes forming (58), with a dopant-containing precursor in contact with the silicon surface (14) of the substrate (12), an emitter junction (16) proximate to the silicon surface (14) by doping the substrate (12). The method (50) further includes, while the chamber is maintained at the high or raised temperature, forming (62) a passivation layer (19) on the graded-density silicon anti-reflection surface (14).

  15. Variations of mitotic index in normal and dysplastic squamous epithelium of the uterine cervix as a function of endometrial maturation.

    PubMed

    Fadare, Oluwole; Yi, Xiaofang; Liang, Sharon X; Ma, Yanling; Zheng, Wenxin

    2007-09-01

    Cervical intraepithelial neoplasia is a premalignant (dysplastic) lesion that is characterized by abnormal cellular proliferation, maturation and nuclear atypia. The intraepithelial distribution, density, and nature (typical or atypical) of mitotic figures are routinely utilized diagnostic criteria to grade dysplasia and to distinguish high-grade dysplasia from potential histologic mimics such as transitional metaplasia, atrophy or immature squamous metaplasia. In this study, we evaluated the total mitotic indices of the cervical epithelia in hysterectomy specimens from patients with and without dysplastic lesions and investigated a possible relationship between mitotic index and hormonal status, using the endometrial maturation phase as a surrogate indicator of the latter. Two hundred seventy-four cervices from hysterectomy specimens (135 cases without dysplasia, 33, 35 and 71 cases with grades 1, 2 and 3 cervical intraepithelial neoplasia, respectively) were analyzed. A cervical mitotic index (total mitotic figures/10 high-power fields in the most proliferative area) was determined for each case. The endometrium in each case was classified into atrophic, early proliferative, late proliferative and secretory. For all three dysplasia grades, cases in the proliferative endometrium group always had a higher average mitotic index than those in the secretory and atrophic endometrium groups; this observation also held true for the benign cases. Furthermore, in all three dysplasia grades, the average mitotic index was always lowest in the atrophic endometrium group. Although the mitotic index showed expected patterns of increases with increasing dysplasia grades for most of the endometrial phases, this was not a universal finding. Notably, the average mitotic index for our cervical intraepithelial neoplasia 1 cases with late proliferative endometrium was higher than our cervical intraepithelial neoplasia 2 cases with secretory and atrophic endometrium. It is concluded

  16. Rethinking ovarian cancer II: reducing mortality from high-grade serous ovarian cancer

    PubMed Central

    Bowtell, David D.; Böhm, Steffen; Ahmed, Ahmed A.; Aspuria, Paul-Joseph; Bast, Robert C.; Beral, Valerie; Berek, Jonathan S.; Birrer, Michael J.; Blagden, Sarah; Bookman, Michael A.; Brenton, James; Chiappinelli, Katherine B.; Martins, Filipe Correia; Coukos, George; Drapkin, Ronny; Edmondson, Richard; Fotopoulou, Christina; Gabra, Hani; Galon, Jérôme; Gourley, Charlie; Heong, Valerie; Huntsman, David G.; Iwanicki, Marcin; Karlan, Beth Y.; Kaye, Allyson; Lengyel, Ernst; Levine, Douglas A.; Lu, Karen H.; McNeish, Iain A.; Menon, Usha; Narod, Steve A.; Nelson, Brad H.; Nephew, Kenneth P.; Pharoah, Paul; Powell, Daniel J.; Ramos, Pilar; Romero, Iris L.; Scott, Clare L.; Sood, Anil K.; Stronach, Euan A.; Balkwill, Frances R.

    2016-01-01

    High-grade serous ovarian cancer (HGSOC) accounts for 70-80% of ovarian cancer deaths, and overall survival has not changed significantly for several decades. In this Opinion article, we outline a set of research priorities that we believe will reduce incidence and improve outcomes for women with this disease. This ‘roadmap’ for HGSOC was determined after extensive discussions at an Ovarian Cancer Action meeting in January 2015. PMID:26493647

  17. Radiologic and Clinical Outcomes of Surgery in High Grade Spondylolisthesis Treated with Temporary Distraction Rod

    PubMed Central

    Hootkani, Alireza; Jarahi, Lida; Rezvan, Manizheh; Moayedpour, Amir

    2015-01-01

    Background Surgical techniques used in the treatment of patients with high grade lumbar spondylolisthesis (> 50% slippage) are usually associated with a great deal of controversies. We aim to evaluate the surgical outcomes of high grade spondylolisthesis treated with an intraoperative temporary distraction rod. Methods We retrospectively studied 21 patients (14 females and 7 males), aged 50.4 ± 9.2 years, who had high grade lumbar spondylolisthesis that was treated with intraoperative temporary distraction rods, neural decompression, pedicular screw fixation, and posterolateral fusion involving one more intact upper vertebra. The mean follow-up period was 39.2 months. Radiologic and clinical outcomes were measured by slip angle, slip percentage, correction rate, Oswestry Disability Index (ODI), visual analogue scale (VAS), patient's satisfaction rate in the pre- and postoperative period. Data were analyzed by SPSS ver. 11.5. Results Analysis of the preoperative visits and final follow-up visits indicated that surgery could improve ODI, lumbar VAS, and leg VAS from 60.5% to 8.2%, from 6.7 to 2.2, and from 6.9 to 1.3, respectively. Slip angle and slip percentage were also changed from -8° to -15° and from 59.2% to 21.4%, respectively. Mean correction rate at the final follow-up visit was 64.1%. Loss of correction was insignificant and a neurologic complication occurred in one patient due to misplacement of one screw. Excellent and good levels of satisfaction were observed in 90.5% of the patients. Conclusions In the surgical treatment of refractory high grade spondylolisthesis, the use of a temporary distraction rod to reduce the slipped vertebra in combination with neural decompression, posterolateral fusion, and longer instrumentation is associated with satisfactory clinical and radiologic outcomes. PMID:25729523

  18. 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

  19. Tumor Associated Tissue Eosinophilia in Oral Squamous Cell Carcinoma: A Histo-Chemical Analysis

    PubMed Central

    Sahni, Priya; Patel, Anil; Md, Shylaja; Hallur, Jayadeva; Gujjar, Pavan Kumar

    2015-01-01

    Background Tumor associated tissue eosinophilia (TATE) is believed to play a significant role in biological behavior of the carcinoma. Eosinophils are involved in immune reaction. Various studies have been carried out regarding their role in tumor progression or regulation. In oral squamous cell carcinoma (OSCC), eosinophils are associated with favourable or unfavourable prognosis and hence their role is yet unclear. To compare the tissue eosinophils in OSCC and normal tissue and to correlate the expression of TATE in different grades of OSCC. Method Study comprised 30 cases, 6 normal and 24 histopathologically diagnosed with OSCC. 4 micron thick sections were stained using 1% congo red solution. The sections were examined under high power (×40) and 10 consecutive microscopic fields were studied. The average number of eosinophils were statistically analysed. Results The tabulated results showed that the median value of tissue eosinophils, increased in OSCC compared to normal mucosa. Analysis on different grades of carcinoma showed a higher TATE in Well differentiated squamous cell carcinoma as compared to other grades. Conclusion The higher eosinophil count in OSCC compare to normal tissue might have a role in stromal invasion and infiltration. TATE can be used as an indicator of favourable prognosis in OSCC. PMID:28223881

  20. High expression of podoplanin in squamous cell carcinoma of the tongue occurs predominantly in patients ≤40 years but does not correlate with tumour spread

    PubMed Central

    Lindell Jonsson, Eva; Boldrup, Linda; Califano, Luigi; Coates, Philip J; Tartaro, Gianpaolo; Lo Muzio, Lorenzo; Fåhraeus, Robin; Colella, Giuseppe; Dell'Aversana Orabona, Giovanni; Loljung, Lotta; Santagata, Mario; Rossiello, Riccardo; Wilms, Torben; Danielsson, Karin; Laurell, Göran

    2015-01-01

    Abstract More than 30% of patients with squamous cell carcinoma (SCC) of the mobile tongue have clinically undetectable lymph node metastasis. Tumour cells can spread as single cells or collectively. A protein known to play a role in both processes is podoplanin, which is expressed in endothelial cells not only in lymph vessels but also in some aggressive tumours with high invasive and metastatic potential. Here we studied samples from 129 patients with primary SCC of the tongue for expression of podoplanin using immunohistochemistry. mRNA levels were analysed in another 27 cases of tongue SCC with adjacent clinically tumour‐free tongue tissue and 14 tongue samples from healthy donors. Higher levels of podoplanin were seen in tumours compared to both normal tongue and clinically normal tongue in the tumour vicinity. No association was found between levels of podoplanin, presence of lymph node metastases or other clinical factors. Patients aged 40 or less were more likely to express high levels of podoplanin protein compared to older patients (p = 0.027). We conclude that levels of podoplanin in primary tongue SCCs are not associated with lymph node metastases. However, tongue SCCs arising in young patients (≤40 years of age) are more likely to express high levels of podoplanin than tongue SCCs that arise in the more elderly. The data suggest that podoplanin has a distinctive role in young patients, who are known to have a poor prognosis: these patients may, therefore, benefit from podoplanin inhibitory therapies. PMID:27499910

  1. High expression of stathmin 1 is a strong prognostic marker in oral squamous cell carcinoma patients treated by docetaxel-containing regimens.

    PubMed

    Harada, Koji; Ferdous, Tarannum; Harada, Toyoko; Ueyama, Yoshiya

    2017-02-01

    Stathmin 1 is an oncoprotein that regulates cell cycle by modulating microtubule dynamics and can cause uncontrolled cell proliferation in mutated state. The present study examined stathmin 1 expression in 49 patients with oral squamous cell carcinoma (OSCC) treated with docetaxel (Doc)-containing regimens by immunohistochemical staining. Moreover, we investigated the relationship between stathmin 1 expression and clinicopathological features, as well as the prognosis of above patients. Stathmin 1 could be detected in the cytoplasm of tumor cells in OSCC tissues though its expression level was variable. There was no correlation between stathmin 1 expression and patient gender, or age in OSCC. However, stathmin 1 expression of tumor cell was significantly correlated with T classification (P = 0.0017), N classification (P = 0.0171), stage (P < 0.0001), therapeutic efficacy (P < 0.0001), and patient outcome (P = 0.0387). In addition, high expression of stathmin 1 in tumor cells was associated with shorter overall survival (OS, P = 0.0017). Multivariate analysis also revealed that high expression of stathmin 1 was a predictor of reduced survival (P = 0.0241). These findings suggest that patients with OSCC tumors showing high expression of stathmin 1 might have poor therapeutic effects and worse clinical outcomes in OSCC treated with Doc-containing regimen.

  2. High expression of podoplanin in squamous cell carcinoma of the tongue occurs predominantly in patients ≤40 years but does not correlate with tumour spread.

    PubMed

    Sgaramella, Nicola; Lindell Jonsson, Eva; Boldrup, Linda; Califano, Luigi; Coates, Philip J; Tartaro, Gianpaolo; Lo Muzio, Lorenzo; Fåhraeus, Robin; Colella, Giuseppe; Dell'Aversana Orabona, Giovanni; Loljung, Lotta; Santagata, Mario; Rossiello, Riccardo; Wilms, Torben; Danielsson, Karin; Laurell, Göran; Nylander, Karin

    2016-01-01

    More than 30% of patients with squamous cell carcinoma (SCC) of the mobile tongue have clinically undetectable lymph node metastasis. Tumour cells can spread as single cells or collectively. A protein known to play a role in both processes is podoplanin, which is expressed in endothelial cells not only in lymph vessels but also in some aggressive tumours with high invasive and metastatic potential. Here we studied samples from 129 patients with primary SCC of the tongue for expression of podoplanin using immunohistochemistry. mRNA levels were analysed in another 27 cases of tongue SCC with adjacent clinically tumour-free tongue tissue and 14 tongue samples from healthy donors. Higher levels of podoplanin were seen in tumours compared to both normal tongue and clinically normal tongue in the tumour vicinity. No association was found between levels of podoplanin, presence of lymph node metastases or other clinical factors. Patients aged 40 or less were more likely to express high levels of podoplanin protein compared to older patients (p = 0.027). We conclude that levels of podoplanin in primary tongue SCCs are not associated with lymph node metastases. However, tongue SCCs arising in young patients (≤40 years of age) are more likely to express high levels of podoplanin than tongue SCCs that arise in the more elderly. The data suggest that podoplanin has a distinctive role in young patients, who are known to have a poor prognosis: these patients may, therefore, benefit from podoplanin inhibitory therapies.

  3. Predicting College Grades and Degree Completion Using High School Grades and SAT Scores: The Role of Student Ethnicity and First Language

    ERIC Educational Resources Information Center

    Zwick, Rebecca; Sklar, Jeffrey C.

    2005-01-01

    The degree to which SAT scores and high school grade-point average (GPA) predicted first-year college GPA (FGPA) and college graduation was examined for four groups: Hispanic students whose first language was Spanish and Hispanic, Black, and White students whose first language was English. The percentage of variance in FGPA jointly explained by…

  4. Primary high grade sarcoma of the specialised prostatic stroma: a case report with clinico-pathological considerations.

    PubMed

    Fraggetta, F; Pepe, P; Giunta, M L; Aragona, F

    2008-12-01

    Malignant tumours of the prostate other than carcinomas are rare. One such malignant tumours arising from the specialised stromal tissue of the prostate is stromal prostatic sarcoma (namely low-grade and high-grade). Herein, we report the clinico-pathological features of a high grade stromal sarcoma of the prostate occurring in a 65-year-old man who presented for urinary obstructive symptoms. The clinical picture suggested a benign prostatic hyperplasia, and surgery consisting in a transcapsular adenomectomy was performed. Following a pathological diagnosis of high grade prostatic stromal sarcoma, a radical cystoprostatectomy and bilateral pelvic node dissection was performed showing residual high grade stromal sarcoma of the prostate and incidental in situ urothelial carcinoma of the bladder. No further medical treatments were planned. One year after surgery the patient is well with no evidence of local disease or distant metastases.

  5. Patient and caregiver perceptions of communication of prognosis in high grade glioma.

    PubMed

    Lobb, E A; Halkett, G K B; Nowak, A K

    2011-08-01

    This study sought the views of patients and their caregivers on their experience of being diagnosed with high grade glioma. Purposive sampling was used to recruit 19 patients and 21 caregivers from the medical oncology unit of a tertiary hospital. A semi-structured face-to-face interview was conducted. Interviews were audio-taped and transcribed verbatim. Data was analysed based on Grounded Theory and using the constant comparison method. This paper focuses on patient and carer perceptions of the initial communication about the diagnosis of high grade glioma and its prognosis. Themes identified included: (a) shock at hearing the diagnosis; (b) trying to understand and process prognostic information when still in shock; (c) the perception of hope being taken away; (d) individualizing prognostic information; and (e) clinicians' lack of communication skills. This study shows that the first communication of prognosis to patients with high grade glioma and their caregivers requires careful negotiation. It illustrates the inability of individuals to process detailed prognostic information when in a state of initial shock and distress. The importance of balancing honesty with hope in the communication of a poor prognosis is highlighted. We recommend that clinicians seek patient preferences for the amount and type of information they require and that prognostic information be individualized. Detailed discussions of prognosis should only take place with senior medical staff, or advanced trainees who have demonstrated acceptable communication skills.

  6. Subungual squamous cell carcinoma*

    PubMed Central

    Padilha, Carolina Barbosa de Sousa; Balassiano, Laila Klotz de Almeida; Pinto, Julyana Calegari; de Souza, Flávia Crespo Schueler; Kac, Bernard Kawa; Treu, Curt Mafra

    2016-01-01

    Although subungual squamous cell carcinoma is rare, it is the most common primary malignant neoplasms in this location. The higher incidence occurs in the fingernails, but involvement of the toenails is also possible. Subungual squamous cell carcinoma often looks like other more common benign lesions, such as fungal infection, onychomycosis, or viral wart. These factors, together with a general lack of awareness of this disease among physicians, often result in delayed diagnosis. Therefore, it is underdiagnosed, with few reports in the literature. The authors present a case of a man with a diagnosis of subungual squamous cell carcinoma in the hallux, without bone involvement, which was submitted to the appropriate surgical treatment. PMID:28099608

  7. Ovarian high-grade serous carcinoma with a noninvasive growth pattern simulating a serous borderline tumor.

    PubMed

    Imamura, Hiroko; Ohishi, Yoshihiro; Aman, Murasaki; Shida, Kaai; Shinozaki, Tomoko; Yasutake, Nobuko; Sonoda, Kenzo; Kato, Kiyoko; Oda, Yoshinao

    2015-10-01

    Ovarian serous borderline tumors (SBTs) being a precursor of low-grade serous carcinomas are morphologically characterized by noninvasive growth and low-grade cytology. On the other hand, many pathologists regard cytologically high-grade, noninvasive (HG-noninv) ovarian serous tumors resembling SBTs in low magnification as conventional high-grade serous carcinomas (HGSCs) by personal experiences. Nonetheless, there are no established molecular characteristic of such tumors. In this study, therefore, we attempted to provide the molecular evidence. We selected 37 ovarian serous tumors that exhibited a cytologically HG-noninv growth pattern, including 36 tumors that coexisted with conventional invasive HGSC components (HG-inv) and a single tumor exclusively composed of pure HG-noninv. Histologically, all HG-noninv showed many mitotic figures, and serous tubal intraepithelial carcinomas were identified in 3 tumors with HG-noninv. Immunohistochemically, most HG-noninv showed aberrant p53 expression, frequent IMP3 positivity, p16 overexpression, a high MIB-1 labeling index, and infrequent PAX2. By molecular analysis, the pure HG-noninv and 13 HGSCs with HG-noninv showed TP53 mutations, but KRAS/BRAF mutations were not detected in any of them. In 1 tumor, we detected an identical TP53 mutation in both HG-noninv and HG-inv components by using laser capture microdissection. These immunohistochemical and molecular features of HG-noninv were similar to those of conventional invasive HGSCs but different from those of SBTs. In conclusion, our results showed that a cytologically HG-noninv growth pattern simulating an SBT is a morphological spectrum of HGSC, but not a true SBT.

  8. Combined cytotoxic effect of UV-irradiation and TiO2 microbeads in normal urothelial cells, low-grade and high-grade urothelial cancer cells.

    PubMed

    Imani, Roghayeh; Veranič, Peter; Iglič, Aleš; Kreft, Mateja Erdani; Pazoki, Meysam; Hudoklin, Samo

    2015-03-01

    The differentiation of urothelial cells results in normal terminally differentiated cells or by alternative pathways in low-grade or high-grade urothelial carcinomas. Treatments with traditional surgical and chemotherapeutical approaches are still inadequate and expensive, as bladder tumours are generally highly recurrent. In such situations, alternative approaches, using irradiation of the cells and nanoparticles, are promising. The ways in which urothelial cells, at different differentiation levels, respond to UV-irradiation (photolytic treatment) or to the combination of UV-irradiation and nanoparticles (photocatalytic treatment), are unknown. Here we tested cytotoxicity of UV-irradiation on (i) normal porcine urothelial cells (NPU), (ii) human low-grade urothelial cancer cells (RT4), and (iii) human high-grade urothelial cancer cells (T24). The results have shown that 1 minute of UV-irradiation is enough to kill 90% of the cells in NPU and RT4 cultures, as determined by the live/dead viability assay. On the other hand, the majority of T24 cells survived 1 minute of UV-irradiation. Moreover, even a prolonged UV-irradiation for 30 minutes killed <50% of T24 cells. When T24 cells were pre-supplemented with mesoporous TiO2 microbeads and then UV-irradiated, the viability of these high-grade urothelial cancer cells was reduced to <10%, which points to the highly efficient cytotoxic effects of TiO2 photocatalysis. Using electron microscopy, we confirmed that the mesoporous TiO2 microbeads were internalized into T24 cells, and that the cell's ultrastructure was heavily compromised after UV-irradiation. In conclusion, our results show major differences in the sensitivity to UV-irradiation among the urothelial cells with respect to cell differentiation. To achieve an increased cytotoxicity of urothelial cancer cells, the photocatalytic approach is recommended.

  9. Doxorubicin-cisplatin chemotherapy for high-grade nonosteogenic sarcoma of bone. Comparison of treatment and control groups

    PubMed Central

    Waddell, Andrea E.; Davis, Aileen M.; Ahn, Henry; Wunder, Jay S.; Blackstein, Martin E.; Bell, Robert S.

    1999-01-01

    Objective To evaluate the role of chemotherapy with a combination of doxorubicin (adriamycin) and cisplatin in high-grade, nonosteogenic, non-Ewing’s sarcoma (non-OSA) of bone. Design A case series comparison with a literature-derived control group. Setting A university-affiliated tertiary care centre. Patients Thirty patients with a diagnosis of non-OSA. Of these, 8 had low-grade disease (grade 1 or 2) and 22 had high-grade disease (grade 3). Eleven of the 22 with high-grade disease had malignant fibrous histiocytoma. Seventeen patients with nonmetastatic high-grade non-OSA were compared with a literature cohort of 37 patients who met the eligibility criteria of nonmetastatic, high-grade non-OSA treated with surgery, with or without radiotherapy. The mean follow-up was 25.2 months. Interventions Eight patients with low-grade tumour underwent surgery alone; 22 patients with high-grade tumour underwent surgery and 6 courses of adriamycin (75 mg/m2 every 3 weeks) and cisplatin (100 mg/m2 every 3 weeks). Main outcome measures Disease-free survival and overall survival in those with high-grade tumours treated with or without chemotherapy. Results Of 8 patients who had low-grade tumours and underwent surgery alone, 3 had systemic relapse. Of the 22 having high-grade tumours, 4 did not receive chemotherapy because of age and comorbid conditions. Of the other 18, 13 received 3 courses of chemotherapy preoperatively and 3 courses postoperatively, 4 received all 6 courses postoperatively and 1 received all chemotherapy preoperatively to treat metastatic disease. In the 17-patient cohort used for comparison with the literature control group, disease-free survival was 57% at a mean follow-up of 25.6 months and overall survival was 57% at a mean follow-up of 30.1 months. In the control group, disease-free survival was 16% at a mean follow-up of 20.9 months and overall survival was 26% at a mean follow-up of 29.9 months. These differences are significant: p = 0.0000, χ2 = 41

  10. [Lichen sclerosus and squamous cell carcinoma].

    PubMed

    Gutiérrez-Pascual, M; Vicente-Martín, F J; López-Estebaranz, J L

    2012-01-01

    Lichen sclerosus is a chronic inflammatory disease that can progress to malignancy. The literature indicates an association with anogenital squamous cell carcinoma and verrucous carcinoma. Two pathogenic pathways, differentiated vulvar and penile intraepithelial neoplasias, which have recently been described in relation to squamous cell carcinoma, are both highly associated with genital lichen sclerosus independently of human papilloma virus (HPV) infection. Furthermore, tumor-promoting molecular changes unrelated to HPV infection have been demonstrated and may explain the malignant potential of lichen sclerosus. The possible relationship between HPV and genital lichen sclerosus currently remains open to discussion, and the prognostic importance of the overlapping of these 2 diseases is still unclear. This review considers the relationship between lichen sclerosus and squamous cell and verrucous carcinomas, the possible oncogenic mechanisms involved, and their possible association with HPV infection.

  11. Lichen sclerosus and squamous cell carcinoma.

    PubMed

    Gutiérrez-Pascual, M; Vicente-Martín, F J; López-Estebaranz, J L

    2012-01-01

    Lichen sclerosus is a chronic inflammatory disease that can progress to malignancy. The literature indicates an association with anogenital squamous cell carcinoma and verrucous carcinoma. Two pathogenic pathways, differentiated vulvar and penile intraepithelial neoplasias, which have recently been described in relation to squamous cell carcinoma, are both highly associated with genital lichen sclerosus independently of human papilloma virus (HPV) infection. Furthermore, tumor-promoting molecular changes unrelated to HPV infection have been demonstrated and may explain the malignant potential of lichen sclerosus. The possible relationship between HPV and genital lichen sclerosus currently remains open to discussion, and the prognostic importance of the overlapping of these 2 diseases is still unclear. This review considers the relationship between lichen sclerosus and squamous cell and verrucous carcinomas, the possible oncogenic mechanisms involved, and their possible association with HPV infection.

  12. Squamous metaplasia of the rete ovarii in a Zebu cow

    PubMed Central

    2012-01-01

    Background Stratified keratinizing squamous epithelium in the ovary has been associated with the diagnosis of ovarian teratoma in cows. Recently, the diagnosis of “epidermoid cyst” has been proposed. A case of squamous metaplasia of the rete ovarii in a Zebu cow is described in this report. Case presentation A crossbreed Zebu cow had both ovaries enlarged with multiple cysts. Most cysts were lined by well differentiated keratinizing stratified squamous epithelium and filled with keratinized lamellar material. Some cysts were lined by an epithelial layer that ranged from single cuboidal, double cuboidal epithelium, stratified non keratinized epithelium, and areas of keratinizing stratified squamous epithelium. Single or double layered cuboidal epithelia of the cysts expressed low molecular weight cytokeratin 7, whose expression was absent in the keratinizing stratified squamous epithelia of same cysts. Conversely, high molecular weight cytokeratins 1, 5, 10, and 14 were strongly expressed by the keratinizing stratified epithelium. Conclusion Squamous metaplasia of the rete ovarii was diagnosed. Squamous metaplasia of the rete ovarii, may account for some of the previously described squamous lesions in the ovary, which may have been misinterpreted as teratoma or epidermoid cysts. PMID:23217175

  13. Ovarian low and high grade serous carcinomas: hidden divergent features in the tumor microenvironment

    PubMed Central

    Buttarelli, Marianna; Martinelli, Enrica; Mascilini, Floriana; Petrillo, Marco; Ferrandina, Gabriella; Scambia, Giovanni; Gallo, Daniela

    2016-01-01

    Only recently low-grade serous carcinoma (LGSOC) of the ovary has been recognized as a disease entity distinct from the more common high-grade serous carcinoma (HGSOC), with significant differences in pathogenesis and clinical and pathologic features. The present study aimed at evaluating whether the different natural histories and patterns of response to therapy demonstrated for LGSOC and HGSOC, along with a diverse genomic landscape, may also reside in the supporting tumor stroma, specifically in the state of differentiation and activation of tumor associated macrophages (TAMs). TAMs play complex roles in tumorigenesis since they are believed to possess both tumor rejecting (M1 macrophages) and tumor promoting (M2 macrophages) activities. Here we showed that, when compared to HGSOC (n = 55), LGSOC patients (n = 25) exhibited lower density of tumor-infiltrating CD68+ macrophage, along with an attenuated M2-skewed (CD163+) phenotype. Accordingly, assessment of intratumoral vascularization and of matrix metalloproteinase 9 expression (a key protein involved in tumor invasion and metastasis) revealed lower expression in LGSOC compared to HGSOC patients, in line with emerging evidence supporting a role for TAMs in all aspects of tumor initiation, growth, and development. In conclusion, results from the present study demonstrate that microenvironmental factors contribute greatly to determine clinical and pathological features that differentiate low and high grade serous ovarian carcinomas. This understanding may increase possibilities and opportunities to improve disease control and design new therapeutic strategies. PMID:27462782

  14. Relationship between high- and low-grade Archean terranes: Implications for early Earth paleogeography

    NASA Technical Reports Server (NTRS)

    Eriksson, K. A.

    1986-01-01

    The Western Gneiss Terrain (WGT) of the Yilgarn Block, Western Australia was studied. The WGT forms an arcuate belt of Archean gneisses that flank the western margin of the Yilgarn Block. In general the WGT is composed of high-grade orthogneisses and paragneisses which contain supracrustal belts composed largely of siliciclastic metasediments and subordinate iron formation. The platformal nature of the metasedimentary belts and lack of obvious metavolcanic lithologies contrasts with the composition of typical Yilgarn greenstones to the east. Radiometric data from WGT rocks indicates that these rocks are significantly older than Yilgarn rocks to the east (less than 3.3 Ga) and this has led to the suggestion that the WGT represents sialic basement to Yilgarn granite-greenstone belts. The Mount Narryer region exposes the northernmost occurrence of high-grade metasediments within the WGT and consists of quartz-rich clastic metasediments at upper amphibolite to granulite grade. Most occurrences of supracrustal rocks in this region comprise isolated lenses within the gneissic basement. However, at Mount Narryer a unique sequence of metaclastics with preserved bedding provide an unusual window into the parentage of similar supracrustal bodies in this region.

  15. Dynamic susceptibility contrast and dynamic contrast-enhanced MRI characteristics to distinguish microcystic meningiomas from traditional Grade I meningiomas and high-grade gliomas.

    PubMed

    Hussain, Namath S; Moisi, Marc D; Keogh, Bart; McCullough, Brendan J; Rostad, Steven; Newell, David; Gwinn, Ryder; Foltz, Gregory; Mayberg, Marc; Aguedan, Brian; Good, Valerie; Fouke, Sarah J

    2016-06-10

    IV astrocytomas (p < 0.001 for both). Preoperative DCE imaging indicated mean kTrans values of 0.49 ± 0.20 min(-1) in Grade I meningiomas of the meningoepithelial subtype (n = 12), 0.27 ± 0.12 min(-1) for Grade IV astrocytomas (n = 54), and 1.35 ± 0.74 min(-1) for Grade I meningiomas of the MM subtype (n = 6). The kTrans was significantly higher in the MM variants than in the corresponding nonmicrocystic Grade 1 meningiomas and Grade IV astrocytomas (p < 0.001 for both). Intraoperative blood loss tended to increase with increased normalized CBV (R = 0.45, p = 0.085). CONCLUSIONS An enhancing cystic lesion with a normalized CBV greater than 10.3 ml or a kTrans greater than 0.88 min(-1) should prompt radiologists and surgeons to consider the diagnosis of MM rather than traditional Grade I meningioma or high-grade glioma in planning surgical care. Higher normalized CBVs tend to be associated with increased intraoperative blood loss.

  16. Fatigue of Austempered Ductile Iron with Two Strength Grades in Very High Cycle Regime

    NASA Astrophysics Data System (ADS)

    Zhang, Jiwang; Li, Wei; Song, Qingpeng; Zhang, Ning; Lu, Liantao

    2016-03-01

    In this study, Austempered ductile irons (ADIs) with two different strength grades were produced and the fatigue properties were measured at 109 cycles. The results show that the S-N curves give a typical step-wise shape and there is no fatigue limit in the very high cycle fatigue regime. The two grades ADI have the similar fracture behaviors and fatigue failure can initiate from defects at specimen surface and subsurface zone. On the fracture surfaces of some specimens, the `granular-bright-facet' area with rich carbon distribution is observed in the vicinity of the defect. The microstructure affects the crack behaviors at the early propagation stage. The ADI with upper and lower bainite shows higher fatigue strength compared with the ADI with coarse upper bainite.

  17. High-grade glioma management and response assessment—recent advances and current challenges

    PubMed Central

    Khan, M.N.; Sharma, A.M.; Pitz, M.; Loewen, S.K.; Quon, H.; Poulin, A.; Essig, M.

    2016-01-01

    The management of high-grade gliomas (hggs) is complex and ever-evolving. The standard of care for the treatment of hggs consists of surgery, chemotherapy, and radiotherapy. However, treatment options are influenced by multiple factors such as patient age and performance status, extent of tumour resection, biomarker profile, and tumour histology and grade. Follow-up cranial magnetic resonance imaging (mri) to differentiate treatment response from treatment effect can be challenging and affects clinical decision-making. An assortment of advanced radiologic techniques—including perfusion imaging with dynamic susceptibility contrast mri, dynamic contrast-enhanced mri, diffusion-weighted imaging, proton spectroscopy, mri subtraction imaging, and amino acid radiotracer imaging—can now incorporate novel physiologic data, providing new methods to help characterize tumour progression, pseudoprogression, and pseudoresponse. In the present review, we provide an overview of current treatment options for hgg and summarize recent advances and challenges in imaging technology. PMID:27536188

  18. NAGC Pre-K-Grade 12 Gifted Education Programming Standards: A Guide to Planning and Implementing High-Quality Services

    ERIC Educational Resources Information Center

    Johnsen, Susan K., Ed.

    2012-01-01

    The new Pre-K-Grade 12 Gifted Education Programming Standards should be part of every school district's repertoire of standards to ensure that the learning needs of advanced students are being met. "NAGC Pre-K-Grade 12 Gifted Education Programming Standards: A Guide to Planning and Implementing High-Quality Services" details six standards that…

  19. Successful Transition to High School: A Randomized Controlled Trial of the Barr Model with 9th Grade Students

    ERIC Educational Resources Information Center

    Corsello, Maryann; Sharma, Anu; Jerabek, Angela

    2015-01-01

    Ninth grade is a pivotal year for students. Numerous studies find that academic performance in 9th grade often sets the student's trajectory throughout the high school years, as well as the probability of graduation. The Building Assets Reducing Risks (BARR) model is a comprehensive approach that addresses developmental, academic, and school…

  20. A Case of High-grade Transitional Cell Carcinoma of the Bladder in a Pediatric Patient With Turner Syndrome.

    PubMed

    Aguiar, Liza; Danialan, Richard; Kim, Christina

    2015-06-01

    Transitional cell carcinoma is a rare entity in children, especially in the first decade of life. The majority of these tumors are of low grade and noninvasive. We report an interesting case of a high-grade superficial transitional cell carcinoma in a 3-year-old girl with Turner syndrome.

  1. High Interest - Low Vocabulary Science Books, Reading Level Grades 1-4 (Prepared for the Remedial Reading Teacher).

    ERIC Educational Resources Information Center

    Gott, Margaret E., Comp.; Wailes, James R., Comp.

    This booklist is intended for elementary school science students with high interest and low vocabulary skills. The Spache Readability Scale, Dale-Chall formula, sentence structure, paragraph flow, illustration, and diagram analysis or publishers stated grade level were used to determine grade level designations. The included interest level varies…

  2. Gender Differences in Sense of Justice about Grades: A Comparative Study of High School Students in Israel and Germany

    ERIC Educational Resources Information Center

    Resh, Nura; Dalbert, Claudia

    2007-01-01

    Assessing students' aptitude and educational performance and grading them on a hierarchical scale is a universal feature of the schooling process. In light of grades' instrumental, motivational, and symbolic saliency in students' school experience, it is not surprising they are highly "valued goods," and the process of their fair or…

  3. The Silencing of Latino Student "Voice": Puerto Rican and Mexican Narratives in Eighth Grade and High School.

    ERIC Educational Resources Information Center

    Quiroz, Pamela Anne

    2001-01-01

    Narratives of Puerto Rican and Mexican American students, written in 8th grade and then 11th grade, describe who they are and illustrate school-sponsored silencing, with student critiques of their educational experience ignored by schools. The narratives help explain the Hispanic student high dropout rate, reasons behind students' academic…

  4. STAR and AKR1B10 are down-regulated in high-grade endometrial cancer.

    PubMed

    Sinreih, Maša; Štupar, Saša; Čemažar, Luka; Verdenik, Ivan; Frković Grazio, Snježana; Smrkolj, Špela; Rižner, Tea Lanišnik

    2017-02-21

    Endometrial cancer is the most frequent gynecological malignancy in the developed world. The majority of cases are estrogen dependent, and are associated with diminished protective effects of progesterone. Endometrial cancer is also related to enhanced inflammation and decreased differentiation. In our previous studies, we examined the expression of genes involved in estrogen and progesterone actions in inflammation and tumor differentiation, in tissue samples from endometrial cancer and adjacent control endometrium. The aims of the current study were to examine correlations between gene expression and several demographic characteristics, and to evaluate changes in gene expression with regard to histopathological and clinical characteristics of 51 patients. We studied correlations and differences in expression of 38 genes involved in five pathophysiological processes: (i) estrogen-stimulated proliferation; (ii) estrogen-dependent carcinogenesis; (iii) diminished biosynthesis of progesterone: (iv) enhanced formation of progesterone metabolites; and (v) increased inflammation and decreased differentiation. Spearman correlation coefficient analysis shows that expression of PAQR7 correlates with age, expression of SRD5A1, AKR1B1 and AKR1B10 correlate with body mass, while expression of SRD5A1 and AKR1B10 correlate with body mass index. When patients with endometrial cancer were stratified based on menopausal status, histological grade, myometrial invasion, lymphovascular invasion, and FIGO stage, Mann-Whitney U tests revealed significantly decreased expression of STAR (4.4-fold; adjusted p=0.009) and AKR1B10 (9-fold; adjusted p=0.003) in high grade versus low grade tumors. Lower levels of STAR might lead to decreased de-novo steroid hormone synthesis and tumor differentiation, and lower levels of AKR1B10 to diminished elimination of toxic electrophilic carbonyl compounds in high-grade endometrial cancer. These data thus reveal the potential of STAR and AKR1B10 as

  5. The eastern limit of Acadian high grade metamorphism in northern New England: Implications for the location of the Acadian Suture''

    SciTech Connect

    West, D.P. Jr. . Dept. of Geological Sciences)

    1993-03-01

    Identifying the eastern limit of Acadian high grade metamorphism in New England is complicated by the presence of pre-Devonian high grade relics, locally intense Late Paleozoic thermal overprints, and post-metamorphic faults. New [sup 40]Ar/[sup 39]Ar mineral ages from along the eastern margin of high grade metamorphism in Maine and New Hampshire help delineate the eastern limit of Devonian amphibolite facies metamorphism thereby placing constraints on the location of the Acadian suture. In New Hampshire, Acadian high grade metamorphism extends southeast at least as far as the Campbell Hill fault and perhaps as far as the Flint Hill fault. New [sup 40]Ar/[sup 39]Ar hornblende ages and previously published U-Pb monazite ages from the Massabesic Gneiss Complex are Permian indicating high grade Alleghanian metamorphism. New [sup 40]Ar/[sup 39]Ar hornblende ages from the Rye Formation, although complicated by excess argon, are considerably older, indicating an earlier Pre-Silurian amphibolite facies metamorphism affected these rocks. North of Portland, [sup 40]Ar/[sup 39]Ar hornblende ages east of the Norumbega Fault Zone from high grade rocks of the Casco Bay Group have ages that range from Middle Devonian to Early Carboniferous, consistent with diachronous cooling following Acadian metamorphism. Further northeast, in upper amphibolite facies rocks of the Passagassawakeag Gneiss, new [sup 40]Ar/[sup 39]Ar hornblende ages range from 385--395 Ma suggesting that these rocks were also affected by high grade Acadian metamorphism.

  6. High-grade renal injuries are often isolated in sports-related trauma

    PubMed Central

    Patel, Darshan P.; Redshaw, Jeffrey D.; Breyer, Benjamin N.; Smith, Thomas G.; Erickson, Bradley A.; Majercik, Sarah D.; Gaither, Thomas W.; Craig, James R.; Gardner, Scott; Presson, Angela P.; Zhang, Chong; Hotaling, James M.; Brant, William O.; Myers, Jeremy B.

    2016-01-01

    Introduction Most high-grade renal injuries (American Association for Surgery of Trauma (AAST) grades III–V) result from motor vehicle collisions associated with numerous concomitant injuries. Sports-related blunt renal injury tends to have a different mechanism, a solitary blow to the flank. We hypothesized that high-grade renal injury is often isolated in sports-related renal trauma. Material and methods We identified patients with AAST grades III–V blunt renal injuries from four level 1 trauma centres across the United States between 1/2005 and 1/2014. Patients were divided into “Sport” or “Non-sport” related groups. Outcomes included rates of hypotension (systolic blood pressure <90 mm Hg), tachycardia (>110 bpm), concomitant abdominal injury, and procedural/surgical intervention between sports and non-sports related injury. Results 320 patients met study criteria. 18% (59) were sports-related injuries with the most common mechanisms being skiing, snowboarding and contact sports (25%, 25%, and 24%, respectively). Median age was 24 years for sports and 30 years for non-sports related renal injuries (p = 0.049). Males were more commonly involved in sports related injuries (85% vs. 72%, p = 0.011). Median injury severity score was lower for sports related injuries (10 vs. 27, p < 0.001). There was no difference in renal abbreviated injury scale scores. Sports related trauma was more likely to be isolated without other significant injury (69% vs. 39% (p < 0.001)). Haemodynamic instability was present in 40% and 51% of sports and non-sports renal injuries (p = 0.30). Sports injuries had lower transfusion (7% vs. 47%, p < 0.001) and lower mortality rates (0% vs. 6%, p = 0.004). There was no difference in renal-specific procedural interventions between the two groups (17% sports vs. 18% non-sports, p = 0.95). Conclusions High-grade sports-related blunt renal trauma is more likely to occur in isolation without other abdominal or thoracic injuries and

  7. A Rare Collision Tumour of Uterus- Squamous Cell Carcinoma and Endometrial Stromal Sarcoma

    PubMed Central

    Gupta, Bindiya; Pathre, Abhishek; Rajaram, Shalini; Goyal, Neerja

    2017-01-01

    Collision tumours are defined by co-existence of two tumours in the same or adjacent organs which are topographically and histologically distinct with minimal or no histological admixture. Collision tumours have been described in many organs notably thyroid, brain, adrenal gland, stomach and rarely uterus. Most of the collision tumours reported in uterus have two components; an adenocarcinoma and a sarcoma. We report a case of a 60-year-old lady who presented with complaints of post-menopausal bleeding. A cervical biopsy was performed which showed a non-keratinizing squamous cell carcinoma of cervix. Intra-operatively the uterus was bulky with a 6 cm x 5 cm polypoidal mass in the endometrial canal along with a 2 cm friable cervical growth. The fleshy uterine cavity mass was a spindle cell tumour with moderate pleomorphism and frequent mitosis. It was immunopositive for CD10 and negative for smooth muscle actin and cytokeratin 5/6. The other growth showed non-keratinizing squamous cell carcinoma which was positive for cytokeratin 5/6. Based on the distinct topographical location and limited areas of tumour admixture of the two tumours, a diagnosis of collision tumour of uterus comprising of endometrial stromal sarcoma (high grade) uterus and squamous cell carcinoma cervix was made. PMID:28384878

  8. RNA Chromogenic in situ Hybridization Assay with Clinical Automated Platform is a Sensitive Method in Detecting High-risk Human Papillomavirus in Squamous Cell Carcinoma.

    PubMed

    Mendez-Pena, Javier E; Sadow, Peter M; Nose, Vania; Hoang, Mai P

    2017-03-13

    Detection of active human papillomavirus (HPV) is clinically important, as its presence has been shown to correlate with favorable clinical outcomes and better response to treatment in oropharyngeal squamous cell carcinomas (SCC). Using a clinical automated platform, we compared the performance of commercially available HPV DNA and RNA in situ hybridization (ISH) probes in archival tissues of 57 SCC. Importantly, a clinical automated platform gives 1) consistent and reproducible results for HPV ISH and 2) better standardization across clinical laboratories. Compared to polymerase chain reaction (PCR) results, RNA ISH exhibited 93% concordance versus 81% of DNA ISH. RNA ISH was more sensitive than DNA ISH (100% versus 88%), and more specific (87% versus 74%). When only accounting for 2-3+ positivity, sensitivity was 92% for RNA ISH versus 73% for DNA ISH, highlighting the ease of interpretation. p16 exhibited 96% sensitivity while specificity was only 55%. In 3 cases both RNA and DNA ISH were positive while PCR results were negative, suggesting that ISH methods might be a more sensitive method. Performing on a clinical automated platform, RNA ISH is sensitive in determining high-risk HPV status in formalin-fixed paraffin-embedded tissues and has the potential of being a standalone clinical test.

  9. Simultaneous fingerprint and high-wavenumber fiber-optic Raman spectroscopy improves in vivo diagnosis of esophageal squamous cell carcinoma at endoscopy

    PubMed Central

    Wang, Jianfeng; Lin, Kan; Zheng, Wei; Yu Ho, Khek; Teh, Ming; Guan Yeoh, Khay; Huang, Zhiwei

    2015-01-01

    This work aims to evaluate clinical value of a fiber-optic Raman spectroscopy technique developed for in vivo diagnosis of esophageal squamous cell carcinoma (ESCC) during clinical endoscopy. We have developed a rapid fiber-optic Raman endoscopic system capable of simultaneously acquiring both fingerprint (FP)(800–1800 cm−1) and high-wavenumber (HW)(2800–3600 cm−1) Raman spectra from esophageal tissue in vivo. A total of 1172 in vivo FP/HW Raman spectra were acquired from 48 esophageal patients undergoing endoscopic examination. The total Raman dataset was split into two parts: 80% for training; while 20% for testing. Partial least squares-discriminant analysis (PLS-DA) and leave-one patient-out, cross validation (LOPCV) were implemented on training dataset to develop diagnostic algorithms for tissue classification. PLS-DA-LOPCV shows that simultaneous FP/HW Raman spectroscopy on training dataset provides a diagnostic sensitivity of 97.0% and specificity of 97.4% for ESCC classification. Further, the diagnostic algorithm applied to the independent testing dataset based on simultaneous FP/HW Raman technique gives a predictive diagnostic sensitivity of 92.7% and specificity of 93.6% for ESCC identification, which is superior to either FP or HW Raman technique alone. This work demonstrates that the simultaneous FP/HW fiber-optic Raman spectroscopy technique improves real-time in vivo diagnosis of esophageal neoplasia at endoscopy. PMID:26243571

  10. Expression of aldehyde dehydrogenase family 1 member A1 and high mobility group box 1 in oropharyngeal squamous cell carcinoma in association with survival time

    PubMed Central

    Qian, Xu; Coordes, Annekatrin; Kaufmann, Andreas M.; Albers, Andreas E.

    2016-01-01

    Despite the development of novel multimodal treatment combinations in advanced oropharyngeal squamous cell carcinoma (OSCC), outcomes remain poor. The identification of specifically validated biomarkers is required to understand the underlying molecular mechanisms, to evaluate treatment efficiency and to develop novel therapeutic targets. The present study, therefore, examined the presence of aldehyde dehydrogenase family 1 member A1 (ALDH1A1) and high mobility group box 1 (HMGB1) expression in primary OSCC and analyzed the impact on survival time. In 59 patients with OSCC, the expression of ALDH1A1, p16 and HMGB1, and their clinicopathological data were analyzed. HMGB1 positivity was significantly increased in patients with T1-2 stage disease compared with T3-4 stage disease (P<0.001), whereas ALDH1A1 positivity was not. ALDH1A1+ tumors showed significantly lower differentiation than ALDH1A1− tumors (P=0.018). Multivariate analysis showed that ALDH1A1 positivity (P=0.041) and nodal status (N2-3) (P=0.036) predicted a poor prognosis. In this patient cohort, ALDH1A1 and nodal status were identified as independent predictors of a shorter overall survival time. The study results, therefore, provide evidence of the prognostic value of ALDH1A1 as a marker for cancer stem cells and nodal status in OSCC patients. PMID:27900016

  11. Expression of aldehyde dehydrogenase family 1 member A1 and high mobility group box 1 in oropharyngeal squamous cell carcinoma in association with survival time.

    PubMed

    Qian, Xu; Coordes, Annekatrin; Kaufmann, Andreas M; Albers, Andreas E

    2016-11-01

    Despite the development of novel multimodal treatment combinations in advanced oropharyngeal squamous cell carcinoma (OSCC), outcomes remain poor. The identification of specifically validated biomarkers is required to understand the underlying molecular mechanisms, to evaluate treatment efficiency and to develop novel therapeutic targets. The present study, therefore, examined the presence of aldehyde dehydrogenase family 1 member A1 (ALDH1A1) and high mobility group box 1 (HMGB1) expression in primary OSCC and analyzed the impact on survival time. In 59 patients with OSCC, the expression of ALDH1A1, p16 and HMGB1, and their clinicopathological data were analyzed. HMGB1 positivity was significantly increased in patients with T1-2 stage disease compared with T3-4 stage disease (P<0.001), whereas ALDH1A1 positivity was not. ALDH1A1(+) tumors showed significantly lower differentiation than ALDH1A1(-) tumors (P=0.018). Multivariate analysis showed that ALDH1A1 positivity (P=0.041) and nodal status (N2-3) (P=0.036) predicted a poor prognosis. In this patient cohort, ALDH1A1 and nodal status were identified as independent predictors of a shorter overall survival time. The study results, therefore, provide evidence of the prognostic value of ALDH1A1 as a marker for cancer stem cells and nodal status in OSCC patients.

  12. Simultaneous fingerprint and high-wavenumber fiber-optic Raman spectroscopy improves in vivo diagnosis of esophageal squamous cell carcinoma at endoscopy

    NASA Astrophysics Data System (ADS)

    Wang, Jianfeng; Lin, Kan; Zheng, Wei; Yu Ho, Khek; Teh, Ming; Guan Yeoh, Khay; Huang, Zhiwei

    2015-08-01

    This work aims to evaluate clinical value of a fiber-optic Raman spectroscopy technique developed for in vivo diagnosis of esophageal squamous cell carcinoma (ESCC) during clinical endoscopy. We have developed a rapid fiber-optic Raman endoscopic system capable of simultaneously acquiring both fingerprint (FP)(800-1800 cm-1) and high-wavenumber (HW)(2800-3600 cm-1) Raman spectra from esophageal tissue in vivo. A total of 1172 in vivo FP/HW Raman spectra were acquired from 48 esophageal patients undergoing endoscopic examination. The total Raman dataset was split into two parts: 80% for training; while 20% for testing. Partial least squares-discriminant analysis (PLS-DA) and leave-one patient-out, cross validation (LOPCV) were implemented on training dataset to develop diagnostic algorithms for tissue classification. PLS-DA-LOPCV shows that simultaneous FP/HW Raman spectroscopy on training dataset provides a diagnostic sensitivity of 97.0% and specificity of 97.4% for ESCC classification. Further, the diagnostic algorithm applied to the independent testing dataset based on simultaneous FP/HW Raman technique gives a predictive diagnostic sensitivity of 92.7% and specificity of 93.6% for ESCC identification, which is superior to either FP or HW Raman technique alone. This work demonstrates that the simultaneous FP/HW fiber-optic Raman spectroscopy technique improves real-time in vivo diagnosis of esophageal neoplasia at endoscopy.

  13. Number Sense-Based Strategies Used by High-Achieving Sixth Grade Students Who Experienced Reform Textbooks

    ERIC Educational Resources Information Center

    Alsawaie, Othman N.

    2012-01-01

    The purpose of this study was to explore strategies used by high-achieving 6th grade students in the United Arab Emirates (UAE) to solve basic arithmetic problems involving number sense. The sample for the study consisted of 15 high-achieving boys and 15 high-achieving girls in grade 6 from 2 schools in the Emirate of Abu Dhabi, UAE. Data for the…

  14. Recurrence Patterns and Survival for Patients With Intermediate- and High-Grade Myxofibrosarcoma

    SciTech Connect

    Haglund, Karl E.; Raut, Chandrajit P.; Nascimento, Alessandra F.; Wang, Qian; George, Suzanne; Baldini, Elizabeth H.

    2012-01-01

    Purpose: Myxofibrosarcoma (MFS) is a rare sarcoma with a predilection for multiple local recurrences (LR), for which optimal treatment has not been defined. We reviewed our experience to determine the impact of surgery and radiation therapy (RT) on pattern of recurrence, limb salvage, and overall survival (OS). Methods and Materials: Between 1995 and 2005, 36 patients with localized intermediate- or high-grade MFS were treated at our institution. Data on clinicopathologic features, treatments, and patient outcomes were reviewed and analyzed. Results: Median age was 72.5 years (range, 42-96 years). Median tumor size was 7.5 cm, and 34 tumors (94%) were high grade. All patients underwent surgery at our institution, including re-resections in 20 patients (56%) after initial surgery elsewhere. Margins were microscopically positive in 9 patients (25%). RT was given to 28 patients (78%) pre - and/or postoperatively. After a median follow-up of 3.5 years (range, 0.4-12.4 years), 11 patients (31%) developed LR. There were no significant predictors for LR on univariate analysis, including margin status or use of RT. Limb salvage was ultimately achieved in only 5 of 11 LRs (45%) because of multiple subsequent LRs. Distant recurrence (DR) occurred in 6 patients (17%). Median and 4-year OS were 96 months and 65%, respectively. Seven patients (19%) died of tumor-related causes, 6 of whom had DRs. On univariate analysis, tumor size was associated with OS. Conclusions: Despite aggressive surgery and RT, intermediate- and high-grade MFS are associated with a high rate of LR that adversely affects limb preservation. More aggressive local treatment strategies are necessary.

  15. Microstructural evolution of nuclear grade graphite induced by ion irradiation at high temperature environment

    NASA Astrophysics Data System (ADS)

    Tsai, Shuo-Cheng; Huang, E.-Wen; Kai, Ji-Jung; Chen, Fu-Rong

    2013-03-01

    This study simulates the Wigner Effect of nuclear-grade graphite in a High Temperature Gas-cooled Reactor (HTGR). The graphite was artificially irradiated with 3 MeV C2+ ions to mimic the fast neutron-radiation damage of the HTGR core environment. The irradiation temperatures were controlled between the range of 500-800 °C in a high vacuum environment of 10-7 torr. This high-dosage radiation creates enormous amounts of Frenkel pairs, which induce lattice swelling. These Frenkel vacancies and interstitials generate new strain fields and, hence, store energy in the distorted crystalline structure. The structural integrity of nuclear grade graphite was quantified using high-resolution transmission electron microscopy (HRTEM). The microstructure was estimated by the fast Fourier transform of HRTEM images. Within the samples irradiated with 10 dpa at 600 °C, the d-spacing of {0 0 0 2} expanded from 0.336 nm to 0.396 nm accompanying with the greatest distorted graphite microstructure. The c-axis of graphite swelled approximately 18% and the disorder coefficient was 1.10 ± 0.17 (1/nm). The synchrotron X-ray experimental results, gauged from 500 μm3 volume, suggesting that the ion-implanted graphite only deformed locally and epitaxially. This study also presents possible mechanisms.

  16. Petrology and Geochronology of High-Grade Metamorphic Rocks from Cedros Island, Baja California, Mexico

    NASA Astrophysics Data System (ADS)

    Gonzales, D.; Leech, M. L.

    2014-12-01

    High-grade metamorphic rocks exposed on Cedros Island, Baja California, Mexico, record the Mesozoic subduction history of western North America. Blocks of amphibolite, blueschist, and eclogite crop out in a serpentinite-matrix mélange on the southeast and southwestern parts of Cedros Island. Amphibolite blocks contain Amp + Ep + Ab + Chl ± Ms ± Grt ± Ttn ± Qz; blueschist blocks have the assemblage Na-Amp + Ms + Lw + Qz ± Ttn ± Grt ± Jd ± Chl; and eclogite blocks are comprised primarily of Omp + Grt with retrograde Na-Amp + Ms + Lw. Blueschists from Cedros have been dated using 40Ar/39Ar step-heating of white mica and sodic amphiboles that yield ages from 103 ± 4 Ma to 94.9 ± 1.1 Ma, respectively, that represent cooling during exhumation. Apatite fission-track dating gives ages from 32 ± 4 Ma to 22 ± 3 Ma that record exhumation through the upper crust. Related Mesozoic subduction zone rocks of the Franciscan Complex crop out in a serpentinite-matrix mélange along coastal northern California. The Franciscan rocks are older, yielding 40Ar/39Ar step-heating ages of hornblende from amphibolite ranging from 159 to 156 Ma and represent an older part of the subduction history of the oceanic Farallon plate along western North America. I will determine the prograde and peak metamorphic P-T conditions for these high-grade rocks using petrography, mineral chemistries, and isochemical phase diagram modeling with Perple_X to generate complete P-T paths. I will then supplement these data with Sm-Nd and Lu-Hf geochronology for these high-grade Cedros rocks to evaluate their subduction/exhumation history, and develop a tectonic model for these southernmost Franciscan-type rocks. Ultimately, I will compare my results to Franciscan rocks in northern California to better understand the Mesozoic subduction margin of western North America.

  17. Architectural patterns of ovarian/pelvic high-grade serous carcinoma.

    PubMed

    Bromley, Amy B; Altman, Alon D; Chu, Pamela; Nation, Jill G; Nelson, Gregg S; Ghatage, Praful; Kalloger, Steve E; Han, Guangming; Köbel, Martin

    2012-09-01

    We describe the architectural patterns of advanced ovarian/pelvic high-grade serous carcinomas that have been treated with upfront surgery, followed by adjuvant chemotherapy or neoadjuvant chemotherapy, followed by interval debulking to explore the association with the chemotherapeutic response. For 70 cases of advanced (i.e. stage III/IV) high-grade serous carcinomas (33 platinum resistant/intermediate, 37 platinum sensitive; 24 neoadjuvantly treated, 44 primary surgery), all tumor-containing histologic slides were reviewed by 1 of 3 pathologists. Histologic type was confirmed and the following features were assessed: major architectural pattern and the presence of any of 8 predefined minor architectural patterns (papillary, transitional cell carcinoma-like, micropapillary, microcystic, nested papillary, slit-like, glandular, solid). A semiquantitative assessment of psammoma bodies, histiocytic response, necrosis, nuclear atypia, and single-cell invasion was performed. Mitotic count was performed in 10 HPF and 1 HPF was counted for intraepithelial lymphocytes. The morphologic features were tested for an association with previous neoadjuvant chemotherapy and response to chemotherapy (resistant/intermediate versus chemotherapy-sensitive cases stratified by neoadjuvant chemotherapy), which was carried out using χ tests for categorical variables and analysis of variance for continuous data. Combinations of features were analyzed using unsupervised clustering (Wald). Although 8 of 18 features were significantly different when samples from neoadjuvantly treated patients were compared with those not previously treated, no individual histomorphologic feature or a combination of features was associated with response to chemotherapy. Further subtyping of high-grade serous carcinomas will likely need ancillary molecular markers that may have a greater potential to identify cases that will not respond to platinum-based chemotherapy.

  18. New generation of high average power industry grade ultrafast ytterbium fiber lasers

    NASA Astrophysics Data System (ADS)

    Yusim, Alex; Samartsev, Igor; Shkurikhin, Oleg; Myasnikov, Daniil; Bordenyuk, Andrey; Platonov, Nikolai; Kancharla, Vijay; Gapontsev, Valentin

    2016-03-01

    We report an industrial grade picosecond and femtosecond pulse Yb fiber lasers with >100 μJ pulse energy and hundreds of Watts of average power for improved laser machining speed of sapphire and glass. This highly efficient laser offers >25% wall plug efficiency within a compact 3U rack-mountable configuration plus a long >2m fiber delivery cable. Reconfigurable features such as controllable repetition rate, fine pulse duration control, burst mode operation and adjustable pulse energy permit the customer to tailor the laser to their application.

  19. High-performance single-photon generation with commercial-grade optical fiber

    SciTech Connect

    Soeller, Christoph; Silberhorn, Christine; Cohen, Offir; Smith, Brian J.; Walmsley, Ian A.

    2011-03-15

    High-quality quantum sources are of paramount importance for the implementation of quantum technologies. We present here a heralded single-photon source based on commercial-grade polarization-maintaining optical fiber. The heralded photons exhibit a purity of at least 0.84 and an unprecedented heralding efficiency into a single-mode fiber of 85%. The birefringent phase-matching condition of the underlying four-wave mixing process can be controlled mechanically to optimize the wavelength tuning needed for interfacing multiple sources, as is required for large-scale entanglement generation.

  20. Current and future directions for Phase II trials in high-grade glioma.

    PubMed

    Alexander, Brian M; Lee, Eudocia Q; Reardon, David A; Wen, Patrick Y

    2013-04-01

    Despite surgery, radiation and chemotherapy, the prognosis for high-grade glioma (HGG) is poor. Our understanding of the molecular pathways involved in gliomagenesis and progression has increased in recent years, leading to the development of novel agents that specifically target these pathways. Results from most single-agent trials have been modest at best, however. Despite the initial success of antiangiogenesis agents in HGG, the clinical benefit is short-lived and most patients eventually progress. Several novel agents, multi-targeted agents and combination therapies are now in clinical trials for HGG and several more strategies are being pursued.

  1. Vesigenurtacel-L (HS-410) in the management of high-grade nonmuscle invasive bladder cancer.

    PubMed

    Keehn, Aryeh; Gartrell, Benjamin; Schoenberg, Mark P

    2016-12-01

    Unlike other malignancies, the death rate of bladder cancer has not declined in several decades, highlighting the need for new treatment options. In the emerging era of immunotherapy, therapeutic cancer vaccines are an attractive option to cure, control and prevent cancer. Despite this, finding a feasible and efficacious vaccine platform has proven elusive across all malignancies. Vesigenurtacel-L is the first whole cell, allogeneic vaccine intended to treat high-grade, nonmuscle invasive bladder cancer. This type of vaccine technology for bladder cancer is novel, and has the potential to be both economically and logistically feasible.

  2. Development of the Single Graded Groove high-performance heat pipe

    NASA Technical Reports Server (NTRS)

    Ambrose, J. H.; Holmes, H. R.

    1991-01-01

    This paper describes the development of a new nonarterial heat pipe with a nominal transport capability of 100,000 W in. Data are presented for one-g transport capability as a function of tilt and working fluid quantity. The transport capability agrees well with theoretical predictions. The LMSC Graded Groove Heat Pipe exhibits the high throughput and excellent heat transfer characteristics of earlier arterial designs such as the LMSC Tapered Artery Heat Pipe. At the same time, it suffers none of the priming difficulties associated with the arterial designs.

  3. High-grade, nonmyogenic pulmonary artery sarcoma: rare findings on coronary angiography.

    PubMed

    Ramjee, Vimal; Lewis, Melinda M; Clements, Stephen D

    2011-01-01

    Pulmonary artery sarcomas are exceptionally rare, and they are often misdiagnosed as chronic pulmonary thromboemboli. Early and accurate diagnosis is crucial to the prognosis of patients who have pulmonary artery sarcomas.Herein, we describe the case of a 74-year-old man who presented with dyspnea and was initially thought to have a pulmonary embolus. Anticoagulation with unfractionated heparin was ineffective. Rare angiographic findings during routine cardiac catheterization led to the diagnosis of a high-grade, nonmyogenic, primary pulmonary artery sarcoma. This case illustrates the usefulness of angiographic findings as an adjunct to conventional diagnostic methods in correctly identifying this rare, aggressive malignancy.

  4. Unique genetic and epigenetic mechanisms driving paediatric diffuse high-grade glioma.

    PubMed

    Jones, Chris; Baker, Suzanne J

    2014-10-01

    Diffuse high-grade gliomas (HGGs) of childhood are a devastating spectrum of disease with no effective cures. The two-year survival for paediatric HGG ranges from 30%, for tumours arising in the cerebral cortex, to less than 10% for diffuse intrinsic pontine gliomas (DIPGs), which arise in the brainstem. Recent genome-wide studies provided abundant evidence that unique selective pressures drive HGG in children compared to adults, identifying novel oncogenic mutations connecting tumorigenesis and chromatin regulation, as well as developmental signalling pathways. These new genetic findings give insights into disease pathogenesis and the challenges and opportunities for improving patient survival in these mostly incurable childhood brain tumours.

  5. High expression of glucose-regulated protein 78 (GRP78) is associated with metastasis and poor prognosis in patients with esophageal squamous cell carcinoma

    PubMed Central

    Ren, Peng; Chen, Chuangui; Yue, Jie; Zhang, Jianguo; Yu, Zhentao

    2017-01-01

    Background Glucose-regulated protein 78 (GRP78) plays an important role in the invasion and metastasis of many human cancers. However, the role of this protein in the progression of invasion and metastasis in esophageal squamous cell carcinoma (ESCC) remains elusive. Patients and methods Immunohistochemistry and Western blot were performed to analyze GRP78 expression in 92 patients with primary ESCC. The correlation of GRP78 expression with clinicopathological factors was analyzed. In vitro, the expression levels of GRP78 were downregulated by small interfering RNA transfection in TE-1 and CaEs-17 ESCC lines. Cell invasion and migration assays were applied to determine the invasion and migratory abilities of ESCC cells. Results Compared with GRP78 in adjacent normal esophageal tissues, GRP78 was overexpressed in ESCC tissues. High GRP78 expression was significantly correlated with positive lymph node metastasis (P=0.035) and advanced tumor stage (P=0.017). Survival analysis revealed that high GRP78 expression was significantly associated with shorter overall survival (P=0.037). In multivariate analysis, GRP78 overexpression was identified as an independent prognostic factor for overall survival (P=0.011). si-GRP78 can significantly decrease the GRP78 expression level and reverse the invasion and migratory abilities of ESCC cells in TE-1 and CaEs-17 cell lines. Conclusion These findings demonstrated that high expression of GRP78 was associated with disease progression and metastasis in ESCC and might serve as a novel prognostic marker for patients with ESCC. PMID:28228658

  6. Increased expression of sialic acid in cervical biopsies with squamous intraepithelial lesions

    PubMed Central

    2010-01-01

    Background Altered sialylation has been observed during oncogenic transformation. Sialylated oligosaccharides of glycoproteins and glycolipids have been implicated in tumor progression and metastases. In the cervical cancer high levels of sialic acid have been reported in the patients serum, and an increased of total sialic acid concentration has been reported for the cervical neoplasia and cervical cancer. This study investigates the changes in expression and distribution of α2,3-linked sialic acid and α2,6- linked sialic acid in low and high squamous intraepithelial lesions and in normal tissue. Methods Lectin histochemistry was used to examine the expression and distribution of sialic acid in different grades of cervical neoplasia. We applied Maackia amurensis lectin, which interacts with α2,3-linked sialic acid and Sambucus nigra lectin specific for α2,6-linked sialic acid. Results The histochemical analysis showed that α2,3-linked sialic acid and α2,6- linked sialic acid increased in intensity and distribution in concordance with the grade of squamous intraepithelial lesion (SIL). These results are in concordance with a previous study that reports increased RNAm levels of three sialyltransferases. Conclusions These results show that the change in sialylation occurs before cancer development and may play an important role in cellular transformation. These findings provide the basis for more detailed studies of the possible role of cell surface glycoconjugates bearing sialic acid in the cellular cervix transformation. PMID:21092209

  7. Role of protein biomarkers in the detection of high-grade disease in cervical cancer screening programs.

    PubMed

    Brown, Charlotte A; Bogers, Johnannes; Sahebali, Shaira; Depuydt, Christophe E; De Prins, Frans; Malinowski, Douglas P

    2012-01-01

    Since the Pap test was introduced in the 1940s, there has been an approximately 70% reduction in the incidence of squamous cell cervical cancers in many developed countries by the application of organized and opportunistic screening programs. The efficacy of the Pap test, however, is hampered by high interobserver variability and high false-negative and false-positive rates. The use of biomarkers has demonstrated the ability to overcome these issues, leading to improved positive predictive value of cervical screening results. In addition, the introduction of HPV primary screening programs will necessitate the use of a follow-up test with high specificity to triage the high number of HPV-positive tests. This paper will focus on protein biomarkers currently available for use in cervical cancer screening, which appear to improve the detection of women at greatest risk for developing cervical cancer, including Ki-67, p16(INK4a), BD ProEx C, and Cytoactiv HPV L1.

  8. Structural patterns in high grade terrain in parts of Tamil Nadu and Karnataka

    NASA Technical Reports Server (NTRS)

    Sugavanam, E. B.; Vidyadharan, K. T.

    1988-01-01

    Detailed geological mapping in parts of Tamil Nadu and Karnataka has brought out vast areas occupied by highly deformed charnockite and high grade gneisses. These areas, similar to high grade shield terrains in other parts of the world have the impress of extensive tectonic reworking multideformation and polymetamorphism and are closely associated with layered ultramafics, shelf type sediments and different igneous events. In North Arcot and Charmapuri districts of Tamil Nadu and Kollegal taluk in Mysore district in Karnataka, charnockite is intensely cofolded with a supracrustal succession of layered ultramafics, pyroxene granulite, pink granolites, magnetite quartzite and khondalites. These areas have undergone five phases of deformation, five generations of basic dyke activities, four phases of migmatisation and two periods of metallogeny. Geochronological data ranges from 2900 m.y. to 750 m.y. In working out the tectanostratigraphy of the above areas the basic dykes of different generations have served as major time markers. In addition, the persistent strike continuity of linear bands of pyroxene granulite, pink granolite and magnetite quartzite has been of great utility in using them as structural markers for bringing out the complex structural history in these areas.

  9. 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.

  10. Histopathologic risk factors in oral and oropharyngeal squamous cell carcinoma variants: an update with special reference to HPV-related carcinomas.

    PubMed

    El-Mofty, Samir K

    2014-07-01

    Accurate identification of the microscopic risk factors of oral and oropharyngeal (OP) squamous cell carcinomas (SCC) and their morphologic variants is of at most importance, as these generally determine treatment modalities, prognosis and overall patient outcome. The great majority of oral and oropharyngeal squamous cell carcinomas are microscopically described as kerartinizing squamous cell carcinoma (KSCC). They bear certain resemblance to keratinizing stratified squamous epithelium. Tobacco habits and excessive consumption of alcoholic beverages have been considered to be the main etiologic agents in these carcinomas. The tumors occurred in older patients more commonly affected the oral tongue and floor of the mouth with well established morphologic risk factors including tumor grade, pattern of invasion and perineural involvement. Within the last 30 years however, the advent and expanding prevalence of high risk human papillomavirus (HPV) as an important etiologic agent for head and neck squamous cell carcinoma, particularly in the OP, has resulted in a significant change in the established morphologic criteria for risk assessment. The majority of HPV relate carcinomas of the OP are nonkeratinizing squamous cell carcinoma (NKSCC). These tumors are found to be more responsive to treatment with a favorable patient outcome and good prognosis. Consequently, alterations in treatment protocols aimed at de-escalation are currently being evaluated. More recently, other morphologic variants that are HPV positive are reported with increasing frequency in the OP and other head and neck sites. As a result, several clinical and pathologic questions have emerged. Importantly, whether the virus is biologically active in these tumors and involved in their pathogenesis, and second, what are the clinical implications with regard to patient management and outcome in the HPV-related variants. Examples of HPV-related squamous cell carcinoma variants that will be addressed here are

  11. Cognitive strategies and quality of life of patients with high-grade glioma.

    PubMed

    Lucchiari, C; Botturi, A; Silvani, A; Lamperti, E; Gaviani, P; Innocenti, A; Finocchiaro, C Y; Masiero, M; Pravettoni, G

    2015-12-01

    The purpose of this study was to analyze the psychological well-being, quality of life, and cognitive strategies activated by patients with high-grade glioma. We hypothesized that the self-perceived quality of life is modulated by physical and psychological factors and that in order to understand this modulation more psychometric approaches are necessary. Data were collected from a sample of 73 consecutive patients with a histological diagnosis of primary malignant brain cancer (grade IV glioblastoma and grade III anaplastic astrocytoma) hospitalized in a specialized Italian center. The Functional Assessment of Cancer Therapy (FACT) scale and the Schedule of Evaluation of Individual Quality of Life-Direct Weighting (SEIQoL-DW) scale were used to assess quality of life. The mean FACT-Brain (Br) score was 122.37. Similarly, the median SEIQoL-DW score was 72.9 out of a maximum value of 100. No gender effect was found in relation to overall quality of life. Patients with high depression and/or anxiety scores reported lower quality of life (QoL) scores in all the instruments considered. We did not find any gender effect concerning depression and anxiety levels. However, we found that men and women, though having similar physical and functional well-being, reported different QoL determinants, since men seem to rely more on physical adjustment, while women activate more introspective strategies. Positive actions, family issues, negative thoughts, health, and positive thoughts were found to be the most reported themes. In conclusion, the present study strongly suggests that a positive psychological adjustment is possible also in the event of a severe diagnosis and during aggressive treatments, but QoL determinants might be considered too in order to help health professionals to understand patients' experience and to meet their needs.

  12. Intensity-modulated radiotherapy in high-grade gliomas: Clinical and dosimetric results

    SciTech Connect

    Narayana, Ashwatha . E-mail: narayana@mskcc.org; Yamada, Josh; Berry, Sean; Shah, Priti B.S.; Hunt, Margie; Gutin, Philip H.; Leibel, Steven A.

    2006-03-01

    Purpose: To report preliminary clinical and dosimetric data from intensity-modulated radiotherapy (IMRT) for malignant gliomas. Methods and Materials: Fifty-eight consecutive high-grade gliomas were treated between January 2001 and December 2003 with dynamic multileaf collimator IMRT, planned with the inverse approach. A dose of 59.4-60 Gy at 1.8-2.0 Gy per fraction was delivered. A total of three to five noncoplanar beams were used to cover at least 95% of the target volume with the prescription isodose line. Glioblastoma accounted for 70% of the cases, and anaplastic oligodendroglioma histology (pure or mixed) was seen in 15% of the cases. Surgery consisted of biopsy only in 26% of the patients, and 80% received adjuvant chemotherapy. Results: With a median follow-up of 24 months, 85% of the patients have relapsed. The median progression-free survival time for anaplastic astrocytoma and glioblastoma histology was 5.6 and 2.5 months, respectively. The overall survival time for anaplastic glioma and glioblastoma was 36 and 9 months, respectively. Ninety-six percent of the recurrences were local. No Grade IV/V late neurologic toxicities were noted. A comparative dosimetric analysis revealed that regardless of tumor location, IMRT did not significantly improve target coverage compared with three-dimensional planning. However, IMRT resulted in a decreased maximum dose to the spinal cord, optic nerves, and eye by 16%, 7%, and 15%, respectively, owing to its improved dose conformality. The mean brainstem dose also decreased by 7%. Intensity-modulated radiotherapy delivered with a limited number of beams did not result in an increased dose to the normal brain. Conclusions: It is unlikely that IMRT will improve local control in high-grade gliomas without further dose escalation compared with conventional radiotherapy. However, it might result in decreased late toxicities associated with radiotherapy.

  13. A phase I study afatinib/carboplatin/paclitaxel induction chemotherapy followed by standard chemoradiation in HPV-negative or high-risk HPV-positive locally advanced stage III/IVa/IVb head and neck squamous cell carcinoma

    PubMed Central

    Chung, Christine H.; Rudek, Michelle A.; Kang, Hyunseok; Marur, Shanthi; John, Pritish; Tsottles, Nancy; Bonerigo, Sarah; Veasey, Andy; Kiess, Ana; Quon, Harry; Cmelak, Anthony; Murphy, Barbara A.; Gilbert, Jill

    2015-01-01

    Introduction Afatinib is an ErbB family receptor inhibitor with efficacy in head and neck squamous cell carcinoma (HNSCC). A phase I trial was conducted to determine the maximally tolerated dose (MTD) of afatinib in combination with carboplatin and paclitaxel as induction chemotherapy (IC). Material and Methods Patients with newly diagnosed, locally advanced HPV-negative or HPV-positive HNSCC with a significant smoking history were enrolled. Afatinib alone was given daily for two weeks as lead-in and subsequently given with carboplatin AUC 6 mg/ml*min and paclitaxel 175 mg/m2 every 21 days as IC. Afatinib was started at a dose of 20 mg daily and dose escalated using a modified Fibonacci design. After completion of IC, afatinib was discontinued and patients received concurrent cisplatin 40 mg/m2 weekly and standard radiation. Toxicity was assessed using CTCAE version 4.0. Results Seven of nine patients completed afatinib lead-in and IC. Five patients had partial response and two patients had stable disease after IC. Dose level 1 (afatinib 20 mg) was well tolerated with one grade 3 (ALT elevation) and one grade 4 (neutropenia) toxicities. However, dose level 2 (afatinib 30 mg) was not well tolerated with nine grade 3 (pneumonia, abdominal pain, diarrhea, pancytopenia, and UTI), two grade 4 (sepsis) and one grade 5 (death) toxicities. Conclusions The MTD of afatinib given with carboplatin AUC 6 mg/ml*min and paclitaxel 175 mg/m2 is 20 mg daily. Combination of afatinib at doses higher than 20 mg with carboplatin and paclitaxel should be administered with caution due to the toxicities. PMID:26705063

  14. Surveillance of Anaemia: Mapping and Grading the High Risk Territories and Populations

    PubMed Central

    Amirapu, Pallavi

    2016-01-01

    Introduction Surveillance of anaemia is an ongoing process for assessing iron status and anaemia prevalence among individuals and the communities they live in. Measuring blood haemoglobin levels is the commonest method espoused worldwide for screening individuals and populations for anaemia and iron deficiency. World Health Organization (WHO) proposed a classification of public health significance of anaemia in populations on the basis of prevalence estimated from blood levels of haemoglobin. India falls under “Severe public health problem” category. An attempt has been made to categorise “Severe public health problem” into grades of severity that will help in prioritising the states and districts for targeted action. Aim To adapt the “WHO Classification of anaemia as a problem of public health significance” and to use the same to identify and map high risk population groups in the southern states of India. Materials and Methods The category of ’Severe Public Health Problem’ has been graded based on prevalence of anaemia. Secondary data published in the District Level Household and Facility Survey - 4 is analysed for five states and 1 UT (Union Territory) of southern part of India. Choropleth Mapping was done to visually depict the intensity of anaemia problem across the geographic territories. Results Children from 6 months to 59 months were having highest prevalence of both, anaemia (68%) and severe anaemia (10%). This was followed by pregnant women aged 15 to 49 years and Girl Child 6 to 9 years. Four of the Southern states of India including Andhra Pradesh, Karnataka, Telangana and Tamil Nadu fall in the Grade 2 SPHP (Severe Public Health Problem) Conclusion The sixteen districts fall under Grade 3 Severe Public Health Problem in the states of Andhra Pradesh, Karnataka and Telangana, require special focus for identifying and addressing the determinants of such high prevalence of Anaemia. These populations and territories require priority in the

  15. Formation conditions of high-grade gold-silver ore of epithermal Tikhoe deposit, Russian Northeast

    NASA Astrophysics Data System (ADS)

    Volkov, A. V.; Kolova, E. E.; Savva, N. E.; Sidorov, A. A.; Prokof'ev, V. Yu.; Ali, A. A.

    2016-09-01

    The Tikhoe epithermal deposit is located in the Okhotsk-Chukotka volcanic belt (OChVB) 250 km northeast of Magadan. Like other deposits belonging to the Ivan'insky volcanic-plutonic depression (VTD), the Tikhoe deposit is characterized by high-grade Au-Ag ore with an average Au grade of 23.13 gpt Au and Au/Ag ratio varying from 1: 1 to 1: 10. The detailed explored Tikhoe-1 orebody is accompanied by a thick (20 m) aureole of argillic alteration. Pyrite is predominant among ore minerals; galena, arsenopyrite, sphalerite, Ag sulfosalts, fahlore, electrum, and küstelite are less abundant. The ore is characterized by abundant Sebearing minerals. Cu-As geochemical specialization is noted for silver minerals. Elevated Se and Fe molar fractions of the main ore minerals are caused by their formation in the near-surface argillic alteration zone. The veins and veinlets of the Tikhoe-1 ore zone formed stepwise at a temperature of 230 to 105°C from Nachloride solution enriched in Mg and Ca cations with increasing salinity. The parameters of the ore-forming fluid correspond to those of epithermal low-sulfidation deposits and assume the formation of high-grade ore under a screening unit of volcanic rocks. In general, the composition of the ore-forming fluid fits the mineralogy and geochemistry of ore at this deposit. The similarity of the ore composition and parameters of the ore-forming fluid between the Tikhoe and Julietta deposits is noteworthy. Meanwhile, differences are mainly related to the lower temperature and fluid salinity at the Julietta deposit with respect to the Tikhoe deposit. The fluid at the Julietta deposit is depleted in most components compared with that at the Tikhoe deposit except for Sb, Cd, and Ag. The results testify to a different erosion level at the deposits as derivatives of the same ore-forming system. The large scale of the latter allows us to predict the discovery of new high-grade objects, including hidden mineralization, which is not exposed at

  16. 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

  17. High RAB25 expression is associated with good clinical outcome in patients with locally advanced head and neck squamous cell carcinoma

    PubMed Central

    Téllez-Gabriel, Marta; Arroyo-Solera, Irene; León, Xavier; Gallardo, Alberto; López, Montserrat; Céspedes, Maria V; Casanova, Isolda; López-Pousa, Antonio; Quer, Miquel; Mangues, Maria A; Barnadas, Agustí; Mangues, Ramón; Pavón, Miguel A

    2013-01-01

    Currently there are no molecular markers able to predict clinical outcome in locally advanced head and neck squamous cell carcinoma (HNSCC). In a previous microarray study, RAB25 was identified as a potential prognostic marker. The aim of this study was to analyze the association between RAB25 expression and clinical outcome in patients with locally advanced HNSCC treated with standard therapy. In a retrospective immunohistochemical study (n = 97), we observed that RAB25-negative tumors had lower survival (log-rank, P = 0.01) than patients bearing positive tumors. In an independent prospective mRNA study (n = 117), low RAB25 mRNA expression was associated with poor prognosis. Using classification and regression tree analysis (CART) we established two groups of patients according to their RAB25 mRNA level and their risk of death. Low mRNA level was associated with poor local recurrence-free (log-rank, P = 0.005), progression-free (log-rank, P = 0.002) and cancer-specific (log-rank, P < 0.001) survival. Multivariate Cox model analysis showed that low expression of RAB25 was an independent poor prognostic factor for survival (hazard ratio: 3.84, 95% confidence interval: 1.93–7.62, P < 0.001). Patients whose tumors showed high RAB25 expression had a low probability of death after treatment. We also found lower RAB25 expression in tumors than in normal tissue (Mann–Whitney U, P < 0.001). Moreover, overexpression of RAB25 in the UM-SCC-74B HNSCC cell line increased cisplatin sensitivity, and reduced cell migration and invasion. Our findings support a tumor suppressor role for RAB25 in HNSCC and its potential use to identify locally advanced patients with a high probability of survival after genotoxic treatment. PMID:24403269

  18. Performance of a Branch Chain RNA In Situ Hybridization Assay for the Detection of High-risk Human Papillomavirus in Head and Neck Squamous Cell Carcinoma.

    PubMed

    Kerr, Darcy A; Arora, Kshitij S; Mahadevan, Krishnan K; Hornick, Jason L; Krane, Jeffrey F; Rivera, Miguel N; Ting, David T; Deshpande, Vikram; Faquin, William C

    2015-12-01

    High-risk human papillomavirus (HR-HPV) is a major etiologic agent in a subset of head and neck squamous cell carcinomas (HNSCCs), and its recognition has prognostic and predictive implications. The availability of a sensitive and specific test to assess HR-HPV status is limited. We evaluate an RNA in situ hybridization (ISH) method using branch chain technology to detect HR-HPV and compare its results with DNA ISH, p16 immunohistochemistry, and polymerase chain reaction (PCR). Tissue sections from 54 patients were stained with a manual RNA ISH assay (ViewRNA), which detects 14 HR-HPV types, an automated DNA ISH assay, and p16 immunohistochemistry. Most cases (83%, n=45) were also tested on an automated platform for 14 HR-HPV types and 1 limited to HPV 16/18. PCR was performed in all cases and was successful in 93% (n=50). The RNA ISH assay produced results in 96% of the cases with strong signals and was easily interpreted. HR-HPV was detected in more cases (63%, n=34) by RNA ISH than by DNA ISH (39%, n=21). Compared with PCR, both ISH platforms were 94% specific. RNA ISH was more sensitive (91%) than DNA ISH (65%), and RNA ISH correlated more strongly with p16 immunostaining. HPV 16 represented 89% of HR-HPV detected. The cocktail HPV 16/18 platform was concordant with the pooled HR-HPV assay in all expected cases. The automated assay demonstrated high concordance (96%) with the manual version, showed decreased background, and should allow for easy implementation into the workflow of the diagnostic pathology laboratory.

  19. Validation of a diagnostic algorithm for the discrimination of actinic keratosis from normal skin and squamous cell carcinoma by means of high-definition optical coherence tomography.

    PubMed

    Marneffe, Alice; Suppa, Mariano; Miyamoto, Makiko; Del Marmol, Véronique; Boone, Marc

    2016-09-01

    Actinic keratoses (AKs) commonly arise on sun-damaged skin. Visible lesions are often associated with subclinical lesions on surrounding skin, giving rise to field cancerization. To avoid multiple biopsies to diagnose subclinical/early invasive lesions, there is an increasing interest in non-invasive diagnostic tools, such as high-definition optical coherence tomography (HD-OCT). We previously developed a HD-OCT-based diagnostic algorithm for the discrimination of AK from squamous cell carcinoma (SCC) and normal skin. The aim of this study was to test the applicability of HD-OCT for non-invasive discrimination of AK from SCC and normal skin using this algorithm. Three-dimensional (3D) HD-OCT images of histopathologically proven AKs and SCCs and images of normal skin were collected. All images were shown in a random sequence to three independent observers with different experience in HD-OCT, blinded to the clinical and histopathological data and with different experience with HD-OCT. Observers classified each image as AK, SCC or normal skin based on the diagnostic algorithm. A total of 106 (38 AKs, 16 SCCs and 52 normal skin sites) HD-OCT images from 71 patients were included. Sensitivity and specificity for the most experienced observer were 81.6% and 92.6% for AK diagnosis and 93.8% and 98.9% for SCC diagnosis. A moderate interobserver agreement was demonstrated. HD-OCT represents a promising technology for the non-invasive diagnosis of AKs. Thanks to its high potential in discriminating SCC from AK, HD-OCT could be used as a relevant tool for second-level examination, increasing diagnostic confidence and sparing patients unnecessary excisions.

  20. High-risk HPV genotypes and P16INK4a expression in a cohort of head and neck squamous cell carcinoma patients in Singapore.

    PubMed

    Tan, Louise Soo Yee; Fredrik, Petersson; Ker, Liang; Yu, Feng Gang; Wang, De Yun; Goh, Boon Cher; Loh, Kwok Seng; Lim, Chwee Ming

    2016-12-27

    Human papillomavirus (HPV), especially HPV16 genotype, is associated with oropharyngeal squamous cell carcinoma (OPSCC). We aim to determine the prevalence and characterize the high-risk (HR)-HPV genotypes in head and neck SCC (HNSCC) in a South-East Asian multi-ethnic society in Singapore and examine its prognostic significance.159 HNSCC archival tissue samples were retrieved and tumour DNA was screened for 18 HR-HPV genotypes using a PCR-based assay (Qiagen, digene HPV genotyping RH test). P16 protein overexpression was identified using immunohistochemistry (IHC). Statistical correlation between clinical outcomes were performed between HPV-positive and negative HNSCC patients.Six HR-HPVs (HPV16, 18, 31, 45, 56, 68) were detected in 90.6% of HNSCC; and 79.9% had multiple HPV genotypes detected. HPV31 and HPV45 were the most prevalent (79.2% and 87.4%, respectively); and HPV16 was predominantly found in OPSCC (p < 0.001). HPV-DNA PCR assay yielded a high sensitivity (96%) but low specificity (11%) when compared to p16 immunohistochemistry as the reference standard.P16-positive HNSCC was predominantly observed in OPSCC (73.7%; p = 0.005); and p16-positive OPSCC exhibited improved overall survival compared to p16-negative OPSCC (p = 0.022). Similarly, smoking and alcohol consumption were poor prognostic factors of overall survival (p = 0.007; p = 0.01) in OPSCC patients.HR-HPVs were identified in 90.6% of HNSCC patients using the HPV-DNA PCR assay. This test had a poor specificity when compared to p16 IHC; making it an unreliable detection technique in selecting patients for radiation dose de-escalation treatment protocol. P16-positive tumor was predominantly found in the oropharynx these patients demonstrated better overall survival than those with p16-negative OPSCC.

  1. High-risk HPV genotypes and P16INK4a expression in a cohort of head and neck squamous cell carcinoma patients in Singapore

    PubMed Central

    Tan, Louise Soo Yee; Fredrik, Petersson; Ker, Liang; Yu, Feng Gang; Wang, De Yun; Goh, Boon Cher; Loh, Kwok Seng; Lim, Chwee Ming

    2016-01-01

    Human papillomavirus (HPV), especially HPV16 genotype, is associated with oropharyngeal squamous cell carcinoma (OPSCC). We aim to determine the prevalence and characterize the high-risk (HR)-HPV genotypes in head and neck SCC (HNSCC) in a South-East Asian multi-ethnic society in Singapore and examine its prognostic significance. 159 HNSCC archival tissue samples were retrieved and tumour DNA was screened for 18 HR-HPV genotypes using a PCR-based assay (Qiagen, digene HPV genotyping RH test). P16 protein overexpression was identified using immunohistochemistry (IHC). Statistical correlation between clinical outcomes were performed between HPV-positive and negative HNSCC patients. Six HR-HPVs (HPV16, 18, 31, 45, 56, 68) were detected in 90.6% of HNSCC; and 79.9% had multiple HPV genotypes detected. HPV31 and HPV45 were the most prevalent (79.2% and 87.4%, respectively); and HPV16 was predominantly found in OPSCC (p < 0.001). HPV-DNA PCR assay yielded a high sensitivity (96%) but low specificity (11%) when compared to p16 immunohistochemistry as the reference standard. P16-positive HNSCC was predominantly observed in OPSCC (73.7%; p = 0.005); and p16-positive OPSCC exhibited improved overall survival compared to p16-negative OPSCC (p = 0.022). Similarly, smoking and alcohol consumption were poor prognostic factors of overall survival (p = 0.007; p = 0.01) in OPSCC patients. HR-HPVs were identified in 90.6% of HNSCC patients using the HPV-DNA PCR assay. This test had a poor specificity when compared to p16 IHC; making it an unreliable detection technique in selecting patients for radiation dose de-escalation treatment protocol. P16-positive tumor was predominantly found in the oropharynx these patients demonstrated better overall survival than those with p16-negative OPSCC. PMID:27893418

  2. Incidental nonuterine high-grade serous carcinomas arise in the fallopian tube in most cases: further evidence for the tubal origin of high-grade serous carcinomas.

    PubMed

    Gilks, C Blake; Irving, Julie; Köbel, Martin; Lee, Chenghan; Singh, Naveena; Wilkinson, Nafisa; McCluggage, W Glenn

    2015-03-01

    Most nonuterine high-grade serous carcinomas (HGSCs) in women with hereditary breast and ovarian cancer syndrome, due to germline BRCA1/2 mutation, arise in the fimbria of the fallopian tube. However, the site of origin of sporadic HGSC, which is usually widely disseminated at presentation, is not well established. We sought to characterize cases of HGSC discovered incidentally in patients not known to be at high risk, in order to determine the site distribution and possible origin of sporadic HGSC. Incidental microscopic, non-mass-forming cases of serous tubal intraepithelial carcinoma or HGSC in salpingo-oophorectomy specimens in which the tubes and ovaries had been extensively examined were identified. No patients were known or suspected BRCA1/2 mutation carriers. Twenty-one cases were identified (mean age: 57 y). Surgery was for benign disease (n=15), uterine endometrioid adenocarcinoma or atypical hyperplasia (n=3), bladder carcinoma (n=1), or ovarian serous borderline tumor (n=2). In 16 of 21 cases, the lesion was confined to the fallopian tube (unilateral in 14 cases, bilateral in 2). There was serous tubal intraepithelial carcinoma in all cases and invasive HGSC into the underlying lamina propria in 8 of these 16 cases; the invasive focus measured 1.3 cm or less in every case. In the remaining 5 cases, there was fallopian tube mucosal and ovarian involvement; in 2 of these cases, there was also microscopic peritoneal involvement. Sporadic cases of nonuterine HGSC arise in the fallopian tube fimbria in a large majority of cases, providing further evidence for the tubal origin of these neoplasms.

  3. Therapeutic Targeting of Histone Modifications in Adult and Pediatric High-Grade Glioma

    PubMed Central

    Williams, Maria J.; Singleton, Will G. B.; Lowis, Stephen P.; Malik, Karim; Kurian, Kathreena M.

    2017-01-01

    Recent exciting work partly through The Cancer Genome Atlas has implicated epigenetic mechanisms including histone modifications in the development of both pediatric and adult high-grade glioma (HGG). Histone lysine methylation has emerged as an important player in regulating gene expression and chromatin function. Lysine (K) 27 (K27) is a critical residue in all seven histone 3 variants and the subject of posttranslational histone modifications, as it can be both methylated and acetylated. In pediatric HGG, two critical single-point mutations occur in the H3F3A gene encoding the regulatory histone variant H3.3. These mutations occur at lysine (K) 27 (K27M) and glycine (G) 34 (G34R/V), both of which are involved with key regulatory posttranscriptional modifications. Therefore, these mutations effect gene expression, cell differentiation, and telomere maintenance. In recent years, alterations in histone acetylation have provided novel opportunities to explore new pharmacological targeting, with histone deacetylase (HDAC) overexpression reported in high-grade, late-stage proliferative tumors. HDAC inhibitors have shown promising therapeutic potential in many malignancies. This review focuses on the epigenetic mechanisms propagating pediatric and adult HGGs, as well as summarizing the current advances in clinical trials using HDAC inhibitors.

  4. ZnO/(ZnMg)O single quantum wells with high Mg content graded barriers

    SciTech Connect

    Laumer, Bernhard; Schuster, Fabian; Wassner, Thomas A.; Stutzmann, Martin; Rohnke, Marcus; Schoermann, Joerg; Eickhoff, Martin

    2012-06-01

    ZnO/Zn{sub 1-x}Mg{sub x}O single quantum wells (SQWs) were grown by plasma-assisted molecular beam epitaxy on c-plane sapphire substrates. Compositional grading allows the application of optimized growth conditions for the fabrication of Zn{sub 1-x}Mg{sub x}O barriers with high crystalline quality and a maximum Mg content of x = 0.23. High resolution x-ray diffraction reveals partial relaxation of the graded barriers. Due to exciton localization, the SQW emission is found to consist of contributions from donor-bound and free excitons. While for narrow SQWs with well width d{sub W}{<=}2.5nm, the observed increase of the exciton binding energy is caused by quantum confinement, the drop of the photoluminescence emission below the ZnO bulk value found for wide SQWs is attributed to the quantum-confined Stark effect. For a Mg content of x = 0.23, a built-in electric field of 630 kV/cm is extracted, giving rise to a decrease of the exciton binding energy and rapid thermal quenching of the SQW emission characterized by an activation energy of (24 {+-} 4) meV for d{sub W} = 8.3 nm.

  5. Fine-needle aspiration diagnosis of high grade adenoid cystic carcinoma metastatic to the pancreas.

    PubMed

    David, Doina; Masineni, Sreeharsha N; Giorgadze, Tamar

    2015-02-01

    Pancreatic tumors are mostly primary tumors, with only rare metastatic tumors described in the literature. Here we report an unusual case of fine-needle aspiration (FNA) diagnosis of high grade adenoid cystic carcinoma of the parotid gland metastatic to the pancreas. The aspirate smears were moderately cellular and revealed numerous basaloid neoplastic cells. The cytomorphologic differential diagnosis included primary pancreatic tumor with small cell morphology as well as metastatic tumors. By immunocytochemistry, the tumor cells were positive for cytokeratins (AE1/AE3, CAM5.2, and CK7), and CD117 (C-KIT), and negative for CD45, WT1, synaptophysin, chromogranin, CD56, TTF-1, and CK20. The cytomorphologic features and immunoprofile in our case were consistent with high-grade carcinoma metastases from patient's known salivary gland primary. To the best of our knowledge, this case is the first reported encounter of FNA diagnosis of pancreatic metastasis with small cell morphology from a salivary gland neoplasm as primary site.

  6. Early presentation of de novo high grade glioma with epileptic seizures: electroclinical and neuroimaging findings.

    PubMed

    Rossi, Rosario; Figus, Andrea; Corraine, Simona

    2010-10-01

    We report the clinical, EEG and neuroradiologic findings from three adult patients who developed new-onset seizure disorders as early clinical manifestations of de novo high grade glioma. The malignancies could not be recognised at the time of the first epileptic seizure because of minimal non-specific brain abnormalities, which showed no signs of necrosis or significant contrast enhancement on computed tomography and magnetic resonance imaging. Focal EEG abnormalities were recorded in all cases and appeared consistent with the neuroradiologic findings. The patients regained normal neurological status after the first seizure but rapidly developed space-occupying necrotic lesions. Two patients underwent surgery and received histological diagnoses of the tumours. Another patient was finally diagnosed with a malignant glioma based on the neuroradiologic picture and rapid progression of the cerebral lesion. It should be noted that in adult patients, new-onset epileptic seizures might reveal the presence of malignant gliomas at a very early stage in the tumour formation process. This report indicates that typical anatomoradiologic features of de novo high grade glioma, such as necrosis and rim-contrast enhancement, could be absent at the time of the first epileptic seizure but become clear within a short period after clinical presentation.

  7. The Effect of High School Socioeconomic Status on the Predictive Validity of SAT Scores and High School Grade-Point Average

    ERIC Educational Resources Information Center

    Zwick, Rebecca; Himelfarb, Igor

    2011-01-01

    Research has often found that, when high school grades and SAT scores are used to predict first-year college grade-point average (FGPA) via regression analysis, African-American and Latino students, are, on average, predicted to earn higher FGPAs than they actually do. Under various plausible models, this phenomenon can be explained in terms of…

  8. Prediction of high-grade cervical intraepithelial neoplasia in cytologically normal women by human papillomavirusesting

    PubMed Central

    Carozzi, F; Ronco, G; Confortini, M; Noferini, D; Maddau, C; Ciatto, S; Segnan, N

    2000-01-01

    Human papillomavirus (HPV) testing has been suggested for primary screening of cervical cancer. Prediction of future high-grade cervical lesions is crucial for effectiveness and cost. We performed a case control study in a retrospective cohort of women with at least two cervical smears, all but the last one being negative, from the organized cervical screening programme in Florence, Italy. We searched for high-risk HPV in all previous, archival, smears from cases (new histologically confirmed cervical intraepithelial neoplasia (CIN) grade II or worse) and in one previous smear from each control (last smear cytologically normal, matched by age and interval (latency) from last smear). We applied polymerase chain reaction (PCR), and the b-globin gene was used as a DNA preservation marker. High-risk HPV was identified in 71/92 (77.17%) previous smears from 79 cases and 17/332 controls (5.12%). The odds ratio (OR) was 63.76 (95% CI 30.57–132.96). Among cases the proportion of HPV-positive smears declined slightly with increasing latency. Among cases, HPV was found in 81.24% (95% CI 69.93–88.96%) of smears with latency < 4 years and in 67.80% (95% CI 47.72–82.93%) of those taken at longer intervals, up to 6 years. These findings suggest that testing for high-risk HPV allows predicting 80% of CINII/III 3 years before the cytological diagnosis and two thirds 6 years before. They also suggest that testing women negative for high-risk HPV at longer interval and strictly following-up women who are HPV positive could be an effective strategy for cervical cancer screening. © 2000 Cancer Research Campaign http://www.bjcancer.com PMID:11076654

  9. Bazex Syndrome in Lung Squamous Cell Carcinoma: High Expression of Epidermal Growth Factor Receptor in Lesional Keratinocytes with Th2 Immune Shift

    PubMed Central

    Amano, Maki; Hanafusa, Takaaki; Chikazawa, Sakiko; Ueno, Makiko; Namiki, Takeshi; Igawa, Ken; Miura, Keiko; Yokozeki, Hiroo

    2016-01-01

    An 82-year-old Japanese man was referred for detailed examination of hyperkeratotic erythematous plaques on his palms and soles for 6 months. Two weeks before his first visit, he had undergone lung lobectomy for right lung squamous cell carcinoma (SCC). Laboratory findings showed elevations of eosinophil counts, serum IgE, thymus and activation-regulated chemokine, SCC antigen, and soluble interleukin-2 receptor levels. Histological results of a skin biopsy involving the left palm showed psoriasiform dermatitis. Before lung lobectomy, the hyperkeratotic erythematous plaques on the palms and soles and the erythemas on the trunk and extremities were difficult to treat with topical steroids. After lobectomy, the skin symptoms dramatically and rapidly subsided with topical steroids. Therefore, we diagnosed Bazex syndrome (BS), also known as acrokeratosis paraneoplastica, as a paraneoplastic cutaneous disease in lung SCC. The mild eosinophilia subsided and levels of SCC antigen, IgE, and soluble interleukin-2 receptor were reduced. BS is a paraneoplastic cutaneous disease characterized by acral psoriasiform lesions associated with an underlying neoplasm. In a previous report, a shift to the Th2 immune condition was found in patients with non-small cell lung cancer, as shown in our patient. Epidermal growth factor receptor (EGFR) is also known as tumor growth factor-α receptor; it is increased in psoriatic keratinocytes. In our case, EGFR expression increased in lesional keratinocytes 2 weeks after surgery and decreased 4 weeks after surgery. We speculate that a shift to Th2 immune reactions in lung SCC may be the pathogenesis of BS, whereby lesional keratinocytes highly express EGFR in parallel with disease activity. PMID:28101024

  10. High b-Value Diffusion MRI to Differentiate Recurrent Tumors from Posttreatment Changes in Head and Neck Squamous Cell Carcinoma: A Single Center Prospective Study

    PubMed Central

    Acampora, Angela; Manzo, Gaetana; Fenza, Giacomo; Busto, Giuseppina; Serino, Antonietta; Manto, Andrea

    2016-01-01

    Recently DW-MR Imaging has shown promising results in distinguishing between recurrent tumors and posttreatment changes in Head and Neck Squamous Cell Carcinoma (HNSSC). Aim of this study was to evaluate the diagnostic performances of DWI at high b-value (b = 2000 s/mm2) compared to standard b-value (b = 1000 s/mm2) and ADCratio values (ADCratio = ADC2000/ADC1000 × 100) to differentiate recurrent tumors from posttreatment changes after treatment of HSNCC. 20 patients (16 M, 4 F) underwent MR Imaging between 2 and 16 months (mean 7) after treatment. Besides morphological sequences, we performed single-shot echo-planar DWI at b = 1000 s/mm2 and b = 2000 s/mm2, and corresponding ADC maps were generated (ADC1000 and ADC2000, resp.). By considering contrast-enhanced T1-weighted images as references, ROIs were drawn in order to evaluate mean ADC1000, ADC2000, and ADCratio. The mean ADC1000 and ADC2000 in recurrent tumors were significantly lower than those in posttreatment changes (P = 0.001 and P = 0.016, resp.). Moreover, the mean ADCratio between the two groups showed a statistically significant difference (P = 0.002). Sensitivity, specificity, and accuracy of ADCratio were 82.0%, 100%, and 90%, respectively, by considering an optimal cutoff value of 65.5%. ADCratio is a promising value to differentiate between recurrent tumors and posttreatment changes in HNSCC and may be more useful than ADC1000 and ADC2000. PMID:27376081

  11. High b-Value Diffusion MRI to Differentiate Recurrent Tumors from Posttreatment Changes in Head and Neck Squamous Cell Carcinoma: A Single Center Prospective Study.

    PubMed

    Acampora, Angela; Manzo, Gaetana; Fenza, Giacomo; Busto, Giuseppina; Serino, Antonietta; Manto, Andrea

    2016-01-01

    Recently DW-MR Imaging has shown promising results in distinguishing between recurrent tumors and posttreatment changes in Head and Neck Squamous Cell Carcinoma (HNSSC). Aim of this study was to evaluate the diagnostic performances of DWI at high b-value (b = 2000 s/mm(2)) compared to standard b-value (b = 1000 s/mm(2)) and ADCratio values (ADCratio = ADC2000/ADC1000 × 100) to differentiate recurrent tumors from posttreatment changes after treatment of HSNCC. 20 patients (16 M, 4 F) underwent MR Imaging between 2 and 16 months (mean 7) after treatment. Besides morphological sequences, we performed single-shot echo-planar DWI at b = 1000 s/mm(2) and b = 2000 s/mm(2), and corresponding ADC maps were generated (ADC1000 and ADC2000, resp.). By considering contrast-enhanced T1-weighted images as references, ROIs were drawn in order to evaluate mean ADC1000, ADC2000, and ADCratio. The mean ADC1000 and ADC2000 in recurrent tumors were significantly lower than those in posttreatment changes (P = 0.001 and P = 0.016, resp.). Moreover, the mean ADCratio between the two groups showed a statistically significant difference (P = 0.002). Sensitivity, specificity, and accuracy of ADCratio were 82.0%, 100%, and 90%, respectively, by considering an optimal cutoff value of 65.5%. ADCratio is a promising value to differentiate between recurrent tumors and posttreatment changes in HNSCC and may be more useful than ADC1000 and ADC2000.

  12. Food preparation methods, drinking water source, and esophageal squamous cell carcinoma in the high-risk area of Golestan, Northeast Iran.

    PubMed

    Golozar, Asieh; Etemadi, Arash; Kamangar, Farin; Fazeltabar Malekshah, Akbar; Islami, Farhad; Nasrollahzadeh, Dariush; Abedi-Ardekani, Behnoosh; Khoshnia, Masoud; Pourshams, Akram; Semnani, Shahriar; Marjani, Haji Amin; Shakeri, Ramin; Sotoudeh, Masoud; Brennan, Paul; Taylor, Philip; Boffetta, Paolo; Abnet, Christian; Dawsey, Sanford; Malekzadeh, Reza

    2016-03-01

    Cooking practices and water sources have been associated with an increased risk of cancer, mainly through exposure to carcinogens such as heterocyclic amines, polycyclic aromatic hydrocarbons, and nitrates. Using data from the Golestan case-control study, carried out between 2003 and 2007 in a high-risk region for esophageal squamous cell carcinoma (ESCC), we sought to investigate the association between food preparation and drinking water sources and ESCC. Information on food preparation methods, sources of drinking water, and dietary habits was gathered from 300 cases and 571 controls matched individually for age, sex, and neighborhood using a structured questionnaire and a semiquantitative food frequency questionnaire. Multivariate conditional logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CI) adjusted for potential confounders and other known risk factors including socioeconomic status and smoking. More than 95% of the participants reported eating meat, mostly red meat. Red meat consumption above the 75th percentile increased the odds of ESCC by 2.82-fold (95% CI: 1.21-6.57). Fish intake was associated with a significant 68% decrease in ESCC odds (26%, 86%). Among meat eaters, ORs (95% CI) for frying meat (red or white) and fish were 3.34 (1.32-8.45) and 2.62 (1.24-5.5). Drinking unpiped water increased ESCC odds by 4.25 times (2.23-8.11). The OR for each 10-year increase in the duration of drinking unpiped water was 1.47 (1.22-1.78). Our results suggest roles for red meat intake, drinking water source, and food preparation methods in ESCC, even after adjusting for a large number of potential confounders.

  13. High-grade serous ovarian cancer 3 years after bilateral salpingectomy: A case report

    PubMed Central

    Sato, Emi; Nakayama, Kentaro; Ishikawa, Masako; Nakamura, Kohei; Ishibashi, Tomoka; Kyo, Satoru

    2017-01-01

    Although epithelial ovarian cancer commonly originates from the ovarian surface epithelium and/or ovarian inclusion cysts, it was recently proposed that high-grade serous ovarian cancer (HGSC) develops from the Fallopian tubes. In our department, we encountered a case of HGSC that contradicts the hypothesis of a tubal origin for HGSC. A 51-year-old postmenopausal woman had undergone hysterectomy, left oophorectomy and bilateral salpingectomy for uterine myoma. Three years later, the patient was diagnosed with stage IV ovarian cancer and underwent primary debulking surgery. The pathological examination revealed HGSC, although there was no evidence of serous tubal intraepithelial carcinoma or any other type of cancer in the previously resected left ovary and bilateral Fallopian tubes. Moreover, p53 overexpression was not detected in the right ovarian cancer specimen, while paired box gene 8, a marker of Fallopian tube epithelium, was highly expressed. Therefore, HGSC may develop from an inclusion cyst with metaplasia of from the ovarian surface epithelium.

  14. ADVANCED MR IMAGING METHODS FOR PLANNING AND MONITORING RADIATION THERAPY IN PATIENTS WITH HIGH GRADE GLIOMA

    PubMed Central

    Lupo, Janine M.; Nelson, Sarah J.

    2016-01-01

    This review explores how the integration of advanced imaging methods with high quality anatomic images significantly improves the characterization, target definition, assessment of response to therapy, and overall management of patients with high-grade glioma. Metrics derived from diffusion, perfusion, and susceptibility weighted MR imaging in conjunction with MR spectroscopic imaging, allows us to characterize regions of edema, hypoxia, increased cellularity, and necrosis within heterogeneous tumor and surrounding brain tissue. Quantification of such measures may provide a more reliable initial representation of tumor delineation and response to therapy than changes in the contrast enhancing or T2 lesion alone and have a significant impact on targeting resection, planning radiation, and assessing treatment effectiveness. In the long-term, implementation of these imaging methodologies can also aid in the identification of recurrent tumor and its differentiation from treatment-related confounds and facilitate the detection of radiation-induced vascular injury in otherwise normal appearing brain tissue. PMID:25219809

  15. CIGS absorber layer with double grading Ga profile for highly efficient solar cells

    NASA Astrophysics Data System (ADS)

    Saadat, M.; Moradi, M.; Zahedifar, M.

    2016-04-01

    It is well-known that the band gap grading in CIGS solar cells is crucial for achieving highly efficient solar cells. We stimulate a CIGS solar cell and investigate the effects of the band gap grading on performance of the CIGS solar cell, where Ga/(Ga + In) ratio (GGI) at back (Cb) and front (Cf) of the absorber layer are considered constant. Our simulations show that by increasing the GGI at middle of CIGS absorber layer (Cm), the JSC decreases and VOC increases independent of the distance of the Cm from the back contact (Xm). For Cm lower than Cf, JSC increases and VOC decreases when the Xm shifts to the front of the CIGS layer. The behavior of JSC and VOC became reverse for the case of Cm greater than Cf. Almost in all of the structures, efficiency and FF have same behaviors. Our simulations show that the highest efficiency is obtained at Cm = 0.8 and Xm = 200 nm.

  16. “Reverse Bohlman” technique for the treatment of high grade spondylolisthesis in an adult population

    PubMed Central

    Macagno, Angel E.; Hasan, Saqib; Jalai, Cyrus M.; Worley, Nancy; de Moura, Alexandre B.; Spivak, Jeffrey; Bendo, John A.; Passias, Peter G.

    2016-01-01

    Background/aims Surgical techniques for effective high-grade spondylolisthesis (HGS) remain controversial. This study aims to evaluate radiographic/clinical outcomes in HGS patients treated using modified “Reverse Bohlman” (RB) technique. Methods Review of consecutive HGS patients undergoing RB at a single university-center from 2006 to 2013. Clinical, surgical, radiographic parameters collected. Results Six patients identified: five with L5-S1 HGS with L4-L5 instability and one had an L4-5 isthmic spondylolisthesis and grade 1 L5-S1 isthmic spondylolisthesis. Two interbody graft failures and one L5-S1 pseudoarthrosis. Postoperative improvement of anterolisthesis (62.3% vs. 49.6%, p = 0.003), slip angle (10 vs. 5°, p = 0.005), and lumbar lordosis (49 vs. 57.5°, p = 0.049). Conclusions RB technique for HGS recommended when addressing adjacent level instability/slip. PMID:26955227

  17. Altered splicing leads to reduced activation of CPEB3 in high-grade gliomas

    PubMed Central

    Skubal, Magdalena; Gielen, Gerrit H.; Waha, Anke; Gessi, Marco; Kaczmarczyk, Lech; Seifert, Gerald; Freihoff, Dorothee; Freihoff, Johannes; Pietsch, Torsten; Simon, Matthias; Theis, Martin; Steinhäuser, Christian; Waha, Andreas

    2016-01-01

    Cytoplasmic polyadenylation element binding proteins (CPEBs) are auxiliary translational factors that associate with consensus sequences present in 3′UTRs of mRNAs, thereby activating or repressing their translation. Knowing that CPEBs are players in cell cycle regulation and cellular senescence prompted us to investigate their contribution to the molecular pathology of gliomas–most frequent of intracranial tumors found in humans. To this end, we performed methylation analyses in the promoter regions of CPEB1-4 and identified the CPEB1 gene to be hypermethylated in tumor samples. Decreased expression of CPEB1 protein in gliomas correlated with the rising grade of tumor malignancy. Abundant expression of CPEBs2-4 was observed in several glioma specimens. Interestingly, expression of CPEB3 positively correlated with tumor progression and malignancy but negatively correlated with protein phosphorylation in the alternatively spliced region. Our data suggest that loss of CPEB3 activity in high-grade gliomas is caused by expression of alternatively spliced variants lacking the B-region that overlaps with the kinase recognition site. We conclude that deregulation of CPEB proteins may be a frequent phenomenon in gliomas and occurs on the level of transcription involving epigenetic mechanism as well as on the level of mRNA splicing, which generates isoforms with compromised biological properties. PMID:27256982

  18. Upregulation of MICA on high-grade invasive operable breast carcinoma.

    PubMed

    Madjd, Zahra; Spendlove, Ian; Moss, Robert; Bevin, Shaun; Pinder, Sarah E; Watson, Nicholas F S; Ellis, Ian; Durrant, Lindy G

    2007-10-22

    The MHC class I chain-related gene A (MICA) is frequently expressed on the surface of intestinal epithelium and by many epithelial tumours. MICA is a stress-induced antigen which was identified as an activator of natural killer cells via interaction with the NKG2D receptor. We have raised a rabbit polyclonal antibody against a synthetic peptide that recognises denatured MICA on both Western blots and in formalin-fixed paraffin-embedded sections. In the present study this antibody was used to undertake a definitive study of 530 breast cancer cases with mean follow up of 7 years to determine the prognostic significance of MICA expression. To detect any association between MICA expression and NK infiltration, whole sections of 50 tumours were also analysed for CD56 staining. Univariate analysis showed significant relationships between MICA expression and histological grade (P = 0.006), lymph node stage (P = 0.013), Nottingham Prognostic Index (NPI, P = 0.002), the presence of vascular invasion (P = 0.045) and tumour type (P = 0.023). Upregulation of MICA was more often found in histological grade 3, poor prognosis (NPI >5.4) tumours. Association of high MICA expression with NK cell infiltration was not demonstrated, as very few NK cells were present in whole breast sections. Our results suggest that induced expression of MICA may be an indicator of poor prognosis in breast carcinoma and is indicative of a tumour environment that has undergone stresses such as apoptosis, necrosis, or hypoxia.

  19. FDG-PET predicts survival in recurrent high-grade gliomas treated with bevacizumab and irinotecan

    PubMed Central

    Colavolpe, Cécile; Chinot, Olivier; Metellus, Philippe; Mancini, Julien; Barrie, Maryline; Bequet-Boucard, Céline; Tabouret, Emeline; Mundler, Olivier; Figarella-Branger, Dominique; Guedj, Eric

    2012-01-01

    Prognosis of recurrent high-grade glioma (HGG) is poor, although bevacizumab has been documented in that context. This study aimed to determine the independent prognostic value of fluorodeoxyglucose (FDG)-PET on progression-free survival (PFS) and overall survival (OS) of recurrent HGG after combined treatment with bevacizumab and irinotecan, compared with other documented prognostic variables. Twenty-five adult patients with histologically proven HGG were included at recurrence. Brain FDG-PET imaging was performed within 6 weeks of starting chemotherapy with bevacizumab and irinotecan. Response based on MRI was assessed every 2 months according to revised assessment in Neuro-Oncology (RANO) criteria. Median PFS and OS were 4 months (range, 0.9–10.4 months) and 7.2 months (range, 1.2–41.7 months), respectively. At 6 months, PFS and OS rate were 16.0% and 72.0%. FDG uptake was the most powerful predictor of both PFS and OS, using either univariate or multivariate analysis, among all variables tested: histological grade, Karnofsky performance status, steroid intake, and number of previous treatments. Moreover, FDG uptake was also prognostic of response to bevacizumab-based therapy. This study provides the first evidence that pretreatment FDG-PET can serve as an imaging biomarker in recurrent HGG for predicting survival following anti-angiogenic therapy with bevacizumab. PMID:22379188

  20. Endoscopic mucosal resection for high-grade dysplasia and intramucosal carcinoma: a Canadian experience

    PubMed Central

    Yamashita, Denise Tami; Li, Chao; Bethune, Drew; Henteleff, Harry; Ellsmere, James

    2017-01-01

    Background Endoscopic mucosal resection (EMR) is increasingly being used as a first-line treatment for Barrett esophagus (BE) with high-grade dysplasia (HGD) and intramucosal adenocarcinoma (IMC). We reviewed our experience with endoscopic treatment of BE with HGD and IMC at our institution with respect to eradication rates, complications and long-term recurrence. Methods We performed a single-centre retrospective review of all patients referred between October 2010 and August 2014 for EMR with dysplastic BE or IMC. We performed EMR using a cap-fitted endoscope, and the procedure was repeated every 3 months until eradication or progression of disease. Results A total of 28 patients were identified: 16 with dysplastic BE (14 HGD, 1 low-grade dysplasia, 1 intermediate dysplasia) and 12 with IMC. Complete eradication of HGD was achieved in 11 of 14 (79%) patients. Three of 12 (25%) patients initially referred with suspected IMC were found to have invasive adenocarcinoma on EMR. Eradication was successful in 8 of 9 (89%) patients with true IMC, with 1 patient progressing to salvage esophagectomy. Complications occurred in 2 of 28 (7%) patients; both had esophageal strictures managed with dilatation. Median duration of follow-up was 371 days. Conclusion Our experience supports the safety of EMR as a first-line treatment for patients with BE with dysplasia and IMC in early short-term follow-up. PMID:28338468

  1. The supporting effects of high luminous conditions on grade 3 oral reading fluency scores.

    PubMed

    Mott, Michael S; Robinson, Daniel H; Williams-Black, Thea H; McClelland, Susan S

    2014-01-01

    The universality of the impact of daylight is a common thread that defines humanity. Day light affects us in a variety of ways -visually, psychologically and biologically. Artificial lighting research has explored ways in which artificial lighting may substitute for daylight and enhance human health and wellbeing. Recently, a study by Mott et al. 2011 found that the usage of high intensity, yet glare free lighting, (referred to as Focus light setting) during reading instruction increased grade 3 students' oral reading fluency (ORF) scores, a key index of reading comprehension. The current study further explored the effect of Focus lighting during literacy instruction with at-risk grade 3 students (n = 172). Over the course of an academic year, the Focus lighting students increased their ORF scores at a greater rate than did the Normal lighting students. These findings, in combination with earlier lighting research, suggest that artificial lighting plays a key role in helping to create an effective learning environment to ensure children reach their full potential. More systematic research, however, is needed to understand the mechanisms by which artificial lighting may contribute to the learning environment: visually, biologically and/or psychologically.

  2. The 9th Grade Shock and the High School Dropout Crisis

    PubMed Central

    Pharris-Ciurej, Nikolas; Hirschman, Charles; Willhoft, Joseph

    2011-01-01

    Retrospective questions on educational attainment in national surveys and censuses tend to over-estimate high school graduation rates by 15 to 20 percentage points relative to administrative records. Administrative data on educational enrollment are, however, only available at the aggregate level (state, school district, and school levels) and the recording of inter-school transfers are generally incomplete. With access to linked individual-level administrative records from a very large “West Coast metropolitan school district” we track patterns of high school attrition and on-time high school graduation of individual students. Even with adjustments for the omission of out-of-district transfers (estimates of omission are presented), the results of this study show that failure in high school, as indexed by retention and attrition, are almost as common as on-time high school graduation. In addition to the usual risk factors of disadvantaged background, we find that the “9th grade shock”—an unpredicted decline in academic performance upon entering high school—is a key mechanism behind the continuing crisis of high school attrition. PMID:23017804

  3. Potential role for magnetoencephalography in distinguishing low- and high-grade gliomas: a preliminary study with histopathological confirmation.

    PubMed

    Wilson, Tony W; Heinrichs-Graham, Elizabeth; Aizenberg, Michele R

    2012-05-01

    Gliomas are the most common form of tumor in the CNS and are exceptionally heterogeneous. Accurately characterizing gliomas, in terms of grade and type, is essential for predicting the rate of tumor progression. Histopathological grading and analysis based on biopsied tissue remains the gold standard, but non- and semi-invasive neuroimaging also plays a key role. Neuroimaging has been used to guide and optimize biopsies for several decades, but more recently molecular imaging and variants of MRI have shown promise in independently predicting glioma grade. Here we evaluated whether magnetoencephalographic (MEG) measurements of population-level physiology within the glioma space were predictive of the inherent grade of the tissue, based on definitive histopathological analyses. High-density MEG data were recorded from 11 patients who were undergoing functional mapping in preparation for resective surgery. The primary results indicated that glioma grade was positively correlated with the local amplitude of activity within the glioma space in the theta (4-7 Hz), alpha (8-14 Hz), and beta bands (14-30 Hz). Additionally, activity within the glioma was significantly elevated relative to the nonaffected homologue area in the same frequency bands. These results indicate that pathological levels of synchronization exist within the tumor space and that MEG may be a viable tool for noninvasively differentiating gliomas by their grade. Although these results should be considered preliminary and are only correlative in nature, these data suggest that MEG can potentially detect neurophysiological signatures or markers that predict the inherent grade of a glial tumor.

  4. High-Grade Partial and Retracted (<2 cm) Proximal Hamstring Ruptures

    PubMed Central

    Piposar, Jonathan R.; Vinod, Amrit V.; Olsen, Joshua R.; Lacerte, Edward; Miller, Suzanne L.

    2017-01-01

    Background: High-grade partial proximal hamstring tears and complete tears with retraction less than 2 cm are a subset of proximal hamstring injuries where, historically, treatment has been nonoperative. It is unknown how nonoperative treatment compares with operative treatment. Hypothesis: The clinical and functional outcomes of nonoperative and operative treatment of partial/complete proximal hamstring tears were compared. We hypothesize that operative treatment of these tears leads to better clinical and functional results. Study Design: Case series; Level of evidence, 4. Methods: A retrospective review identified patients with a high-grade partial or complete proximal hamstring rupture with retraction less than 2 cm treated either operatively or nonoperatively from 2007 to 2015. All patients had an initial period of nonoperative treatment. Surgery was offered if patients had continued pain and/or limited function refractory to nonoperative treatment with physical therapy. Outcome measures were each patient’s strength perception, ability to return to activity, Lower Extremity Functional Scale (LEFS) score, Short Form–12 (SF-12) physical and mental component outcome scores, distance traversed by a single-leg hop, and Biodex hamstring strength testing. Results: A total of 25 patients were enrolled in the study. The 15 patients who were treated nonoperatively sustained injuries at a mean age of 55.73 ± 14.83 years and were evaluated 35.47 ± 30.35 months after injury. The 10 patients who elected to have surgery sustained injuries at 50.40 ± 6.31 years of age (P = .23) and were evaluated 30.11 ± 19.43 months after surgery. LEFS scores were significantly greater for the operative group compared with the nonoperative group (77/80 vs 64.3/80; P = .01). SF-12 physical component scores for the operative group were also significantly greater (P = .03). Objectively, operative and nonoperative treatment modalities showed no significant difference in terms of single

  5. Origin and molecular pathogenesis of ovarian high-grade serous carcinoma.

    PubMed

    Kurman, R J

    2013-12-01

    A new paradigm for the pathogenesis of ovarian cancer has recently been proposed which helps to explain persistent problems in describing the development and diverse morphology of these neoplasms. The paradigm incorporates recent advances in our understanding of the molecular pathogenesis of epithelial 'ovarian' cancer with new insights into the origin of these tumors. Correlated clinicopathologic and molecular genetic studies led to the development of a dualistic model that divides all the various histologic types of epithelial ovarian carcinomas into two broad categories designated 'type I' and 'type II'. The prototypic type I tumor is low-grade serous carcinoma and the prototypic type II tumor is high-grade serous carcinomas (HGSCs). As the serous tumors comprise ∼70% of all epithelial ovarian tumors and account for the majority of deaths, the serous tumors will be the subject of this review. There are marked differences between the low-grade and high-grade serous tumors. Briefly, the former are indolent, present in stage I (tumor confined to the ovary) and develop from well-established precursors, so-called 'atypical proliferative (borderline) tumors,' which are characterized by specific mutations, including KRAS, BRAF and ERBB2; they are relatively genetically stable. In contrast, HGSCs are aggressive, present in the advanced stage, and develop from intraepithelial carcinomas in the fallopian tube. They harbor TP53 mutations in over 95% of cases, but rarely harbor the mutations detected in the low-grade serous tumors. At the time of diagnosis they demonstrate marked chromosomal aberrations but over the course of the disease these changes remain relatively stable. Along with the recent advances in understanding the molecular pathogenesis of these tumors, studies have demonstrated that the long sought for precursor of ovarian HGSC appears to develop from an occult intraepithelial carcinoma in the fimbrial region of the fallopian tube designated 'serous tubal

  6. Stratified epithelium in prostatic adenocarcinoma: a mimic of high-grade prostatic intraepithelial neoplasia.

    PubMed

    Hameed, Omar; Humphrey, Peter A

    2006-07-01

    Typically glands of prostatic adenocarcinoma have a single cell lining, although stratification can be seen in invasive carcinomas with a cribriform architecture, including ductal carcinoma. The presence and diagnostic significance of stratified cells within non-cribriform carcinomatous prostatic glands has not been well addressed. The histomorphological features and immunohistochemical profile of cases of non-cribriform prostatic adenocarcinoma with stratified malignant glandular epithelium were analyzed. These cases were identified from needle biopsy cases from the consultation files of one of the authors and from a review of 150 consecutive in-house needle biopsy cases of prostatic adenocarcinoma. Immunohistochemistry was performed utilizing antibodies reactive against high molecular weight cytokeratin (34betaE12), p63 and alpha-methylacyl-coenzyme-A racemase (AMACR). A total of 8 cases were identified, including 2 from the 150 consecutive in-house cases (1.3%). In 4 cases, the focus with glands having stratified epithelium was the sole carcinomatous component in the biopsy, while such a component represented 5-30% of the invasive carcinoma seen elsewhere in the remaining cases. The main attribute in all these foci was the presence of glandular profiles lined by several layers of epithelial cells with cytological and architectural features resembling flat or tufted high-grade prostatic intraepithelial neoplasia, but lacking basal cells as confirmed by negative 34betaE12 and/or p63 immunostains in all cases. The AMACR staining profile of the stratified foci was variable, with 4 foci showing positivity, and 3 foci being negative, including two cases that displayed AMACR positivity in adjacent non-stratified prostatic adenocarcinoma. Prostatic adenocarcinoma with stratified malignant glandular epithelium can be identified in prostate needle biopsy samples harboring non-cribriform prostatic adenocarcinoma and resembles glands with high-grade prostatic

  7. High grade anorectal stricture complicating Crohn's disease: endoscopic treatment using insulated-tip knife

    PubMed Central

    Chon, Hyung Ku; Shin, Ik Sang; Kim, Sang Wook

    2016-01-01

    Endoscopic treatments have emerged as an alternative to surgery, in the treatment of benign colorectal stricture. Unlike endoscopic balloon dilatation, there is limited data on endoscopic electrocautery incision therapy for benign colorectal stricture, especially with regards to safety and long-term patency. We present a case of a 29-year-old female with Crohn's disease who had difficulty in defecation and passing thin stools. A pelvic magnetic resonance imaging scan, gastrograffin enema, and sigmoidoscopy showed a high-grade anorectal stricture. An endoscopic insulated-tip knife incision was successfully performed to resolve the problem. From our experience, we suggest that endoscopic insulated-tip knife treatment may be a feasible and effective modality for patients with short-segment, very rigid, fibrotic anorectal stricture. PMID:27433152

  8. Predicting conduct problems: can high-risk children be identified in kindergarten and grade 1?

    PubMed

    Bennett, K J; Lipman, E L; Brown, S; Racine, Y; Boyle, M H; Offord, D R

    1999-08-01

    Externalizing behavior symptoms (EBS) in childhood are a strong predictor of future conduct problems. This study evaluated their predictive accuracy using logistic regression and receiver operating characteristic curve techniques. EBS, alone and in combination with other child and familial risk factors, were used to predict conduct problems 30 months later in a nonclinic population of kindergartners and Grade 1 children. The sensitivity (Sn) and positive predictive value (PPV) of EBS alone were below preset criteria of > or = 50% for each (prevalence < or = 15%). Sn and PPV increased when other child and familial factors were combined with symptoms but did not exceed the preset criteria. From a developmental perspective, substantial stability of EBS exists over time. However, from the perspective of prevention science, significant levels of misclassification will occur when EBS are used to designate high-risk status under the low-prevalence conditions of normal populations.

  9. High-Grade Mixed Adenoneuroendocrine Carcinoma in the Cecum: A Case Report

    PubMed Central

    Shin, Sang Ho; Jung, Sung Hee; Jang, Ji Woong; Kang, Min Seok; Kim, Sang Il; Kim, Ji Hye; Lee, Jun Ho

    2017-01-01

    Gastrointestinal neoplasms with an exocrine and a neuroendocrine component are rare. Such neoplasms are called “mixed adenoneuroendocrine carcinomas” (MANECs) according to the most recent World Health Organization classification of gastrointestinal tract neoplasms. MANECs have no specific findings that distinguish them from pure adenocarcinomas. In addition, the optimal management strategy of MANECs is largely unknown. We describe the case of a 32-year-old man with dizziness and abdominal bloating. A cecal mass was suspected based on an image study done at a local clinic. We evaluated the cecal mass by using colonoscopy, contrast enhanced computed tomography of the abdomen, positron emission tomography-computed tomography, and laboratory studies. The patient underwent a right hemicolectomy and adjuvant chemotherapy. The final histopathological diagnosis was a high-grade MANEC of the ascending colon, tumor stage T3N2M0. PMID:28289663

  10. Integrated Proteogenomic Characterization of Human High-Grade Serous Ovarian Cancer.

    PubMed

    Zhang, Hui; Liu, Tao; Zhang, Zhen; Payne, Samuel H; Zhang, Bai; McDermott, Jason E; Zhou, Jian-Ying; Petyuk, Vladislav A; Chen, Li; Ray, Debjit; Sun, Shisheng; Yang, Feng; Chen, Lijun; Wang, Jing; Shah, Punit; Cha, Seong Won; Aiyetan, Paul; Woo, Sunghee; Tian, Yuan; Gritsenko, Marina A; Clauss, Therese R; Choi, Caitlin; Monroe, Matthew E; Thomas, Stefani; Nie, Song; Wu, Chaochao; Moore, Ronald J; Yu, Kun-Hsing; Tabb, David L; Fenyö, David; Bafna, Vineet; Wang, Yue; Rodriguez, Henry; Boja, Emily S; Hiltke, Tara; Rivers, Robert C; Sokoll, Lori; Zhu, Heng; Shih, Ie-Ming; Cope, Leslie; Pandey, Akhilesh; Zhang, Bing; Snyder, Michael P; Levine, Douglas A; Smith, Richard D; Chan, Daniel W; Rodland, Karin D

    2016-07-28

    To provide a detailed analysis of the molecular components and underlying mechanisms associated with ovarian cancer, we performed a comprehensive mass-spectrometry-based proteomic characterization of 174 ovarian tumors previously analyzed by The Cancer Genome Atlas (TCGA), of which 169 were high-grade serous carcinomas (HGSCs). Integrating our proteomic measurements with the genomic data yielded a number of insights into disease, such as how different copy-number alternations influence the proteome, the proteins associated with chromosomal instability, the sets of signaling pathways that diverse genome rearrangements converge on, and the ones most associated with short overall survival. Specific protein acetylations associated with homologous recombination deficiency suggest a potential means for stratifying patients for therapy. In addition to providing a valuable resource, these findings provide a view of how the somatic genome drives the cancer proteome and associations between protein and post-translational modification levels and clinical outcomes in HGSC. VIDEO ABSTRACT.

  11. Numerical study of a highly efficient solar cell with graded band gap design

    NASA Astrophysics Data System (ADS)

    Tan, Ming-Hsuan; Tseng, Hung-Ruei; Kuo, Chien-Ting; Hsu, Shun-Chieh; Lo, Yen-Hua; Tsai, Che-Pin; Cheng, Yuh-Jen; Lin, Chien-Chung

    2015-05-01

    A linearly graded band gap design in the intrinsic layer of a p-i-n solar cell is studied numerically. An ideal model using Matlab® is built and the device performance is calculated using continuity equations and an effective band gap model under various band gap combinations. The power conversion efficiency (PCE) can be as high as 30.21%, while the abrupt junction reference device only exhibits 29.25% under the same parameters. This design is also evaluated using the commercial TCAD software APSYS®, and the calculations show optimal efficiency enhancements of about 1.14-fold that of the abrupt junction device in an AlAs/GaAs system and 2.05-fold that in an InGaN/GaN system.

  12. Non-routine Tracers for PET Imaging of High-grade Glioma.

    PubMed

    Frosina, Guido

    2016-07-01

    Thorough imaging is crucial for diagnosis and treatment of high-grade gliomas (HGG), lethal brain tumours with median survival ranging 1-5 years after diagnosis. Positron-emission tomography (PET) is acquiring importance in imaging of HGG since it has the formidable advantage of providing information on tumour metabolism that may be critical for correct diagnosis and treatment planning. Recently employed PET tracers designed for the non-routine investigation of specific aspects of HGG metabolism, including hypoxia, neoangiogenesis, expression of integrins and stem cell markers, are reviewed herein. A thorough choice from among these non-routine tracers may provide important metabolic information complementing those obtained with more common PET analyses, for the sake of diagnostic, prognostic, treatment planning or research purposes.

  13. Total Artificial Heart Implantation After Undifferentiated High-Grade Sarcoma Excision

    PubMed Central

    Kremer, Jamila; Farag, Mina; Arif, Rawa; Brcic, Andreas; Sabashnikov, Anton; Schmack, Bastian; Popov, Aron-Frederik; Karck, Matthias; Dohmen, Pascal M.; Ruhparwar, Arjang; Weymann, Alexander

    2016-01-01

    Background Total artificial heart (TAH) implantation in patients with aggressive tumor infiltration of the heart can be challenging. Case Report We report on a patient with a rare primary undifferentiated high-grade spindle cell sarcoma of the mitral valve and in the left atrium, first diagnosed in 2014. The referring center did a first resection in 2014. In the course of 17 months, computer tomography (CT) scan again showed massive invasion of the mitral valve and left atrium. Partial resection and mitral valve replacement was not an option. We did a subtotal heart excision with total artificial heart implantation. In this report we discuss complications, risk factors, and perioperative management of this patient. Conclusions Patients with aggressive tumors of the heart can be considered for TAH implantation. PMID:27803495

  14. Preparation of high grade YBCO powders and pellets through the glycerol route

    NASA Astrophysics Data System (ADS)

    Kamat, R. V.; Vittal Rao, T. V.; Pillai, K. T.; Vaidya, V. N.; Sood, D. D.

    1991-10-01

    Superconducting powders and pellets of Y-Ba-Cu-O were prepared by a new solution route. Nitrates of Y, Ba and Cu were heated with a controlled amount of glycerol to get a dry powder which on suitable heat treatment gave high grade YBCO powder/pellets. Characterisation was done by X-ray diffractometry, thermogravimetry, differential thermal analysis and also by measuring the surface area, carbon-content, bulk-density, transition temperature and the critical current. The pellets could be densified to 94% theoretical density (TD) and had a superconducting transition width of 1 K. The critical current densities were in the range of 200-500 A/cm 2.

  15. Why is weapons grade plutonium more hazardous to work with than highly enriched uranium?

    SciTech Connect

    Cournoyer, Michael E.; Costigan, Stephen A.; Schake, Bradley S.

    2015-08-01

    Highly Enriched Uranium and Weapons grade plutonium have assumed positions of dominant importance among the actinide elements because of their successful uses as explosive ingredients in nuclear weapons and the place they hold as key materials in the development of industrial use of nuclear power. While most chemists are familiar with the practical interest concerning HEU and WG Pu, fewer know the subtleties among their hazards. In this study, a primer is provided regarding the hazards associated with working with HEU and WG Pu metals and oxides. The care that must be taken to safely handle these materials is emphasized and the extent of the hazards is described. The controls needed to work with HEU and WG Pu metals and oxides are differentiated. Given the choice, one would rather work with HEU metal and oxides than WG Pu metal and oxides.

  16. Why is weapons grade plutonium more hazardous to work with than highly enriched uranium?

    DOE PAGES

    Cournoyer, Michael E.; Costigan, Stephen A.; Schake, Bradley S.

    2015-08-01

    Highly Enriched Uranium and Weapons grade plutonium have assumed positions of dominant importance among the actinide elements because of their successful uses as explosive ingredients in nuclear weapons and the place they hold as key materials in the development of industrial use of nuclear power. While most chemists are familiar with the practical interest concerning HEU and WG Pu, fewer know the subtleties among their hazards. In this study, a primer is provided regarding the hazards associated with working with HEU and WG Pu metals and oxides. The care that must be taken to safely handle these materials is emphasizedmore » and the extent of the hazards is described. The controls needed to work with HEU and WG Pu metals and oxides are differentiated. Given the choice, one would rather work with HEU metal and oxides than WG Pu metal and oxides.« less

  17. A case of Peutz-Jeghers syndrome associated with high-grade intramucosal neoplasia.

    PubMed

    Fan, Ru-Ying; Sheng, Jian-Qiu

    2015-01-01

    Peutz-Jeghers syndrome (PJS) is a rare, inherited autosomal dominant disease characterized by mucocutaneous pigmentation and polyps in the gastrointestinal tract. Here, we report the rare case of a 64-year-old female patient with pigmentation on her lips and extremities for over 63 years and intermittent abdominal pain and, diarrhea for 3 years. The presence of intestinal and colorectal hamartomatous polyps was confirmed. The removal and characterization of her rectal polyp showed it to be a typical hamartomatous polyp with a portion of it being an adenoma with high-grade intramucosal neoplasia. A survey of the patient's family identified 9 people in the family with Peutz-Jeghers syndrome and three of them have already died from colorectal cancer. This case study serves as an example of how imperative it is to survey the patient about their family history in order to detect early cancerous lesions.

  18. Easy and fast detection and genotyping of high-risk human papillomavirus by dedicated DNA microarrays.

    PubMed

    Albrecht, Valérie; Chevallier, Anne; Magnone, Virginie; Barbry, Pascal; Vandenbos, Fanny; Bongain, André; Lefebvre, Jean-Claude; Giordanengo, Valérie

    2006-11-01

    Persistent cervical high-risk human papillomavirus (HPV) infection is correlated with an increased risk of developing a high-grade cervical intraepithelial lesion. A two-step method was developed for detection and genotyping of high-risk HPV. DNA was firstly amplified by asymmetrical PCR in the presence of Cy3-labelled primers and dUTP. Labelled DNA was then genotyped using DNA microarray hybridization. The current study evaluated the technical efficacy of laboratory-designed HPV DNA microarrays for high-risk HPV genotyping on 57 malignant and non-malignant cervical smears. The approach was evaluated for a broad range of cytological samples: high-grade squamous intraepithelial lesions (HSIL), low-grade squamous intraepithelial lesions (LSIL) and atypical squamous cells of high-grade (ASC-H). High-risk HPV was also detected in six atypical squamous cells of undetermined significance (ASC-US) samples; among them only one cervical specimen was found uninfected, associated with no histological lesion. The HPV oligonucleotide DNA microarray genotyping detected 36 infections with a single high-risk HPV type and 5 multiple infections with several high-risk types. Taken together, these results demonstrate the sensitivity and specificity of the HPV DNA microarray approach. This approach could improve clinical management of patients with cervical cytological abnormalities.

  19. Endoscopic Detection of Early Esophageal Squamous Cell Carcinoma in Patients with Achalasia: Narrow-Band Imaging versus Lugol's Staining.

    PubMed

    Ide, Edson; Carneiro, Fred Olavo Aragão Andrade; Frazão, Mariana Souza Varella; Chaves, Dalton Marques; Sallum, Rubens Antônio Aissar; de Moura, Eduardo Guimarães Hourneaux; Sakai, Paulo; Cecconello, Ivan; Maluf-Filho, Fauze

    2013-01-01

    Chromoendoscopy with Lugol's staining remains the gold standard technique for detecting superficial SCC. An alternative technique, such as narrow-band imaging (NBI), for "optical staining" would be desirable, since NBI is a simpler technique and has no known complications. In this study, we compare NBI without magnification and chromoendoscopy with Lugol's staining for detecting high-grade dysplasia and intramucosal esophageal squamous cell carcinoma (SCC) in patients with achalasia. This was a prospective observational study of 43 patients with achalasia referred to the Gastrointestinal Endoscopy Unit of the Hospital of Clinics, São Paulo, University Medical School, Brazil, from October 2006 to February 2007. Conventional examinations with white light, NBI, and Lugol staining were consecutively performed, and the suspected lesions were mapped, recorded, and sent for biopsy. The results of the three methods were compared regarding sensitivity, specificity, accuracy, positive predictive value, negative predictive value, positive likelihood value, and negative likelihood value. Of the 43 patients, one was diagnosed with esophageal squamous cell carcinoma, and it was detected by all of the methods. NBI technology without magnification has high sensitivity and negative predictive value for detecting superficial esophageal squamous cell carcinoma, and it has comparable results with those obtained with Lugol's staining.

  20. Squamous carcinoma of the nasopharynx

    SciTech Connect

    Moloy, P.J.; Chung, Y.T.; Krivitsky, P.B.; Kim, R.C.

    1985-07-01

    Nasophryngeal carcinoma is an unusual neoplasm among squamous cell carcinomas of the head and neck. The tumor is rare in most parts of the world but is strikingly common in several Asian subpopulations, notably Chinese in Hong Kong and Guangdong Province. The Epstein-Barr virus is intimately related to the disease and elicits the formation of antibodies that are useful for diagnosis and follow-up study. The virus has not been conclusively shown to cause nasopharyngeal cancer, however. Histologically, nasopharyngeal carcinoma is anaplastic in 75% of cases and better differentiated in 25% of patients. All tumors are treated by high-dose radiation to the primary site and both sides of the neck. Surgical treatment, in the neck only, is reserved for irradiation failures. The prognosis is better in patients younger than 40 years, in patients without clinical cervical nodal involvement and, unexpectedly, in patients with anaplastic tumors. 18 references, 2 figures, 2 tables.

  1. Wingspan Stent for High-Grade Symptomatic Vertebrobasilar Artery Atherosclerotic Stenosis

    SciTech Connect

    Li Jian Zhao Zhenwei Gao Guodong Deng Jianping; Yu Jia; Gao Li; Yuan Yang; Qv Youzhi

    2012-04-15

    Purpose: This study was designed to present the treatment outcomes with Wingspan stent angioplasty of high-grade intracranial vertebrobasilar artery (VBA) stenosis in symptomatic patients. Methods: Between 2007 and 2010, the records of 30 patients with 31 intracranial high-grade VBA stenoses (all{>=}70%) who underwent elective stenting due to the failure of medical therapy were retrospectively reviewed. Clinical evaluation was performed based on the modified Rankin scale and the National Institutes of Health Stroke Scale. Results: In all cases, the stent deployment was technically successful. The mean stenosis decreased significantly from 82.28 {+-} 8.02% (range, 72-99%) to 11.18 {+-} 7.28% (range, 0-25%) after stent-assisted angioplasty (P < 0.05). Periprocedure complications occurred in 3 (10%) of 30 patients; there were 2 cases of perforator strokes and 1 case of transient flow insufficiency with stent overlap. Clinical follow-up (mean, 17.81 {+-} 11.49 months; range, 5-40 months) was available for 27 patients, and angiographic follow-up (mean, 9.95 {+-} 5.74 months, range, 5-20 months) was available for 19 patients. Only one case demonstrated recurrent symptoms with restenosis ({>=}50%). There were no recurrent ischemic events and no cases of restenosis in the other patients. Conclusions: According to our data, the Wingspan stent for symptomatic intracranial VBA stenoses is a safe and efficacious treatment alternative in cases with recurrent symptoms despite medical therapy. However, the improvement of outcome requires the reduction in the rate of procedure-related complications and long-term outcomes still have to be demonstrated.

  2. Preparation of High-Grade Powders from Tomato Paste Using a Vacuum Foam Drying Method.

    PubMed

    Sramek, Martin; Schweiggert, Ralf Martin; van Kampen, Andreas; Carle, Reinhold; Kohlus, Reinhard

    2015-08-01

    We present a rapid and gentle drying method for the production of high-grade tomato powders from double concentrated tomato paste, comparing results with powders obtained by foam mat air drying and freeze dried powders. The principle of this method consists of drying tomato paste in foamed state at low temperatures in vacuum. The formulations were dried at temperatures of 50, 60, and 70 °C and vacuum of 200 mbar. Foam stability was affected by low serum viscosity and the presence of solid particles in tomato paste. Consequently, serum viscosity was increased by maltodextrin addition, yielding optimum stability at tomato paste:maltodextrin ratio of 2.4:1 (w/w) in dry matter. Material foamability was improved by addition of 0.5% (w/w, fresh weight) egg white. Because of solid particles in tomato paste, foam air filling had to be limited to critical air volume fraction of Φ = 0.7. The paste was first pre-foamed to Φ = 0.2 and subsequently expanded in vacuo. After drying to a moisture content of 5.6% to 7.5% wet base (w.b.), the materials obtained were in glassy state. Qualities of the resulting powders were compared with those produced by freeze and air drying. Total color changes were the least after vacuum drying, whereas air drying resulted in noticeable color changes. Vacuum foam drying at 50 °C led to insignificant carotenoid losses, being equivalent to the time-consuming freeze drying method. In contrast, air drying caused lycopene and β-carotene losses of 18% to 33% and 14% to 19% respectively. Thus, vacuum foam drying enables production of high-grade tomato powders being qualitatively similar to powders obtained by freeze drying.

  3. Surgical Versus Nonsurgical Treatment for High-Grade Spondylolisthesis in Children and Adolescents

    PubMed Central

    Xue, Xuhong; Wei, Xiaochun; Li, Li

    2016-01-01

    Abstract The optimal management of high-grade spondylolisthesis in children and adolescent is controversial. There is a paucity of literature regarding operatively or nonoperative management in this setting. To assessment of the current state of evidence regarding high-grade spondylolisthesis treatment with the goal of obtaining outcome comparisons in these patients managed either operatively or nonoperatively. We performed a systematic literature search up to November 2014, using Medline, Embase, and The Cochrane Library. The analysis and eligibility criteria were documented according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA-guidelines) and Cochrane Back Review Group editorial board. We used the Newcastle–Ottawa quality assessment scale (NOS-scale) to assess the quality. Five observational studies were considered eligible for analysis based on the evaluation of 1596 identified papers. The mean overall difference in the Scoliosis Research Society questionnaire 22 between the surgical and nonsurgical groups was not statistically significant (95% CI: −0.17 to 0.21, P = 0.84). The pooled mean difference in progression of slip between the surgical and nonsurgical groups was no significant difference (OR: 0.47, 95% CI: 0.12–1.81, P = 0.27, I2 = 0%). Because of the preponderance of uncontrolled case series, low-quality evidence indicates that the quality of life and progression of slips was no significant difference between surgery and nonoperation group. Nonoperative patients had no radiologic progression of their slip during the follow-up period. PMID:26986134

  4. Surgical Treatment Strategies for High-Grade Spondylolisthesis: A Systematic Review

    PubMed Central

    Poorman, Caroline E.; Yang, Sun; Boniello, Anthony J.; Jalai, Cyrus M.; Worley, Nancy; Lafage, Virginie

    2015-01-01

    Background HGS is a severe deformity most commonly affecting L5-S1 vertebral segment. Treatment available for HGS includes a range of different surgical options: full or partial reduction of translation and/or abnormal alignment and in situ fusion with or without decompression. Various instrumented or non-instrumented constructs are available, and surgical approach varies from anterior/posterior to combined depending on surgeon preference and experience. The aim of this systematic review was to review the literature on lumbosacral high-grade spondylolisthesis (HGS), identify patients at risk for progression to higher-grade slip and evaluate various surgical strategies to report on complications and radiographic and clinical outcomes. Methods Systematic search of PubMed, Cochrane and Google Scholar for papers relevant to HGS was performed. 19 articles were included after title, abstract, and full-text review and grouped to analyze baseline radiographic parameters and the effect of surgical approach, instrumentation, reduction and decompression on patient radiographic and clinical outcomes. Results There is a lack of high-quality studies pertaining to surgical treatment for HGS, and a majority of included papers were Level III or IV based on the JBJS Levels of Evidence Criteria. Conclusions Surgical treatment for HGS can vary depending on patient age. There is strong evidence of an association between increased pelvic incidence (PI) and presence of HGS and moderately strong evidence that patients with unbalanced pelvis can benefit from correction of lumbopelvic parameters with partial reduction. Surgeons need to weigh the benefits of fixing the deformity with the risks of potential complications, assessing patient satisfaction as well as their understanding of the possible complications. However, further research is necessary to make more definitive conclusions on surgical treatment guidelines for HGS. Level of Evidence II PMID:26512344

  5. Pilot study of estramustine added to radiosurgery and radiotherapy for treatment of high grade glioma.

    PubMed

    Landy, Howard; Markoe, Arnold; Potter, Priscilla; Lasalle, Garrett; Marini, Angela; Savaraj, Niramol; Reis, Isildinha; Heros, Deborah; Wangpaichitr, Medhi; Feun, Lynn

    2004-01-01

    Patients with high grade glioma generally have poor prognoses. Addition of radiosensitizing agents might improve the response to irradiation. The chemotherapeutic agent estramustine sensitizes experimental gliomas to radiation. Gliomas express estramustine binding proteins, and cytotoxic concentrations of estramustine metabolites are found in gliomas after oral administration. Twenty three patients, aged 25-78, with new or recurrent high grade glioma were treated with estramustine and radiosurgery and/or radiotherapy. Patients with recurrent tumors were treated with estramustine and Gamma Knife stereotactic radiosurgery; eligible tumors were limited to 4 cm maximal diameter. Patients with newly diagnosed tumors were treated with estramustine and fractionated radiotherapy, with radiosurgery also performed if the tumor was less than 4 cm maximal diameter. Estramustine (16 mg/kg per day orally) was started three days prior to radiosurgery, or, if only radiotherapy was performed, on the first day of radiotherapy. Estramustine was continued until the completion of radiosurgery and/or radiotherapy (72 Gy, 60 fractions, 1.2 Gy bid over 6 weeks). Of the 13 patients treated for newly diagnosed glioblastoma, median survival was 16 months with 38% 2-year survival. Of five patients treated for recurrent glioblastoma, survival was 3, 8, 9, 15, and 23 + months. Two patients with recurrent anaplastic astrocytoma survived for 24 and 48+ months. One patient with recurrent anaplastic mixed glioma survived 5+ months. Two patients with newly diagnosed anaplastic oligodendroglioma survived 20 and 42+ months. Four of the new glioblastoma patients developed deep vein thrombosis. The results of this pilot study indicate some benefit, and further investigation incorporating estramustine into clinical trials is suggested.

  6. Hypofractionated Stereotactic Radiation Therapy in Recurrent High-Grade Glioma: A New Challenge

    PubMed Central

    Navarria, Pierina; Ascolese, Anna Maria; Tomatis, Stefano; Reggiori, Giacomo; Clerici, Elena; Villa, Elisa; Maggi, Giulia; Bello, Lorenzo; Pessina, Federico; Cozzi, Luca; Scorsetti, Marta

    2016-01-01

    Purpose The aim of this study was to evaluate outcomes of hypofractionated stereotactic radiation therapy (HSRT) in patients re-treated for recurrent high-grade glioma. Materials and Methods From January 2006 to September 2013, 25 patients were treated. Six patients underwent radiation therapy alone, while 19 underwent combined treatment with surgery and/or chemotherapy. Only patients with Karnofsky Performance Status (KPS) > 70 and time from previous radiotherapy greater than 6 months were re-irradiated. The mean recurrent tumor volume was 35 cm3 (range, 2.46 to 116.7 cm3), and most of the patients (84%) were treated with a total dose of 25 Gy in five fractions (range, 20 to 50 Gy in 5-10 fractions). Results The median follow-up was 18 months (range, 4 to 36 months). The progression-free survival (PFS) at 1 and 2 years was 72% and 34% and the overall survival (OS) 76% and 50%, respectively. No severe toxicity was recorded. In univariate and multivariate analysis extent of resection at diagnosis significantly influenced PFS and OS (p < 0.01). Patients with smaller recurren tumor volume treated had better local control and survival. Indeed, the 2-year PFS was 40% (≤ 50 cm3) versus 11% (p=0.1) and the 2-year OS 56% versus 33% (> 50 cm3), respectively (p=0.26). Conclusion In our experience, HSRT could be a safe and feasible therapeutic option for recurrent high grade glioma even in patients with larger tumors. We believe that a multidisciplinary evaluation is mandatory to assure the best treatment for selected patients. Local treatment should also be considered as part of an integrated approach. PMID:25761491

  7. PAR1 is selectively over expressed in high grade breast cancer patients: a cohort study

    PubMed Central

    Hernández, Norma A; Correa, Elma; Avila, Esther P; Vela, Teresa A; Pérez, Víctor M

    2009-01-01

    Background The protease-activated receptor (PAR1) expression is correlated with the degree of invasiveness in cell lines. Nevertheless it has never been directed involved in breast cancer patients progression. The aim of this study was to determine whether PAR1 expression could be used as predictor of metastases and mortality. Methods In a cohort of patients with infiltrating ductal carcinoma studied longitudinally since 1996 and until 2007, PAR1 over-expression was assessed by immunoblotting, immunohistochemistry, and flow citometry. Chi-square and log rank tests were used to determine whether there was a statistical association between PAR1 overexpression and metastases, mortality, and survival. Multivariate analysis was performed including HER1, stage, ER and nodes status to evaluate PAR1 as an independent prognostic factor. Results Follow up was 95 months (range: 2–130 months). We assayed PAR1 in a cohort of patients composed of 136 patients; we found PAR1 expression assayed by immunoblotting was selectively associated with high grade patients (50 cases of the study cohort; P = 0.001). Twenty-nine of 50 (58%) patients overexpressed PAR1, and 23 of these (46%) developed metastases. HER1, stage, ER and PAR1 overexpression were robustly correlated (Cox regression, P = 0.002, P = 0.024 and P = 0.002 respectively). Twenty-one of the 50 patients (42%) expressed both receptors (PAR1 and HER1 P = 0.0004). We also found a statistically significant correlation between PAR1 overexpression and increased mortality (P = 0.0001) and development of metastases (P = 0.0009). Conclusion Our data suggest PAR1 overexpression may be involved in the development of metastases in breast cancer patient and is associated with undifferentiated cellular progression of the tumor. Further studies are needed to understand PAR1 mechanism of action and in a near future assay its potential use as risk factor for metastasis development in high grade breast cancer patients. PMID:19538737

  8. 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

  9. Simultaneous Bilateral Carotid Stenting for Symptomatic Bilateral High-Grade Carotid Stenosis: A Retrospective Clinical Investigation

    PubMed Central

    Ye, Ziming; Liu, Ying; Deng, Xiao; Chen, Xiangren; Lin, Cuiting; Tang, Yanyan; Su, Ying; Fang, Lanji; Wu, Yuan; Qin, Chao

    2016-01-01

    Background This retrospective clinical investigation aimed to evaluate the short-term effectiveness and safety of SBCAS for symptomatic bilateral high-grade CS. Material/Methods From 2009 to 2014, 145 patients were recruited. Among them, 70 underwent SBCAS, and other 75 patients underwent SAMM and served as controls. The immediate postprocedural complications and postprocedural neurological evaluation, as well as restenosis at 6-month and 1-year follow-ups in the SBCAS group are reported. Additionally, baseline risk factors for ischemic stroke, adverse effects of drugs, and outcomes at 30-day, 6-month, and 1-year follow-ups were compared between the 2 groups. Results Our data did not reveal significant differences between the 2 groups in baseline risk factors for ischemic stroke. In the SBCAS group, both HPS (5.7%) and HD (40%) occurred, but they were not very severe, and no patients had postprocedural neurological deficit. Moreover, restenosis only occurred in 3 patients at 3 stent placement sites (4.3%) at 1-year follow-up. Adverse effects of drugs did not occur in SBCAS group, but adverse effects of Bayer aspirin and Lipitor occurred in 4 patients (5.4%) and 18 patients (24.3%), respectively, at 6-month follow-up in the control group. Furthermore, there were significant differences in outcomes between the 2 groups at 30-day, 6-month, and 1-year follow-ups, in that NIHSS, CS ratio, and incidence of endpoint events, as well as 1-year cumulative probability of endpoint events, were all lower in the SBCAS group than in the control group (p<0.05). Conclusions Compared to SAMM, we found that SBCAS was more effective and safer for symptomatic bilateral high-grade CS. PMID:27542158

  10. High-definition fiber tractography for the evaluation of perilesional white matter tracts in high-grade glioma surgery.

    PubMed

    Abhinav, Kumar; Yeh, Fang-Cheng; Mansouri, Alireza; Zadeh, Gelareh; Fernandez-Miranda, Juan C

    2015-09-01

    Conventional white matter (WM) imaging approaches, such as diffusion tensor imaging (DTI), have been used to preoperatively identify the location of affected WM tracts in patients with intracranial tumors in order to maximize the extent of resection and potentially reduce postoperative morbidity. DTI, however, has limitations that include its inability to resolve multiple crossing fibers and its susceptibility to partial volume effects. Therefore, recent focus has shifted to more advanced WM imaging techniques such as high-definition fiber tractography (HDFT). In this paper, we illustrate the application of HDFT, which in our preliminary experience has enabled accurate depiction of perilesional tracts in a 3-dimensional manner in multiple anatomical compartments including edematous zones around high-grade gliomas. This has facilitated accurate surgical planning. This is illustrated by using case examples of patients with glioblastoma multiforme. We also discuss future directions in the role of these techniques in surgery for gliomas.

  11. Raman spectroscopic analysis of oral squamous cell carcinoma and oral dysplasia in the high-wavenumber region

    NASA Astrophysics Data System (ADS)

    Carvalho, Luis Felipe C. S.; Bonnier, Franck; O'Callaghan, Kate; O'Sullivan, Jeff; Flint, Stephen; Neto, Lazaro P. M.; Soto, Cláudio A. T.; dos Santos, Laurita; Martin, Airton A.; Byrne, Hugh J.; Lyng, Fiona M.

    2015-06-01

    Raman spectroscopy can provide a molecular-level signature of the biochemical composition and structure of cells with excellent spatial resolution and could be useful to monitor changes in composition for early stage and non-invasive cancer diagnosis, both ex-vivo and in vivo. In particular, the fingerprint spectral region (400-1,800 cm-1) has been shown to be very promising for optical biopsy purposes. However, limitations to discrimination of dysplastic and inflammatory processes based on the fingerprint region still persist. In addition, the Raman spectral signal of dysplastic cells is one important source of misdiagnosis of normal versus pathological tissues. The high wavenumber region (2,800-3,600 cm-1) provides more specific information based on N-H, O-H and C-H vibrations and can be used to identify the subtle changes which could be important for discrimination of samples. In this study, we demonstrate the potential of the highwavenumber spectral region by collecting Raman spectra of nucleoli, nucleus and cytoplasm from oral epithelial cancer (SCC-4) and dysplastic (DOK) cell lines and from normal oral epithelial primary cells, in vitro, which were then analyzed by area under the curve as a method to discriminate the spectra. In this region, we will show the discriminatory potential of the CH vibrational modes of nucleic acids, proteins and lipids. This technique demonstrated more efficient discrimination than the fingerprint region when we compared the cell cultures.

  12. High incidence of metastatic disease in primary high grade and large extremity soft tissue sarcomas treated without chemotherapy

    PubMed Central

    Leidinger, Benedikt; Heyse, Thomas; Schuck, Andreas; Buerger, Horst; Mommsen, Philipp; Bruening, Thomas; Fuchs, Susanne; Gosheger, Georg

    2006-01-01

    Background The risk of metastasis and the survival in patients with primary extremity soft tissue sarcomas is worse when tumour size is large and the grade of malignancy is high. Such tumours may receive chemotherapy and/or radiation therapy (RTX) for optimising local control. Irradiation can either be applied preoperatively or after tumour resection. The question arises if the kind of RTX in the absence of chemotherapy influences the outcome concerning local control, metastatic disease, survival and complications. Methods We retrospectively reviewed the clinical outcome of 233 patients with a primary extremity soft tissue sarcoma treated between 1990 – 2000 with a mean follow-up of 35.8 (4–120) months in our institute. 41 patients had high grade, deep and large tumours (>8 cm), an AJCC stage III (no evidence of metastasis prior to treatment) and were treated with limb salvage surgery and irradiation but stayed without additional chemotherapy. Two groups of patients were compared: the first group received postoperative RTX after tumour resection (n = 33); the second group was treated with preoperative RTX (n = 8). Both groups did not differ concerning clinical parameters. We analysed primary and secondary outcomes. Results 56% (23/41) of the population developed metastatic disease, 24% (10/41) local recurrence. The risk of metastasis was higher in the group with preoperative irradiation (p = 0.046). The overall (p = 0.0248) and relapse free survival (p = 0.104) were worse in this group. The delay to tumour resection amounted 8 weeks on average in the preoperative group. Local control was not different (p = 0.38) in both study groups. Wound infections and other combined therapy related complications were equally distributed (p = 0.22). Conclusion Without chemotherapy there remains a high risk of metastasis in AJCC grade 3 patients. In high risk patients treated without chemotherapy the elapsed time to tumour resection after preoperative radiation might

  13. Squamous cell carcinoma.

    PubMed

    Webb, Julie L; Burns, Rachel E; Brown, Holly M; LeRoy, Bruce E; Kosarek, Carrie E

    2009-03-01

    Squamous cell carcinoma (SCC) is a relatively common, malignant neoplasm of dogs and cats that can arise in a variety of locations. The gross appearance of SCC can be variable and nonspecific, so definitive diagnosis requires microscopic examination of the tissue (cytology or histology). Several treatment modalities exist, but surgical excision, if possible, is regarded as the best treatment option. Early diagnosis and treatment of SCC are key because small, early-stage tumors are the most amenable to treatment and carry the best prognosis.

  14. VRK2 identifies a subgroup of primary high-grade astrocytomas with a better prognosis

    PubMed Central

    2013-01-01

    Background Malignant astrocytomas are the most common primary brain tumors and one of the most lethal among human cancers despite optimal treatment. Therefore, the characterization of molecular alterations underlying the aggressive behavior of these tumors and the identification of new markers are thus an important step towards a better patient stratification and management. Methods and results VRK1 and VRK2 (Vaccinia-related kinase-1, -2) expression, as well as proliferation markers, were determined in a tissue microarray containing 105 primary astrocytoma biopsies. Kaplan Meier and Cox models were used to find clinical and/or molecular parameters related to overall survival. The effects of VRK protein levels on proliferation were determined in astrocytoma cell lines. High levels of both protein kinases, VRK1 or VRK2, correlated with proliferation markers, p63 or ki67. There was no correlation with p53, reflecting the disruption of the VRK-p53-DRAM autoregulatory loop as a consequence of p53 mutations. High VRK2 protein levels identified a subgroup of astrocytomas that had a significant improvement in survival. The potential effect of VRK2 was studied by analyzing the growth characteristics of astrocytoma cell lines with different EGFR/VRK2 protein ratios. Conclusion High levels of VRK2 resulted in a lower growth rate suggesting these cells are more indolent. In high-grade astrocytomas, VRK2 expression constitutes a good prognostic marker for patient survival. PMID:24079673

  15. Prophylactic salpingectomy and prophylactic salpingoophorectomy for adnexal high-grade serous epithelial carcinoma: A reappraisal.

    PubMed

    Oliver Perez, M Reyes; Magriñá, Javier; García, Alvaro Tejerizo; Jiménez Lopez, Jesus Salvador

    2015-12-01

    At present, there is no effective screening of ovarian cancer. Primary prevention may be the only strategy to decrease the mortality from ovarian cancer, not only in women at high risk but also at low risk. Several recent studies have identified the distal fimbriae end of the fallopian tubes as primary precursor of High-grade serous carcinoma. Serous tubal intraepithelial carcinomas and occult invasive serous carcinomas have been identified in 2-17% of the fallopian tubes of BRCA1/2 positive women undergoing risk-reducing salpingo-oophorectomy. Removal of the fallopian tubes with ovarian preservation has been suggested as a reasonable strategy that could reduce the risk of developing ovarian carcinoma in both low and high-risk women. It has been proposed after childbearing in women at high risk to be followed by bilateral oophorectomy at a later date. Bilateral salpingectomy is also suggested for low risk women, at the time of other benign gynaecologic surgery as a primary preventive strategy. Some studies have shown a risk reduction of ovarian cancer in women with bilateral prophylactic salpingectomy. Current research regarding bilateral salpingoophorectomy as primary prevention approach of ovarian cancer is reviewed here. In addition, the potential use of bilateral salpingectomy as prevention approach of ovarian cancer is discussed.

  16. Intra-Arterial Infusion Chemotherapy Using Cisplatin With Radiotherapy for Stage III Squamous Cell Carcinoma of the Cervix

    SciTech Connect

    Kaneyasu, Yuko Nagai, Nobutaka; Nagata, Yasushi; Hashimoto, Yasutoshi; Yuki, Shintaro; Murakami, Yuji; Kenjo, Masahiro; Kakizawa, Hideaki; Toyota, Naoyuki; Fujiwara, Hisaya; Kudo, Yoshiki; Ito, Katsuhide

    2009-10-01

    Purpose: To examine the effectiveness of concomitant intra-arterial infusion chemotherapy (IAIC) using cisplatin (CDDP) with radiotherapy for Stage III squamous cell carcinoma of the cervix. Materials and Methods: We analyzed 29 cases of Stage III squamous cell carcinoma of the uterine cervix treated with radiotherapy and IAIC of CDDP from 1991 to 2006. External-beam therapy was given to the whole pelvis using four opposing parallel fields with an 18-MV linear accelerator unit. A central shield was used after 30-40 Gy with external whole-pelvic irradiation, and the total dose was 50 Gy. High-dose-rate brachytherapy was given with {sup 192}Ir microSelectron. The dose at Point A was 6 Gy per fraction, 2 fractions per week, and the total number of fractions was either 3 or 4. Two or three courses of IAIC were given concomitantly with CDDP 120 mg or carboplatin 300 mg. Results: We confirmed excellent medicine distribution directly by using computed tomographic angiography. The 5-year overall survival rate for Stage III patients was 62%, the cause-specific survival rate was 70%, and the local relapse-free survival rate was 89%. Local recurrence, distant metastasis, and occurrences of both were 7%, 38%, and 3%, respectively. The incidence of severe acute hematologic adverse reactions (Grade {>=}3) was 27% for all patients; however, all recovered without interruption of radiotherapy. Severe nonhematologic effects (Grade {>=}3) were 3%, including nausea and ileus. Only 1 patient's radiotherapy was interrupted for a period of 1 week because of ileus. Severe late complication rates (Grade {>=}3) for the bladder, rectum, and intestine were 3%, 3%, and 10%, respectively. Conclusion: A combination of IAIC and systemic chemotherapy should be considered to improve the prognosis of patients with Stage III squamous cell carcinoma of the cervix.

  17. Amplification of FRS2 and activation of FGFR/FRS2 signaling pathway in high-grade liposarcoma.

    PubMed

    Zhang, Keqiang; Chu, Kevin; Wu, Xiwei; Gao, Hanlin; Wang, Jinhui; Yuan, Yate-Ching; Loera, Sofia; Ho, Kimberley; Wang, Yafan; Chow, Warren; Un, Frank; Chu, Peiguo; Yen, Yun

    2013-02-15

    Fibroblast growth factor (FGF) receptor (FGFR) substrate 2 (FRS2) is an adaptor protein that plays a critical role in FGFR signaling. FRS2 is located on chromosome 12q13-15 that is frequently amplified in liposarcomas. The significance of FRS2 and FGFR signaling in high-grade liposarcomas is unknown. Herein, we first comparatively examined the amplification and expression of FRS2 with CDK4 and MDM2 in dedifferentiated liposarcoma (DDLS) and undifferentiated high-grade pleomorphic sarcoma (UHGPS). Amplification and expression of the three genes were identified in 90% to 100% (9-11 of 11) of DDLS, whereas that of FRS2, CDK4, and MDM2 were observed in 55% (41 of 75), 48% (36 of 75), and 44% (33/75) of clinically diagnosed UHGPS, suggesting that these "UHGPS" may represent DDLS despite lacking histologic evidence of lipoblasts. Immunohistochemical analysis of phosphorylated FRS2 protein indicated that the FGFR/FRS2 signaling axis was generally activated in about 75% of FRS2-positive high-grade liposarcomas. Moreover, we found that FRS2 and FGFRs proteins are highly expressed and functional in three high-grade liposarcoma cell lines: FU-DDLS-1, LiSa-2, and SW872. Importantly, the FGFR selective inhibitor NVP-BGJ-398 significantly inhibited the growth of FU-DDLS-1 and LiSa-2 cells with a concomitant suppression of FGFR signal transduction. Attenuation of FRS2 protein in FU-DDLS-1 and LiSa-2 cell lines decreased the phosphorylated extracellular signal-regulated kinase 1/2 and AKT and repressed cell proliferation. These findings indicate that analysis of FRS2 in combination with CDK4 and MDM2 will more accurately characterize pathologic features of high-grade liposarcomas. Activated FGFR/FRS2 signaling may play a functional role in the development of high-grade liposarcomas, therefore, serve as a potential therapeutic target.

  18. High-grade neuroendocrine carcinomas of the lung highly express enhancer of zeste homolog 2, but carcinoids do not.

    PubMed

    Findeis-Hosey, Jennifer J; Huang, Jiaoti; Li, Faqian; Yang, Qi; McMahon, Loralee A; Xu, Haodong

    2011-06-01

    Enhancer of zeste homolog 2, the catalytic subunit of polycomb repressive complex 2, is a histone methyltransferase and plays an important role in cell proliferation and cell cycle regulation. It has been shown to be overexpressed in a number of malignant neoplasms. This study aimed to determine the expression pattern of enhancer of zeste homolog 2 in neuroendocrine tumors of the lung and the potential of enhancer of zeste homolog 2 to serve as a biomarker to segregate carcinoids from high-grade neuroendocrine carcinomas. Fifty-four cases, including 25 typical carcinoids, 7 atypical carcinoids, 9 large-cell neuroendocrine carcinomas, and 13 small-cell lung carcinomas, were immunohistochemically studied using a monoclonal antibody against enhancer of zeste homolog 2. All 13 small-cell lung carcinomas demonstrated moderate to strong nuclear staining with 12 exhibiting more than 90% of tumor cells staining. All 9 large-cell neuroendocrine carcinomas were moderately to strongly positive for enhancer of zeste homolog 2, with 6 cases having staining in more than 80% of tumor cells. In contrast, all 25 typical carcinoids and 6 atypical carcinoids showed only rare scattered enhancer of zeste homolog 2-positive tumor cells, with 1 case of atypical carcinoid exhibiting moderate staining in 40% of tumor cells. A subsequent validation study of the 14 specimens of lung or mediastinal lymph node biopsy and fine-needle aspiration, including 6 small-cell lung carcinomas, 2 large-cell neuroendocrine carcinomas, 5 typical carcinoids, and 1 atypical carcinoid, was performed. Enhancer of zeste homolog 2 was diffusely and strongly positive in all small-cell lung carcinomas and large-cell neuroendocrine carcinomas, even with severe crush artifact, whereas it was only positive in rare tumor cells in carcinoids. These findings support the formulation that enhancer of zeste homolog 2 may play an important role in the regulation of biologic behavior of high-grade neuroendocrine carcinomas

  19. College Performance and Retention: A Meta-Analysis of the Predictive Validities of ACT® Scores, High School Grades, and SES

    ERIC Educational Resources Information Center

    Westrick, Paul A.; Le, Huy; Robbins, Steven B.; Radunzel, Justine M. R.; Schmidt, Frank L.

    2015-01-01

    This meta-analysis examines the strength of the relationships of ACT® Composite scores, high school grades, and socioeconomic status (SES) with academic performance and persistence into the 2nd and 3rd years at 4-year colleges and universities. Based upon a sample of 189,612 students at 50 institutions, ACT Composite scores and high school grade…

  20. The Consistency between Human Raters and an Automated Essay Scoring System in Grading High School Students' English Writing

    ERIC Educational Resources Information Center

    Tsai, Min-hsiu

    2012-01-01

    This study investigates the consistency between human raters and an automated essay scoring system in grading high school students' English compositions. A total of 923 essays from 23 classes of 12 senior high schools in Taiwan (Republic of China) were obtained and scored manually and electronically. The results show that the consistency between…

  1. Predicting from Earlier Substance Abuse and Earlier Grade Point Average to Failure to Graduate from High School.

    ERIC Educational Resources Information Center

    Friedman, Alfred S.; And Others

    1985-01-01

    Examined failure to graduate from high school as a function of grade point average and substance abuse among Phildelphia high school students (N=427). Results of multiple regression analyses indicated that the gradepoint averages are more powerful predictors to eventual failure to graduate than are "Drug Severity Index" scores. (BL)

  2. Treatment of adult and pediatric high-grade gliomas with Withaferin A: antitumor mechanisms and future perspectives.

    PubMed

    Marlow, Megan M; Shah, Sumedh S; Véliz, Eduardo A; Ivan, Michael E; Graham, Regina M

    2017-01-01

    Resistance mechanisms employed by high-grade gliomas allow them to successfully evade current standard treatment of chemotherapy and radiation treatment. Withaferin A (WA), utilized in Ayurvedic medicine for centuries, is attracting attention for its antitumor capabilities. Here we review pertinent literature on WA as a high-grade glioma treatment, and discuss the cancerous mechanisms it affects. WA is relatively nontoxic and has shown potential in crossing the blood-brain barrier. WA prevents p53 alterations and inactivates overexpressed MDM2 through ARF and ROS production. Furthermore, WA upregulates Bax, inducing mitochondrial death cascades, inhibits mutated Akt, mTOR, and NF-κB pathways, and inhibits angiogenesis in tumors. Therapy with WA for high-grade gliomas is supported through the literature. Further investigation is warranted and encouraged to fully unearth its abilities against malignant gliomas.

  3. AGENT ORANGE AS A RISK FACTOR FOR HIGH-GRADE PROSTATE CANCER

    PubMed Central

    Ansbaugh, Nathan; Shannon, Jackilen; Mori, Motomi; Farris, Paige E.; Garzotto, Mark

    2014-01-01

    PURPOSE Agent Orange exposure (AOe) is a potential risk factor for the development of prostate cancer (PCa). However, it is unknown whether AOe specifically increases the risk of lethal PCa. This study aimed to determine the association between AOe and the risk of detecting high-grade PCa (HGPCa, Gleason ≥ 7) on biopsy in a US Veteran cohort. METHODS Risk factors included clinico-demographic and laboratory data from veterans referred for an initial prostate biopsy. Outcomes were defined as the presence versus the absence of PCa, HGPCa, or low-grade PCa (LGPCa, Gleason ≤6) in biopsy specimens. Risk amongst AOe veterans relative to unexposed veterans was estimated with multivariate logistic regression. Separate models determined whether AOe was associated with an increased risk of PCa, HGPCa or LGPCa. RESULTS Of 2720 Veterans biopsied, PCa was diagnosed in 896 (32.9%); 459 (16.9%) had HGPCa. AOe was associated with a 52% increase in overall risk of PCa detection (aOR = 1.52, 95% CI: 1.07–2.13). AOe did not confer an increase in risk of LGPCa (aOR = 1.24, 95% CI: 0.81 to 1.91), although a 75% increase in risk of HGPCa (aOR = 1.75, 95% CI: 1.12 to 2.74) was observed. AOe was associated with a 2.1 fold increase (95% CI: 1.22 to 3.62, p<0.01) in Gleason 8 or higher PCa. CONCLUSION The increased risk of PCa associated with AOe is driven by an increased risk of HGPCa in men undergoing initial prostate biopsy. These findings could aid in improved PCa screening for Vietnam-era Veterans. PMID:23670242

  4. Characterizing and targeting PDGFRA alterations in pediatric high-grade glioma

    PubMed Central

    Koschmann, Carl; Zamler, Daniel; MacKay, Alan; Robinson, Dan; Wu, Yi-Mi; Doherty, Robert; Marini, Bernard; Tran, Dustin; Garton, Hugh; Muraszko, Karin; Robertson, Patricia; Leonard, Marcia; Zhao, Lili; Bixby, Dale; Peterson, Luke; Camelo-Piragua, Sandra; Jones, Chris; Mody, Rajen; Lowenstein, Pedro R.; Castro, Maria G.

    2016-01-01

    Pediatric high-grade glioma (HGG, WHO Grade III and IV) is a devastating brain tumor with a median survival of less than two years. PDGFRA is frequently mutated/amplified in pediatric HGG, but the significance of this finding has not been fully characterized. We hypothesize that alterations of PDGFRA will promote distinct prognostic and treatment implications in pediatric HGG. In order to characterize the impact of PDGFR pathway alterations, we integrated genomic data from pediatric HGG patients (n=290) from multiple pediatric datasets and sequencing platforms. Integration of multiple human datasets showed that PDGFRA mutation, but not amplification, was associated with older age in pediatric HGG (P= <0.0001). In multivariate analysis, PDGFRA mutation was correlated with worse prognosis (P = 0.026), while PDGFRA amplification was not (P = 0.11). By Kaplan-Meier analysis, non-brainstem HGG with PDGFRA amplification carried a worse prognosis than non-brainstem HGG without PDGFRA amplification (P = 0.021). There were no pediatric patients with PDGFRA-amplified HGG that survived longer than two years. Additionally, we performed paired molecular profiling (germline / tumor / primary cell culture) and targeting of an infant thalamic HGG with amplification and outlier increased expression of PDGFRA. Dasatinib inhibited proliferation most effectively. In summary, integration of the largest genomic dataset of pediatric HGG to date, allowed us to highlight that PDGFRA mutation is found in older pediatric patients and that PDGFRA amplification is prognostic in non-brainstem HGG. Future precision-medicine based clinical trials for pediatric patients with PDGFRA-altered HGG should consider the optimized delivery of dasatinib. PMID:27582545

  5. High Efficiency Tandem Thin-Perovskite/Polymer Solar Cells with a Graded Recombination Layer.

    PubMed

    Liu, Yao; Renna, Lawrence A; Bag, Monojit; Page, Zachariah A; Kim, Paul; Choi, Jaewon; Emrick, Todd; Venkataraman, D; Russell, Thomas P

    2016-03-23

    Perovskite-containing tandem solar cells are attracting attention for their potential to achieve high efficiencies. We demonstrate a series connection of a ∼ 90 nm thick perovskite front subcell and a ∼ 100 nm thick polymer:fullerene blend back subcell that benefits from an efficient graded recombination layer containing a zwitterionic fullerene, silver (Ag), and molybdenum trioxide (MoO3). This methodology eliminates the adverse effects of thermal annealing or chemical treatment that occurs during perovskite fabrication on polymer-based front subcells. The record tandem perovskite/polymer solar cell efficiency of 16.0%, with low hysteresis, is 75% greater than that of the corresponding ∼ 90 nm thick perovskite single-junction device and 65% greater than that of the polymer single-junction device. The high efficiency of this hybrid tandem device, achieved using only a ∼ 90 nm thick perovskite layer, provides an opportunity to substantially reduce the lead content in the device, while maintaining the high performance derived from perovskites.

  6. Using multiple chemical systems in zircon to unravel the evolution of high-grade terranes

    NASA Astrophysics Data System (ADS)

    Clark, Chris; Taylor, Richard

    2016-04-01

    Since the turn of the century the rare earth element (REE) partitioning between zircon and garnet has facilitated the coupling of U-Pb ages to metamorphism, particularly in the granulite facies. The combination of in situ analysis and rapid data acquisition, particularly through combined techniques such as Laser Ablation Split Stream (LASS), means that complex terranes can be interrogated with increasing detail. However this detail provided by large datasets must also be combined with an understanding of the processes involved, for example the relative mobility of the REE and U-Pb systems with zircon grains that have withstood intense P-T conditions to varying degrees. For example, some high-temperature metapelites that seem to have all the right ingredients for the "equilibrium" to be achieved (e.g. they contain garnet, zircon, monazite and rutile, they've melted and experienced temperatures in excess of 900 °C) display variations in the REE partitioning between zircon and garnet that varies over the length-scale of a single thin section. This presentation seeks to highlight some complexities in the application of these undoublty useful techniques to high-temperature metamorphic rocks from a number of terranes and hopefully provide some useful comments on developing more efficient strategies to characterise the P-T-t evolution of high-grade terranes.

  7. Implications of Eighth Grade Algebra I on High School Mathematics Achievement

    ERIC Educational Resources Information Center

    Bayard, Robert

    2012-01-01

    As of 2008, approximately 40% of eighth grade students in the United States enroll in Algebra I (National Council of Teachers of Mathematics, 2008). Although research has shown that students have more opportunities to take advanced mathematics courses by taking eighth grade Algebra I, in the United States, approximately only one-third to one-half…

  8. Alcohol Use and the Grades of Middle and High School Students: Does School Choice Have Effects?

    ERIC Educational Resources Information Center

    Austin, Wesley; Heath, Cary

    2012-01-01

    This article addresses the question of whether youth drinking leads to lower grades for public and private school students. Instrumental variables (IV) regressions are used to investigate differences in the relationship between drinking and grades based on whether students attend a public or private school. The regressions reveal that drinking…

  9. Geophysical evidences for a thick crust south of Palghat-Tiruchi gap in the High Grade Terrains of South India

    NASA Technical Reports Server (NTRS)

    Mishra, D. C.

    1988-01-01

    The regional gravity and magnetic features of the South Indian Shield were discussed. The prominent regional gravity low of 20 to 30 mgls over the charnockite terrain of South India, coupled with the correlation of a steep gravity gradient with a prominent shear zone to the north, can be interpreted in terms of increased crustal thickness in the South Indian high-grade terrain. There is some support for this from deep seismic sounding. The magnetic signature of the high-grade terrain is also distinctive, and Mishra argued that the Palghat-Tiruchi line might represent a Precambrian boundary such as a suture between two distinct crustal blocks.

  10. Frequent EGFR Positivity and Overexpression in High-Grade Areas of Human MPNSTs

    PubMed Central

    Tabone-Eglinger, Séverine; Bahleda, Radislav; Côté, Jean-François; Terrier, Philippe; Vidaud, Dominique; Cayre, Anne; Beauchet, Alain; Théou-Anton, Nathalie; Terrier-Lacombe, Marie-José; Lemoine, Antoinette; Penault-Llorca, Frédérique; Le Cesne, Axel; Emile, Jean-François

    2008-01-01

    Malignant peripheral nerve sheath tumours (MPNSTs) are highly malignant and resistant. Transformation might implicate up regulation of epidermal growth factor receptor (EGFR). Fifty-two MPNST samples were studied for EGFR, Ki-67, p53, and survivin expression by immunohistochemistry and for EGFR amplification by in situ hybridization. Results were correlated with clinical data. EGFR RNA was also quantified by RT-PCR in 20 other MPNSTs and 14 dermal neurofibromas. Half of the patients had a neurofibromatosis type 1 (NF1). EGFR expression, detected in 86% of MPNSTs, was more frequent in NF1 specimens and closely associated with high-grade and p53-positive areas. MPNSTs expressed more EGFR transcripts than neurofibromas. No amplification of EGFR locus was observed. NF1 status was the only prognostic factor in multivariate analysis, with median survivals of 18 and 43 months for patients with or without NF1. Finally, EGFR might become a new target for MPNSTs treatment, especially in NF1-associated MPNSTs. PMID:18769552

  11. High-grade astroblastoma in a child: Report of one case and review of literature

    PubMed Central

    de la Garma, Victor Hugo Escobar; Arcipreste, Arturo Ayala; Vázquez, Felipe Padilla; Aguilar, Ricardo Ramírez; Castruita, Uriel Oliva; Guerra, Rafael Mendizábal

    2014-01-01

    Background: Astroblastoma is a rare glial neoplastic lesion that affects children and adolescents; its histogenesis remains uncertain. It is considered to account for 0.5% of all glial neoplasms, and two different subtypes have been defined based upon histologic characteristics. Case Description: We present the case of a 9-year-old girl who presented with headache, motor symptoms, and seizures few days before she was admitted to our institution. Computed tomography (CT) and magnetic resonance imaging (MRI) scans showed an intra-axial heterogeneous frontoparietal lesion with a striking “bubbly” appearance in MRI T2-weighted sequences and features of intracranial hypertension. Gross total resection of the tumor was achieved and the histopathologic diagnosis revealed high-grade astroblastoma. We reviewed the current published cases of astroblastoma to highlight the demographic, clinical, radiologic, and pathologic data. Conclusion: Astroblastomas are a distinct clinicopathologic entity, with well-described radiologic, pathologic, and cytogenetic features. Its recurrence is high and efforts must be made to elucidate the role and usefulness of radiotherapy and chemotherapy in these tumors. PMID:25101206

  12. Highly mobile ferroelastic domain walls in compositionally graded ferroelectric thin films

    DOE PAGES

    Damodaran, Anoop; Okatan, M. B.; Kacher, J.; ...

    2016-02-15

    Domains and domain walls are critical in determining the response of ferroelectrics, and the ability to controllably create, annihilate, or move domains is essential to enable a range of next-generation devices. Whereas electric-field control has been demonstrated for ferroelectric 180° domain walls, similar control of ferroelastic domains has not been achieved. Here, using controlled composition and strain gradients, we demonstrate deterministic control of ferroelastic domains that are rendered highly mobile in a controlled and reversible manner. Through a combination of thin-film growth, transmission-electron-microscopy-based nanobeam diffraction and nanoscale band-excitation switching spectroscopy, we show that strain gradients in compositionally graded PbZr1-xTixO3 heterostructuresmore » stabilize needle-like ferroelastic domains that terminate inside the film. These needle-like domains are highly labile in the out-of-plane direction under applied electric fields, producing a locally enhanced piezoresponse. This work demonstrates the efficacy of novel modes of epitaxy in providing new modalities of domain engineering and potential for as-yet-unrealized nanoscale functional devices.« less

  13. Highly mobile ferroelastic domain walls in compositionally graded ferroelectric thin films

    SciTech Connect

    Damodaran, Anoop; Okatan, M. B.; Kacher, J.; Gammer, C.; Vasudevan, Rama; Pandya, S.; Dedon, L. R.; Mangalam, R. V.; Jesse, Stephen; Balke, Nina; Minor, Andrew; Kalinin, Sergei V.; Martin, Lane W. W.

    2016-02-15

    Domains and domain walls are critical in determining the response of ferroelectrics, and the ability to controllably create, annihilate, or move domains is essential to enable a range of next-generation devices. Whereas electric-field control has been demonstrated for ferroelectric 180° domain walls, similar control of ferroelastic domains has not been achieved. Here, using controlled composition and strain gradients, we demonstrate deterministic control of ferroelastic domains that are rendered highly mobile in a controlled and reversible manner. Through a combination of thin-film growth, transmission-electron-microscopy-based nanobeam diffraction and nanoscale band-excitation switching spectroscopy, we show that strain gradients in compositionally graded PbZr1-xTixO3 heterostructures stabilize needle-like ferroelastic domains that terminate inside the film. These needle-like domains are highly labile in the out-of-plane direction under applied electric fields, producing a locally enhanced piezoresponse. This work demonstrates the efficacy of novel modes of epitaxy in providing new modalities of domain engineering and potential for as-yet-unrealized nanoscale functional devices.

  14. Efficient molecular subtype classification of high-grade serous ovarian cancer.

    PubMed

    Leong, Huei San; Galletta, Laura; Etemadmoghadam, Dariush; George, Joshy; Köbel, Martin; Ramus, Susan J; Bowtell, David

    2015-07-01

    High-grade serous carcinomas (HGSCs) account for approximately 70% of all epithelial ovarian cancers diagnosed. Using microarray gene expression profiling, we previously identified four molecular subtypes of HGSC: C1 (mesenchymal), C2 (immunoreactive), C4 (differentiated), and C5 (proliferative), which correlate with patient survival and have distinct biological features. Here, we describe molecular classification of HGSC based on a limited number of genes to allow cost-effective and high-throughput subtype analysis. We determined a minimal signature for accurate classification, including 39 differentially expressed and nine control genes from microarray experiments. Taqman-based (low-density arrays and Fluidigm), fluorescent oligonucleotides (Nanostring), and targeted RNA sequencing (Illumina) assays were then compared for their ability to correctly classify fresh and formalin-fixed, paraffin-embedded samples. All platforms achieved > 90% classification accuracy with RNA from fresh frozen samples. The Illumina and Nanostring assays were superior with fixed material. We found that the C1, C2, and C4 molecular subtypes were largely consistent across multiple surgical deposits from individual chemo-naive patients. In contrast, we observed substantial subtype heterogeneity in patients whose primary ovarian sample was classified as C5. The development of an efficient molecular classifier of HGSC should enable further biological characterization of molecular subtypes and the development of targeted clinical trials.

  15. The Potential of Targeting Ribosome Biogenesis in High-Grade Serous Ovarian Cancer

    PubMed Central

    Yan, Shunfei; Frank, Daniel; Son, Jinbae; Hannan, Katherine M.; Hannan, Ross D.; Chan, Keefe T.; Pearson, Richard B.; Sanij, Elaine

    2017-01-01

    Overall survival for patients with ovarian cancer (OC) has shown little improvement for decades meaning new therapeutic options are critical. OC comprises multiple histological subtypes, of which the most common and aggressive subtype is high-grade serous ovarian cancer (HGSOC). HGSOC is characterized by genomic structural variations with relatively few recurrent somatic mutations or dominantly acting oncogenes that can be targeted for the development of novel therapies. However, deregulation of pathways controlling homologous recombination (HR) and ribosome biogenesis has been observed in a high proportion of HGSOC, raising the possibility that targeting these basic cellular processes may provide improved patient outcomes. The poly (ADP-ribose) polymerase (PARP) inhibitor olaparib has been approved to treat women with defects in HR due to germline BRCA mutations. Recent evidence demonstrated the efficacy of targeting ribosome biogenesis with the specific inhibitor of ribosomal RNA synthesis, CX-5461 in v-myc avian myelocytomatosis viral oncogene homolog (MYC)-driven haematological and prostate cancers. CX-5461 has now progressed to a phase I clinical trial in patients with haematological malignancies and phase I/II trial in breast cancer. Here we review the currently available targeted therapies for HGSOC and discuss the potential of targeting ribosome biogenesis as a novel therapeutic approach against HGSOC. PMID:28117679

  16. Clonal evolution of high-grade serous ovarian carcinoma from primary to recurrent disease.

    PubMed

    Castellarin, Mauro; Milne, Katy; Zeng, Thomas; Tse, Kane; Mayo, Michael; Zhao, Yongjun; Webb, John R; Watson, Peter H; Nelson, Brad H; Holt, Robert A

    2013-03-01

    High-grade serous carcinoma (HGSC) is the most common and fatal form of ovarian cancer. While most tumours are highly sensitive to cytoreductive surgery and platinum- and taxane-based chemotherapy, the majority of patients experience recurrence of treatment-resistant tumours. The clonal origin and mutational adaptations associated with recurrent disease are poorly understood. We performed whole exome sequencing on tumour cells harvested from ascites at three time points (primary, first recurrence, and second recurrence) for three HGSC patients receiving standard treatment. Somatic point mutations and small insertions and deletions were identified by comparison to constitutional DNA. The clonal structure and evolution of tumours were inferred from patterns of mutant allele frequencies. TP53 mutations were predominant in all patients at all time points, consistent with the known founder role of this gene. Tumours from all three patients also harboured mutations associated with cell cycle checkpoint function and Golgi vesicle trafficking. There was convergence of germline and somatic variants within the DNA repair, ECM, cell cycle control, and Golgi vesicle pathways. The vast majority of somatic variants found in recurrent tumours were present in primary tumours. Our findings highlight both known and novel pathways that are commonly mutated in HGSC. Moreover, they provide the first evidence at single nucleotide resolution that recurrent HGSC arises from multiple clones present in the primary tumour with negligible accumulation of new mutations during standard treatment.

  17. Formation of high-grade ignimbrites Part II. A pyroclastic suspension current model with implications also for low-grade ignimbrites

    NASA Astrophysics Data System (ADS)

    Freundt, Armin

    Analogue experiments in part I led to the conclusion that pyroclastic flows depositing very high-grade ignimbrite move as dilute suspension currents. In the thermo-fluid-dynamical model developed, the degree of cooling of expanded turbulent pyroclastic flows dynamically evolves in response to entrainment of air and mass loss to sedimentation. Initial conditions of the currents are derived from column-collapse modeling for magmas with an initial H2O content of 1-3wt.% erupting through circular vents and caldera ring-fissures. The flows spread either longitudinally or radially from source up to a runout distance that increases with higher mass flux but decreases with higher gas content, temperature, bottom slope and coarser initial grain size. Progressive dilution by entrainment and sedimentation causes pyroclastic currents to transform into buoyant ash plumes at the runout distance. The ash plumes reach stratospheric heights and distribute 30-80% of the erupted material as widespread co-ignimbrite ash. Pyroclastic suspension currents with initial mass fluxes of 107-1012kg/s can spread for tens of kilometers with only limited cooling, although they move as supercritical, strongly entraining currents for the eruption conditions considered here. With increasing eruption mass flux, cooling during passage through the fountain diminishes while cooling during flow transport increases. The net effect is that eruption temperature exerts the prime control on emplacement temperature. Pyroclastic suspension currents can form welded ignimbrite across their entire extent if eruption temperature is To>1.3.Tmw, the minimum welding temperature. High eruption rates, a large fraction of fine ash, and a ring-fissure vent favor the formation of extensive high-grade ignimbrite. For very hot eruptions producing sticky, partially molten pyroclasts, analysis of particle aggregation systematics shows that factors favoring longer runout also favor more efficient aggregation, which reduces

  18. Coherent effects of high-energy particles in a graded Si(1-x)Ge(x) crystal.

    PubMed

    Bagli, E; Bandiera, L; Guidi, V; Mazzolari, A; De Salvador, D; Maggioni, G; Berra, A; Lietti, D; Prest, M; Vallazza, E; Abrosimov, N V

    2013-04-26

    A graded Si(1-x)Ge(x) crystal has been manufactured for operation with high-energy protons to excite coherent interactions of the particles with the crystal such as channeling and volume reflection. The crystal had the shape of a parallelepiped though its (111) atomic planes were curved at a radius of 25.6 m because of the graded Ge content. The crystal was exposed to a 400  GeV/c proton beam at the external lines of CERN Super Proton Synchrotron to probe its capability to steer high-energy particles. Measured deflection efficiency was 62.0% under planar channeling and 96.0% under volume reflection. Such values are critically compared to their counterparts for a standard bent Si crystal under peer conditions. A Monte Carlo simulation of the dynamics of channeled and volume reflected particles in a graded crystal including the effect of Ge impurities and of lattice dislocations has been carried out. We found that the effect of crystal imperfections spoiled the efficiency of channeling while it negligibly affected the performance of volume reflection. We finally propose the usage of the graded crystal as a primary scatterer to aid halo collimation for the new generation of hadronic machines. As a unique feature, a properly cut graded crystal circumvents the problem of the miscut angle, which is currently a severe limitation for implementation of crystal-assisted collimation.

  19. Diffusion-weighted imaging-based probabilistic segmentation of high- and low-proliferative areas in high-grade gliomas

    PubMed Central

    Fritzsche, Klaus H.; Thieke, Christian; Klein, Jan; Parzer, Peter; Weber, Marc-André; Stieltjes, Bram

    2012-01-01

    Abstract The apparent diffusion coefficient (ADC) derived from diffusion-weighted imaging (DWI) correlates inversely with tumor proliferation rates. High-grade gliomas are typically heterogeneous and the delineation of areas of high and low proliferation is impeded by partial volume effects and blurred borders. Commonly used manual delineation is further impeded by potential overlap with cerebrospinal fluid and necrosis. Here we present an algorithm to reproducibly delineate and probabilistically quantify the ADC in areas of high and low proliferation in heterogeneous gliomas, resulting in a reproducible quantification in regions of tissue inhomogeneity. We used an expectation maximization (EM) clustering algorithm, applied on a Gaussian mixture model, consisting of pure superpositions of Gaussian distributions. Soundness and reproducibility of this approach were evaluated in 10 patients with glioma. High- and low-proliferating areas found using the clustering correspond well with conservative regions of interest drawn using all available imaging data. Systematic placement of model initialization seeds shows good reproducibility of the method. Moreover, we illustrate an automatic initialization approach that completely removes user-induced variability. In conclusion, we present a rapid, reproducible and automatic method to separate and quantify heterogeneous regions in gliomas. PMID:22487677

  20. A novel, integrated PET-guided MRS technique resulting in more accurate initial diagnosis of high-grade glioma.

    PubMed

    Kim, Ellen S; Satter, Martin; Reed, Marilyn; Fadell, Ronald; Kardan, Arash

    2016-06-01

    Glioblastoma multiforme (GBM) is the most common and lethal malignant glioma in adults. Currently, the modality of choice for diagnosing brain tumor is high-resolution magnetic resonance imaging (MRI) with contrast, which provides anatomic detail and localization. Studies have demonstrated, however, that MRI may have limited utility in delineating the full tumor extent precisely. Studies suggest that MR spectroscopy (MRS) can also be used to distinguish high-grade from low-grade gliomas. However, due to operator dependent variables and the heterogeneous nature of gliomas, the potential for error in diagnostic accuracy with MRS is a concern. Positron emission tomography (PET) imaging with (11)C-methionine (MET) and (18)F-fluorodeoxyglucose (FDG) has been shown to add additional information with respect to tumor grade, extent, and prognosis based on the premise of biochemical changes preceding anatomic changes. Combined PET/MRS is a technique that integrates information from PET in guiding the location for the most accurate metabolic characterization of a lesion via MRS. We describe a case of glioblastoma multiforme in which MRS was initially non-diagnostic for malignancy, but when MRS was repeated with PET guidance, demonstrated elevated choline/N-acetylaspartate (Cho/NAA) ratio in the right parietal mass consistent with a high-grade malignancy. Stereotactic biopsy, followed by PET image-guided resection, confirmed the diagnosis of grade IV GBM. To our knowledge, this is the first reported case of an integrated PET/MRS technique for the voxel placement of MRS. Our findings suggest that integrated PET/MRS may potentially improve diagnostic accuracy in high-grade gliomas.

  1. Expression of Prostanoid EP3 Receptors in Oral Squamous Epithelium and Oral Squamous Cell Carcinoma

    PubMed Central

    Ishfaq, Muhammad; Nagi, A. H.

    2015-01-01

    Objectives. To carry out a descriptive analysis of the expression of the EP3 receptors of PGE2 in different histological grades of OSCC and adjacent normal epithelium. Material and Methods. A total of 46 patients presenting with various histological subtypes and grades of OSCC were recruited from Maxillofacial Surgery Department of Nishtar Institute of Dentistry Multan. Microscopically tumour subtyping and histological grading according to Anneroth's grading system were carried out. Immunohistochemical staining with rabbit polyclonal EP3 receptor antibody was performed and sections were scored for intensity and proportion of positive adjacent squamous epithelial and tumour cells. Results. Out of 46 patients n = 28 (60.9%) were well differentiated, n = 15 (32.6%) were moderately differentiated, and only n = 3 (6.5%) were poorly differentiated. All n = 46 cases of OSCC were positive for EP3 receptor antibody, n = 14 (30.4%) cases had strong intensity of anti EP3 antibody staining in tumour tissue, n = 17 (37%) cases showed moderate intensity, and n = 15 (32.6%) cases showed weak intensity. Conclusion. Prostanoid EP3 receptors are widely but variably expressed in OSCC. Most of well differentiated OSCC cases show a moderate to strong expression of EP3 receptors. However, insignificant statistical relation to histological grades of OSCC has been observed. This might be due to small sample size of the study. PMID:25741449

  2. Catching Up: Effect of the Talent Development Ninth-Grade Instructional Interventions in Reading and Mathematics in High-Poverty High Schools

    ERIC Educational Resources Information Center

    Balfanz, Robert; Legters, Nettie; Jordan, Will

    2004-01-01

    Little is known about the feasibility and rapidity with which the academic learning of students who enter high school multiple years behind grade level can be accelerated. This study uses multiple regression analyses of standardized test and survey data from high-poverty high schools in two large urban districts to evaluate initial effects of the…

  3. BMP and TGFbeta pathways in human central chondrosarcoma: enhanced endoglin and Smad 1 signaling in high grade tumors

    PubMed Central

    2012-01-01

    Background As major regulators of normal chondrogenesis, the bone morphogenic protein (BMP) and transforming growth factor β (TGFB) signaling pathways may be involved in the development and progression of central chondrosarcoma. In order to uncover their possible implication, the aim of this study was to perform a systematic quantitative study of the expression of BMPs, TGFBs and their receptors and to assess activity of the corresponding pathways in central chondrosarcoma. Methods Gene expression analysis was performed by quantitative RT-PCR in 26 central chondrosarcoma and 6 healthy articular cartilage samples. Expression of endoglin and nuclear localization of phosphorylated Smad1/5/8 and Smad2 was assessed by immunohistochemical analysis. Results The expression of TGFB3 and of the activin receptor-like kinase ALK2 was found to be significantly higher in grade III compared to grade I chondrosarcoma. Nuclear phosphorylated Smad1/5/8 and Smad2 were found in all tumors analyzed and the activity of both signaling pathways was confirmed by functional reporter assays in 2 chondrosarcoma cell lines. Immunohistochemical analysis furthermore revealed that phosphorylated Smad1/5/8 and endoglin expression were significantly higher in high-grade compared to low-grade chondrosarcoma and correlated to each other. Conclusions The BMP and TGFβ signaling pathways were found to be active in central chondrosarcoma cells. The correlation of Smad1/5/8 activity to endoglin expression suggests that, as described in other cell types, endoglin could enhance Smad1/5/8 signaling in high-grade chondrosarcoma cells. Endoglin expression coupled to Smad1/5/8 activation could thus represent a functionally important signaling axis for the progression of chondrosarcoma and a regulator of the undifferentiated phenotype of high-grade tumor cells. PMID:23088614

  4. Definitive Reirradiation for Locoregionally Recurrent Non-Small Cell Lung Cancer With Proton Beam Therapy or Intensity Modulated Radiation Therapy: Predictors of High-Grade Toxicity and Survival Outcomes

    SciTech Connect

    McAvoy, Sarah; Ciura, Katherine; Wei, Caimiao; Rineer, Justin; Liao, Zhongxing; Chang, Joe Y.; Palmer, Matthew B.; Cox, James D.; Komaki, Ritsuko; Gomez, Daniel R.

    2014-11-15

    Purpose: Intrathoracic recurrence of non-small cell lung cancer (NSCLC) after initial treatment remains a dominant cause of death. We report our experience using proton beam therapy and intensity modulated radiation therapy for reirradiation in such cases, focusing on patterns of failure, criteria for patient selection, and predictors of toxicity. Methods and Materials: A total of 102 patients underwent reirradiation for intrathoracic recurrent NSCLC at a single institution. All doses were recalculated to an equivalent dose in 2-Gy fractions (EQD2). All patients had received radiation therapy for NSCLC (median initial dose of 70 EQD2 Gy), with median interval to reirradiation of 17 months and median reirradiation dose of 60.48 EQD2 Gy. Median follow-up time was 6.5 months (range, 0-72 months). Results: Ninety-nine patients (97%) completed reirradiation. Median local failure-free survival, distant metastasis-free survival (DMFS), and overall survival times were 11.43 months (range, 8.6-22.66 months), 11.43 months (range, 6.83-23.84 months), and 14.71 (range, 10.34-20.56 months), respectively. Toxicity was acceptable, with rates of grade ≥3 esophageal toxicity of 7% and grade ≥3 pulmonary toxicity of 10%. Of the patients who developed local failure after reirradiation, 88% had failure in either the original or the reirradiation field. Poor local control was associated with T4 disease, squamous histology, and Eastern Cooperative Oncology Group performance status score >1. Concurrent chemotherapy improved DMFS, but T4 disease was associated with poor DMFS. Higher T status, Eastern Cooperative Oncology Group performance status ≥1, squamous histology, and larger reirradiation target volumes led to worse overall survival; receipt of concurrent chemotherapy and higher EQD2 were associated with improved OS. Conclusions: Intensity modulated radiation therapy and proton beam therapy are options for treating recurrent non-small cell lung cancer. However, rates of

  5. A comparison of geochemical core scanning methods on high-grade metamorphic COSC-1 cores

    NASA Astrophysics Data System (ADS)

    Harms, Ulrich; Hierold, Johannes; Meima, Jeannette; Rammlmair, Dieter; Kollaske, Tina

    2016-04-01

    Micro-XRF core scanning of marine and lacustrine sediment cores provides geochemical data for many elements and has become a standard tool in paleoclimate and environmental studies. In contrast, such investigations are unusual on crystalline cores due to limitations such as crystal lattice reflections. We tested micro-XRF scanning on gneisses and mylonites of the COSC-1 ICDP project in the Swedish Caledonides. The data obtained was compared with new high-resolution half-split core surface mapping using an ED-XRF instrument (50 μm res.) and Laser Induced Breakdown Spectroscopy (LIBS) core scanner (200 μm res.). In addition, an assessment was made with whole-core box oversight XRF scanning (Minalyze AB) with 10 cm resolution. High-grade metamorphic rocks including metasedimentary leucocratic gneisses and intercalated mica-rich mylonites of the lower Seve Nappe drilled during COSC-1 have been investigated to compare scanning methods. All data sets show a clear compositional step between gneiss and mylonite indicating a metasedimentary mixed layer origin (sandy to clayey) of the source rocks with extremely limited metasomatic exchange. Micro-XRF profiles are in full accord with high-resolution mapping data but cannot reproduce the detailed structural information provided by mapping data. LIBS data include light elements such as Li that are not measurable with XRF methods and confirm a sharp non-metasomatic transition between gneisses and mylonite. The whole-core box XRF scans are extremely useful to scan the 2500 m of cored material in a short time compared with other methods, and the data is very helpful, for example, for geochemical reconstructing of lithologies.

  6. The Impact of Interactive Whiteboard Technology on Ninth Grade English at Selected Rural High Schools in Upstate South Carolina

    ERIC Educational Resources Information Center

    Smith, Mark S.

    2013-01-01

    The purpose of this study was to determine the impact of interactive whiteboard technology on ninth grade English End of Course scores in two high schools in the Upstate of South Carolina in the school year 2011-2012. This study also sought to determine what impact interactive whiteboard technology had on the factors of gender, socio-economic…

  7. Weighting for Recognition: Accounting for Advanced Placement and Honors Courses when Calculating High School Grade Point Average

    ERIC Educational Resources Information Center

    Sadler, Philip M.; Tai, Robert H.

    2007-01-01

    Honors and advanced placement (AP) courses are commonly viewed as more demanding than standard high school offerings. Schools employ a range of methods to account for such differences when calculating grade point average and the associated rank in class for graduating students. In turn, these statistics have a sizeable impact on college admission…

  8. Effects of Partner's Ability on the Achievement and Conceptual Organization of High-Achieving Fifth-Grade Students.

    ERIC Educational Resources Information Center

    Carter, Glenda; Jones, M. Gail; Rua, Melissa

    2003-01-01

    Investigates high-achieving fifth-grade students' achievement gains and conceptual reorganization on convection. Features an instructional sequence of three dyadic inquiry investigations related to convection currents as well as pre- and post-assessment consisting of a multiple-choice test, a card sorting task, construction of a concept map, and…

  9. The Effects of Cardio-Syntactic Analysis Instruction on Writing Scores in a 11th Grade High School Classroom

    ERIC Educational Resources Information Center

    Kariuki, Patrick N.; Blair, Paul W.

    2015-01-01

    The purpose of this research was to determine the effects of Cardio-Syntactic Analysis instruction on writing scores in an 11th grade English class. The sample consisted of 35 students enrolled in an Honor's English 11 class at Volunteer high School, in Church Hill, TN. The class was randomly assigned into an experimental group of 17 students and…

  10. The Effects of Part-Time Employment on High School Students' Grade Point Averages and Rate of School Attendance.

    ERIC Educational Resources Information Center

    Heffez, Jack

    To determine what effects employment will have on high school students' grade point averages and rate of school attendance, the author involved fifty-six students in an experiment. Twenty-eight students were employed part-time under the Youth Incentive Entitlement Project (YIEP). The twenty-eight students in the control group were eligible for…

  11. Effects of Self-Graphing on Written Expression of Fourth Grade Students with High-Incidence Disabilities

    ERIC Educational Resources Information Center

    Stotz, Kate E.; Itoi, Madoka; Konrad, Moira; Alber-Morgan, Sheila R.

    2008-01-01

    The purpose of this study was to determine the effects of self-graphing on the writing of 3 fourth grade students with high-incidence disabilities. Measures of written expression included total number of words written and number of correct word sequences. During intervention, students self-graphed their total number of words written in response to…

  12. Helping Students Make the Transition into High School: The Effect of Ninth Grade Academies on Students' Academic and Behavioral Outcomes

    ERIC Educational Resources Information Center

    Somers, Marie-Andrée; Garcia, Ivonne

    2016-01-01

    Ninth Grade Academies (NGAs)--also called Freshman Academies--have attracted national attention as a particularly intensive and promising approach for supporting a successful transition for high school freshmen. An NGA is a self-contained learning community for ninth-graders that operates as a school within a school. NGAs have four core structural…

  13. Reflections on Teaching and Learning the Arts: A Middle-Grade Classroom and a High School for the Arts

    ERIC Educational Resources Information Center

    Barilla, Rosemary; Brown, Tina Boyer

    2015-01-01

    Rosemary Barilla, a middle-grade language arts teacher, inspired by her own dedication to the arts, describes the ways she integrates the fine arts into her classroom program that is designed to teach reading and writing. Tina Boyer Brown, a founding teacher at The Chicago High School for the Arts (ChiArts®), describes the school as a place where…

  14. Online Reading Comprehension among Seventh Grade Students with High Incidence Disabilities in Inclusive Settings: A Mixed Methods Study

    ERIC Educational Resources Information Center

    Robbins, Katherine R.

    2010-01-01

    Because research exploring how students with disabilities read and comprehend on the Internet is scarce, a mixed methods study was implemented to determine if Internet Reciprocal Teaching (IRT) is an effective intervention for improving online reading comprehension among seventh grade students with high-incidence disabilities in inclusive…

  15. A Comparative Study of Teachers' Attitudes and Practices regarding Homework in the Elementary, Middle, and High School Grades

    ERIC Educational Resources Information Center

    Peltier, Courtney Pisarich

    2011-01-01

    The purpose of this study was to examine the attitudes and practices of elementary, middle, and high school teachers regarding homework. In addition, the study sought to find if there was a relationship between the teachers' attitudes and practices of homework, as well as finding the differences between the grade levels. The questionnaire used…

  16. High-grade undifferentiated pleomorphic sarcoma of the pelvis: A case report and review of literature

    PubMed Central

    Agafonoff, Slava; Vaidya, Shrikant K.; DeFade, Brian

    2016-01-01

    High-grade spindle cell sarcomas are rare undifferentiated pleomorphic cancers that present a treatment challenge to urological practices, especially when they present in the pelvis. We report a 46-year-old male patient who presented to our urology clinic with urinary retention after having a Foley catheter placed at an outlying facility. A voiding trial was attempted, but the patient failed this trial. This failure resulted in cystoscopy with bilateral retrograde pyelograms, which revealed a compressed bladder due to extrinsic compression. This finding had been evaluated with a computed tomography (CT) scan with and without intravenous contrast that showed a 14 cm pelvic mass with bladder displacement and compression. A fine needle aspiration was done at this outlying facility, prior to referral to our office, and it confirmed spindle cell pathology. The mass was surgically excised with the histology revealing a pelvic spindle cell sarcoma with positive surgical margins. Further, metastatic work-up with CT/positron emission tomography revealed bone and lung metastasis. The patient is currently undergoing chemotherapy and radiation. In this case study, we will review staging, management, differential diagnosis, chemotherapy, and radiation. PMID:27453666

  17. Recurrent somatic mutations in ACVR1 in pediatric midline high-grade astrocytoma.

    PubMed

    Fontebasso, Adam M; Papillon-Cavanagh, Simon; Schwartzentruber, Jeremy; Nikbakht, Hamid; Gerges, Noha; Fiset, Pierre-Olivier; Bechet, Denise; Faury, Damien; De Jay, Nicolas; Ramkissoon, Lori A; Corcoran, Aoife; Jones, David T W; Sturm, Dominik; Johann, Pascal; Tomita, Tadanori; Goldman, Stewart; Nagib, Mahmoud; Bendel, Anne; Goumnerova, Liliana; Bowers, Daniel C; Leonard, Jeffrey R; Rubin, Joshua B; Alden, Tord; Browd, Samuel; Geyer, J Russell; Leary, Sarah; Jallo, George; Cohen, Kenneth; Gupta, Nalin; Prados, Michael D; Carret, Anne-Sophie; Ellezam, Benjamin; Crevier, Louis; Klekner, Almos; Bognar, Laszlo; Hauser, Peter; Garami, Miklos; Myseros, John; Dong, Zhifeng; Siegel, Peter M; Malkin, Hayley; Ligon, Azra H; Albrecht, Steffen; Pfister, Stefan M; Ligon, Keith L; Majewski, Jacek; Jabado, Nada; Kieran, Mark W

    2014-05-01

    Pediatric midline high-grade astrocytomas (mHGAs) are incurable with few treatment targets identified. Most tumors harbor mutations encoding p.Lys27Met in histone H3 variants. In 40 treatment-naive mHGAs, 39 analyzed by whole-exome sequencing, we find additional somatic mutations specific to tumor location. Gain-of-function mutations in ACVR1 occur in tumors of the pons in conjunction with histone H3.1 p.Lys27Met substitution, whereas FGFR1 mutations or fusions occur in thalamic tumors associated with histone H3.3 p.Lys27Met substitution. Hyperactivation of the bone morphogenetic protein (BMP)-ACVR1 developmental pathway in mHGAs harboring ACVR1 mutations led to increased levels of phosphorylated SMAD1, SMAD5 and SMAD8 and upregulation of BMP downstream early-response genes in tumor cells. Global DNA methylation profiles were significantly associated with the p.Lys27Met alteration, regardless of the mutant histone H3 variant and irrespective of tumor location, supporting the role of this substitution in driving the epigenetic phenotype. This work considerably expands the number of potential treatment targets and further justifies pretreatment biopsy in pediatric mHGA as a means to orient therapeutic efforts in this disease.

  18. Candidate genes and pathways downstream of PAX8 involved in ovarian high-grade serous carcinoma

    PubMed Central

    Soriano, Amata Amy; Monticelli, Antonella; Affinito, Ornella; Cocozza, Sergio; Zannini, Mariastella

    2016-01-01

    Understanding the biology and molecular pathogenesis of ovarian epithelial cancer (EOC) is key to developing improved diagnostic and prognostic indicators and effective therapies. Although research has traditionally focused on the hypothesis that high-grade serous carcinoma (HGSC) arises from the ovarian surface epithelium (OSE), recent studies suggest that additional sites of origin exist and a substantial proportion of cases may arise from precursor lesions located in the Fallopian tubal epithelium (FTE). In FTE cells, the transcription factor PAX8 is a marker of the secretory cell lineage and its expression is retained in 96% of EOC. We have recently reported that PAX8 is involved in the tumorigenic phenotype of ovarian cancer cells. In this study, to uncover genes and pathways downstream of PAX8 involved in ovarian carcinoma we have determined the molecular profiles of ovarian cancer cells and in parallel of Fallopian tube epithelial cells by means of a silencing approach followed by an RNA-seq analysis. Interestingly, we highlighted the involvement of pathways like WNT signaling, epithelial-mesenchymal transition, p53 and apoptosis. We believe that our analysis has led to the identification of candidate genes and pathways regulated by PAX8 that could be additional targets for the therapy of ovarian carcinoma. PMID:27259239

  19. Role of the immune system in the peritoneal tumor spread of high grade serous ovarian cancer.

    PubMed

    Auer, Katharina; Bachmayr-Heyda, Anna; Sukhbaatar, Nyamdelger; Aust, Stefanie; Schmetterer, Klaus G; Meier, Samuel M; Gerner, Christopher; Grimm, Christoph; Horvat, Reinhard; Pils, Dietmar

    2016-09-20

    The immune system plays a critical role in cancer progression and overall survival. Still, it is unclear if differences in the immune response are associated with different patterns of tumor spread apparent in high grade serous ovarian cancer patients and previously described by us. In this study we aimed to assess the role of the immune system in miliary (widespread, millet-sized lesions) and non-miliary (bigger, exophytically growing implants) tumor spread. To achieve this we comprehensively analyzed tumor tissues, blood, and ascites from 41 patients using immunofluorescence, flow cytometry, RNA sequencing, multiplexed immunoassays, and immunohistochemistry. Results showed that inflammation markers were systemically higher in miliary. In contrast, in non-miliary lymphocyte and monocyte/macrophage infiltration into the ascites was higher as well as the levels of PD-1 expression in tumor associated cytotoxic T-lymphocytes and PD-L1 expression in tumor cells. Furthermore, in ascites of miliary patients more epithelial tumor cells were present compared to non-miliary, possibly due to the active down-regulation of anti-tumor responses by B-cells and regulatory T-cells. Summarizing, adaptive immune responses prevailed in patients with non-miliary spread, whereas in patients with miliary spread a higher involvement of the innate immune system was apparent while adaptive responses were counteracted by immune suppressive cells and factors.

  20. The impact of chemo brain on the patient with a high-grade glioma.

    PubMed

    Lucas, Michele R

    2010-01-01

    Health-related quality of life for patients with high-grade gliomas has always been poor. The multiple insults to the brain-tumor existence and surgical procedures, irradiation, the level of stress and anxiety suffered and the adjuvant medications--steroids and anti-convulsants, all combine to diminish their health-related quality of life. Prior to the development of chemotherapy agents capable of penetrating the blood brain barrier, prognosis was 6 to 18 months. Life expectancy was short and there was little time to address the health-related quality of life. The newer agents have served to extend life, but have added another condition to the existing poor health-related quality of life, i.e., chemo brain. Chemo brain affects all cognitive function. The patients have great difficulty processing information. They have reduced attentional and concentration capability and cannot learn new information. The overall impact on their lives renders them unemployable and places a great burden on their families and on society. This chapter provides an overview of the patient experience and the burden placed on their families and on society.

  1. High-Grade Tumor Budding Stratifies Early-Stage Cervical Cancer with Recurrence Risk

    PubMed Central

    Xu, Xia; Guo, Shuang; Wang, Zehua

    2016-01-01

    Objectives This study investigated prognostic significance of tumor budding in early-stage cervical cancer (ESCC) following radical surgery and its contribution to improve the stratification of patients with recurrence risk. Methods The archival medical records and H&E-stained slides of 643 patients with IA2-IIA stage cervical cancer who underwent radical surgery were retrospectively reviewed. Clinicopathological parameters were noted, and tumor buds were counted using immunohistochemistry for each case. The prognostic significance of tumor budding was analyzed. Prediction models that comprised tumor budding were established, and the performance was compared between the novel models and classic criteria via log-rank test and receiver operating characteristic analysis. Results Tumors with high-grade tumor budding (HTB) exhibited a substantially increased risk of recurrence (hazard ratio = 4.287, P < 0.001). Nine predictive models for recurrence were established, in which HTB was combined with recognized risk factors. The model using of at least two risk factors of HTB, tumor size ≥ 4 cm, deep stromal invasion of outer 1/3, and lymphovascular space invasion to stratify patients with an intermediate risk was most predictive of recurrence compared with the classic criteria. Conclusions Tumor budding is an independent, unfavorable, prognostic factor for ESCC patients following radical surgery and holds promise for improved recurrence risk stratification. PMID:27861522

  2. Recycling of an electric arc furnace flue dust to obtain high grade ZnO.

    PubMed

    Ruiz, Oscar; Clemente, Carmen; Alonso, Manuel; Alguacil, Francisco Jose

    2007-03-06

    The production of steel in electric arc furnace (EAF) generates a by-product called EAF dusts. These steelmaking flue dusts are classified in most industrialized countries as hazardous residues because the heavy metals contained in them, tend to leach under slightly acidic rainfall conditions. However, and at the same time they contain zinc species which can be used as a source to obtain valuable by-products. The present investigation shows results on the processing of an EAF flue dust using ammonium carbonate solutions. Once zinc is dissolved: ZnO + 4NH3 + H2O --> Zn(NH3)4(2+) + 2OH- with other impurities (i.e. cadmium and copper), these are eliminated from the zinc solution via cementation with metallic zinc. The purified zinc solution was evaporated (distilled) until precipitation of a zinc carbonate species, which then was calcined to yield a zinc oxide of a high grade. For the unattacked dust residue from the leaching operation, mainly composed of zinc ferrite, several options can be considered: back-recycling to the furnace, further treatment by sodium hydroxide processing or a more safely dumping due to its relatively inertness.

  3. Longitudinal Impact of Two Universal Preventive Interventions in First Grade on Educational Outcomes in High School

    PubMed Central

    Bradshaw, Catherine P.; Zmuda, Jessika H.; Kellam, Sheppard G.; Ialongo, Nicholas S.

    2013-01-01

    This study examined the longitudinal effects of 2 first-grade universal preventive interventions on academic outcomes (e.g., achievement, special education service use, graduation, postsecondary education) through age 19 in a sample of 678 urban, primarily African American children. The classroom-centered intervention combined the Good Behavior Game (H. H. Barrish, Saunders, & Wolfe, 1969) with an enhanced academic curriculum, whereas a second intervention, the Family–School Partnership, focused on promoting parental involvement in educational activities and bolstering parents’ behavior management strategies. Both programs aimed to address the proximal targets of aggressive behavior and poor academic achievement. Although the effects varied by gender, the classroom-centered intervention was associated with higher scores on standardized achievement tests, greater odds of high school graduation and college attendance, and reduced odds of special education service use. The intervention effects of the Family–School Partnership were in the expected direction; however, only 1 effect reached statistical significance. The findings of this randomized controlled trial illustrate the long-term educational impact of preventive interventions in early elementary school. PMID:23766545

  4. Clinical trial end points for high-grade glioma: the evolving landscape*

    PubMed Central

    Reardon, David A.; Galanis, Evanthia; DeGroot, John F.; Cloughesy, Timothy F.; Wefel, Jeffrey S.; Lamborn, Kathleen R.; Lassman, Andrew B.; Gilbert, Mark R.; Sampson, John H.; Wick, Wolfgang; Chamberlain, Marc C.; Macdonald, David R.; Mehta, Minesh P.; Vogelbaum, Michael A.; Chang, Susan M.; Van den Bent, Martin J.; Wen, Patrick Y.

    2011-01-01

    To review the strengths and weaknesses of primary and auxiliary end points for clinical trials among patients with high-grade glioma (HGG). Recent advances in outcome for patients with newly diagnosed and recurrent HGG, coupled with the development of multiple promising therapeutics with myriad antitumor actions, have led to significant growth in the number of clinical trials for patients with HGG. Appropriate clinical trial design and the incorporation of optimal end points are imperative to efficiently and effectively evaluate such agents and continue to advance outcome. Growing recognition of limitations weakening the reliability of traditional clinical trial primary end points has generated increasing uncertainty of how best to evaluate promising therapeutics for patients with HGG. The phenomena of pseudoprogression and pseudoresponse have made imaging-based end points, including overall radiographic response and progression-free survival, problematic. Although overall survival is considered the “gold-standard” end point, recently identified active salvage therapies such as bevacizumab may diminish the association between presalvage therapy and overall survival. Finally, advances in imaging as well as the assessment of patient function and well being have strengthened interest in auxiliary end points assessing these aspects of patient care and outcome. Better appreciation of the strengths and limitations of primary end points will lead to more effective clinical trial strategies. Technical advances in imaging as well as improved survival for patients with HGG support the further development of auxiliary end points evaluating novel imaging approaches as well as measures of patient function and well being. PMID:21310734

  5. Role of the immune system in the peritoneal tumor spread of high grade serous ovarian cancer

    PubMed Central

    Auer, Katharina; Bachmayr-Heyda, Anna; Sukhbaatar, Nyamdelger; Aust, Stefanie; Schmetterer, Klaus G.; Meier, Samuel M.; Gerner, Christopher; Grimm, Christoph; Horvat, Reinhard; Pils, Dietmar

    2016-01-01

    The immune system plays a critical role in cancer progression and overall survival. Still, it is unclear if differences in the immune response are associated with different patterns of tumor spread apparent in high grade serous ovarian cancer patients and previously described by us. In this study we aimed to assess the role of the immune system in miliary (widespread, millet-sized lesions) and non-miliary (bigger, exophytically growing implants) tumor spread. To achieve this we comprehensively analyzed tumor tissues, blood, and ascites from 41 patients using immunofluorescence, flow cytometry, RNA sequencing, multiplexed immunoassays, and immunohistochemistry. Results showed that inflammation markers were systemically higher in miliary. In contrast, in non-miliary lymphocyte and monocyte/macrophage infiltration into the ascites was higher as well as the levels of PD-1 expression in tumor associated cytotoxic T-lymphocytes and PD-L1 expression in tumor cells. Furthermore, in ascites of miliary patients more epithelial tumor cells were present compared to non-miliary, possibly due to the active down-regulation of anti-tumor responses by B-cells and regulatory T-cells. Summarizing, adaptive immune responses prevailed in patients with non-miliary spread, whereas in patients with miliary spread a higher involvement of the innate immune system was apparent while adaptive responses were counteracted by immune suppressive cells and factors. PMID:27665539

  6. YAP Induces High-Grade Serous Carcinoma in Fallopian Tube Secretory Epithelial Cells

    PubMed Central

    Hua, Guohua; Lv, Xiangmin; He, Chunbo; Remmenga, Steven W.; Rodabough, Kerry J.; Dong, Jixin; Yang, Liguo; Lele, Subodh M.; Yang, Peixin; Zhou, Jin; Karst, Alison; Drapkin, Ronny I.; Davis, John S.; Wang, Cheng

    2015-01-01

    Accumulating evidence indicates that ovarian high-grade serous carcinoma (HGSC) originates from Fallopian tube secretory epithelial cells (FTSECs). However, the molecular mechanisms underlying the initiation and progression of HGSC derived from FTSECs remains unclear. In the present study, we found that the Hippo/YAP signaling pathway plays a critical role in the initiation and progression of Fallopian tube and ovarian HGSC. Importantly, YAP was overexpressed in inflammatory and cancerous Fallopian tube tissues. Further, overexpression of wild-type YAP, or constitutively active YAP in immortalized FTSECs, induced cell proliferation, migration, colony formation, and tumorigenesis. Moreover, the Hippo/YAP and the fibroblast growth factor (FGF) signaling pathways formed an autocrine/paracrine positive feedback loop to drive the progression of the FTSECs-derived HGSC. Evidence in this study strongly suggests that combined therapy with inhibitors of YAP (such as verteporfin) and FGFRs (such as BGJ398) can provide a novel therapeutic strategy to treat Fallopian tube and ovarian HGSC. PMID:26364602

  7. Recurrent somatic mutations in ACVR1 in pediatric midline high-grade astrocytoma

    PubMed Central

    Fontebasso, Adam M.; Papillon-Cavanagh, Simon; Schwartzentruber, Jeremy; Nikbakht, Hamid; Gerges, Noha; Fiset, Pierre-Olivier; Bechet, Denise; Faury, Damien; De Jay, Nicolas; Ramkissoon, Lori; Corcoran, Aoife; Jones, David T W; Sturm, Dominik; Johann, Pascal; Tomita, Tadanori; Goldman, Stewart; Nagib, Mahmoud; Bendel, Anne; Goumnerova, Liliana; Bowers, Daniel C.; Leonard, Jeffrey R.; Rubin, Joshua B.; Alden, Tord; Browd, Samuel; Geyer, J. Russell; Leary, Sarah; Jallo, George; Cohen, Kenneth; Gupta, Nalin; Prados, Michael D.; Carret, Anne-Sophie; Ellezam, Benjamin; Crevier, Louis; Klekner, Almos; Bognar, Laszlo; Hauser, Peter; Garami, Miklos; Myseros, John; Dong, Zhifeng; Siegel, Peter M.; Malkin, Hayley; Ligon, Azra; Albrecht, Steffen; Pfister, Stefan M.; Ligon, Keith L.; Majewski, Jacek; Jabado, Nada; Kieran, Mark W

    2014-01-01

    Midline pediatric high-grade astrocytomas (pHGAs) are incurable with few treatment targets identified. Most tumors harbor K27M mutations on histone 3 variants. In 40 treatment-naïve midline pHGAs, 39 analyzed by whole-exome sequencing, we find additional somatic mutations specific to tumor location. Gain-of-function mutations in ACVR1 occur in tumors of the pons in conjunction with H3.1 K27M, while FGFR1 mutations/fusions occur in thalamic tumors associated with H3.3 K27M. Hyper-activation of the bone morphogenetic protein (BMP)/ACVR1 developmental pathway in pHGAs harbouring ACVR1 mutations led to increased phospho-SMAD1/5/8 expression and up-regulation of BMP downstream early response genes in tumour cells. Global DNA methylation profiles were significantly associated with the K27M mutation regardless of the mutant H3 variant and irrespective of tumor location, supporting its role in driving the epigenetic phenotype. This significantly expands the potential treatment targets and further justifies pre-treatment biopsy in pHGA as a means to orient therapeutic efforts in this disease. PMID:24705250

  8. IR/IGF1R signaling as potential target for treatment of high-grade osteosarcoma

    PubMed Central

    2013-01-01

    Background High-grade osteosarcoma is an aggressive tumor most often developing in the long bones of adolescents, with a second peak in the 5th decade of life. Better knowledge on cellular signaling in this tumor may identify new possibilities for targeted treatment. Methods We performed gene set analysis on previously published genome-wide gene expression data of osteosarcoma cell lines (n=19) and pretreatment biopsies (n=84). We characterized overexpression of the insulin-like growth factor receptor (IGF1R) signaling pathways in human osteosarcoma as compared with osteoblasts and with the hypothesized progenitor cells of osteosarcoma – mesenchymal stem cells. This pathway plays a key role in the growth and development of bone. Since most profound differences in mRNA expression were found at and upstream of the receptor of this pathway, we set out to inhibit IR/IGF1R using OSI-906, a dual inhibitor for IR/IGF1R, on four osteosarcoma cell lines. Inhibitory effects of this drug were measured by Western blotting and cell proliferation assays. Results OSI-906 had a strong inhibitory effect on proliferation of 3 of 4 osteosarcoma cell lines, with IC50s below 100 nM at 72 hrs of treatment. Phosphorylation of IRS-1, a direct downstream target of IGF1R signaling, was inhibited in the responsive osteosarcoma cell lines. Conclusions This study provides an in vitro rationale for using IR/IGF1R inhibitors in preclinical studies of osteosarcoma. PMID:23688189

  9. High expression of TGF-β1 in the vaginal incisional margin predicts poor prognosis in patients with stage Ib-IIa cervical squamous cell carcinoma.

    PubMed

    Fan, Dong-Mei; Wang, Xin-Jun; He, Tao; Wang, Yan; Zhou, Dan; Kong, Guo-Qiang; Jiang, Tao; Zhang, Mei-Mei

    2012-04-01

    This study evaluated the relationship between altered cytoplasmic expression of TGF-β1 in tissues of the vaginal incisional margin and vaginal cancer recurrence in patients with stage Ib-IIa cervical squamous cell carcinoma (CSCC). This paper also discusses the prognostic value of TGF-β1 expression at these locations. We found that TGF-β1 expression in the vaginal margin had a close association with vaginal recurrence of stage Ib-IIa CSCC and was an independent prognostic marker of this disease.

  10. High histologic grade and increased relative content of tryptophan in breast cancer using ratios from fingerprint fluorescence spectral peaks

    NASA Astrophysics Data System (ADS)

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

    2015-03-01

    Histologic grade is a very important, but underappreciated, parameter of breast cancer aggressiveness. Despite its importance, it has historically not been included as one of the criteria for staging of this cancer. In this study, spectral fluorescence profiles from patients with breast carcinoma were acquired. Ratios of emission peaks at 340 over 440,460 nm from biomolecules in malignant and normal samples were calculated. Cancerous over normal ratios (double ratio (DR) method) were evaluated with respect to tumor characteristics. Increased tryptophan content in breast cancer tissues correlates strongly with high grade, but not with lymph node metastases, estrogen receptor, progesterone receptor or Her-2-Neu receptor status.

  11. Amplification of the telomerase RNA component gene as a new genetic marker for disease progression and prognosis in esophageal squamous cell carcinoma.

    PubMed

    Wang, J-D; Ma, J; Wang, F-Y; Peng, L-B; Wang, X; Shi, S-S; Ma, H-H; Lu, Z-F; Lu, G-M; Zhou, X-J

    2013-01-01

    Amplification of the human telomerase RNA component (TERC) gene was found in esophageal squamous cell carcinoma (ESCC). However, its roles in the progression and prognosis of ESCC have not been well understood. The amplification of TERC in normal mucosa, low-grade and high-grade intraepithelial neoplasia, and invasive ESCC samples were evaluated using a fluorescence in situ hybridization assay. The amplification of TERC invariably occurred in high-grade intraepithelial neoplasia and invasive ESCC, partially occurred in low-grade intraepithelial neoplasia specimens, and seldom occurred in normal mucosa. The average signal ratio of TERC to chromosome 3 centromere-specific probe (TERC/CSP3) was 1.00 ± 0.01 (average ± standard deviation) in normal mucosas, 1.01 ± 0.08 in low-grade intraepithelial neoplasias, 1.39 ± 0.26 in high-grade intraepithelial neoplasias, and 1.56 ± 0.41 in invasive ESCC. High TERC/CSP3 ratio was positively associated with lymph node metastasis (P = 0.005) and advanced tumor stage (P = 0.045). Patients with high amplification of TERC had poor survival (P = 0.01). The amplification of TERC could be used as a new genomic marker for disease progression and prognosis of ESCC. The amplified TERC gene may be a potential therapeutic target for ESCC.

  12. Expression of SRSF3 is Correlated with Carcinogenesis and Progression of Oral Squamous Cell Carcinoma

    PubMed Central

    Peiqi, Liu; Zhaozhong, Guo; Yaotian, Yin; Jun, Jia; Jihua, Guo; Rong, Jia

    2016-01-01

    Objective: Oral squamous cell carcinoma (OSCC) is the most common malignancy of head and neck with high mortality rates. The mechanisms of initiation and development of OSCC remain largely unknown. Dysregulated alternative splicing of pre-mRNA has been associated with OSCC. Splicing factor SRSF3 is a proto-oncogene and overexpressed in multiple cancers. The aim of this study was to uncover the relationship between SRSF3 and carcinogenesis and progression of oral squamous cell carcinoma. Design and Methods: The expression of SRSF3 in oral normal, dysplasia, or carcinoma tissues was analyzed by immunohistochemistry. The expression levels of EMT-related genes were quantified by real-time quantitative RT-PCR. The expression of SRSF3 in DMBA treated primary cultured oral epithelial cells were analyzed by western blot. Result: SRSF3 is overexpressed in oral cancer and moderate or severe dysplasia tissues. Patients with high grade cancer or lymphatic metastasis showed up-regulated expression of SRSF3. Knockdown of SRSF3 repressed the expression of Snail and N-cadherin in vitro. Carcinogen DMBA treated primary cultured oral epithelial cells showed significantly increased SRSF3 level than in control cells. Conclusion: Our results suggested that SRSF3 is associated with the initiation and development of OSCC and may be a biomarker and therapeutic target of OSCC. PMID:27429590

  13. Kinase domain activation of FGFR2 yields high-grade lung adenocarcinoma sensitive to a Pan-FGFR inhibitor in a mouse model of NSCLC.

    PubMed

    Tchaicha, Jeremy H; Akbay, Esra A; Altabef, Abigail; Mikse, Oliver R; Kikuchi, Eiki; Rhee, Kevin; Liao, Rachel G; Bronson, Roderick T; Sholl, Lynette M; Meyerson, Matthew; Hammerman, Peter S; Wong, Kwok-Kin

    2014-09-01

    Somatic mutations in FGFR2 are present in 4% to 5% of patients diagnosed with non-small cell lung cancer (NSCLC). Amplification and mutations in FGFR genes have been identified in patients with NSCLCs, and clinical trials are testing the efficacy of anti-FGFR therapies. FGFR2 and other FGFR kinase family gene alterations have been found in both lung squamous cell carcinoma and lung adenocarcinoma, although mouse models of FGFR-driven lung cancers have not been reported. Here, we generated a genetically engineered mouse model (GEMM) of NSCLC driven by a kinase domain mutation in FGFR2. Combined with p53 ablation, primary grade 3/4 adenocarcinoma was induced in the lung epithelial compartment exhibiting locally invasive and pleiotropic tendencies largely made up of multinucleated cells. Tumors were acutely sensitive to pan-FGFR inhibition. This is the first FGFR2-driven lung cancer GEMM, which can be applied across different cancer indications in a preclinical setting.

  14. Analysis of DNA Copy Number Alterations in Ovarian Serous Tumors Identifies New Molecular Genetic Changes in Low-grade and High-grade Carcinomas

    PubMed Central

    Kuo, Kuan-Ting; Guan, Bin; Feng, Yuanjian; Mao, Tsui-Lien; Chen, Xu; Jinawath, Natini; Wang, Yue; Kurman, Robert J.; Shih, Ie-Ming; Wang, Tian-Li

    2009-01-01

    Ovarian serous carcinoma, the most common and lethal type of ovarian cancer, was thought to develop from two distinct molecular pathways. High-grade (HG) serous carcinomas contain frequent TP53 mutations while low-grade (LG) carcinomas arise from serous borderline tumors (SBT) and harbor mutations in KRAS/BRAF/ERBB2 pathway. However, the molecular alterations involved in the progression from SBT to LG carcinoma remain largely unknown. As well, the extent of deletion of tumor suppressors in ovarian serous carcinomas has not been well-studied. To further address these two issues, we assessed DNA copy number changes among affinity-purified tumor cells from 37 ovarian serous neoplasms including SBT, LG and HG tumors using high density 250K SNP arrays. Chromosomal instability index as measured by changes in DNA copy number was significantly higher in HG than in LG serous carcinomas. Hemizygous ch1p36 deletion was common in LG serous carcinomas but was rarely seen in SBT. This region contains several candidate tumor suppressors including miR-34a. In contrast, in HG serous carcinomas, significant numbers of amplifications and deletions including homozygous deletions were identified. Among homozygous deletions, loci containing Rb1, CDKN2A/B, CSMD1, and DOCK4 were most common, being present in 10.6%, 6.4%, 6.4% and 4.3%, respectively, in independent 47 affinity-purified HG serous carcinomas. Except the CDKN2A/B region, these homozygous deletions were not present in either SBT or LG tumors. Our study provides a genome-wide homozygous deletion profiles in HG serous carcinomas, serving as a molecular foundation to study tumor suppressors in ovarian cancer. PMID:19383911

  15. Convection-enhanced delivery catheter placements for high-grade gliomas: complications and pitfalls.

    PubMed

    Shahar, Tal; Ram, Zvi; Kanner, Andrew A

    2012-04-01

    Convection-enhanced delivery (CED) of compounds into brain tumors reportedly circumvents the blood brain barrier. CED intends to increase drug delivery to malignant cells, reaching high local therapeutic concentration and decreasing or eliminating systemic side effects. Clinical experience and published data on catheter placement (CP) surgery are scarce. We propose practical and technical guidelines for planning CED based on our experience. We retrospectively analyzed the medical charts and relevant neuroimages of 25 patients following the insertion of 64 CED catheters. The patients were enrolled in at least one of four clinical trials using CED for treating recurrent glioblastoma multiforme in our institution between 2003-2006. Intra- and postoperative complications related to CP surgery and the difficulties and pitfalls of planning were evaluated. There were 29 CP surgeries. Forty-four peritumoral brain tissue catheters were inserted in 16 CP surgeries following tumor resection in 16 patients, and 20 catheters were placed into the tumor in 13 procedures in 10 patients. The lesions were in or near eloquent brain tissue areas in 13 of all CP surgeries. Complications included increased edema (31%), infection (6.9%), bleeding (6.9%) and seizures (13.8%). Significant neurological deterioration occurred in 4 patients (13.8%). Difficulties in adhering to CP surgery guidelines included lesion site (superficial, mesial temporal lobe, proximity to CSF spaces), proximity to eloquent cortical areas, tissue density that interfered with the trajectory, and technical limitations of stereotactic instruments. CED procedures for high-grade gliomas may be associated with surgical morbidity. Adherence to guidelines might be difficult because of lesion site and complicated by brain and tumor tissue characteristics. This should be considered while planning clinical trials that use convection-based technology.

  16. The End-of-Life Phase of High-Grade Glioma Patients: Dying With Dignity?

    PubMed Central

    Taphoorn, Martin J.B.; Uitdehaag, Bernard; Heimans, Jan J.; Deliens, Luc; Reijneveld, Jaap C.; Pasman, H. Roeline W.

    2013-01-01

    Background. In the end-of-life (EOL) phase, high-grade glioma (HGG) patients have a high symptom burden and often lose independence because of physical and cognitive dysfunction. This might affect the patient's personal dignity. We aimed to (a) assess the proportion of HGG patients dying with dignity as perceived by their relatives and (b) identify disease and care factors correlated with dying with dignity in HGG patients. Methods. We approached relatives of a cohort of 155 deceased HGG patients for the study. Participants completed a questionnaire concerning the EOL phase of the patient, covering several subthemes: (a) symptoms and signs, (b) health-related quality of life, (c) decision making, (d) place and quality of EOL care, and (e) dying with dignity. Results. Relatives of 81 patients participated and 75% indicated that the patient died with dignity. These patients had fewer communication deficits, experienced fewer transitions between health care settings in the EOL phase, and more frequently died at their preferred place of death. Relatives were more satisfied with the physician providing EOL care and reported that the physician adequately explained treatment options. Multivariate analysis identified satisfaction with the physician, the ability to communicate, and the absence of transitions between settings as most predictive of a dignified death. Conclusions. Physicians caring for HGG patients in the EOL phase should timely focus on explaining possible treatment options, because patients experience communication deficits toward death. Physicians should strive to allow patients to die at their preferred place and avoid transitions during the last month of life. PMID:23335620

  17. A Molecular Portrait of High-Grade Ductal Carcinoma In Situ

    PubMed Central

    Abba, Martin C.; Gong, Ting; Lu, Yue; Lee, Jaeho; Zhong, Yi; Lacunza, Ezequiel; Butti, Matias; Takata, Yoko; Gaddis, Sally; Shen, Jianjun; Estecio, Marcos R.; Sahin, Aysegul A.; Aldaz, C. Marcelo

    2016-01-01

    Ductal carcinoma in situ (DCIS) is a noninvasive precursor lesion to invasive breast carcinoma. We still have no understanding on why only some DCIS lesions evolve to invasive cancer whereas others appear not to do so during the life span of the patient. Here, we performed full exome (tumor vs. matching normal), transcriptome, and methylome analysis of 30 pure high-grade DCIS (HG-DCIS) and 10 normal breast epithelial samples. Sixty-two percent of HG-DCIS cases displayed mutations affecting cancer driver genes or potential drivers. Mutations were observed affecting PIK3CA (21% of cases), TP53 (17%), GATA3 (7%), MLL3 (7%) and single cases of mutations affecting CDH1, MAP2K4, TBX3, NF1, ATM, and ARID1A. Significantly, 83% of lesions displayed numerous large chromosomal copy number alterations, suggesting they might precede selection of cancer driver mutations. Integrated pathway-based modeling analysis of RNA-seq data allowed us to identify two DCIS subgroups (DCIS-C1 and DCIS-C2) based on their tumor-intrinsic subtypes, proliferative, immune scores, and in the activity of specific signaling pathways. The more aggressive DCIS-C1 (highly proliferative, basal-like, or ERBB2+) displayed signatures characteristic of activated Treg cells (CD4+/CD25+/FOXP3+) and CTLA4+/CD86+ complexes indicative of a tumor-associated immunosuppressive phenotype. Strikingly, all lesions showed evidence of TP53 pathway inactivation. Similarly, ncRNA and methylation profiles reproduce changes observed postinvasion. Among the most significant findings, we observed upregulation of lncRNA HOTAIR in DCIS-C1 lesions and hypermethylation of HOXA5 and SOX genes. We conclude that most HG-DCIS lesions, in spite of representing a preinvasive stage of tumor progression, displayed molecular profiles indistinguishable from invasive breast cancer. PMID:26249178

  18. Penile squamous cell carcinoma: a review of the literature and case report treated with Mohs micrographic surgery*

    PubMed Central

    Marchionne, Elizabeth; Perez, Caroline; Hui, Andrea; Khachemoune, Amor

    2017-01-01

    The majority of penile carcinoma is squamous cell carcinoma. Although uncommon in the United States, it represents a larger proportion of cancers in the underdeveloped world. Invasive squamous cell carcinoma may arise from precursor lesions or de novo , and has been associated with lack of circumcision and HPV infection. Early diagnosis is imperative as lymphatic spread is associated with a poor prognosis. Radical surgical treatment is no longer the mainstay, and penile sparing treatments now are often used, including Mohs micrographic surgery. Therapeutic decisions should be made with regard to the size and location of the tumor, as well as the functional desires of the patient. It is critical for the dermatologist to be familiar with the evaluation, grading/staging, and treatment advances of penile squamous cell carcinoma. Herein, we present a review of the literature regarding penile squamous cell carcinoma, as well as a case report of invasive squamous cell carcinoma treated with Mohs micrographic surgery. PMID:28225964

  19. Transcranial electro-hyperthermia combined with alkylating chemotherapy in patients with relapsed high-grade gliomas: phase I clinical results.

    PubMed

    Wismeth, Caecilia; Dudel, Christine; Pascher, Christina; Ramm, Paul; Pietsch, Torsten; Hirschmann, Birgit; Reinert, Christiane; Proescholdt, Martin; Rümmele, Petra; Schuierer, Gerhard; Bogdahn, Ulrich; Hau, Peter

    2010-07-01

    Non-invasive loco-regional electro-hyperthermia (EHT) plus alkylating chemotherapy is occasionally used as salvage treatment in the relapse of patients with high-grade gliomas. Experimental data and retrospective studies suggest potential effects. However, no prospective clinical results are available. We performed a single-center prospective non-controlled single-arm Phase I trial. Main inclusion criteria were recurrent high-grade glioma WHO Grade III or IV, age 18-70, and Karnofsky performance score > or = 70. Primary endpoints were dose-limiting toxicities (DLT) and maximum tolerated dose (MTD) with the combined regimen. Groups of 3 or 4 patients were treated 2-5 times a week in a dose-escalation scheme with EHT. Alkylating chemotherapy (ACNU, nimustin) was administered at a dose of 90 mg/m(2) on day 1 of 42 days for up to six cycles or until tumor progression (PD) or DLT occurred. Fifteen patients with high-grade gliomas were included. Relevant toxicities were local pain and increased focal neurological signs or intracranial pressure. No DLT occurred. In some patients, the administration of mannitol during EHT or long-term use of corticosteroids was necessary to resolve symptoms. Although some patients showed responses in their primarily treated sites, the pattern of response was not well defined. EHT plus alkylating chemotherapy is tolerable in patients with relapse of high-grade gliomas. Episodes of intracranial pressure were, at least, possibly attributed to EHT but did not cause DLTs. A Phase II trial targeting treatment effects is warranted on the basis of the results raised in this trial.

  20. Papanicolaou test in the detection of high-grade cervical lesions: a re-evaluation based on cytohistologic non-correlation rates in 356 concurrently obtained samples.

    PubMed

    Carns, Bhavini; Fadare, Oluwole

    2008-01-01

    Studies evaluating the routine Papanicolaou (Pap) test have traditionally used as the reference gold standard, the diagnoses on the follow-up histologic samples. Since the latter are typically obtained days to weeks after the Pap test, the accuracy of the resultant comparison may be affected by interim factors, such as regression of human papillomavirus, new lesion acquisitions or colposcopy-associated variability. A subset of our clinicians have routinely obtained cervical cytology samples immediately prior to their colposcopic procedures, which presented a unique opportunity to re-evaluate the test performance of liquid-based cervical cytology in detecting the most clinically significant lesions (i.e. cervical intraepithelial neoplasia 2 or worse: CIN2+), using as gold standard, diagnoses on cervical biopsies that were essentially obtained simultaneously. For each patient, cytohistologic non-correlation between the Pap test and biopsy was considered to be present when either modality displayed a high-grade squamous intraepithelial lesion (HGSIL)/CIN2+ while the other displayed a less severe lesion. Therefore, HGSIL/CIN2+ was present in both the Pap test and biopsy in true positives, and absent in both modalities in true negatives. In false positives, the Pap test showed HGSIL while the biopsy showed less than a CIN2+. In false negatives, Pap tests displaying less than a HGSIL were associated with biopsies displaying CIN2+. Combinations associated with "atypical" interpretations were excluded. A cytohistologic non-correlation was present in 17 (4.8%) of the 356 combinations reviewed. The non-correlation was attributed, by virtue of having the less severe interpretation, to the Pap test in all 17 cases. There were 17, 322, 0, and 17 true positives, true negatives, false positives and false negatives respectively. The sensitivity, specificity, positive predictive value and negative predictive value of the Pap test, at a diagnostic threshold of HGSIL, in identifying

  1. A Low-Cost HPV Immunochromatographic Assay to Detect High-Grade Cervical Intraepithelial Neoplasia

    PubMed Central

    Scapulatempo-Neto, Cristovam; Stein, Maíra Degiovani; Resende, Julio Cesar Possati; Antoniazzi, Márcio; Villa, Luisa Lina; Levi, José Eduardo; Longatto-Filho, Adhemar; Fregnani, José Humberto Tavares Guerreiro

    2016-01-01

    Objective To evaluate the reproducibility and accuracy of the HPV16/18-E6 test. Methods The study population was comprised of 448 women with a previously abnormal Pap who were referred to the Barretos Cancer Hospital (Brazil) for diagnosis and treatment. Two cervical samples were collected immediately before colposcopy, one for the hr-HPV-DNA test and cytology and the other for the HPV16/18-E6 test using high-affinity monoclonal antibodies (mAb). Women with a histologic diagnosis of cervical intraepithelial neoplasia grade 2 or 3 were considered to be positive cases. Different strategies using a combination of screening methods (HPV-DNA) and triage tests (cytology and HPV16/18-E6) were also examined and compared. Results The HPV16/18-E6 test exhibited a lower positivity rate compared with the HPV-DNA test (19.0% vs. 29.3%, p<0.001) and a moderate/high agreement (kappa = 0.68, 95%CI: 0.60–0.75). It also exhibited a significantly lower sensitivity for CIN2+ and CIN3+ detection compared to the HPV-DNA test and a significantly higher specificity. The HPV16/18-E6 test was no different from cytology in terms of sensitivity, but it exhibited a significantly higher specificity in comparison to ASCH+. A triage test after HPV-DNA detection using the HPV16/18-E6 test exhibited a significantly higher specificity compared with a triage test of ASCH+ to CIN2+ (91.8% vs. 87.4%, p = 0.04) and CIN3+ (88.6% vs. 84.0%, p = 0.05). Conclusion The HPV16/18-E6 test exhibited moderate/high agreement with the HPV-DNA test but lower sensitivity and higher specificity for the detection of CIN2+ and CIN3+. In addition, its performance was quite similar to cytology, but because of the structural design addressed for the detection of HPV16/18-E6 protein, the test can miss some CIN2/3+ lesions caused by other high-risk HPV types. PMID:27764154

  2. The NER-related gene GTF2H5 predicts survival in high-grade serous ovarian cancer patients

    PubMed Central

    Kamieniak, Marta M.; Muñoz-Repeto, Ivan; Borrego, Salud; Hernando, Susana; Hernández-Agudo, Elena; Heredia Soto, Victoria; Márquez-Rodas, Ivan; Echarri, María José; Lacambra-Calvet, Carmen; Sáez, Raquel; Redondo, Andrés; Benítez, Javier

    2016-01-01

    Objective We aimed to evaluate the prognostic and predictive value of the nucleotide excision repair-related gene GTF2H5, which is localized at the 6q24.2-26 deletion previously reported by our group to predict longer survival of high-grade serous ovarian cancer patients. Methods In order to test if protein levels of GTF2H5 are associated with patients' outcome, we performed GTF2H5 immunohistochemical staining in 139 high-grade serous ovarian carcinomas included in tissue microarrays. Upon stratification of cases into high- and low-GTF2H5 staining categories (> and ≤ median staining, respectively) Kaplan-Meier and log-rank test were used to estimate patients’ survival and assess statistical differences. We also evaluated the association of GTF2H5 with survival at the transcriptional level by using the on-line Kaplan-Meier plotter tool, which includes gene expression and survival data of 855 high-grade serous ovarian cancer patients from 13 different datasets. Finally, we determined whether stable short hairpin RNA-mediated GTF2H5 downregulation modulates cisplatin sensitivity in the SKOV3 and COV504 cell lines by using cytotoxicity assays. Results Low expression of GTF2H5 was associated with longer 5-year survival of patients at the protein (hazard ratio [HR], 0.52; 95% CI, 0.29 to 0.93; p=0.024) and transcriptional level (HR, 0.80; 95% CI, 0.65 to 0.97; p=0.023) in high-grade serous ovarian cancer patients. We confirmed the association with 5-year overall survival (HR, 0.55; 95% CI, 0.38 to 0.78; p=0.0007) and also found an association with progression-free survival (HR, 0.72; 95% CI, 0.54 to 0.96; p=0.026) in a homogenous group of 388 high-stage (stages III-IV using the International Federation of Gynecology and Obstetrics staging system), optimally debulked high-grade serous ovarian cancer patients. GTF2H5-silencing induced a decrease of the half maximal inhibitory concentration upon cisplatin treatment in GTF2H5-silenced ovarian cancer cells. Conclusion Low

  3. [Surveillance study on use of over-the-counter drug and health food by school pharmacist for grade-schooler, junior high school student, and high school students].

    PubMed

    Anraku, Makoto; Tomida, Hisao; Sato, Eiji; Tabuchi, Norihiko; Yoshitomi, Hironori; Okamura, Nobuyuki; Taguchi, Katsuhide; Kondo, Yuko; Murakami, Nobuyuki

    2011-01-01

    In recent years, it is necessary to acquire knowledge not only about medicine but also over-the-counter (OTC) drugs and health food for children, because lowering trend in the age of the health hazard by improper use of health food is reported. Therefore, in order to estimate the extent of use of OTC drugs and health food, the school pharmacists administered a questionnaire to students in grade-school (n=123), junior high school (n=303), and high school (n=115) in Fukuyama city. As a result of the questionnaire survey, surprisingly, the usage ratio of OTC drugs and health food showed the most increase in grade-schooler. The trigger of use of health food is "parents' recommendations" in the lower grades, otherwise the ratio of "use by themselves" was increased in the higher grades. Moreover, a remarkable difference was observed by the kinds of use in students with or without exercise. Interestingly, exercise group expected "physical strength" effects than no exercise group. In addition, the ratio of consultation to the pharmacist at the time of purchase of OTC drugs and health food was low in all grade students. In particular, the ratio of consultation to the pharmacist at the time of purchase of health food was very low in high school students. Therefore, to provide accurate information of medicine and health food for students, the school pharmacist should engage not only in routine work but also in positive guidance about OTC drugs and health food in the future.

  4. Integrated Proteogenomic Characterization of Human High-Grade Serous Ovarian Cancer

    SciTech Connect

    Zhang, Hui; Liu, Tao; Zhang, Zhen; Payne, Samuel H.; Zhang, Bai; McDermott, Jason E.; Zhou, Jian-Ying; Petyuk, Vladislav A.; Chen, Li; Ray, Debjit; Sun, Shisheng; Yang, Feng; Chen, Lijun; Wang, Jing; Shah, Punit; Cha, Seong Won; Aiyetan, Paul; Woo, Sunghee; Tian, Yuan; Gritsenko, Marina A.; Clauss, Therese R.; Choi, Caitlin; Monroe, Matthew E.; Thomas, Stefani; Nie, Song; Wu, Chaochao; Moore, Ronald J.; Yu, Kun-Hsing; Tabb, David L.; Fenyö, David; Bafna, Vineet; Wang, Yue; Rodriguez, Henry; Boja, Emily S.; Hiltke, Tara; Rivers, Robert C.; Sokoll, Lori; Zhu, Heng; Shih, Ie-Ming; Cope, Leslie; Pandey, Akhilesh; Zhang, Bing; Snyder, Michael P.; Levine, Douglas A.; Smith, Richard D.; Chan, Daniel W.; Rodland, Karin D.

    2016-07-01

    Ovarian cancer remains the most lethal gynecological malignancy in the developed world, despite recent advances in genomic information and treatment. To better understand this disease, define an integrated proteogenomic landscape, and identify factors associated with homologous repair deficiency (HRD) and overall survival, we performed a comprehensive proteomic characterization of ovarian high-grade serous carcinomas (HGSC) previously characterized by The Cancer Genome Atlas (TCGA). We observed that messenger RNA transcript abundance did not reliably predict abundance for 10,030 proteins across 174 tumors. Clustering of tumors based on protein abundance identified five subtypes, two of which correlated robustly with mesenchymal and proliferative subtypes, while tumors characterized as immunoreactive or differentiated at the transcript level were intermixed at the protein level. At the genome level, HGSC is characterized by a complex landscape of somatic copy number alterations (CNA), which individually do not correlate significantly with survival. Correlation of CNAs with protein abundances identified loci with significant trans regulatory effects mapping to pathways associated with proliferation, cell motility/invasion, and immune regulation, three known hallmarks of cancer. Using the trans regulated proteins we also created models significantly correlated with patient survival by multivariate analysis. Integrating protein abundance with specific post-translational modification data identified subnetworks correlated with HRD status; specifically, acetylation of Lys12 and Lys16 on histone H4 was associated with HRD status. Using quantitative phosphoproteomics data covering 4,420 proteins as reflective of pathway activity, we identified the PDGFR and VEGFR signaling pathways as significantly up-regulated in patients with short overall survival, independent of PDGFR and VEGFR protein levels, potentially informing the use of anti-angiogenic therapies. Components of

  5. Glucocorticoid Receptor Activation Inhibits Chemotherapy-induced Cell Death in High-grade Serous Ovarian Carcinoma

    PubMed Central

    Stringer-Reasor, Erica M.; Baker, Gabrielle M.; Skor, Maxwell N.; Kocherginsky, Masha; Lengyel, Ernst; Fleming, Gini F.; Conzen, Suzanne D.

    2015-01-01

    Objectives To test the hypothesis that glucocorticoid receptor (GR) activation increases resistance to chemotherapy in high-grade serous ovarian cancer (HGS-OvCa) and that treatment with a GR antagonist will improve sensitivity to chemotherapy. Methods GR expression was assessed in OvCa cell lines by qRT-PCR and Western blot analysis and in xenografts and primary human tumors using immunohistochemistry (IHC). We also examined the effect of GR activation versus inhibition on chemotherapy-induced cytotoxicity in OvCa cell lines and in a xenograft model. Results With the exception of IGROV-1 cells, all OvCa cell lines tested had detectable GR expression by Western blot and qRT-PCR analysis. Twenty-five out of the 27 human primary HGS-OvCas examined expressed GR by IHC. No cell line expressed detectable progesterone receptor (PR) or androgen receptor (AR) by Western blot analysis. In vitro assays showed that in GR-positive HeyA8 and SKOV3 cells, dexamethasone (100 nM) treatment upregulated the pro-survival genes SGK1 and MKP1/DUSP1 and inhibited carboplatin/gemcitabine-induced cell death. Concurrent treatment with two GR antagonists, either mifepristone (100 nM) or CORT125134 (100 nM), partially reversed these effects. There was no anti-apoptotic effect of dexamethasone on chemotherapy-induced cell death in IGROV-1 cells, which did not have detectable GR protein. Mifepristone treatment alone was not cytotoxic in any cell line. HeyA8 OvCa xenograft studies demonstrated that adding mifepristone to carboplatin/gemcitabine increased tumor shrinkage by 48% compared to carboplatin/gemcitabine treatment alone (P=0.0004). Conclusions These results suggest that GR antagonism sensitizes GR+ OvCa to chemotherapy-induced cell death through inhibition of GR-mediated cell survival pathways. PMID:26115975

  6. Change in Pattern of Relapse After Antiangiogenic Therapy in High-Grade Glioma

    SciTech Connect

    Narayana, Ashwatha; Kunnakkat, Saroj D.; Medabalmi, Praveen; Golfinos, John; Parker, Erik; Knopp, Edmond; Zagzag, David; Eagan, Patricia; Gruber, Deborah; Gruber, Michael L.

    2012-01-01

    Purpose: Local recurrence is the dominant pattern of relapse in high-grade glioma (HGG) after conventional therapy. The recent use of antiangiogenic therapy has shown impressive radiologic and clinical responses in adult HGG. The preclinical data suggesting increased invasiveness after angiogenic blockade have necessitated a detailed analysis of the pattern of recurrence after therapy. Methods and Materials: A total of 162 consecutive patients with HGG, either newly diagnosed (n = 58) or with recurrent disease (n = 104) underwent therapy with bevacizumab at 10 mg/kg every 2 weeks and conventional chemotherapy with or without involved field radiotherapy until disease progression. The pattern of recurrence and interval to progression were the primary aims of the present study. Diffuse invasive recurrence (DIR) was defined as the involvement of multiple lobes with or without crossing the midline. Results: At a median follow-up of 7 months (range, 1-37), 105 patients had recurrence, and 79 patients ultimately developed DIR. The interval to progression was similar in the DIR and local recurrence groups (6.5 and 6.3 months, p = .296). The hazard risk of DIR increased exponentially with time and was similar in those with newly diagnosed and recurrent HGG (R{sup 2} = 0.957). The duration of bevacizumab therapy increased the interval to recurrence (p < .0001) and improved overall survival (p < .0001). However, the pattern of relapse did not affect overall survival (p = .253). Conclusion: Along with an increase in median progression-free survival, bevacizumab therapy increased the risk of DIR in HGG patients. The risk of increased invasion with prolonged angiogenic blockade should be addressed in future clinical trials.

  7. In vivo tumor growth of high-grade serous ovarian cancer cell lines

    PubMed Central

    Mitra, Anirban; Davis, David A.; Tomar, Sunil; Roy, Lynn; Gurler, Hilal; Xie, Jia; Lantvit, Daniel D.; Cardenas, Horacio; Fang, Fang; Liu, Yueying; Loughran, Elizabeth; Yang, Jing; Stack, M. Sharon; Emerson, Robert E; Cowden Dahl, Karen D.; Barbolina, Maria; Nephew, Kenneth P.; Matei, Daniela; Burdette, Joanna E.

    2015-01-01

    Objective Genomic studies of ovarian cancer (OC) cell lines frequently used in research revealed that these cells do not fully represent high-grade serous ovarian cancer (HGSOC), the most common OC histologic type. However, OC lines that appear to genomically resemble HGSOC have not been extensively used and their growth characteristics in murine xenografts are essentially unknown. Methods To better understand growth patterns and characteristics of HGSOC cell lines in vivo, CAOV3, COV362, KURAMOCHI, NIH-OVCAR3, OVCAR4, OVCAR5, OVCAR8, OVSAHO, OVKATE, SNU119, UWB1.289 cells were assessed for tumor formation in nude mice. Cells were injected intraperitoneally (i.p.) or subcutaneously (s.c.) in female athymic nude mice and allowed to grow (maximum of 90 days) and tumor formation was analyzed. All tumors were sectioned and assessed using H&E staining and immunohistochemistry for p53, PAX8 and WT1 expression. Results Six lines (OVCAR3, OVCAR4, OVCAR5, OVCAR8, CAOV3, and OVSAHO) formed i.p xenografts with HGSOC histology. OVKATE and COV362 formed s.c. tumors only. Rapid tumor formation was observed for OVCAR3, OVCAR5 and OVCAR8, but only OVCAR8 reliably formed ascites. Tumors derived from OVCAR3, OVCAR4, and OVKATE displayed papillary features. Of the 11 lines examined, three (Kuramochi, SNU119 and UWB1.289) were non-tumorigenic. Conclusions Our findings help further define which HGSOC cell models reliably generate tumors and/or ascites, critical information for preclinical drug development, validating in vitro findings, imaging and prevention studies by the OC research community. PMID:26050922

  8. Symptoms and problems in the end-of-life phase of high-grade glioma patients.

    PubMed

    Sizoo, Eefje M; Braam, Lies; Postma, Tjeerd J; Pasman, H Roeline W; Heimans, Jan J; Klein, Martin; Reijneveld, Jaap C; Taphoorn, Martin J B

    2010-11-01

    Despite multimodal treatment, it is not possible to cure high-grade glioma (HGG) patients. Therefore, the aim of treatment is not only to prolong life, but also to prevent deterioration of health-related quality of life as much as possible. When the patient's condition declines and no further tumor treatment seems realistic, patients in the Netherlands are often referred to a primary care physician for end-of-life care. This end-of-life phase has not been studied adequately yet. The purpose of this study was to explore specific problems and needs experienced in the end-of-life phase of patients with HGG. We retrospectively examined the files of 55 patients who received treatment in our outpatient clinic and died between January 2005 and August 2008. The clinical nurse specialist in neuro-oncology maintained contact on a regular basis with (relatives of) HGG patients once tumor treatment for recurrence was no longer given. She systematically asked for signs and symptoms. The majority of the patients experienced loss of consciousness and difficulty with swallowing, often arising in the week before death. Seizures occurred in nearly half of the patients in the end-of-life phase and more specifically in one-third of the patients in the week before dying. Other common symptoms reported in the end-of-life phase are progressive neurological deficits, incontinence, progressive cognitive deficits, and headache. Our study demonstrates that HGG patients, unlike the general cancer population, have specific symptoms in the end-of-life phase. Further research is needed in order to develop specific palliative care guidelines for these patients.

  9. The prognostic value of IDH mutations and MGMT promoter status in secondary high-grade gliomas.

    PubMed

    Juratli, T A; Kirsch, M; Geiger, K; Klink, B; Leipnitz, E; Pinzer, T; Soucek, S; Schrock, E; Schrok, E; Schackert, G; Krex, D

    2012-12-01

    Reports about the prognostic value of IDH mutations and the promoter region of the O6-Methyl-guanyl-methyl-transferase gene in secondary high-grade gliomas (sHGG) are few in number. We investigated the prognostic value of IDH mutations and methylation of the promoter region of the MGMT gene in 99 patients with sHGG and analyzed the clinical course of those tumors. Patients with sHGG were screened for IDH mutations by direct sequencing, and, for promoter status of MGMT gene, by the methylation-specific polymerase chain reaction. A total of 48 of 99 patients (48.5 %) had secondary anaplastic gliomas (Group 1), while 51 patients had secondary glioblastomas (Group 2). The median survival time after malignant progression of all patients with sHGG and with an IDH mutation was 4 years, which is significantly longer than in patients with wild-type IDH (1.2 years, p = 0.009). Patients' survival was not significantly influenced by the tumors' MGMT promoter status, both in Group 1- 9.7 years vs. 6.1 years, methylated vs. unmethylated promoter (p = 0.330)-as well as in Group 2-1.5 years vs. 1.6 years, methylated versus unmethylated promoter (p = 0.829). In our population, the IDH mutation status was not associated with increased PFS or median survival time in sGBM patients. However, patients with secondary anaplastic glioma and IDH mutation had a significantly improved outcome. In addition, IDH mutations are a more powerful prognostic marker concerning both PFS and MS than the MGMT promoter status in those patients.

  10. Associations of High-Grade Glioma With Glioma Risk Alleles and Histories of Allergy and Smoking

    PubMed Central

    Lachance, Daniel H.; Yang, Ping; Johnson, Derek R.; Decker, Paul A.; Kollmeyer, Thomas M.; McCoy, Lucie S.; Rice, Terri; Xiao, Yuanyuan; Ali-Osman, Francis; Wang, Frances; Stoddard, Shawn M.; Sprau, Debra J.; Kosel, Matthew L.; Wiencke, John K.; Wiemels, Joseph L.; Patoka, Joseph S.; Davis, Faith; McCarthy, Bridget; Rynearson, Amanda L.; Worra, Joel B.; Fridley, Brooke L.; O’Neill, Brian Patrick; Buckner, Jan C.; Il’yasova, Dora; Jenkins, Robert B.; Wrensch, Margaret R.

    2011-01-01

    Glioma risk has consistently been inversely associated with allergy history but not with smoking history despite putative biologic plausibility. Data from 855 high-grade glioma cases and 1,160 controls from 4 geographic regions of the United States during 1997–2008 were analyzed for interactions between allergy and smoking histories and inherited variants in 5 established glioma risk regions: 5p15.3 (TERT), 8q24.21 (CCDC26/MLZE), 9p21.3 (CDKN2B), 11q23.3 (PHLDB1/DDX6), and 20q13.3 (RTEL1). The inverse relation between allergy and glioma was stronger among those who did not (odds ratioallergy-glioma = 0.40, 95% confidence interval: 0.28, 0.58) versus those who did (odds ratioallergy-glioma = 0.76, 95% confidence interval: 0.59, 0.97; Pinteraction = 0.02) carry the 9p21.3 risk allele. However, the inverse association with allergy was stronger among those who carried (odds ratioallergy-glioma = 0.44, 95% confidence interval: 0.29, 0.68) versus those who did not carry (odds ratioallergy-glioma = 0.68, 95% confidence interval: 0.54, 0.86) the 20q13.3 glioma risk allele, but this interaction was not statistically significant (P = 0.14). No relation was observed between glioma risk and smoking (odds ratio = 0.92, 95% confidence interval: 0.77, 1.10; P = 0.37), and there were no interactions for glioma risk of smoking history with any of the risk alleles. The authors’ observations are consistent with a recent report that the inherited glioma risk variants in chromosome regions 9p21.3 and 20q13.3 may modify the inverse association of allergy and glioma. PMID:21742680

  11. ALA PDT for high grade dysplasia in Barrett's oesophagus: review of a decade's experience

    NASA Astrophysics Data System (ADS)

    Bown, Stephen G.; Mackenzie, Gary D.; Dunn, Jason M.; Thorpe, Sally M.; Lovat, Laurence B.

    2009-06-01

    We have been investigating PDT with 5 aminolaevulinic acid (ALA) for the treatment of high grade dysplasia (HGD) in Barrett's oesophagus (BO) for over a decade. This drug has inherent advantages over porfimer sodium (Photofrin), the current approved photosensitiser in the UK and USA, which causes strictures in 18-50% and light sensitivity for up to three months. ALA has a lower rate of oesophageal strictures due to its preferential activity in the mucosa, sparing the underlying muscle, and patients are only light sensitive for 1-2 days. Within a randomised controlled trial, we demonstrated that an ALA dose of 60mg/kg activated by 1000J/cm red laser light is the most effective. Using these values we achieved complete reversal of HGD at 1 year in 89% of 27 patients. A randomised controlled trial of ALA vs porfimer sodium PDT for HGD is currently under way with end points of efficacy and safety. 50 of 66 patients have been recruited. Preliminary data suggest ALA PDT is safer with a trend to higher efficacy. Late relapse can occur in 20% of patients. New prognostic markers, in particular aneuploidy, are helping us to identify and target patients at risk of late relapse. Furthermore optical biopsy techniques such as elastic scattering spectroscopy (ESS) may allow detection of nuclear abnormalities in vivo and enable us to target areas of interest whilst reducing sampling error. PDT faces new challenges for the treatment of HGD in BO, with the recent introduction of balloon based radiofrequency ablation. This technique appears simpler and as effective as PDT, but follow up is currently short and long term safety data is lacking. In our experience ALA PDT is currently the most effective minimally invasive treatment for HGD in BO. This work was undertaken at UCLH/UCL who received a proportion of funding from the Department of Health's NIHR Biomedical Research Centres funding scheme.

  12. Small RNAs and the competing endogenous RNA network in high grade serous ovarian cancer tumor spread

    PubMed Central

    Bachmayr-Heyda, Anna; Auer, Katharina; Sukhbaatar, Nyamdelger; Aust, Stefanie; Deycmar, Simon; Reiner, Agnes T.; Polterauer, Stephan; Dekan, Sabine; Pils, Dietmar

    2016-01-01

    High grade serous ovarian cancer (HGSOC) is among the most deadly malignancies in women, frequently involving peritoneal tumor spread. Understanding molecular mechanisms of peritoneal metastasis is essential to develop urgently needed targeted therapies. We described two peritoneal tumor spread types in HGSOC apparent during surgery: miliary (numerous millet-sized implants) and non-miliary (few big, bulky implants). The former one is defined by a more epithelial-like tumor cell characteristic with less immune cell reactivity and with significant worse prognosis, even if corrected for typical clinicopathologic factors. 23 HGSOC patients were enrolled in this study. Isolated tumor cells from fresh tumor tissues of ovarian and peritoneal origin and from ascites were used for ribosomal RNA depleted RNA and small RNA sequencing. RT-qPCR was used to validate results and an independent cohort of 32 patients to validate the impact on survival. Large and small RNA sequencing data were integrated and a new gene-miRNA set analysis method was developed. Thousands of new small RNAs (miRNAs and piwi-interacting RNAs) were predicted and a 13 small RNA signature was developed to predict spread type from formalin-fixed paraffin-embedded tissues. Furthermore, integrative analyses of RNA sequencing and small RNA sequencing data revealed a global upregulation of the competing endogenous RNA network in tumor tissues of non-miliary compared to miliary spread, i.e. higher expression of circular RNAs and long non-coding RNAs compared to coding RNAs but unchanged abundance of small RNAs. This global deregulated expression pattern could be co-responsible for the spread characteristic, miliary or non-miliary, in ovarian cancer. PMID:27172797

  13. Whole-exome sequencing identified mutational profiles of high-grade colon adenomas

    PubMed Central

    Kim, Tae-Min; Rhee, Je-Keun; Park, Hyeon-Chun; Sung, Min Kim; Kim, Sung Soo; Hyeok, Chang An; Lee Hyung, Sug; Chung, Yeun-Jun

    2017-01-01

    Although gene-to-gene analyses identified genetic alterations such as APC, KRAS and TP53 mutations in colon adenomas, it is largely unknown whether there are any others in them. Mutational profiling of high-grade colon adenoma (HGCA) that just precedes colon carcinoma might identify not only novel adenoma-specific genes but also critical genes for its progression to carcinoma. For this, we performed whole-exome sequencing (WES) of 12 HGCAs and identified 11 non-hypermutated and one hypermutated (POLE-mutated) cases. We identified 22 genes including APC, KRAS, TP53, GNAS, NRAS, SMAD4, ARID2, and PIK3CA with non-silent mutations in the cancer Census Genes. Bi-allelic and mono-allelic APC alterations were found in nine and one HGCAs, respectively, while the other two harbored wild-type APC. Five HGCAs harbored either mono-allelic (four HGCAs) or bi-allelic (one HGCA) SMAD4 mutation or 18q loss that had been known as early carcinoma-specific changes. We identified MTOR, ACVR1B, GNAQ, ATM, CNOT1, EP300, ARID2, RET and MAP2K4 mutations for the first time in colon adenomas. Our WES data is largely matched with the earlier ‘adenoma-carcinoma model’ (APC, KRAS, NRAS and GNAS mutations), but there are newly identified SMAD4, MTOR, ACVR1B, GNAQ, ATM, CNOT1, EP300, ARID2, RET and MAP2K4 mutations in this study. Our findings provide resource for understanding colon premalignant lesions and for identifying genomic clues for differential diagnosis and therapy options for colon adenomas and carcinomas. PMID:28179590

  14. Transcriptional Consequence and Impaired Gametogenesis with High-Grade Aneuploidy in Arabidopsis thaliana

    PubMed Central

    Chen, I-Ju; Liu, Yu-Chen; Chung, Mei-Chu; Lo, Wan-Sheng

    2014-01-01

    Aneuploidy features a numerical chromosome variant that the number of chromosomes in the nucleus of a cell is not an exact multiple of the haploid number, which may have an impact on morphology and gene expression. Here we report a tertiary trisomy uncovered by characterizing a T-DNA insertion mutant (aur2-1/+) in the Arabidopsis (Arabidopsis thaliana) AURORA2 locus. Whole-genome analysis with DNA tiling arrays revealed a chromosomal translocation linked to the aur2-1 allele, which collectively accounted for a tertiary trisomy 2. Morphologic, cytogenetic and genetic analyses of aur2-1 progeny showed impaired male and female gametogenesis to various degrees and a tight association of the aur2-1 allele with the tertiary trisomy that was preferentially inherited. Transcriptome analysis showed overlapping and distinct gene expression profiles between primary and tertiary trisomy 2 plants, particularly genes involved in response to stress and various types of external and internal stimuli. Additionally, transcriptome and gene ontology analyses revealed an overrepresentation of nuclear-encoded organelle-related genes functionally involved in plastids, mitochondria and peroxisomes that were differentially expressed in at least three if not all Arabidopsis trisomics. These observations support a previous hypothesis that aneuploid cells have higher energy requirement to overcome the detrimental effects of an unbalanced genome. Moreover, our findings extend the knowledge of the complex nature of the T-DNA insertion event influencing plant genomic integrity by creating high-grade trisomy. Finally, gene expression profiling results provide useful information for future research to compare primary and tertiary trisomics for the effects of aneuploidy on plant cell physiology. PMID:25514186

  15. Pertussis Toxin Is a Robust and Selective Inhibitor of High Grade Glioma Cell Migration and Invasion

    PubMed Central

    Wang, Lei; Natali, Letizia; Karimi-Mostowfi, Nicki; Brifault, Coralie; Gonias, Steven L.

    2016-01-01

    In high grade glioma (HGG), extensive tumor cell infiltration of normal brain typically precludes identifying effective margins for surgical resection or irradiation. Pertussis toxin (PT) is a multimeric complex that inactivates diverse Gi/o G-protein coupled receptors (GPCRs). Despite the broad continuum of regulatory events controlled by GPCRs, PT may be applicable as a therapeutic. We have shown that the urokinase receptor (uPAR) is a major driver of HGG cell migration. uPAR-initiated cell-signaling requires a Gi/o GPCR, N-formyl Peptide Receptor 2 (FPR2), as an essential co-receptor and is thus, PT-sensitive. Herein, we show that PT robustly inhibits migration of three separate HGG-like cell lines that express a mutated form of the EGF Receptor (EGFR), EGFRvIII, which is constitutively active. PT also almost completely blocked the ability of HGG cells to invade Matrigel. In the equivalent concentration range (0.01–1.0 μg/mL), PT had no effect on cell survival and only affected proliferation of one cell line. Neutralization of EGFRvIII expression in HGG cells, which is known to activate uPAR-initiated cell-signaling, promoted HGG cell migration. The increase in HGG cell migration, induced by EGFRvIII neutralization, was entirely blocked by silencing FPR2 gene expression or by treating the cells with PT. When U87MG HGG cells were cultured as suspended neurospheres in serum-free, growth factor-supplemented medium, uPAR expression was increased. HGG cells isolated from neurospheres migrated through Transwell membranes without loss of cell contacts; this process was inhibited by PT by >90%. PT also inhibited expression of vimentin by HGG cells; vimentin is associated with epithelial-mesenchymal transition and worsened prognosis. We conclude that PT may function as a selective inhibitor of HGG cell migration and invasion. PMID:27977780

  16. Rare Earth Element Partition Coefficients During High-Grade Metamorphism: Experiments, Realities, And Large Datasets

    NASA Astrophysics Data System (ADS)

    Taylor, R.; Clark, C.; Kylander-Clark, A. R.; Hacker, B. R.

    2015-12-01

    For 15 years rare earth element (REE) partitioning between zircon and garnet has facilitated the coupling of U-Pb ages to metamorphism, particularly in the granulite facies. The combination of in situ analysis and rapid data acquisition, particularly through combined techniques such as laser ablation split stream (LASS), means that complex terranes can be interrogated with increasing detail. However this detail provided by large datasets must also be combined with an understanding of the processes involved, for example the relative mobility of the REE, Ti, U and Pb within zircon grains that have withstood intense P-T conditions to varying degrees. Care must also be taken in identifying open system conditions, for example the presence or passage of partial melts that result in non-equilibrium, or very localised equilibrium, between the phases of interest. Visualisation of REE partition coefficients (DREE) becomes more complex with large datasets particularly when dealing with variably recrystallised zircon grains or multiple generations of garnet. Simple methods of visualising the important partitioning parameters identify temperature trends in experimental datasets [1, 2]. These trends can be used as clear indicators of zircon growing or recrystallizing in the presence of stable garnet and may be used as thermometers for zircon growth and for the identification of thermal peaks. Investigation of zircon-garnet DREE values in both long-lived high grade terranes (e.g. S. India), and complex polymetamorphic terranes (e.g. Enderby Land, E. Antarctica) provides insight into how partitioning information can be carefully interrogated, by looking at systematic or erratic variations from experimental data, even when dealing with issues such as variably recrystallised zircon and melt migration. Rubatto and Hermann, (2007). Chemical Geology. Taylor et al., (2015). Journal Metamorphic Geology.

  17. The future of high-grade glioma: Where we are and where are we going

    PubMed Central

    Rhun, Emilie Le; Taillibert, Sophie; Chamberlain, Marc C.

    2015-01-01

    High-grade glioma (HGG) are optimally treated with maximum safe surgery, followed by radiotherapy (RT) and/or systemic chemotherapy (CT). Recently, the treatment of newly diagnosed anaplastic glioma (AG) has changed, particularly in patients with 1p19q codeleted tumors. Results of trials currenlty ongoing are likely to determine the best standard of care for patients with noncodeleted AG tumors. Trials in AG illustrate the importance of molecular characterization, which are germane to both prognosis and treatment. In contrast, efforts to improve the current standard of care of newly diagnosed glioblastoma (GB) with, for example, the addition of bevacizumab (BEV), have been largely disappointing and furthermore molecular characterization has not changed therapy except in elderly patients. Novel approaches, such as vaccine-based immunotherapy, for newly diagnosed GB are currently being pursued in multiple clinical trials. Recurrent disease, an event inevitable in nearly all patients with HGG, continues to be a challenge. Both recurrent GB and AG are managed in similar manner and when feasible re-resection is often suggested notwithstanding limited data to suggest benefit from repeat surgery. Occassional patients may be candidates for re-irradiation but again there is a paucity of data to commend this therapy and only a minority of selected patients are eligible for this approach. Consequently systemic therapy continues to be the most often utilized treatment in recurrent HGG. Choice of therapy, however, varies and revolves around re-challenge with temozolomide (TMZ), use of a nitrosourea (most often lomustine; CCNU) or BEV, the most frequently used angiogenic inhibitor. Nevertheless, no clear standard recommendation regarding the prefered agent or combination of agents is avaliable. Prognosis after progression of a HGG remains poor, with an unmet need to improve therapy. PMID:25722939

  18. Expression of CD74 in high Grade Gliomas: A Potential Role in Temozolomide Resistance

    PubMed Central

    Kitange, Gaspar J.; Carlson, Brett L.; Schroeder, Mark A.; Decker, Paul A.; Morlan, Bruce W.; Wu, Wenting; Ballman, Karla V.; Giannini, Caterina; Sarkaria, Jann N.

    2011-01-01

    Temozolomide (TMZ) is the most effective chemotherapeutic agent for glioblastoma (GBM). Resistance to this methylating agent is linked to DNA repair enzyme O6-methylguanine-DNA methyltransferase (MGMT). However, in recent studies MGMT status was not completely accurate as a predictor of TMZ response in GBM, suggesting other mechanisms of resistance. As part of an effort aimed at discovery of genes involved in TMZ resistance in GBM, the expression of CD74 was evaluated in GBM patient samples and the influence of CD74 on TMZ response was evaluated in GBM tumor models. Reverse transcription-polymerase-chain reaction (RT-PCR) demonstrated differential expression of CD74 mRNA among the GBM xenografts; 8 of 20 (40%) expressed CD74 mRNA. In a preliminary evaluation of whether CD74 expression might influence TMZ response, CD74 mRNA expression levels were inversely associated with in vivo TMZ resistance in 20 GBM xenograft lines (median survival 122 vs. 62.5 days; r=−0.48 p = 0.032). In follow up to this observation, CD74 shRNA knock down in U87 cells significantly suppressed in vitro proliferation and increased TMZ sensitivity as compared to a non-specific control shRNA. Consistent with an effect on proliferation and survival, silencing of CD74 by shRNA was associated with reduced Akt and Erk1/2 activation in response to stimulation by CD74 ligand macrophage-migration inhibition factor (MIF). Lastly, expression of CD74 protein was assessed in patient samples (9 anaplastic astrocytoma [AA], and 62 GBM) by immunohistochemistry, and appreciable expression was observed in 28% of samples. Collectively, these findings suggest that CD74 is expressed in a subset of high grade gliomas and may contribute to TMZ resistance. PMID:20443131

  19. The 1999-00 Preliminary North Carolina State Testing Results: Multiple Choice, Grade 3 Pretest, End-of-Grade, High School Comprehensive, and End-of-Course Tests.

    ERIC Educational Resources Information Center

    Bazemore, Mildred; Geary, Monica; Barbour, Ken; Barefoot, Angela

    This report presents preliminary results from four sets of tests that are part of the North Carolina state testing program. The Grade 3 Pretest is a multiple choice reading and mathematics test administered to students at the beginning of third grade. This pretest was administered to more than 102,000 students in the 1999-2000 school year, and…

  20. Bevacizumab salvage therapy following progression in high-grade glioma patients treated with VEGF receptor tyrosine kinase inhibitors.

    PubMed

    Scott, Brian J; Quant, Eudocia C; McNamara, Margaret B; Ryg, Peter A; Batchelor, Tracy T; Wen, Patrick Y

    2010-06-01

    Agents targeting the vascular endothelial growth factor (VEGF) pathway are being used with increasing frequency in patients with recurrent high-grade glioma. The effect of more than one antiangiogenic therapy given in succession has not been established. We reviewed the efficacy of bevacizumab, a VEGF-A monoclonal antibody, in patients who progressed following prior therapy with VEGF receptor tyrosine kinase inhibitors (R-TKi). Seventy-three patients with recurrent high-grade gliomas received VEGF R-TKi (cediranib, sorafenib, pazopanib, or sunitinib) as part of phase I or II clinical trials. Twenty-four of these patients with glioblastoma progressed and received bevacizumab-containing regimens immediately after R-TKi. Those who stopped R-TKi therapy for reasons other than disease progression, or received a treatment that did not include bevacizumab, were excluded from the analysis. The efficacy of bevacizumab-containing regimens in these 24 patients was evaluated. During R-TKi therapy, 6 of 24 patients (25%) had a partial response (PR) to treatment. The 6-month progression-free survival (APF6) was 16.7% and median time-to-progression (TTP) was 14.3 weeks. Grade III/IV toxicities were seen in 13 of 24 patients (54%). Subsequently with bevacizumab salvage therapy, 5 of 24 patients (21%) had a PR, the APF6 was 12.5%, and the median TTP was 8 weeks. Five of 24 patients had grade III/IV toxicities (21%). The median overall survival (OS) from the start of R-TKi therapy was 9.2 months (range: 2.8-34.1+), whereas the median OS after bevacizumab was 5.2 months (range: 1.3-28.9+). Bevacizumab retains modest activity in high-grade glioma patients who progress on R-TKi. However, the APF6 of 12.5% in this cohort of patients indicates that durable tumor control is not achieved for most patients.

  1. Diagnostic Value of Autoantibodies against Ezrin in Esophageal Squamous Cell Carcinoma

    PubMed Central

    Li, Lan; Liu, Ming; Lin, Jian-Bang; Hong, Xin-Bin; Chen, Wen-Xia; Guo, Hong; Xu, Li-Yan

    2017-01-01

    Esophageal squamous cell carcinoma (ESCC), one of the most common malignancies worldwide, is a highly aggressive and homogeneous entity occurring in esophageal squamous epithelium, and a reliable noninvasive test for early detection is needed. A recent study showed that serum autoantibodies against Ezrin could be detected in patients with pancreatic cancer. Here, we assessed whether autoantibodies against Ezrin could have diagnostic relevance for early ESCC. We analyzed autoantibodies against Ezrin in sera of 98 normal controls and 149 patients with ESCC. Ezrin autoantibodies levels were evaluated by enzyme-linked immunosorbent assay (ELISA). Results showed that higher levels of autoantibodies against Ezrin were observed in serum samples from patients with ESCC than in serum from normal controls (P < 0.0001). Based on a cutoff value of 0.319, the sensitivity and specificity of autoantibodies against Ezrin for diagnosis of ESCC were 27.5% and 95.9%, respectively. Compared with normal controls, the positive rate of autoantibodies against Ezrin was significantly elevated in patients with early-stage ESCC (P < 0.0001). Moreover, there was no significant difference of positivity of autoantibodies against Ezrin in ESCC patients categorized according to age, gender, tumor size, tumor invasion depth, tumor site, histological grade, lymph node status, or tumor stage. Our study indicates that the presence of autoantibodies against Ezrin is significantly associated with ESCC. PMID:28298808

  2. Squamous cell carcinoma of the anal sac in a spotted hyena (Crocuta crocuta).

    PubMed

    Goodnight, Andrea L; Traslavina, Ryan P; Emanuelson, Karen; Affolter, Verena K; Gaffney, Patricia M; Vernau, William; Williams, Colette; Wu, Connie I-kuan; Sturges, Beverly K; Lowenstine, Linda J

    2013-12-01

    A 25-yr-old spayed female spotted hyena (Crocuta crocuta) developed intermittent right pelvic limb lameness that persisted following conservative medical therapy. No obvious musculoskeletal lesions were noted on initial physical exam; however, spinal radiography was suspicious for possible intervertebral degenerative joint disease or discospondylitis. Despite prolonged medical therapy, the lameness progressed to minimal weight bearing and marked muscle atrophy of the right pelvic limb. Electromyography showed spontaneous activity in the muscles of right sciatic nerve distribution. Sensory and motor nerve conduction velocities in the right tibial and peroneal nerves were undetectable and markedly reduced, respectively. A magnetic resonance imaging (MRI) scan revealed a large, space-occupying mass on the right side of the sacrum and pelvis. Antemortem fine-needle aspiration of the mass and postmortem histopathology resulted in diagnosis of a high-grade squamous cell carcinoma of the anal sac. Squamous cell carcinoma of the anal sac is very rare in domestic dogs and previously unreported in spotted hyenas.

  3. [Concurrent radiochemotherapy in the treatment of squamous cell oral and oropharyngeal cancer].

    PubMed

    Semin, D Iu; Medvedev, V S; Marbynskiĭ, Iu S; Gulidov, I A; Isaev, P A; Radzhanova, M U; Derbugov, D N; Pol'kin, V V

    2010-01-01

    The aim of this study was to evaluate the end results of the radiochemotherapy of 237 patients with squamous cell carcinoma of oral mucosa (locally advanced, stage III-IV, - 134; 56.4%, and metastases to regional lymph nodes of the neck - 91; 38.4%) carried out at the Center's Clinic. Interstitial neutron (252 californium) plus polychemotherapy was given to 26 (11%) (group 1); neutron + distant radio + polychemotherapy - 34 (14 %) (group 2); distant fractionated radiotherapy + polychemotherapy - 177 (75%) (group 3). Complete response was reported in 190 (80.2%); partial - 44 (18.6%) and stabilization - 3 (1.3%). Overall response was 98.8%; 5-year survival - 64.5 +/- 3.3%, irrespective of tumor site, grade and method of treatment. Concomitant modality proved highly effective, free from toxic and functional or cosmetic harm.

  4. Factors in seventh grade academics associated with performance levels on the tenth grade biology end of course test in selected middle and high schools in northwest Georgia

    NASA Astrophysics Data System (ADS)

    Ward, Jennifer Henry

    This study attempted to identify factors in seventh grade academics that are associated with overall success in tenth grade biology. The study addressed the following research questions: Are there significant differences in performance levels in seventh grade Criterion Referenced Competency Test (CRCT) scores in science, math, reading, and language arts associated with performance categories in tenth grade biology End of Course Test (EOCT) and the following demographic variables : gender, ethnicity, socioeconomic status, disability category, and English language proficiency level? Is there a relationship among the categorical variables on the tenth grade biology EOCT and the same five demographic variables? Retrospective causal comparative research was used on a representative sample from the middle schools in three North Georgia counties who took the four CRCTs in the 2006-2007 school year, and took the biology EOCT in the 2009-2010 school year. Chi square was used to determine the relationships of the various demographic variables on three biology EOCT performance categories. Twoway ANOVA determined relationships between the seventh grade CRCT scores of students in the various demographic groups and their performance levels on the biology EOCT. Students' performance levels on the biology EOCT matched their performance levels on the seventh grade CRCTs consistently. Females performed better than males on all seventh grade CRCTs. Black and Hispanic students did worse than White and Asian/Asian Indian students on the math CRCT. Students living in poverty did worse on reading and language arts CRCTs than students who were better off. Special education students did worse on science, reading, and language arts CRCTs than students not receiving special education services. English language learners did worse than native English speakers on all seventh grade CRCTs. These findings suggest that remedial measures may be taken in the seventh grade that could impact

  5. Expression of E6, p53 and p21 proteins and physical state of HPV16 in cervical cytologies with and without low grade lesions

    PubMed Central

    Tagle, Diana K Jiménez; Sotelo, Daniel Hernández; Illades-Aguiar, Berenice; Leyva-Vazquez, Marco A; Alfaro, Eugenia Flores; Coronel, Yaneth Castro; Hernández, Oscar del Moral; Romero, Luz del Carmen Alarcón

    2014-01-01

    The aim of this study was to determine the correlation between expression of HPV16 E6, p53 and p21 proteins and the physical state of HPV16 in cervical cytologies without squamous intraepithelial lesions (Non-SIL) and with low grade squamous intraepithelial lesions (LSIL), both with HPV16 infection. 101 liquid-based cytological samples were analyzed. 50 samples were without squamous intraepithelial lesions (Non-IL) and 51 samples of low grade squamous intraepithelial lesions (LSIL), both with HPV16 infection. HPV16 infection was determined by PCR-RFLP, and the physical state of HPV16 by in situ hybridization with tyramide-amplification. The expression of E6, p53 and p21 proteins was evaluated by immunocytochemistry. The expression of HPV16 E6 protein was significantly higher in LSIL that in Non-SIL samples (p=0.006). We found a significant correlation between E6 expression and the physical state of HPV16 in Non-SIL (p=0.049). Our results suggest that high expression of E6 in LSIL is an early event of cervical carcinogenesis and perhaps can be used as an early marker. PMID:24482706

  6. Expression of E6, p53 and p21 proteins and physical state of HPV16 in cervical cytologies with and without low grade lesions.

    PubMed

    Tagle, Diana K Jiménez; Sotelo, Daniel Hernández; Illades-Aguiar, Berenice; Leyva-Vazquez, Marco A; Alfaro, Eugenia Flores; Coronel, Yaneth Castro; Hernández, Oscar Del Moral; Romero, Luz Del Carmen Alarcón

    2014-01-01

    The aim of this study was to determine the correlation between expression of HPV16 E6, p53 and p21 proteins and the physical state of HPV16 in cervical cytologies without squamous intraepithelial lesions (Non-SIL) and with low grade squamous intraepithelial lesions (LSIL), both with HPV16 infection. 101 liquid-based cytological samples were analyzed. 50 samples were without squamous intraepithelial lesions (Non-IL) and 51 samples of low grade squamous intraepithelial lesions (LSIL), both with HPV16 infection. HPV16 infection was determined by PCR-RFLP, and the physical state of HPV16 by in situ hybridization with tyramide-amplification. The expression of E6, p53 and p21 proteins was evaluated by immunocytochemistry. The expression of HPV16 E6 protein was significantly higher in LSIL that in Non-SIL samples (p=0.006). We found a significant correlation between E6 expression and the physical state of HPV16 in Non-SIL (p=0.049). Our results suggest that high expression of E6 in LSIL is an early event of cervical carcinogenesis and perhaps can be used as an early marker.

  7. The Value of SAT Scores and High School Grades in the Selection of Honors Program Candidates from the Perspective of Honors Students and Graduates

    ERIC Educational Resources Information Center

    Roszkowski, Michael J.; Nigro, Richard A.

    2015-01-01

    Admission to honors programs is competitive and typically relies heavily on the applicant's high school grades and SAT scores. Research shows that of the two criteria, the stronger predictor of performance in an honors curriculum is the high school record, which would imply that grades should receive the greater emphasis. We surveyed current…

  8. The Effect of the Involvement within Career Academies by Elective Participation of Eleventh and Twelfth Grade High School Students during the Implementation Year

    ERIC Educational Resources Information Center

    Johnston, Nancy A.

    2010-01-01

    The purpose of this study was to determine the effect of elective participation in one of three implementation year Career Academies, Education, Entrepreneurship, or Finance, on upper-class high school academic grades, Grade Point Average, and school academy participation measures. Significance of the junior and senior year of high school, the…

  9. A Comparison of Brain Wave Patterns of High and Low Grade Point Average Students During Rest, Problem Solving, and Stress Situations.

    ERIC Educational Resources Information Center

    Montor, Karel

    The purpose of this study was to compare brain wave patterns produced by high and low grade point average students, while they were resting, solving problems, and subjected to stress situations. The study involved senior midshipmen at the United States Naval Academy. The high group was comprised of those whose cumulative grade point average was…

  10. Disentangling the Role of High School Grades, "SAT"® Scores, and SES in Predicting College Achievement. Research Report. ETS RR-13-09

    ERIC Educational Resources Information Center

    Zwick, Rebecca

    2013-01-01

    Focusing on high school grade-point average (HSGPA) in college admissions may foster ethnic diversity and communicate the importance of high school performance. It has further been claimed that HSGPA is the best single predictor of college grades and that it is more equitable than test scores because of a smaller association with socioeconomic…

  11. Ki67, p27 and p53 Expression in Squamous Epithelial Lesions of Larynx.

    PubMed

    Mondal, Debashri; Saha, Kaushik; Datta, Chhanda; Chatterjee, Uttara; Sengupta, Arunabho

    2013-04-01

    Precise assessment of the biological behavior and progression of squamous epithelial lesions of the larynx with a view to predict the prognosis and therapeutic challenges remains an elusive goal. The knowledge and data regarding the expression of proliferative markers indicating the biological activity in different histological grades of squamous epithelial lesions are lacking till date. To evaluate the relationship between Ki67, p27 and p53 expression as well as topographic distribution of Ki67 with the histological subtypes or grades of laryngeal squamous intraepithelial and invasive lesions. Sixty-two consecutive cases with histologically documented intraepithelial and invasive squamous lesion were studied for Ki67, p27 and p53 expression. Mann-Whitney U, Kruskal-Wallis and Spearman's correlation tests were used for statistical analysis. The mean Ki67 labeling index in hyperplasia, dysplasia and carcinoma were 12.15, 22.03 and 35.53 % respectively and this difference was statistically significant (P < 0.05). There was strong positive correlation between Ki67 labeling index and increasing grades of squamous lesions. p27 expression was progressively decreased and p53 expression was progressively increased as the lesions progressed from hyperplasia to dysplasia and dysplasia to carcinoma. The topographic distribution of Ki67 positive cells increased with progressive grades of dysplasia. The Ki67 labeling index correlates well with the histological grade of both intraepithelial and invasive lesions of the larynx. And the topographic distribution of Ki67 expression depends on the grade of the dysplasia. Hence, Ki67 expression has a definite role in predicting the biological behavior of the lesions.

  12. Tandem High-Dose Chemotherapy and Autologous Stem Cell Transplantation for High-Grade Gliomas in Children and Adolescents

    PubMed Central

    2017-01-01

    With the aim to investigate the outcome of tandem high-dose chemotherapy and autologous stem cell transplantation (HDCT/auto-SCT) for high-grade gliomas (HGGs), we retrospectively reviewed the medical records of 30 patients with HGGs (16 glioblastomas, 7 anaplastic astrocytomas, and 7 other HGGs) between 2006 and 2015. Gross or near total resection was possible in 11 patients. Front-line treatment after surgery was radiotherapy (RT) in 14 patients and chemotherapy in the remaining 16 patients including 3 patients less than 3 years of age. Eight of 12 patients who remained progression free and 5 of the remaining 18 patients who experienced progression during induction treatment underwent the first HDCT/auto-SCT with carboplatin + thiotepa + etoposide (CTE) regimen and 11 of them proceeded to the second HDCT/auto-SCT with cyclophosphamide + melphalan (CyM) regimen. One patient died from hepatic veno-occlusive disease (VOD) during the second HDCT/auto-SCT; otherwise, toxicities were manageable. Four patients in complete response (CR) and 3 of 7 patients in partial response (PR) or second PR at the first HDCT/auto-SCT remained event free: however, 2 patients with progressive tumor experienced progression again. The probabilities of 3-year overall survival (OS) after the first HDCT/auto-SCT in 11 patients in CR, PR, or second PR was 58.2% ± 16.9%. Tumor status at the first HDCT/auto-SCT was the only significant factor for outcome after HDCT/auto-SCT. There was no difference in survival between glioblastoma and other HGGs. This study suggests that the outcome of HGGs in children and adolescents after HDCT/auto-SCT is encouraging if the patient could achieve CR or PR before HDCT/auto-SCT. PMID:28049229

  13. [Clinical significance and distribution of BRCA genes mutation in sporadic high grade serous ovarian cancer].

    PubMed

    Liu, W L; Wang, Z Z; Zhao, J Z; Hou, Y Y; Wu, X X; Li, W; Dong, B; Tong, T T; Guo, Y J

    2017-01-25

    Objective: To investigate the mutations of BRCA genes in sporadic high grade serous ovarian cancer (HGSOC) and study its clinical significance. Methods: Sixty-eight patients between January 2015 and January 2016 from the Affiliated Cancer Hospital of Zhengzhou University were collected who were based on pathological diagnosis of ovarian cancer and had no reported family history, and all patients firstly hospitalized were untreated in other hospitals before. (1) The BRCA genes were detected by next-generation sequencing (NGS) method. (2) The serum tumor markers included carcinoembryonic antigen (CEA), CA(125), CA(199), and human epididymis protein 4 (HE4) were detected by the chemiluminescence methods, and their correlation was analyzed by Pearson linear correlation. Descriptive statistics and comparisons were performed using two-tailed t-tests, Pearson's chi square test, Fisher's exact tests or logistic regression analysis as appropriate to research the clinicopathologic features associated with BRCA mutations, including age, International Federation of Gynecology and Obstetrics (FIGO) stage, platinum-based chemotherapy sensitivity, distant metastases, serum tumor markers (STM) . Results: (1) Fifteen cases (22%, 15/68) BRCA mutations were identified (BRCA1: 11 cases; BRCA2: 4 cases), and four novel mutations were observed. (2) The levels of CEA, CA(199), and HE4 were lower in BRCA mutations compared to that in control group, while no significant differences were found (P>0.05), but the level of CA(125) was much higher in BRCA mutation group than that in controls (t=-3.536, P=0.003). Further linear regression analysis found that there was a significant linear correlation between CA(125) and HE4 group (r=0.494, P<0.01), and the same correlation as CEA and CA(199) group (r=0.897, P<0.01). (3) Single factor analysis showed that no significant differences were observed in onset age, FIGO stage, distant metastasis, and STM between BRCA(+) and BRCA(-) group (P>0

  14. Recognition and characterisation of high-grade ignimbrites from the Neoproterozoic rhyolitic volcanism in southernmost Brazil

    NASA Astrophysics Data System (ADS)

    Sommer, Carlos Augusto; Lima, Evandro Fernandes; Machado, Adriane; Rossetti, Lucas de Magalhães May; Pierosan, Ronaldo

    2013-11-01

    Neoproterozoic magmatism in southern Brazil is associated with translithospheric shear belts and strike-slip basins in a post-collisional setting related to the last stages of the Brasilian-Pan African Orogenic Cycle. It evolved from an association of high-K calc-alkaline, leucocratic-peraluminous and continental tholeiitic magmas, to an association with shoshonitic magmas and, eventually, to an association with magmas of the sodic mildly alkaline series. This magmatism varies from metaluminous to peralkaline and exhibits alkaline sodic affinity. A large volcanism is related to this alkaline sodic magmatism and is named the Acampamento Velho Formation. This unit was coeval with subaerial siliciclastic sedimentation in post-collisional basins preserved in the region. The Acampamento Velho Formation consists of pyroclastic and effusive volcanic deposits, which are mainly silicic, emplaced under subaerial conditions. The best exposures of this volcanism occur on the Ramada and Taquarembó plateaus, located southwest of Rio Grande do Sul in southernmost Brazil. The pyroclastic flow deposits are composed mainly of juvenile fragments such as pumices, shards and crystal fragments. Welding is very effective in these units. High-grade ignimbrites occur at the base and intermediate portions of the deposits and rheoignimbrites are observed at the top. The pre-eruptive temperature calculations, which were obtained at the saturation of zircon, revealed values between 870 °C and 978 °C for Taquarembó Plateau and 850 °C-946 °C for Ramada Plateau. The calculated viscosity values vary from 6.946 to 8.453 log η (Pas) for the rheoignimbrites and 7.818 to 10.588 log η (Pas) for the ignimbrites. Zr contents increase toward the top of the pyroclastic sequence, which indicates an increase in peralkalinity and determines the reduction in viscosity for clasts at the upper portions of the flows. The patterns of the structures of the ignimbrites and rheoignimbrites in the Taquaremb

  15. Potential targets for lung squamous cell carcinoma

    Cancer.gov

    Researchers have identified potential therapeutic targets in lung squamous cell carcinoma, the second most common form of lung cancer. The Cancer Genome Atlas (TCGA) Research Network study comprehensively characterized the lung squamous cell carcinoma gen

  16. Aiming High and Falling Short: California's Eighth-Grade Algebra-for-All Effort

    ERIC Educational Resources Information Center

    Domina, Thurston; McEachin, Andrew; Penner, Andrew; Penner, Emily

    2015-01-01

    The United States is in the midst of an effort to intensify middle school mathematics curricula by enrolling more 8th graders in Algebra. California is at the forefront of this effort, and in 2008, the state moved to make Algebra the accountability benchmark test for 8th-grade mathematics. This article takes advantage of this unevenly implemented…

  17. Music in the High School. A Syllabus in Music, Grades 9-12.

    ERIC Educational Resources Information Center

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

    In this curriculum guide a flexible music program is offered that provides a variety of interesting and challenging courses for pupils in grades 9 through 12. The objective is to present a musical education program to meet the wide range of needs of different pupils many of whom will use music as a hobby or to enrich their cultural background.…

  18. Relationship between Grade One Achievement and Academic Performance through High School.

    ERIC Educational Resources Information Center

    Simner, Marvin L.; Barnes, Michael J.

    The major purpose of this study was to determine what relationship currently exists between grade 1 marks and later school achievement. Complete academic records were obtained on two samples of students from rural towns in Southwestern Ontario. Each sample contained all the children born between 1964 and 1971 who attended their town's major public…

  19. Choose Life! Unborn Children and the Right to Life. Junior High Level: Grades 7-8.

    ERIC Educational Resources Information Center

    National Catholic Educational Association, Washington, DC.

    This curriculum is designed to assist Catholic school teachers and parish catechists in their efforts to foster a pro-life attitude in students in grades 7 and 8. Following an introduction is the curriculum which features six lessons. These are: (1) Unique in all the world; (2) The first nine months of human life; (3) The hard facts about…

  20. Course Outlines for English--Junior High School, Grades 7 and 8.

    ERIC Educational Resources Information Center

    Burbank Unified School District, CA.

    Designed for seventh and eighth grade English teachers, this curriculum guide contains (1) a course description; (2) educational goals; (3) teaching perspective; (4) a set of general principles; (5) a list of questions that teachers ask, along with answers; (6) an overview; and (7) directions for writing as a process, higher level thinking skills,…

  1. MOTIVATIONAL FACTORS INFLUENCING ACADEMIC ACHIEVEMENT OF ELEVENTH GRADE PUERTO RICAN HIGH SCHOOL STUDENTS.

    ERIC Educational Resources Information Center

    FARQUHAR, WILLIAM M.; CHRISTENSEN, EDWARD W.

    THIS STUDY INVOLVED--(1) EXPLORING ACADEMIC MOTIVATIONAL FACTORS IN PUERTO RICAN 11TH-GRADE STUDENTS, (2) CREATING A MEASURE FOR THESE FACTORS WHICH MIGHT BE USABLE IN OTHER LATIN AMERICAN AREAS, AND (3) INVESTIGATING THE CHILD-REARING AND OTHER PSYCHO-SOCIAL FACTORS RELATED TO ACADEMIC ACHIEVEMENT. THE METHOD INVOLVED THREE STAGES--(1)…

  2. Higher Grades and Repeated Recurrence of Hepatic Encephalopathy May Be Related to High Serum Manganese Levels.

    PubMed

    Kobtan, Abdelrahman A; El-Kalla, Ferial S; Soliman, Hanan H; Zakaria, Soha S; Goda, Mohamed A

    2016-02-01

    Hepatic encephalopathy is a serious complication of liver failure. Until now, the precise pathophysiologic mechanisms are not fully determined. It has been demonstrated that manganese plays an important role in the pathogenesis of hepatic encephalopathy. Therefore, we studied manganese levels in serum of cirrhotic patients with hepatic encephalopathy in relation to grading and recurrence of hepatic encephalopathy. One hundred persons were enrolled in the study, 80 cirrhotic patients with or without encephalopathy and 20 healthy controls. Hepatic encephalopathy was diagnosed clinically and by laboratory findings. Serum manganese levels were measured in all participants. The grading of hepatic encephalopathy was significantly correlated to the severity of liver dysfunction. The mean serum manganese level was significantly higher in cirrhotic patients than in controls and in cirrhotic patients with encephalopathy than in those without encephalopathy. It was also significantly higher in patients with advanced grading of hepatic encephalopathy. Serum manganese level was positively correlated to number of recurrences of encephalopathy during a 6-month follow-up period. Serum manganese levels were able to predict recurrence of hepatic encephalopathy within 6 months following the episode. Serum manganese levels are positively correlated to the modified Child-Pugh score of cirrhosis as well as grading and number of recurrences of hepatic encephalopathy. Higher manganese levels seem to be related to worsening of the condition, and its measurement may be used as a predictor of repeated recurrences.

  3. Survey of Montgomery County Public School Eleventh Grade High School Students.

    ERIC Educational Resources Information Center

    Campbell, William E.; Hemenway, David A.

    In spring 1984, a survey was conducted by Montgomery College (MC) to ascertain the postsecondary educational goals of Montgomery County Public School (MCPS) 11th grade students; to understand students' perceptions of MC; to identify the criteria students use in college selection; and to assess the needs of entering students. Students at 18 of the…

  4. Turning Points: A Transitional Story of Grade Seven Music Students' Participation in High School Band Programmes

    ERIC Educational Resources Information Center

    Gouzouasis, Peter; Henrey, Julia; Belliveau, George

    2008-01-01

    As a framework for our study, a broad set of themes related to the retention of students in music programmes are presented to enhance our understanding of how to retain band students. Data were collected from grade seven students comprising four focus groups. We used ethnodrama, an arts-based educational research approach, to represent results as…

  5. Choose Life! Unborn Children and the Right to Life. Senior High Level: Grades 9-12.

    ERIC Educational Resources Information Center

    National Catholic Educational Association, Washington, DC.

    This curriculum is designed to assist Catholic school teachers and parish catechists in their efforts to foster a pro-life attitude in students in grades 9-12. Following an introduction is the curriculum, which features six lessons. These are: (1) The miracle of human life; (2) Responsible parenthood versus abortion; (3) Abortion is no solution;…

  6. Grade Span.

    ERIC Educational Resources Information Center

    Renchler, Ron

    2000-01-01

    This issue reviews grade span, or grade configuration. Catherine Paglin and Jennifer Fager's "Grade Configuration: Who Goes Where?" provides an overview of issues and concerns related to grade spans and supplies profiles of eight Northwest schools with varying grade spans. David F. Wihry, Theodore Coladarci, and Curtis Meadow's…

  7. The high expression of TC1 (C8orf4) was correlated with the expression of β-catenin and cyclin D1 and the progression of squamous cell carcinomas of the tongue.

    PubMed

    Zhang, Peng; Cao, Hong-Yi; Bai, Lin-Lin; Li, Wei-Nan; Wang, Yuan; Chen, Song-Yan; Zhang, Li; Yang, Lian-He; Xu, Hong-Tao; Wang, En-Hua

    2015-09-01

    Thyroid cancer 1 (TC1, C8orf4) plays important roles in many signaling pathways, such as Wnt/β-catenin signaling pathway, and is involved in the development of many cancers. The objective of this study was to examine the expression of TC1 and investigate the associations among TC1, β-catenin, Chibby, cyclin D1, and the clinicopathological factors of oral tongue squamous cell carcinomas (OTSCCs). The expressions of TC1, β-catenin, Chibby, and cyclin D1 were examined in 109 cases of OTSCCs using immunohistochemistry. The expression of TC1 was observed in all cases of OTSCCs but was negative or weak in normal squamous epithelial tissues of tongue. The high expression of TC1 was correlated with the advanced TNM stage (P = 0.042), the abnormal expression of β-catenin (correlation coefficient = 0.314, P = 0.001) and the expression of cyclin D1 (correlation coefficient = 0.274, P = 0.006) in OTSCCs. But we did not find any associations between TC1 and Chibby. The abnormal expression of β-catenin was correlated with the poor differentiation (P = 0.035), advanced TNM stage (P = 0.048) and the expression of cyclin D1 (correlation coefficient = 0.422, P < 0.001). In conclusion, the high expression of TC1 was common in OTSCCs and correlated with the expression of β-catenin and cyclin D1 and the progression of OTSCCs. The high expression level of TC1 might promote the progression of OTSCCs by enhancing the activity of Wnt signaling pathway.

  8. High-Grade Acute Organ Toxicity as a Positive Prognostic Factor in Primary Radiochemotherapy for Anal Carcinoma

    SciTech Connect

    Wolff, Hendrik Andreas; Raus, Ismene; Jung, Klaus; Schueler, Phillip; Herrmann, Markus Karl; Hennies, Steffen; Vorwerk, Hilke; Hille, Andrea; Hess, Clemens Friedrich; Christiansen, Hans

    2011-04-01

    Purpose: To test for a possible correlation between high-grade acute organ toxicity during primary radiochemotherapy and treatment outcome for patients with anal carcinoma. Methods and Materials: From 1991 to 2009, 72 patients with anal carcinoma were treated at our department (10 patients had stage I, 28 patients had stage II, 11 patients had stage IIIA, and 13 patients had stage IIIB cancer [Union Internationale Contre le Cancer criteria]). All patients received normofractionated (1.8 Gy/day, five times/week) whole-pelvis irradiation including iliac and inguinal lymph nodes with a cumulative dose of 50.4 Gy. Concomitant chemotherapy regimen consisted of two cycles of 5-fluorouracil (1,000 mg/m{sup 2}total body surface area (TBSA)/day as continuous intravenous infusion on days 1-4 and 29-32) and mitomycin C (10 mg/m{sup 2}/TBSA, intravenously on days 1 and 29). Toxicity during treatment was monitored weekly, and any incidence of Common Toxicity Criteria (CTC) grade of {>=}3 for skin reaction, cystitis, proctitis, or enteritis was assessed as high-grade acute organ toxicity for later analysis. Results: We found significant correlation between high-grade acute organ toxicity and overall survival, locoregional control, and stoma-free survival, which was independent in multivariate analysis from other possible prognostic factors: patients with a CTC acute organ toxicity grade of {>=}3 had a 5-year overall survival rate of 97% compared to 30% in patients without (p < 0.01, multivariate analysis; 97% vs. 48%, p = 0.03 for locoregional control, and 95% vs. 59%, p = 0.05 for stoma-free survival). Conclusions: Our data indicate that normal tissue and tumor tissue may behave similarly with respect to treatment response, since high-grade acute organ toxicity during radiochemotherapy showed itself to be an independent prognostic marker in our patient population. This hypothesis should be further analyzed by using biomolecular and clinical levels in future clinical trials.

  9. High-temperature thermo-mechanical behavior of functionally graded materials produced by plasma sprayed coating: Experimental and modeling results

    NASA Astrophysics Data System (ADS)

    Choi, Kang Hyun; Kim, Hyun-Su; Park, Chang Hyun; Kim, Gon-Ho; Baik, Kyoung Ho; Lee, Sung Ho; Kim, Taehyung; Kim, Hyoung Seop

    2016-09-01

    Thermal barrier coatings are widely used in aerospace industries to protect exterior surfaces from harsh environments. In this study, functionally graded materials (FGMs) were investigated with the aim to optimize their high temperature resistance and strength characteristics. NiCrAlY bond coats were deposited on Inconel-617 superalloy substrate specimens by the low vacuum plasma spraying technique. Functionally graded Ni-yttria-stabilized zirconia (YSZ) coatings with gradually varying amounts of YSZ (20%-100%) were fabricated from composite powders by vacuum plasma spraying. Heat shield performance tests were conducted using a high- temperature plasma torch. The temperature distributions were measured using thermocouples at the interfaces of the FGM layers during the tests. A model for predicting the temperature at the bond coating-substrate interface was established. The temperature distributions simulated using the finite element method agreed well with the experimental results.

  10. Computer aided morphometric analysis of oral leukoplakia and oral squamous cell carcinoma.

    PubMed

    Gupta, K; Gupta, J; Miglani, R

    2016-01-01

    We compared the changes in the cells in the basal layer of normal mucosa, oral leukoplakia with dysplasia and different grades of oral squamous cell carcinoma (OSCC) using computer aided image analysis of tissue sections. We investigated three morphometric parameters: nuclear area (NA), cell area (CA) and their ratio (NA:CA). NA and NA:CA ratio showed a statistically significant increase from dysplasia to increasing grades of OSCC. Nuclear size was useful for differentiating normal tissue, potentially malignant leukoplakia and OSCC.

  11. Characteristics of eighth-grade students who initiate self-care in elementary and junior high school.

    PubMed

    Dwyer, K M; Richardson, J L; Danley, K L; Hansen, W B; Sussman, S Y; Brannon, B; Dent, C W; Johnson, C A; Flay, B R

    1990-09-01

    The purpose of this paper is to examine whether children who care for themselves for longer periods of time are at increased risk of poor grades, truancy, anger, family conflict, stress, risk-taking, and peer influences (in addition to the increased risk of substance use previously reported). Demographic characteristics of eighth-grade students who initiate self-care in junior high school are compared with those initiating self-care in elementary school. Further, increased risks for those initiating self-care in elementary school are examined. Over two thirds of the respondents (67.8%) cared for themselves after school without adult supervision at some time during the week; 23.5% for 1 to 4 hours per week, 15.7% for 5 to 10 hours per week, and 28.6% for 11 or more hours per week. Of those in self-care, 48.5% initiated self-care during elementary school and 51.5% during junior high school. Students who were in the highest category of self-care (greater than or equal to 11 hours per week) vs those in self-care zero hours per week were 1.5 to 2 times as likely to score high on risk-taking, anger, family conflict, and stress, to be more likely to see their friends as their major source of influence, and to attend more parties. The self-reports of academic grades did not differ. The grade of initiation of self-care (elementary vs junior high school) conferred additional risk for drinking alcohol (odds ratio = 1.4), risk-taking tendencies (odds ratio = 1.5), and attending parties (odds ratio = 1.6).

  12. Combination chemotherapy for intermediate and high grade non-Hodgkin's lymphoma.

    PubMed Central

    Dhaliwal, H. S.; Rohatiner, A. Z.; Gregory, W.; Richards, M. A.; Johnson, P. W.; Whelan, J. S.; Gallagher, C. J.; Matthews, J.; Ganesan, T. S.; Barnett, M. J.

    1993-01-01

    One hundred and eighteen consecutive adults with newly diagnosed intermediate and high-grade non-Hodgkin's lymphoma were treated with chemotherapy comprising Doxorubicin, Cyclophosphamide, Vincristine and Prednisolone with mid-cycle Methotrexate (MTX) and leucovorin rescue ('CHOP-M'). Intrathecal MTX was given with each treatment cycle as central nervous system (CNS) prophylaxis. 'Clinical remission' was achieved in 70/110 evaluable patients (64%), complete remission: 45/110, (41%), good partial remission: 25/110 (23%). Twenty two patients (19%) died prior to completion of therapy, 18 patients had persistent disease. Hyponatremia (< 137 mmol l-1), advanced age and hypoalbuminaemia (< 32 g l-1) correlated adversely with achievement of CR (P = 0.0007, 0.0005 and 0.04 respectively). With a minimum follow up of 41 years, 47 of the seventy patients (67%) in whom clinical remission was achieved remain well, 19 have developed recurrent disease, resulting in an actuarial projected remission duration of 70% at 8 years. Four died in CR. There has been only one isolated CNS recurrence. On univariate analysis, hypoalbuminaemia, hyponatremia and beta 2 microglobulin (> 3) correlated with unfavourable outcome in terms of duration of remission (P = 0.0009, 0.007 and 0.04 respectively). On multivariate analysis, only the serum sodium (0.002) and advanced age (0.01) were predictive for remission duration. Fifty patients (45%) are alive, the overall actuarial projected survival is thus 42% at 8 years. On univariate analysis, age, hypoalbuminaemia, hyponatraemia, liver involvement and the presence of B symptoms correlated unfavourably with survival. On multivariate analysis, hypoalbuminaemia, advanced age, hyponatraemia, male gender (aged > 50) and diffuse large cell or large cell, immunoblastic histology (Working Formulation) had an adverse effect (P = 0.003, < 0.0001, < 0.0001, 0.002, and 0.03). It was further possible, using cut-off points of 32 g l-1 and 136 mmol l-1 for albumin

  13. Human papillomavirus 16 non-European variants are preferentially associated with high-grade cervical lesions.

    PubMed

    Freitas, Luciana Bueno; Chen, Zigui; Muqui, Elaine Freire; Boldrini, Neide Aparecida Tosato; Miranda, Angélica Espinosa; Spano, Liliana Cruz; Burk, Robert D

    2014-01-01

    HPV16 accounts for 50-70% of cervical cancer cases worldwide. Characterization of HPV16 variants previously indicated that they differ in risks for viral persistence, progression to cervical precancer and malignant cancer. The aim of this study was to examine the association of severity of disease with HPV16 variants identified in specimens (n = 281) obtained from a Cervical Pathology and Colposcopy outpatient clinic in the University Hospital of Espírito Santo State, Southeastern Brazil, from April 2010 to November 2011. All cytologic and histologic diagnoses were determined prior to definitive treatment. The DNA was isolated using QIAamp DNA Mini Kit and HPV was detected by amplification with PGMY09/11 primers and positive samples were genotyped by RFLP analyses and reverse line blot. The genomes of the HPV16 positive samples were sequenced, from which variant lineages were determined. Chi2 statistics was performed to test the association of HPV16 variants between case and control groups. The prevalence of HR-HPV types in high-grade disease with an OR = 4.6 (1.07-20.2, p = 0.05). The association of HPV16 NE variants with an increased risk of CIN3+ is consistent with an HPV16 genetically determined enhanced oncogenicity. The prevalence of genetic variants of HPV16 is distributed across different geographical areas and with recent population admixture, only empiric data will provide information on the highest risk HPV16 variants within a given population.

  14. Matricellular protein CCN1 (CYR61) expression is associated with high-grade ductal carcinoma in situ.

    PubMed

    Saglam, Ozlen; Dai, Feng; Husain, Seema; Zhan, Yilei; Toruner, Gokce; Haines, G Kenneth

    2014-06-01

    Cysteine-rich protein 61, connective tissue growth factor, and nephroblastoma overexpressed gene (CCN) comprise a family of matricellular proteins that have multiple physiologic functions including development, tissue repair, cell adhesion, migration, and proliferation. The expression of CCN1, cyclin D1, β-catenin, and p53 was explored by immunohistochemistry in different grades of ductal carcinoma in situ (DCIS) cases. These cases did not contain any infiltrating carcinoma components. In addition, all cysteine-rich protein 61 gene exons (encoding the CCN1 protein) were sequenced in 30 samples. Allred and H-scores were calculated for expression in both DCIS and the surrounding benign breast tissue. All cases of DCIS showed degrees of cytoplasmic CCN1 staining with median H-scores of 170, 160, and 60 in grades 3, 2, and 1, respectively (P = .043). Twelve of 28 DCIS 3, 1 of 15 DCIS 2, and 0 of 18 DCIS 1 also showed nuclear staining for CCN1. The cytoplasmic staining difference was preserved when the cases were divided into estrogen receptor (ER)+/DCIS grade 1, ER+/DCIS 2 and 3, and ER-/DCIS 2 and 3 by the H-score (P = .037). Cyclin D1 expression was positively correlated with the CCN1 cytoplasmic H-score in all DCIS samples (P = .038). Membranous β-catenin expression correlated with the grade of intraepithelial carcinoma by both H-score (P = .047) and Allred score (P = .026). Our results suggest that CCN1 has a role in the development of intraepithelial carcinoma. CCN1 expression correlates with grade of DCIS independent of ER status. It can induce cell cycle progression through cyclin D1. It is warranted to study high expression of CCN1 in DCIS as an independent risk factor in a larger cohort.

  15. Randomized phase II/III trial of post-operative chemoradiotherapy comparing 3-weekly cisplatin with weekly cisplatin in high-risk patients with squamous cell carcinoma of head and neck: Japan Clinical Oncology Group Study (JCOG1008).

    PubMed

    Kunieda, Futoshi; Kiyota, Naomi; Tahara, Makoto; Kodaira, Takeshi; Hayashi, Ryuichi; Ishikura, Satoshi; Mizusawa, Junki; Nakamura, Kenichi; Fukuda, Haruhiko; Fujii, Masato

    2014-08-01

    A randomized Phase II/III study was launched in Japan to evaluate the non-inferiority of concurrent chemoradiotherapy with weekly cisplatin (40 mg/m(2)) compared with concurrent chemoradiotherapy with 3-weekly cisplatin (100 mg/m(2)) for post-operative high-risk patients with locally advanced squamous cell carcinoma of head and neck. This study began in October 2012, and a total of 260 patients will be accrued from 18 institutions within 5 years. The primary endpoint of the Phase II part is proportion of treatment completion and that of the Phase III part is overall survival. The secondary endpoints are relapse-free survival, local relapse-free survival, nutrition-support-free survival, non-hospitalized treatment period during permissible treatment period and adverse events. This trial was registered at the UMIN Clinical Trials Registry as UMIN 000009125 [http://www.umin.ac.jp/ctr/].

  16. Low-grade metastases in high-grade clear cell renal cell carcinomas: A clinicopathologic study of 4 cases with an insight into the role of mesenchymal-to-epithelial transition process.

    PubMed

    López, José I; Mosteiro, Lorena; Guarch, Rosa; Larrinaga, Gorka; Pulido, Rafael; Angulo, Javier C

    2016-02-01

    Clear cell renal cell carcinoma (CCRCC) frequently develops distant metastases. However, high-grade primary CCRCC rarely leads to low-grade metastases. Cellular changes occurring during neoplastic progression known as epithelial-to-mesenchymal and mesenchymal-to-epithelial transitions explain this apparent contradiction. Four high-grade CCRCCs, which lead to low-grade metastases, are analyzed in this study, with the focus on epithelial-to-mesenchymal and mesenchymal-to-epithelial processes. Clinicopathologic data have been collected retrospectively and immunohistochemistry has been performed with E-cadherin, N-cadherin, vimentin, and WT-1. Three cases had organ-confined disease (2 pT2 and 1 pT1b). Three cases were G3 and 1 case was G4. Lung (3 cases), bone (2 cases), and pancreas (1 case) were the metastatic organs (2 patients developed multiple metastases). Metastases were G1 in all the cases. Average elapsed time between the primary tumor and the metastasis was 35.5 months. Three patients died of disease after 36, 120, and 180 months of follow-up, respectively. One patient is alive without disease after 75 months of follow-up. E-cadherin and N-cadherin showed concordant immunostaining patterns between primaries and metastases but inverse when correlated with Fuhrman grade. Hence, E-cadherin was positive in G3 cases and negative in G4, whereas N-cadherin was negative in G3 and positive in G4. Vimentin was positive in primaries and metastases only in 2 cases. WT-1 was consistently negative in all cases. In conclusion, pathologists must remember that high-grade CCRCC may develop low-grade metastases. Cadherin switching seems to be related to Fuhrman grade in this group of cases. This preliminary observation must be confirmed in longer studies.

  17. Molecular diagnostic assays for cervical neoplasia: emerging markers for the detection of high-grade cervical disease.

    PubMed

    Malinowski, Douglas P

    2005-04-01

    The accurate detection and diagnosis of cervical carcinoma and its malignant precursors (collectively referred to as high-grade cervical disease) represents one of the current challenges in clinical medicine and cytopathology. The advent of molecular diagnostics and the use of whole-genome profiling using DNA microarrays promises to yield improved understanding of the disease process with the subsequent development of more accurate diagnostic procedures based upon these discoveries. Recent reports describing a variety of experimental approaches have identified a series of candidate genes that are overexpressed in cervical carcinoma. In this article, representative examples of these markers and the resulting translational research will be reviewed within the context of improved cervical disease detection. An emerging class of markers, the minichromosome maintenance protein family of DNA licensing factors (MCM-2, MCM-6, MCM-7), shows promise for the specific detection of high-grade cervical disease using simple antibody-based immunochemistry formats. These proteins are overexpressed in cervical disease as a result of infection by oncogenic strains of human papillomavirus (HPV) and subsequent uncontrolled activation of gene transcription and aberrant S-phase induction, mediated through the E2F transcription factor pathway. This behavior appears to be a hallmark of high-grade cervical disease and provides the link between oncogenic HPV infections and the molecular behavior of cervical neoplasia (CN). The use of these molecular descriptors of CN in simple immunochemistry formats compatible with conventional cytology preparations is anticipated to improve the screening and detection of cervical disease within the healthcare system.

  18. Concurrent Nontuberculous Mycobacteria Infection and High-Grade Anterior Mediastinal Extraskeletal Osteosarcoma (ESOS): Is There a Connection?

    PubMed Central

    Faz, Gabriel T.; Eltorky, Mahmoud; Karnath, Bernard

    2016-01-01

    Patient: Male, 59 Final Diagnosis: High-grade anterior mediastinal extraskeletal osteosarcoma Symptoms: Dyspnea • hemoptysis Medication: — Clinical Procedure: Biopsy Specialty: Oncology Objective: Rare disease Background: Extraskeletal osteosarcomas (ESOS) of the mediastinum are extremely rare and may present with concurrent nontuberculous mycobacteria infection. Case Report: We present the second documented case of high-grade anterior mediastinal extraskeletal osteosarcoma in a 59-year-old man with a history of treated, latent tuberculosis (TB). Sputum samples grew Mycoplasma avium complex and Mycobacterium fortuitum. Imaging showed a right-sided 7.6 cm mass with compression of the main bronchus. Subsequent biopsy with vimentin staining established the diagnosis of ESOS. Due to the patient’s rapidly declining performance status, he was not deemed a candidate for surgery or chemotherapy. He subsequently expired within one month of presentation. Conclusions: We present a unique case of high-grade anterior mediastinum ESOS and a review of the literature regarding all documented cases of ESOS to date. We suggest there is a possible link between mediastinal masses and nontuberculous mycobacteria infection. PMID:27539718

  19. Reversibility of High-Grade Atrioventricular Block with Revascularization in Coronary Artery Disease without Infarction: A Literature Review

    PubMed Central

    Cardoso, Rhanderson; Alfonso, Carlos E.; Coffey, James O.

    2016-01-01

    Complete atrioventricular (AV) block is known to be reversible in some cases of acute inferior wall myocardial infarction (MI). The reversibility of high-grade AV block in non-MI coronary artery disease (CAD), however, is rarely described in the literature. Herein we perform a literature review to assess what is known about the reversibility of high-grade AV block after right coronary artery revascularization in CAD patients who present without an acute MI. To illustrate this phenomenon we describe a case of 2 : 1 AV block associated with unstable angina, in which revascularization resulted in immediate and durable restoration of 1 : 1 AV conduction, thereby obviating the need for permanent pacemaker implantation. The literature review suggests two possible explanations: a vagally mediated response or a mechanism dependent on conduction system ischemia. Due to the limited understanding of AV block reversibility following revascularization in non-acute MI presentations, it remains difficult to reliably predict which patients presenting with high-grade AV block in the absence of MI may have the potential to avoid permanent pacemaker implantation via coronary revascularization. We thus offer this review as a potential starting point for the approach to such patients. PMID:26925272

  20. Computer Based Correlation of the Texture of P63 Expressed Nuclei with Histological Tumour Grade, in Laryngeal Carcinomas

    PubMed Central

    Ninos, Konstantinos; Kalatzis, Ioannis; Ravazoula, Panagiota; Sakelaropoulos, George; Panayiotakis, George; Economou, George; Cavouras, Dionisis

    2014-01-01

    Background. P63 immunostaining has been considered as potential prognostic factor in laryngeal cancer. Considering that P63 is mainly nuclear stain, a possible correlation between the texture of P63-stained nuclei and the tumor's grade could be of value to diagnosis, since this may be related to biologic information imprinted as texture on P63 expressed nuclei. Objective. To investigate the association between P63 stained nuclei and histologic grade in laryngeal tumor lesions. Methods. Biopsy specimens from laryngeal tumour lesions of 55 patients diagnosed with laryngeal squamous cell carcinomas were immunohistochemically (IHC) stained for P63 expression. Four images were digitized from each patient's IHC specimens. P63 positively expressed nuclei were identified, the percentage of P63 expressed nuclei was computed, and 118 textural, morphological, shape, and architectural features were calculated from each one of the 55 laryngeal lesions. Data were split into the low grade (21 grade I lesions) and high grade (34 grade II and grade III lesions) classes for statistical analysis. Results. With advancing grade, P63 expression decreased, P63 stained nuclei appeared of lower image intensity, more inhomogeneous, of higher local contrast, contained smaller randomly distributed dissimilar structures and had irregular shape. Conclusion. P63 expressed nuclei contain important information related to histologic grade. PMID:25763351

  1. Progress on the carbothermic production of solar-grade silicon using high-purity starting materials

    SciTech Connect

    Schultz, F.W.; Aulich, H.A.; Fenzi, H.J.; Hecht, M.D.

    1984-05-01

    Solar-grade silicon was produced by carbothermic reduction (CR) in a 70 kW arc-furnace. Silicon suitable for solar cells with an efficiency > 10% was obtained form silicon dioxide of different origin and purified carbon. The importance of a low P- and B-concentration (<10/sup 17/a/cm/sup 3/) in the silicon produced was established. Cells made from CR-Si were successfully processed into modules using conventional technology.

  2. Cyclic oxidation to high temperature of ASTM - A53 grade B

    NASA Astrophysics Data System (ADS)

    Pérez, D.; Marulanda, J. L.; Santos, A.

    2017-01-01

    Samples of ASTM A53 steel grade B underwent 500 oxidation cycles at 600°C. Scanning Electron Microscopy (SEM), Energy Dispersive Spectroscopy (EDS) and X-Ray Diffraction (XRD) were performed to study the morphology, composition and phase structure of Fe2O3 y Fe3O4 layers on oxidation surface. Such layers were homogenous and poorly adhesive. Mass loss was significant due to absence of protective oxides and inevitable flaking, leaving the substrate exposed to corrosive environment.

  3. [Primary orbital squamous cell carcinoma].

    PubMed

    Campos Arbulú, Ana L; Sadava, Emmanuel E; Sánchez Ruiz, Alejandro; Fernández Vila, Juan M; Dillon, Horacio S; Mezzadri, Norberto A

    2017-01-01

    Primary orbital squamous cell carcinoma is a rare entity. There is little published literature. We report a case of primary squamous cell carcinoma of the orbital soft tissues. Surgical resection offered the best treatment for the patient. Complete resection of the lesion was achieved. The patient received adjuvant radiotherapy due to the proximity of the lesion to the surgical margins. Surgical treatment is feasible and should be considered as part of the surgeon's arsenal. However, therapeutic decisions must be made on a case-by-case basis.

  4. Identification of a novel inactivating mutation in Isocitrate Dehydrogenase 1 (IDH1-R314C) in a high grade astrocytoma

    PubMed Central

    van Lith, Sanne A. M.; Navis, Anna C.; Lenting, Krissie; Verrijp, Kiek; Schepens, Jan T. G.; Hendriks, Wiljan J. A. J.; Schubert, Nil A.; Venselaar, Hanka; Wevers, Ron A.; van Rooij, Arno; Wesseling, Pieter; Molenaar, Remco J.; van Noorden, Cornelis J. F.; Pusch, Stefan; Tops, Bastiaan; Leenders, William P. J.

    2016-01-01

    The majority of low-grade and secondary high-grade gliomas carry heterozygous hotspot mutations in cytosolic isocitrate dehydrogenase 1 (IDH1) or the mitochondrial variant IDH2. These mutations mostly involve Arg132 in IDH1, and Arg172 or Arg140 in IDH2. Whereas IDHs convert isocitrate to alpha-ketoglutarate (α-KG) with simultaneous reduction of NADP+ to NADPH, these IDH mutants reduce α-KG to D-2-hydroxyglutarate (D-2-HG) while oxidizing NADPH. D-2-HG is a proposed oncometabolite, acting via competitive inhibition of α-KG-dependent enzymes that are involved in metabolism and epigenetic regulation. However, much less is known about the implications of the metabolic stress, imposed by decreased α-KG and NADPH production, for tumor biology. We here present a novel heterozygous IDH1 mutation, IDH1R314C, which was identified by targeted next generation sequencing of a high grade glioma from which a mouse xenograft model and a cell line were generated. IDH1R314C lacks isocitrate-to-α-KG conversion activity due to reduced affinity for NADP+, and differs from the IDH1R132 mutants in that it does not produce D-2-HG. Because IDH1R314C is defective in producing α-KG and NADPH, without concomitant production of the D-2-HG, it represents a valuable tool to study the effects of IDH1-dysfunction on cellular metabolism in the absence of this oncometabolite. PMID:27460417

  5. Invasive Ocular Surface Squamous Neoplasia Masquerading as Nodular Scleritis.

    PubMed

    Sharma, Medha; Sundar, Dheepak; Vanathi, Murugesan; Meel, Rachna; Kashyap, Seema; Chawla, Rohan; Tandon, Radhika

    The authors report a rare case of ocular surface squamous neoplasia with intraocular involvement that had an initial masquerade presentation of recurrent anterior nodular scleritis. A 35-year-old male patient presented with right eye recurrent anterior nodular scleritis for which a lamellar patch graft was done. Two months later, the patient presented with recurrence of symptoms. Histopathology review revealed the presence of well-differentiated squamous cell malignancy. A high index of suspicion for malignancy is required in such cases when they do not respond to conventional therapy.

  6. Endocervical glandular involvement, multicentricity, and extent of the disease are features of high-grade cervical intraepithelial neoplasia.

    PubMed

    Güdücü, Nilgün; Sidar, Güliz; Başsüllü, Nuray; Türkmen, Ilknur; Dünder, Ilkkan

    2013-08-01

    This study aimed to evaluate the rate of endocervical glandular involvement, positive surgical margins, multicentricity, and disease extent between low-grade and high-grade cervical intraepithelial lesions after loop electrosurgical excision procedure (LEEP). Pathology medical records of patients who underwent LEEP were reviewed retrospectively. Patients with negative LEEP results were excluded. Loop electrosurgical excision procedure reports of patients with cervical intraepithelial neoplasia (CIN) 1, 2, and 3 were compared. There was no statistically significant difference between patients with CIN 1 (n=24), CIN 2 (n=27), and CIN 3 (n=64) when age and surgical margin positivity were considered. Endocervical glandular involvement, multicentricity, and disease extent were higher in patients with CIN 3 (P=.001, P=.002, and P=.001, respectively). In conclusion, we recommend that patients with endocervical glandular involvement, lesions involving more than two-thirds of the LEEP specimen, and multicentricity be followed up more closely.

  7. Gankyrin Is Frequently Overexpressed in Cervical High Grade Disease and Is Associated with Cervical Carcinogenesis and Metastasis

    PubMed Central

    Qian, Wenyan; Dong, Yu; Yang, Yongbin; Liu, Zhiqiang; Feng, Youji; Ma, Ding; Zhang, Zhenbo; Wu, Sufang

    2014-01-01

    Our previous studies have showed that Gankyrin expression is correlated with a malignant phenotype in endometrial carcinoma. Here, we investigated the possible role of Gankyrin in cervical disease. The increasing protein level of Gankyrin was observed in high-grade cervical intraepithelial neoplasia and carcinoma compared with benign cervical tissues and low-grade cervical intraepithelial neoplasia. In para-carcinoma tissues, it was found interestingly that there was no lymph node metastasis when nuclei Gankyrin was positively expressed, but lymph node metastasis rate was 30% (6/20) when nuclei Gankyrin was negatively expressed. In vitro, the transfection of Gankyrin resulted in markedly up-regulating of Vimentin, β-catenin and Twist2, as well as down-regulating of E-cadherin in cervical carcinoma cells. Our results suggested that Gankyrin may be functional in cervical carcinogenesis and metastasis. PMID:24751719

  8. Births, Selected Grade Comparisons, High School Graduates, and Number Entering College for the State and the Counties, 1961 through 1996. Statistical Report Series.

    ERIC Educational Resources Information Center

    Ward-Besser, Gail; Hearn, Cynthia A.

    State and county estimates of basic statistics relevant to educational planning in South Carolina are presented. The report includes actual and projected counts for grades 9 and 12, as well as actual and projected counts of first grade membership, high school graduates, and graduates who enter a college degree program. Enrollment figures have been…

  9. Multivoxel magnetic resonance spectroscopy identifies enriched foci of cancer stem-like cells in high-grade gliomas

    PubMed Central

    He, Tao; Qiu, Tianming; Wang, Xiaodong; Gui, Hongxing; Wang, Xilong; Hu, Qikuan; Xia, Hechun; Qi, Gaoyang; Wu, Jinsong; Ma, Hui

    2017-01-01

    Objective This study investigated the correlation between choline/creatine (Cho/Cr) ratios determined by multivoxel proton magnetic resonance spectroscopy (1H-MRS) and the distribution of cancer stem-like cells (CSLCs) in high-grade gliomas. Patients and methods Sixteen patients with high-grade gliomas were recruited and underwent 1H-MRS examination before surgery to identify distinct tumor regions with variable Cho/Cr ratios. Using intraoperative neuronavigation, tumor tissues were accurately sampled from regions with high and low Cho/Cr ratios within each tumor. The distribution of CSLCs in samples from glioma tissue regions with different Cho/Cr ratios was quantified by neurosphere culture, immunohistochemistry, and Western blot. Results The mean neurosphere formation rate in tissues with high Cho/Cr ratios was significantly increased compared with that in low Cho/Cr ratio tissues (13.94±5.94 per 100 cells vs 8.04±3.99 per 100 cells, P<0.001). Immunohistochemistry indicated that tissues with high Cho/Cr ratios had elevated expression of CD133, nestin, and CD15, relative to low Cho/Cr ratio tissue samples (23.6%±3.8% vs 18.3%±3.3%, 25.2%±4.5% vs 19.8%±2.8%, 24.5%±3.8% vs 17.8%±2.2%, respectively; all P<0.001). Western blot demonstrated that relative CD133 and nestin protein expression in high Cho/Cr ratio regions was significantly higher than that in low Cho/Cr ratio tissue samples (0.50±0.17 vs 0.30±0.08, 0.45±0.13 vs 0.27±0.07, respectively; both P<0.001). The protein expression levels of CD133 and nestin were highly correlated with Cho/Cr ratios (r=0.897 and r=0.861, respectively). Conclusion Cho/Cr ratios correlate with the distribution of CSLCs in high-grade gliomas, and this may assist in identifying foci enriched with CSLCs and thus improve the management of high-grade gliomas. PMID:28115854

  10. A Pilot Study of Hypofractionated Stereotactic Radiation Therapy and Sunitinib in Previously Irradiated Patients With Recurrent High-Grade Glioma

    SciTech Connect

    Wuthrick, Evan J.; Curran, Walter J.; Camphausen, Kevin; Lin, Alexander; Glass, Jon; Evans, James; Andrews, David W.; Axelrod, Rita; Shi, Wenyin; Werner-Wasik, Maria; Haacke, E. Mark; Hillman, Gilda G.; Dicker, Adam P.

    2014-10-01

    Purpose/Objective(s): Angiogenic blockade with irradiation may enhance the therapeutic ratio of radiation therapy (RT) through vascular normalization. We sought to determine the safety and toxicity profile of continuous daily-dosed sunitinib when combined with hypofractionated stereotactic RT (fSRT) for recurrent high-grade gliomas (rHGG). Methods and Materials: Eligible patients had malignant high-grade glioma that recurred or progressed after primary surgery and RT. All patients received a minimum of a 10-day course of fSRT, had World Health Organization performance status of 0 to 1, and a life expectancy of >3 months. During fSRT, sunitinib was administered at 37.5 mg daily. The primary endpoint was acute toxicity, and response was assessed via serial magnetic resonance imaging. Results: Eleven patients with rHGG were enrolled. The fSRT doses delivered ranged from 30 to 42 Gy in 2.5- to 3.75-Gy fractions. The median follow-up time was 40 months. Common acute toxicities included hematologic disorders, fatigue, hypertension, and elevated liver transaminases. Sunitinib and fSRT were well tolerated. One grade 4 mucositis toxicity occurred, and no grade 4 or 5 hypertensive events or intracerebral hemorrhages occurred. One patient had a nearly complete response, and 4 patients had stable disease for >9 months. Two patients (18%) remain alive and progression-free >3 years from enrollment. The 6-month progression-free survival was 45%. Conclusions: Sunitinib at a daily dose of 37.5 mg given concurrently with hypofractionated stereotactic reirradiation for rHGG yields acceptable toxicities and an encouraging 6-month progression-free survival.

  11. Favorable Prognosis in Patients With High-Grade Glioma With Radiation Necrosis: The University of Colorado Reoperation Series

    SciTech Connect

    Rusthoven, Kyle E.; Olsen, Christine; Franklin, Wilbur; Kleinschmidt-DeMasters, B.K.; Kavanagh, Brian D.; Gaspar, Laurie E.; Lillehei, Kevin; Waziri, Allen; Damek, Denise M.; Chen, Changhu

    2011-09-01

    Purpose: To analyze the pathology, outcomes, and prognostic factors in patients with high-grade glioma undergoing reoperation after radiotherapy (RT). Methods and Materials: Fifty-one patients with World Health Organization Grade 3-4 glioma underwent reoperation after prior RT. The median dose of prior RT was 60 Gy, and 84% received chemotherapy as part of their initial treatment. Estimation of the percentage of necrosis and recurrent tumor in each reoperation specimen was performed. Pathology was classified as RT necrosis if {>=}80% of the specimen was necrotic and as tumor recurrence if {>=}20% was tumor. Predictors of survival were analyzed using log-rank comparisons and Cox proportional hazards regression. Results: The median interval between the completion of RT and reoperation was 6.7 months (range, 1-59 months). Pathologic analysis showed RT necrosis in 27% and recurrence in 73% of cases. Thirteen patients required a reoperation for uncontrolled symptoms. Among them, 1 patient (8%) had pathology showing RT necrosis, and 12 (92%) had tumor recurrence. Median survival after reoperation was longer for patients with RT necrosis (21.8 months vs. 7.0 months, p = 0.047). In 7 patients with Grade 4 tumors treated with temozolomide-based chemoradiation with RT necrosis, median survival from diagnosis and reoperation were 30.2 months and 21.8 months, respectively. Conclusions: Patients with RT necrosis at reoperation have improved survival compared with patients with tumor recurrence. Future efforts to intensify local therapy and increase local tumor control in patients with high-grade glioma seem warranted.

  12. Clinical investigation survival prediction in high-grade gliomas by MRI perfusion before and during early stage of RT

    SciTech Connect

    Cao Yue . E-mail: yuecao@med.umich.edu; Tsien, Christina I.; Nagesh, Vijaya; Junck, Larry; Haken, Randall ten; Ross, Brian D.; Chenevert, Thomas L.; Lawrence, Theodore S.

    2006-03-01

    Purpose: To determine whether cerebral blood volume (CBV) and cerebral blood flow can predict the response of high-grade gliomas to radiotherapy (RT) by taking into account spatial heterogeneity and temporal changes in perfusion. Methods and Materials: Twenty-three patients with high-grade gliomas underwent conformal RT, with magnetic resonance imaging perfusion before and at Weeks 1-2 and 3-4 during RT. Tumor perfusion was classified as high, medium, or low. The prognostic values of pre-RT perfusion and the changes during RT for early prediction of tumor response to RT were evaluated. Results: The fractional high-CBV tumor volume before RT and the fluid-attenuated inversion recovery imaging tumor volume were identified as predictors for survival (p = 0.01). Changes in tumor CBV during the early treatment course also predicted for survival. Better survival was predicted by a decrease in the fractional low-CBV tumor volume at Week 1 of RT vs. before RT, a decrease in the fractional high-CBV tumor volume at Week 3 vs. Week 1 of RT, and a smaller pre-RT fluid-attenuated inversion recovery imaging tumor volume (p = 0.01). Conclusion: Early temporal changes during RT in heterogeneous regions of high and low perfusion in gliomas might predict for different physiologic responses to RT. This might also open the opportunity to identify tumor subvolumes that are radioresistant and might benefit from intensified RT.

  13. Amplification of papillomaviral DNA sequences from a high proportion of feline cutaneous in situ and invasive squamous cell carcinomas using a nested polymerase chain reaction.

    PubMed

    Munday, John S; Kiupel, Matti; French, Adrienne F; Howe, Laryssa

    2008-10-01

    Squamous cell carcinomas (SCCs) are common skin tumours of cats. Previous studies have suggested that papillomaviral (PV) DNA is detectible within some feline SCCs. A PV DNA sequence has been previously amplified from five feline bowenoid in situ carcinomas (BISCs). Primers specific for this sequence were used in a nested polymerase chain reaction to compare PV detection rates in SCCs to rates within non-SCC skin lesions. Papillomaviral DNA was amplified from 20 of 20 BISC, 17 of 20 invasive SCC and 3 of 17 non-SCC controls. The rate of PV amplification from feline cutaneous SCCs was significantly higher than from non-SCC lesions. These results confirm that feline cutaneous SCCs are associated with PV infection. In humans, there is evidence that PVs promote SCC development within sun-exposed skin. The demonstrated association between PVs and feline cutaneous SCCs suggests, but does not prove, that PVs may also promote feline SCC development. If PVs are oncogenic in cats, prevention of PV infection may reduce feline cutaneous SCC development. To the authors' knowledge, this is the first time that PV DNA has been amplified from a non-SCC sample of feline skin.

  14. Phase I Clinical Trial Assessing Temozolomide and Tamoxifen With Concomitant Radiotherapy for Treatment of High-Grade Glioma

    SciTech Connect

    Patel, Shilpen; DiBiase, Steven; Meisenberg, Barry; Flannery, Todd; Patel, Ashish; Dhople, Anil; Cheston, Sally; Amin, Pradip

    2012-02-01

    Purpose: The new standard treatment of glioblastoma multiforme is concurrent radiotherapy (RT) and temozolomide. The proliferation of high-grade gliomas might be partly dependent on protein kinase C-mediated pathways. Tamoxifen has been shown in vitro to inhibit protein kinase C through estrogen receptor-independent antineoplastic effects. This Phase I trial was designed to determine the maximal tolerated dose (MTD) of tamoxifen when given with temozolomide and concurrent RT to patients with high-grade gliomas. Methods and Materials: A total of 17 consecutive patients in four cohorts with World Health Organization Grade 3 (n = 2) and 4 (n = 15) gliomas were given tamoxifen twice daily during 6 weeks of concurrent RT and temozolomide. Eligibility included histologic diagnosis, age >18 years old, Karnofsky performance status {>=}60, and no previous brain RT or chemotherapy. The starting dose was 50 mg/m{sup 2} divided twice daily. If no dose-limiting toxicities (DLTs) occurred in 3 patients, the dose was escalated in 25-mg/m{sup 2} increments until the MTD was reached. When {>=}2 patients within a cohort experienced a DLT, the MTD had been exceeded. Temozolomide was given with RT at 75 mg/m{sup 2}. A dose of 60 Gy in 2 Gy/d fractions to a partial brain field was delivered. Results: A total of 6 patients in Cohort 4 had received tamoxifen at 125 mg/m{sup 2}. One patient was excluded, and the fourth patient developed Grade 4 thrombocytopenia (DLT). Thus, 3 more patients needed to be enrolled. A deep venous thrombosis (DLT) occurred in the sixth patient. Thus, the MTD was 100 mg/m{sup 2}. Conclusions: The MTD of tamoxifen was 100 mg/m{sup 2} when given concurrently with temozolomide 75 mg/m{sup 2} and RT. Tamoxifen might have a role in the initial treatment of high-grade gliomas and should be studied in future Phase II trials building on the newly established platform of concurrent chemoradiotherapy.

  15. The Effects of Grade Level and Other Factors on the Achievement in Project Physics among High School Physics Students.

    ERIC Educational Resources Information Center

    Fletcher, Richard Kenard, Jr.

    This study was designed to determine experimentally the relationship between achievement and grade level for 64 tenth-grade students, 48 eleventh-grade students, and 95 twelfth-grade physics students. All students were enrolled in the Project Physics course in their respective schools. The Physics Achievement Test (PAT) and the algebra I and II…

  16. Technology as a Tool for Understanding: a Pipeline of Curriculum-based Programs for Grades 4 to high school

    NASA Astrophysics Data System (ADS)

    Schuster, G.

    2006-05-01

    New NASA-funded educational initiatives make for a pipeline of products meeting the needs of today's educators in inner city schools, for NASA Explorer Schools and across the nation. Three projects include training and include: 1) WDLC [Weather Data Learning Center] , a math achievement program with data entry, inquiry-based investigations, and the application of math using weather maps and imagery for Grade 4; 2) Project 3D-VIEW, where students in Grades 5 and 6 become experts in air, life, water, land and Earth systems using 3D technologies requiring 3D glasses. A formal literacy and math piece are included, and 1200 teachers will be provided training and materials free beginning in Fall 2006, and 3) Signals of Spring, where students in Grades 7 to 8, or high school, use NASA data to explain the movement of dozens of birds, land and marine animals that are tracked by satellite. Comprehensive content in life and Earth science is taught with curricular activities, interactive mapping, image interpretation, and online journals and common misconceptions are dispelled. Scientist involvement and support for a project is essential for students who are developing process skills and performing science activities. Current research partners include Columbia University's Teachers College and Stanford University's School of Education.

  17. Subungual Squamous Cell Carcinoma: The Diagnostic Challenge and Clinical Pearls

    PubMed Central

    Kok, Wai Leong; Lee, Joyce Siong See; Chio, Martin Tze-wei

    2016-01-01

    Subungual squamous cell carcinoma is a rare entity and difficult to diagnose as its clinical presentation may resemble benign conditions. This case report highlights the need to maintain a high clinical index of suspicion, and recommends a practical approach for subungual conditions. Dermoscopy and a biopsy for histology are important adjuncts to clinch the diagnosis. PMID:27920677

  18. Prognostic impact of HER3 based on protein and mRNA expression in high-grade serous ovarian carcinoma.

    PubMed

    Unger, Ulrike; Denkert, Carsten; Braicu, Ioana; Sehouli, Jalid; Dietel, Manfred; Loibl, Sibylle; Darb-Esfahani, Silvia

    2017-02-01

    HER3 is a member of the epidermal growth factor family and was predominantly described as a negative prognostic factor in various solid tumors as well as in ovarian cancer. In this study, we investigated HER3 on protein and mRNA expression in histologically defined subtypes of ovarian cancer looking for an influence on patient's survival. Altogether, we examined HER3 in ovarian high-grade serous (HGSC, n = 320), low-grade serous (LGSC, n = 55), endometrioid (EC, n = 33), and clear cell (CCC, n = 48) carcinomas using immunohistochemistry (IHC) and quantitative real-time reverse transcription PCR (qRT-PCR). Univariate and multivariate analyses were performed to explore the association between HER3 and overall survival (OS) as well as progression-free survival (PFS). In HGSC, high HER3 mRNA expression was a favorable prognostic factor for PFS (P = 0.008) and OS (P = 0.052), while for high HER3 protein expression, a trend towards better survival was seen (OS P = 0.064; PFS P = 0.099). A subgroup of HGSC with negative HER3 staining and negative HER3 mRNA levels showed most unfavorable OS and PFS (P = 0.002 and P = 0.004, respectively). Using the multivariate Cox regression model, HER3 was predictive for prolonged PFS (HR, 0.48; 95% CI, 0.26-0.88; P = 0.018). All in all, we cannot confirm the reported negative prognostic impact of HER3 expression in high-grade serous ovarian carcinoma and moreover find a rather positive prognostic implication of HER3 in this major ovarian cancer histological subtype.

  19. Inferring protoliths of high-grade metamorphic gneisses of the Erzgebirge using zirconology, geochemistry and comparison with lower-grade rocks from Lusatia (Saxothuringia, Germany)

    NASA Astrophysics Data System (ADS)

    Tichomirowa, Marion; Sergeev, Sergey; Berger, Hans-Jürgen; Leonhardt, Dietmar

    2012-09-01

    Protoliths of highly metamorphosed gneisses from the Erzgebirge are deduced from the morphology, age and chemistry of zircons as well as from whole rock geochemistry and are compared with lower-grade rocks of Lusatia. Gneisses with similar structural appearance and/or geochemical pattern may have quite different protoliths. The oldest rocks in the Erzgebirge are paragneisses representing meta-greywackes and meta-conglomerates. The youngest group of zircon of meta-greywackes that did not undergo Pb loss represents the youngest igneous component for source rocks (about 575 Ma). Similar ages and zircon morphology reflect the subordinate formation of new zircon grains or only zircon rims in the augengneiss from Bärenstein and Wolkenstein, which probably represent metamorphic equivalents to Lower Cambrian two-mica granodiorites from Lusatia. Bulk rock chemistry, intense fracturing and high U and Th concentrations of zircons suggest deformation-induced and fluid-enhanced recrystallisation of zircon grains. Temperatures during tectonic overprinting—too low to reset zircon ages—indicate mid- or upper crustal levels for shearing recorded in these augengneisses. Lower Cambrian (~540 Ma) granodiorites are widespread in Lusatia but are exclusively represented by the Freiberg gneiss dome in the Eastern Erzgebirge. Ordovician protolith ages were recorded by zircons from the augengneisses of the Reitzenhain-Catherine dome and the Schwarzenberg dome (Western Erzgebirge) documenting significant regional differences between the eastern and the western Erzgebirge (~540 vs. ~490 Ma). In the Western Erzgebirge, most meta-volcanic rocks (muscovite gneisses) and meta-granites (mainly red augengneisses) yield Ordovician zircon ages, whereas in the Eastern part, similar rocks mainly recorded Lower Cambrian protolith ages. Zircon overprinting was highest within discrete tectonic zones where the combination of fluid infiltration and deformation induced variable degrees