Science.gov

Sample records for age tumor site

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

    PubMed Central

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

    2011-01-01

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

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

    PubMed

    Yoshimasu, Kouichi; Tanaka, Kazuhiro; Kiyohara, Chikako

    2005-06-01

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

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

    PubMed

    Kodama, M; Kodama, T; Murakami, M

    2000-01-01

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

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

    SciTech Connect

    Rockwell, S.

    1981-02-01

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

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

    PubMed

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

    1990-01-01

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

  6. Cervical lymph node metastases from remote primary tumor sites

    PubMed Central

    López, Fernando; Rodrigo, Juan P.; Silver, Carl E.; Haigentz, Missak; Bishop, Justin A.; Strojan, Primož; Hartl, Dana M.; Bradley, Patrick J.; Mendenhall, William M.; Suárez, Carlos; Takes, Robert P.; Hamoir, Marc; Robbins, K. Thomas; Shaha, Ashok R.; Werner, Jochen A.; Rinaldo, Alessandra; Ferlito, Alfio

    2016-01-01

    Although most malignant lymphadenopathy in the neck represent lymphomas or metastases from head and neck primary tumors, occasionally, metastatic disease from remote, usually infraclavicular, sites presents as cervical lymphadenopathy with or without an obvious primary tumor. In general, these tumors metastasize to supraclavicular lymph nodes, but occasionally may present at an isolated higher neck level. A search for the primary tumor includes information gained by histology, immunohistochemistry, and evaluation of molecular markers that may be unique to the primary tumor site. In addition, 18F-fluoro-2-deoxyglocose positron emission tomography combined with CT (FDG-PET/CT) has greatly improved the ability to detect the location of an unknown primary tumor, particularly when in a remote location. Although cervical metastatic disease from a remote primary site is often incurable, there are situations in which meaningful survival can be achieved with appropriate local treatment. Management is quite complex and requires a truly multidisciplinary approach. PMID:26713674

  7. Cervical lymph node metastases from remote primary tumor sites.

    PubMed

    López, Fernando; Rodrigo, Juan P; Silver, Carl E; Haigentz, Missak; Bishop, Justin A; Strojan, Primož; Hartl, Dana M; Bradley, Patrick J; Mendenhall, William M; Suárez, Carlos; Takes, Robert P; Hamoir, Marc; Robbins, K Thomas; Shaha, Ashok R; Werner, Jochen A; Rinaldo, Alessandra; Ferlito, Alfio

    2016-04-01

    Although most malignant lymphadenopathy in the neck represent lymphomas or metastases from head and neck primary tumors, occasionally, metastatic disease from remote, usually infraclavicular, sites presents as cervical lymphadenopathy with or without an obvious primary tumor. In general, these tumors metastasize to supraclavicular lymph nodes, but occasionally may present at an isolated higher neck level. A search for the primary tumor includes information gained by histology, immunohistochemistry, and evaluation of molecular markers that may be unique to the primary tumor site. In addition, 18F-fluoro-2-deoxyglocose positron emission tomography combined with CT (FDG-PET/CT) has greatly improved the ability to detect the location of an unknown primary tumor, particularly when in a remote location. Although cervical metastatic disease from a remote primary site is often incurable, there are situations in which meaningful survival can be achieved with appropriate local treatment. Management is quite complex and requires a truly multidisciplinary approach. © 2015 Wiley Periodicals, Inc. Head Neck 38: E2374-E2385, 2016. PMID:26713674

  8. Age incidence and site distribution of mammary dysplasias in young beagle bitches.

    PubMed

    Warner, M R

    1976-07-01

    The age incidence and site distribution of 2,142 mammary dysplasias were documented for 39 beagle bitches 6 months to 4 years of age. Lesion onset was at 2-3 years of age, at which time more than 50% of the females had dysplasias. Dysplasias appeared before palpable tumors. Posterior mammae developed more lesions than did anterior mammae. Thus the gradient for early onset of lesions coincided with the gradient for tumor frequency reported previously; a preneoplastic potential is suggested for (some) dysplasias. Problems of defining normal tissue are discussed. PMID:1034018

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

    PubMed Central

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

    2015-01-01

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

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

    SciTech Connect

    Campisi, Judith

    2004-08-15

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

  11. Impact of Treatment Site in Adolescents and Young Adults With Central Nervous System Tumors

    PubMed Central

    Wolfson, Julie; Sun, Can-Lan; Kang, Tongjun; Wyatt, Laura; D’Appuzzo, Massimo

    2014-01-01

    Background Adolescents and young adults (AYAs; aged 15–39 years) have inferior survival in comparison with younger (aged 0–14 years) cancer patients. Impact of care at specialized centers such as National Cancer Institute–designated Comprehensive Cancer Centers (NCICCC) for AYAs of all ages or the Children’s Oncology Group (COG) for AYAs aged 15 to 21 years with central nervous system (CNS) tumors remains unstudied. Methods We constructed a cohort of 560 children and 784 AYAs with CNS tumors reported to the Los Angeles cancer registry from 1998 to 2008. Cox and logistic regression models were used, with two-sided P values from Wald χ2 tests. Results In Cox regression analysis restricted to World Health Organization (WHO) grade II tumors, patients of all ages saw worse outcome if not treated at NCICCC/COG sites (non-NCICCC/COG vs NCICCC/COG: hazard ratio [HR] =1.73; 95% confidence interval [CI] = 1.09 to 2.72). Furthermore, the worse outcome for AYAs compared with children (HR = 1.90; 95% CI = 1.21 to 2.98; P = .005) was abrogated (HR = 1.35; 95% CI = 0.79 to 2.29; P = .27) by care at NCICCC/COGs. Those less likely to receive care at NCICCC/COG sites included young AYAs (aged 15–21 years vs children: odds ratio [OR] = 0.23; 95% CI = 0.11 to 0.48; P < .001) and older AYAs (aged 22–39 years) with low socioeconomic status (OR = 0.39; 95% CI = 0.17 to 0.89; P = .02), public/no insurance (OR = 0.30; 95% CI = 0.12 to 0.71; P < .01), and distance to care greater than 5 miles (OR = 0.29; 95% CI = 0.15 to 0.57; P < .001). Conclusions Population-based data reveal that care at NCICCC/COG sites mitigates inferior outcome in AYAs with WHO grade II CNS tumors compared with children. Compared with children, AYAs are less likely to receive care at NCICCC/COGs. Insurance, socioeconomic status, and distance serve as barriers to care at NCICCCs for older AYAs. PMID:25178694

  12. Aging and auditory site of lesion.

    PubMed

    Otto, W C; McCandless, G A

    1982-01-01

    The purpose of this study was to examine and quantify the functional auditory problems of presbycusis through a battery of recently developed diagnostic tests and to evaluate the usefulness of these tests with an elderly population. Diagnostic measures used were impedence measures, speech discrimination tests, synthetic sentence identification, compressed speech, two measures of tone decay, the short increment sensitivity index, a digit span test, and auditory brain stem response audiometry. Significant differences were found between scores for elderly subjects and those of young subjects who had similar audiograms. Use of the Metz test as an objective measure of recruitment yielded results suggesting a higher incidence of recruitment than evidenced by previous studies using loudness balancing procedures. The Olsen-Noffsinger procedure of quantifying tone decay revealed a greater difference between age groups than did the Suprathreshold Adaptation Test. Synthetic sentence identification revealed the most consistent age effect among the tests of central auditory function. Auditory brain stem response audiometry revealed several examples of abnormally long interpeak latencies. It is concluded that there is both behavioral and electrophysiological evidence of central and peripheral auditory disorder frequently accompanying senescence. PMID:7095318

  13. Placental site trophoblastic tumor: A case report and literature review

    PubMed Central

    Zeng, Xianling; Liu, Xi; Tian, Quan; Xue, Yan; An, Ruifang

    2015-01-01

    Summary Here, we report a case of a placental site trophoblastic tumor (PSTT) in a 36-year-old Chinese woman 10 months after a normal pregnancy. Two months postpartum, the woman presented with abnormal vaginal discharge and her condition was overlooked by her local hospital. The woman did not receive further attention until a mass with a heterogeneous echo was found in an ultrasound examination eight months postpartum. The final diagnosis was confirmed by histological examinations in conjunction with immunohistochemical studies. Since the patient had potential risk factors, she was successfully treated with a hysterectomy and peri- and post-operative chemotherapy. The latest follow-up (16 months after diagnosis) was uneventful, and the patient exhibited no signs of recurrence or metastasis. PMID:26361566

  14. Clinical, Biologic, and Prognostic Differences on the Basis of Primary Tumor Site in Neuroblastoma: A Report From the International Neuroblastoma Risk Group Project

    PubMed Central

    Vo, Kieuhoa T.; Matthay, Katherine K.; Neuhaus, John; London, Wendy B.; Hero, Barbara; Ambros, Peter F.; Nakagawara, Akira; Miniati, Doug; Wheeler, Kate; Pearson, Andrew D.J.; Cohn, Susan L.; DuBois, Steven G.

    2014-01-01

    Purpose Neuroblastoma (NB) is a heterogeneous tumor arising from sympathetic tissues. The impact of primary tumor site in influencing the heterogeneity of NB remains unclear. Patients and Methods Children younger than age 21 years diagnosed with NB or ganglioneuroblastoma between 1990 and 2002 and with known primary site were identified from the International Neuroblastoma Risk Group database. Data were compared between sites with respect to clinical and biologic features, as well as event-free survival (EFS) and overall survival (OS). Results Among 8,369 children, 47% had adrenal tumors. All evaluated clinical and biologic variables differed statistically between primary sites. The features that were > 10% discrepant between sites were stage 4 disease, MYCN amplification, elevated ferritin, elevated lactate dehydrogenase, and segmental chromosomal aberrations, all of which were more frequent in adrenal versus nonadrenal tumors (P < .001). Adrenal tumors were more likely than nonadrenal tumors (adjusted odds ratio, 2.09; 95% CI, 1.67 to 2.63; P < .001) and thoracic tumors were less likely than nonthoracic tumors (adjusted odds ratio, 0.20; 95% CI, 0.11 to 0.39; P < .001) to have MYCN amplification after controlling for age, stage, and histologic grade. EFS and OS differed significantly according to the primary site (P < .001 for both comparisons). After controlling for age, MYCN status, and stage, patients with adrenal tumors had higher risk for events (hazard ratio, 1.13 compared with nonadrenal tumors; 95% CI, 1.03 to 1.23; P = .008), and patients with thoracic tumors had lower risk for events (HR, 0.79 compared with nonthoracic; 95% CI, 0.67 to 0.92; P = .003). Conclusion Clinical and biologic features show important differences by NB primary site, with adrenal and thoracic sites associated with inferior and superior survival, respectively. Future studies will need to investigate the biologic origin of these differences. PMID:25154816

  15. Interest of somatostatin receptors scintigraphy for imaging differentiated thyroid carcinoma tumor sites

    SciTech Connect

    Giammarile, F.; Lumbroso, J.; Schlumberger, M.

    1995-05-01

    Despite the fact that differentiated thyroid carcinoma (DTC) is not classified as a neuroendocrine tumor, there is an increasing interest for the use of somatostatin receptors scintigraphy (SRS) in this disease. We evaluated SRS in DTC patients having no or a poor radioiodine uptake at the level of their tumor sites. Nine patients (pts) (7 men, 2 women; aged from 52 to 65 years) were previously treated (surgery of the primary: 9/9pts; followed by cervical radiotherapy: 4/9pts; radioiodine therapy: 8/9pts; surgery or radiotherapy to bone metastases: 2/9 pts) for DTC (papillary form: 6 pts; follicular; 1 pts; insular: 2 pts). They were explored by conventional imaging modalities (CIM) including Tc-99m MDP bone scans. High activity radioiodine scans were obtained 5 days after I-131 therapy. SRS was carried out during thyroxine therapy using Indium-111 pentetreotide (120 MBq) with imaging at 4 and 24 hours after injection (whole body scans and, when necessary, SPECT). Thyroglobulin blood level ranged from 120 to 60,000ng/ml. SRS was positive at the level of all tumor sites in 8/9 pts; radioiodine scans were negative in 4 pts (1pt with an insular DTC, 3 pt with a papillary DTC), slightly positive in 2 pts (papillary DTC), positive only on part of tumor sites in 1 pts (insular DTC), positive in 1 pt (follicular DTC) and not done in 1 pt. SRS demonstrated 3 new tumor sites (1 to bone, 1 to lung and 1 to mediastinal lymph nodes) in 2 pts; in an other pt, SRS clarified out a doubtful Tc-99m bone scan result and led to definitive confirmation of bone metastases. We had only 1 false negative result in 1 pt having pulmonary metastases (slightly positive radioiodine scan) which had been stable in size on CT for 6 years. These results indicate that, when radioiodine scans are ineffective, SRS is a powerful modality for imaging DTC tumor sites.

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

    PubMed Central

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

    2015-01-01

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

  17. SALL4 expression in gestational trophoblastic tumors: a useful tool to distinguish choriocarcinoma from placental site trophoblastic tumor and epithelioid trophoblastic tumor.

    PubMed

    Stichelbout, Morgane; Devisme, Louise; Franquet-Ansart, Hélène; Massardier, Jérôme; Vinatier, Denis; Renaud, Florence; Kerdraon, Olivier

    2016-08-01

    SALL4 has important functions in embryonic stem cells. The aim of this study was to investigate SALL4 expression in gestational trophoblastic neoplasia. We hypothesized that it could help to distinguish choriocarcinoma, the presumed most primitive form of gestational trophoblastic neoplasia, from placental site trophoblastic tumor and epithelioid trophoblastic tumor, which would be more differentiated variants. This study included 31 gestational trophoblastic neoplasias: 19 choriocarcinomas, 9 placental site trophoblastic tumors, 1 epithelioid trophoblastic tumor, and 2 mixed tumors comprising a placental site trophoblastic tumor and an epithelioid trophoblastic tumor. Unlike usual markers of gestational trophoblastic neoplasia (p63, human chorionic gonadotrophin and human placental lactogen), SALL4 was expressed in 100% of choriocarcinomas and it was not detected in any placental site trophoblastic tumor and epithelioid trophoblastic tumor. However, the proportion of positive cells varied in a wide range, from 10% to 70%, reflecting the fact that SALL4 was specifically present in mononuclear cells consistent with neoplastic cytotrophoblast. So, SALL4 may be helpful in the differential diagnosis of gestational trophoblastic neoplasias. PMID:27068524

  18. Single synchronous pulmonary metastasis from placental site trophoblastic tumor and teratoma.

    PubMed

    Billè, Andrea; Girelli, Lara; Colecchia, Maurizio; Pastorino, Ugo

    2015-01-01

    Placental site trophoblastic tumor (PSTT) is a rare variant of gestational trophoblastic tumor (GTN), accounting for 1-2% of all GTNs. Primary testicular PSTTs are extremely rare. Thirty percent of patients with PSTT show multiple lung and brain metastases at the time of diagnosis. We present the first case of a synchronous single pulmonary trophoblastic placental tumor metastasis together with a teratoma and a mixed germinal tumor of the testis, treated with minimally invasive lung metastasectomy. PMID:25908040

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

    PubMed

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

    2016-09-01

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

  20. Extradigital Glomus Tumor-a Rare Cause for Undiagnosed Chronic Pain in Unusal Sites.

    PubMed

    Venugopal, P R

    2015-12-01

    Glomus tumor is a benign vascular tumor derived from the modified smooth muscle cells of the glomus body. The single most common site is the subungual region of the finger, but other common sites include the palm, wrist, forearm, and foot. In this article, we present a rare situation of glomus tumor occurring on the back of the chest over the scapular area in an elderly male patient. The tumor cells exhibited positive expression for CD34 and smooth muscle actin. This paper highlights the fact that a glomus tumor is a benign neoplasm that may occur in multiple locations. Therefore, the significance of a histological and immunohistochemical approach for a correct characterization of this lesion is required. PMID:27011481

  1. Granular cell tumor in two oral anatomic sites.

    PubMed

    Serpa, Marianna Sampaio; Costa-Neto, Hugo; de Oliveira, Patrícia Teixeira; da Silveira, Éricka Janine Dantas; de Medeiros, Ana Miryam Costa

    2016-10-01

    Granular cell tumor (GCT) is an uncommon benign soft tissue neoplasm, which usually presents as a solitary nodule, appearing especially in the tongue. There are few cases of multiple oral GCT in the English-language literature, with only three cases reported in the last 20 years. This report describes a case of two oral GCT in a young patient and provides a literature review from 1995 to 2015. Clinical characteristics of the reviewed cases were retrieved and compared with the present case. Exceptionally, the current case was the only one that occurred in an adolescent and solely affected the oral cavity. Besides the oral cavity, the other cases also observed GCT lesions in the skin. Although rare, it is important to know multiple oral GCT clinical and histopathological characteristics so they can be correctly diagnosed, treated and followed up. PMID:27007285

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

    PubMed

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

    2015-03-01

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

  3. Variation in Insurance Status by Patient Demographics and Tumor Site Among Nonelderly Adult Patients With Cancer

    PubMed Central

    Grant, Stephen R.; Walker, Gary V.; Guadagnolo, B. Ashleigh; Koshy, Matthew; Allen, Pamela K.; Mahmood, Usama

    2016-01-01

    BACKGROUND In the United States, an estimated 48 million individuals live without health insurance. The purpose of the current study was to explore the variation in insurance status by patient demographics and tumor site among nonelderly adult patients with cancer. METHODS A total of 688,794 patients aged 18 to 64 years who were diagnosed with one of the top 25 incident cancers (representing 95% of all cancer diagnoses) between 2007 and 2010 in the Surveillance, Epidemiology, and End Results (SEER) database were analyzed. Patient characteristics included age, race, sex, marital status, and rural or urban residence. County-level demographics included percent poverty level. Insurance status was defined as having non-Medicaid insurance, Medicaid coverage, or no insurance. RESULTS On multivariate logistic regression analyses, younger age, male sex, nonwhite race, being unmarried, residence in counties with higher levels of poverty, and rural residence were associated with being uninsured versus having non-Medicaid insurance (all P <.001). The highest rates of non-Medicaid insurance were noted among patients with prostate cancer (92.3%), melanoma of the skin (92.5%), and thyroid cancer (89.5%), whereas the lowest rates of non-Medicaid insurance were observed among patients with cervical cancer (64.2%), liver cancer (67.9%), and stomach cancer (70.9%) (P <.001). Among uninsured individuals, the most prevalent cancers were lung cancer (14.9%), colorectal cancer (12.1%), and breast cancer (10.2%) (P <.001). Lung cancer caused the majority of cancer mortality in all insurance groups. CONCLUSIONS Rates of insurance coverage vary greatly by demographics and by cancer type. The expansion of health insurance coverage would be expected to disproportionally benefit certain demographic populations and cancer types. PMID:25917222

  4. Site-Specific Epithelial-Mesenchymal Interactions in Digestive Neuroendocrine Tumors

    PubMed Central

    Dumortier, Jérôme; Ratineau, Christelle; Scoazec, Jean-Yves; Pourreyron, Céline; Anderson, Wena; Jacquier, Marie-France; Blanc, Martine; Bernard, Christine; Bellaton, Claire; Remy, Lionel; Chayvialle, Jean-Alain; Roche, Colette

    2000-01-01

    Little is known about the functional interactions between digestive neuroendocrine tumor cells and their stromal microenvironment. The focus of our study is whether mesenchymal cells modulate peptide expression, cell proliferation, and invasiveness in digestive neuroendocrine tumor cells. We designed an experimental in vivo and in vitro study using the mouse enteroendocrine cell line STC-1. In vivo, STC-1 cells were injected subcutaneously in 18 immunosuppressed newborn rats. At day 21, all animals presented poorly differentiated neuroendocrine tumors with lung metastases. Subcutaneous tumors were usually limited by a capsule containing basement membrane components and myofibroblasts that presented a low mitotic index. Lung tumors were devoid of capsule and poor in myofibroblasts, and their mitotic index was high. The profile of peptide expression in STC-1 tumors was different from that of cultured STC-1 cells. In vitro, STC-1 cells were cultured with fibroblasts of different origins, including dermis, lung, digestive tract, and liver. Based on their origin, myofibroblasts differentially modulated hormone synthesis, proliferation, spreading, and adhesion of STC-1 cells. In conclusion, our results show that site-specific functional interactions between mesenchymal and neuroendocrine cells may contribute to modulating the behavior of digestive neuroendocrine tumors, depending on their growth site. PMID:10666396

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

    PubMed Central

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

    2015-01-01

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

  6. Ovarian cancer survival by tumor dominance, a surrogate for site of origin

    PubMed Central

    Ivanova, Anna; Loo, Anneli; Tworoger, Shelley; Crum, Christopher P.; Fan, Isabel; McLaughlin, John R.; Rosen, Barry; Risch, Harvey; Narod, Steven A.; Kotsopoulos, Joanne

    2015-01-01

    Objectives Recent studies suggest that a proportion of ovarian tumors may actually originate in the distal fallopian tube. The objective of this study was to examine the relationship between dominance (a surrogate for site of origin) and survival following a diagnosis of epithelial ovarian cancer. Methods We classified 1,386 tumors as dominant (putatively originating in the ovary and non-dominant (putatively originating in the fallopian tube), using parameters obtained from pathology reports. Dominant tumors were restricted to one ovary or one involved ovary that exceeded the other in dimension by at least two-fold, while non-dominant tumors were identified as having a greater likelihood of a tubal origin if the disease was equally distributed across the ovaries. Cox proportional hazards models were used to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs) associated with dominance. Results Non-dominant tumors were more likely to be serous, stage III/IV, and be associated with a BRCA1/2 mutation, increasing parity and use of estrogen hormone replacement therapy (P ≤ 0.01). In contrast, 46% and 26% of the dominant tumors were serous and endometrioid, respectively, with a more even distribution of stage (P < 0.0001). Women with a non-dominant tumor had an increased risk of death compared to women with a dominant tumor (multivariate HR = 1.28; 95%CI 1.02–1.60). Findings were similar in our analysis restricted to serous only subtypes (HR = 1.28; 95%CI 1.01–1.63). Conclusion These preliminary findings suggest significantly worse survival among women diagnosed with a tumor putatively arising from fallopian tube. PMID:25771796

  7. The Tumor-Promoting Flow of Cells Into, Within and Out of the Tumor Site: Regulation by the Inflammatory Axis of TNFα and Chemokines.

    PubMed

    Ben-Baruch, Adit

    2012-08-01

    Tumors are dynamic organs, in which active processes of cell motility affect disease course by regulating the composition of cells at the tumor site. While sub-populations of tumor-promoting leukocytes are recruited inward and endothelial cell migration stands in the basis of vascular branching throughout the tumor, cancer cells make their way out of the primary site towards specific metastatic sites. This review describes the independent and cross-regulatory roles of inflammatory chemokines and of the inflammatory cytokine tumor necrosis factor α (TNFα) in determining cell motility processes that eventually have profound effects on tumor growth and metastasis. First, the effects of inflammatory chemokines such as CCL2 (MCP-1), CCL5 (RANTES) and CXCL8 (IL-8) are described, regulating the inward flow of leukocyte sub-populations with pro-tumoral activities, such as tumor-associated macrophages (TAM), myeloid-derived suppressor cells (MDSC), tumor-associated neutrophils (TAN), Th17 cells and Tregs. Then, the ability of inflammatory chemokines to induce endothelial cell migration, sprouting and tube formation is discussed, with its implications on tumor angiogenesis. This part is followed by an in depth description of the manners by which TNFα potentiates the above activities of the inflammatory chemokines, alongside with its ability to directly induce migratory processes in the tumor cells thus promoting metastasis. Note worthy is the ability of TNFα to induce in the tumor cells the important process of epithelial-to-mesenchymal transition (EMT). Emphasis is given to the ability of TNFα to establish an inflammatory network with the chemokines, and in parallel to form a cell re-modeling network together with transforming growth factor β (TGFβ). The review concludes by discussing the implications of such networks on disease course, and on the future design of therapeutic measures in cancer. PMID:22190050

  8. Ganglioglioma arising from olfactory sheath: A rare site of an uncommon tumor.

    PubMed

    Singla, Navneet; Gupta, Kirti; Kapoor, Ankur

    2016-06-01

    Gangliogliomas are rare slow growing tumors with a mixed population of dysplastic ganglion cells and glial components, reported at variable sites within the central nervous system, including the frontal, parietal and occipital lobes, the striatum, cerebellum, pituitary and pineal glands as well as the spinal cord. Rarely gangliogliomas have been reported arising within the cranial nerves, including the optic and trigeminal nerve. We present the first patient, to our knowledge, where such a tumor originated from the olfactory sheath. Migration defects leading to entrapment of sensory neurons during development is believed to be responsible for the pathogenesis of these lesions. The extent of surgical extirpation and histopathological anaplasia are important prognosticators. While gangliogliomas are rare tumors, it is crucial to consider them in the differential diagnosis of non-enhancing, poorly localized lesions along the cranial nerves. PMID:26874814

  9. Inhibition by alcohols of the localization of radioactive nitrosonornicotine in sites of tumor formation

    SciTech Connect

    Waddell, W.J.; Marlowe, C.

    1983-06-01

    Oral administration of ethanol, n-butanol, or t-butanol to mice 20 minutes before injection of carbon-14-labeled nitrosonornicotine inhibited the localization of radioactivity in bronchial and salivary duct epithelium and in the liver. Localization of radioactivity in the nasal epithelium and esophagus was not significantly reduced. These alcohols therefore may selectively inhibit tumor formation in three of the five sites where this carcinogen typically acts.

  10. Tumor Suppressor Activity of Profilin Requires a Functional Actin Binding Site

    PubMed Central

    Wittenmayer, Nina; Jandrig, Burkhard; Rothkegel, Martin; Schlüter, Kathrin; Arnold, Wolfgang; Haensch, Wolfgang; Scherneck, Siegfried; Jockusch, Brigitte M.

    2004-01-01

    Profilin 1 (PFN1) is a regulator of the microfilament system and is involved in various signaling pathways. It interacts with many cytoplasmic and nuclear ligands. The importance of PFN1 for human tissue differentiation has been demonstrated by the findings that human cancer cells, expressing conspicuously low PFN1 levels, adopt a nontumorigenic phenotype upon raising their PFN1 level. In the present study, we characterize the ligand binding site crucial for profilin's tumor suppressor activity. Starting with CAL51, a human breast cancer cell line highly tumorigenic in nude mice, we established stable clones that express PFN1 mutants differentially defective in ligand binding. Clones expressing PFN1 mutants with reduced binding to either poly-proline-stretch ligands or phosphatidyl-inositol-4,5-bisphosphate, but with a functional actin binding site, were normal in growth, adhesion, and anchorage dependence, with only a weak tendency to elicit tumors in nude mice, similar to controls expressing wild-type PFN1. In contrast, clones expressing a mutant with severely reduced capacity to bind actin still behaved like the parental CAL51 and were highly tumorigenic. We conclude that the actin binding site on profilin is instrumental for normal differentiation of human epithelia and the tumor suppressor function of PFN1. PMID:14767055

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

    PubMed Central

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

    2014-01-01

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

  12. Localized experimental bone metastasis drives osteolysis and sensory hypersensitivity at distant non-tumor-bearing sites.

    PubMed

    Abdelaziz, Dareen M; Stone, Laura S; Komarova, Svetlana V

    2015-08-01

    Patients with breast cancer metastasis to bone suffer from inadequate pain relief. Animal models provide increased understanding of cancer-induced bone and sensory alterations. The objective of this study was to investigate the measures of pain at distant non-tumor-bearing sites in animals with localized bone metastasis. Immunocompetent BALB/c mice are injected intra-tibially with murine mammary carcinoma cells (4T1) or saline, and the sensitivity to mechanical and thermal stimuli in the contralateral paw was examined. In addition to previously demonstrated development of osteolysis and hypersensitivity to mechanical and thermal stimuli in the cancer-injected tibia, these animals exhibited an increase in sensory hypersensitivity in the contralateral limb. No bone lesions were evident on radiographs of the contralateral limbs. Histomorphometry detected decreased bone volume per tissue volume and increased osteoclast number in the contralateral tibia and vertebral bones of cancer-bearing animals. Neuroplasticity was examined by immunofluorescence for calcitonin gene-related peptide (CGRP) in sensory neurons and glial fibrillary acidic protein (GFAP) in lumbar spinal cords. CGRP-immunoreactivity and GFAP-immunoreactivity were significantly elevated both ipsilateral and contralateral in tumor-bearing animals. The anti-inflammatory and osteolysis-targeting drug rapamycin reduced hypersensitivity to mechanical and cold stimuli, attenuated GFAP over-expression, and lowered osteoclast number. The osteoclast-targeting drug pamidronate reduced sensitivity to cold and protected against bone loss. Localized bone cancer drives hypersensitivity, bone remodeling, and sensory neuron plasticity at sites distant from the primary tumor area. Drugs targeting these mechanisms may be useful in the treatment of pain distant from the primary tumor site. PMID:26208488

  13. Bioremediation of Southern Mediterranean oil polluted sites comes of age.

    PubMed

    Daffonchio, Daniele; Ferrer, Manuel; Mapelli, Francesca; Cherif, Ameur; Lafraya, Alvaro; Malkawi, Hanan I; Yakimov, Michail M; Abdel-Fattah, Yasser R; Blaghen, Mohamed; Golyshin, Peter N; Kalogerakis, Nicolas; Boon, Nico; Magagnini, Mirko; Fava, Fabio

    2013-09-25

    Mediterranean Sea is facing a very high risk of oil pollution due to the high number of oil extractive and refining sites along the basin coasts, and the intense maritime traffic of oil tankers. All the Mediterranean countries have adopted severe regulations for minimizing pollution events and bioremediation feasibility studies for the most urgent polluted sites are undergoing. However, the analysis of the scientific studies applying modern 'meta-omics' technologies that have been performed on marine oil pollution worldwide showed that the Southern Mediterranean side has been neglected by the international research. Most of the studies in the Mediterranean Sea have been done in polluted sites of the Northern side of the basin. Those of the Southern side are poorly studied, despite many of the Southern countries being major oil producers and exporters. The recently EU-funded research project ULIXES has as a major objective to increase the knowledge of the bioremediation potential of sites from the Southern Mediterranean countries. ULIXES is targeting four major polluted sites on the coastlines of Egypt, Jordan, Morocco and Tunisia, including seashore sands, lagoons, and oil refinery polluted sediments. The research is designed to unravel, categorize, catalogue, exploit and manage the diversity and ecology of microorganisms thriving in these polluted sites. Isolation of novel hydrocarbon degrading microbes and a series of state of the art 'meta-omics' technologies are the baseline tools for improving our knowledge on biodegradation capacities mediated by microbes under different environmental settings and for designing novel site-tailored bioremediation approaches. A network of twelve European and Southern Mediterranean partners is cooperating for plugging the existing gap of knowledge for the development of novel bioremediation processes targeting such poorly investigated polluted sites. PMID:23727339

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

    PubMed

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

    2013-10-01

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

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

    PubMed

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

    2016-05-01

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

  16. Vaccine-induced tumor regression requires a dynamic cooperation between T cells and myeloid cells at the tumor site.

    PubMed

    Thoreau, Maxime; Penny, HweiXian Leong; Tan, KarWai; Regnier, Fabienne; Weiss, Julia Miriam; Lee, Bernett; Johannes, Ludger; Dransart, Estelle; Le Bon, Agnès; Abastado, Jean-Pierre; Tartour, Eric; Trautmann, Alain; Bercovici, Nadège

    2015-09-29

    Most cancer immunotherapies under present investigation are based on the belief that cytotoxic T cells are the most important anti-tumoral immune cells, whereas intra-tumoral macrophages would rather play a pro-tumoral role. We have challenged this antagonistic point of view and searched for collaborative contributions by tumor-infiltrating T cells and macrophages, reminiscent of those observed in anti-infectious responses. We demonstrate that, in a model of therapeutic vaccination, cooperation between myeloid cells and T cells is indeed required for tumor rejection. Vaccination elicited an early rise of CD11b+ myeloid cells that preceded and conditioned the intra-tumoral accumulation of CD8+ T cells. Conversely, CD8+ T cells and IFNγ production activated myeloid cells were required for tumor regression. A 4-fold reduction of CD8+ T cell infiltrate in CXCR3KO mice did not prevent tumor regression, whereas a reduction of tumor-infiltrating myeloid cells significantly interfered with vaccine efficiency. We show that macrophages from regressing tumors can kill tumor cells in two ways: phagocytosis and TNFα release. Altogether, our data suggest new strategies to improve the efficiency of cancer immunotherapies, by promoting intra-tumoral cooperation between macrophages and T cells. PMID:26337837

  17. Vaccine-induced tumor regression requires a dynamic cooperation between T cells and myeloid cells at the tumor site

    PubMed Central

    Thoreau, Maxime; Penny, HweiXian Leong; Tan, KarWai; Regnier, Fabienne; Weiss, Julia Miriam; Lee, Bernett; Johannes, Ludger; Dransart, Estelle; Le Bon, Agnès; Abastado, Jean-Pierre; Tartour, Eric

    2015-01-01

    Most cancer immunotherapies under present investigation are based on the belief that cytotoxic T cells are the most important anti-tumoral immune cells, whereas intra-tumoral macrophages would rather play a pro-tumoral role. We have challenged this antagonistic point of view and searched for collaborative contributions by tumor-infiltrating T cells and macrophages, reminiscent of those observed in anti-infectious responses. We demonstrate that, in a model of therapeutic vaccination, cooperation between myeloid cells and T cells is indeed required for tumor rejection. Vaccination elicited an early rise of CD11b+ myeloid cells that preceded and conditioned the intra-tumoral accumulation of CD8+ T cells. Conversely, CD8+ T cells and IFNγ production activated myeloid cells were required for tumor regression. A 4-fold reduction of CD8+ T cell infiltrate in CXCR3KO mice did not prevent tumor regression, whereas a reduction of tumor-infiltrating myeloid cells significantly interfered with vaccine efficiency. We show that macrophages from regressing tumors can kill tumor cells in two ways: phagocytosis and TNFα release. Altogether, our data suggest new strategies to improve the efficiency of cancer immunotherapies, by promoting intra-tumoral cooperation between macrophages and T cells. PMID:26337837

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

    PubMed

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

    2009-01-01

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

  19. Teacher Professionalization in the Age of Social Networking Sites

    ERIC Educational Resources Information Center

    Kimmons, Royce; Veletsianos, George

    2015-01-01

    As teacher education students become professionals, they face a number of tensions related to identity, social participation, and work-life balance, which may be further complicated by social networking sites (SNS). This qualitative study sought to articulate tensions that arose between professionalization influences and teacher education student…

  20. Tumor site prediction using spatiotemporal detection of subclinical hyperemia in experimental photocarcinogenesis

    NASA Astrophysics Data System (ADS)

    Konger, Raymond L.; Xu, Zhengbin; Sahu, Ravi P.; Kim, Young L.

    2014-03-01

    We demonstrate that a spatial and temporal analysis of subclinical hyperemia reliably predicts specific areas at high risk for skin tumor development during photocarcinogenesis. To determine detailed spatiotemporal patterns of inflammatory angiogenesis foci in a relatively large area, we developed a mesoscopic (between microscopic and macroscopic) imaging approach. This method relies on our earlier finding that the combination of a spectral analysis of hemoglobin with diffuse-light-suppressed imaging can increase the image resolution, contrast and penetration depth to visualize microvasculature Hgb content in the large tissue area. In our recent study, SKH1 hairless albino mice were irradiated for 10 weeks with a carcinogen dose of UVB. Using our newly developed mesoscopic imaging methods, we imaged the mice over 20 - 30 weeks after stopping UVB, and excised hyperemic/non-hyperemic areas at several different timepoints. We show that persistent hyperemic foci can predict future tumor formation. In particular, our imaging approach allows us to assess the spatial and temporal extent of subclinical inflammatory foci, which in turn can predict sites of future overlying tumor formation. In addition, although COX-2 inhibitors are known to suppress skin cancer development in humans, it remains unclear whether the chemopreventive activity of COX-2 inhibitors are chiefly attributable to their anti-inflammatory effects. Our study provides evidence that subclinical subepithelial inflammatory foci occur prior to overt tumor formation, and that these areas are highly predictive for future tumor formation, that celecoxib's ability to suppress tumorigenesis is tightly linked to its ability to reduce the area of subclinical inflammatory foci.

  1. The site of tumor development determines immunogenicity via temporal mobilization of antigen-laden dendritic cells in draining lymph nodes.

    PubMed

    Joncker, Nathalie T; Bettini, Sarah; Boulet, Delphine; Guiraud, Martine; Guerder, Sylvie

    2016-03-01

    The elimination of solid tumors largely depends on effective T-cell priming by dendritic cells (DCs). For decades, studies focusing on antitumoral immune responses have been performed with tumors transplanted subcutaneously (s.c.). These studies however do not take into account the heterogeneous tissue distribution and functionality of the different DC subsets. Given the crucial role of DCs in inducing protective immune response, we postulated that the anatomic location of tumor development may greatly impact tumor immunogenicity. We therefore implanted tumor cells either in the DC-rich dermis environment or in the s.c. tissue that mainly contains macrophages and monocytes. We showed that intradermal (i.d.), but not s.c. tumors are rapidly rejected in a T-cell-dependent manner and induce protective T-cell responses. The rejection of i.d. tumors correlates with rapid recruitment of dermal DCs presenting the tumor antigen to both CD4 and CD8 T cells in the draining lymph nodes (dLNs). The same DC subsets were mobilized upon s.c. tumor transplantation but with delayed kinetics. Altogether, our results show that the anatomical site of tumor development influences tumor immunogenicity, notably by controlling the kinetics of DC mobilization in the draining LNs. PMID:26626316

  2. Regulatory T cells prevent CD8 T cell maturation by inhibiting CD4 Th cells at tumor sites.

    PubMed

    Chaput, Nathalie; Darrasse-Jèze, Guillaume; Bergot, Anne-Sophie; Cordier, Corinne; Ngo-Abdalla, Stacie; Klatzmann, David; Azogui, Orly

    2007-10-15

    Natural regulatory T cells (Tregs) are present in high frequencies among tumor-infiltrating lymphocytes and in draining lymph nodes, supposedly facilitating tumor development. To investigate their role in controlling local immune responses, we analyzed intratumoral T cell accumulation and function in the presence or absence of Tregs. Tumors that grew in normal BALB/c mice injected with the 4T1 tumor cell line were highly infiltrated by Tregs, CD4 and CD8 cells, all having unique characteristics. Most infiltrating Tregs expressed low levels of CD25Rs and Foxp3. They did not proliferate even in the presence of IL-2 but maintained a strong suppressor activity. CD4 T cells were profoundly anergic and CD8 T cell proliferation and cytotoxicity were severely impaired. Depletion of Tregs modified the characteristics of tumor infiltrates. Tumors were initially invaded by activated CD4(+)CD25(-) T cells, which produced IL-2 and IFN-gamma. This was followed by the recruitment of highly cytotoxic CD8(+) T cells at tumor sites leading to tumor rejection. The beneficial effect of Treg depletion in tumor regression was abrogated when CD4 helper cells were also depleted. These findings indicate that the massive infiltration of tumors by Tregs prevents the development of a successful helper response. The Tregs in our model prevent Th cell activation and subsequent development of efficient CD8 T cell activity required for the control of tumor growth. PMID:17911581

  3. The Middle Stone Age of the northern Kenyan Rift: age and context of new archaeological sites from the Kapedo Tuffs.

    PubMed

    Tryon, Christian A; Roach, Neil T; Logan, M Amelia V

    2008-10-01

    Rift Valley sites in southern Ethiopia and northern Kenya preserve the oldest fossil remains attributed to Homo sapiens and the earliest archaeological sites attributed to the Middle Stone Age (MSA). New localities from the Kapedo Tuffs augment the sparse sample of MSA sites from the northern Kenya Rift. Tephrostratigraphic correlation with dated pyroclastic deposits from the adjacent volcano Silali suggests an age range of 135-123ka for archaeological sites of the Kapedo Tuffs. Comparisons of the Kapedo Tuffs archaeological assemblages with those from the adjacent Turkana and Baringo basins show broad lithic technological similarity but reveal that stone raw material availability is a key factor in explaining typologically defined archaeological variability within this region. Spatially and temporally resolved comparisons such as this provide the best means to link the biological and behavioral variation manifest in the record of early Homo sapiens. PMID:18672269

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

    PubMed Central

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

    2015-01-01

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

  5. Chondroblastoma of the Medial Malleolus: A Case Report of A Rare Tumor at an Extremely Uncommon Site

    PubMed Central

    Tiwari, Mukesh; Chaturvedi, Hemant; Patel, Vaibhav; Matti, Rajarshi

    2016-01-01

    Introduction: Tumors of the medial malleolus are rare. Chondrogenic tumors of the medial malleolus are extremely rare. Chondroblastoma of the medial malleolus has not been reported previously in the English literature. The purpose is to present a rare tumor occurring at an unusual site and its successful management. Case Presentation: We report a case of a 30 years old female with chondroblastoma of the medial malleolus with its clinical features, radiographic features, differential diagnosis, and management at an unusual site. Treatment comprised of an open biopsy followed by aggressive curettage, phenolization and bone cement. Symptoms resolved after treatment with resumption of normal activities and no signs of recurrence at 1 year follow-up. Conclusion: This case appears to be the first reported case of chondroblastoma occurring at medial malleolus. The present case report will increase the awareness of this rare tumor occurring at this unusual site thereby avoiding any chance of misdiagnosis. PMID:27299121

  6. H+ stoichiometry of sites 1 + 2 of the respiratory chain of normal and tumor mitochondria.

    PubMed

    Villalobo, A; Alexandre, A; Lehninger, A L

    1984-09-01

    The mechanistic stoichiometry for vectorial H+ ejection coupled to electron transport through energy-conserving segments 1 + 2 was determined on cyanide-inhibited mitochondria from rat liver, rat heart, and Ehrlich ascites tumor cells, and on rat liver mitoplasts with ferricyanide or ferricytochrome c as electron acceptors. K+ (+ valinomycin) and Ca2+ were employed as permeant cations. Three different methods were employed. In the first, known pulses of ferricyanide were added, and the total H+ ejected was determined with a glass electrode. Such measurements gave H+/2e-values exceeding 7.0 for both normal and tumor mitochondria with beta-hydroxybutyrate and other NAD-linked substrates; uptake of Ca2+ was also measured and gave the expected q+/2e-ratios. The second type of measurement was initiated by addition of ferricytochrome c to rat liver mitoplasts, with H+ ejection monitored with the glass electrode and ferricytochrome c reduction by dual-wavelength spectrophotometry; the H+/2e-ratios generally exceeded 7.0. In the third type of measurement, mixing and dilution artifacts were eliminated by oxidizing ferrocytochrome c in situ with a small amount of ferricyanide. H+/2e-ratios for rat liver mitoplasts oxidizing beta-hydroxybutyrate consistently approached or exceeded 7.5. Over 150 measurements made under a variety of conditions gave observed H+/2e-ejection ratios significantly exceeding 7.0, which correlated closely with H+/2e-measurements on sites 1 + 2 + 3, sites 2 + 3, and site 2. Factors leading to the deficit of the observed ratios from the integral value 8 for sites 1 + 2 were discussed. PMID:6091552

  7. Tumor

    MedlinePlus

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

  8. Ages of fossil bones from British interglacial sites

    USGS Publications Warehouse

    Szabo, B. J.; Collins, D.

    1975-01-01

    THE time gap between the upper limit of radiocarbon dating (???60,000 yr BP) and the lower limit of dates generally obtainable using the K-Ar method (???250,000 yr BP) accounts for the scarcity of dates for the last two interglaciations (the Ipswichian and Hoxnian of Britain; the Eemian and Holsteinian of northern Europe). Accordingly, the ages of such important fossils as the Swanscombe and Steinheim skulls can only be guessed at. For that reason, the adaptation of a method that may date these interglacial periods is highly desirable. We discuss here the application of a uranium-series dating technique pertaining to that span of time. ?? 1975 Nature Publishing Group.

  9. Small numbers of residual tumor cells at the site of primary inoculation are critical for anti-tumor immunity following challenge at a secondary location.

    PubMed

    Kakinuma, Takashi; Nadiminti, Hari; Lonsdorf, Anke S; Murakami, Takashi; Perez, Bradford A; Kobayashi, Hisataka; Finkelstein, Steven E; Pothiawala, Gulnar; Belkaid, Yasmine; Hwang, Sam T

    2007-07-01

    Luciferase-transduced B16 murine melanoma cells (luc-B16) inoculated in ear skin do not form tumors but prevent tumor formation by luc-B16 cells injected into the footpad. To determine the requirements for such immunity, we followed the fate of luc-B16 cells following ear injection. Surprisingly, small numbers of viable luc-B16 cells were detected in tumor-free mouse skin for up to 60 days post-inoculation. After 1 week, the number of Foxp3(+)CD4(+)CD25(+) T cells (along with foxp3 mRNA expression) increased rapidly in the injected ear skin. Residual tumor cells in ears were reduced in mice treated with anti-CD25 mAb and in CD4-deficient mice, but increased in CD8-deficient mice. Strikingly, the loss of luc-B16 cells in the ear skin, either spontaneously or following amputation of the injected ear, resulted in significantly enhanced tumor formation by parental and luciferase-expressing B16 cells after footpad injection. These studies suggest that small numbers of tumor cells (possibly regulated by CD4(+)CD25(+) regulatory T cells expressing Foxp3) are required for effective host anti-tumor responses at alternate inoculation sites. PMID:17139493

  10. 230Th/U ages Supporting Hanford Site-Wide Probabilistic Seismic Hazard Analysis

    SciTech Connect

    Paces, James B.

    2014-08-31

    This product represents a USGS Administrative Report that discusses samples and methods used to conduct uranium-series isotope analyses and resulting ages and initial 234U/238U activity ratios of pedogenic cements developed in several different surfaces in the Hanford area middle to late Pleistocene. Samples were collected and dated to provide calibration of soil development in surface deposits that are being used in the Hanford Site-Wide probabilistic seismic hazard analysis conducted by AMEC. The report includes description of sample locations and physical characteristics, sample preparation, chemical processing and mass spectrometry, analytical results, and calculated ages for individual sites. Ages of innermost rinds on a number of samples from five sites in eastern Washington are consistent with a range of minimum depositional ages from 17 ka for cataclysmic flood deposits to greater than 500 ka for alluvium at several sites.

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

    PubMed Central

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

    2009-01-01

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

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

    SciTech Connect

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

    2011-10-22

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

  13. A solitary fibrous tumor with concurrent meningioma at the same site: A case report and review of the literature

    PubMed Central

    YAN, HUA; LUO, KAI; LIU, BAOLONG; KANG, JIANMIN

    2016-01-01

    The present study describes a case of a solitary fibrous tumor (SFT) concurrent with meningioma in the same anatomical region. The patient was admitted to Tianjin Huanhu Hospital (Tianjin, China) presenting with progressive eyesight impairment, dizziness and right hemiparesis. Cranial magnetic resonance imaging revealed two primary tumors co-occurring at the same site. One lesion was a solid lesion located in the left frontal convex with homogeneous enhancement, and was closely associated with the dura mater; thus, it was suspected that the lesion was a meningioma. The second lesion was cystic and solid with an irregular shape, and was located next to the first tumor; this lesion was believed to be a hemangiopericytoma or astrocytoma. The patient underwent a left temporoparietal craniectomy and a complete excision of the two tumors was achieved. Subsequent pathological examination of the resected tissues confirmed that the two tumors were a secretory meningioma and a SFT, respectively. Immunohistochemistry is important in differentiating SFTs from other tumors. Currently, a total tumor resection is the optimal treatment strategy when managing these rare lesions, often with no requirement for adjuvant post-operative therapy; however, long-term follow-up is essential to detect any signs of recurrence. The possibility of multiple tumors should be taken into consideration when performing clinical examination. To further understand the mechanisms underlying the occurrence of multiple intracranial tumors, further research is required, alongside an increased number of case reports. PMID:27284369

  14. Cutaneous Resonance Running Time Varies with Age, Body Site and Gender in a Normal Chinese Population

    PubMed Central

    Xin, Shujun; Man, Wenyan; Fluhr, Joachim W.; Song, Shunpeng; Elias, Peter M; Man, Mao-Qiang

    2010-01-01

    Background/objectives One phenomenon of skin aging is loss of cutaneous elasticity. Measurement of cutaneous resonance running time (CRRT) is a method to assess skin elasticity. Yet, information regarding directional changes of CRRT associated with age, body sites and gender is not yet available. In the present study, we assessed whether changes in CRRT vary with age, body sites and gender in a normal Chinese population. Methods A Reviscometer was used to measure CRRTs in various directions on the left dorsal hand, the forehead and the left canthus of 806 normal Chinese volunteers, aged 2.5-94 years. Results With aging, CRRTs decreased in all directions on the hand, the forehead, and the canthus. A more dramatic reduction of CRRTs on the forehead and the canthus were observed at both the 2–8 and 3–9 o’clock directions. CRRTs in males aged 11– 20 years old were longer than those in females at some directions on all three body sites. Females between 21 and 40 years old showed longer CRRTs than males in some directions of the hand. There were no gender differences in subjects aged 0–10 (except on the canthus) and over 81 years old. Conclusion CRRTs vary with age, body sites and gender. PMID:21039906

  15. Renal myelolipoma: a rare extra-adrenal tumor in a rare site: a case report and review of the literature

    PubMed Central

    2013-01-01

    Introduction Myelolipomas are uncommon, benign tumors composed of mature adipose tissue and hematopoietic elements. They mostly occur in the adrenal glands, but extra-adrenal myelolipomas have also been reported in other locations such as the presacral region, retroperitoneum, pelvis and mediastinum. Here, we present a case of an extra-adrenal myelolipoma in a rare site: the renal parenchyma. To the best of our knowledge, it is only the third case reported in this unusual location. Case presentation We report a case of primary myelolipoma occurring in the kidney of a 55-year-old Moroccan man. We describe the radiological and clinicopathologic features of this unusual tumor with a review of the literature, and we discuss differential diagnosis of retroperitoneal myelolipomas. Conclusion This case is noteworthy because the tumor site was unusual. Although renal myelolipoma is rare, it should be considered in the differential diagnosis of lesions in this site. PMID:23556993

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

    PubMed

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

    2015-03-01

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

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

    PubMed

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

    2010-06-01

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

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

    PubMed Central

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

    2014-01-01

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

  19. Relation between primary tumor FDG avidity and site of first distant metastasis in patients with breast cancer

    PubMed Central

    Lim, Chae Hong; Moon, Seung Hwan; Cho, Young Seok; Im, Young-Hyuck; Choe, Yearn Seong; Kim, Byung-Tae; Lee, Kyung-Han

    2016-01-01

    Abstract Identification of tumor imaging features associated with metastatic pattern may allow better understanding of cancer dissemination. Here, we investigated how primary tumor 18F-fluorodeoxyglucose (FDG) avidity influences the first site of breast cancer metastasis. Subjects were 264 patients with advanced breast cancer who underwent positron emission tomography/computed tomography at diagnosis and had metastasis at presentation (n = 193) or metastatic relapse after surgery (n = 71). Primary tumor FDG avidity (maximum SUV [SUVmax] ≥10.1) was compared with histology and first metastatic sites. The most common site of first metastasis was the bone, occurring in 62.7% of patients with metastasis at presentation and 38.0% of those with metastatic relapse. First metastasis to lung occurred in 30.1% and 35.2%, and to liver in 25.4% and 15.2% of respective groups. In patients with metastasis at presentation, primary tumors were FDG avid in 98/193 cases, and this was associated with more frequent first metastasis to lung (37.8% vs 22.1%; P = 0.018). In patients with metastasis relapse, primary tumors were FDG avid in 31/71 cases, and this was associated with more frequent first metastasis to lung (48.4% vs 25.0%; P = 0.041) and liver (29.0% vs 5.0%; P = 0.008). In patients with metastasis relapse, primary tumors that were FDG avid but hormone receptor negative had more first metastasis to lung (57.9% vs 26.9%; P = 0.016). FDG-avid primary breast tumors have favored first spread to the lung and liver, which suggests that tumor cells with heightened glycolytic activity better colonize these organs. PMID:27512840

  20. Relation between primary tumor FDG avidity and site of first distant metastasis in patients with breast cancer.

    PubMed

    Lim, Chae Hong; Moon, Seung Hwan; Cho, Young Seok; Im, Young-Hyuck; Choe, Yearn Seong; Kim, Byung-Tae; Lee, Kyung-Han

    2016-08-01

    Identification of tumor imaging features associated with metastatic pattern may allow better understanding of cancer dissemination. Here, we investigated how primary tumor F-fluorodeoxyglucose (FDG) avidity influences the first site of breast cancer metastasis.Subjects were 264 patients with advanced breast cancer who underwent positron emission tomography/computed tomography at diagnosis and had metastasis at presentation (n = 193) or metastatic relapse after surgery (n = 71). Primary tumor FDG avidity (maximum SUV [SUVmax] ≥10.1) was compared with histology and first metastatic sites.The most common site of first metastasis was the bone, occurring in 62.7% of patients with metastasis at presentation and 38.0% of those with metastatic relapse. First metastasis to lung occurred in 30.1% and 35.2%, and to liver in 25.4% and 15.2% of respective groups. In patients with metastasis at presentation, primary tumors were FDG avid in 98/193 cases, and this was associated with more frequent first metastasis to lung (37.8% vs 22.1%; P = 0.018). In patients with metastasis relapse, primary tumors were FDG avid in 31/71 cases, and this was associated with more frequent first metastasis to lung (48.4% vs 25.0%; P = 0.041) and liver (29.0% vs 5.0%; P = 0.008). In patients with metastasis relapse, primary tumors that were FDG avid but hormone receptor negative had more first metastasis to lung (57.9% vs 26.9%; P = 0.016).FDG-avid primary breast tumors have favored first spread to the lung and liver, which suggests that tumor cells with heightened glycolytic activity better colonize these organs. PMID:27512840

  1. Site specific effect of tobacco addiction in upper aerodigestive tract tumors: a retrospective clinicopathological study.

    PubMed

    Kumar, Ashok; Sharma, Amita; Ahlawat, Babita; Sharma, Sonam

    2014-01-01

    An institutional study was carried out in 102 patients to investigate the site specific effect of addictions, that is, tobacco smoking and tobacco chewing (smokeless), both independently and synergistically in development of malignancies in upper aerodigestive tract through retrograde questionnaire. The histopathologically proven cases were interviewed regarding different forms of addictions followed by clinical examination and investigations for grading (according to Modified Broadmann's method) and TNM staging (according to UICC) according to the tumor site. Statistical analysis was done by Pearson test. Out of all proven cases of cancers, 29.4% were only tobacco chewers (smokeless), 25.5% were only smokers, 42.2% were having both types of tobacco addictions (smoke and smokeless), and only 2.9% were having no addiction. Out of only tobacco chewers (smokeless), 83.3% were of oral cavity cancers, 6.7% were of oro- and hypopharynx and the rest were of others. Among only smokers, 69.2% cases were of laryngeal and oro- and hypopharynx as compared to 11.5% of oral cavity cancers (nearly 6 times). Tobacco (smokeless) chewing is associated with oral cancers whereas tobacco smoking is associated with laryngeal and hypopharyngeal carcinoma. Both smoking and smokeless tobacco act in synergy with each other. PMID:25431788

  2. Analysis of Dose at the Site of Second Tumor Formation After Radiotherapy to the Central Nervous System

    SciTech Connect

    Galloway, Thomas J.; Indelicato, Daniel J.; Amdur, Robert J.; Morris, Christopher G.; Swanson, Erika L.; Marcus, Robert B.

    2012-01-01

    Purpose: Second tumors are an uncommon complication of multimodality treatment of childhood cancer. The present analysis attempted to correlate the dose received as a component of primary treatment and the site of the eventual development of a second tumor. Methods and Materials: We retrospectively identified 16 patients who had received radiotherapy to sites in the craniospinal axis and subsequently developed a second tumor. We compared the historical fields and port films of the primary treatment with the modern imaging of the second tumor locations. We classified the location of the second tumors as follows: in the boost field; marginal to the boost field, but in a whole-brain field; in a whole-brain field; marginal to the whole brain/primary treatment field; and distant to the field. We divided the dose received into 3 broad categories: high dose (>45 Gy), moderate dose (20-36 Gy), and low dose (<20 Gy). Results: The most common location of the second tumor was in the whole brain field (57%) and in the moderate-dose range (81%). Conclusions: Our data contradict previous publications that suggested that most second tumors develop in tissues that receive a low radiation dose. Almost all the second tumors in our series occurred in tissue within a target volume in the cranium that had received a moderate dose (20-36 Gy). These findings suggest that a major decrease in the brain volume that receives a moderate radiation dose is the only way to substantially decrease the second tumor rate after central nervous system radiotherapy.

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

    PubMed

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

    2008-03-01

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

  4. Genome-wide CpG island methylation and intergenic demethylation propensities vary among different tumor sites.

    PubMed

    Lee, Seung-Tae; Wiemels, Joseph L

    2016-02-18

    The epigenetic landscape of cancer includes both focal hypermethylation and broader hypomethylation in a genome-wide manner. By means of a comprehensive genomic analysis on 6637 tissues of 21 tumor types, we here show that the degrees of overall methylation in CpG island (CGI) and demethylation in intergenic regions, defined as 'backbone', largely vary among different tumors. Depending on tumor type, both CGI methylation and backbone demethylation are often associated with clinical, epidemiological and biological features such as age, sex, smoking history, anatomic location, histological type and grade, stage, molecular subtype and biological pathways. We found connections between CGI methylation and hypermutability, microsatellite instability, IDH1 mutation, 19p gain and polycomb features, and backbone demethylation with chromosomal instability, NSD1 and TP53 mutations, 5q and 19p loss and long repressive domains. These broad epigenetic patterns add a new dimension to our understanding of tumor biology and its clinical implications. PMID:26464434

  5. Genome-wide CpG island methylation and intergenic demethylation propensities vary among different tumor sites

    PubMed Central

    Lee, Seung-Tae; Wiemels, Joseph L.

    2016-01-01

    The epigenetic landscape of cancer includes both focal hypermethylation and broader hypomethylation in a genome-wide manner. By means of a comprehensive genomic analysis on 6637 tissues of 21 tumor types, we here show that the degrees of overall methylation in CpG island (CGI) and demethylation in intergenic regions, defined as ‘backbone’, largely vary among different tumors. Depending on tumor type, both CGI methylation and backbone demethylation are often associated with clinical, epidemiological and biological features such as age, sex, smoking history, anatomic location, histological type and grade, stage, molecular subtype and biological pathways. We found connections between CGI methylation and hypermutability, microsatellite instability, IDH1 mutation, 19p gain and polycomb features, and backbone demethylation with chromosomal instability, NSD1 and TP53 mutations, 5q and 19p loss and long repressive domains. These broad epigenetic patterns add a new dimension to our understanding of tumor biology and its clinical implications. PMID:26464434

  6. Primary tumor prevalence has an impact on the constituent ratio of metastases to the jaw but not on metastatic sites

    PubMed Central

    Zhang, Fu-gui; Hua, Cheng-ge; Shen, Mo-lun; Tang, Xiu-fa

    2011-01-01

    This article provides an overview of metastases to jaws (MJ), mainly concerning the differences between American and Chinese patients, and exploring the relationship between the primary tumors' prevalence (PTP) and constituent ratio of MJ. Information concerning of 399 MJ cases in 215 papers, including one new case in our hospital, was subjected to statistic analysis. The main clinical features of MJ, such as constituent ratio of PTP and that of MJ, metastatic sites, treatments, and prognosis were summarized. Breast, lung, kidney, prostate and thyroid (in descending order) were the leading primary sites of MJ. Furthermore, the constituent ratio of MJ was found to be correlated with that of PTP in all subjects including American and Chinese subjects in our study. As to metastatic sites in the mandible, a specific “M” shaped pattern appeared regardless of the tumor type or constituent ratios of MJ were in all subjects. Almost all subjects received traditionally palliative treatments, and the prognosis was quite poor. The PTP had a significant impact on the constituent ratio of MJ. However, it was the properties of the microenvironment rather than characteristics or constituent ratios of tumor cells, that decided the metastatic sites in various tumor subjects. PMID:21789963

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

    PubMed Central

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

    2007-01-01

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

  8. Feasibility of multi-site clinical structural neuroimaging studies of aging using legacy data.

    PubMed

    Fennema-Notestine, Christine; Gamst, Anthony C; Quinn, Brian T; Pacheco, Jenni; Jernigan, Terry L; Thal, Leon; Buckner, Randy; Killiany, Ron; Blacker, Deborah; Dale, Anders M; Fischl, Bruce; Dickerson, Brad; Gollub, Randy L

    2007-01-01

    The application of advances in biomedical computing to medical imaging research is enabling scientists to conduct quantitative clinical imaging studies using data collected across multiple sites to test new hypotheses on larger cohorts, increasing the power to detect subtle effects. Given that many research groups have valuable existing (legacy) data, one goal of the Morphometry Biomedical Informatics Research Network (BIRN) Testbed is to assess the feasibility of pooled analyses of legacy structural neuroimaging data in normal aging and Alzheimer's disease. The present study examined whether such data could be meaningfully reanalyzed as a larger combined data set by using rigorous data curation, image analysis, and statistical modeling methods; in this case, to test the hypothesis that hippocampal volume decreases with age and to investigate findings of hippocampal asymmetry. This report describes our work with legacy T1-weighted magnetic resonance (MR) and demographic data related to normal aging that have been shared through the BIRN by three research sites. Results suggest that, in the present application, legacy MR data from multiple sites can be pooled to investigate questions of scientific interest. In particular, statistical analyses suggested that a mixed-effects model employing site as a random effect best fits the data, accounting for site-specific effects while taking advantage of expected comparability of age-related effects. In the combined sample from three sites, significant age-related decline of hippocampal volume and right-dominant hippocampal asymmetry were detected in healthy elderly controls. These expected findings support the feasibility of combining legacy data to investigate novel scientific questions. PMID:17999200

  9. The ability of live three-dimensional transesophageal echocardiography to evaluate the attachment site of intracardiac tumors.

    PubMed

    Khairnar, Prakash; Hsiung, Ming C; Mishra, Stuti; Nanda, Navin C; Daly, David D; Nayyar, Gaurav; Patel, Adilahmed; Mishra, Jaymala; Chuang, Yi-Cheng; Tsai, Shen-Kou; Yin, Wei-Hsin; Wei, Jeng

    2011-10-01

    In this study, a case of a right ventricular myxoma and a case of a right ventricular hemangioma are used to demonstrate the ability of live three-dimensional transesophageal echocardiography (3DTEE) to assess the site of tumor attachment. Because 3DTEE has the ability to visualize desired structures in multiple planes, we defined the attached portion of the tumors and measured the en face view dimensions. In addition, the improved ability of 3DTEE to evaluate tissue characteristics allowed differentiation of the heterogeneous myxoma and highly vascular hemangioma. On the contrary, because two-dimensional (2D) TEE only allows structures to be viewed in a 2D plane, the attachment site can be located but complete delineation and measurement of area is not possible. As surgical options become less invasive, accurate attachment site location and size will become more important to ensure complete excision. PMID:21929586

  10. School Age Center Connections: Site-Based Management Strategies for Implementation of Quality Programs.

    ERIC Educational Resources Information Center

    Willis, Dahna R.

    This paper describes the outcomes of a practicum that initiated site-based-management strategies to support the consistent implementation of a quality school-age child-care program. Implemented at a multisite child-care center, the program sought to enhance staff members' job satisfaction and maximize their opportunities for professional growth…

  11. Covalent disulfide-linked anti-CEA diabody allows site-specific conjugation and radiolabeling for tumor targeting applications

    PubMed Central

    Olafsen, Tove; Cheung, Chia-wei; Yazaki, Paul J.; Li, Lin; Sundaresan, Gobalakrishnan; Gambhir, Sanjiv S.; Sherman, Mark A.; Williams, Lawrence E.; Shively, John E.; Raubitschek, Andrew A.; Wu, Anna M.

    2014-01-01

    An engineered anti-carcinoembryonic antigen (CEA) diabody (scFv dimer, 55 kDa) was previously constructed from the murine anti-CEA T84.66 antibody. Tumor targeting, imaging and biodistribution studies in nude mice bearing LS174T xenografts with radiolabeled anti-CEA diabody demonstrated rapid tumor uptake and fast blood clearance, which are favorable properties for an imaging agent. Current radiolabeling approaches result in random modification of the protein surface, which may impair immunoreactivity especially for smaller antibody fragments. Site-specific conjugation approaches can direct modifications to reactive groups located away from the binding site. Here, cysteine residues were introduced into the anti-CEA diabody at three different locations, to provide specific thiol groups for chemical modification. One version (with a C-terminal Gly-Gly-Cys) existed exclusively as a disulfide-bonded dimer. This cysteine-modified diabody (Cys-diabody) retained high binding to CEA and demonstrated tumor targeting and biodistribution properties identical to the non-covalent diabody. Furthermore, following reduction of the disulfide bond, the Cys-diabody could be chemically modified using a thiol-specific bifunctional chelating agent, for radiometal labeling. Thus, the Cys-diabody provides a covalently linked alternative to conventional diabodies, which can be reduced and modified site-specifically. This format will provide a versatile platform for targeting a variety of agents to CEA-positive tumors. PMID:14985534

  12. Identification of a Tumor Specific, Active-Site Mutation in Casein Kinase 1α by Chemical Proteomics

    PubMed Central

    Okerberg, Eric S.; Hainley, Anna; Brown, Heidi; Aban, Arwin; Alemayehu, Senait; Shih, Ann; Wu, Jane; Patricelli, Matthew P.; Kozarich, John W.; Nomanbhoy, Tyzoon; Rosenblum, Jonathan S.

    2016-01-01

    We describe the identification of a novel, tumor-specific missense mutation in the active site of casein kinase 1α (CSNK1A1) using activity-based proteomics. Matched normal and tumor colon samples were analyzed using an ATP acyl phosphate probe in a kinase-targeted LC-MS2 platform. An anomaly in the active-site peptide from CSNK1A1 was observed in a tumor sample that was consistent with an altered catalytic aspartic acid. Expression and analysis of the suspected mutant verified the presence of asparagine in the probe-labeled, active-site peptide for CSNK1A1. Genomic sequencing of the colon tumor samples confirmed the presence of a missense mutation in the catalytic aspartic acid of CSNK1A1 (GAC→AAC). To our knowledge, the D163N mutation in CSNK1A1 is a newly defined mutation to the conserved, catalytic aspartic acid of a protein kinase and the first missense mutation identified using activity-based proteomics. The tumorigenic potential of this mutation remains to be determined. PMID:27031502

  13. Imaging site-specific peptide-targeting in tumor tissues using spectral-domain optical coherence tomography

    NASA Astrophysics Data System (ADS)

    Ma, Lixin; Zhang, Miao; Yu, Ping

    2011-03-01

    We report imaging studies on site-specific peptide-targeting in tumor tissues using newly developed optical peptide probes and spectral-domain optical coherence tomography (SD-OCT). The system used two broadband superluminescent light emission diodes with different central wavelengths. An electro-optic modulation in the reference beam was used to get full-range deep imaging inside tumor tissues. The optical probes were based on Bombesin (BBN) that is a fourteen amino acid peptide. BBN has high binding affinity to gastrin-releasing peptide (GRP) receptors overexpressed on several human cancer cell lines. Fluorescence BBN probes were developed by conjugating the last eight residues of BBN, -Q-W-A-V-G-H-L-M-(NH2), with Alexa Flour 680 or Alexa Fluor 750 dye molecules via amino acid linker -G-G-G. The SD-OCT imaging can identify normal tissue and tumor tissue through the difference in scattering coefficient, and trace the BBN conjugate probes through the absorption of the dye molecules using the twowavelength algorithm. We performed the specific uptake and receptor-blocking experiments of the optical BBN probes in severely compromised immunodeficient mouse model bearing human PC-3 prostate tumor xenografts. Tumor and muscle tissues were collected and used for SD-OCT imaging. The SD-OCT images showed fluorescence traces of the BBN probes in the peptide-targeted tumor tissues. Our results demonstrated that SD-OCT is a potential tool for preclinical and clinical early cancer detection.

  14. Relationship of oral cancer with age, sex, site distribution and habits.

    PubMed

    Patel, Mandakini Mansukh; Pandya, Amrish N

    2004-04-01

    Many studies are carried out regarding age incidence, tobacco smoking and sites of oral cancer, but in Gujarat tobacco chewing in form of Gutkha is more common than smoking and start during preteen years. Tobacco chewing causing chronic inflammation, submucous fibrosis and oral cancer. This study was conducted on 504 patients to find out if there is increasing incidence of oral cancer in lower age group and its relation with sex as well which site was commonly affected. There was statistically significant increase in oral cancer in lower age group, and anatomically anterior part of oral cavity showed involvement in 61.32% of cases. Though males were affected more but female cases were 25%. So tobacco chewing has got detrimental effect on oral cavity. PMID:16295466

  15. Age-specific productivity and nest site characteristics of Cooper's hawks (Accipiter cooperii)

    USGS Publications Warehouse

    Moore, K.R.; Henny, C.J.

    1984-01-01

    Nesting Cooper's Hawks (Accipiter cooperii) were studied in northeastern Oregon. Second-year (SY) males did not breed, but 22 percent of the breeding females were SY's. Mean clutch size (P = 0.012) and mean number of young fledged per pair that laid eggs (P < 0.10) were lower for SY females than for adult (after second year [ASY}) females; however, an equal percentage of the eggs (excluding a collected sample egg) yielded fledged young for each age class. Stepwise discriminant analysis suggested differences in structural characteristics of the nest site habitat for ASY and SY females, i.e., SY female nest sites were associated with younger successional stages than ASY female nest sites. Nests of both age groups were built in trees with high crown volume, but ASY females utilized mistletoe (Arceuthobium sp.) for nest structures more frequently (P < 0.01) than SY females.

  16. Metabolic effects of cachectin/tumor necrosis factor are modified by site of production. Cachectin/tumor necrosis factor-secreting tumor in skeletal muscle induces chronic cachexia, while implantation in brain induces predominantly acute anorexia.

    PubMed

    Tracey, K J; Morgello, S; Koplin, B; Fahey, T J; Fox, J; Aledo, A; Manogue, K R; Cerami, A

    1990-12-01

    We have developed a murine model of wasting by injecting intracerebrally cells which continuously secrete h-cachectin/TNF (CHO-TNF) to: (a) determine the effects of cachectin/TNF produced continuously in the central nervous system (CNS), and (b) compare the metabolic effects of cachectin/TNF-secreting tumor in the brain to the cachexia caused by CHO-TNF tumor in peripheral tissue (IM). Intracerebral CHO-TNF tumors produced increased serum h-cachectin/TNF levels with lethal hypophagia and weight loss (mean survival time of 11 d); these changes were not observed in association with nonsecretory control brain tumors. The metabolic consequences of intracerebral cachectin/TNF production were indistinguishable from acute, lethal starvation: whole-body lipid content was decreased significantly but protein was conserved. Although intramuscular cachectin/TNF-secreting tumors caused similar increases of serum h-cachectin/TNF levels, profound anorexia did not develop; wasting developed after a longer period of tumor burden (50 d) with classical signs of cachexia (i.e., anemia and depletion of both protein and lipid). These studies provide a reproducible animal model of site-specific cytokine production and suggest that, regardless of serum levels, cachectin/TNF produced locally in brain influences both the rate of development of wasting and its net metabolic effects. PMID:2254457

  17. Assessment of setup uncertainties for various tumor sites when using daily CBCT for more than 2200 VMAT treatments.

    PubMed

    Oh, Young-Kee; Baek, Jong-Geun; Kim, Ok-Bae; Kim, Jin-Hee

    2014-01-01

    The aim of this study was assess the patient setup errors for various tumor sites based on clinical data from a sufficient number of treatments with volumetric-modulated arc therapy (VMAT) using daily pretreatment CBCT imaging guidance. In addition, we calculated and compared the planning target volume (PTV) margins for all disease sites based on an analysis of specific systematic and random errors in our institution. All patients underwent pretreatment kV-CBCT imaging. The various tumor sites were divided into four categories; 21 brain (438 fractions), 35 head-and-neck tumors (H&N, 933 fractions), 19 thorax and abdomen tumors (T&A, 313 fractions), and 17 prostate cancer tumors (546 fractions). Overall distributions of setup corrections in all directions, frequencies of 3D vector lengths, institution-specific setup error, and PTV margins were analyzed. The longitudinal distribution for the T&A site represented an asymmetric offset in the negative direction. Rotational distributions were comparable for all treatment sites, and the prostate site had the narrowest distribution of ≤ ± 2°. The cumulative frequencies of 3D vector length of ≥ 7 mm were rare for brain lesions and H&N, but more common for T&A and prostate lesions at 25.6% and 12.1%, respectively. The overall mean error for all treatment sites were within ± 1 mm and ± 0.1°, with the exception of the T&A site, which had overall mean error of 2 mm in the negative longitudinal direction. The largest magnitude of systematic error and random error for the brain lesions and H&N was 1.4 mm in the translational directions, and 3.3 mm for T&A and prostate lesions. The PTV margins required in this analysis are ≤ 4 mm for the brain lesions and H&N in all translational directions, but ranged from 4 to 10 mm for T&A and prostate lesions. Analysis of each institution's specific setup errors using daily CBCT is essential for determining PTV margins and reducing setup uncertainties, because setup errors vary

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

    PubMed

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

    2015-10-20

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

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

    PubMed Central

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

    2015-01-01

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

  20. Comparison of nanoparticle penetration into solid tumors and sites of inflammation: studies using targeted and nontargeted liposomes

    PubMed Central

    Poh, Scott; Chelvam, Venkatesh; Low, Philip S

    2015-01-01

    Aim: The vast majority of nanomedicine research is focused on the use of nanoparticles for the diagnosis and treatment of cancer. However, the dense extracellular matrix of solid tumors restricts nanoparticle penetration, raising the question of whether the best applications of nanomedicines lie in oncology. Materials & methods: In this study, the uptake of folate-conjugated liposomes was compared between folate receptor-expressing tumors and folate receptor+ inflammatory lesions within the same mouse. Results: We demonstrate here that both folate-targeted and nontargeted liposomes accumulate more readily at sites of inflammation than in solid tumors. Conclusion: These data suggest that nanosized imaging and therapeutic agents may be better suited for the treatment and diagnosis of inflammatory/autoimmune diseases than cancer. PMID:25996118

  1. Inducible Expression of B7-H1 (PD-L1) and Its Selective Role in Tumor Site Immune Modulation

    PubMed Central

    Sanmamed, Miguel F.; Chen, Lieping

    2015-01-01

    Immune evasion is an important hallmark of cancer, and a better understanding of this mechanism is essential for the development of effective strategies against cancer. The B7 homolog 1 (B7-H1)/programmed cell death 1 (PD-1) pathway has been demonstrated as a major mechanism of immune evasion in tumor site, and its blockade therapy shows very encouraging results in clinical trials. Inducible B7-H1 expression in tumor microenvironment is complex, with multidimensional interactions and expression by different subsets of hematopoietic and nonhematopoietic cells. Understanding these interactions and how tumors take advantage of this pathway can help us design future strategies for better therapeutic efficacy and to overcome resistances. PMID:25098285

  2. A generational comparison of social networking site use: the influence of age and social identity.

    PubMed

    Barker, Valerie

    2012-01-01

    An online survey (N=256) compared social networking site (SNS) use among younger (millennial: 18-29) and older (baby-boomer: 41-64) subscribers focusing on the influence of collective self-esteem and group identity on motives for SNS use. Younger participants reported higher positive collective self-esteem, social networking site use for peer communication, and social compensation. Regardless of age, participants reporting high collective self-esteem and group identity were more likely to use social networking sites for peer communication and social identity gratifications, while those reporting negative collective self-esteem were more likely to use social networking sites for social compensation. The theoretical implications of the strong relationship between social identity gratifications and social compensation are discussed. PMID:22808625

  3. Collagen cross-linking in sun-exposed and unexposed sites of aged human skin

    NASA Technical Reports Server (NTRS)

    Yamauchi, M.; Prisayanh, P.; Haque, Z.; Woodley, D. T.

    1991-01-01

    A recently described nonreducible, acid-heat stable compound, histidinohydroxylysinonorleucine (HHL), is a collagen cross-link isolated from mature skin tissue. Its abundance is related to chronologic aging of skin. The present communication describes the quantity of HHL from aged human skin of the same individuals in sun-exposed (wrist) and unexposed (buttock) sites. Punch biopsies were obtained from these sites from nine people of age 60 or older. HHL contents (moles/mole of collagen) at these sites were for wrist 0.13 +/- 0.07 and for buttock 0.69 +/- 0.17 (mean +/- SD, p less than 0.001). In addition, it was found that acute irradiation of the cross-linked peptides with UVA (up to 250 J/cm2) and UVB (up to 1 J/cm2) had no effect on HHL structure. The same treatment significantly degraded another nonreducible, stable collagen cross-link, pyridinoline. The results suggest that chronic sunlight exposure may be associated with an impediment to normal maturation of human dermal collagen resulting in tenuous amount of HHL. Thus, the process of photoaging in dermal collagen is different from that of chronologic aging in human skin.

  4. Primary Ewing Family of Tumors of the Jaw has a better Prognosis compared to Tumors of Extragnathic sites

    PubMed Central

    Owosho, Adepitan A.; Ko, Eugene; Rosenberg, Haley I.; Yom, SaeHee K.; Antonescu, Cristina R.; Huryn, Joseph M.; Estilo, Cherry L.

    2016-01-01

    Purpose Primary Ewing sarcoma of the jaw is rare. The aim of this study was to describe new cases of primary Ewing sarcoma of the jaw and investigate reported prognostic factors of Ewing sarcoma in this series and treatment outcome. Materials and Methods Six patients with primary Ewing sarcoma of the jaw were treated at the Memorial Sloan Kettering Cancer Center (MSKCC) from 1992 through 2013. Clinical data, pathology reports, treatment prescribed, treatment regimens, outcome, and follow-up information were reviewed. Results Five of 6 patients were female and 5 cases were in the mandible. No patient presented with metastatic disease at diagnosis. All cases were positive for CD99, and 3 patients with genetic confirmation were positive for EWS-FLI1 fusion or EWSR1 gene rearrangement. All patients received induction multiagent chemotherapy and surgical resection and 2 patients received adjuvant radiotherapy. Total (grade IV) or nearly total (grade III) tumor necrosis in 3 of 5 patients (60%) assessed for histologic response to chemotherapy indicated intense sensitivity. All patients were alive and free of disease, with no history of local recurrence, at a median follow-up period of 6.5 years. Conclusion Patients with primary Ewing sarcoma of the jaw have a good prognosis and metastasis is an uncommon occurrence at initial presentation. PMID:26679553

  5. Geophysical prospection on an Early Iron Age Cult Site near Frankfurt/Oder, Germany

    NASA Astrophysics Data System (ADS)

    Ullrich, Burkart; Kaufmann, Georg; Beilke-Voigt, Ines

    2010-05-01

    The Free University of Berlin and the Humboldt University of Berlin hosts the excellence cluster 264 Topoi, "The Formation and Transformation of Space and Knowledge in Ancient Civilizations". The Excellence Cluster pursues the goal of researching the interdependence of space and knowledge in the civilizations of the Ancient Near East, the Mediterranean, and Black Sea region and parts of the Eurasian steppe from the 6th millennium BC to around AD 500. Within this excellence cluster, the project A-I-11 "Lossow near Frankfurt/Oder - An Early Iron Age Cult Site of the Ancient Peripheral Zone" examines the evolution of an important cult site in Central Europe. The castle mound of Lossow was built as a fortified settlement in the late Bronze Age (10th century B.C.). After a phase of around 200 years, a supra-regionally significant, early Iron Age cult centre developed on this site (8th-6th century B.C.). Several pieces of evidence indicate that the locality had a central-site character. Typical for the site are well-shapes shafts, filled with large amounts of human and animal bones. The shafts with a diameter of about 1 meter and a depth of about 5 to 7 meters are a great challenge to near surface geophysics. Here, geophysical methods (geomagnetic gradiometry, geoelectric imaging, georadar survey) have been used to obtain a large-scale conclusive picture of the sub-surface both within the castle mount and around the perimeter. While the magnetic results reveal numerous archaeological artefacts, geoelectric imaging decipers the subsurface structure of the site.

  6. An age for Kajong, a Miocene fossil site east of Lake Turkana, Kenya

    NASA Astrophysics Data System (ADS)

    Brown, Francis H.; Jicha, Brian R.; Leakey, R. E.

    2016-02-01

    The Kajong Formation in Marsabit District, northern Kenya has yielded a Miocene mammalian fauna consisting of nine taxa. It is capped by a basalt 40Ar/39Ar dated at 19.1 ± 0.1 Ma, and a volcanic clast from a conglomerate within the formation yielded an age of 20.3 Ma, only slightly older. The entire fauna from this site thus lies close to the base of the Miocene Epoch and is older than 19.2 Ma. The site has yielded some of the oldest examples of Archaeobelodon filholi, Prodeinotherium hobleyi, and Gomphotherium sp. in east Africa.

  7. Skin tumor immunity: Site does matter for antigen presentation by DCs.

    PubMed

    Waithman, Jason; Gebhardt, Thomas; Bedoui, Sammy

    2016-03-01

    The immune system has the ability to specifically identify and eliminate tumors, but the underlying mechanisms responsible for this phenomenon are not fully understood. A study published in this issue of the European Journal of Immunology now provides new insights into this important problem. Joncker et al. [Eur. J. Immunol. 2016. 46: 609-618] show that the timely mobilization of tumor antigen-bearing dendritic cells (DCs) from the periphery to the lymph nodes is critical for effective antitumor T-cell immunity, and that DCs present tumor antigens much more efficiently when encountered in the skin rather than in the subcutaneous tissues. PMID:26842676

  8. Meta-Analysis of DNA Tumor-Viral Integration Site Selection Indicates a Role for Repeats, Gene Expression and Epigenetics

    PubMed Central

    Doolittle-Hall, Janet M.; Cunningham Glasspoole, Danielle L.; Seaman, William T.; Webster-Cyriaque, Jennifer

    2015-01-01

    Oncoviruses cause tremendous global cancer burden. For several DNA tumor viruses, human genome integration is consistently associated with cancer development. However, genomic features associated with tumor viral integration are poorly understood. We sought to define genomic determinants for 1897 loci prone to hosting human papillomavirus (HPV), hepatitis B virus (HBV) or Merkel cell polyomavirus (MCPyV). These were compared to HIV, whose enzyme-mediated integration is well understood. A comprehensive catalog of integration sites was constructed from the literature and experimentally-determined HPV integration sites. Features were scored in eight categories (genes, expression, open chromatin, histone modifications, methylation, protein binding, chromatin segmentation and repeats) and compared to random loci. Random forest models determined loci classification and feature selection. HPV and HBV integrants were not fragile site associated. MCPyV preferred integration near sensory perception genes. Unique signatures of integration-associated predictive genomic features were detected. Importantly, repeats, actively-transcribed regions and histone modifications were common tumor viral integration signatures. PMID:26569308

  9. Brain site-specific proteome changes in aging-related dementia

    PubMed Central

    Manavalan, Arulmani; Mishra, Manisha; Feng, Lin; Sze, Siu Kwan; Akatsu, Hiroyasu; Heese, Klaus

    2013-01-01

    This study is aimed at gaining insights into the brain site-specific proteomic senescence signature while comparing physiologically aged brains with aging-related dementia brains (for example, Alzheimer's disease (AD)). Our study of proteomic differences within the hippocampus (Hp), parietal cortex (pCx) and cerebellum (Cb) could provide conceptual insights into the molecular mechanisms involved in aging-related neurodegeneration. Using an isobaric tag for relative and absolute quantitation (iTRAQ)-based two-dimensional liquid chromatography coupled with tandem mass spectrometry (2D-LC-MS/MS) brain site-specific proteomic strategy, we identified 950 proteins in the Hp, pCx and Cb of AD brains. Of these proteins, 31 were significantly altered. Most of the differentially regulated proteins are involved in molecular transport, nervous system development, synaptic plasticity and apoptosis. Particularly, proteins such as Gelsolin (GSN), Tenascin-R (TNR) and AHNAK could potentially act as novel biomarkers of aging-related neurodegeneration. Importantly, our Ingenuity Pathway Analysis (IPA)-based network analysis further revealed ubiquitin C (UBC) as a pivotal protein to interact with diverse AD-associated pathophysiological molecular factors and suggests the reduced ubiquitin proteasome degradation system (UPS) as one of the causative factors of AD. PMID:24008896

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

    PubMed Central

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

    2014-01-01

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

  11. Greater Bone Formation Induction Occurred in Aged than Young Cancellous Bone Sites

    NASA Technical Reports Server (NTRS)

    Ke, H. Z.; Jee, W. S. S.; Ito, H.; Setterberg, R. B.; Li, M.; Lin, B. Y.; Liang, X. G.; Ma, Y. F.

    1993-01-01

    We have determined the differences in the effects of continual prostaglandin E(sub 2) (PGE(sub 2) treatment in aged (non-growing) and young (growing) cancellous bone sites in 7-month-old Sprague-Dawley rats. The sites involved are the aged distal tibial metaphysis (DTM) with a closed epiphysis and the young proximal tibial metaphysis (PTM) with a slow growing, open epiphysis. The study involved rats treated with 0, 1, 3 or 6 mg PGE(sub 2)/kg/d for 60, 120 and 180 days. Static and dynamic histomorphometry of percent trabecular area, and tissue-referent bone formation rate (BFR/TV) were determined in both DTM and PTM. In pretreatment controls, the secondary spongiosa of the two metaphyses contain the same amount of cancellous bone (11% in DTM vs. 13% in PTM), but markedly less bone formation in DTM (0.6%/y in DTM vs. 41.5%/y in PTM). After 60 days of 6 mg PGE(sub 2)/kg/d treatment, %Tb.Ar was increased 607% in DTM and 199% in PTM, BFR/TV was increased to nearly 14 fold in DTM and only 5 fold in PTM. These results indicated the aged metaphysis of the DTM was much more responsive to PGE(sub 2) treatment than young, growing metaphysis of the PTM. The results of 120 and 180 days treatment did not significantly differ from 60 days treatment in both sites, indicating that the effect of continuous daily PGE2 treatment were in equilibrium after 60 days. We concluded that aged metaphysis was much more responsive to PGE(sub 2) treatment than young growing metaphysis.

  12. Age and skeletal sites affect BMP-2 responsiveness of human bone marrow stromal cells.

    PubMed

    Osyczka, Anna Maria; Damek-Poprawa, Monika; Wojtowicz, Aleksandra; Akintoye, Sunday O

    2009-01-01

    Bone marrow stromal cells (BMSCs) contain osteoprogenitors responsive to stimulation by osteogenic growth factors like bone morphogenetic proteins (BMPs). When used as grafts, BMSCs can be harvested from different skeletal sites such as axial, appendicular, and orofacial bones, but the lower therapeutic efficacy of BMPs on BMSCs-responsiveness in humans compared to animal models may be due partly to effects of skeletal site and age of donor. We previously reported superior differentiation capacity and osteogenic properties of orofacial BMSCs relative to iliac crest BMSCs in same individuals. This study tested the hypothesis that recombinant human BMP-2 (rhBMP-2) stimulates human BMSCs differently based on age and skeletal site of harvest. Adult maxilla, mandible, and iliac crest BMSCs from same individuals and pediatric iliac crest BMSCs were comparatively assessed for BMP-2 responsiveness under serum-containing and serum-free insulin-supplemented culture conditions. Adult orofacial BMSCs were more BMP-2-responsive than iliac crest BMSCs based on higher gene transcripts of alkaline phosphatase, osteopontin, and osteogenic transcription factors MSX-2 and Osterix in serum-free insulin-containing medium. Pediatric iliac crest BMSCs were more responsive to rhBMP-2 than adult iliac crest BMSCs based on higher expression of alkaline phosphatase and osteopontin in serum-containing medium. Unlike orofacial BMSCs, MSX-2 and Osterix transcripts were similarly expressed by adult and pediatric iliac crest BMSCs in response to rhBMP-2. These data demonstrate that age and skeletal site-specific differences exist in BMSC osteogenic responsiveness to BMP-2 stimulation and suggest that MSX-2 and Osterix may be potential regulatory transcription factors in BMP-mediated osteogenesis of adult orofacial cells. PMID:19637063

  13. Age and Skeletal Sites Affect BMP-2 Responsiveness of Human Bone Marrow Stromal Cells

    PubMed Central

    Osyczka, Anna M.; Damek-Poprawa, Monika; Wojtowicz, Aleksandra; Akintoye, Sunday O.

    2010-01-01

    Bone marrow stromal cells (BMSCs) contain osteoprogenitors responsive to stimulation by osteogenic growth factors like bone morphogenetic proteins (BMPs). When used as grafts, BMSCs can be harvested from different skeletal sites such as axial, appendicular and orofacial bones, but the lower therapeutic efficacy of BMPs on BMSCs-responsiveness in humans compared to animal models may be partly due to effects of skeletal site and age of donor. We previously reported superior differentiation capacity and osteogenic properties of orofacial BMSCs relative to iliac crest BMSCs in same individuals. This study tested the hypothesis that recombinant human BMP-2 (rhBMP-2) stimulates human BMSCs differently based on age and skeletal site of harvest. Adult maxilla, mandible and iliac crest BMSCs from same individuals and pediatric iliac crest BMSCs were comparatively assessed for BMP-2 responsiveness under serum-containing and serum-free insulin-supplemented culture conditions. Adult orofacial BMSCs were more BMP-2-responsive than iliac crest BMSCs based on higher gene transcripts of alkaline phosphatase, osteopontin and osteogenic transcription factors MSX-2 and Osterix in serum-free insulin-containing medium. Pediatric iliac crest BMSCs were more responsive to rhBMP-2 than adult iliac crest BMSCs based on higher expression of alkaline phosphatase and osteopontin in serum-containing medium. Unlike orofacial BMSCs, MSX-2 and Osterix transcripts were similarly expressed by adult and pediatric iliac crest BMSCs in response to rhBMP-2. These data demonstrate that age and skeletal site-specific differences exist in BMSC osteogenic responsiveness to BMP-2 stimulation and suggest that MSX-2 and Osterix may be potential regulatory transcription factors in BMP-mediated osteogenesis of adult orofacial cells. PMID:19637063

  14. DNA methylation levels at individual age-associated CpG sites can be indicative for life expectancy

    PubMed Central

    Lin, Qiong; Weidner, Carola I.; Costa, Ivan G.; Marioni, Riccardo E.; Ferreira, Marcelo R. P.; Deary, Ian J.; Wagner, Wolfgang

    2016-01-01

    DNA-methylation (DNAm) levels at age-associated CpG sites can be combined into epigenetic aging signatures to estimate donor age. It has been demonstrated that the difference between such epigenetic age-predictions and chronological age is indicative for of all-cause mortality in later life. In this study, we tested alternative epigenetic signatures and followed the hypothesis that even individual age-associated CpG sites might be indicative for life-expectancy. Using a 99-CpG aging model, a five-year higher age-prediction was associated with 11% greater mortality risk in DNAm profiles of the Lothian Birth Cohort 1921 study. However, models based on three CpGs, or even individual CpGs, generally revealed very high offsets in age-predictions if applied to independent microarray datasets. On the other hand, we demonstrate that DNAm levels at several individual age-associated CpGs seem to be associated with life expectancy – e.g., at CpGs associated with the genes PDE4C and CLCN6. Our results support the notion that small aging signatures should rather be analysed by more quantitative methods, such as site-specific pyrosequencing, as the precision of age-predictions is rather low on independent microarray datasets. Nevertheless, the results hold the perspective that simple epigenetic biomarkers, based on few or individual age-associated CpGs, could assist the estimation of biological age. PMID:26928272

  15. Solid variant of orbital angioleiomyoma: An unusual tumor at an unusual site

    PubMed Central

    Nair, Akshay Gopinathan; Jain, Vandana; Gopinathan, Indumati; Murthy, Anuradha

    2016-01-01

    We describe the clinicopathological features of a solid variant of orbital angioleiomyoma. A review of clinical records, diagnostic, and radiographic studies combined with histopathological evaluation with standard histochemical staining and immunohistochemistry was conducted. A 22-year-old male patient presented with a mass in the region of the left lacrimal gland that was gradually increasing over the past 2 years. Radiological and clinical examinations showed no signs suspicious of a malignancy and fine needle aspiration cytology was inconclusive. Therefore, an excision biopsy was performed. On histopathological examination, the picture was consistent with a benign spindle cell tumor. Immunohistochemistry showed positivity for CD 34 and CD 31 (markers for vascular endothelium). The tumor also showed positivity for smooth muscle actin and Ki-67 proliferative index was low. Angioleiomyomas are rarely encountered in the orbit and has features seen in leiomyoma as well as some vascular tumor elements. In most cases, surgical excision is usually curative. PMID:27488159

  16. Solid variant of orbital angioleiomyoma: An unusual tumor at an unusual site.

    PubMed

    Nair, Akshay Gopinathan; Jain, Vandana; Gopinathan, Indumati; Murthy, Anuradha

    2016-06-01

    We describe the clinicopathological features of a solid variant of orbital angioleiomyoma. A review of clinical records, diagnostic, and radiographic studies combined with histopathological evaluation with standard histochemical staining and immunohistochemistry was conducted. A 22-year-old male patient presented with a mass in the region of the left lacrimal gland that was gradually increasing over the past 2 years. Radiological and clinical examinations showed no signs suspicious of a malignancy and fine needle aspiration cytology was inconclusive. Therefore, an excision biopsy was performed. On histopathological examination, the picture was consistent with a benign spindle cell tumor. Immunohistochemistry showed positivity for CD 34 and CD 31 (markers for vascular endothelium). The tumor also showed positivity for smooth muscle actin and Ki-67 proliferative index was low. Angioleiomyomas are rarely encountered in the orbit and has features seen in leiomyoma as well as some vascular tumor elements. In most cases, surgical excision is usually curative. PMID:27488159

  17. Tumoral calcinosis in the neck region involving an unusual site in a hemodialysis patient.

    PubMed

    Pan, Chien-Wei; Chen, Rong-Fong

    2016-05-01

    Tumoral calcinosis is a rare disorder characterized by calcium salt deposition in the periarticular soft tissue region. It often occurs in the hip, elbow, shoulder, foot, and wrist. Soft tissue calcification associated with tumoral calcinosis is rare in the head and neck. The present case describes a 65- year-old male who had been on hemodialysis for 3 years. A bulky mass, containing chalky amorphous calcified material, occurred at the lower neck and superior mediastinum. Chronic renal failure is a common condition associated with secondary tumoral calcinosis. The pathogenesis has been progressively unraveled, which indicates that secondary hyperparathyroidism and tissue injury play a part in multifactorial calcification. Laryngoscope, 126:E196-E198, 2016. PMID:26608820

  18. Catecholamine Metabolism in Paraganglioma and Pheochromocytoma: Similar Tumors in Different Sites?

    PubMed Central

    Grouzmann, Eric; Tschopp, Oliver; Triponez, Frédéric; Matter, Maurice; Bilz, Stefan; Brändle, Michael; Drechser, Tilman; Sigrist, Sarah; Zulewski, Henryk; Henzen, Christoph; Fischli, Stefan; Abid, Karim

    2015-01-01

    Pheochromocytoma (PHEO) and paraganglioma (PGL) are catecholamine-producing neuroendocrine tumors that arise respectively inside or outside the adrenal medulla. Several reports have shown that adrenal glucocorticoids (GC) play an important regulatory role on the genes encoding the main enzymes involved in catecholamine (CAT) synthesis i.e. tyrosine hydroxylase (TH), dopamine β-hydroxylase (DBH) and phenylethanolamine N-methyltransferase (PNMT). To assess the influence of tumor location on CAT metabolism, 66 tissue samples (53 PHEO, 13 PGL) and 73 plasma samples (50 PHEO, 23 PGL) were studied. Western blot and qPCR were performed for TH, DBH and PNMT expression. We found a significantly lower intra-tumoral concentration of CAT and metanephrines (MNs) in PGL along with a downregulation of TH and PNMT at both mRNA and protein level compared with PHEO. However, when PHEO were partitioned into noradrenergic (NorAd) and mixed tumors based on an intra-tumoral CAT ratio (NE/E >90%), PGL and NorAd PHEO sustained similar TH, DBH and PNMT gene and protein expression. CAT concentration and composition were also similar between NorAd PHEO and PGL, excluding the use of CAT or MNs to discriminate between PGL and PHEO on the basis of biochemical tests. We observed an increase of TH mRNA concentration without correlation with TH protein expression in primary cell culture of PHEO and PGL incubated with dexamethasone during 24 hours; no changes were monitored for PNMT and DBH at both mRNA and protein level in PHEO and PGL. Altogether, these results indicate that long term CAT synthesis is not driven by the close environment where the tumor develops and suggest that GC alone is not sufficient to regulate CAT synthesis pathway in PHEO/PGL. PMID:25946206

  19. Catecholamine metabolism in paraganglioma and pheochromocytoma: similar tumors in different sites?

    PubMed

    Grouzmann, Eric; Tschopp, Oliver; Triponez, Frédéric; Matter, Maurice; Bilz, Stefan; Brändle, Michael; Drechser, Tilman; Sigrist, Sarah; Zulewski, Henryk; Henzen, Christoph; Fischli, Stefan; Abid, Karim

    2015-01-01

    Pheochromocytoma (PHEO) and paraganglioma (PGL) are catecholamine-producing neuroendocrine tumors that arise respectively inside or outside the adrenal medulla. Several reports have shown that adrenal glucocorticoids (GC) play an important regulatory role on the genes encoding the main enzymes involved in catecholamine (CAT) synthesis i.e. tyrosine hydroxylase (TH), dopamine β-hydroxylase (DBH) and phenylethanolamine N-methyltransferase (PNMT). To assess the influence of tumor location on CAT metabolism, 66 tissue samples (53 PHEO, 13 PGL) and 73 plasma samples (50 PHEO, 23 PGL) were studied. Western blot and qPCR were performed for TH, DBH and PNMT expression. We found a significantly lower intra-tumoral concentration of CAT and metanephrines (MNs) in PGL along with a downregulation of TH and PNMT at both mRNA and protein level compared with PHEO. However, when PHEO were partitioned into noradrenergic (NorAd) and mixed tumors based on an intra-tumoral CAT ratio (NE/E >90%), PGL and NorAd PHEO sustained similar TH, DBH and PNMT gene and protein expression. CAT concentration and composition were also similar between NorAd PHEO and PGL, excluding the use of CAT or MNs to discriminate between PGL and PHEO on the basis of biochemical tests. We observed an increase of TH mRNA concentration without correlation with TH protein expression in primary cell culture of PHEO and PGL incubated with dexamethasone during 24 hours; no changes were monitored for PNMT and DBH at both mRNA and protein level in PHEO and PGL. Altogether, these results indicate that long term CAT synthesis is not driven by the close environment where the tumor develops and suggest that GC alone is not sufficient to regulate CAT synthesis pathway in PHEO/PGL. PMID:25946206

  20. Morcellator's Port-site Metastasis of a Uterine Smooth Muscle Tumor of Uncertain Malignant Potential After Minimally Invasive Myomectomy.

    PubMed

    Bogani, Giorgio; Ditto, Antonino; Martinelli, Fabio; Signorelli, Mauro; Chiappa, Valentina; Lorusso, Domenica; Sabatucci, Ilaria; Carcangiu, Maria L; Fiore, Marco; Gronchi, Alessandro; Raspagliesi, Francesco

    2016-01-01

    Since the safety warning from the US Food and Drug Administration on the use of power morcellators, minimally invasive procedures involving the removal of uterine myomas and large uteri are under scrutiny. Growing evidence suggests that morcellation of undiagnosed uterine malignancies is associated with worse survival outcomes of patients affected by uterine sarcoma. However, to date, only limited data regarding morcellation of low-grade uterine neoplasms are available. In the present article, we reported a case of a (morcellator) port-site implantation of a smooth muscle tumor that occurred 6 years after laparoscopic morcellation of a uterine smooth muscle tumor of uncertain potential. This case highlights the effects of intra-abdominal morcellation, even in low-grade uterine neoplasms. Caution should be used when determining techniques for tissue extraction; the potential adverse consequences of morcellation should be more fully explored. PMID:26851127

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

    PubMed

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

    2012-08-01

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

  2. Brain tumor (image)

    MedlinePlus

    Brain tumors are classified depending on the exact site of the tumor, the type of tissue involved, benign ... tendencies of the tumor, and other factors. Primary brain tumors can arise from the brain cells, the meninges ( ...

  3. Determination of gonad doses during robotic stereotactic radiosurgery for various tumor sites

    SciTech Connect

    Zorlu, Faruk; Dugel, Gozde; Ozyigit, Gokhan; Hurmuz, Pervin; Cengiz, Mustafa; Yildiz, Ferah; Akyol, Fadil; Gurkaynak, Murat

    2013-04-15

    Purpose: The authors evaluated the absorbed dose received by the gonads during robotic stereotactic radiosurgery (SRS) for the treatment of different tumor localizations. Methods: The authors measured the gonad doses during the treatment of head and neck, thoracic, abdominal, or pelvic tumors in both RANDO phantom and actual patients. The computerized tomography images were transferred to the treatment planning system. The contours of tumor and critical organs were delineated on each slice, and treatment plans were generated. Measurements for gonad doses were taken from the geometric projection of the ovary onto the skin for female patients, and from the scrotal skin for male patients by attaching films and Thermoluminescent dosimeters (TLDs). SRS was delivered with CyberKnife (Accuray Inc., Sunnyvale, CA). Results: The median gonadal doses with TLD and film dosimeter in actual patients were 0.19 Gy (range, 0.035-2.71 Gy) and 0.34 Gy (range, 0.066-3.18 Gy), respectively. In the RANDO phantom, the median ovarian doses with TLD and film dosimeter were 0.08 Gy (range, 0.03-0.159 Gy) and 0.05 Gy (range, 0.015-0.13 Gy), respectively. In the RANDO phantom, the median testicular doses with TLD and film dosimeter were 0.134 Gy (range 0.056-1.97 Gy) and 0.306 Gy (range, 0.065-2.25 Gy). Conclusions: Gonad doses are below sterility threshold in robotic SRS for different tumor localizations. However, particular attention should be given to gonads during robotic SRS for pelvic tumors.

  4. IODP Expedition 351 Izu-Bonin-Mariana Arc Origins: Age model for Site U1438

    NASA Astrophysics Data System (ADS)

    Morris, Antony; Maffione, Marco; Kender, Sev; Aljahdali, Mohammed; Bandini, Alexandre; Guerra, Rodrigo do Monte

    2015-04-01

    We report preliminary paleomagnetic and paleontological results from International Ocean Discovery Program (IODP) Expedition 351, which recovered an unprecedented ~1.4 km thick volcaniclastic sedimentary record documenting the initiation and subsequent evolution of the Izu-Bonin-Mariana (IBM) intra-oceanic arc-basin system. Magnetostratigraphic and biostratigraphic constraints provide a high-resolution temporal framework for interpretation of this record. Paleomagnetic analyses of archive half core samples provide a continuous record of the geomagnetic field inclination down to 847 mbsf that allows construction of a detailed site magnetostratigraphy that closely matches the Geomagnetic Polarity Timescale (Gradstein et al., 2012). A total of 87 geomagnetic reversals have been recognized in the studied succession, extending back to ~36 Ma. Despite sporadic microfossil occurrences in parts, calcareous nannofossils, planktonic foraminifera and radiolarians each contribute to the age model for the entire Site. All nannofossil marker species for Oligocene to Eocene Zones NP25 to NP19/20 are recognised. Beneath paleomagnetic control (847-1449 mbsf), foraminifera and radiolarians provide the only age control. The most salient features of the age model are that: (i) average linear sedimentation rates during the Plio-Pleistocene range from 1.4 to 2.2 cm/ka; (ii) there was a reduction in sedimentation rates to 0.25 - 0.5 cm/ka throughout the Miocene; and (iii) sedimentation rates sharply increase again in the Oligocene to Late Eocene to a maximum of ~20 cm/ka. These quantitative constraints closely match (non-quantitative) inferences based on the lithostratigraphy of the site, with fine-grained/coarse-grained sediments dominating in periods with low/high sedimentation rates respectively.

  5. IODP Expedition 351 Izu-Bonin-Mariana Arc Origins: Age Model for Site U1438

    NASA Astrophysics Data System (ADS)

    Morris, A.; Aljahdali, M. H.; Bandini, A. N.; do Monte Guerra, R.; Kender, S.; Maffione, M.

    2014-12-01

    We report preliminary paleomagnetic and paleontological results from International Ocean Discovery Program (IODP) Expedition 351, which recovered an unprecedented ~1.4 km thick volcaniclastic sedimentary record documenting the initiation and subsequent evolution of the Izu-Bonin-Mariana (IBM) intra-oceanic arc-basin system. Magnetostratigraphic and biostratigraphic constraints provide a high-resolution temporal framework for interpretation of this record.Paleomagnetic analyses of archive half core samples provide a continuous record of the geomagnetic field inclination down to 847 mbsf that allows construction of a detailed site magnetostratigraphy that closely matches the Geomagnetic Polarity Timescale (Gradstein et al., 2012). A total of 87 geomagnetic reversals have been recognized in the studied succession, extending back to ~36 Ma. Despite sporadic microfossil occurrences in parts, calcareous nannofossils, planktonic foraminifera and radiolarians each contribute to the age model for the entire Site. All nannofossil marker species for Oligocene to Eocene Zones NP25 to NP19/20 are recognised. Beneath paleomagnetic control (847-1449 mbsf), foraminifera and radiolarians provide the only age control.The most salient features of the age model are that: (i) average linear sedimentation rates during the Plio-Pleistocene range from 1.4 to 2.2 cm/ka; (ii) there was a reduction in sedimentation rates to 0.25 - 0.5 cm/ka throughout the Miocene; and (iii) sedimentation rates sharply increase again in the Oligocene to Late Eocene to a maximum of ~20 cm/ka. These quantitative constraints closely match (non-quantitative) inferences based on the lithostratigraphy of the site, with fine-grained/coarse-grained sediments dominating in periods with low/high sedimentation rates respectively.

  6. GPR Surveys for Archaeological Investigation in a Bronze Age site from NW Portugal

    NASA Astrophysics Data System (ADS)

    Gonçalves, L.; Sampaio, H. A.; Bettencourt, A. M. S.; Alves, M. I. C.

    2012-04-01

    This work describes the use of Ground-penetrating Radar (GPR) surveys in the identification and mapping of subtle cultural remains, from Pego Late Bronze Age settlement, located near the city of Braga, in NW Portugal. Bronze Age settlements from NW Portugal are characterized by the presence archaeological structures such as storage pits, postholes and trenches. These subtle structures have a very low dielectric contrast, making them quite difficult to detect in GPR surveys. In the case of Pego Site, previous investigations using conventional archaeological techniques, during a rescue excavation, partially revealed a residential area, a necropolis, and a stockade foundation trench that encircle the whole settlement. Different GPR prospection approaches were performed using GSSI Sir 3000 System, with 400 MHz antennae, with the objective of identify and define the borders between the different areas of human occupation inside the settlement. For the GPR survey, a grid-based approach with closely spaced parallels transects was defined, covering different areas inside the site. A first survey was conducted with a pseudo-3D methodology, with 50 cm profile separation, followed by a second survey with a dense data acquisition methodology, with 10 cm profile separation. Processed two-dimensional GPR profiles and constructed amplituded-slice maps were produced and analysed. Wave velocities were determined by reflected wave methods and by Hyperbola-Fitting method. The background analysis of the archaeological and geological features of the site, integrated with the preliminary interpretation of GPR data (profiles and amplitude slice-maps) suggest the presence of flat graves, in the west part of the site, and storage pits, post holes and some small trenches, in the centre and north area of the settlement. This interpretation indicates that the settlement is individualized in two different areas, a necropolis and a residential area, such as the first archaeological study

  7. Cross-sectional and longitudinal changes in DNA methylation with age: an epigenome-wide analysis revealing over 60 novel age-associated CpG sites

    PubMed Central

    Florath, Ines; Butterbach, Katja; Müller, Heiko; Bewerunge-Hudler, Melanie; Brenner, Hermann

    2014-01-01

    Understanding the role of epigenetic modifications, e.g. DNA methylation, in the process of aging requires the characterization of methylation patterns in large cohorts. We analysed >480 000 CpG sites using Infinium HumanMethylation450 BeadChip (Illumina) in whole blood DNA of 965 participants of a population-based cohort study aged between 50 and 75 years. In an exploratory analysis in 400 individuals, 200 CpG sites with the highest Spearman correlation coefficients for the association between methylation and age were identified. Of these 200 CpGs, 162 were significantly associated with age, which was verified in an independent cohort of 498 individuals using mixed linear regression models adjusted for gender, smoking behaviour, age-related diseases and random batch effect and corrected for multiple testing by Bonferroni. In another independent cohort of 67 individuals without history of major age-related diseases and with a follow-up of 8 years, we observed a gain in methylation at 96% (52%, significant) of the positively age-associated CpGs and a loss at all (89%, significant) of the negatively age-associated CpGs in each individual while getting 8 years older. A regression model for age prediction based on 17 CpGs as predicting variables explained 71% of the variance in age with an average accuracy of 2.6 years. In comparison with cord blood samples obtained from the Ulm Birth Cohort Study, we observed a more than 2-fold change in mean methylation levels from birth to older age at 86 CpGs. We were able to identify 65 novel CpG sites with significant association of methylation with age. PMID:24163245

  8. Spatial patterns of microbial diversity and activity in an aged creosote-contaminated site

    PubMed Central

    Mukherjee, Shinjini; Juottonen, Heli; Siivonen, Pauli; Lloret Quesada, Cosme; Tuomi, Pirjo; Pulkkinen, Pertti; Yrjälä, Kim

    2014-01-01

    Restoration of polluted sites via in situ bioremediation relies heavily on the indigenous microbes and their activities. Spatial heterogeneity of microbial populations, contaminants and soil chemical parameters on such sites is a major hurdle in optimizing and implementing an appropriate bioremediation regime. We performed a grid-based sampling of an aged creosote-contaminated site followed by geostatistical modelling to illustrate the spatial patterns of microbial diversity and activity and to relate these patterns to the distribution of pollutants. Spatial distribution of bacterial groups unveiled patterns of niche differentiation regulated by patchy distribution of pollutants and an east-to-west pH gradient at the studied site. Proteobacteria clearly dominated in the hot spots of creosote pollution, whereas the abundance of Actinobacteria, TM7 and Planctomycetes was considerably reduced from the hot spots. The pH preferences of proteobacterial groups dominating in pollution could be recognized by examining the order and family-level responses. Acidobacterial classes came across as generalists in hydrocarbon pollution whose spatial distribution seemed to be regulated solely by the pH gradient. Although the community evenness decreased in the heavily polluted zones, basal respiration and fluorescein diacetate hydrolysis rates were higher, indicating the adaptation of specific indigenous microbial populations to hydrocarbon pollution. Combining the information from the kriged maps of microbial and soil chemistry data provided a comprehensive understanding of the long-term impacts of creosote pollution on the subsurface microbial communities. This study also highlighted the prospect of interpreting taxa-specific spatial patterns and applying them as indicators or proxies for monitoring polluted sites. PMID:25105905

  9. Spatial patterns of microbial diversity and activity in an aged creosote-contaminated site.

    PubMed

    Mukherjee, Shinjini; Juottonen, Heli; Siivonen, Pauli; Lloret Quesada, Cosme; Tuomi, Pirjo; Pulkkinen, Pertti; Yrjälä, Kim

    2014-10-01

    Restoration of polluted sites via in situ bioremediation relies heavily on the indigenous microbes and their activities. Spatial heterogeneity of microbial populations, contaminants and soil chemical parameters on such sites is a major hurdle in optimizing and implementing an appropriate bioremediation regime. We performed a grid-based sampling of an aged creosote-contaminated site followed by geostatistical modelling to illustrate the spatial patterns of microbial diversity and activity and to relate these patterns to the distribution of pollutants. Spatial distribution of bacterial groups unveiled patterns of niche differentiation regulated by patchy distribution of pollutants and an east-to-west pH gradient at the studied site. Proteobacteria clearly dominated in the hot spots of creosote pollution, whereas the abundance of Actinobacteria, TM7 and Planctomycetes was considerably reduced from the hot spots. The pH preferences of proteobacterial groups dominating in pollution could be recognized by examining the order and family-level responses. Acidobacterial classes came across as generalists in hydrocarbon pollution whose spatial distribution seemed to be regulated solely by the pH gradient. Although the community evenness decreased in the heavily polluted zones, basal respiration and fluorescein diacetate hydrolysis rates were higher, indicating the adaptation of specific indigenous microbial populations to hydrocarbon pollution. Combining the information from the kriged maps of microbial and soil chemistry data provided a comprehensive understanding of the long-term impacts of creosote pollution on the subsurface microbial communities. This study also highlighted the prospect of interpreting taxa-specific spatial patterns and applying them as indicators or proxies for monitoring polluted sites. PMID:25105905

  10. Age-related and site-specific adaptation of the arterial endothelial cytoskeleton during atherogenesis.

    PubMed Central

    Yost, J. C.; Herman, I. M.

    1988-01-01

    The authors probed the vascular endothelial cell cytoskeleton in strains of pigeons that are atherosclerosis-susceptible and disease-resistant, namely, the White Carneau and Show Racer pigeons. Endothelial cell actin and myosin were localized with the use of affinity-purified antibodies in conjunction with indirect immunofluorescence microscopy. The endothelial cell cytoskeleton was characterized in a site-specific and time-dependent manner by examination of arterial segments from each strain of pigeons. Anti-actin and anti-myosin fluorescence staining patterns of endothelial cells lining the ascending aorta, aortic arch, and thoracic aorta from the White Carneau and Show Racer pigeons sacrificed at 1 and 12 months of age were compared and analyzed. In the Show Racer, irrespective of arterial site or chronologic age, endothelial cell cytoskeletal organization is similar. Actin and myosin fluorescence is brightest at the cortex, where endothelial cells meet their neighbors. There is also an amorphous (diffuse) fluorescence throughout the cytoplasm. In addition to the diffuse and cortical cytoskeletal fluorescence in the endothelial cells of the Show Racers, the White Carneau also possess a unique cytoskeletal array of linear fluorescence, ie, the endothelial cell ridge. At 1 month of age, anti-actin staining of endothelial cell ridges averages 28.5 mu in length in the ascending aorta, 28.0 mu in the aortic arch, and 40.0 mu in the thoracic aorta. At the same time, anti-myosin fluorescence extends past both ends of the anti-actin-stained endothelial cell ridge fluorescence. In the ascending aorta, anti-myosin labeling of endothelial cell ridges is 3.5 times longer than anti-actin staining. This staining is absent in the aortic arch, whereas the thoracic aorta possesses endothelial cell ridges that extend over the entire length of the vessel segment. At 12 months of age, actin-stained endothelial cell ridges increase 1.6- and 1.4-fold in the ascending aorta and aortic

  11. Effects of ageing on elution behaviour of nitrogenous compounds in disposed wastes from landfill sites.

    PubMed

    Nishio, Takayuki

    2014-01-01

    Comparative studies of elution and cation exchange capacity (CEC) tests were applied to aged and fresh municipal and industrial solid wastes to examine the effects of ageing on the long-term elution behaviour of nitrogen on leachate in municipal and industrial solid waste landfill sites. Nitrogen in the leachate gradually eluted as organic nitrogen, but not upon transformation of organic nitrogen to elutable inorganic nitrogen compounds in the solid waste. Ammonium in the solid waste, retained similar to its interaction with clay minerals in soil, elutes when exposed to leachate by being replaced with highly concentrated cations or loses its positive charge in high pH in the leachate, which percolates down from the upper layer of the disposed waste. The quantity of ammonium adsorbed into the aged wastes through CEC measurement process by replacement with ammonium acetate was higher than that onto the fresh wastes. That difference in quantities can serve as an index of the ability of the solid waste to withhold ammonium in the leachate that percolates down the landfill layer. Those results demonstrate that ammonification of organic nitrogen in the waste is not the crucial step of the elution of nitrogenous compounds into leachate. PMID:25145199

  12. Disabling the mitotic spindle and tumor growth by targeting a cavity-induced allosteric site of survivin

    PubMed Central

    Berezov, A; Cai, Z; Freudenberg, JA; Zhang, H; Cheng, X; Thompson, T; Murali, R; Greene, MI; Wang, Q

    2012-01-01

    Survivin is a member of the inhibitor of apoptosis protein family and has an essential role in mitosis. Survivin is overexpressed in a large variety of human cancers and represents an attractive target for cancer therapy. Epidermal growth factor receptor and Her/neu-transformed human tumors in particular exhibit high levels of survivin. The survivin protein forms dimers through a conserved region that is critical for subcellular localization and biological functions of the protein. We identified small molecules that target a specific cavity adjacent to the survivin dimerization surfaces. S12, a lead compound identified in the screen, can bind to the survivin protein at the intended target site. Moreover, S12 alters spindle formation, causing mitotic arrest and cell death, and inhibits tumor growth in vitro and in vivo. Cell death occurs in premetaphase stage following mitotic arrest and is not a consequence of general toxicity. Thus, the study validates a novel therapeutic target site in the survivin protein and provides a promising strategy to develop a new class of therapeutic small molecules for the treatment of human cancers. PMID:21892210

  13. Transcriptional profiling of genes at the human common fragile site FRA1H in tumor-derived cell lines.

    PubMed

    Pelliccia, Franca; Curatolo, Angela; Limongi, Zaira M; Bosco, Nazario; Rocchi, Angela

    2007-10-15

    Common fragile sites (CFSs) are chromosome regions that exhibit gaps and breaks when the cells are exposed to replication stress and to some DNA-binding compounds. In cancer cells, the CFSs are frequently involved in recurrent chromosome rearrangements. Furthermore, altered expression of associated genes, known or potential oncogenes, and tumor-suppressor genes has often been observed. Seventeen of the 88 listed CFSs have been analyzed at the molecular level, but the basis of their fragility has not been clarified. In the present work, the nine genes TGFB2, IARS2, MARK1, TAF1A, TP53BP2, ADPRT, including a very large gene ESRRG and two microRNA genes, MIRN194-1 and MIRN215, localized in the fragile site FRA1H, were investigated by polymerase chain reaction (PCR) for homozygous deletions and by real-time PCR for modification or loss of gene expression in a panel of 19 cancer cell lines. The expression level of five (ESRRG, TGFB2, MIRN194-1, MIRN215, and MARK1) of the nine genes studied presented significant modifications in some of the 19 examined tumor-derived cell lines compared to their normal control tissues. Because of their function, these genes could have a role in neoplastic transformation. PMID:17954271

  14. Primary Tumor Site as a Predictor of Treatment Outcome for Definitive Radiotherapy of Advanced-Stage Oral Cavity Cancers

    SciTech Connect

    Lin, Chien-Yu; Wang, Hung-Ming; Kang, Chung-Jan; Lee, Li-Yu; Huang, Shiang-Fu; Fan, Kang-Hsing; Chen, Eric Yen-Chao

    2010-11-15

    Purpose: To evaluate the outcome of definitive radiotherapy (RT) for oral cavity cancers and to assess prognostic factors. Methods and Materials: Definitive RT was performed on 115 patients with oral cavity cancers at Stages III, IVA, and IVB, with a distribution of 6%, 47%, and 47%, respectively. The median dose of RT was 72Gy (range, 62-76Gy). Cisplatin-based chemotherapy was administered to 95% of the patients. Eleven patients underwent salvage surgery after RT failure. Results: Eight-eight (76.5%) patients responded partially and 23 (20%) completely; of the patients who responded, 18% and 57%, respectively, experienced a durable effect of treatment. The 3-year overall survival, disease-specific survival, and progression-free survival were 22%, 27%, and 25%, respectively. The 3-year PFS rates based on the primary tumor sites were as follows: Group I (buccal, mouth floor, and gum) 51%, Group II (retromolar and hard palate) 18%, and Group III (tongue and lip) 6% (p < 0.0001). The 3-year progression-free survival was 41% for N0 patients and 19% for patients with N+ disease (p = 0.012). The T stage and RT technique did not affect survival. The patients who underwent salvage surgery demonstrated better 3-year overall survival and disease-specific survival (53% vs. 19%, p = 0.015 and 53% vs. 24%, p = 0.029, respectively). Subsite group, N+, and salvage surgery were the only significant prognostic factors for survival after multivariate analysis. Conclusion: The primary tumor site and neck stage are prognostic predictors in advanced-stage oral cancer patients who received radical RT. The primary tumor extension and RT technique did not influence survival.

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

    PubMed

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

    2014-02-01

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

  16. Does Local Recurrence of Prostate Cancer After Radiation Therapy Occur at the Site of Primary Tumor? Results of a Longitudinal MRI and MRSI Study

    SciTech Connect

    Arrayeh, Elnasif; Westphalen, Antonio C.; Kurhanewicz, John; Roach, Mack; Jung, Adam J.; Carroll, Peter R.; Coakley, Fergus V.

    2012-04-01

    Purpose: To determine if local recurrence of prostate cancer after radiation therapy occurs at the same site as the primary tumor before treatment, using longitudinal magnetic resonance (MR) imaging and MR spectroscopic imaging to assess dominant tumor location. Methods and Materials: This retrospective study was HIPAA compliant and approved by our Committee on Human Research. We identified all patients in our institutional prostate cancer database (1996 onward) who underwent endorectal MR imaging and MR spectroscopic imaging before radiotherapy for biopsy-proven prostate cancer and again at least 2 years after radiotherapy (n = 124). Two radiologists recorded the presence, location, and size of unequivocal dominant tumor on pre- and postradiotherapy scans. Recurrent tumor was considered to be at the same location as the baseline tumor if at least 50% of the tumor location overlapped. Clinical and biopsy data were collected from all patients. Results: Nine patients had unequivocal dominant tumor on both pre- and postradiotherapy imaging, with mean pre- and postradiotherapy dominant tumor diameters of 1.8 cm (range, 1-2.2) and 1.9 cm (range, 1.4-2.6), respectively. The median follow-up interval was 7.3 years (range, 2.7-10.8). Dominant recurrent tumor was at the same location as dominant baseline tumor in 8 of 9 patients (89%). Conclusions: Local recurrence of prostate cancer after radiation usually occurs at the same site as the dominant primary tumor at baseline, suggesting supplementary focal therapy aimed at enhancing local tumor control would be a rational addition to management.

  17. Design of site specific radiopharmaceuticals for tumor imaging. (Parts I and II)

    SciTech Connect

    Van Dort, M.E.

    1983-01-01

    Part I. Synthetic methods were developed for the preparation of several iodinated benzoic acid hydrazides as labeling moieties for indirect tagging of carbonyl-containing bio-molecules and potential tumor-imaging agents. Biodistribution studies conducted in mice on the derivatives having the I-125 label ortho to a phenolic OH demonstrated a rapid in vivo deiodination. Part II. The reported high melanin binding affinity of quinoline and other heterocyclic antimalarial drugs led to the development of many analogues of such molecules as potential melanoma-imaging agents. Once such analogue iodochloroquine does exhibit high melanin binding, but has found limited clinical use due to appreciable accumulation in non-target tissues such as the adrenal cortex and inner ear. This project developed a new series of candidate melanoma imaging agents which would be easier to radio-label, could yield higher specific activity product, and which might demonstrate more favorable pharmacokinetic and dosimetric characteristics compared to iodochloroquine.

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

    PubMed Central

    2013-01-01

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

  19. Low density lipoprotein aged in plasma forms clusters resembling subendothelial droplets: aggregation via surface sites.

    PubMed

    De Spirito, Marco; Brunelli, Roberto; Mei, Giampiero; Bertani, Francesca R; Ciasca, Gabriele; Greco, Giulia; Papi, Massimiliano; Arcovito, Giuseppe; Ursini, Fulvio; Parasassi, Tiziana

    2006-06-01

    In early phases of atherogenesis, droplets and vesicles accumulate in the subendothelial extracellular space of arterial intima. There is much evidence to suggest that these droplets, ranging between 100 and 400 nm, derive from modified low-density lipoprotein (LDL). In investigations of the formation mechanism of these droplets, LDL fusion was previously induced in vitro by proteolysis, lipolysis, oxidation, and vigorous shaking, but all treatments failed to reproduce the size distribution range of in vivo droplets, mostly resulting, instead, in particles with a diameter intermediate between that of one and two LDL. Our approach was meant to mimic LDL aging in plasma. LDL isolated from plasma that was incubated overnight at 37 degrees C is slightly modified in the secondary structure of its protein component and is primed to form very large aggregates according to a reaction-limited mechanism. This mechanism requires interactions between selected surface sites, whereas massive fusion is ruled out. In the frame of the general theory for colloids, the aggregation of LDL aged in plasma fulfills all the requirements of the reaction-limited mechanism, encompassing 1), exponential growth; 2), fractal structure, with the dimension of elementary constituent still consistent with a single LDL; and 3), extreme polydispersity of aggregates, with shape and dimension very close to that of droplets observed in vivo. PMID:16533854

  20. Low Density Lipoprotein Aged in Plasma Forms Clusters Resembling Subendothelial Droplets: Aggregation via Surface Sites

    PubMed Central

    De Spirito, Marco; Brunelli, Roberto; Mei, Giampiero; Bertani, Francesca R.; Ciasca, Gabriele; Greco, Giulia; Papi, Massimiliano; Arcovito, Giuseppe; Ursini, Fulvio; Parasassi, Tiziana

    2006-01-01

    In early phases of atherogenesis, droplets and vesicles accumulate in the subendothelial extracellular space of arterial intima. There is much evidence to suggest that these droplets, ranging between 100 and 400 nm, derive from modified low-density lipoprotein (LDL). In investigations of the formation mechanism of these droplets, LDL fusion was previously induced in vitro by proteolysis, lipolysis, oxidation, and vigorous shaking, but all treatments failed to reproduce the size distribution range of in vivo droplets, mostly resulting, instead, in particles with a diameter intermediate between that of one and two LDL. Our approach was meant to mimic LDL aging in plasma. LDL isolated from plasma that was incubated overnight at 37°C is slightly modified in the secondary structure of its protein component and is primed to form very large aggregates according to a reaction-limited mechanism. This mechanism requires interactions between selected surface sites, whereas massive fusion is ruled out. In the frame of the general theory for colloids, the aggregation of LDL aged in plasma fulfills all the requirements of the reaction-limited mechanism, encompassing 1), exponential growth; 2), fractal structure, with the dimension of elementary constituent still consistent with a single LDL; and 3), extreme polydispersity of aggregates, with shape and dimension very close to that of droplets observed in vivo. PMID:16533854

  1. The active site of oxidative phosphorylation and the origin of hyperhomocysteinemia in aging and dementia.

    PubMed

    McCully, Kilmer S

    2015-01-01

    The active site of oxidative phosphorylation and adenosine triphosphate (ATP) synthesis in mitochondria is proposed to consist of two molecules of thioretinamide bound to cobalamin, forming thioretinaco, complexed with ozone, oxygen, nicotinamide adenine dinucleotide. and inorganic phosphate, TR2CoO3O2NAD(+)H2PO4(-). Reduction of the pyridinium nitrogen of the nicotinamide group by an electron from electron transport complexes initiates polymerization of phosphate with adenosine diphosphate, yielding nicotinamide riboside and ATP bound to thioretinaco ozonide oxygen. A second electron reduces oxygen to hydroperoxyl radical, releasing ATP from the active site. A proton gradient is created within F1F0 ATPase complexes of mitochondria by reaction of protons with reduced nicotinamide riboside and with hydroperoxyl radical, yielding reduced nicotinamide riboside and hydroperoxide. The hyperhomocysteinemia of aging and dementia is attributed to decreased synthesis of adenosyl methionine by thioretinaco ozonide and ATP, causing decreased allosteric activation of cystathionine synthase and decreased allosteric inhibition of methylenetetrahydrofolate reductase and resulting in dysregulation of methionine metabolism. PMID:25887881

  2. Ages of tuff beds at East African early hominid sites and sediments in the Gulf of Aden

    USGS Publications Warehouse

    Sarna-Wojcicki, A. M.; Meyer, C.E.; Roth, P.H.; Brown, F.H.

    1985-01-01

    The early hominids of East Africa were dated by determining the ages of tuff beds at the sites. Despite much research using palaeomagnetic and K/Ar-dating techniques, some of those ages are still controversial 1,2. To obtain independent age estimates for these tephra layers, we have examined cores from DSDP Sites 231 and 232 in the Gulf of Aden (Fig. 1a) which consist mainly of calcareous nannofossil ooze, but also contain rare tephra horizons3 dated by interpolation from the established nannofossil stratigraphy (Fig. 1b). Chemical analysis confirms that the identity and sequence of these horizons is the same as that at the East African sites. We conclude that the age of the Tulu Bor Tuff is <3.4 Myr and hence that the Hadar hominid specimens are also

  3. Near-Infrared Light-Responsive Hydrogel for Specific Recognition and Photothermal Site-Release of Circulating Tumor Cells.

    PubMed

    Lv, Song-Wei; Liu, Ya; Xie, Min; Wang, Jing; Yan, Xue-Wei; Li, Zhen; Dong, Wei-Guo; Huang, Wei-Hua

    2016-06-28

    Isolation of single circulating tumor cells (CTCs) from patients is a very challenging technique that may promote the process of individualized antitumor therapies. However, there exist few systems capable of highly efficient capture and release of single CTCs with high viability for downstream analysis and culture. Herein, we designed a near-infrared (NIR) light-responsive substrate for highly efficient immunocapture and biocompatible site-release of CTCs by a combination of the photothermal effect of gold nanorods (GNRs) and a thermoresponsive hydrogel. The substrate was fabricated by imprinting target cancer cells on a GNR-pre-embedded gelatin hydrogel. Micro/nanostructures generated by cell imprinting produce artificial receptors for cancer cells to improve capture efficiency. Temperature-responsive gelatin dissolves rapidly at 37 °C; this allows bulk recovery of captured CTCs at physiological temperature or site-specific release of single CTCs by NIR-mediated photothermal activation of embedded GNRs. Furthermore, the system has been applied to capture, individually release, and genetically analyze CTCs from the whole blood of cancer patients. The multifunctional NIR-responsive platform demonstrates excellent performance in capture and site-release of CTCs with high viability, which provides a robust and versatile means toward individualized antitumor therapies and also shows promising potential for dynamically manipulating cell-substrate interactions in vitro. PMID:27299807

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

    SciTech Connect

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

    1986-07-01

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

  5. Interaction of P-glycoprotein with anti-tumor drugs: the site, gate and pathway.

    PubMed

    Zhang, Junqiao; Li, Debing; Sun, Tianyang; Liang, Lijun; Wang, Qi

    2015-09-01

    Understanding the mechanism and pathway of anti-cancer drugs to be pumped out by P-glycoprotein (P-gp) in cancer cell is very important for the successful chemotherapy. P-gp is a member of ATP-binding cassette (ABC) transporters. In this study, random accelerated molecular dynamics (RAMD) simulation was used to explore the potential egress pathway of ligands from the binding pocket. This could be considered as a reverse process of drug binding. The most possible portal of drugs to dissociate is TM4/TM6, which is almost the same for different drugs, such as paclitaxel and doxorubicin. The interactions in the binding site are found to be remarkably stronger than that outside of the binding site. The results were suggested by the free energy calculation between P-gp and different drugs from metadynamics simulation. All the results indicate that the flexibility of inner residues, especially the residue Phe339, is very important for the drugs to access the binding site. PMID:26205623

  6. Quantification of global mitochondrial DNA methylation levels and inverse correlation with age at two CpG sites

    PubMed Central

    Mawlood, Shakhawan K.; Dennany, Lynn; Watson, Nigel; Dempster, John; Pickard, Benjamin S.

    2016-01-01

    Mammalian ageing features biological attrition evident at cellular, genetic and epigenetic levels. Mutation of mitochondrial DNA, and nuclear DNA methylation changes are well established correlates of ageing. The methylation of mitochondrial DNA (mtDNA) is a new and incompletely described phenomenon with unknown biological control and significance. Here we describe the bisulphite sequencing of mtDNA from 82 individuals aged 18‐91 years. We detected low and variable levels of mtDNA methylation at 54 of 133 CpG sites interrogated. Regression analysis of methylation levels at two CpG sites (M1215 and M1313) located within the 12S ribosomal RNA gene showed an inverse correlation with subject age suggesting their utility as epigenetic markers of ageing. PMID:26887692

  7. High-dose cyclophosphamide induces specific tumor immunity with concomitant recruitment of LAMP1/CD107a-expressing CD4-positive T cells into tumor sites.

    PubMed

    Naito, Tatsushi; Baba, Tomohisa; Takeda, Kazuyoshi; Sasaki, Soichiro; Nakamoto, Yasunari; Mukaida, Naofumi

    2015-09-28

    Cancer chemotherapy regimens, particularly those employing high-dose cytotoxic drugs such as cyclophosphamide (CTX), have been considered to be immune suppressive. However, we observed that a single administration of high-dose CTX abolished tumors arising from subcutaneous injection of a mouse hepatoma cell line and subsequently induced specific tumor immunity. Depletion of T cells, specifically CD4(+) T cells, abrogated the CTX-mediated tumor regression. CTX treatment induced the rapid recruitment of CD4(+) T cells into the tumors, and these recruited cells initiated expression of LAMP1/CD107a, a cytotoxic granule molecule, and granzyme B in the absence of antigen presentation at draining lymph nodes and proliferation in the tumor tissues. Moreover, CTX enhanced the expression of a CC chemokine, CCL3, in tumor tissues, and CTX-mediated tumor regression was attenuated in mice deficient in CCR5, the receptor for this chemokine. Consistently, less CTX-induced accumulation of intratumoral LAMP1/CD107a-expressing CD4(+) T cells was observed in mice receiving splenocytes derived from CCR5-deficient mice than in those receiving splenocytes derived from WT mice. Thus, CTX induces the expression of CCL3, which induces the intratumoral migration of CD4(+) T cells expressing cytotoxic molecules, leading to tumor eradication and subsequent specific tumor immunity. PMID:26116901

  8. A redundant nuclear protein binding site contributes to negative regulation of the mouse mammary tumor virus long terminal repeat.

    PubMed Central

    Bramblett, D; Hsu, C L; Lozano, M; Earnest, K; Fabritius, C; Dudley, J

    1995-01-01

    The tissue specificity of mouse mammary tumor virus (MMTV) expression is controlled by regulatory elements in the MMTV long terminal repeat (LTR). These regulatory elements include the hormone response element, located approximately between -200 and -75, as well as binding sites for NF-1, Oct-1 (OTF-1), and mammary gland enhancer factors. Naturally occurring MMTV deletion variants isolated from T-cell and kidney tumors, transgenic-mouse experiments with MMTV LTR deletions, and transient transfection assays with LTR constructs indicate that there are additional transcription regulatory elements, including a negative regulatory element (NRE), located upstream of the hormone response element. To further define this regulatory region, we have constructed a series of BAL 31 deletion mutants in the MMTV LTR for use in transient transfection assays. These assays indicated that deletion of two regions (referred to as promoter-distal and -proximal NREs) between -637 and -201 elevated basal MMTV promoter activity in the absence of glucocorticoids. The region between -637 and -264 was surveyed for the presence of nuclear protein binding sites by gel retardation assays. Only one type of protein complex (referred to as NRE-binding protein or NBP) bound exclusively to sites that mapped to the promoter-distal and -proximal NREs identified by BAL 31 mutations. The promoter-proximal binding site was mapped further by linker substitution mutations and transfection assays. Mutations that mapped to a region containing an inverted repeat beginning at -287 relative to the start of transcription elevated basal expression of a reporter gene driven by the MMTV LTR. A 59-bp DNA fragment from the distal NRE also bound the NBP complex. Gel retardation assays showed that mutations within both inverted repeats of the proximal NRE eliminated NBP binding and mutations within single repeats altered NBP binding. Intriguingly, the NBP complex was detected in extracts from T cells and lung cells but

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

    PubMed

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

    2014-01-01

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

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

    PubMed Central

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

    2008-01-01

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

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

    PubMed Central

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

    2016-01-01

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

  12. A Simple Way to Enhance Doxil® Therapy: Drug Release from Liposomes at the Tumor Site by Amphiphilic Block Copolymer

    PubMed Central

    Zhao, Yi; Alakhova, Daria Y.; Kim, Jong Oh; Bronich, Tatiana K.; Kabanov, Alexander V.

    2013-01-01

    The antitumor efficacy of Doxil® is hindered by the poor release of the active drug from the liposome at the tumor sites. This study investigates a possibility to enhance drug release from the liposomes and increase therapeutic efficacy of Doxil® by administering Pluronic block copolymers once the liposomal drug accumulates in the tumor sites. In our study, the fluorescence de-quenching experiments were designed to investigate the drug release from liposome by Pluronic P85. MTT cytotoxicity assay and confocal microscopy images were carried out to determine whether Pluronic P85 could facilitate release of Dox from Doxil®. Anti-tumor growth and distribution of drug were evaluated when Pluronic P85 was injected 1 hr, 48 hrs, or 96 hrs after the Doxil® administration in A2780 human ovarian cancer xenografts. Addition of Pluronic P85 resulted in release of Dox from the liposomes accompanied with significant increases of Dox delivery and cytotoxic effect in cancer cells. The greatest anti-tumor effect of single injection of Doxil® was achieved when Pluronic P85 was administered 48 hrs after Doxil®. The Confocal tile scanning images of tumor section showed that copolymer treatment induced the release of the drug in the tumors from the vessels regions to the bulk of the tumor. No release of the drug remaining in circulation was observed. Our study has demonstrated a simple approach for localized release of Dox from liposome by Pluronic P85 at the tumor site, which was therapeutically beneficial. PMID:23474033

  13. Assembly And Initial Characterization Of A Panel Of 85 Genomically Validated Cell Lines From Diverse Head And Neck Tumor Sites

    PubMed Central

    Zhao, Mei; Sano, Daisuke; Pickering, Curtis R.; Jasser, Samar A.; Henderson, Ying C.; Clayman, Gary L.; Sturgis, Erich M.; Ow, Thomas J.; Lotan, Reuben; Carey, Thomas E.; Sacks, Peter G.; Grandis, Jennifer R.; Sidransky, David; Heldin, Nils Erik; Myers, Jeffrey N.

    2011-01-01

    Purpose Human cell lines are useful for studying cancer biology and pre-clinically modeling cancer therapy, but can be misidentified and cross contamination is unfortunately common. The purpose of this study was to develop a panel of validated head and neck cell lines representing the spectrum of tissue sites and histologies that could be used for studying the molecular, genetic, and phenotypic diversity of head and neck cancer. Methods A panel of 122 clinically and phenotypically diverse head and neck cell lines from head and neck squamous cell carcinoma (HNSCC), thyroid cancer, cutaneous squamous cell carcinoma, adenoid cystic carcinoma, oral leukoplakia, immortalized primary keratinocytes, and normal epithelium, was assembled from the collections of several individuals and institutions. Authenticity was verified by performing short tandem repeat (STR) analysis. Human papillomavirus (HPV) status and cell morphology were also determined. Results Eighty-five of the 122 cell lines had unique genetic profiles. HPV-16 DNA was detected in 2 cell lines. These 85 cell lines included cell lines from the major head and neck primary tumor sites, and close examination demonstrates a wide range of in vitro phenotypes. Conclusion This panel of 85 genomically validated head and neck cell lines represents a valuable resource for the head and neck cancer research community that can help advance understanding of the disease by providing a standard reference for cell lines that can be utilized for biological as well as preclinical studies. PMID:21868764

  14. Site-specific in situ growth of a cyclized protein-polymer conjugate with improved stability and tumor retention.

    PubMed

    Hu, Jin; Zhao, Wenguo; Gao, Yan; Sun, Mengmeng; Wei, Yen; Deng, Haiteng; Gao, Weiping

    2015-04-01

    A major disadvantage of therapeutic proteins is their instability to external stressors during storage, transport and use. Here, we report site-specific in situ growth of a cyclized protein-polymer conjugate with improved in vitro and in vivo stability. Green fluorescence protein (GFP) was genetically fused at its N- and C-termini with two sortase recognition sequences pentaglycine and LPETG, respectively to yield a linear GFP (l-GFP). A cyclized GFP (c-GFP) was generated from the l-GFP by sortase-catalyzed cyclization. A maleimide-functionalized atom transfer radical polymerization (ATRP) initiator was selectively attached to a free cysteine residue genetically engineered at the C-terminus of GFP to form a macroinitiator (c-GFP-Br). Subsequent in situ ATRP of oligo(ethylene glycol) methyl ether methacrylate (OEGMA) from the c-GFP-Br generated a site-specific (C-terminal) and stoichiometric (1:1) c-GFP-POEGMA conjugate with almost quantitative conversion and highly retained activity. Notably, the c-GFP-POEGMA conjugate showed 9- and 310-fold increases in thermal stability as compared to the l-GFP and its counterpart l-GFP-POEGMA, respectively. Additionally, the conjugate displayed significantly improved tumor retention relative to the l-GFP and l-GFP-POEGMA. The method developed may be applicable to a variety of therapeutic proteins to improve their in vitro and in vivo stability. PMID:25682156

  15. Clinically Significant Prostate Cancer Local Recurrence After Radiation Therapy Occurs at the Site of Primary Tumor: Magnetic Resonance Imaging and Step-Section Pathology Evidence

    SciTech Connect

    Pucar, Darko Hricak, Hedvig; Shukla-Dave, Amita; Kuroiwa, Kentaro; Drobnjak, Marija; Eastham, James; Scardino, Peter T.; Zelefsky, Michael J.

    2007-09-01

    Purpose: To determine whether prostate cancer local recurrence after radiation therapy (RT) occurs at the site of primary tumor by retrospectively comparing the tumor location on pre-RT and post-RT magnetic resonance imaging (MRI) and using step-section pathology after salvage radical prostatectomy (SRP) as the reference standard. Methods and Materials: Nine patients with localized prostate cancer were treated with intensity modulated RT (69-86.4 Gy), and had pre-RT and post-RT prostate MRI, biopsy-proven local recurrence, and SRP. The location and volume of lesions on pre-RT and post-RT MRI were correlated with step-section pathology findings. Tumor foci >0.2 cm{sup 3} and/or resulting in extraprostatic disease on pathology were considered clinically significant. Results: All nine significant tumor foci (one in each patient; volume range, 0.22-8.63 cm{sup 3}) were detected both on pre-RT and post-RT MRI and displayed strikingly similar appearances on pre-RT and post-RT MRI and step-section pathology. Two clinically insignificant tumor foci ({<=}0.06 cm{sup 3}) were not detected on imaging. The ratios between tumor volumes on pathology and on post-RT MRI ranged from 0.52 to 2.80. Conclusions: Our study provides a direct visual confirmation that clinically significant post-RT local recurrence occurs at the site of primary tumor. Our results are in agreement with reported clinical and pathologic results and support the current practice of boosting the radiation dose within the primary tumor using imaging guidance. They also suggest that monitoring of primary tumor with pre-RT and post-RT MRI could lead to early detection of local recurrence amenable to salvage treatment.

  16. Age of Giordano Bruno crater as deduced from the morphology of its secondaries at the Luna 24 landing site

    NASA Astrophysics Data System (ADS)

    Basilevsky, A. T.; Head, J. W.

    2012-12-01

    We undertook a photogeologic study of Lunar Reconnaissance Orbiter Camera (LROC) Narrow Angle Camera (NAC) images of the ejecta of the very young 22-km diameter crater Giordano Bruno (GB) and for the Luna 24 landing site region, where secondary craters from Giordano Bruno are observed. Using the technique of Basilevsky (1976) for estimating the absolute ages of small lunar craters based on their morphologic prominence and size, craters near the Luna 24 site considered to be secondaries of Giordano Bruno crater and craters superposed on ejecta of Giordano Bruno crater are found to have approximately the same age: somewhere between 5 and 10 m.y. This suggests that the craters at the Luna 24 site are indeed secondaries of GB crater and that this age range is an estimate for the time of GB crater formation. Our results generally agree with estimates derived from counts of small craters superposed on GB ejecta: 1-10 m.y. and with the exposure age of one of the samples derived from Zone I of the Luna 24 core. Plescia et al. (2010b) interpreted a large fraction of the craters superposed on GB ejecta and floor not as primary craters, but rather as secondary craters formed from the GB event itself. On this basis, it was postulated that GB may be formed by an historic impact. Our new data and analysis do not support an age as young as historical. The general agreement of our results for age determination for the GB secondaries of the Luna 24 area, and for craters superposed on the GB ejecta, with the age estimate based on crater count and with the mentioned exposition age of one of the Luna 24 samples, also validates the technique of Basilevsky (1976). A special study of the Luna 24 samples should be undertaken designed to find records of the formation age of the crater on whose rim Luna 24 landed, thus better constraining the age of GB crater.

  17. Surface ages and rates of erosion at the Calico Archaeological Site in the Mojave Desert, Southern California

    NASA Astrophysics Data System (ADS)

    Owen, Lewis A.; Davis, Teresa; Caffee, Marc W.; Budinger, Fred; Nash, David

    2011-01-01

    Erosion rates and surface exposure ages were determined at the Calico Archaeological Site in the Calico Hills of the Mojave Desert, California, using 10Be terrestrial cosmogenic nuclides (TCN) methods. The Calico Hills are composed of Miocene lacustrine deposits of the Barstow Formation and fanglomerates/debris flows of the Pleistocene Yermo Deposits. These deposits are highly denuded and dissected by arroyos that have surfaces armored with chert. Surface erosion rates based on cosmogenic 10Be concentrations in stream sediments range from 19 to 39 m/Ma, with an average of 30.5 ± 6.2 m/Ma. Surface boulders have 10Be TCN ages that range from 27 ka to 198 ka, reflecting significant erosion of the Calico Hills. The oldest boulder age (197 ± 20 ka) places a minimum limit on the age of Yermo deposits. Depth profile ages at four locations within the study area have minimum ages that range from 31 to 84 ka and erosion rate-corrected surface exposure ages ranging from 43 to 139 ka. These surface exposure ages support the view that the surfaces in Yermo deposits formed during the Late Pleistocene to latest Middle Pleistocene. This chronology has important implications for interpreting the context of possible artifacts/geofacts at the site that might provide evidence for early human occupation of North America, and for reconstructing paleoenvironment change and landscape evolution in the region.

  18. Estimates of percolation rates and ages of water in unsaturated sediments at two Mojave Desert sites, California-Nevada

    USGS Publications Warehouse

    Prudic, D.E.

    1994-01-01

    Thick unsaturated zones in arid regions increasingly are being sought for the burial of radioactive and other hazardous wastes. Estimating percolation rates of water from precipitation at proposed burial sites is important for site assessment. Chloride profiles in unsaturated sediments are used to show differences and similarities in the rates of perco- lation at two sites in the Mojave Desert of southern Nevada and southeastern California; the first is an existing burial site for low-level radioactive waste in the Amargosa Desert, and the second is a proposed waste-burial site in Ward Valley. The Mojave Desert is one of the most arid regions of the United States. Chloride concentrations in pore water of unsaturated sediments peak between depths of 2 and 3 meters at both the Amargosa Desert and Ward Valley, sites; maximum chloride concentration is 9,000 milligrams per liter at the Amargosa Desert site and 15,000 milligrams per liter at the Ward Valley, site. Below a depth of 10 meters, however, chloride concentrations at the Amargosa Desert site decrease to less than 50 milligrams per liter, whereas concentrations at the Ward Valley site are greater than 2,300 milligrams per liter. Estimated age of water at a depth of 10 meters at both sites is between ]6,000 and 33,000 years. Below a depth of 10 meters, estimated age of water in the sediments at the Ward Valley site is considerably older than at the Amargosa Desert site because of the greater chloride concentrations at the Ward Valley site. The dilute chloride concentrations in the pore water below a depth of 10 meters at the Amargosa Desert site could indicate that the sediments were flushed with water in the past. The climate in the region was wetter and cooler from about 30,000 to 18,000 years ago. Perhaps increased precipitation or more frequent flooding of the Amargosa River resulted in deep percolation at the site. Downward percolation of water since that time seems limited to the upper 10 meters. The

  19. Site-specifically biotinylated VEGF(121) for near-infrared fluorescence imaging of tumor angiogenesis.

    PubMed

    Wang, Hui; Chen, Kai; Niu, Gang; Chen, Xiaoyuan

    2009-01-01

    The vascular endothelial growth factor (VEGF)/VEGF receptor (VEGFR) pathway is considered to be one of the most important regulators of angiogenesis and a key target in anticancer treatment. Imaging VEGFR expression can serve as a new paradigm for assessing the efficacy of antiangiogenic cancer therapy, improving cancer management, and elucidating the role and modulation of VEGF/VEGFR signaling during cancer development and intervention. In this study we developed an Avi-tagged VEGF(121) protein, which is site-specifically biotinylated in the presence of bacterial BirA biotin ligase. BirA biotinylated VEGF(121)-Avi (VEGF(121)-Avib) forms a stable complex with streptavidin-IRDye800 (SA800) that retains high affinity for VEGFR in vitro and allows receptor specific targeting in vivo in a 67NR murine xenograft model. In contrast, chemical coupling of IRDye800 abrogated the VEGFR binding ability of the modified protein both in vitro and in vivo. The VEGF(121)-Avib/SA800 complex (VEGF-Avib/SA800) may be used for quantitative and repetitive near-infrared fluorescence imaging of VEGFR expression and translated into clinic for evaluating cancer and other angiogenesis related diseases. PMID:19099493

  20. Site-Specific Drug-Releasing Polypeptide Nanocarriers Based on Dual-pH Response for Enhanced Therapeutic Efficacy against Drug-Resistant Tumors

    PubMed Central

    Dong, Yaqiong; Yang, Jun; Liu, Hongmei; Wang, Tianyou; Tang, Suoqin; Zhang, Jinchao; Zhang, Xin

    2015-01-01

    To enhance effective drug accumulation in drug-resistant tumors, a site-specific drug-releasing polypeptide system (PEG-Phis/Pasp-DOX/CA4) was exploited in response to tumor extracellular and intracellular pH. This system could firstly release the embedded tumor vascular inhibitor (CA4) to transiently 'normalize' vasculature and facilitate drug internalization to tumors efficiently, and then initiate the secondary pH-response to set the conjugated active anticancer drug (DOX) free in tumor cells. The encapsulated system (PEG-Phis/DOX/CA4), both CA4 and DOX embedding in the nanoparticles, was used as a control. Comparing with PEG-Phis/DOX/CA4, PEG-Phis/Pasp-DOX/CA4 exhibited enhanced cytotoxicity against DOX-sensitive and DOX-resistant cells (MCF-7 and MCF-7/ADR). Moreover, PEG-Phis/Pasp-DOX/CA4 resulted in enhanced therapeutic efficacy in drug-resistant tumors with reduced toxicity. These results suggested that this site-specific drug-releasing system could be exploited as a promising treatment for cancers with repeated administration. PMID:26000060

  1. Topological transition of the parametric expression site of tumor suppressor inactivation as a marker evidence of environmental hormone-oriented cancer risk increase.

    PubMed

    Kodama, M; Murakami, M; Kodama, T

    1999-08-01

    The present study is an extension of our recent study in which we attempted statistical analysis of the data assembly of age-adjusted incidence rates (AAIRs) of a tumor without topological data manipulation for each of 20 individual tumors in scope, for each of 6 cancer registration areas in space, and for a period of early 1960's to mid 1980's in time. This time, a data assembly of log AAIR changes in time and space first passed through the process of topological data manipulation, and then underwent the sequential regression analysis so that we could assess the fitness of log AAIR changes either in space or in time to the equilibrium model of the law of mass action from the viewpoint of the interaction between oncogene activation and tumor suppressor gene inactivation. For the sake of comparison, the fitness of the cancer risk data to the equilibrium model was assessed in the framework of 3 sets of coordinates: a) the original (x org, y org) coordinates in which most of the log AAIR data assemblies in their data variations were classified as the oncogene activation type in the field of centripetal force (r seq=-1.000). b) The rect (X rect, Y rect) coordinates in which the log AAIR data assemblies were very often classified as the tumor suppressor gene inactivation type in the field of centrifugal force (r seq=+1.000). c) The para (X para, Y para) coordinates in which the log AAIR data assemblies were mostly classified as the intermediate type as regards the fitness to the equilibrium model. The rect-coordinates and the para-coordinates, 2 variants of angular rotation of the original coordinates, were so designed as to allow their X-axes to run each at a right angle and parallel to the regression line of the original pair data block. The results obtained were as follows: a) poor fitness of the log AAIR changes in space to the equilibrium model in the rect-coordinates was found in male breast cancer, male thyroid cancer, female esophageal cancer, female laryngeal

  2. Feasibility and safety of outpatient brachytherapy in 37 patients with brain tumors using the GliaSite Radiation Therapy System.

    PubMed

    Chino, Kazumi; Silvain, Daniel; Grace, Ana; Stubbs, James; Stea, Baldassarre

    2008-07-01

    Temporary, low dose rate brachytherapy to the margins of resected brain tumors, using a balloon catheter system (GliaSite Radiation Therapy System) and liquid I-125 radiation source (Iotrex), began in 2002 at the University of Arizona Medical Center. Initially, all patients were treated on an inpatient basis. For patient convenience, we converted to outpatient therapy. In this article we review the exposure data and safety history for the 37 patients treated as outpatients. Proper patient selection and instruction is crucial to having a successful outpatient brachytherapy program. A set of evaluation criteria and patient instructions were developed in compliance with the U.S. Nuclear Regulatory Commission's document NUREG-1556 Volume 9 (Appendix U) and Arizona State Nuclear regulatory guidelines, which specify acceptable exposure rates for outpatient release in this setting. Of the 37 patients monitored, 26 patients were treated for recurrent glioblastoma multiforme (GBM), six for primary GBM, and five for metastatic brain tumors. All 37 patients and their primary caregivers gave signed agreement to follow a specific set of instructions and were released for the duration of brachytherapy (3-7 days). The typical prescription dose was 60 Gy delivered at 0.5 cm from the balloon surface. Afterloaded activities in these patients ranged from 90.9 to 750.0 mCi and measured exposure rates at 1 m from the head were less than 14 mR/h. The mean exposure to the caretaker measured by personal radiation Landauer Luxel + whole body dosimeters for 25 caretakers was found to be 9.6 mR, which was significantly less than the mean calculated exposure of 136.8 mR. For properly selected patients, outpatient brachytherapy is simple and can be performed within established regulatory guidelines. PMID:18697562

  3. Feasibility and safety of outpatient brachytherapy in 37 patients with brain tumors using the GliaSite Radiation Therapy System

    SciTech Connect

    Chino, Kazumi; Silvain, Daniel; Grace, Ana; Stubbs, James; Stea, Baldassarre

    2008-07-15

    Temporary, low dose rate brachytherapy to the margins of resected brain tumors, using a balloon catheter system (GliaSite Radiation Therapy System) and liquid I-125 radiation source (Iotrex), began in 2002 at the University of Arizona Medical Center. Initially, all patients were treated on an inpatient basis. For patient convenience, we converted to outpatient therapy. In this article we review the exposure data and safety history for the 37 patients treated as outpatients. Proper patient selection and instruction is crucial to having a successful outpatient brachytherapy program. A set of evaluation criteria and patient instructions were developed in compliance with the U.S. Nuclear Regulatory Commission's document NUREG-1556 Volume 9 (Appendix U) and Arizona State Nuclear regulatory guidelines, which specify acceptable exposure rates for outpatient release in this setting. Of the 37 patients monitored, 26 patients were treated for recurrent glioblastoma multiforme (GBM), six for primary GBM, and five for metastatic brain tumors. All 37 patients and their primary caregivers gave signed agreement to follow a specific set of instructions and were released for the duration of brachytherapy (3-7 days). The typical prescription dose was 60 Gy delivered at 0.5 cm from the balloon surface. Afterloaded activities in these patients ranged from 90.9 to 750.0 mCi and measured exposure rates at 1 m from the head were less than 14 mR/h. The mean exposure to the caretaker measured by personal radiation Landauer Luxel+ whole body dosimeters for 25 caretakers was found to be 9.6 mR, which was significantly less than the mean calculated exposure of 136.8 mR. For properly selected patients, outpatient brachytherapy is simple and can be performed within established regulatory guidelines.

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

    PubMed Central

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

    2015-01-01

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

  5. Micromorphological investigation on ring road sediments of the Early Bronze Age site Tell Chuera, Syria

    NASA Astrophysics Data System (ADS)

    Fritzsch, Dagmar; Thiemeyer, Heinrich

    2010-05-01

    Tell Chuera is an Early Bronze Age settlement mount in NE-Syria close to the Turkish border. With a diameter of almost 1 km and a height of 18 m it is one of the biggest tells in the region between the rivers Balikh and Khabur. In 1958 the structures of the city wall was known first by Orthmann (1990). This city wall was built of air-dried mud bricks. The age of the founding of this construction is not yet clear. The earliest pottery from the place is dated around 2500 BC to 2350 BC. Inside the fortification a road was detected, which was first excavated by Novak (1995). We took sediment monoliths in 2004 from a new trench, which shows the same situation of the road. A geomagnetic prospection, that included the whole site, suggests that the road was part of the planned extension of the lower town and serves as a circular road (Meyer, in prep.). The micromorphological investigation focussed on the question, how the road was used. Did animals have had access to the town? The thin sections show different indications of the anthropogenic influence. In all samples pseudomorphs after straw are visible. In many parts ash, charred wood fragments, bone fragments, melted material and fragments of basalt and flint were observable, too. These materials are typical for sediments in streets (cf. Goldberg & Macphail, 2006). In some parts of the thin sections faecal spherulites and dung remains with faecal spherulites give an idea that ruminants used the road as well as men. Trampling structures support this assumption. Moreover, leaching of calcite, its redeposition in mottles, pseudomycels and concretions, hydromorphic stains and the translocation of silt indicate postdepositional pedogenic processes. Literature Goldberg, P., & Macphail, R. I. (2006). Practical and theoretical geoarchaeology: UK Blackwell Publishing. Meyer, J.-W. (in prep.). Überlegungen zur Siedlungsstruktur - eine erste Analyse der Ergebnisse der geomagnetischen Prospektion. In J.-W. Meyer (Ed.), Ausgrabungen

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

    SciTech Connect

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

    1980-03-01

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

  7. Hypothalamic tumor

    MedlinePlus

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

  8. Modeling Site-Based Decision Making: School Practices in the Age of Accountability

    ERIC Educational Resources Information Center

    Bauer, Scott C.; Bogotch, Ira E.

    2006-01-01

    Purpose: The primary purpose is to present empirical measures of variables relating to practices engaged in by site-based teams, and then to use these variables to test a model predicting significant outcomes of site-based decision making. The practice variables of site-based management (SBM) teams are essential in promoting research within a…

  9. Difference in radiocarbon ages of carbonized material from the inner and outer surfaces of pottery from a wetland archaeological site

    PubMed Central

    MIYATA, Yoshiki; MINAMI, Masayo; ONBE, Shin; SAKAMOTO, Minoru; MATSUZAKI, Hiroyuki; NAKAMURA, Toshio; IMAMURA, Mineo

    2011-01-01

    AMS (Accelerator Mass Spectrometry) radiocarbon dates for eight potsherds from a single piece of pottery from a wetland archaeological site indicated that charred material from the inner pottery surfaces (5052 ± 12 BP; N = 5) is about 90 14C years older than that from the outer surfaces (4961 ± 22 BP; N = 7). We considered three possible causes of this difference: the old wood effect, reservoir effects, and diagenesis. We concluded that differences in the radiocarbon ages between materials from the inner and outer surfaces of the same pot were caused either by the freshwater reservoir effect or by diagenesis. Moreover, we found that the radiocarbon ages of carbonized material on outer surfaces (soot) of pottery from other wetland archaeological sites were the same as the ages of material on inner surfaces (charred food) of the same pot within error, suggesting absence of freshwater reservoir effect or diagenesis. PMID:21986315

  10. Difference in radiocarbon ages of carbonized material from the inner and outer surfaces of pottery from a wetland archaeological site.

    PubMed

    Miyata, Yoshiki; Minami, Masayo; Onbe, Shin; Sakamoto, Minoru; Matsuzaki, Hiroyuki; Nakamura, Toshio; Imamura, Mineo

    2011-01-01

    AMS (Accelerator Mass Spectrometry) radiocarbon dates for eight potsherds from a single piece of pottery from a wetland archaeological site indicated that charred material from the inner pottery surfaces (5052 ± 12 BP; N = 5) is about 90 (14)C years older than that from the outer surfaces (4961 ± 22 BP; N = 7). We considered three possible causes of this difference: the old wood effect, reservoir effects, and diagenesis. We concluded that differences in the radiocarbon ages between materials from the inner and outer surfaces of the same pot were caused either by the freshwater reservoir effect or by diagenesis. Moreover, we found that the radiocarbon ages of carbonized material on outer surfaces (soot) of pottery from other wetland archaeological sites were the same as the ages of material on inner surfaces (charred food) of the same pot within error, suggesting absence of freshwater reservoir effect or diagenesis. PMID:21986315

  11. Debatable aspects of initial human colonization of Siberia and age of the Karama site in the Altai Mountains

    NASA Astrophysics Data System (ADS)

    Zykin, V. S.; Zykina, V. S.; Smolyaninova, L. G.

    2016-05-01

    Debatable aspects of age, stratigraphic position, and natural conditions of the oldest stratified Early Paleolithic Karama site in the Altai Mountains are critically revised. The extensive geological, stratigraphic, and paleontological data allow the sufficiently well-substantiated assumption that accumulation of the Karama Formation and existence of the Early Paleolithic Karama site correspond to a long period of climate warming in the Early Pleistocene correlated with the Tiglian of northwestern Europe lasting from 2.23 to 1.59 Ma. The age model proposed for the formation of the Quaternary sequence in the Anui River valley, which includes the artifact-containing deposits of the Karama site, seems to be the most probable one proceeding from interpretation of available data on the geological structure, stratigraphy, paleomagnetism, and paleontological and lithological properties of Upper Cenozoic sequences observable both in the Anui River valley and in Siberian areas adjacent to the Altai mountainous region.

  12. Aging.

    PubMed

    Park, Dong Choon; Yeo, Seung Geun

    2013-09-01

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

  13. Aging

    PubMed Central

    Park, Dong Choon

    2013-01-01

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

  14. Body mass index in adolescent anorexia nervosa patients in relation to age, time point and site of admission.

    PubMed

    Bühren, Katharina; von Ribbeck, Linda; Schwarte, Reinhild; Egberts, Karin; Pfeiffer, Ernst; Fleischhaker, Christian; Wewetzer, Christoph; Kennes, Lieven N; Dempfle, Astrid; Herpertz-Dahlmann, Beate

    2013-07-01

    Body mass index (BMI) at admission is an important predictor of outcome in adolescent eating disorders. However, few studies have investigated BMI at admission, its changes in recent years, or modifying factors, such as duration of illness and age at onset in different geographical regions. Thus, this study aimed to investigate changes in BMI at admission over the past decade in one clinic, the differences in BMI between various treatment sites and the influence of duration of illness before admission and age at admission. Our sample consisted of 158 adolescent female patients with anorexia nervosa (AN) admitted between 2001 and 2009 to a major university hospital and 169 adolescent female patients recruited in a multicenter study between 2007 and 2010. We assessed the differences between departments in different regions of Germany in the multi-site sample. Changes over time in age-adjusted BMI and age at admission as well as modifying factors for age-adjusted BMI at admission, such as age at admission and duration of illness, were assessed in a representative local sample. There were no significant differences between departments in different regions of Germany. Over the course of the local study, there was a small but significant increase in the age-adjusted BMI score and absolute BMI at admission. In addition, there was a positive association between year of admission and age at admission. Older adolescents with AN had a lower age-adjusted BMI score and a longer duration of illness at the time of admission. The BMI at admission, which is one of the most important predictors of outcome in AN, has increased slightly during the past 10 years. Education strategies for parents and professionals should continue to be improved to further shorten the duration of illness before admission, especially for older adolescents. PMID:23392754

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2015-01-01

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

  17. Multi-site tumor sampling (MSTS) improves the performance of histological detection of intratumor heterogeneity in clear cell renal cell carcinoma (CCRCC)

    PubMed Central

    Guarch, Rosa; Cortés, Jesús M.

    2016-01-01

    Current standard-of-care tumor sampling protocols for CCRCC (and other cancers) are not efficient at detecting intratumoural heterogeneity (ITH). We have demonstrated in silico that an alternative protocol, multi-site tumor sampling (MSTS) based upon the divide and conquer (DAC) algorithm, can significantly increase the efficiency of ITH detection without extra costs. Now we test this protocol on routine hematoxylin-eosin (HE) sections in a series of 38 CCRCC cases. MSTS was found to outperform traditional sampling when detecting either high grade (p=0.0136) or granular/eosinophilic cells (p=0.0114). We therefore propose that MSTS should be used in routine clinical practice.

  18. A Generational Comparison of Social Networking Site Use: The Influence of Age and Social Identity

    ERIC Educational Resources Information Center

    Barker, Valerie

    2012-01-01

    An online survey (N = 256) compared social networking site (SNS) use among younger (millennial: 18-29) and older (baby-boomer: 41-64) subscribers focusing on the influence of collective self-esteem and group identity on motives for SNS use. Younger participants reported higher positive collective self-esteem, social networking site use for peer…

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed Central

    2013-01-01

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

  1. Wolf's post-herpetic isotopic response: Infections, tumors, and immune disorders arising on the site of healed herpetic infection.

    PubMed

    Ruocco, Vincenzo; Ruocco, Eleonora; Brunetti, Giampiero; Russo, Teresa; Gambardella, Alessio; Wolf, Ronni

    2014-01-01

    Herpes simplex viruses (HSV-1/HSV-2) and varicella-zoster virus (VZV) have several characteristics in common. Both are epidermoneurotropic, cause skin eruptions accompanied by sensory symptoms (itch, pain), damage peripheral sensory nerve fibers and cutaneous nerve endings, and interfere with neuromediator release, which can alter local mechanisms of immune control. For this reason, herpes-infected areas may become a preferential location for the subsequent onset of immunity-related skin disorders (infections, tumors, and dysimmune reactions), an event first reported by a neurologist and focused on by two brothers, a dermatologist and a pediatrician. The phenomenon therefore named Wolf's post-herpetic isotopic response (PHIR) refers to the occurrence of a new skin disorder at the site of a previous and already healed herpetic eruption (herpes zoster in most cases). Until now, we have been able to gather 189 well-documented cases of PHIR (all reported in the reference section), but our list is far from being complete. Some of the most emblematic cases are briefly described here. In some circumstances, the opposite of PHIR occurs, with diffuse skin disorders or eruptions that selectively spare herpes-infected areas (Wolf's post-herpetic isotopic nonresponse). Experimental investigations with patch testing have been performed in seven patients who were sensitized to nickel and had had herpes zoster in the past years. The tests were carried out bilaterally on the affected dermatomes and on the unaffected contralateral ones. The uneven immune responses we obtained have shown that the immune behavior of an herpes zoster-affected dermatome can be different from that of the corresponding contralateral dermatome, thus supporting the existence of immune dysregulation in herpes-infected areas. PMID:25160097

  2. Auger electron spectroscopy for the determination of sex and age related Ca/P ratio at different bone sites

    SciTech Connect

    Balatsoukas, Ioannis; Kourkoumelis, Nikolaos; Tzaphlidou, Margaret

    2010-10-15

    The Ca/P ratio of normal cortical and trabecular rat bone was measured by Auger electron spectroscopy (AES). Semiquantitative analysis was carried out using ratio techniques to draw conclusions on how age, sex and bone site affect the relative composition of calcium and phosphorus. Results show that Ca/P ratio is not sex dependent; quite the opposite, bone sites exhibit variations in elemental stoichiometry where femoral sections demonstrate higher Ca/P ratio than rear and front tibias. Age-related changes are more distinct for cortical bone in comparison with the trabecular bone. The latter's Ca/P ratio remains unaffected from all the parameters under study. This study confirms that AES is able to successfully quantify bone mineral main elements when certain critical points, related to the experimental conditions, are addressed effectively.

  3. Site-specific AGE modifications in the ECM: a role for glyoxal in protein damage in diabetes

    PubMed Central

    Voziyan, Paul; Brown, Kyle L.; Chetyrkin, Sergei; Hudson, Billy

    2014-01-01

    Non-enzymatic modification of proteins in hyperglycemia is a major proposed mechanism of diabetic complications. Specifically, advanced glycation end products (AGEs) derived from hyperglycemia-induced reactive carbonyl species (RCS) can have pathogenic consequences when they target functionally critical protein residues. Modification of a small number of these critical residues, often undetectable by the methodologies relying on measurements of total AGE levels, can cause significant functional damage. Therefore, detection of specific sites of protein damage in diabetes is central to understanding molecular basis of diabetic complications and for identification of biomarkers which are mechanistically linked to the disease. The current paradigm of RCS-derived protein damage places the major focus on methylglyoxal (MGO), an intermediate of cellular glycolysis. We propose that glyoxal (GO) is a major contributor to extracellular matrix (ECM) damage in diabetes. Here, we review the current knowledge and provide new data about GO-derived site-specific ECM modification in experimental diabetes. PMID:23492568

  4. Auger electron spectroscopy for the determination of sex and age related Ca/P ratio at different bone sites

    NASA Astrophysics Data System (ADS)

    Balatsoukas, Ioannis; Kourkoumelis, Nikolaos; Tzaphlidou, Margaret

    2010-10-01

    The Ca/P ratio of normal cortical and trabecular rat bone was measured by Auger electron spectroscopy (AES). Semiquantitative analysis was carried out using ratio techniques to draw conclusions on how age, sex and bone site affect the relative composition of calcium and phosphorus. Results show that Ca/P ratio is not sex dependent; quite the opposite, bone sites exhibit variations in elemental stoichiometry where femoral sections demonstrate higher Ca/P ratio than rear and front tibias. Age-related changes are more distinct for cortical bone in comparison with the trabecular bone. The latter's Ca/P ratio remains unaffected from all the parameters under study. This study confirms that AES is able to successfully quantify bone mineral main elements when certain critical points, related to the experimental conditions, are addressed effectively.

  5. Dating and context of three middle stone age sites with bone points in the Upper Semliki Valley, Zaire.

    PubMed

    Brooks, A S; Helgren, D M; Cramer, J S; Franklin, A; Hornyak, W; Keating, J M; Klein, R G; Rink, W J; Schwarcz, H; Smith, J N

    1995-04-28

    The extent to which the earliest anatomically modern humans in Africa exhibited behavioral and cognitive traits typical of Homo sapiens sapiens is controversial. In eastern Zaire, archaeological sites with bone points have yielded dates older than 89(-15)+22 thousand years ago by several techniques. These include electron spin resonance, thermoluminescence, optically stimulated luminescence, uranium series, and amino acid racemization. Faunal and stratigraphic data are consistent with this age. PMID:7725099

  6. Relative age of Camelot crater and crater clusters near the Apollo 17 landing site

    USGS Publications Warehouse

    Lucchitta, B.K.

    1979-01-01

    Topographic profiles and depth-diameter ratios from the crater Camelot and craters of the central cluster in the Apollo 17 landing area suggest that these craters are of the same age. Therefore, layers that can be recognized in the deep-drill core and that can be identified as ejecta deposits from Camelot or from the cluster craters should yield similar emplacement ages. ?? 1979.

  7. Luminescence ages for three 'Middle Palaeolithic' sites in the Nihewan Basin, northern China, and their archaeological and palaeoenvironmental implications

    NASA Astrophysics Data System (ADS)

    Guo, Yu-Jie; Li, Bo; Zhang, Jia-Fu; Yuan, Bao-Yin; Xie, Fei; Roberts, Richard Graham

    2016-05-01

    The Nihewan Basin is a key region for studying the Palaeolithic archaeology of East Asia. However, because of the lack of suitable dating methods and representative lithic technologies in this region, the 'Middle Palaeolithic' sites in this basin have been designated based mainly on stratigraphic correlation, which may be unreliable. In this study, three Palaeolithic sites, Motianling, Queergou and Banjingzi, which have been assigned previously to the 'Middle Palaeolithic', are dated based on luminescence dating of K-feldspar grains. Our results show that the cultural layers at Motianling, Queergou and Banjingzi have ages of 315 ± 13, 268 ± 13 and 86 ± 4 ka (corresponding to Marine Isotope Stages 9, 8 and 5), respectively, suggesting that Motianling and Queergou should be assigned to the Lower Palaeolithic, while the age of Banjingzi is consistent with a Middle Palaeolithic attribution. Our results suggest that reassessing the age of 'Middle Palaeolithic' sites in the Nihewan Basin, and elsewhere in North China, is crucial for understanding the presence or absence of the Middle Palaeolithic phase in China. Our dating results also indicate that the Sanggan River developed sometime between about 270 and 86 ka ago.

  8. Luminescence ages for three 'Middle Palaeolithic' sites in the Nihewan Basin, northern China, and their archaeological and palaeoenvironmental implications

    NASA Astrophysics Data System (ADS)

    Guo, Yu-Jie; Li, Bo; Zhang, Jia-Fu; Yuan, Bao-Yin; Xie, Fei; Roberts, Richard Graham

    2016-05-01

    The Nihewan Basin is a key region for studying the Palaeolithic archaeology of East Asia. However, because of the lack of suitable dating methods and representative lithic technologies in this region, the 'Middle Palaeolithic' sites in this basin have been designated based mainly on stratigraphic correlation, which may be unreliable. In this study, three Palaeolithic sites, Motianling, Queergou and Banjingzi, which have been assigned previously to the 'Middle Palaeolithic', are dated based on luminescence dating of K-feldspar grains. Our results show that the cultural layers at Motianling, Queergou and Banjingzi have ages of 315 ± 13, 268 ± 13 and 86 ± 4 ka (corresponding to Marine Isotope Stages 9, 8 and 5), respectively, suggesting that Motianling and Queergou should be assigned to the Lower Palaeolithic, while the age of Banjingzi is consistent with a Middle Palaeolithic attribution. Our results suggest that reassessing the age of 'Middle Palaeolithic' sites in the Nihewan Basin, and elsewhere in North China, is crucial for understanding the presence or absence of the Middle Palaeolithic phase in China. Our dating results also indicate that the Sanggan River developed sometime between about 270 and 86 ka ago.

  9. FORM AND AGING OF PLUTONIUM IN SAVANNAH RIVER SITE WASTE TANK 18

    SciTech Connect

    Hobbs, D.

    2012-02-24

    This report provides a summary of the effects of aging on and the expected forms of plutonium in Tank 18 waste residues. The findings are based on available information on the operational history of Tank 18, reported analytical results for samples taken from Tank 18, and the available scientific literature for plutonium under alkaline conditions. These findings should apply in general to residues in other waste tanks. However, the operational history of other waste tanks should be evaluated for specific conditions and unique operations (e.g., acid cleaning with oxalic acid) that could alter the form of plutonium in heel residues. Based on the operational history of other tanks, characterization of samples from the heel residues in those tanks would be appropriate to confirm the form of plutonium. During the operational period and continuing with the residual heel removal periods, Pu(IV) is the dominant oxidation state of the plutonium. Small fractions of Pu(V) and Pu(VI) could be present as the result of the presence of water and the result of reactions with oxygen in air and products from the radiolysis of water. However, the presence of Pu(V) would be transitory as it is not stable at the dilute alkaline conditions that currently exists in Tank 18. Most of the plutonium that enters Savannah River Site (SRS) high-level waste (HLW) tanks is freshly precipitated as amorphous plutonium hydroxide, Pu(OH){sub 4(am)} or hydrous plutonium oxide, PuO{sub 2(am,hyd)} and coprecipitated within a mixture of hydrous metal oxide phases containing metals such as iron, aluminum, manganese and uranium. The coprecipitated plutonium would include Pu{sup 4+} that has been substituted for other metal ions in crystal lattice sites, Pu{sup 4+} occluded within hydrous metal oxide particles and Pu{sup 4+} adsorbed onto the surface of hydrous metal oxide particles. The adsorbed plutonium could include both inner sphere coordination and outer sphere coordination of the plutonium. PuO{sub 2

  10. Synergistic active targeting of dually integrin αvβ3/CD44-targeted nanoparticles to B16F10 tumors located at different sites of mouse bodies.

    PubMed

    Shi, Sanjun; Zhou, Min; Li, Xin; Hu, Min; Li, Chenwen; Li, Min; Sheng, Fangfang; Li, Zhuoheng; Wu, Guolin; Luo, Minghe; Cui, Huanhuan; Li, Ziwei; Fu, Ruoqiu; Xiang, Mingfeng; Xu, Jing; Zhang, Qian; Lu, Laichun

    2016-08-10

    Conventional enhanced permeation and retention (EPR) mediates the effects of many drugs, including the accumulation of nanocarriers at tumor sites, but its efficiency remains low. In this study, this limitation was overcome by developing a dual-targeting delivery system based on hyaluronan (HA, a major ligand of CD44) and tetraiodothyroacetic acid (tetrac, a specific ligand of αvβ3), which was exploited to carry docetaxel (DTX) for the synergistic active targeting to tumors. First, a tetrac-HA (TeHA) conjugate was synthesized and grafted onto the surfaces of solid lipid nanoparticles (SLNs) (TeHA-SLNs/DTX), with a high encapsulation efficiency of >91.6%. The resulting SLNs exhibited an approximately toroid morphology revealed using TEM. The cellular uptake and cytotoxicity of various formulations on CD44/αvβ3-enriched B16F10 cells were then assessed, and both results confirmed the selective uptake and high cytotoxicity of the TeHA-SLNs/DTX in a TeHA-dependent manner. In vivo imaging and vessel distribution tests revealed the efficiency of synergistic active targeting was higher than that of EPR-mediated passive targeting by the TeHA-SLNs to αvβ3-expressing tumor blood vessels and CD44-expressing tumor cells via selective targeting. Finally, in both xenograft tumor mice and in situ lung metastasis tumor mice, tumor growth was significantly inhibited by TeHA-SLNs/DTX. Therefore, TeHA-SLNs are an efficient system for the dual-targeted delivery of drugs to treat cancer in vivo. PMID:27235150

  11. Correlating planned radiation dose to the cochlea with primary site and tumor stage in patients with head and neck cancer treated with intensity-modulated radiation therapy

    SciTech Connect

    Zhang, Jeanette; Qureshi, Muhammad M.; Kovalchuk, Nataliya; Truong, Minh Tam

    2014-04-01

    The aim of the study was to determine tumor characteristics that predict higher planned radiation (RT) dose to the cochlea in patients with head and neck cancer (HNC) treated with intensity-modulated radiotherapy (IMRT). From 2004 to 2012, 99 patients with HNC underwent definitive IMRT to a median dose of 69.96 Gy in 33 fractions, with the right and left cochlea-vestibular apparatus contoured for IMRT optimization as avoidance structures. If disease involvement was adjacent to the cochlea, preference was given to tumor coverage by prescription dose. Descriptive statistics were calculated for dose-volume histogram planning data, and mean planning dose to the cochlea (from left or right cochlea, receiving the greater amount of RT dose) was correlated to primary site and tumor stage. Mean (standard deviation) cochlear volume was 1.0 (0.60) cm{sup 3} with maximum and mean planned doses of 31.9 (17.5) Gy and 22.1 (13.7) Gy, respectively. Mean planned dose (Gy) to cochlea by tumor site was as follows: oral cavity (18.6, 14.4), oropharynx (21.7, 9.1), nasopharynx (36.3, 10.4), hypopharynx (14.9, 7.1), larynx (2.1, 0.62), others including the parotid gland, temporal bone, and paranasal sinus (33.6, 24.0), and unknown primary (25.6, 6.7). Average mean planned dose (Gy) to the cochlea in T0-T2 and T3-T4 disease was 22.0 and 29.2 Gy, respectively (p = 0.019). By site, a significant difference was noted for nasopharynx and others (31.6 and 50.7, p = 0.012) but not for oropharynx, oral cavity, and hypopharynx. Advanced T category predicted for higher mean cochlear dose, particularly for nasopharyngeal, parotid gland, temporal bone, and paranasal sinus HNC sites.

  12. DNA-flow cytometry of head and neck carcinoma: the importance of uniform tissue sampling and tumor sites.

    PubMed

    Westerbeek, H A; Mooi, W J; Begg, C; Dessing, M; Balm, A J

    1992-01-01

    Flow cytometric DNA ploidy measurements using deparaffinized tumor specimens were performed on 46 squamous cell carcinomas of the head and neck, including 22 carcinomas of the oropharynx, 18 carcinomas of the larynx and six carcinomas of the oral cavity. Aneuploidy was found in 14 of these tumors with carcinomas of the larynx and oral cavity showing almost equal percentages of DNA aneuploidy (10/18 and 3/6, respectively). In contrast, only 1 of the oropharyngeal carcinomas was aneuploid. Accurate microscopy-controlled sampling of tumor tissue from the histological tissue blocks was found to be mandatory in order to obtain reliable ploidy measurements. PMID:1642865

  13. Inferring primary tumor sites from mutation spectra: a meta-analysis of histology-specific aberrations in cancer-derived cell lines.

    PubMed

    Dietlein, Felix; Eschner, Wolfgang

    2014-03-15

    Next-generation sequencing technologies have led to profound characterization of mutation spectra for several cancer types. Hence, we sought to systematically compare genomic aberrations between primary tumors and cancer lines. For this, we compiled publically available sequencing data of 1651 genes across 905 cell lines. We used them to characterize 23 distinct primary tumor sites by a novel approach that is based on Bayesian spam-filtering techniques. Thereby, we confirmed the strong overall similarity of alterations between patient samples and cell culture. However, we also identified several suspicious mutations, which had not been associated with their cancer types before. Based on these characterizations, we developed the inferring cancer origins from mutation spectra (ICOMS) tool. On our cell line collection, the algorithm reached a prediction specificity rate of 79%, which strongly variegated between primary cancer sites. On an independent validation cohort of 431 primary tumor samples, we observed a similar accuracy of 71%. Additionally, we found that ICOMS could be employed to deduce further attributes from mutation spectra, including sub-histology and compound sensitivity. Thus, thorough classification of site-specific mutation spectra for cell lines may decipher further genome-phenotype associations in cancer. PMID:24163242

  14. The Long and Winding Road: from the high affinity choline uptake site to clinical trials for malignant brain tumors

    PubMed Central

    Lowenstein, Pedro R.; Castro, Maria G.

    2016-01-01

    Malignant brain tumors are one of the most lethal cancers. They originate from glial cells and invade throughout the brain. Current standard of care involves surgical resection, radiotherapy and chemotherapy, and median survival is currently ~14–20 months post-diagnosis. Glioma tumors are highly infiltrative. Given that the brain immune system is deficient in priming systemic immune responses to glioma antigens present within the brain, we proposed to reconstitute the brain immune system to achieve immunological priming from within the brain. Two adenoviral vectors are injected into the resection cavity or remaining tumor. One adenoviral vector expresses the HSV-1 derived thymidine kinase which converts ganciclovir into a compound only cytotoxic to dividing glioma cells. The second adenovirus expresses the cytokine fms-like tyrosine kinase 3 ligand (Flt3L). Flt3L differentiates precursors into dendritic cells and acts as a chemokine for dendritic cells. HSV-1/ganciclovir killing of tumor cells releases tumor antigens that are taken up by dendritic cells within the brain tumor microenvironment. Tumor killing also releases HMGB1, a TLR2 agonist that activates dendritic cells. HMGB1 activated dendritic cells, loaded with glioma antigens, migrate to cervical lymph nodes to stimulate a systemic CD8+ T cells cytotoxic immune response against glioma. This immune response is specific to glioma tumors, induces immunological memory, and does neither cause brain toxicity nor autoimmune responses. An IND was granted by the FDA on 4/7/2011. A Phase I, first in person, to test whether re-engineering the brain immune system is potentially therapeutic is ongoing. PMID:27288077

  15. Evaluating the All-Ages Lead Model Using SiteSpecific Data: Approaches and Challenges

    EPA Science Inventory

    Lead (Pb) exposure continues to be a problem in the United States. Even after years of progress in reducing environmental levels, CDC estimates at least 500,000 U.S. children ages 1-5 years have blood Pb levels (BLL) above the CDC reference level of 5 µg/dL. Childhood Pb ex...

  16. Cosmic ray exposure ages of features and events at the Apollo landing sites

    NASA Technical Reports Server (NTRS)

    Arvidson, R.; Crozaz, G.; Drozd, R. J.; Hohenberg, C. M.; Morgan, C. J.

    1975-01-01

    Cosmic-ray exposure ages of lunar samples have been used to date surface features related to impact cratering and downslope movement of material. Only when multiple samples related to a feature have the same rare-gas exposure age or when a single sample has the same Kr-81 -Kr and track-exposure age can a feature be considered as reliably dated. Based on these criteria, there are only five well-dated lunar features: Cone Crater (Apollo 14), 26 m.y,; North Ray Crater (Apollo 16), 50 m.y.; South Ray Crater (Apollo 16), 2 m.y.; the emplacement of the Station 6 boulders (Apollo 17), 22 m.y.; and the emplacement of the Station 7 boulder (Apollo 17), 28 m.y. Other features are tentatively dated or have limits set on their ages: Bench Crater (Apollo 12), upper limit of 99 m.y.; Baby Ray Crater (Apollo 16), upper limit of 2 m.y.; Shorty Crater (Apollo 17), approximately 30 m.y.; Camelot Crater (Apollo 17) upper limit of 140 m.y.; the emplacement of the Station 2 boulder 1 (Apollo 17), 45 to 55 m.y.; and the slide which generated the light mantle (Apollo 17), lower limit of 50 m.y.

  17. A multi-site cutting device implements efficiently the divide-and-conquer strategy in tumor sampling

    PubMed Central

    Lopez, Jose I.; Cortes, Jesus M.

    2016-01-01

    We recently showed that in order to detect intra-tumor heterogeneity a Divide-and-Conquer (DAC) strategy of tumor sampling outperforms current routine protocols. This paper is a continuation of this work, but here we focus on DAC implementation in the Pathology Laboratory. In particular, we describe a new simple method that makes use of a cutting grid device and is applied to clear cell renal cell carcinomas for DAC implementation. This method assures a thorough sampling of large surgical specimens, facilitates the demonstration of intratumor heterogeneity, and saves time to pathologists in the daily practice. The method involves the following steps: 1. Thin slicing of the tumor (by hand or machine), 2. Application of a cutting grid to the slices ( e.g., a French fry cutter), resulting in multiple tissue cubes with fixed position within the slice, 3. Selection of tissue cubes for analysis, and finally, 4. Inclusion of selected cubes into a cassette for histological processing (with about eight tissue fragments within each cassette). Thus, using our approach in a 10 cm in-diameter-tumor we generate 80 tumor tissue fragments placed in 10 cassettes and, notably, in a tenth of time. Eighty samples obtained across all the regions of the tumor will assure a much higher performance in detecting intratumor heterogeneity, as proved recently with synthetic data. PMID:27540472

  18. A multi-site cutting device implements efficiently the divide-and-conquer strategy in tumor sampling.

    PubMed

    Lopez, Jose I; Cortes, Jesus M

    2016-01-01

    We recently showed that in order to detect intra-tumor heterogeneity a Divide-and-Conquer (DAC) strategy of tumor sampling outperforms current routine protocols. This paper is a continuation of this work, but here we focus on DAC implementation in the Pathology Laboratory. In particular, we describe a new simple method that makes use of a cutting grid device and is applied to clear cell renal cell carcinomas for DAC implementation. This method assures a thorough sampling of large surgical specimens, facilitates the demonstration of intratumor heterogeneity, and saves time to pathologists in the daily practice. The method involves the following steps: 1. Thin slicing of the tumor (by hand or machine), 2. Application of a cutting grid to the slices ( e.g., a French fry cutter), resulting in multiple tissue cubes with fixed position within the slice, 3. Selection of tissue cubes for analysis, and finally, 4. Inclusion of selected cubes into a cassette for histological processing (with about eight tissue fragments within each cassette). Thus, using our approach in a 10 cm in-diameter-tumor we generate 80 tumor tissue fragments placed in 10 cassettes and, notably, in a tenth of time. Eighty samples obtained across all the regions of the tumor will assure a much higher performance in detecting intratumor heterogeneity, as proved recently with synthetic data. PMID:27540472

  19. The Effects of Age, Adiposity, and Physical Activity on the Risk of Seven Site-Specific Fractures in Postmenopausal Women.

    PubMed

    Lacombe, Jason; Cairns, Benjamin J; Green, Jane; Reeves, Gillian K; Beral, Valerie; Armstrong, Miranda Eg

    2016-08-01

    Risk factors for fracture of the neck of the femur are relatively well established, but those for fracture at other sites are little studied. In this large population study we explore the role of age, body mass index (BMI), and physical activity on the risk of fracture at seven sites in postmenopausal women. As part of the Million Women Study, 1,154,821 postmenopausal UK women with a mean age of 56.0 (SD 4.8) years provided health and lifestyle data at recruitment in 1996 to 2001. All participants were linked to National Health Service (NHS) hospital records for day-case or overnight admissions with a mean follow-up of 11 years per woman. Adjusted absolute and relative risks for seven site-specific incident fractures were calculated using Cox regression models. During follow-up, 4931 women had a fracture of the humerus; 2926 of the forearm; 15,883 of the wrist; 9887 of the neck of the femur; 1166 of the femur (not neck); 3199 a lower leg fracture; and 10,092 an ankle fracture. Age-specific incidence rates increased gradually with age for fractures of forearm, lower leg, ankle, and femur (not neck), and steeply with age for fractures of neck of femur, wrist, and humerus. When compared to women with desirable BMI (20.0 to 24.9 kg/m(2) ), higher BMI was associated with a reduced risk of fracture of the neck of femur, forearm, and wrist, but an increased risk of humerus, femur (not neck), lower leg, and ankle fractures (p < 0.001 for all). Strenuous activity was significantly associated with a decreased risk of fracture of the humerus and femur (both neck and remainder of femur) (p < 0.001), but was not significantly associated with lower leg, ankle, wrist, and forearm fractures. Postmenopausal women are at a high lifetime risk of fracture. BMI and physical activity are modifiable risk factors for fracture, but their associations with fracture risk differ substantially across fracture sites. © 2016 The Authors. Journal of Bone and Mineral Research published

  20. The Long and Winding Road: From the High-Affinity Choline Uptake Site to Clinical Trials for Malignant Brain Tumors.

    PubMed

    Lowenstein, P R; Castro, M G

    2016-01-01

    Malignant brain tumors are one of the most lethal cancers. They originate from glial cells which infiltrate throughout the brain. Current standard of care involves surgical resection, radiotherapy, and chemotherapy; median survival is currently ~14-20 months postdiagnosis. Given that the brain immune system is deficient in priming systemic immune responses to glioma antigens, we proposed to reconstitute the brain immune system to achieve immunological priming from within the brain. Two adenoviral vectors are injected into the resection cavity or remaining tumor. One adenoviral vector expresses the HSV-1-derived thymidine kinase which converts ganciclovir into a compound only cytotoxic to dividing glioma cells. The second adenovirus expresses the cytokine fms-like tyrosine kinase 3 ligand (Flt3L). Flt3L differentiates precursors into dendritic cells and acts as a chemokine that attracts dendritic cells to the brain. HSV-1/ganciclovir killing of tumor cells releases tumor antigens that are taken up by dendritic cells within the brain tumor microenvironment. Tumor killing also releases HMGB1, an endogenous TLR2 agonist that activates dendritic cells. HMGB1-activated dendritic cells, loaded with glioma antigens, migrate to cervical lymph nodes to stimulate a systemic CD8+ T cells cytotoxic immune response against glioma. This immune response is specific to glioma tumors, induces immunological memory, and does neither cause brain toxicity nor autoimmune responses. An IND was granted by the FDA on 4/7/2011. A Phase I, first in person trial, to test whether reengineering the brain immune system is potentially therapeutic is ongoing. PMID:27288077

  1. Saint-Gaudens National Historic Site: Home of a Gilded Age Icon. Teaching with Historic Places.

    ERIC Educational Resources Information Center

    Percoco, James A.

    Augustus Saint-Gaudens (1848-1907) was a renowned 19th-century U.S. sculptor whose artistic training and talent ensured his place in Gilded Age society. In 1885, he was drawn to Cornish, New Hampshire, to find a place where he could model his latest commission, a statue of Abraham Lincoln. He and his wife established a summer home and studio in an…

  2. Syphilis among middle-aged female sex workers in China: a three-site cross-sectional study

    PubMed Central

    Liu, Hongjie; Dumenci, Levent; Morisky, Donald E; Xu, Yongfang; Li, Xiaojing; Jiang, Baofa

    2016-01-01

    Objectives This study addresses the lack of empirical studies about the epidemic of syphilis among middle-aged female sex workers (FSWs). The objectives of this study were to investigate prevalence of syphilis, and its potential risk factors among middle-aged FSWs in China. Design A cross-sectional study with respondent-driven sampling (RDS). Setting A multisite study conducted at three Chinese cites (Nanning, Hefei, and Qingdao) with different levels of sexually transmitted diseases in 2014. Participants 1245 middle-aged female sex workers who were over 35 years old (about 400 per study site). Main outcome measures Unprotected commercial sex, and syphilis and HIV infection were biologically tested and measured. Results The RDS-adjusted prevalence of active syphilis was 17.3% in Hefei, 9.9% in Qingdao, and 5.4% in Nanning. The RDS-adjusted prevalence of prevalent syphilis was between 6.8% and 33.6% in the three cities. The proportion of unprotected sex in the past 48 h verified by the prostate-specific antigen test (PSA) was between 27.8% and 42.4%. Multiple log-binomial regression analyses indicate that middle-aged FSWs who had 5 or more clients in the past week prior to interviews and engaged in unprotected sex were more likely to be active syphilitic cases. Middle-aged FSWs who had rural residency were less likely to be active syphilitic cases. Conclusions In contrast with previous studies that reported low prevalence of syphilis and high prevalence of protected sex among FSWs in China, both the prevalence of syphilis and unprotected sex were high among middle-aged FSWs. Evidence-based intervention programmes should be developed and evaluated among this vulnerable population in China and other countries with similar settings. PMID:27165644

  3. The effects of site, supplemental food, and age on survivorship of Carolina Chickadees and implications for dispersal through- riparian corridors

    USGS Publications Warehouse

    Doherty, P.F.; Grubb, T.G.

    2000-01-01

    Few studies have examined survivorship of animals in forest fragments differing in size, and none has used appropriate mark-recapture analysis techniques taking into account probability of recapture. Using Program MARK, a flexible mark-recapture software package, we estimated annual survival rates of Carolina Chickadees over a 5-yr period in a fragmented landscape in Ohio. The probability of survival was related to site (riparian woodland or woodlot area) and increased with the presence of supplemental food. While there was little evidence for an age difference in apparent survival in woodlots, young birds appeared to survive less well in forested river corridors. This last result was quite likely due, at least in part, to age-specific dispersal, suggesting that river corridors function as important dispersal routes for young birds.

  4. Matuyama-age lithic tools from the Sima del Elefante site, Atapuerca (northern Spain).

    PubMed

    Parés, Josep M; Pérez-González, Alfredo; Rosas, Antonio; Benito, A; Bermúdez de Castro, J M; Carbonell, E; Huguet, R

    2006-02-01

    Paleomagnetic results obtained from the sedimentary fill at the Sima del Elefante site in Atapuerca, Spain, reveal a geomagnetic reversal, interpreted as the Matuyama-Brunhes boundary (0.78 Ma). The uppermost lithostratigraphic units (E17 through E19), which contain Mode II and III archaeological assemblages, display normal polarity magnetization, whereas the six lowermost units (E9 through E16) yield negative latitudinal virtual geomagnetic pole positions. Units E9 through E13, all of which display reverse magnetic polarity, contain Mode I (Oldowan) lithic tools, testifying to the presence of humans in the early Pleistocene (0.78-1.77 Ma). PMID:16249015

  5. Differential influence of organ site on three subpopulations of a single mouse mammary tumor at two distinct steps in metastasis.

    PubMed

    Aslakson, C J; Rak, J W; Miller, B E; Miller, F R

    1991-02-01

    Tumor subpopulations 66c14, 168FARN, and 4T07 are drug-resistant variants selected from sister subpopulations derived from a single mouse mammary tumor. These subpopulations are heterogeneous in their capacities to form experimental metastatic growth in the lungs and liver. Initial survival kinetics of arrested cells, determined by the clearance of 125IUdR-labelled cells, and subsequent growth rates, determined by sequential recovery of clonogenic tumor cells from occult metastases, both correlated with organ-colonizing potential as determined by necropsy. The growth rates of these 3 subpopulations were determined in vitro in monolayer and in situ in the subcutis, in the liver following intrasplenic injection, and in the lung following intravenous injection. Clonogenic potential of all 3 lines was similar in vitro (54-59%). Growth rates in vitro (population doubling times 16.5-21 hr) and in the subcutis (tumor volume doubling times 5.2-7.4 days) were similar for the 3 subpopulations, but differed significantly in the liver and lungs. For line 4T07, the most metastatic line to both lung and liver, population doubling times in vitro and in the lung and liver were similar, ranging from 17 to 26 hr. For lines 66c14 and 168FARN, the growth rates in lungs and livers were much slower than in vitro. Line 66c14, which is relatively more metastatic to the lungs, grew much faster in the lung (39 hours) than in the liver (91 hr), but line 168FARN, which is relatively more metastatic to the liver, grew at a faster rate in the liver (37 hr) than in the lung (63 hr). Thus, 3 tumor subpopulations (seeds) derived from a single tumor were differentially affected by host organ factors (soil) at 2 distinct stages in the metastatic process. PMID:1993557

  6. Site specific discrete PEGylation of (124)I-labeled mCC49 Fab' fragments improves tumor MicroPET/CT imaging in mice.

    PubMed

    Ding, Haiming; Carlton, Michelle M; Povoski, Stephen P; Milum, Keisha; Kumar, Krishan; Kothandaraman, Shankaran; Hinkle, George H; Colcher, David; Brody, Rich; Davis, Paul D; Pokora, Alex; Phelps, Mitchell; Martin, Edward W; Tweedle, Michael F

    2013-11-20

    The tumor-associated glycoprotein-72 (TAG-72) antigen is highly overexpressed in various human adenocarcinomas and anti-TAG-72 monoclonal antibodies, and fragments are therefore useful as pharmaceutical targeting vectors. In this study, we investigated the effects of site-specific PEGylation with MW 2-4 kDa discrete, branched PEGylation reagents on mCC49 Fab' (MW 50 kDa) via in vitro TAG72 binding, and in vivo blood clearance kinetics, biodistribution, and mouse tumor microPET/CT imaging. mCC49Fab' (Fab'-NEM) was conjugated at a hinge region cysteine with maleimide-dPEG 12-(dPEG24COOH)3 acid (Mal-dPEG-A), maleimide-dPEG12-(dPEG12COOH)3 acid (Mal-dPEG-B), or maleimide-dPEG12-(m-dPEG24)3 (Mal-dPEG-C), and then radiolabeled with iodine-124 ((124)I) in vitro radioligand binding assays and in vivo studies used TAG-72 expressing LS174T human colon carcinoma cells and xenograft mouse tumors. Conjugation of mCC49Fab' with Mal-dPEG-A (Fab'-A) reduced the binding affinity of the non PEGylated Fab' by 30%; however, in vivo, Fab'-A significantly lengthened the blood retention vs Fab'-NEM (47.5 vs 28.1%/ID at 1 h, 25.1 vs 8.4%/ID at 5 h, p < 0.01), showed excellent tumor to background, better microPET/CT images due to higher tumor accumulation, and increased tumor concentration in excised tissues at 72 h by 130% (5.09 ± 0.83 vs 3.83 ± 1.50%ID/g, p < 0.05). Despite the strong similarity of the three PEGylation reagents, PEGylation with Mal-dPEG-B or -C reduced the in vitro binding affinity of Fab'-NEM by 70%, blood retention, microPET/CT imaging tumor signal intensity, and residual 72 h tumor concentration by 49% (3.83 ± 1.50 vs 1.97 ± 0.29%ID/g, p < 0.05) and 63% (3.83 ± 1.50 vs 1.42 ± 0.35%ID/g, p < 0.05), respectively. We conclude that remarkably subtle changes in the structure of the PEGylation reagent can create significantly altered biologic behavior. Further study is warranted of conjugates of the triple branched, negatively charged Mal-dPEG-A. PMID:24175669

  7. Use of radium isotopes to determine the age and origin of radioactive barite at oil-field production sites

    USGS Publications Warehouse

    Zielinski, R.A.; Otton, J.K.; Budahn, J.R.

    2001-01-01

    Radium-bearing barite (radiobarite) is a common constituent of scale and sludge deposits that form in oil-field production equipment. The barite forms as a precipitate from radium-bearing, saline formation water that is pumped to the surface along with oil. Radioactivity levels in some oil-field equipment and in soils contaminated by scale and sludge can be sufficiently high to pose a potential health threat. Accurate determinations of radium isotopes (226Ra+228Ra) in soils are required to establish the level of soil contamination and the volume of soil that may exceed regulatory limits for total radium content. In this study the radium isotopic data are used to provide estimates of the age of formation of the radiobarite contaminant. Age estimates require that highly insoluble radiobarite approximates a chemically closed system from the time of its formation. Age estimates are based on the decay of short-lived 228Ra (half-life=5.76 years) compared to 226Ra (half-life=1600 years). Present activity ratios of 228Ra/226Ra in radiobarite-rich scale or highly contaminated soil are compared to initial ratios at the time of radiobarite precipitation. Initial ratios are estimated by measurements of saline water or recent barite precipitates at the site or by considering a range of probable initial ratios based on reported values in modern oil-field brines. At sites that contain two distinct radiobarite sources of different age, the soils containing mixtures of sources can be identified, and mixing proportions quantified using radium concentration and isotopic data. These uses of radium isotope data provide more description of contamination history and can possibly address liability issues. Copyright ?? 2000 .

  8. The Ysterfontein 1 Middle Stone Age site, South Africa, and early human exploitation of coastal resources.

    PubMed

    Klein, Richard G; Avery, Graham; Cruz-Uribe, Kathryn; Halkett, David; Parkington, John E; Steele, Teresa; Volman, Thomas P; Yates, Royden

    2004-04-20

    Human fossils and the genetics of extant human populations indicate that living people derive primarily from an African population that lived within the last 200,000 years. Yet it was only approximately 50,000 years ago that the descendants of this population spread to Eurasia, where they swamped or replaced the Neanderthals and other nonmodern Eurasians. Based on archaeological observations, the most plausible hypothesis for the delay is that Africans and Eurasians were behaviorally similar until 50,000 years ago, and it was only at this time that Africans developed a behavioral advantage. The archaeological findings come primarily from South Africa, where they suggest that the advantage involved much more effective use of coastal resources. Until now, the evidence has come mostly from deeply stratified caves on the south (Indian Ocean) coast. Here, we summarize results from recent excavations at Ysterfontein 1, a deeply stratified shelter in a contrasting environment on the west (Atlantic) coast. The Ysterfontein 1 samples of human food debris must be enlarged for a full comparison to samples from other relevant sites, but they already corroborate two inferences drawn from south coast sites: (i) coastal foragers before 50,000 years ago did not fish routinely, probably for lack of appropriate technology, and (ii) they collected tortoises and shellfish less intensively than later people, probably because their populations were smaller. PMID:15007171

  9. The Ysterfontein 1 Middle Stone Age site, South Africa, and early human exploitation of coastal resources

    PubMed Central

    Klein, Richard G.; Avery, Graham; Cruz-Uribe, Kathryn; Halkett, David; Parkington, John E.; Steele, Teresa; Volman, Thomas P.; Yates, Royden

    2004-01-01

    Human fossils and the genetics of extant human populations indicate that living people derive primarily from an African population that lived within the last 200,000 years. Yet it was only ≈50,000 years ago that the descendants of this population spread to Eurasia, where they swamped or replaced the Neanderthals and other nonmodern Eurasians. Based on archaeological observations, the most plausible hypothesis for the delay is that Africans and Eurasians were behaviorally similar until 50,000 years ago, and it was only at this time that Africans developed a behavioral advantage. The archaeological findings come primarily from South Africa, where they suggest that the advantage involved much more effective use of coastal resources. Until now, the evidence has come mostly from deeply stratified caves on the south (Indian Ocean) coast. Here, we summarize results from recent excavations at Ysterfontein 1, a deeply stratified shelter in a contrasting environment on the west (Atlantic) coast. The Ysterfontein 1 samples of human food debris must be enlarged for a full comparison to samples from other relevant sites, but they already corroborate two inferences drawn from south coast sites: (i) coastal foragers before 50,000 years ago did not fish routinely, probably for lack of appropriate technology, and (ii) they collected tortoises and shellfish less intensively than later people, probably because their populations were smaller. PMID:15007171

  10. The lipoma of tongue - A rare site for a tumor: Case report and review of the literature

    PubMed Central

    Baonerkar, Hemant A.; Vora, Meena; Sorathia, Rakesh; Shinde, Swapnil

    2015-01-01

    Lipoma is the most common tumor of the human body, but their presences in the oral cavity are very rare. Reported cases of lipoma of tongue in English literature are very few. Here, we report a case of lipoma of tongue in 63-year-old male patient, with its clinical presentation, the histological picture, classification, and brief review of the literature. PMID:26752882

  11. Chromosome site for Epstein-Barr virus DNA in a Burkitt tumor cell line and in lymphocytes growth-transformed in vitro.

    PubMed Central

    Henderson, A; Ripley, S; Heller, M; Kieff, E

    1983-01-01

    The Epstein-Barr virus (EBV) genome stably persists in latently infected Burkitt tumor cells and growth-transformed B lymphocytes. These cells usually contain multiple copies of episomal viral DNA. Cytological hybridization of recombinant viral DNA fragments to metaphase chromosomes of two latently infected cell lines demonstrates that viral DNA localizes to both chromatids of one homologue of chromosome 1 in Namalwa, a Burkitt tumor cell line, and to both chromatids of one homologue of chromosome 4 in IB4, a cell line with transformed growth properties in vitro. The site of chromosome association remains stable in a clone of IB4 cells. Probes from five separate regions of the EBV genome hybridize to the same chromosome regions. A previously undescribed achromatic site is identified within the region of EBV chromosome cytological hybridization. These observations suggest that most or all of the EBV genome is integrated into the chromosomal DNA of Namalwa and IB4 cells. Although the chromosomal sites of EBV DNA association are among those regions with homology to the EBV IR3 repeated DNA sequence, EBV IR3 did not mediate recombination between EBV and chromosomal DNA. Images PMID:6300885

  12. Identification and quantification of biomarkers and polycyclic aromatic hydrocarbons (PAHs) in an aged mixed contaminated site: from source to soil.

    PubMed

    Kao, Nien-Hsin; Su, Ming-Chien; Fan, Jheng-Rong; Chung, Ying-Yung

    2015-05-01

    The sources of the spill and the contaminated soils of an aged oil spill contaminated site with unknown mixed pollutants were investigated by using a set of developed forensic chemical procedures which include analysis of oil products, site investigation, gas chromatography/mass spectrometry (GC/MS) screening, biomarker identification, and finally, the confirmation of pollutants. Adamantanes (17 compounds), 10 bicyclic sesquiterpanes, 6 newly detected compounds, 16 polycyclic aromatic hydrocarbons, and 10 alkylated naphthalenes compounds in several gasoline, diesel oil samples, and contaminated soil samples were examined and quantified. GC/MS method, retention indices, relative response factors, and diagnostic ratio were used to identify and quantify pollutant compounds. The study revealed the key factors for distinguishing among gasoline and diesel oil products in the market, created a new set of retention indices for 10 bicyclic sesquiterpane compounds, and discovered 6 quantifiable compounds in analysis of fresh oil products. The suggested diagnostic ratios for BSs and the new compounds in the analysis of the biomarker show the differences among diesel products, link between the source of pollutants with contaminated soil, and the recognition of the signs of an aged spill, and the indications of weathering effects. PMID:25712884

  13. Age calibrated relative paleointensity for the last 1.5 Myr at IODP Site U1308 (North Atlantic)

    NASA Astrophysics Data System (ADS)

    Channell, J. E. T.; Hodell, D. A.; Xuan, C.; Mazaud, A.; Stoner, J. S.

    2008-09-01

    Integrated Ocean Drilling Program (IODP) Site U1308 (central North Atlantic) records paleomagnetic directional and relative paleointensity (RPI) variations for the last 1.5 Myr, in 110 m of the sediment sequence at a mean sedimentation rate of 7.3 cm/kyr. A detailed benthic oxygen isotope record was combined with RPI to produce an integrated, high-resolution magneto-isotopic stratigraphy for Site U1308. Apart from the well-known polarity reversals in this interval, the Punaruu excursion is recorded at 1092 ka and the Cobb Mountain Subchron in the 1182-1208 ka interval. The paleointensity proxies are determined as slopes of NRM versus ARM and NRM versus ARMAQ (ARM acquisition) with linear correlation coefficients to monitor the quality of the linear fit. The RPI record for Site U1308 is compared with the three other paleointensity records (one from the Western Equatorial Pacific and two from the North Atlantic) that cover the same time interval and have accompanying oxygen isotope records. The Match protocol of Lisiecki and Lisiecki (2002) is used to optimize the correlation of paleointensity records. Beginning with the original (published) age models for each record, the Match routine is used to optimize the RPI correlations to Site U1308, with checks to ensure compatibility with oxygen isotope records. Squared wavelet coherence (WTC) indicates significant improvement in RPI (and oxygen isotope) correlations after matching each RPI record to Site U1308, particularly for periods > 10 kyr. The level of coherence for the Atlantic RPI records and the lower resolution Pacific record implies synchronous global variability (at scales > 10 kyr) that can be attributed to the axial dipole geomagnetic field.

  14. Site and age class variation of hematologic parameters for female Greater Sage Grouse (Centrocercus urophasianus) of Northern Nevada.

    PubMed

    Dyer, Kathryn J; Perryman, Barry L; Holcombe, Dale W

    2010-01-01

    Decreases in Greater Sage Grouse (Centrocercus urophasianus) numbers throughout the western United States have been attributed to declining habitat quantity and quality. Improving our understanding of how interannual ecologic site variability affects nutritional status and fitness of different bird age classes will lead to improved land management and conservation strategies. Greater Sage Grouse were sampled from two Population Management Units located in northern Nevada, United States: Tuscarora (TU) and Lone Willow (LW) during 15 March-11 April 2004 and 14-20 March 2005. Twenty (16 yearlings, four adults) and 17 (7 yearlings, 10 adults) female Sage Grouse were captured and bled during 2004, and 12 (four yearlings, eight adults) and 14 (10 yearlings, four adults) were sampled during 2005 in TU and LW, respectively. Samples were evaluated to examine the effect of site, age, and year on specific hematologic and serum chemistry parameters. Several differences between age classes, sites, and years were detected for a number of fitness indicators; however, actual values fell within normal ranges of variation for Sage Grouse or other avian species. Differences were also detected for several parameters more closely related to reproductive fitness, including total plasma and serum proteins, and serum calcium and phosphorus. Yearlings had lower plasma protein (P<0.0001) and lower serum protein than did adults (P=0.0003). In 2004, TU yearlings had lower serum calcium levels than the adults, and in 2005, LW yearlings had lower levels than adults (P=0.008). Females on the TU site had lower serum phosphorus than the LW females (P<0.0001). Overall, adult females weighed more than yearlings (P=0.0004). Lower values found in yearlings, and on the TU management unit, indicate a lower production potential, particularly in unfavorable years. A lower intrinsic ability of yearlings to reproduce, combined with lower nutrition potentials and associated annual variations on certain types

  15. CHEMICAL SELECTIVITY OF NUCLEOBASE ADDUCTION RELATIVE TO IN VIVO MUTATION SITES ON EXON 7 FRAGMENT OF P53 TUMOR SUPPRESSOR GENE

    PubMed Central

    Malla, Spundana; Kadimisetty, Karteek; Fu, You-Jun; Choudhary, Dharamainder; Jansson, Ingela; Schenkman, John B.; Rusling, James F.

    2015-01-01

    Damage to p53 tumor suppressor gene is found in half of all human cancers. Databases integrating studies of large numbers of tumors and cancer cell cultures show that mutation sites of specific p53 codons are correlated with specific types of cancers. If the most frequently damaged p53 codons in vivo correlate with the most frequent chemical damage sites in vitro, predictions of organ-specific cancer risks might result. Herein, we describe LC-MS/MS methodology to reveal codons with metabolite-adducted nucleobases by LC-MS/MS for oligonucleotides longer than 20 base pairs. Specifically, we used a known carcinogen, benzo[a]pyrene-7,8-dihydrodiol-9,10-epoxide (BPDE) to determine the most frequently adducted nucleobases within codons. We used a known sequence of 32 base pairs (bp) representing part of p53 exon 7 with 5 possible reactive hot spots. This is the first nucleobase reactivity study of a double stranded DNA p53 fragment featuring more than 20 base pairs with multiple reactive sites. We reacted the 32 bp fragment with benzo[a]pyrene metabolite BPDE that undergoes nucleophilic substitution by DNA bases. Liquid chromatography-mass spectrometry (LC-MS/MS) was used for sequencing of oligonucleotide products from the reacted 32 bp fragment after fragmentation by a restriction endonuclease. Analysis of the adducted p53 fragment compared with unreacted fragment revealed guanines of codons 248 and 244 as most frequently targeted, which are also mutated with high frequency in human tumors. Codon 248 is mutated in non-small cell and small cell lung, head and neck, colorectal and skin cancer, while codon 244 is mutated in small cell lung cancer, all of which involve possible BDPE exposure. Results suggest the utility of this approach for screening of adducted p53 gene by drugs and environmental chemicals to predict risks for organ specific cancers. PMID:26417421

  16. Geologic evidence for age of deposits at Hueyatlaco archeological site, Vasequillo, Mexico

    USGS Publications Warehouse

    Steen-McIntyre, V.; Fryxell, R.; Malde, H.E.

    1981-01-01

    Direct tracing of beds during excavation in May 1973, confirmed that the artifact-bearing layers at Hueyatlaco underlie 10 m of fine-grained, water-laid deposits that constitute part of the wide-spread Valsequillo gravels. Dissection of these deposits by the adjacent Ri??o Atoyac has reached a depth of 50 m. The stratigraphic section at Hueyatlaco includes four distinctive tephra units. The oldest one occupies a small channel in a series of cut-and-fill stream deposits that have yielded bifacial tools. It lies more than a meter above flat-lying, fine-grained beds from which edge-retouched tools have been recovered. The three other tephra units occur higher in the section. Fission-track ages on zircon phenocrysts from two of the younger tephra layers (370,000 ?? 200,000 and 600,000 ?? 340,000 yr, 2??) agree with concordant uranium-series dates for a camel pelvis that was found associated with bifacial tools at Hueyatlaco (245,000 ?? 40,000 yr by 230Th and > 180,000 yr by 231Pa). These dates are compatible with the depth of burial and subsequent dissection of the Hueyatlaco deposits, as well as with the degree of hydration of volcanic glass shards and with the extent of etching of heavy-mineral phenocrysts from within the tephra layers. These findings suggest to us that further search for archaeological remains in deposits as old as those at Hueyatlaco would be warranted. ?? 1981.

  17. Catheter tip cultures on open-heart surgery patients: associations with site of catheter and age of patients.

    PubMed Central

    Freeman, R; Hjersing, N; Burridge, A

    1981-01-01

    The results of culture of 668 catheter tips from 422 patients are analysed with relation to the site of the catheter and the age of the patient. Coagulase-negative staphylococci were the most common bacterial isolate, but Gram-negative bacilli were found in the venous lines, femoral artery lines, and peripheral lines. Isolations of Gram-negative bacilli were associated with age, being found mainly in those under 1 year and those over 40 years of age. Typing of coagulase-negative staphylococci revealed that Staphylococcus epidermidis is the only variety found in peripheral lines and in lines inserted after operation for complications (central venous, sub-clavian, and long lines), whereas other types occur (along with Staphylococcus epidermidis) in the other lines (left atrial, arterial, and venous). Use of extra lines for the management of postoperative complications thereby increases the risk of Staphylococcus epidermidis gaining access to the circulation. A subgroup of venous lines used to administer inotropic agents was found to be sterile on culture, and this was the result of the anti-oxidant (sodium metabisulphite) in the inotrope solution acting as an antiseptic. PMID:7314004

  18. Geologic evidence for age of deposits at Hueyatlaco archeological site, Vasequillo, Mexico

    NASA Astrophysics Data System (ADS)

    Steen-McIntyre, Virginia; Fryxell, Roald; Malde, Harold E.

    1981-07-01

    Direct tracing of beds during excavation in May 1973, confirmed that the artifact-bearing layers at Hueyatlaco underlie 10 m of fine-grained, water-laid deposits that constitute part of the wide-spread Valsequillo gravels. Dissection of these deposits by the adjacent Río Atoyac has reached a depth of 50 m. The stratigraphic section at Hueyatlaco includes four distinctive tephra units. The oldest one occupies a small channel in a series of cut-and-fill stream deposits that have yielded bifacial tools. It lies more than a meter above flat-lying, fine-grained beds from which edge-retouched tools have been recovered. The three other tephra units occur higher in the section. Fission-track ages on zircon phenocrysts from two of the younger tephra layers (370,000 ± 200,000 and 600,000 ± 340,000 yr, 2σ) agree with concordant uranium-series dates for a camel pelvis that was found associated with bifacial tools at Hueyatlaco (245,000 ± 40,000 yr by 230Th and > 180,000 yr by 231Pa). These dates are compatible with the depth of burial and subsequent dissection of the Hueyatlaco deposits, as well as with the degree of hydration of volcanic glass shards and with the extent of etching of heavy-mineral phenocrysts from within the tephra layers. These findings suggest to us that further search for archaeological remains in deposits as old as those at Hueyatlaco would be warranted.

  19. Maturation of cortical auditory evoked potentials (CAEPs) to speech recorded from frontocentral and temporal sites: three months to eight years of age

    PubMed Central

    Yu, Yan H.; Wagner, Monica

    2014-01-01

    The goal of the current analysis was to examine the maturation of cortical auditory evoked potentials (CAEPs) from three months of age to eight years of age. The superior frontal positive-negative-positive sequence (P1, N2, P2) and the temporal site, negative-positive-negative sequence (possibly, Na, Ta, Tb of the T-complex) were examined. Event-related potentials were recorded from 63 scalp sites to a 250- ms vowel. Amplitude and latency of peaks were measured at left and right frontal sites (near Fz) and at left and right temporal sites (T7 and T8). In addition the largest peak (typically corresponding to P1) was selected from global field power (GFP). The results revealed a large positive peak (P1) easily identified at frontal sites across all ages. The N2 emerged after 6 months of age and the following P2 between 8 and 30 months of age. The latencies of these peaks decreased exponentially with the most rapid decrease observed for P1. For amplitude, only P1 showed a clear relationship with age, becoming more positive in a somewhat linear fashion. At the temporal sites only a negative peak, which might be Na, was clearly observed at both left and right sites in children older than 14 months and peaking between 100 and 200 ms. P1 measures at frontal sites and Na peak latencies were moderately correlated. The temporal negative peak latency showed a different maturational timecourse (linear in nature) than the P1 peak, suggesting at least partial independence. Distinct Ta (positive) and Tb (negative) peaks, following Na and peaking between 120 and 220 ms were not consistently found in most age groups of children, except Ta which was present in 7 year olds. Future research, which includes manipulation of stimulus factors, and use of modeling techniques will be needed to explain the apparent, protracted maturation of the temporal site measures in the current study. PMID:25219893

  20. Maturation of cortical auditory evoked potentials (CAEPs) to speech recorded from frontocentral and temporal sites: three months to eight years of age.

    PubMed

    Shafer, Valerie L; Yu, Yan H; Wagner, Monica

    2015-02-01

    The goal of the current analysis was to examine the maturation of cortical auditory evoked potentials (CAEPs) from three months of age to eight years of age. The superior frontal positive-negative-positive sequence (P1, N2, P2) and the temporal site, negative-positive-negative sequence (possibly, Na, Ta, Tb of the T-complex) were examined. Event-related potentials were recorded from 63 scalp sites to a 250-ms vowel. Amplitude and latency of peaks were measured at left and right frontal sites (near Fz) and at left and right temporal sites (T7 and T8). In addition, the largest peak (typically corresponding to P1) was selected from global field power (GFP). The results revealed a large positive peak (P1) easily identified at frontal sites across all ages. The N2 emerged after 6 months of age and the following P2 between 8 and 30 months of age. The latencies of these peaks decreased exponentially with the most rapid decrease observed for P1. For amplitude, only P1 showed a clear relationship with age, becoming more positive in a somewhat linear fashion. At the temporal sites only a negative peak, which might be Na, was clearly observed at both left and right sites in children older than 14 months and peaking between 100 and 200 ms. P1 measures at frontal sites and Na peak latencies were moderately correlated. The temporal negative peak latency showed a different maturational timecourse (linear in nature) than the P1 peak, suggesting at least partial independence. Distinct Ta (positive) and Tb (negative) peaks, following Na and peaking between 120 and 220 ms were not consistently found in most age groups of children, except Ta which was present in 7 year olds. Future research, which includes manipulation of stimulus factors, and use of modeling techniques will be needed to explain the apparent, protracted maturation of the temporal site measures in the current study. PMID:25219893

  1. Chronic toxic and carcinogenic effects of cadmium chloride in male DBA/2NCr and NFS/NCr mice: strain-dependent association with tumors of the hematopoietic system, injection site, liver, and lung.

    PubMed

    Waalkes, M P; Rehm, S

    1994-07-01

    Although the acute toxic effects of cadmium in mice vary greatly with strain, relatively little is known about strain differences in cadmium carcinogenesis. Therefore, this work was performed to assess the chronic toxic and carcinogenic effects of cadmium in two strains of mice generally thought to be susceptible to the acute effects of cadmium. Male DBA/2NCr (DBA) and NFS/NCr (NFS) mice were given CdCl2 (40 mumol/kg, sc) either as a single dose (1 x 40) or as weekly doses for 16 weeks (16 x 40) starting at 8 weeks of age. Controls received saline. The animals were observed for the next 104 weeks and mice at risk were defined as those surviving to the time of appearance of a particular tumor. Cadmium-induced dose-related increases in lymphoma (primarily follicular center cell) incidence (1 x 40, 11 cases/23 mice at risk; 16 x 40, 16/28) over control (7/27) in DBA mice but not in NFS mice. Only NFS mice receiving repeated cadmium injections (16 x 40) showed sarcoma development at the injection site (9/35), as no sarcomas occurred in control NFS mice or any group of DBA mice. On the other hand, cadmium-treated (16 x 40) NFS mice, but not DBA mice, had more hepatocellular adenomas and carcinomas (9/27) than control (1/15) but only at the high dose (16 x 40). More cadmium-treated NFS mice had pulmonary tumors than controls, but only at the lower dose (1 x 40). Although testicular tumors were rare, nonneoplastic lesions (fibrosis and mineralization) were induced by cadmium to a similar extent in both strains. Clearly cadmium carcinogenicity varies widely with strain, indicating a genetic basis to susceptibility. The basis of these strain differences deserves further study. PMID:7958559

  2. A comparison of clinical and surgical outcomes between laparo-endoscopic single-site surgery and traditional multiport laparoscopic surgery for adnexal tumors

    PubMed Central

    Lee, In Ok; Yoon, Jung Won; Chung, Dawn; Yim, Ga Won; Nam, Eun Ji; Kim, Sunghoon; Kim, Sang Wun

    2014-01-01

    Objective The purpose of this study was to compare clinical and surgical outcomes between laparo-endoscopic single-site (LESS) surgery and traditional multiport laparoscopic (TML) surgery for treatment of adnexal tumors. Methods Medical records were reviewed for patients undergoing surgery for benign adnexal tumors between January 2008 and April 2012 at our institution. All procedures were performed by the same surgeon. Clinical and surgical outcomes for patients undergoing LESS surgery using Glove port were compared with those patients undergoing TML surgery. Results A review of 129 patient cases undergoing LESS surgery using Glove port and 100 patient cases undergoing TML surgery revealed no significant differences in the baseline characteristics of the two groups. The median operative time was shorter in the LESS group using Glove port at 44 minutes (range, 19-126 minutes) than the TML group at 49 minutes (range, 20-196 minutes) (P=0.0007). There were no significant differences between in the duration of postoperative hospital stay, change in hemoglobin levels, pain score or the rate of complications between the LESS and TML groups. Conclusion LESS surgery showed comparable clinical and surgical outcomes to TML surgery, and required less operative time. Future prospective trials are warranted to further define the benefits of LESS surgery for adnexal tumor treatment. PMID:25264529

  3. Fibromatosis of the Sigmoid Colon With CTNNB1 (β-Catenin) Gene Mutation, Arising at the Site of Ileocolic Anastomosis for Resection of Gastrointestinal Stromal Tumor.

    PubMed

    Thway, Khin; Abou Sherif, Sara; Riddell, Angela M; Mudan, Satvinder

    2016-05-01

    We describe a case of intra-abdominal fibromatosis, which occurred in a 44-year-old woman who had a previous history of gastrointestinal stromal tumor (GIST) of the sigmoid mesocolon, which was treated with imatinib and resection. A mass was detected at the site of ileocolic anastomosis of the previous small bowel resection and sigmoid colectomy, nearly 3 years later. Clinically, this was suspected to represent recurrent GIST and was excised, but histology and mutational analysis showed desmoid-type fibromatosis with a mutation in codon 41 of exon 3 of the CTNNB1 (β-catenin) gene. The occurrence of fibromatosis at the site of excision of GIST is very rare, but its recognition is important as the treatment of the two neoplasms differs significantly. As imaging cannot reliably distinguish between these 2 entities, histological diagnosis is crucial for correct clinical management. PMID:26721303

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

    PubMed

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

    2012-01-01

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

  5. Ependymoma: a heterogeneous tumor of uncertain origin and limited therapeutic options.

    PubMed

    Dorfer, Christian; Tonn, Joerg; Rutka, James T

    2016-01-01

    Ependymomas are tumors that typically occur with an age-based site preference, with adults harboring supratentorial and spinal tumors and pediatric tumors being mainly in the posterior fossa. Despite their similar histologic appearance, the prognosis varies significantly by age and tumor location, with a better prognosis in increasing age. The mainstay of treatment remains surgical excision with or without radiation therapy as the tumor biology is poorly understood and chemotherapy is generally considered to be ineffective. More recently, molecular biology data have increased our understanding of the genetic and epigenetic changes that drive these tumors, but still it will take a lot of effort to find effective chemotherapeutic regimens. Currently, we are trying to define a subset of tumors, for which radiation therapy can be avoided. PMID:26948369

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

    PubMed

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

    2016-09-01

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

  7. Acquired Tumor Cell Radiation Resistance at the Treatment Site Is Mediated Through Radiation-Orchestrated Intercellular Communication

    SciTech Connect

    Aravindan, Natarajan; Aravindan, Sheeja; Pandian, Vijayabaskar; Khan, Faizan H.; Ramraj, Satish Kumar; Natt, Praveen; Natarajan, Mohan

    2014-03-01

    Purpose: Radiation resistance induced in cancer cells that survive after radiation therapy (RT) could be associated with increased radiation protection, limiting the therapeutic benefit of radiation. Herein we investigated the sequential mechanistic molecular orchestration involved in radiation-induced radiation protection in tumor cells. Results: Radiation, both in the low-dose irradiation (LDIR) range (10, 50, or 100 cGy) or at a higher, challenge dose IR (CDIR), 4 Gy, induced dose-dependent and sustained NFκB-DNA binding activity. However, a robust and consistent increase was seen in CDIR-induced NFκB activity, decreased DNA fragmentation, apoptosis, and cytotoxicity and attenuation of CDIR-inhibited clonal expansion when the cells were primed with LDIR prior to challenge dose. Furthermore, NFκB manipulation studies with small interfering RNA (siRNA) silencing or p50/p65 overexpression unveiled the influence of LDIR-activated NFκB in regulating CDIR-induced DNA fragmentation and apoptosis. LDIR significantly increased the transactivation/translation of the radiation-responsive factors tumor necrosis factor-α (TNF-α), interleukin-1α (IL-1α), cMYC, and SOD2. Coculture experiments exhibit LDIR-influenced radiation protection and increases in cellular expression, secretion, and activation of radiation-responsive molecules in bystander cells. Individual gene-silencing approach with siRNAs coupled with coculture studies showed the influence of LDIR-modulated TNF-α, IL-1α, cMYC, and SOD2 in induced radiation protection in bystander cells. NFκB inhibition/overexpression studies coupled with coculture experiments demonstrated that TNF-α, IL-1α, cMYC, and SOD2 are selectively regulated by LDIR-induced NFκB. Conclusions: Together, these data strongly suggest that scattered LDIR-induced NFκB-dependent TNF-α, IL-1α, cMYC, and SOD2 mediate radiation protection to the subsequent challenge dose in tumor cells.

  8. Transcriptional activation of the tumor suppressor and differentiation gene S100A2 by a novel p63-binding site.

    PubMed

    Kirschner, Ralf D; Sänger, Katja; Müller, Gerd A; Engeland, Kurt

    2008-05-01

    S100A2 is generally found expressed in the epidermis and was recently shown to play a crucial role in the differentiation of keratinocytes. Also known as CaN19, S100A2 was identified as a potential tumor suppressor. Expression of S100A2 is upregulated by p53. The proteins p63 and p73 are related to p53 and are expressed as several splice variants with partially overlapping tasks but also functions different from p53. It had been shown that p63 proteins with mutations in their DNA-binding domain cause severe phenotypes in man as autosomal dominantly inherited disease including EEC, AEC, SHFM, LMS and ADULT syndromes. Here we show that S100A2 is a transcriptional target of p63/p73 family members, particularly the p63 splice variant TAp63gamma. The regulation is mediated by a novel transcriptional element in the S100A2 promoter which is bound by TAp63gamma but not by p53. Mutant p63 proteins derived from EEC and ADULT syndrome patients cannot activate S100A2 transcription whereas SHFM-related mutants still can stimulate the S100A2 promoter. Consistent with a function in tumor suppression S100A2 expression is stimulated upon DNA damage. After doxorubicin treatment p63gamma proteins are recruited to the S100A2 promoter in vivo. This may indicate a function of the p63-dependent S100A2 regulation in tumor suppression. PMID:18388131

  9. Assessment of the "fish tumors or other deformities" beneficial use impairment in brown bullhead (Ameiurus nebulosus): I. Orocutaneous tumors

    USGS Publications Warehouse

    Blazer, V.S.; Rafferty, S.D.; Baumman, P.C.; Smith, S.B.; Obert, E.C.

    2009-01-01

    The "fish tumor or other deformities" beneficial use impairment (BUI) occurs at 9 of the 12 areas of concern (AOC) on Lake Erie. As point sources are mitigated and remediation occurs, AOC are faced with determining delisting criteria. The lack of standardized analyses for this BUI has confounded that process. For orocutaneous tumors, different criteria (presumptive tumors and/or abnormal barbels) and methodology (gross versus microscopic observations) have been used. Hence, this project evaluated tumors at numerous AOC and non-AOC sites and compared methodology. In 1998-2000 the prevalence of presumptive orocutaneous tumors and barbel abnormalities was compared in brown bullhead (Ameiurus nebulosus) collected at eight AOC. The Black (46.7%), Buffalo (29.3%), Cuyahoga (58.9%), and Detroit (26.5%) rivers and Presque Isle Bay (28.6%) had high prevalences of orocutaneous tumors, while the Niagara (10%), Maumee (3.9%) and Ashtabula (4.4%) rivers were lower. From 2002 to 2007 the prevalence of orocutaneous tumors at Presque Isle Bay was consistently near 30%. A variety of non-AOC sites, as potential reference sites, were also monitored during this time. By combining years and sites the prevalence of orocutaneous tumors in bullhead (age 2-12 years) at inland lakes was 6.3%, at Long Point Inner Bay was 8.7%, at other bays and harbors was 14.6% and at tributary sites was 12.5%. Overall, 93% of the raised lesions identified as presumptive tumors grossly were verified as neoplasms microscopically. The prevalence of orocutaneous tumors increased with age at both Presque Isle Bay and Long Point Inner Bay, the sites with the largest sample sizes.

  10. Neuroimmune connections in jejunal and ileal Peyer's patches at various bovine ages: potential sites for prion neuroinvasion.

    PubMed

    Defaweux, Valérie; Dorban, Gauthier; Antoine, Nadine; Piret, Joëlle; Gabriel, Annick; Jacqmot, Olivier; Falisse-Poirier, Nandini; Flandroy, Sylvain; Zorzi, Danièle; Heinen, Ernst

    2007-07-01

    During preclinical stages of cattle orally infected with bovine spongiform encephalopathy (BSE), the responsible agent is confined to ileal Peyer's patches (IPP), namely in nerve fibers and in lymph follicles, before reaching the peripheral and central nervous systems. No infectivity has been reported in other bovine lymphoid organs, including jejunal Peyer's patches (JPP). To determine the potential sites for prion neuroinvasion in IPP, we analyzed the mucosal innervation and the interface between nerve fibers and follicular dendritic cells (FDC), two dramatic influences on neuroinvasion. Bovine IPP were studied at three ages, viz., newborn calves, calves less than 12 months old, and bovines older than 24 months, and the parameters obtained were compared with those of JPP. No differences in innervation patterns between IPP and JPP were found. The major difference observed was that, in calves of less than 12 months, IPP were the major mucosal-associated lymphoid organ that possessed a large number of follicles with extended FDC networks. Using a panel of antibodies, we showed that PP in 24-month-old bovines were highly innervated at various strategic sites assumed to be involved in the invasion and replication of the BSE pathogen: the suprafollicular dome, T cell area, and germinal centers. In PP in calves of less than 12 months old, no nerve fibers positive for the neurofilament markers NF-L (70 kDa) and NF-H (200 kDa) were observed in contact with FDC. Thus, in view of the proportion of these protein subunits present in neurofilaments, the innervation of the germinal centers can be said to be an age-dependent dynamic process. This variation in innervation might influence the path of neuroinvasion and, thus, the susceptibility of bovines to the BSE agent. PMID:17406903

  11. Comparison of two site-specifically (18)F-labeled affibodies for PET imaging of EGFR positive tumors.

    PubMed

    Su, Xinhui; Cheng, Kai; Jeon, Jongho; Shen, Bin; Venturin, Gianina Teribele; Hu, Xiang; Rao, Jianghong; Chin, Frederick T; Wu, Hua; Cheng, Zhen

    2014-11-01

    The epidermal growth factor receptor (EGFR) serves as an attractive target for cancer molecular imaging and therapy. Our previous positron emission tomography (PET) studies showed that the EGFR-targeting affibody molecules (64)Cu-DOTA-ZEGFR:1907 and (18)F-FBEM-ZEGFR:1907 can discriminate between high and low EGFR-expression tumors and have the potential for patient selection for EGFR-targeted therapy. Compared with (64)Cu, (18)F may improve imaging of EGFR-expression and is more suitable for clinical application, but the labeling reaction of (18)F-FBEM-ZEGFR:1907 requires a long synthesis time. The aim of the present study is to develop a new generation of (18)F labeled affibody probes (Al(18)F-NOTA-ZEGFR:1907 and (18)F-CBT-ZEGFR:1907) and to determine whether they are suitable agents for imaging of EGFR expression. The first approach consisted of conjugating ZEGFR:1907 with NOTA and radiolabeling with Al(18)F to produce Al(18)F-NOTA-ZEGFR:1907. In a second approach the prosthetic group (18)F-labeled-2-cyanobenzothiazole ((18)F-CBT) was conjugated to Cys-ZEGFR:1907 to produce (18)F-CBT-ZEGFR:1907. Binding affinity and specificity of Al(18)F-NOTA-ZEGFR:1907 and (18)F-CBT-ZEGFR:1907 to EGFR were evaluated using A431 cells. Biodistribution and PET studies were conducted on mice bearing A431 xenografts after injection of Al(18)F-NOTA-ZEGFR:1907 or (18)F-CBT-ZEGFR:1907 with or without coinjection of unlabeled affibody proteins. The radiosyntheses of Al(18)F-NOTA-ZEGFR:1907 and (18)F-CBT-ZEGFR:1907 were completed successfully within 40 and 120 min with a decay-corrected yield of 15% and 41% using a 2-step, 1-pot reaction and 2-step, 2-pot reaction, respectively. Both probes bound to EGFR with low nanomolar affinity in A431 cells. Although (18)F-CBT-ZEGFR:1907 showed instability in vivo, biodistribution studies revealed rapid and high tumor accumulation and quick clearance from normal tissues except the bones. In contrast, Al(18)F-NOTA-ZEGFR:1907 demonstrated high in

  12. Middle Pleistocene lower back and pelvis from an aged human individual from the Sima de los Huesos site, Spain

    PubMed Central

    Bonmatí, Alejandro; Gómez-Olivencia, Asier; Arsuaga, Juan-Luis; Carretero, José Miguel; Gracia, Ana; Martínez, Ignacio; Lorenzo, Carlos; Bérmudez de Castro, José María; Carbonell, Eudald

    2010-01-01

    We report a nearly complete lumbar spine from the Middle Pleistocene site of the Sima de los Huesos (SH) that is assigned to the previously published SH male Pelvis 1 [Arsuaga JL, et al. (1999). Nature 399: 255–258]. The “SH Pelvis 1 individual” is a unique nearly complete lumbo-pelvic complex from the human Middle Pleistocene fossil record, and offers a rare glimpse into the anatomy and past lifeways of Homo heidelbergensis. A revised reconstruction of Pelvis 1, together with the current fossil evidence, confirms our previous hypothesis that the morphology of this pelvis represents the primitive pattern within the genus Homo. Here we argue that this primitive pattern is also characterized by sexual dimorphism in the pelvic canal shape, implying complicated deliveries. In addition, this individual shows signs of lumbar kyphotic deformity, spondylolisthesis, and Baastrup disease. This suite of lesions would have postural consequences and was most likely painful. As a result, the individual’s daily physical activities would have been restricted to some extent. Reexamination of the age-at-death agrees with this individual being over 45 y old, relying on the modern human pattern of changes of the articular surfaces of the os coxae. The presence of degenerative pathological lesions and the advanced age-at-death of this individual make it the most ancient postcranial evidence of an aged individual in the human fossil record. Additional nonpathological SH lumbo-pelvic remains are consistent with previous hypotheses, suggesting a less-pronounced sagittal spinal curvature in Neandertals compared with Homo sapiens. PMID:20937858

  13. Middle Pleistocene lower back and pelvis from an aged human individual from the Sima de los Huesos site, Spain.

    PubMed

    Bonmatí, Alejandro; Gómez-Olivencia, Asier; Arsuaga, Juan-Luis; Carretero, José Miguel; Gracia, Ana; Martínez, Ignacio; Lorenzo, Carlos; Bérmudez de Castro, José María; Carbonell, Eudald

    2010-10-26

    We report a nearly complete lumbar spine from the Middle Pleistocene site of the Sima de los Huesos (SH) that is assigned to the previously published SH male Pelvis 1 [Arsuaga JL, et al. (1999). Nature 399: 255-258]. The "SH Pelvis 1 individual" is a unique nearly complete lumbo-pelvic complex from the human Middle Pleistocene fossil record, and offers a rare glimpse into the anatomy and past lifeways of Homo heidelbergensis. A revised reconstruction of Pelvis 1, together with the current fossil evidence, confirms our previous hypothesis that the morphology of this pelvis represents the primitive pattern within the genus Homo. Here we argue that this primitive pattern is also characterized by sexual dimorphism in the pelvic canal shape, implying complicated deliveries. In addition, this individual shows signs of lumbar kyphotic deformity, spondylolisthesis, and Baastrup disease. This suite of lesions would have postural consequences and was most likely painful. As a result, the individual's daily physical activities would have been restricted to some extent. Reexamination of the age-at-death agrees with this individual being over 45 y old, relying on the modern human pattern of changes of the articular surfaces of the os coxae. The presence of degenerative pathological lesions and the advanced age-at-death of this individual make it the most ancient postcranial evidence of an aged individual in the human fossil record. Additional nonpathological SH lumbo-pelvic remains are consistent with previous hypotheses, suggesting a less-pronounced sagittal spinal curvature in Neandertals compared with Homo sapiens. PMID:20937858

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

    PubMed Central

    2010-01-01

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

  15. LIDAR-based coastal landscape reconstruction and harbour location: The Viking-age royal burial site of Borre (Norway)

    NASA Astrophysics Data System (ADS)

    Draganits, Erich; Doneus, Michael; Gansum, Terje

    2013-04-01

    Airborne light detection and ranging (LIDAR) has found wide application in archaeological research for the detection and documentation of archaeological and palaeo-environmental features. In this study we demonstrate the analysis of an LIDAR derived 1x1 m digital elevation model (DTM) combined with geoarchaeological research of the coastal Viking-age burial site in Borre, Olso Fjord (Norway). Borre is an exceptional burial site in Scandinavia, containing burial mounds up to 40 m in diameter and 6 m height, mentioned in Nordic Sagas, especially in the skaldic poem Ynglingatal, as the burial place of one or two kings of the Ynglinga dynasty. Archaeological findings and radiocarbon ages indicate that the Borre burial ground had been in use broadly between 600-1000 AD. Despite the reasonable expectation that a coastal site connected with the Viking kings of Vestfold, with hall buildings and ship graves demands a harbour, up to now no harbour has not been found with traditional archaeological surveys. Since the area of Borre is affected by a continuous land uplift related to glacial rebound of Scandinavia, any former harbour site is expected to be exposed to the land surface today. The present day vertical crustal uplift is calculated around 2.5 mm/yr in the area of Borre. Burial mounds and surrounding borrow pits as well as geomorphological features of the uplifted coast of Borre have been analysed by the 1x1 m LIDAR-DTM, using hillshade, slope and local relief model for visualisation. Altogether, 41 burial mounds and further 6 potential mounds are visible in the high-resolution DTM. A succession of more than 14 beach ridges, cross-cut by the burial mounds, is visible from the present shore line up to 18 m asl. They are more or less parallel and similar in size, except between at ca. 4-6 m asl, where the most prominent ridge is located, which probably has been enforced artificially. Using published shoreline displacement curves from nearby areas, the shore-line at

  16. The age of three Middle Palaeolithic sites: Single-grain optically stimulated luminescence chronologies for Pech de l'Azé I, II and IV in France.

    PubMed

    Jacobs, Zenobia; Jankowski, Nathan R; Dibble, Harold L; Goldberg, Paul; McPherron, Shannon J P; Sandgathe, Dennis; Soressi, Marie

    2016-06-01

    Optically stimulated luminescence (OSL) measurements were made on individual, sand-sized grains of quartz from Middle Palaeolithic deposits at three sites (Pech de l'Azé I, II and IV) located close to one another in the Dordogne region of southwest France. We were able to calculate OSL ages for 69 samples collected from these three sites. These ages reveal periods of occupation between about 180 and 50 thousand years ago. Our single-grain OSL chronologies largely support previous age estimates obtained by thermoluminescence dating of burnt flints at Pech IV, electron spin resonance dating of tooth enamel at Pech I, II and IV and radiocarbon dating of bone at Pech I and IV, but provide a more complete picture due to the ubiquitous presence of sand-sized quartz grains used in OSL dating. These complete chronologies for the three sites have allowed us to compare the single-grain ages for similar lithic assemblages among the three sites, to test the correlations among them previously proposed by Bordes in the 1970s, and to construct our own correlative chronological framework for the three sites. This shows that similar lithic assemblages occur at around the same time, and that where a lithic assemblage is unique to one or found at two of the Pech sites, there are no deposits of chronologically equivalent age at the other Pech site(s). We interpret this to mean that, at least for these Pech de l'Azé sites, the Mousterian variants show temporal ordering. Whether or not this conclusion applies to the wider region and beyond, the hypothesis that Mousterian industrial variation is temporally ordered cannot be refuted at this time. PMID:27260176

  17. Age-related changes in skin blood flow at four anatomic sites of the body in males studied by xenon-133

    SciTech Connect

    Tsuchida, Y.

    1990-04-01

    The normal skin blood flow in healthy subjects consisting of 28 males whose ages ranged from 20 to 72 years was measured by the xenon-133 clearance method at four different sites of the body to determine the presence of any age-related changes. The following results were obtained: Significant age-related changes were observed in the skin blood flow of the deltoid region, anterior chest, dorsum of the hand, and dorsum of the foot. Normal skin blood flow was demonstrated to be highly dependent on age and to significantly decrease with age. Average skin blood flow at these four regions of those 70 years of age decreased by 30 to 40 percent when compared to that of those 20 years of age. The skin blood flow at the deltoid region of healthy subjects was higher by 6.3 ml/100 gm per minute than that of patients in poor condition with cancer of the head and neck.

  18. Malignant Eccrine Poroma of the Vulva: An Intriguing Case of a Rare Tumor at an Unusual Site.

    PubMed

    Mishra, Pranshu; Sen, Sumit; Sharma, Neha; Sen, Debasish

    2016-01-01

    Malignant eccrine poroma is a rare malignancy of the eccrine sweat glands, occurring most frequently on the lower extremities. It affects both sexes equally usually in the 6(th) to 7(th) decade of life. Metastasis to regional lymph nodes may occur in 20% that may be fatal in 60% cases. Its aggressive nature, rarity of occurrence, and unusual presentations make it very important to be evaluated properly by the clinician. We hereby report a case of a 75-year-old female presenting with two exophytic tumors over her vulva with local extension. On histopathological examination, it was diagnosed as malignant eccrine poroma. On magnetic resonance imaging of the pelvic region, metastatic extension in regional lymph nodes was found. She was treated by radical vulvectomy with bilateral inguinal and femoral lymph node dissection followed by radiotherapy. PMID:27512190

  19. Malignant Eccrine Poroma of the Vulva: An Intriguing Case of a Rare Tumor at an Unusual Site

    PubMed Central

    Mishra, Pranshu; Sen, Sumit; Sharma, Neha; Sen, Debasish

    2016-01-01

    Malignant eccrine poroma is a rare malignancy of the eccrine sweat glands, occurring most frequently on the lower extremities. It affects both sexes equally usually in the 6th to 7th decade of life. Metastasis to regional lymph nodes may occur in 20% that may be fatal in 60% cases. Its aggressive nature, rarity of occurrence, and unusual presentations make it very important to be evaluated properly by the clinician. We hereby report a case of a 75-year-old female presenting with two exophytic tumors over her vulva with local extension. On histopathological examination, it was diagnosed as malignant eccrine poroma. On magnetic resonance imaging of the pelvic region, metastatic extension in regional lymph nodes was found. She was treated by radical vulvectomy with bilateral inguinal and femoral lymph node dissection followed by radiotherapy. PMID:27512190

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

    PubMed Central

    Wang, Longxin; Zhou, Wenquan

    2016-01-01

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

  1. Spinal tumors in children.

    PubMed

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

    2007-10-01

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

  2. Plasma Proteins Modified by Advanced Glycation End Products (AGEs) Reveal Site-specific Susceptibilities to Glycemic Control in Patients with Type 2 Diabetes.

    PubMed

    Greifenhagen, Uta; Frolov, Andrej; Blüher, Matthias; Hoffmann, Ralf

    2016-04-29

    Protein glycation refers to the reversible reaction between aldoses (or ketoses) and amino groups yielding relatively stable Amadori (or Heyns) products. Consecutive oxidative cleavage reactions of these products or the reaction of amino groups with other reactive substances (e.g. α-dicarbonyls) yield advanced glycation end products (AGEs) that can alter the structures and functions of proteins. AGEs have been identified in all organisms, and their contents appear to rise with some diseases, such as diabetes and obesity. Here, we report a pilot study using highly sensitive and specific proteomics approach to identify and quantify AGE modification sites in plasma proteins by reversed phase HPLC mass spectrometry in tryptic plasma digests. In total, 19 AGE modification sites corresponding to 11 proteins were identified in patients with type 2 diabetes mellitus under poor glycemic control. The modification degrees of 15 modification sites did not differ among cohorts of normoglycemic lean or obese and type 2 diabetes mellitus patients under good and poor glycemic control. The contents of two amide-AGEs in human serum albumin and apolipoprotein A-II were significantly higher in patients with poor glycemic control, although the plasma levels of both proteins were similar among all plasma samples. These two modification sites might be useful to predict long term, AGE-related complications in diabetic patients, such as impaired vision, increased arterial stiffness, or decreased kidney function. PMID:26933035

  3. Definition of a physiologic aging autoantigen by using synthetic peptides of membrane protein band 3: localization of the active antigenic sites.

    PubMed

    Kay, M M; Marchalonis, J J; Hughes, J; Watanabe, K; Schluter, S F

    1990-08-01

    Senescent cell antigen (SCA), an aging antigen, is a protein that appears on old cells and marks them for removal by the immune system in mammals. It is derived from band 3, a ubiquitous membrane transport protein found in diverse cell types and tissues. We have used synthetic peptides to identify aging antigenic sites on band 3, using a competitive inhibition assay and immunoblotting with IgG directed against the aging antigen on old cells. Results indicate that: (i) the active antigenic sites of the aging antigen reside on membrane protein band 3 residues that are extracellular regions implicated in anion transport (residues 538-554 and 788-827); (ii) a putative ankyrin-binding-region peptide is not involved in SCA activity; and (iii) carbohydrate moieties are not required for the antigenicity or recognition of SCA because synthetic peptides alone abolish binding of senescent cell IgG to erythrocytes. One of the putative transport sites that contributes to the aging antigen is located toward the carboxyl terminus. A model of band 3 is presented. Localization of the active antigenic site on the band 3 molecule facilitates definition of the molecular changes occurring during aging that initiate molecular as well as cellular degeneration. PMID:1696010

  4. H3K9/36me3 Demethylase KDM4A Promotes Site-Specific Copy Gain and Re-replication of Regions Amplified in Tumors

    PubMed Central

    Black, Joshua C.; Manning, Amity; Van Rechem, Capucine; Kim, Jaegil; Ladd, Brendon; Cho, Juok; Pineda, Cristiana M.; Murphy, Nancy; Daniels, Danette L.; Montagna, Cristina; Lewis, Peter W.; Glass, Kimberly; Allis, C. David; Dyson, Nicholas J.; Getz, Gad; Whetstine, Johnathan R.

    2013-01-01

    SUMMARY Acquired chromosomal instability and copy number alterations are hallmarks of cancer. Enzymes capable of promoting site-specific copy number changes have yet to be identified. Here, we demonstrate that H3K9/36me3 lysine demethylase KDM4A/JMJD2A overexpression leads to localized copy gain of 1q12, 1q21, and Xq13.1 without global chromosome instability. KDM4A amplified tumors have increased copy gains for these same regions. 1q12h copy gain occurs within a single cell cycle, requires S phase and is not stable but regenerated each cell division. Sites with increased copy number are re-replicated and have increased KDM4A, MCM and DNA polymerase occupancy. Suv39h1/KMT1A or HP1γ overexpression suppresses the copy gain, while H3K9/K36 methylation interference promotes gain. Our results demonstrate that overexpression of a chromatin modifier results in site-specific copy gains. This begins to establish how copy number changes could originate during tumorigenesis and demonstrates that transient overexpression of specific chromatin modulators could promote these events. PMID:23871696

  5. Archaeomagnetic dating of a High Middle Age likely iron working site in Corroy-le-Grand (Belgium)

    NASA Astrophysics Data System (ADS)

    Spassov, Simo; Hus, Jozef; Geeraerts, Raoul; Heller, Frédéric

    Archaeological burnt materials and structures provide unique records of direction and intensity of the Earth’s magnetic field in the past, elements that can be absolutely determined applying the archaeomagnetic method. At present, such records within Europe are irregular in both space and time. Presented here is the archaeomagnetic investigation of three kilns that were discovered during a preventive excavation of an archaeological site considered of High Middle Age in Corroy-le-Grand (Belgium) and that are assumed to be related to iron working activities. Archaeological context dating points to kiln operation between the second half of the 10th century until the 12th century AD. As the site is not far from Paris, declination and inclination of the characteristic remanent magnetisation of the kilns were compared with the standard directional secular variation curve for France in order to propose archaeomagnetic dates for the cessation of kiln operation by using probability densities [Lanos, Ph., 2004. Bayesian inference of calibration curves, application to archaeomagnetism. In: Buck, C.E., Millard, A.R. (Eds.), Tools for Constructing Chronologies: Crossing Disciplinary Boundaries. Lecture Notes in Statistics. Springer Verlag, London, pp. 43-82; Lanos, Ph., Le Goff, M., Kovacheva, M., Schnepp, E., 2005. Hierarchical modelling of archaeomagnetic data and curve estimation by moving average technique. Geophysical Journal International 160 (2), 440-476]. This confirms the presumed archaeological age and resulted in more precise time constraints for the last kiln operation. Rock magnetic techniques, proposed by Spassov and Hus [Spassov, S., Hus, J., 2006. Estimating baking temperatures in a Roman pottery kiln by rock magnetic properties: implications of thermochemical alteration for archaeointensity determinations. Geophysical Journal International 167, 592-604], were applied to examine the suitability of the burnt materials from the kilns for archaeointensity

  6. Impact of vegetation cover and stand age on scaling carbon fluxes in the upper Midwest: a multiple eddy flux site study

    NASA Astrophysics Data System (ADS)

    Desai, A. R.; Normeets, A.; Bolstad, P. V.; Chen, J.; Cook, B. D.; Curtis, P. S.; Davis, K. J.; Euskirchen, E.; Gough, C.; Martin, J.; Ricciuto, D. M.; Schmid, H. P.; Tang, J.; Su, H.; Vogel, C.; Wang, W.

    2004-12-01

    Eight permanent and three roving eddy flux towers were used to observe the exchange of carbon dioxide between the ecosystem and atmosphere at fourteen different sites in northern Wisconsin and Michigan (USA) during the growing seasons (May-Sept) of 2002 and 2003. These towers were part of the Chequamegon Ecosystem-Atmosphere Study (ChEAS), the University of Michigan Biological Station (UMBS), and the Michigan Technical University. The sites spanned a range of vegetation types typical of the region (northern hardwood, hemlock-hardwood, mixed forest, red pine, jack pine, pine barrens and shrub wetland). The hardwood and red pine sites also spanned a range of forest stand age (young, intermediate, mature and old). All sites experienced roughly similar climate; thus, comparisons among the sites allow for an examination of the impact of heterogeneous vegetation cover and stand age across a regional landscape. Carbon fluxes at different sites generally reacted similarly in response to variability in climate. Results suggest that both cover type and stand age are important variables for modeling and predicting fluxes in this region. These results have implications for developing methods of scaling carbon dioxide fluxes from sites to regions. These results will be contrasted to a flux decomposition at the WLEF tall tower.

  7. Sites of infection by pythium species in rice seedlings and effects of plant age and water depth on disease development.

    PubMed

    Chun, S C; Schneider, R W

    1998-12-01

    ABSTRACT Seedling disease, caused primarily by several species of Pythium, is one of the major constraints to water-seeded rice production in Louisiana. The disease, also known as water-mold disease, seed rot, and seedling damping-off, causes stand reductions and growth abnormalities. In severe cases, fields must be replanted, which may result in delayed harvests and reduced yields. To develop more effective disease management tactics including biological control, this study was conducted primarily to determine sites of infection in seeds and seedlings; effect of plant age on susceptibility to P. arrhenomanes, P. myriotylum, and P. dissotocum; and minimum exposure times required for infection and seedling death. In addition, the effect of water depth on seedling disease was investigated. Infection rates of seed embryos were significantly higher than those of endosperms for all three Pythium spp. The development of roots from dry-seeded seedlings was significantly reduced by P. arrhenomanes and P. myriotylum at 5 days after planting compared with that of roots from noninoculated controls. Susceptibility of rice to all three species was sharply reduced within 2 to 6 days after planting, and seedlings were completely resistant at 8 days after planting. There was a steep reduction in emergence through the flood water, relative to the noninoculated control, following 2 to 3 days of exposure to inoculum of P. arrhenomanes and P. myriotylum. In contrast, P. dissotocum was much less virulent and required longer exposure times to cause irreversible seedling damage. Disease incidence was higher when seeds were planted into deeper water, implying that seedlings become resistant after they emerge through the flood water. These results suggest that disease control tactics including flood water management need to be employed for a very short period of time after planting. Also, given that the embryo is the primary site of infection and it is susceptible for only a few days, the

  8. Deleted in Malignant Brain Tumors-1 Protein (DMBT1): A Pattern Recognition Receptor with Multiple Binding Sites

    PubMed Central

    Ligtenberg, Antoon J. M.; Karlsson, Niclas G.; Veerman, Enno C. I.

    2010-01-01

    Deleted in Malignant Brain Tumors-1 protein (DMBT1), salivary agglutinin (DMBT1SAG), and lung glycoprotein-340 (DMBT1GP340) are three names for glycoproteins encoded by the same DMBT1 gene. All these proteins belong to the scavenger receptor cysteine-rich (SRCR) superfamily of proteins: a superfamily of secreted or membrane-bound proteins with SRCR domains that are highly conserved down to sponges, the most ancient metazoa. In addition to SRCR domains, all DMBT1s contain two CUB domains and one zona pellucida domain. The SRCR domains play a role in the function of DMBT1s, which is the binding of a broad range of pathogens including cariogenic streptococci, Helicobacter pylori and HIV. Mucosal defense proteins like IgA, surfactant proteins and lactoferrin also bind to DMBT1s through their SRCR domains. The binding motif on the SRCR domains comprises an 11-mer peptide in which a few amino acids are essential for binding (GRVEVLYRGSW). Adjacent to each individual SRCR domain are glycosylation domains, where the attached carbohydrate chains play a role in the binding of influenza A virus and Helicobacter pylori. The composition of the carbohydrate chains is not only donor specific, but also varies between different organs. These data demonstrate a role for DMBT1s as pattern recognition molecules containing various peptide and carbohydrate binding motifs. PMID:21614203

  9. Effect of Transport and Aging Processes on Metal Speciation in Iron Oxyhydroxide Aggregates, Tar Creek Superfund Site, Oklahoma

    NASA Astrophysics Data System (ADS)

    Estes, E. R.; Schaider, L. A.; Shine, J. P.; Brabander, D. J.

    2010-12-01

    Following the cessation of mining activity in the late 20th century, Tar Creek Superfund Site was left highly contaminated by Pb, Zn, and Cd. Tar Creek, which flows through the site and into the Neosho River, has been studied extensively because of its potential to transport metals from the mining site to downstream communities. Previous research identified aggregated iron oxyhydroxide material, which forms when mine seepage mixes with Tar Creek surface water, as a major transport vector of metals. Frequent flooding in Tar Creek deposits aggregates on downstream floodplains, where wetting and drying processes alter the speciation of iron and other metals. This study seeks to better quantify those changes and to determine how transport and aging affects the human and ecological health risk. Sequential extractions of aggregate samples collected from the creek demonstrate that Fe is present in both amorphous (10-35% of Fe extracted) and more crystalline (8-23% of Fe extracted) phases. Substantial portions of heavy metals sorb to amorphous iron oxyhydroxide phases (accounting for 10-30% of Pb and Zn extracted) but are not associated with more crystalline iron oxide phases (representing only 1% or less of the Pb and Zn extracted). Samples have a high organic matter content (18-25% mass loss on ignition), but only Fe was significantly extracted by the oxidizing step targeting organic matter (1-2% of Pb and Zn extracted, but 10-26% of Fe extracted). The majority of metals were extracted by the soluble or residual steps. If metals and organic matter inhibit transformation of amorphous iron oxyhydroxide material to nano and crystalline iron oxides, then a steady-state volume of amorphous iron oxyhydroxide material with a high total sorption capacity may exist within Tar Creek, enhancing the metal flux accommodated by this transport mechanism. Once transported downstream and deposited on floodplains, however, it is hypothesized that repeated changes in soil matrix

  10. Optical and thermoluminescence dating of Middle Stone Age and Kintampo bearing sediments at Birimi, a multi-component archaeological site in Ghana

    NASA Astrophysics Data System (ADS)

    Quickert, Nicole A.; Godfrey-Smith, Dorothy I.; Casey, Joanna L.

    2003-05-01

    We report the first luminescence ages for the archeological and geological sediments forming the substrate of the Birimi archaeological site in the Northern Region of Ghana. The site's significance rests on the fact that it contains a rich collection of artifact assemblages representative of three distinct cultures, and that, on the basis of artifact typology, the earliest assemblage is diagnostic of the Middle Stone Age (MSA) . In situ occurrences of MSA artifacts are found at over 1 m below today's surface. They are overlain by a ceramic-rich complex of a sedentary or semi-sendentary Later Stone Age culture known as the Kintampo. The western half of the site is dominated by the industrial remains of Iron Age smelting activity. Elemental, mineralogical, and sedimentological analysis of the cultural and sub-cultural sedimentary horizons at the site revealed at least three distinct lithostratigraphic units. The quartz sediments are derived from the sandstone of the Gambaga escarpment, mass wasted and accreted fluvially at a rate of 3.2 cm/ka, forming a wide terrace at Birimi. Silts and finer fractions derive from windblown dust, likely from White Volta River and granitic sources to the north. Soil forming processes and wide fluctuations in moisture have progressively reduced the sediments at depth to the resistant quartz and kaolinite, with rich iron oxide coatings, and created two ironstone horizons composed of goethite-cemented quartz nodules. Multiple aliquot green-light stimulated optical ages for 125-150 μm quartz grains yielded ages of 23.6±2.9 and 40.8±11.8 ka for the MSA-bearing sediments, and 58.4±15.3 ka for the base of the terrace. Radiocarbon ages on charcoal from Kintampo-bearing units are 3.36-3.83 ka cal BP, and are supported by thermoluminescence (TL) ages on pottery sherds and burnt house daub fragments of this cultural complex. A 0.4 ka age on sediment from the site's surface confirms that the quartz zeroes well when exposed to natural light

  11. Quantification of Alterations in Cortical Bone Geometry Using Site Specificity Software in Mouse models of Aging and the Responses to Ovariectomy and Altered Loading

    PubMed Central

    Galea, Gabriel L.; Hannuna, Sion; Meakin, Lee B.; Delisser, Peter J.; Lanyon, Lance E.; Price, Joanna S.

    2015-01-01

    Investigations into the effect of (re)modeling stimuli on cortical bone in rodents normally rely on analysis of changes in bone mass and architecture at a narrow cross-sectional site. However, it is well established that the effects of axial loading produce site-specific changes throughout bones’ structure. Non-mechanical influences (e.g., hormones) can be additional to or oppose locally controlled adaptive responses and may have more generalized effects. Tools currently available to study site-specific cortical bone adaptation are limited. Here, we applied novel site specificity software to measure bone mass and architecture at each 1% site along the length of the mouse tibia from standard micro-computed tomography (μCT) images. Resulting measures are directly comparable to those obtained through μCT analysis (R2 > 0.96). Site Specificity analysis was used to compare a number of parameters in tibiae from young adult (19-week-old) versus aged (19-month-old) mice; ovariectomized and entire mice; limbs subjected to short periods of axial loading or disuse induced by sciatic neurectomy. Age was associated with uniformly reduced cortical thickness and site-specific decreases in cortical area most apparent in the proximal tibia. Mechanical loading site-specifically increased cortical area and thickness in the proximal tibia. Disuse uniformly decreased cortical thickness and decreased cortical area in the proximal tibia. Ovariectomy uniformly reduced cortical area without altering cortical thickness. Differences in polar moment of inertia between experimental groups were only observed in the proximal tibia. Aging and ovariectomy also altered eccentricity in the distal tibia. In summary, site specificity analysis provides a valuable tool for measuring changes in cortical bone mass and architecture along the entire length of a bone. Changes in the (re)modeling response determined at a single site may not reflect the response at different locations within the same

  12. Inorganic raw materials economy and provenance of chipped industry in some stone age sites of northern and central Italy.

    PubMed

    Bietti, Amilcare; Boschian, Giovanni; Crisci, Gino Mirocle; Danese, Ermanno; De Francesco, Anna Maria; Dini, Mario; Fontana, Federica; Giampietri, Alessandra; Grifoni, Renata; Guerreschi, Antonio; Liagre, Jérémie; Negrino, Fabio; Radi, Giovanna; Tozzi, Carlo; Tykot, Robert

    2004-06-01

    An opportunistic and local choice of raw materials is typically attested in the Lower and Middle Paleolithic industries throughout Italy. The quality of the raw material usually affected the flaking technology and quality of the products. In the Upper Paleolithic and the Mesolithic, raw material procurement strategies were more complex. Flint was exploited both locally, in areas where abundant outcrops of raw materials were available (such as the Lessini mountains), and in distant localities, after which it was transported or exchanged over medium/long distances. Different routes of exchange were thus followed in the various periods; good reconstruction of these routes have been provided by a study of the Garfagnana sites in Northern Tuscany, and the Mesolithic deposit of Mondeval de Sora (Dolomites). An interesting example of a Late Upper Paleolithic flint quarry and workshop were found in Abruzzo, in the San Bartolomeo shelter. The extended trade of obsidian from Lipari, Palmarola and Sardinia to the Italian Peninsula is attested in the Neolithic, with some differences concerning the age and different areas. PMID:15636064

  13. Potentially disseminated solitary fibrous tumor of the pleura: a case report.

    PubMed

    Nakano, Tomoyuki; Endo, Shunsuke; Tsubochi, Hiroyoshi; Tetsuka, Kenji; Nokubi, Mitsuhiro

    2015-10-01

    We report a case involving a female patient with frequent relapse, pleural dissemination, and port site recurrence (PSR) of a pleural solitary fibrous tumor (SFT). At the age of 55 years, she underwent tumor resection via video-assisted thoracoscopic surgery (VATS). The tumor arose from the mediastinal pleura; it was 7 cm in diameter and well demarcated. Histological examination showed neither hemorrhage nor necrosis, but moderate cellularity was present, and the Ki-67 labeling index was 15%. Despite complete resection, the tumor relapsed in the ipsilateral thoracic cavity 3 years postoperatively, and thoracoscopic complete tumor resection was performed; however, pleural lavage cytology (PLC) showed the presence of tumor cells. Multiple pleural dissemination and PSR developed 7 years after the initial surgery. The port site recurrent tumor was resected with the intercostal muscle via VATS. This case illustrates that a SFT may disseminate despite the fact that histological examination shows no evidence of malignancy. PMID:26623132

  14. [Cartilage tumors : Pathology and radiomorphology].

    PubMed

    Uhl, M; Herget, G; Kurz, P

    2016-06-01

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

  15. Transcription of the putative tumor suppressor gene HCCS1 requires binding of ETS-2 to its consensus near the transcription start site.

    PubMed

    Zhu, Jing De; Fei, Qi; Wang, Peng; Lan, Fei; Mao, Da Qin; Zhang, Hong Yu; Yao, Xue Biao

    2006-09-01

    The hepatocellular carcinoma suppressor 1 (HCCS1) gene was identified by both positional cloning from a predominant region of loss of heterozygosity (17p13.3) in liver cancer and by functional screening for genes affecting cell proliferation in large-scale transfection assays. Its overexpression results in inhibition of cell proliferation in cell culture and tumor growth in nude mice. To understand its transcription regulation, the promoter architecture has been dissected in detail. The major start of transcription was mapped by primer extension to a C residue, 177 nucleotides upstream of the ATG codon. By assessing the promoter activity of a set of linker-scanning mutants of the minimal promoter (-60 to +148 region) in a transient transfection assay, we found that the +1 to + 40 region is critical to HCCS1 gene transcription, containing binding sites for transcription factors NF-kappaB (-21 to +7 and +40 to +26), p53 (+29 to +9) and ETS (+4 to +20 and +23 to +39). Biochemical and molecular analyses revealed that the ETS transcription factors ETS-2 and Elf-1 bind to the two ETS sites in situ and contribute significantly to the transcriptionally active state of the HCCS1 gene, while NF-kappaB, p53 and two other members of the ETS family (ETS-1 and NERF2) appear to play little role. Our observations provide insight into the mechanistic aspects of HCCS1 transcription regulation. PMID:16953216

  16. A Comparison of the Binding Sites of Matrix Metalloproteinases and Tumor Necrosis Factor-α Converting Enzyme: Implications for Selectivity

    PubMed Central

    Lukacova, Viera; Zhang, Yufen; Kroll, Daniel M.; Raha, Soumyendu; Comez, Dogan; Balaz, Stefan

    2009-01-01

    MMPs and TACE (ADAM-17) assume independent, parallel or opposite pathological roles in cancer, arthritis, and several other diseases. For therapeutic purposes, selective inhibition of individual MMPs and TACE is required in most cases due to distinct roles in diseases and the need to preserve activities in normal states. Toward this goal, we compared force-field interaction energies of five ubiquitous inhibitor atoms with flexible binding sites of 24 known human MMPs and TACE. The results indicate that MMPs 1−3, 10, 11, 13, 16, and 17 have at least one subsite very similar to TACE. S3 subsite is the best target for development of specific TACE inhibitors. Specific binding to TACE compared to most MMPs is promoted by placing a negatively charged ligand part at the bottom of S2 subsite, at the entrance of S1’ subsite, or the part of S3’ subsite that is close to catalytic zinc. Numerous other clues, consistent with available experimental data, are provided for design of selective inhibitors. PMID:15801829

  17. Targeting the tumor microenvironment

    PubMed Central

    Bournazou, Eirini; Bromberg, Jacqueline

    2013-01-01

    Persistent JAK-STAT3 signaling is implicated in many aspects of tumorigenesis. Apart from its tumor-intrinsic effects, STAT3 also exerts tumor-extrinsic effects, supporting tumor survival and metastasis. These involve the regulation of paracrine cytokine signaling, alterations in metastatic sites rendering these permissive for the growth of cancer cells and subversion of host immune responses to create an immunosuppressive environment. Targeting this signaling pathway is considered a novel promising therapeutic approach, especially in the context of tumor immunity. In this article, we will review to what extent JAK-STAT3-targeted therapies affect the tumor microenvironment and whether the observed effects underlie responsiveness to therapy. PMID:24058812

  18. Odontogenic Tumors: A Review of 675 Cases in Eastern Libya

    PubMed Central

    Goteti, Saravana HL

    2016-01-01

    Aims: The aim of this study was to determine the relative frequency of odontogenic tumors (OTs) in an Eastern Libyan population based on the 2005 World Health Organization (WHO) classification, and also to compare the actual data with previous studies. Materials and Methods: We retrieved and analyzed 85 OTs from a total of 675 tumors and tumor-like lesions of the oral and perioral structures, for gender, age, tumor site, and frequency. The diagnosis was based on the most recent WHO (2005) classification of OTs. Results: OTs constituted 12.6% of all oral/jaw tumors and tumor-like lesions. Ameloblastoma (28.2%) was the most common type, followed by keratocystic odontogenic tumor (25.2%) and odontoma (19.9%). The male: female ratio was 1.2:1, and maxilla: mandible ratio 1:2. The mean age of occurrence of tumors was 29 years with a peak incidence between 10 and 40 years. Conclusions: OTs are relatively common lesion in this Libyan Population, but the incidence of tumors is neither similar to Caucasians nor Sub-Saharan population. PMID:27013857

  19. Contrasting epidemiology of childhood osteosarcoma, Ewing's tumor, and rhabdomyosarcoma

    SciTech Connect

    Miller, R.W.

    1981-04-01

    Marked dissimilarities in the epidemiology of osteosarcoma, Ewing's tumor, and rhabdomyosarcoma indicate differences in their origins. A major clue to the genesis of Ewing's tumor comes not from defining persons at high risk but from the observation that blacks are at unusually low risk. The neoplasm does not aggregate in families and is not part of any known syndrome. No environmental causes have been identified. By contrast, osteosarcoma may be caused by external or internal ionizing radiation, and it aggregated in families with the same tumor or with dissimilar tumors and in certain genetic disorders of bone. In man and in dogs, the frequency of the neoplasm is related to bone mass and growth. Rhabdomyosarcoma of the upper versus the lower limbs seems related to muscle mass. Age peaks in the occurrence of the tumor elsewhere vary with the anatomic site; head and neck tumors develop in early childhood and urogenital tumors both in early years and in adolescence. The sex ratio (male to female) also varies with the site affected. Rhabdomyosarcoma aggregates with certain other tumors in families and overlaps with osteosarcoma in some of these relationships but is distinguished from that tumor by its excessive occurrence in neurofibromatosis.

  20. [Surgical treatment of eyelid tumors].

    PubMed

    Serra, J M; Valiente, E; Paloma, V; Samayoa, V; Ordiales, G; Mesa, F

    1989-01-01

    Our surgical protocol for reconstruction of eyelid's defects after tumor excision is presented. Each technique is applied depending on the site and extension of the lesion and also on the pathologic characteristics of the tumor. PMID:2490181

  1. U-Pb isotopic results for single shocked and polycrystalline zircons record 550-65.5-Ma ages for a K-T target site and 2700-1850-Ma ages for the Sudbury impact event

    NASA Technical Reports Server (NTRS)

    Krogh, T. E.; Kamo, S. L.; Bohor, B. F.

    1992-01-01

    The refractory mineral zircon develops distinct morphological features during shock metamorphism and retains these features under conditions that would anneal them in other minerals. In addition, weakly shocked zircon grains give primary ages for the impact site, while highly reconstituted (polycrystalline) single grains give ages that approach the age of the impact event. Data for a series of originally coeval grains will define a mixing line that gives both of these ages providing that no subsequent geological disturbances have overprinted the isotopic systematics. In this study, we have shown that the three zircon grain types described by Bohor, from both K-T distal ejecta (Fireball layer, Raton Basin, Colorado) and the Onaping Formation, represent a progressive increase in impact-related morphological change that coincides with a progressive increase in isotopic resetting in zircons from the ejecta and basement rocks. Unshocked grains are least affected by isotopic resetting while polycrystalline grains are most affected. U-Pb isotopic results for 12 of 14 single zircon grains from the Fireball layer plot on or close to a line recording a primary age of 550 +/- 10 Ma and a secondary age of 65.5 +/- 3 Ma. Data for the least and most shocked grains plot closest to the primary and secondary ages respectively. The two other grains each give ages between 300 and 350 Ma. This implies that the target ejecta was dominated by 550-Ma rocks and that the recrystallization features of the zircon were superimposed during the impact event at 65.5 Ma. A predominant age of 550 Ma for zircons from the Fireball layer provides an excellent opportunity to identify the impact site and to test the hypothesis that multiple impacts occurred at this time. A volcanic origin for the Fireball layer is ruled out by shock-related morphological changes in zircon and the fact that the least shocked grains are old. Basement Levack gneisses north of the Sudbury structure have a primary age of

  2. Impaired recovery of brain muscarinic receptor sites following an adaptive down-regulation induced by repeated administration of diisopropyl fluorophosphate in aged rats

    SciTech Connect

    Pintor, A.; Fortuna, S.; De Angelis, S.; Michalek, H. )

    1990-01-01

    Potential age-related differences in the recovery rate of brain cholinesterase activity (ChE) and muscarinic acetylcholine receptor binding sites (mAChRs) following reduction induced by repeated treatment with diisopropyl fluorophosphate (DFP) were evaluated in Sprague-Dawley rats. Male 3- and 24-month old rats were s.c. injected with DFP on alternate days for 2 weeks and killed 48 hr and 7, 14, 21, 28 and 35 days after the last treatment. In the hippocampus and striatum, but not in the cerebral cortex, of control rats there as a significant age-related decline of ChE activity and maximal density of 3H-QNB binding sites (Bmax). The repeated administration of DFP during the first week caused a syndrome of cholinergic stimulation both in aged and young rats. The syndrome was more pronounced, in terms of intensity and duration in aged than in young animals resulting in 40 and 12% mortality, respectively; during the second week the syndrome attenuated in the two age-groups. The percentage inhibition of brain ChE at the end of DFP treatment did not differ between young and surviving aged rats. The down-regulation of mACRs was present in the three brain regions of both young and age rats (from 20 to 40%). Factorial analysis of variance showed significant differences for age, recovery rate, and significant interaction between age and recovery rate, both for ChE and mAChRs in young rats the three brain areas.

  3. Age through tandem correlation of Quaternary relative paleointensity (RPI) and oxygen isotope data at IODP Site U1306 (Eirik Drift, SW Greenland)

    NASA Astrophysics Data System (ADS)

    Channell, J. E. T.; Wright, J. D.; Mazaud, A.; Stoner, J. S.

    2014-03-01

    Planktic oxygen isotope (δ18O) and relative paleointensity (RPI) data are used in tandem to generate an age model for the last 1 Myr from Integrated Ocean Drilling Program (IODP) Site U1306 drilled on the crest of the Eirik Drift (SW Greenland) in 2272 m water depth. For the 1-1.5 Ma interval, the age model is based on RPI alone due to insufficient foraminifera for isotope analyses. Utilizing RPI and δ18O in tandem allows recognition of low-δ18O “events” prior to glacial Terminations I, III, IV, V, VII, VIII, IX and X, that are independently supported by radiocarbon dates through the last deglaciation, and are attributed to local or regional surface-water effects. At Site U1306, Quaternary sedimentation rates (mean ˜15 cm/ka) are elevated during peak glacials and glacial onsets, and are reduced during interglacials, in contrast to the pattern at Site U1305 in 3460 m water depth at the distal toe of the drift, 191 km SW of Site U1306. The contrasting sedimentation-rate pattern appears to hold for the entire ˜1.5 Myr record. The slackening and/or shoaling (due to lowered salinity) of the Deep Western Boundary Current (DWBC) during glacial intervals coincided with greater sediment supply to Site U1306 whereas the deepening, and possibly increased vigor, of the DWBC during interglacial intervals boosted sediment supply to Site U1305.

  4. Tumor Mismatch Repair Immunohistochemistry and DNA MLH1 Methylation Testing of Patients With Endometrial Cancer Diagnosed at Age Younger Than 60 Years Optimizes Triage for Population-Level Germline Mismatch Repair Gene Mutation Testing

    PubMed Central

    Buchanan, Daniel D.; Tan, Yen Y.; Walsh, Michael D.; Clendenning, Mark; Metcalf, Alexander M.; Ferguson, Kaltin; Arnold, Sven T.; Thompson, Bryony A.; Lose, Felicity A.; Parsons, Michael T.; Walters, Rhiannon J.; Pearson, Sally-Ann; Cummings, Margaret; Oehler, Martin K.; Blomfield, Penelope B.; Quinn, Michael A.; Kirk, Judy A.; Stewart, Colin J.; Obermair, Andreas; Young, Joanne P.; Webb, Penelope M.; Spurdle, Amanda B.

    2014-01-01

    Purpose Clinicopathologic data from a population-based endometrial cancer cohort, unselected for age or family history, were analyzed to determine the optimal scheme for identification of patients with germline mismatch repair (MMR) gene mutations. Patients and Methods Endometrial cancers from 702 patients recruited into the Australian National Endometrial Cancer Study (ANECS) were tested for MMR protein expression using immunohistochemistry (IHC) and for MLH1 gene promoter methylation in MLH1-deficient cases. MMR mutation testing was performed on germline DNA of patients with MMR-protein deficient tumors. Prediction of germline mutation status was compared for combinations of tumor characteristics, age at diagnosis, and various clinical criteria (Amsterdam, Bethesda, Society of Gynecologic Oncology, ANECS). Results Tumor MMR-protein deficiency was detected in 170 (24%) of 702 cases. Germline testing of 158 MMR-deficient cases identified 22 truncating mutations (3% of all cases) and four unclassified variants. Tumor MLH1 methylation was detected in 99 (89%) of 111 cases demonstrating MLH1/PMS2 IHC loss; all were germline MLH1 mutation negative. A combination of MMR IHC plus MLH1 methylation testing in women younger than 60 years of age at diagnosis provided the highest positive predictive value for the identification of mutation carriers at 46% versus ≤ 41% for any other criteria considered. Conclusion Population-level identification of patients with MMR mutation-positive endometrial cancer is optimized by stepwise testing for tumor MMR IHC loss in patients younger than 60 years, tumor MLH1 methylation in individuals with MLH1 IHC loss, and germline mutations in patients exhibiting loss of MSH6, MSH2, or PMS2 or loss of MLH1/PMS2 with absence of MLH1 methylation. PMID:24323032

  5. Sinus Tumors

    MedlinePlus

    ... Tumors Nasal Deformities Choanal Atresia Epiphora (Excessive Tearing) Disclosure Statement Printer Friendly Sinus Tumors Abtin Tabaee, MD Introduction Tumors of the nose and paranasal sinuses are rare, accounting for fewer than 1% of all tumors. These ...

  6. Bone tumor

    MedlinePlus

    Tumor - bone; Bone cancer; Primary bone tumor; Secondary bone tumor ... The cause of bone tumors is unknown. They often occur in areas of the bone that grow rapidly. Possible causes include: Genetic defects ...

  7. Age Factor in Business Education Students' Use of Social Networking Sites in Tertiary Institutions in Anambra State, Nigeria

    ERIC Educational Resources Information Center

    Ementa, Christiana Ngozi; Ile, Chika Madu

    2015-01-01

    There are diverse social networking sites which range from those that provide social sharing and interaction to those that provide networks for professionals within same and other fields. Social networking sites require a user to sign up, create a profile and begin sending short messages about what the user is doing or thinking. The study sought…

  8. U-Pb ages of shocked zircon grains link distal K-Pg boundary sites in Spain and Italy with the Chicxulub impact

    NASA Astrophysics Data System (ADS)

    Kamo, Sandra L.; Lana, Cristiano; Morgan, Joanna V.

    2011-10-01

    The U-Pb ages of shocked zircon crystals from the Chicxulub impact crater and Cretaceous-Paleogene (K-Pg) boundary sites in Haiti, the USA, and Canada, and the pattern of decreasing particle size with paleodistance from the crater, have been used as evidence of a genetic link between Chicxulub and the K-Pg boundary. Despite this, the inference that the K-Pg boundary layer formed as a direct consequence of the Chicxulub impact has been repeatedly questioned. Here we present U-Pb (ID-TIMS) ages and textural evidence of shock metamorphosed zircon grains from the K-Pg boundary at Caravaca, Spain, and Petriccio, Italy, that establish a causal connection between the impact and formation of the K-Pg boundary layer. The shocked zircon grains give data that produce a characteristic age pattern, which indicates a primary source age of 549.5 ± 5.7 Ma and a secondary event at the approximate time of impact at 66 Ma. The intensity of the shock features is proportional to the degree of isotopic resetting, and all textural features and ages are analytically identical to those of previously analyzed zircon from Chicxulub and K-Pg boundary sites in North America. Caravaca and Petriccio were > 8000 km from Chicxulub at the time of impact, and are therefore the farthest K-Pg sites identified that can be linked to Chicxulub through the dating of individual shocked zircon grains. We conclude that the combined age data and textural observations provide unambiguous evidence that ejecta from the Chicxulub impact formed the global K-Pg boundary layer. These data cannot be explained by the alternative scenario that the Chicxulub impact occurred ~ 300 ka prior to the K-Pg boundary.

  9. 40Ar 39Ar age constraints on neogene sedimentary beds, Upper Ramparts, half-way Pillar and Canyon village sites, Porcupine river, east-central Alaska

    USGS Publications Warehouse

    Kunk, M.J.; Rieck, H.; Fouch, T.D.; Carter, L.D.

    1994-01-01

    40Ar 39Ar ages of volcanic rocks are used to provide numerical constraints on the age of middle and upper Miocene sedimentary strata collected along the Porcupine River. Intercalated sedimentary rocks north of latitude 67??10???N in the Porcupine terrane of east-central Alaska contain a rich record of plant fossils. The fossils are valuable indicators of this interior region's paleoclimate during the time of their deposition. Integration of the 40Ar 39Ar results with paleomagnetic and sedimentological data allows for refinements in estimating the timing of deposition and duration of selected sedimentary intervals. 40Ar 39Ar plateau age spectra, from whole rock basalt samples, collected along the Upper Ramparts and near Half-way Pillar on the Porcupine River, range from 15.7 ?? 0.1 Ma at site 90-6 to 14.4 ?? 0.1 Ma at site 90-2. With exception of the youngest basalt flow at site 90-2, all of the samples are of reversed magnetic polarity, and all 40Ar 39Ar age spectrum results are consistent with the deposition of the entire stratigraphic section during a single interval of reversed magnetic polarity. The youngest flow at site 90-2 was emplaced during an interval of normal polarity. With age, paleomagnetic and sedimentological data, the ages of the Middle Miocene sedimentary rocks between the basalt flows at sites 90-1 and 90-2 can be assigned to an interval within the limits of analytical precision of 15.2 ?? 0.1 Ma; thus, the sediments were deposited during the peak of the Middle Miocene thermal maximum. Sediments in the upper parts of sites 90-1 and 90-2 were probably deposited during cooling from the Middle Miocene thermal maximum. 40Ar 39Ar results of plagioclase and biotite from a single tephra, collected at sites 90-7 and 90-8 along the Canyon Village section of the Porcupine River, indicate an age of 6.57 ?? 0.02 Ma for its time of eruption and deposition. These results, together with sedimentological and paleomagnetic data, suggest that all of the Upper

  10. Blockade of Tumor Necrosis Factor-Alpha: A Role for Adalimumab in Neovascular Age-Related Macular Degeneration Refractory to Anti-Angiogenesis Therapy?

    PubMed Central

    Fernández-Vega, Beatriz; Fernández-Vega, Álvaro; Rangel, Carlos Mario; Nicieza, Javier; Villota-Deleu, Eva; Vega, José A.; Sanchez-Avila, Ronald M.

    2016-01-01

    Aims To report a case of wet age-related macular degeneration (wet-AMD) refractory to intravitreal anti-vascular endothelial growth factor (anti-VEGF) therapy in a patient who showed visual and anatomical improvement and stabilization after starting a subcutaneous treatment course with adalimumab, an anti-tumor necrosis factor-alpha (TNF-α) drug, for concomitant Crohn's disease. Methods Observational case report of a female patient. Ophthalmological evaluation was performed by slit lamp and ophthalmoscopy (posterior pole and anterior segment). Best-corrected visual acuity (BCVA) was determined, and imaging was performed by fluorescein angiography, indocyanine green angiography, and optical coherence tomography (OCT). Intravitreal therapies used and treatment with anti-TNF-α were recorded. Results A 64-year-old woman with wet-AMD was treated with fourteen intravitreal injections of ranibizumab (0.5 mg) for a period of 40 months with intervals of 1–6 months. She initially showed a good visual and anatomical response to periodic anti-VEGF treatment but during check visits, anatomical and functional responses deteriorated. At the 40-month follow-up, the patient had developed Crohn's disease, and her rheumatologist started treatment with adalimumab (40 mg subcutaneously every 2 weeks). During the 25 months of treatment with adalimumab, the patient did not require any additional intravitreal anti-VEGF treatments because her BCVA, clinical, and OCT findings improved and remained stable. Conclusions We described a case of a patient with wet-AMD refractory to anti-VEGF therapy, which clinically benefited from subcutaneous adalimumab therapy. Treatment with subcutaneous anti-TNF-α in combination with anti-VEGF therapy avoids the high cost and risks related to multiple intravitreal anti-VEGF injections with good functional and anatomic outcomes. PMID:27065854

  11. High-resolution record of geomagnetic excursions in the Matuyama chron constrains the ages of the Feiliang and Lanpo Paleolithic sites in the Nihewan Basin, North China

    NASA Astrophysics Data System (ADS)

    Ao, Hong; An, Zhisheng; Dekkers, Mark J.; Wei, Qi; Pei, Shuwen; Zhao, Hui; Zhao, Hongli; Xiao, Guoqiao; Qiang, Xiaoke; Wu, Dacheng; Chang, Hong

    2012-08-01

    The Nihewan Basin (40°N) in North China is a rich source of Early Pleistocene Paleolithic sites and thus a key area for studying early human evolution in high-latitude (from an early human perspective) East Asia. Here a high-resolution magnetostratigraphic investigation is carried out on a fluvio-lacustrine section in the northeastern Nihewan Basin, which contains the Feiliang and Lanpo Paleolithic sites. Paleomagnetic results suggest that this section records the lower portion of the Brunhes polarity chron and the upper Matuyama polarity chron. Furthermore, the Jaramillo polarity subchron and seven of the nine validated geomagnetic excursions within the Matuyama polarity chron are identified, including the Kamikatsura, Santa Rosa, Intra-Jaramillo, Cobb Mountain, Bjorn, Gardar and Gilsa excursions. The Feiliang artifact layer is located just at the bottom of the Cobb Mountain excursion, thus its age is estimated to be ˜1.2 Ma. The Lanpo artifact layer appears to be coeval with the Gilsa excursion, yielding an estimated age of ˜1.6 Ma. This study provides new evidence for the presence of early humans in North China before 1.5 Ma and documents the powerful role of geomagnetic excursions: they provide valuable age control points for ongoing efforts to date the early Paleolithic sites.

  12. Geo-archaeological investigations of Palaeolithic sites along the Ural Mountains - On the northern presence of humans during the last Ice Age

    NASA Astrophysics Data System (ADS)

    Svendsen, John Inge; Heggen, Herbjørn Presthus; Hufthammer, Anne Karin; Mangerud, Jan; Pavlov, Pavel; Roebroeks, Wil

    2010-11-01

    We review geo-archaeological results from six Palaeolithic sites along the western flank of the northern Ural Mountains. The oldest traces of human activities, dated to around 36-35 14C ka BP (43-40 cal ka), were found in alluvial strata at Mamontovaya Kurya at the Polar Circle - their connection to cultures further south remains uncertain. Slightly younger artefacts were found at the site Zaozer'e, nearly a thousand km further to the south, where a rich archaeological assemblage, dated to 34-33 14C ka BP (39-37 cal ka), was uncovered from underneath several meters of loess. The assemblage contains some small "Middle Palaeolithic like" bifaces alongside distinct Upper Palaeolithic traits, such as well-defined blades. This site also contains some perforated "pendants" made of freshwater molluscs. At the Byzovaya site, located at 65°N and radiocarbon dated to about 30-29 14C ka BP (34-32 cal ka), more than 300 artefacts and several thousand animal remains, mostly of mammoth, were incorporated in coarse-grained debris-flow deposits, sealed by aeolian sand. Pending the results from a new technological analysis of the whole artefact assemblage we can yet not decide whether Byzovaya should be categorized as a Middle- or Upper Palaeolithic site. The finds from Garchi, located in a loess sequence near Zaozer'e, have a similar or slightly younger age than the material from Byzovaya. Also at this site bifacial tools are present; alongside some characteristic triangle projectile points as well as some other elements which have nearly identical counterparts in the Upper Palaeolithic Kostenki/Streletskaya and Sungirian complexes, unambiguously associated with Modern humans. We conclude that the initial human colonisations along the Ural Mountains took place during a relatively favourable period of Marine Isotope Stage 3, when only small mountain glaciers existed in this region. The finds from the Medvezhia Peshera rock shelter have a completely different age (19-16 14C ka BP

  13. Paleoparasitological analysis of coprolites from K2, an Iron Age archaeological site in South Africa: the first finding of Dicrocoelium sp. eggs.

    PubMed

    Dittmar, K; Steyn, M

    2004-02-01

    Until now, Dicrocoelium sp. eggs have only been recorded from European and 1 North American archaeological sites. We present evidence for the first record of Dicrocoelium sp. from an African archaeological site. A paleoparasitological study was conducted on 7 coprolite samples from K2, a Late Iron Age site on the farm Greefswald, in the Northern Province of South Africa. Standard parasitological analysis revealed the presence of Dicrocoelium sp. and Trichuris sp. eggs. Today, the parasite does not occur in this region. Trichurid eggs are a relatively common find in paleoparasitological analysis. The presence of Dicrocoelium sp. provides new clues about the antiquity of this parasite, as well as aspects of ancient environment, climate, and interactions among humans, animals, and parasites. PMID:15040686

  14. U-Pb ages of zircons from sites in Spain and Italy provide more evidence linking the Chicxulub impact to the global K-P boundary layer

    NASA Astrophysics Data System (ADS)

    Morgan, J. V.; Kamo, S.; Lana, C.

    2010-12-01

    The K-P boundary layer possesses an extra-terrestrial signature and contains highly shocked terrestrial minerals. The only plausible explanation for the K-P layer is that it was formed when a large meteorite hit the Earth, causing the ejection of both meteoritic material and shocked fragments of target rock around the globe. There is now universal agreement that the Chicxulub structure is an impact crater, and dating of the impact melt rocks within the crater place it close in age to the K-P boundary. Two significant lines of evidence indicate a genetic link between Chicxulub and the global K-P layer: 1) the size of the ejected particles in the layer decreases with palaeodistance from Chicxulub, and 2) U-Pb dating of shocked zircons from the Chicxulub impact site and in several K-P sites in North America are near-identical in age, texture and lead-loss pattern. However, even with such apparently incontrovertible evidence linking Chicxulub and the K-P boundary, a minority continue to question the link and suggest that the Chicxulub impact occurred ~300 ka before the K-P boundary. Here we present the results of U-Pb isotope dilution thermal ionization mass spectrometry (ID-TIMS) for shock-metamorphosed zircon crystals from the K-P boundary layer at Caravaca, Spain, and Petriccio, Italy. We find that the determined ages form a mixing line between a primary source age of ~549 Ma and the approximate time of impact. This is analytically identical to ages obtained previously for similarly shocked zircon grains at Chicxulub and from K-P boundary sites in North America. Caravaca and Petriccio are the most distal K-P sites that can be directly linked to Chicxulub through the dating of individual shocked zircon grains. These results, along with the completeness of the K-P transition at several sites around the globe, including Caravaca, cannot be explained by the alternative scenario that the Chicxulub impact occurred ~300 ka prior to the K-P boundary.

  15. Tracking Sediment Sources to Pacific Northwest Margin Sites through Radiometric Ages of Clays: Ocean-Land Response to Millenial Scale Climate Change

    NASA Astrophysics Data System (ADS)

    Duncan, R. A.; Pisias, N. G.; Hostetler, S. W.

    2001-12-01

    The terrigenous fraction of marine sediments carries the memory of its source through its mineralogy, composition and age. This signal may also carry important information about tectonic and climatic conditions on the continents and about the mechanisms by which material is transported to the depositional site. Sediments recovered from long piston cores at sites along the Pacific Northwest margin of North America contain highly correlated records of oceanographic and terrestrial vegetation changes over the last full glacial cycle. We speculate that these records reflect principally climate-induced changes in terrestrial vegetation rather than changes in ocean circulation and sediment transport. To test this, we have begun to identify specific sources of terrigenous sediment through 40Ar-39Ar radiometric dating of clays from Pacific NW rivers. Age spectra from 15-20 step heating experiments reveal well-resolved clay formation ages from two size fractions (2-20 and 20-63 micron), and evidence of post-formation Ar-loss from low temperature steps. From these we make several important conclusions: First, the individual river clay ages are distinct from one another, and reflect the age of terranes from which they derive. Thus clay ages fingerprint discharge from specific rivers. Second, plateau (formation) ages for the two size fractions are the same. This is a different observation from that seen in previous K-Ar results, probably because the smaller size fraction has experienced more Ar-loss and K-addition during transport, and thus produces generally younger ages. However, the 40Ar-39Ar experiments reveal the same plateau (formation) ages. Thus the additional information gained from incremental heating is important in better defining the source identity. Third, we can directly measure the composition of phases carrying the age information. Two isotopes (37Ar and 39Ar) determine the Ca and K content of the phase(s) contributing to each step. The K/Ca is not strictly

  16. Effects of Timing, Sex, and Age on Site-Specific Gastrointestinal Permeability Testing in Children and Adults

    PubMed Central

    McOmber, Mark E.; Ou, Ching-Nan; Shulman, Robert J.

    2010-01-01

    Summary Objectives Measurement of gastrointestinal (GI) permeability is used commonly in research and often clinically. Despite its utility, little is known about sugar excretion timeframes or the potential effects of age and gender in GI permeability testing. We sought to determine the timeframes of sugar excretion and the potential effects of age and gender on urinary recovery of the sugars. Methods Healthy adults (n=17) and children (n=15) fasted four hours after the evening meal and then ingested a solution of sucrose, lactulose, mannitol, and sucralose. Urine was collected at 30, 60, and 90 minutes after ingestion and then each time the subjects voided over the next 24 hr. Each urine void was collected separately. Results Median age for the adults was 47.5 yr. (range 21-57 yr.) and for children 10 yr. (5-17). There were no differences between children and adults in mean percent dose of sugar recovered. The time of peak urinary recovery of the sugars was generally similar between children and adults. Sucrose urinary recovery declined with age (P = 0.008; r2 = 0.19) unrelated to gender. Lactulose and sucralose urinary recovery declined with age in females (P = 0.05, r2 = 0.24 and P = 0.011, r2 = 0.41, respectively) but not in males. Conclusions Overall, sugar urinary recovery is comparable in children and adults. Specific sugar urinary recovery may change as a function of age and/or gender. These results need to be taken into account when planning and interpreting GI permeability studies. PMID:20081547

  17. Soft tissue tumors of the penis: a review.

    PubMed

    Katona, Terrence M; Lopez-Beltran, Antonio; MacLennan, Gregory T; Cheng, Lirong; Montironi, Rodolfo; Cheng, Liang

    2006-08-01

    Penile soft tissue tumors comprise 5% of tumors at this site and most have been reported as isolated case reports. The purpose of this review is to aid the practicing surgical pathologist in distinguishing penile soft tissue tumors, such as sarcomatoid squamous cell carcinoma, from other prognostically and therapeutically important entities in the differential diagnosis. Clinical presentation, management, prognosis and factors influencing behavior are reviewed. The immunohistochemical profiles and salient morphologic clues that may help distinguish penile spindle cell tumors from sarcomatoid carcinomas are evaluated. Soft tissue tumors of the penis may be classified as benign or malignant, as superficial or deep and in terms of age at presentation. All are rare. The most common benign soft tissue tumors that affect the penis are vascular neoplasms, followed by tumors of neural, myoid and fibrous origin. Among reported cases, the most frequent malignant penile soft tissue tumors are Kaposi sarcoma and leiomyosarcoma. Correctly diagnosing penile soft tissue tumors is imperative, because the biologic behavior and the clinical management of these neoplasms vary considerably. Distinguishing sarcomas from sarcomatoid carcinoma and melanoma is particularly important. Accurate diagnosis is best facilitated by consideration of all available aspects of the case, including clinical information, histopathologic findings and immunohistochemical results. PMID:16927639

  18. Effects of timing, sex, and age on site-specific gastrointestinal permeability testing in children and adults

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Measurement of gastrointestinal permeability is commonly used in research and often used clinically. Despite its utility, little is known about sugar excretion timeframes or the potential effects of age and sex on GI permeability testing. We seek to determine the timeframes of sugar excretion and th...

  19. The K-Ras 4A isoform promotes apoptosis but does not affect either lifespan or spontaneous tumor incidence in aging mice

    SciTech Connect

    Plowman, Sarah J.; Arends, Mark J.; Brownstein, David G.; Luo Feijun; Devenney, Paul S.; Rose, Lorraine; Ritchie, Ann-Marie; Berry, Rachel L.; Harrison, David J.; Hooper, Martin L.; Patek, Charles E. . E-mail: Charles.Patek@ed.ac.uk

    2006-01-01

    Ras proteins function as molecular switches in signal transduction pathways, and, here, we examined the effects of the K-ras4A and 4B splice variants on cell function by comparing wild-type embryonic stem (ES) cells with K-ras {sup tm{delta}}{sup 4A/tm{delta}}{sup 4A} (exon 4A knock-out) ES cells which express K-ras4B only and K-ras {sup -/-} (exons 1-3 knock-out) ES cells which express neither splice variant, and intestinal epithelium from wild-type and K-ras {sup tm{delta}}{sup 4A/tm{delta}}{sup 4A} mice. RT-qPCR analysis found that K-ras4B expression was reduced in K-ras {sup tm{delta}}{sup 4A/tm{delta}}{sup 4A} ES cells but unaffected in small intestine. K-Ras deficiency did not affect ES cell growth, and K-Ras4A deficiency did not affect intestinal epithelial proliferation. K-ras {sup tm{delta}}{sup 4A/tm{delta}}{sup 4A} and K-ras {sup -/-} ES cells showed a reduced capacity for differentiation following LIF withdrawal, and K-ras {sup -/-} cells were least differentiated. K-Ras4A deficiency inhibited etoposide-induced apoptosis in ES cells and intestinal epithelial cells. However, K-ras {sup tm{delta}}{sup 4A/tm{delta}}{sup 4A} ES cells were more resistant to etoposide-induced apoptosis than K-ras {sup -/-} cells. The results indicate that (1) K-Ras4A promotes apoptosis while K-Ras4B inhibits it, and (2) K-Ras4B, and possibly K-Ras4A, promotes differentiation. The findings raise the possibility that alteration of the K-Ras4A/4B isoform ratio modulates tumorigenesis by differentially affecting stem cell survival and/or differentiation. However, K-Ras4A deficiency did not affect life expectancy or spontaneous overall tumor incidence in aging mice.

  20. Folic acid-targeted disulfide-based cross-linking micelle for enhanced drug encapsulation stability and site-specific drug delivery against tumors.

    PubMed

    Zhang, Yumin; Zhou, Junhui; Yang, Cuihong; Wang, Weiwei; Chu, Liping; Huang, Fan; Liu, Qiang; Deng, Liandong; Kong, Deling; Liu, Jianfeng; Liu, Jinjian

    2016-01-01

    Although the shortcomings of small molecular antitumor drugs were efficiently improved by being entrapped into nanosized vehicles, premature drug release and insufficient tumor targeting demand innovative approaches that boost the stability and tumor responsiveness of drug-loaded nanocarriers. Here, we show the use of the core cross-linking method to generate a micelle with enhanced drug encapsulation ability and sensitivity of drug release in tumor. This kind of micelle could increase curcumin (Cur) delivery to HeLa cells in vitro and improve tumor accumulation in vivo. We designed and synthesized the core cross-linked micelle (CCM) with polyethylene glycol and folic acid-polyethylene glycol as the hydrophilic units, pyridyldisulfide as the cross-linkable and hydrophobic unit, and disulfide bond as the cross-linker. CCM showed spherical shape with a diameter of 91.2 nm by the characterization of dynamic light scattering and transmission electron microscope. Attributed to the core cross-linking, drug-loaded CCM displayed higher Nile Red or Cur-encapsulated stability and better sensitivity to glutathione than noncross-linked micelle (NCM). Cellular uptake and in vitro antitumor studies proved the enhanced endocytosis and better cytotoxicity of CCM-Cur against HeLa cells, which had a high level of glutathione. Meanwhile, the folate receptor-mediated drug delivery (FA-CCM-Cur) further enhanced the endocytosis and cytotoxicity. Ex vivo imaging studies showed that CCM-Cur and FA-CCM-Cur possessed higher tumor accumulation until 24 hours after injection. Concretely, FA-CCM-Cur exhibited the highest tumor accumulation with 1.7-fold of noncross-linked micelle Cur and 2.8-fold of free Cur. By combining cross-linking of the core with active tumor targeting of FA, we demonstrated a new and effective way to design nanocarriers for enhanced drug encapsulation, smart tumor responsiveness, and elevated tumor accumulation. PMID:27051287

  1. Folic acid-targeted disulfide-based cross-linking micelle for enhanced drug encapsulation stability and site-specific drug delivery against tumors

    PubMed Central

    Zhang, Yumin; Zhou, Junhui; Yang, Cuihong; Wang, Weiwei; Chu, Liping; Huang, Fan; Liu, Qiang; Deng, Liandong; Kong, Deling; Liu, Jianfeng; Liu, Jinjian

    2016-01-01

    Although the shortcomings of small molecular antitumor drugs were efficiently improved by being entrapped into nanosized vehicles, premature drug release and insufficient tumor targeting demand innovative approaches that boost the stability and tumor responsiveness of drug-loaded nanocarriers. Here, we show the use of the core cross-linking method to generate a micelle with enhanced drug encapsulation ability and sensitivity of drug release in tumor. This kind of micelle could increase curcumin (Cur) delivery to HeLa cells in vitro and improve tumor accumulation in vivo. We designed and synthesized the core cross-linked micelle (CCM) with polyethylene glycol and folic acid-polyethylene glycol as the hydrophilic units, pyridyldisulfide as the cross-linkable and hydrophobic unit, and disulfide bond as the cross-linker. CCM showed spherical shape with a diameter of 91.2 nm by the characterization of dynamic light scattering and transmission electron microscope. Attributed to the core cross-linking, drug-loaded CCM displayed higher Nile Red or Cur-encapsulated stability and better sensitivity to glutathione than noncross-linked micelle (NCM). Cellular uptake and in vitro antitumor studies proved the enhanced endocytosis and better cytotoxicity of CCM-Cur against HeLa cells, which had a high level of glutathione. Meanwhile, the folate receptor-mediated drug delivery (FA-CCM-Cur) further enhanced the endocytosis and cytotoxicity. Ex vivo imaging studies showed that CCM-Cur and FA-CCM-Cur possessed higher tumor accumulation until 24 hours after injection. Concretely, FA-CCM-Cur exhibited the highest tumor accumulation with 1.7-fold of noncross-linked micelle Cur and 2.8-fold of free Cur. By combining cross-linking of the core with active tumor targeting of FA, we demonstrated a new and effective way to design nanocarriers for enhanced drug encapsulation, smart tumor responsiveness, and elevated tumor accumulation. PMID:27051287

  2. Tumor-Penetrating Peptides

    PubMed Central

    Teesalu, Tambet; Sugahara, Kazuki N.; Ruoslahti, Erkki

    2013-01-01

    Tumor-homing peptides can be used to deliver drugs into tumors. Phage library screening in live mice has recently identified homing peptides that specifically recognize the endothelium of tumor vessels, extravasate, and penetrate deep into the extravascular tumor tissue. The prototypic peptide of this class, iRGD (CRGDKGPDC), contains the integrin-binding RGD motif. RGD mediates tumor-homing through binding to αv integrins, which are selectively expressed on various cells in tumors, including tumor endothelial cells. The tumor-penetrating properties of iRGD are mediated by a second sequence motif, R/KXXR/K. This C-end Rule (or CendR) motif is active only when the second basic residue is exposed at the C-terminus of the peptide. Proteolytic processing of iRGD in tumors activates the cryptic CendR motif, which then binds to neuropilin-1 activating an endocytic bulk transport pathway through tumor tissue. Phage screening has also yielded tumor-penetrating peptides that function like iRGD in activating the CendR pathway, but bind to a different primary receptor. Moreover, novel tumor-homing peptides can be constructed from tumor-homing motifs, CendR elements and protease cleavage sites. Pathologies other than tumors can be targeted with tissue-penetrating peptides, and the primary receptor can also be a vascular “zip code” of a normal tissue. The CendR technology provides a solution to a major problem in tumor therapy, poor penetration of drugs into tumors. The tumor-penetrating peptides are capable of taking a payload deep into tumor tissue in mice, and they also penetrate into human tumors ex vivo. Targeting with these peptides specifically increases the accumulation in tumors of a variety of drugs and contrast agents, such as doxorubicin, antibodies, and nanoparticle-based compounds. Remarkably the drug to be targeted does not have to be coupled to the peptide; the bulk transport system activated by the peptide sweeps along any compound that is present in the

  3. Integration of geophysical, geochemical and microbiological data for a comprehensive small-scale characterization of an aged LNAPL-contaminated site.

    PubMed

    Arato, Alessandro; Wehrer, Markus; Biró, Borbala; Godio, Alberto

    2014-01-01

    Characterization of aged hydrocarbon-contaminated sites is often a challenge due to the heterogeneity of subsurface conditions. Geoelectrical methods can aid in the characterization of such sites due to their non-invasive nature, but need to be supported by geochemical and microbiological data. In this study, a combination of respective methods was used to characterize an aged light non-aqueous phase liquid-contaminated site, which was the scene of a crude oil blow-out in 1994. As a consequence, a significant amount of crude oil was released into the subsurface. Complex resistivity has been acquired, both along single boreholes and in cross-hole configuration, in a two-borehole test site addressed with electrodes, to observe the electrical behaviour at the site over a two-year period (2010-2011). Geoelectrical response has been compared to results of the analysis of hydrocarbon contamination in soil and groundwater samples. Geochemical parameters of groundwater have been observed by collecting samples in a continuous multi-channel tubing (CMT) piezometer system. We have also performed a biological characterization on soil samples by drilling new boreholes close to the monitoring wells. Particular attention has been given to the characterization of the smear zone that is the sub-soil zone affected by the seasonal groundwater fluctuations. In the smear zone, trapped hydrocarbons were present, serving as organic substrate for chemical and biological degradation, as was indicated by an increase of microbial biomass and activity as well as ferrogenic-sulfidogenic conditions in the smear zone. The results show a good agreement between the intense electrical anomaly and the peaks of total organic matter and degradation by-products, particularly enhanced in the smear zone. PMID:24091526

  4. Spinal tumor

    MedlinePlus

    Tumor - spinal cord ... spinal tumors occur in the nerves of the spinal cord itself. Most often these are ependymomas and other ... gene mutations. Spinal tumors can occur: Inside the spinal cord (intramedullary) In the membranes (meninges) covering the spinal ...

  5. Inhibition of IL-17A in tumor microenvironment augments cytotoxicity of tumor-infiltrating lymphocytes in tumor-bearing mice.

    PubMed

    Hayata, Keiji; Iwahashi, Makoto; Ojima, Toshiyasu; Katsuda, Masahiro; Iida, Takeshi; Nakamori, Mikihito; Ueda, Kentaro; Nakamura, Masaki; Miyazawa, Motoki; Tsuji, Toshiaki; Yamaue, Hiroki

    2013-01-01

    It remains controversial whether IL-17A promotes or inhibits cancer progression. We hypothesized that IL-17A that is locally produced in the tumor microenvironment has an important role in angiogenesis and tumor immunity. We investigated the effect of inhibiting IL-17A at tumor sites on tumor growth and on local and systemic anti-tumor immunity. MC38 or B16 cells were inoculated subcutaneously into mice, and intratumoral injection of an adenovirus vector expressing siRNA against the mouse IL-17A gene (Ad-si-IL-17) significantly inhibited tumor growth in both tumor models compared with control mice. Inhibition of IL-17A at tumor sites significantly suppressed CD31, MMP9, and VEGF expression in tumor tissue. The cytotoxic activity of CD8(+) T cells from tumor-infiltrating lymphocytes in mice treated with Ad-si-IL-17 was significantly higher than in control mice; however, CD8(+) T cells from splenocytes had similar activity levels. Suppression of IL-17A at tumor sites led to a Th1-dominant environment, and moreover, eliminated myeloid-derived suppressor cells and regulatory T cells at tumor sites but not in splenocytes. In conclusion, blockade of IL-17A at tumor sites helped suppress tumor growth by inhibiting angiogenesis as well as cytotoxic T lymphocytes activation at tumor sites. PMID:23372655

  6. Correlation of the changes in the framework and active Cu sites for typical Cu/CHA zeolites (SSZ-13 and SAPO-34) during hydrothermal aging.

    PubMed

    Su, Wenkang; Li, Zhenguo; Peng, Yue; Li, Junhua

    2015-11-21

    The relative framework stability of Cu/CHA zeolites (SAPO-34 and SSZ-13) was studied during hydrothermal aging at 800 °C, and the fundamental mechanism for the framework change was investigated. Additionally, the relationship between the variation in the framework and active SCR reaction sites was established. SAPO-34 showed stronger stability during hydrothermal aging than SSZ-13. The results showed that dealumination occurred in the SSZ-13 zeolite, leading to the loss of crystallinity and a severe decrease of the Brönsted acid sites. Simultaneously, the detached Al(OH)3 species deactivated the Cu species by the transformation of isolated Cu(2+) ions to CuAlOx species. While the vacancy in the SAPO-34 framework caused by desilication could be healed with the migration of extra-framework Al and P atoms to the defects. And the Cu species showed a certain degree of aggregation with the improved redox ability of the aged Cu/SAPO-34 zeolite and the acidic properties were well maintained. PMID:26462874

  7. Bone marrow declines as a site of B-cell precursor differentiation with age: relationship to thymus involution.

    PubMed Central

    Ben-Yehuda, A; Szabo, P; Dyall, R; Weksler, M E

    1994-01-01

    The rearrangement of immunoglobulin genes in B-lymphocyte precursors requires the expression of the recombination activating genes (Rag), which leads to the generation of a highly diverse B-cell repertoire. We can use the level of Rag-1 mRNA in the bone marrow as an index of its capacity to support the maturation of B lymphocytes as all detectable bone marrow Rag-1 mRNA is expressed by B-cell precursors. In mouse bone marrow, Rag-1 mRNA increases during the first 2 months of life to reach its maximal level at 2 months of age. This level is maintained until 5 months of age and thereafter declines to a minimum level by 10 months of age. Thus, bone marrow Rag-1 mRNA is highest at the time when thymic function is maximal in euthymic mice. An association between thymic activity and bone marrow Rag-1 gene expression was supported by showing a low level of bone marrow Rag-1 mRNA in athymic nude mice at an age when this gene is maximally expressed in euthymic mice. Another characteristic of B cells in nude mice is their preferential rearrangement of diversity region (D)-proximal heavy-chain variable region (VH) genes. We demonstrated that injection of syngeneic splenic T cells into nude mice not only stimulates an increase in Rag-1 mRNA in their bone marrow B-cell precursors but also restores their random use of VH genes. Most interestingly, injection of supernatant medium from phytohemagglutinin-activated splenic T-cell cultures from young euthymic mice also induces both Rag-1 mRNA in bone marrow B-cell precursors and random use of VH genes. These findings suggest that thymic function can regulate both Rag-1 gene expression and VH gene use by bone marrow B-cell precursors. Images PMID:7991570

  8. Strong Components of Epigenetic Memory in Cultured Human Fibroblasts Related to Site of Origin and Donor Age

    PubMed Central

    Ivanov, Nikolay A.; Tao, Ran; Chenoweth, Joshua G.; Brandtjen, Anna; Mighdoll, Michelle I.; Genova, John D.; McKay, Ronald D.; Jia, Yankai; Weinberger, Daniel R.; Kleinman, Joel E.; Hyde, Thomas M.; Jaffe, Andrew E.

    2016-01-01

    Differentiating pluripotent cells from fibroblast progenitors is a potentially transformative tool in personalized medicine. We previously identified relatively greater success culturing dura-derived fibroblasts than scalp-derived fibroblasts from postmortem tissue. We hypothesized that these differences in culture success were related to epigenetic differences between the cultured fibroblasts by sampling location, and therefore generated genome-wide DNA methylation and transcriptome data on 11 intrinsically matched pairs of dural and scalp fibroblasts from donors across the lifespan (infant to 85 years). While these cultured fibroblasts were several generations removed from the primary tissue and morphologically indistinguishable, we found widespread epigenetic differences by sampling location at the single CpG (N = 101,989), region (N = 697), “block” (N = 243), and global spatial scales suggesting a strong epigenetic memory of original fibroblast location. Furthermore, many of these epigenetic differences manifested in the transcriptome, particularly at the region-level. We further identified 7,265 CpGs and 11 regions showing significant epigenetic memory related to the age of the donor, as well as an overall increased epigenetic variability, preferentially in scalp-derived fibroblasts—83% of loci were more variable in scalp, hypothesized to result from cumulative exposure to environmental stimuli in the primary tissue. By integrating publicly available DNA methylation datasets on individual cell populations in blood and brain, we identified significantly increased inter-individual variability in our scalp- and other skin-derived fibroblasts on a similar scale as epigenetic differences between different lineages of blood cells. Lastly, these epigenetic differences did not appear to be driven by somatic mutation—while we identified 64 probable de-novo variants across the 11 subjects, there was no association between mutation burden and age of the donor (p

  9. Understanding the ecological background of rice agriculture on the Ningshao Plain during the Neolithic Age: pollen evidence from a buried paddy field at the Tianluoshan cultural site

    NASA Astrophysics Data System (ADS)

    Li, Chunhai; Zheng, Yunfei; Yu, Shiyong; Li, Yongxiang; Shen, Huadong

    2012-03-01

    The progressive rise of atmospheric CH4 level since 5 ka has been hypothesized to result from human agricultural activities that turned forested lands, which would otherwise be a carbon sink, into paddy fields. Increasing numbers of Neolithic cultural sites unearthed in coastal eastern China, providing unique opportunities to test this hypothesis. Here, we present detailed pollen data from a buried paddy field at Tianluoshan cultural site on the Ningshao Plain, eastern China, to reconstruct the ecological conditions associated with the establishment of paddy fields. Stratigraphic data, radiocarbon ages, and pollen analyses show that vegetation underwent six phases of evolution and paddy fields were developed from 7000 to 4200 cal. yr BP. We found no evidence of slash-and-burn agriculture at the study site. Together with no presence of the irrigation system, our pollen data suggest the paddy fields at this site originated from wetlands. Hence, our findings do not support the hypothesis that anthropogenic-induced deforestation play ed a significant role in the rise of the atmospheric CH4 rise since the middle Holocene.

  10. Effects of aging herbicide mixtures on soil respiration and plant survival in soils from a pesticide-contaminated site

    SciTech Connect

    Kruger, E.L.; Anhalt, J.C.; Anderson, T.A.

    1996-10-01

    Three herbicides, atrazine, metolachlor, and pendimethalin, were applied individually and in all possible combinations to soil taken from a pesticide-contaminated site in Iowa. The rate of application for each chemical was 50 {mu}g/g, representative of contamination problems at mixing and loading areas of agrochemical dealer sites. Treated soils were incubated at 24{degrees}C in the dark for 0, 21, and 63 d, and soil moisture tension was maintained at -33 kPa. Soil respiration was measured daily by using an infrared gas analyzer for 10 d at the end of each incubation period. Subsamples of treated soils were used in plant germination and survival studies. Concentrations of each herbicide were determined by gas chromatography at day 0, 21, and 63. Soil respiration was elevated for the first 6 d immediately following treatment, and then declined to very low levels. At the end of day 21 and 63, soil respiration remained at very low levels. The half-lives for atrazine, metolachlor, and pendimethalin individually in soil or in combination with one and/or the other herbicide will be reported. The results of germination and survival studies with kochia, giant foxtail, birdsfoot trefoil, crown vetch, and soybean will also be reported.

  11. Magnetostratigraphic age of the Xiantai Paleolithic site in the Nihewan Basin and implications for early human colonization of Northeast Asia

    NASA Astrophysics Data System (ADS)

    Deng, Chenglong; Wei, Qi; Zhu, Rixiang; Wang, Hongqiang; Zhang, Rui; Ao, Hong; Chang, Liao; Pan, Yongxin

    2006-04-01

    Timing of the early habitation and stone technologies in the Nihewan Basin, North China has provided insights into our understanding of early human adaptability to high northern latitudes in East Asia. Here we contribute to this topic with detailed magnetostratigraphic investigation, coupled with mineral magnetic measurements and palynological analyses on a lacustrine sequence in this basin, which contains the Xiantai Paleolithic site. Magnetite and hematite were identified as the main carriers for the characteristic remanent magnetizations. Magnetostratigraphic results show that the Xiantai lacustrine sequence recorded the Brunhes chron, the Jaramillo and the Olduvai subchrons, and successive reverse polarity portions of the intervening Matuyama chron. Stratigraphic correlation in terms of lithology, magnetic susceptibility and magnetic polarity sequences between the Xiantai and Xiaochangliang sections indicates that the Xiantai artefact layer is readily contemporary with the Xiaochangliang artefact layer, which has been previously estimated to be about 1.36 Ma [R.X. Zhu, K.A. Hoffman, R. Potts, C.L. Deng, Y.X. Pan, B. Guo, C.D. Shi, Z.T. Guo, B.Y. Yuan, Y.M. Hou, W.W. Huang, Earliest presence of humans in northeast Asia, Nature 413 (2001) 413-417.]. Early humans of the Xiantai Paleolithic site lived in a steppe paleoenvironment indicated from fossil pollens. Furthermore, the combined evidence of our magnetostratigraphy and previously published magnetochronology and paleoclimate data documents that early humans of North China were able to adjust to an increasing variability of paleoclimates and paleoenvironments over the Early Pleistocene.

  12. Tumor site-specific silencing of NF-κB p65 by targeted hollow gold nanospheres-mediated photothermal transfection

    PubMed Central

    Lu, Wei; Zhang, Guodong; Zhang, Rui; Flores, Leo G; Huang, Qian; Gelovani, Juri G; Li, Chun

    2010-01-01

    Nuclear factor-κB (NF-κB) transcription factor is a critical regulator of the expression of genes involved in tumor formation and progression. Successful RNA interference (RNAi) therapeutics targeting NF-κB is challenged by siRNA delivery systems, which can render targeted in vivo delivery, efficient endo-lysosomal escape and dynamic control over activation of RNAi. Here, we report near-infrared light-inducible NF-κB down-regulation through folate receptor-targeted hollow gold nanospheres carrying siRNA recognizing NF-κB p65 subunit. Using micro-positron emission tomography/computed tomography imaging, the targeted nanoconstructs exhibited significantly higher tumor uptake in nude mice-bearing HeLa cervical cancer xenografts than non-targeted nanoparticles following intravenous administration. Mediated by hollow gold nanospheres, controllable cytoplasmic delivery of siRNA was obtained upon near-infrared light irradiation through photothermal effect. Efficient down-regulation of NF-κB p65 was achieved only in tumors irradiated with near-infrared light, but not in non-irradiated tumors grown in the same mice. Liver, spleen, kidney, and lung were not affected by the treatments, in spite of significant uptake of the siRNA nanoparticles in these organs. We term this mode of action “photothermal transfection”. Combined treatments with p65 siRNA photothermal transfection and irinotecan caused substantially enhanced tumor apoptosis and significant tumor growth delay compared with other treatment regimens. Therefore, photothermal transfection of NF-κB p65 siRNA could effectively sensitize the tumor to chemotherapeutic agents. Because NIR light can penetrate skin and be delivered with high spatiotemporal control, therapeutic RNAi may benefit from this novel transfection strategy while avoiding unwanted side effect. PMID:20388791

  13. Synchrotron radiation-based x-ray analysis of bronze artifacts from an Iron Age site in the Judean hills.

    SciTech Connect

    Friedman, E. S.; Brody, A. J.; Young, M. L.; Almer, J. D.; Serge, C. U.; Mini, S. M.; IIT; Pacific School of Religion; Northwestern Univ.; Northern Illinois Univ.

    2008-07-01

    Seven bronze bangles from Tell en-Nasbeh, northern Judah, were investigated to understand the phase composition and manufacturing process of the artifacts, and possibly suggest a provenance for their origin. Synchrotron x-ray radiation diffraction (XRD) and fluorescence (XRF) were used in the analysis to avoid any destructive sampling and at the same time penetrate through the surface into the core metal. These techniques enabled us to determine that the bangles were not just tin bronze, but leaded tin bronze. Based on excavation reports, it is unlikely that the metal objects were manufactured locally at Tell en-Nasbeh; rather, preliminary XRD and XRF data point towards the neighboring region of Edom as their origin. Despite their political enmity during the Iron Age II, the data suggest that Judahite social demands for bronze may have fostered a strong economic relationship between these two polities.

  14. Estimates of tracer-based piston-flow ages of groundwater from selected sites-National Water-Quality Assessment Program, 1992-2005

    USGS Publications Warehouse

    Hinkle, Stephen R.; Shapiro, Stephanie D.; Plummer, L. Niel; Busenberg, Eurybiades; Widman, Peggy K.; Casile, Gerolamo C.; Wayland, Julian E.

    2011-01-01

    This report documents selected age data interpreted from measured concentrations of environmental tracers in groundwater from 1,399 National Water-Quality Assessment (NAWQA) Program groundwater sites across the United States. The tracers of interest were chlorofluorocarbons (CFCs), sulfur hexafluoride (SF6), and tritium/helium-3 (3H/3He). Tracer data compiled for this analysis primarily were from wells representing two types of NAWQA groundwater studies - Land-Use Studies (shallow wells, usually monitoring wells, in recharge areas under dominant land-use settings) and Major-Aquifer Studies (wells, usually domestic supply wells, in principal aquifers and representing the shallow, used resource). Reference wells (wells representing groundwater minimally impacted by anthropogenic activities) associated with Land-Use Studies also were included. Tracer samples were collected between 1992 and 2005, although two networks sampled from 2006 to 2007 were included because of network-specific needs. Tracer data from other NAWQA Program components (Flow System Studies, which are assessments of processes and trends along groundwater flow paths, and various topical studies) were not compiled herein. Tracer data from NAWQA Land-Use Studies and Major-Aquifer Studies that previously had been interpreted and published are compiled herein (as piston-flow ages), but have not been reinterpreted. Tracer data that previously had not been interpreted and published are evaluated using documented methods and compiled with aqueous concentrations, equivalent atmospheric concentrations (for CFCs and SF6), estimates of tracer-based piston-flow ages, and selected ancillary data, such as redox indicators, well construction, and major dissolved gases (N2, O2, Ar, CH4, and CO2). Tracer-based piston-flow ages documented in this report are simplistic representations of the tracer data. Tracer-based piston-flow ages are a convenient means of conceptualizing groundwater age. However, the piston

  15. [Tumor surgery].

    PubMed

    Hausamen, J E

    2000-05-01

    Surgery is still the primary therapeutic approach in treatment of tumors in the head and neck area, dating back to the early nineteenth century. More than 150 years ago, hemimaxillectomies and mandibular resections as well as hemiglossectomies were already performed by leading surgeons. The block principle we are now following dates back to Crile, who also established the principle of cervical lymph node dissection. Ablative oncologic surgery has always been closely linked with plastic and reconstructive surgery, rendering radical surgical interventions possible without disfiguring patients. The development of facial reconstructive surgery proceeded in stages, in the first instance as secondary reconstruction using tube pedicled flaps. The change to the concept of primary reconstruction occurred via arterialized skin flaps and myocutaneous flaps to the widely accepted and performed free tissue transfer. Free bone grafting, inaugurated earlier and still representing the majority of bone grafting, has been supplemented for certain reconstructive purposes by free vascularized bone transfer from various donor sites. Although the five-year-survival rate of carcinoma of the oral cavity has remained unchanged in the past 30 years, distinctive improvements in tumor surgery can be recorded. This is primarily based on improved diagnostics such as modern imaging techniques and the refinement of surgical techniques. The DOSAK has worked out distinctive guidelines for effective ablative oncologic surgery. Surgical approaches offering wide exposure and carrying low morbidity play a decisive role in radical resections. For this reason, midfacial degloving offers an essential improvement for the resection of midface tumors, especially from an aesthetic point of view. Tumors situated deep behind the viscerocranium at the skull base can be clearly exposed either through a lateral approach following a temporary osteotomy of the mandibular ramus or a transmandibular, transmaxillar, or

  16. Operational Definition of Active and Healthy Aging (AHA): The European Innovation Partnership (EIP) on AHA Reference Site Questionnaire: Montpellier October 20-21, 2014, Lisbon July 2, 2015.

    PubMed

    Bousquet, Jean; Malva, Joao; Nogues, Michel; Mañas, Leocadio Rodriguez; Vellas, Bruno; Farrell, John

    2015-12-01

    A core operational definition of active and healthy aging (AHA) is needed to conduct comparisons. A conceptual AHA framework proposed by the European Innovation Partnership on Active and Healthy Ageing Reference Site Network includes several items such as functioning (individual capability and underlying body systems), well-being, activities and participation, and diseases (including noncommunicable diseases, frailty, mental and oral health disorders). The instruments proposed to assess the conceptual framework of AHA have common applicability and availability attributes. The approach includes core and optional domains/instruments depending on the needs and the questions. A major common domain is function, as measured by the World Health Organization Disability Assessment Schedule 2.0 (WHODAS 2.0). WHODAS 2.0 can be used across all diseases and healthy individuals. It covers many of the AHA dimensions proposed by the Reference Site network. However, WHODAS 2.0 does not include all dimensions proposed for AHA assessment. The second common domain is health-related quality of life (HRQoL). A report of the AHA questionnaire in the form of a spider net has been proposed to facilitate usual comparisons across individuals and groups of interest. PMID:26498697

  17. DMXAA causes tumor site-specific vascular disruption in murine non-small cell lung cancer, and like the endogenous non-canonical cyclic dinucleotide STING agonist, 2'3'-cGAMP, induces M2 macrophage repolarization.

    PubMed

    Downey, Charlene M; Aghaei, Mehrnoosh; Schwendener, Reto A; Jirik, Frank R

    2014-01-01

    The vascular disrupting agent 5,6-dimethylxanthenone-4-acetic acid (DMXAA), a murine agonist of the stimulator of interferon genes (STING), appears to target the tumor vasculature primarily as a result of stimulating pro-inflammatory cytokine production from tumor-associated macrophages (TAMs). Since there were relatively few reports of DMXAA effects in genetically-engineered mutant mice (GEMM), and models of non-small cell lung cancer (NSCLC) in particular, we examined both the effectiveness and macrophage dependence of DMXAA in various NSCLC models. The DMXAA responses of primary adenocarcinomas in K-rasLA1/+ transgenic mice, as well as syngeneic subcutaneous and metastatic tumors, generated by a p53R172HΔg/+; K-rasLA1/+ NSCLC line (344SQ-ELuc), were assessed both by in vivo bioluminescence imaging as well as by histopathology. Macrophage-dependence of DMXAA effects was explored by clodronate liposome-mediated TAM depletion. Furthermore, a comparison of the vascular structure between subcutaneous tumors and metastases was carried out using micro-computed tomography (micro-CT). Interestingly, in contrast to the characteristic hemorrhagic necrosis produced by DMXAA in 344SQ-ELuc subcutaneous tumors, this agent failed to cause hemorrhagic necrosis of either 344SQ-ELuc-derived metastases or autochthonous K-rasLA1/+ NSCLCs. In addition, we found that clodronate liposome-mediated depletion of TAMs in 344SQ-ELuc subcutaneous tumors led to non-hemorrhagic necrosis due to tumor feeding-vessel occlusion. Since NSCLC were comprised exclusively of TAMs with anti-inflammatory M2-like phenotype, the ability of DMXAA to re-educate M2-polarized macrophages was examined. Using various macrophage phenotypic markers, we found that the STING agonists, DMXAA and the non-canonical endogenous cyclic dinucleotide, 2'3'-cGAMP, were both capable of re-educating M2 cells towards an M1 phenotype. Our findings demonstrate that the choice of preclinical model and the anatomical site of a

  18. DMXAA Causes Tumor Site-Specific Vascular Disruption in Murine Non-Small Cell Lung Cancer, and like the Endogenous Non-Canonical Cyclic Dinucleotide STING Agonist, 2′3′-cGAMP, Induces M2 Macrophage Repolarization

    PubMed Central

    Downey, Charlene M.; Aghaei, Mehrnoosh; Schwendener, Reto A.; Jirik, Frank R.

    2014-01-01

    The vascular disrupting agent 5,6-dimethylxanthenone-4-acetic acid (DMXAA), a murine agonist of the stimulator of interferon genes (STING), appears to target the tumor vasculature primarily as a result of stimulating pro-inflammatory cytokine production from tumor-associated macrophages (TAMs). Since there were relatively few reports of DMXAA effects in genetically-engineered mutant mice (GEMM), and models of non-small cell lung cancer (NSCLC) in particular, we examined both the effectiveness and macrophage dependence of DMXAA in various NSCLC models. The DMXAA responses of primary adenocarcinomas in K-rasLA1/+ transgenic mice, as well as syngeneic subcutaneous and metastatic tumors, generated by a p53R172HΔg/+; K-rasLA1/+ NSCLC line (344SQ-ELuc), were assessed both by in vivo bioluminescence imaging as well as by histopathology. Macrophage-dependence of DMXAA effects was explored by clodronate liposome-mediated TAM depletion. Furthermore, a comparison of the vascular structure between subcutaneous tumors and metastases was carried out using micro-computed tomography (micro-CT). Interestingly, in contrast to the characteristic hemorrhagic necrosis produced by DMXAA in 344SQ-ELuc subcutaneous tumors, this agent failed to cause hemorrhagic necrosis of either 344SQ-ELuc-derived metastases or autochthonous K-rasLA1/+ NSCLCs. In addition, we found that clodronate liposome-mediated depletion of TAMs in 344SQ-ELuc subcutaneous tumors led to non-hemorrhagic necrosis due to tumor feeding-vessel occlusion. Since NSCLC were comprised exclusively of TAMs with anti-inflammatory M2-like phenotype, the ability of DMXAA to re-educate M2-polarized macrophages was examined. Using various macrophage phenotypic markers, we found that the STING agonists, DMXAA and the non-canonical endogenous cyclic dinucleotide, 2′3′-cGAMP, were both capable of re-educating M2 cells towards an M1 phenotype. Our findings demonstrate that the choice of preclinical model and the anatomical site of a

  19. New luminescence ages for the Galería Complex archaeological site: resolving chronological uncertainties on the acheulean record of the Sierra de Atapuerca, northern Spain.

    PubMed

    Demuro, Martina; Arnold, Lee J; Parés, Josep M; Pérez-González, Alfredo; Ortega, Ana I; Arsuaga, Juan L; Bermúdez de Castro, José M; Carbonell, Eudald

    2014-01-01

    The archaeological karstic infill site of Galería Complex, located within the Atapuerca system (Spain), has produced a large faunal and archaeological record (Homo sp. aff. heidelbergensis fossils and Mode II lithic artefacts) belonging to the Middle Pleistocene. Extended-range luminescence dating techniques, namely post-infrared infrared stimulated luminescence (pIR-IR) dating of K-feldspars and thermally transferred optically stimulated luminescence (TT-OSL) dating of individual quartz grains, were applied to fossil-bearing sediments at Galería. The luminescence dating results are in good agreement with published chronologies derived using alternative radiometric dating methods (i.e., ESR and U-series dating of bracketing speleothems and combined ESR/U-series dating of herbivore teeth), as well as biochronology and palaeoenvironmental reconstructions inferred from proxy records (e.g., pollen data). For the majority of samples dated, however, the new luminescence ages are significantly (∼50%) younger than previously published polymineral thermoluminescence (TL) chronologies, suggesting that the latter may have overestimated the true burial age of the Galería deposits. The luminescence ages obtained indicate that the top of the basal sterile sands (GIb) at Galería have an age of up to ∼370 thousand years (ka), while the lowermost sub-unit containing Mode II Acheulean lithics (base of unit GIIa) was deposited during MIS 9 (mean age = 313±14 ka; n = 4). The overlying units GIIb-GIV, which contain the richest archaeopalaeontological remains, were deposited during late MIS 8 or early MIS 7 (∼240 ka). Galería Complex may be correlative with other Middle Pleistocene sites from Atapuerca, such as Gran Dolina level TD10 and unit TE19 from Sima del Elefante, but the lowermost archaeological horizons are ∼100 ka younger than the hominin-bearing clay breccias at the Sima de los Huesos site. Our results suggest that both pIR-IR and single-grain TT

  20. New Luminescence Ages for the Galería Complex Archaeological Site: Resolving Chronological Uncertainties on the Acheulean Record of the Sierra de Atapuerca, Northern Spain

    PubMed Central

    Demuro, Martina; Arnold, Lee J.; Parés, Josep M.; Pérez-González, Alfredo; Ortega, Ana I.; Arsuaga, Juan L.; Bermúdez de Castro, José M.; Carbonell, Eudald

    2014-01-01

    The archaeological karstic infill site of Galería Complex, located within the Atapuerca system (Spain), has produced a large faunal and archaeological record (Homo sp. aff. heidelbergensis fossils and Mode II lithic artefacts) belonging to the Middle Pleistocene. Extended-range luminescence dating techniques, namely post-infrared infrared stimulated luminescence (pIR-IR) dating of K-feldspars and thermally transferred optically stimulated luminescence (TT-OSL) dating of individual quartz grains, were applied to fossil-bearing sediments at Galería. The luminescence dating results are in good agreement with published chronologies derived using alternative radiometric dating methods (i.e., ESR and U-series dating of bracketing speleothems and combined ESR/U-series dating of herbivore teeth), as well as biochronology and palaeoenvironmental reconstructions inferred from proxy records (e.g., pollen data). For the majority of samples dated, however, the new luminescence ages are significantly (∼50%) younger than previously published polymineral thermoluminescence (TL) chronologies, suggesting that the latter may have overestimated the true burial age of the Galería deposits. The luminescence ages obtained indicate that the top of the basal sterile sands (GIb) at Galería have an age of up to ∼370 thousand years (ka), while the lowermost sub-unit containing Mode II Acheulean lithics (base of unit GIIa) was deposited during MIS 9 (mean age = 313±14 ka; n = 4). The overlying units GIIb-GIV, which contain the richest archaeopalaeontological remains, were deposited during late MIS 8 or early MIS 7 (∼240 ka). Galería Complex may be correlative with other Middle Pleistocene sites from Atapuerca, such as Gran Dolina level TD10 and unit TE19 from Sima del Elefante, but the lowermost archaeological horizons are ∼100 ka younger than the hominin-bearing clay breccias at the Sima de los Huesos site. Our results suggest that both pIR-IR and single-grain TT

  1. Epidemiological and histopathological patterns of salivary gland tumors in Cameroon

    PubMed Central

    Sando, Zacharie; Fokouo, Jean Valentin; Mebada, Arlette Onomo; Djomou, François; NDjolo, Alexis; Oyono, Jean Louis Essame

    2016-01-01

    Introduction Tumors of salivary glands are rare. According to Johns and Goldsmith in 1989, their annual incidence is less than 1/100000 without noteworthy geographical gap. But other authors suggest that their distribution may vary according to the race and geographical location. In Cameroon, existing studies give incomplete data. Hence, we underwent this study in order to draw the general profile of salivary gland tumors in Cameroon. Methods A retrospective study was carried out on the period spanning from January 2000 to December 2010 (11 years). It was done in nine Pathology services of different hospitals in Yaoundé, Douala and Bamenda. We consulted the archive registers of those services, retaining any patient with salivary gland tumor, whatever the histological type or location. Information gathered was the year of diagnosis, the service, the age and sex, the site of the tumor (gland) the histological type and the benign/ malignant character. Results We recruited a total of 275 files. Women were 56% (154/275) and men 44% (121/275) of the sample. Fifty eight tumors were malignant (21.9%) while 217 were benign (78.1%). The overall mean age was 37.44 years, with extremes between 1 and 84 years. Pleomorphic adenoma (60.36%) was the most common benign tumor. Adenoid cystic carcinoma (31%), mucoepidermoid carcinoma (22.4%) and adenocarcinoma (19%) were the most common malignant tumors. Palate (66.7%), cheek (30%) and lips (3.3%) were the sites were the minor salivary glands were mostly involved. Conclusion The differences with western world authors suggest a geographical variability of salivary gland tumors. PMID:27217890

  2. Methodological Developments in 3d Scanning and Modelling of Archaeological French Heritage Site : the Bronze Age Painted Cave of "LES FRAUX", Dordogne (france)

    NASA Astrophysics Data System (ADS)

    Burens, A.; Grussenmeyer, P.; Guillemin, S.; Carozza, L.; Lévêque, F.; Mathé, V.

    2013-07-01

    For six years, an interdisciplinary team of archaeologists, surveyors, environmentalists and archaeometrists have jointly carried out the study of a Bronze Age painted cave, registrered in the French Historical Monuments. The archaeological cave of Les Fraux (Saint-Martin-de-Fressengeas, Dordogne) forms a wide network of galleries, characterized by the exceptional richness of its archaeological remains such as ceramic and metal deposits, parietal representation and about domestic fireplaces. This cave is the only protohistorical site in Europe wherein are gathered testimonies of domestic, spiritual and artistic activities. Fortunately, the cave was closed at the end of the Bronze Age, following to the collapse of its entrance. The site was re-discovered in 1989 and its study started in 2007. The study in progress takes place in a new kind of tool founded by the CNRS's Institute of Ecology and Environment. The purpose of this observatory is the promotion of new methodologies and experimental studies in Global Ecology. In that framework, 3D models of the cave constitute the common work support and the best way for scientific communication for the various studies conducted on the site by nearly forty researchers. In this specific context, a partnership among archaeologists and surveyors from INSA Strasbourg allows the team to develop, in an interdisciplinary way, new methods of data acquiring based on contact-free measurements techniques in order to acquire a full 3D-documentation. This work is conducted in compliance with the integrity of the site. Different techniques based on Terrestrial Laser Scanning, Digital Photogrammetry and Spatial Imaging System have been used in order to generate a geometric and photorealistic 3D model from the combination of point clouds and photogrammetric images, for both visualization and accurate documentation purposes. Various scales of acquiring and diverse resolutions have been applied according to the subject: global volume cave

  3. The Effect of Age, Gender, and Insertion Site on Marginal Bone Loss around Endosseous Implants: Results from a 3-Year Trial with Premium Implant System

    PubMed Central

    Negri, Massimiliano; Macaluso, Guido M.; Manfredi, Edoardo; Bonanini, Mauro

    2014-01-01

    Objectives. The goal of this study was to evaluate bone changes around endosseous implants in partially edentulous patients. Materials and Methods. A total of 632 two-stage implants were placed in 252 patients. The implants had straight emergence profile, ZirTi surface, 3.3 to 5 mm diameter, and 8.5 to 13 mm length. Bone levels were assessed on orthopantomography immediately after surgery and after 36 months and marginal bone loss (MBL) was calculated from their difference. Results. Cumulative survival rate was 98.73%. Overall MBL was 0.8 mm ± 0.03 (mean ± SEM). Higher MBL was observed around implants in the maxilla than in the mandible (P < 0.007). A relation between implant diameter and MBL (P < 0.0001) was observed in male and, more limitedly, female patients. Older patients had higher MBL in the maxilla, but not in the mandible (P < 0.0001). MBL progressively increased with age in male patients, but reached a peak already in the 50–60 years age group in the female subset (P < 0.001). Conclusions. The overall MBL is consistent with the available literature. Site difference and patient age and gender appear to significantly affect MBL, representing important factors to be considered during implant placement. PMID:25187903

  4. Brain tumors.

    PubMed Central

    Black, K. L.; Mazziotta, J. C.; Becker, D. P.

    1991-01-01

    Recent advances in experimental tumor biology are being applied to critical clinical problems of primary brain tumors. The expression of peripheral benzodiazepine receptors, which are sparse in normal brain, is increased as much as 20-fold in brain tumors. Experimental studies show promise in using labeled ligands to these receptors to identify the outer margins of malignant brain tumors. Whereas positron emission tomography has improved the dynamic understanding of tumors, the labeled selective tumor receptors with positron emitters will enhance the ability to specifically diagnose and greatly aid in the pretreatment planning for tumors. Modulation of these receptors will also affect tumor growth and metabolism. Novel methods to deliver antitumor agents to the brain and new approaches using biologic response modifiers also hold promise to further improve the management of brain tumors. Images PMID:1848735

  5. Mortality and Embolic Potential of Cardiac Tumors

    PubMed Central

    Dias, Ricardo Ribeiro; Fernandes, Fábio; Ramires, Félix José Alvarez; Mady, Charles; Albuquerque, Cícero Piva; Jatene, Fábio Biscegli

    2014-01-01

    Background Cardiac tumors are rare, mostly benign with high embolic potential. Objectives To correlate the histological type of cardiac masses with their embolic potential, implantation site and long term follow up in patients undergoing surgery. Methods Between January 1986 and December 2011, we retrospectively analyzed 185 consecutive patients who underwent excision of intracardiac mass (119 females, mean age 48±20 years). In 145 patients, the left atrium was the origin site. 72% were asymptomatic and prior embolization was often observed (19.8%). The diagnosis was established by echocardiography, magnetic resonance and histological examination. Results Most tumors were located in the left side of the heart. Myxoma was the most common (72.6%), followed by fibromas (6.9%), thrombi (6.4%) and sarcomas (6.4%). Ranging from 0.6cm to 15cm (mean 4.6 ± 2.5cm) 37 (19.8%) patients had prior embolization, stroke 10.2%, coronary 4.8%, peripheral 4.3% 5.4% of hospital death, with a predominance of malignant tumors (40% p < 0.0001). The histological type was a predictor of mortality (rhabdomyomas and sarcomas p = 0.002) and embolic event (sarcoma, lipoma and fibroelastoma p = 0.006), but not recurrence. Tumor size, atrial fibrillation, cavity and valve impairment were not associated with the embolic event. During follow-up (mean 80±63 months), there were 2 deaths (1.1%) and two recurrences 1 and 11 years after the operation, to the same cavity. Conclusion Most tumors were located in the left side of the heart. The histological type was predictor of death and preoperative embolic event, while the implantation site carries no relation with mortality or to embolic event. PMID:25029470

  6. Tenfibgen Ligand Nanoencapsulation Delivers Bi-Functional Anti-CK2 RNAi Oligomer to Key Sites for Prostate Cancer Targeting Using Human Xenograft Tumors in Mice

    PubMed Central

    Trembley, Janeen H.; Unger, Gretchen M.; Korman, Vicci L.; Abedin, Md. Joynal; Nacusi, Lucas P.; Vogel, Rachel I.; Slaton, Joel W.; Kren, Betsy T.; Ahmed, Khalil

    2014-01-01

    Protected and specific delivery of nucleic acids to malignant cells remains a highly desirable approach for cancer therapy. Here we present data on the physical and chemical characteristics, mechanism of action, and pilot therapeutic efficacy of a tenfibgen (TBG)-shell nanocapsule technology for tumor-directed delivery of single stranded DNA/RNA chimeric oligomers targeting CK2αα' to xenograft tumors in mice. The sub-50 nm size TBG nanocapsule (s50-TBG) is a slightly negatively charged, uniform particle of 15 - 20 nm size which confers protection to the nucleic acid cargo. The DNA/RNA chimeric oligomer (RNAi-CK2) functions to decrease CK2αα' expression levels via both siRNA and antisense mechanisms. Systemic delivery of s50-TBG-RNAi-CK2 specifically targets malignant cells, including tumor cells in bone, and at low doses reduces size and CK2-related signals in orthotopic primary and metastatic xenograft prostate cancer tumors. In conclusion, the s50-TBG nanoencapsulation technology together with the chimeric oligomer targeting CK2αα' offer significant promise for systemic treatment of prostate malignancy. PMID:25333839

  7. Age-related decrease in the responsiveness of rat articular chondrocytes to EGF is associated with diminished number and affinity for the ligand of cell surface binding sites.

    PubMed

    Ribault, D; Habib, M; Abdel-Majid, K; Barbara, A; Mitrovic, D

    1998-01-12

    The effect of age on the responsiveness of articular chondrocytes (AC) to epidermal growth factor (EGF) was examined. Cells were isolated by digesting cartilage fragments from the humeral and femoral heads of 21-day old, 8- and 14-month old rats with collagenase. The cells were cultured under standard conditions, as monolayers. DNA synthesis was measured by [3H]thymidine incorporation and cell proliferation by the DNA content of subconfluent cultures. [125I]EGF binding and the amounts of EGF and EGF-receptor mRNAs were determined using confluent cells. DNA synthesis was decreased with age of animals. EGF stimulated DNA synthesis in cultures in 1- and 8-month old rats at low serum concentrations (< 5%), and in cultures in 14-month old animals at high serum concentrations. It also increased 5-day DNA content of cultures compared to serum-treated controls but this effect was weak in cultures in 14-month old rats. The number of high affinity binding sites for [125I]EGF decreased from 37,800 in the 1-month old to 1950 in the 14-month old rat AC. The apparent dissociation constant (Kd) also decreased with age: 0.18 nmol/l in the 1-month old; 0.12 nmol/l in the 8-month old; and 0.07 nmol/l in the 14-month old cells. AC in older rats contained more EGF mRNA and less EGF-receptor mRNA. Incubation of the cells with EGF resulted in down regulation of the EGF- and upregulation of EGF-receptor mRNA expressions. These findings show the age-related quantitative and qualitative alterations in EGF and EGF-receptor which may account, at least in part, for the diminished responsiveness of senescent AC to EGF. PMID:9509392

  8. Estimates of tracer-based piston-flow ages of groundwater from selected sites: National Water-Quality Assessment Program, 2006-2010

    USGS Publications Warehouse

    Shapiro, Stephanie D.; Plummer, L. Niel; Busenberg, Eurybiades; Widman, Peggy K.; Casile, Gerolamo C.; Wayland, Julian E.; Runkle, Donna L.

    2012-01-01

    Piston-flow age dates were interpreted from measured concentrations of environmental tracers from 812 National Water-Quality Assessment (NAWQA) Program groundwater sites from 27 Study Units across the United States. The tracers of interest include chlorofluorocarbons (CFCs), sulfur hexafluoride (SF6), and tritium/helium-3 (3H/3He). Tracer data compiled for this analysis were collected from 2006 to 2010 from groundwater wells in NAWQA studies, including: * Land-Use Studies (LUS, shallow wells, usually monitoring wells, located in recharge areas under dominant land-use settings), * Major-Aquifer Studies (MAS, wells, usually domestic supply wells, located in principal aquifers and representing the shallow drinking water supply), * Flow System Studies (FSS, networks of clustered wells located along a flowpath extending from a recharge zone to a discharge zone, preferably a shallow stream) associated with Land-Use Studies, and * Reference wells (wells representing groundwater minimally impacted by anthropogenic activities) also associated with Land-Use Studies. Tracer data were evaluated using documented methods and are presented as aqueous concentrations, equivalent atmospheric concentrations (for CFCs and SF6), and tracer-based piston-flow ages. Selected ancillary data, such as redox data, well-construction data, and major dissolved-gas (N2, O2, Ar, CH4, and CO2) data, also are presented. Recharge temperature was inferred using climate data (approximated by mean annual air temperature plus 1°C [MAAT +1°C]) as well as major dissolved-gas data (N2-Ar-based) where available. The N2-Ar-based temperatures showed significantly more variation than the climate-based data, as well as the effects of denitrification and degassing resulting from reducing conditions. The N2-Ar-based temperatures were colder than the climate-based temperatures in networks where recharge was limited to the winter months when evapotranspiration was reduced. The tracer-based piston-flow ages

  9. Pediatric Germ Cell Tumors; A 10-year Experience

    PubMed Central

    Khaleghnejad-Tabari, Ahmad; Mirshemirani, Alireza; Rouzrokh, Mohsen; Mohajerzadeh, Leily; Khaleghnejad-Tabari, Nasibeh; Hasas-Yeganeh, Shaghayegh

    2014-01-01

    Objective: The aim of this study was to evaluate the outcome of germ cell tumors in patients admitted to our center during a ten year period. Methods: In a retrospective descriptive study, patients with the pathological diagnosis of germ cell tumor (GCT) were included. All records were evaluated and patients followed by personal visit in clinic or phone call. Data regarding age, sex, tumor site, bio-chemical assay, pathology, treatment and outcomes were gathered. For qualitative variables we computed frequency and percentage and for quantitative variables, mean and standard deviation. Survival analysis was performed using Kaplan-Meier. All statistical analyses were performed by SPSS version16.0. Findings : Forty four patients consisted of 32 girls (72.7%) and 12 boys (27.3%). Their median age was 23 months. The most common pathological tumor types were 18 (40.9%) mature teratomas and 14 (31.8%) yolk sac tumors. Extra gonadal tumors were more prevalent (32 cases) and consisted of 21 (47.7%) sacrcoccygeal, 7 (15.9%) retroperitoneal, 2 (4.4%) mediastinal and 2 (4.4%) cervical tumors. In gonadal tumors 9 patients had ovarian and 3 patients testicular involvement. Staging at the time of diagnosis revealed stage one in 23 (52.3%) cases. All patients were treated surgically and the most common procedure was total resection in 41 (93.2%) patients. Fifteen (34.1%) patients received chemotherapy. In follow-up 31 (77.5%) patients were in complete remission, 9 (22.5%) had died, and 4 cases did not appear to follow-up visits. The median survival was 16 months (IQR 4-49 months). The highest mortality rate was found in patients with yolk sac tumors (8 of 13 cases). Conclusion: The patients with extra-gonadal GCT and a high AFP level have the worst prognosis and lower survival rate. Combination of surgery and chemotherapy can lead to a better prognosis. PMID:25755868

  10. Leiomyosarcoma of the Oropharynx and Neurogenic Tumors in a Young Patient With Turner's Syndrome

    PubMed Central

    Apice, Gaetano; Silvestro, Giustino; Losito, Simona; Botti, Gerardo; Ionna, Francesco; De Rosa, Vincenzo; Borghese, Annamaria; Ninfo, Vito

    2001-01-01

    Patient: A case of Turner's syndrome developing a leiomyosarcoma of the oropharynx and metachronous neurogenic tumors (mediastinal ‘ganglioneuroblastoma intermixed’, subcutaneous neurilemoma) is described. Discussion: To our knowledge, this case is the second reported leiomyosarcoma in a patient with Turner's syndrome. Also the site of involvement (palate and oropharynx) is particularly unusual for the already rare leiomyosarcomas in the young age. PMID:18521442

  11. Tumor Types

    MedlinePlus

    ... acoustic neuroma is also known as a schwannoma, vestibular schwannoma, or neurilemmoma. Characteristics Arises from cells that ... multiple CNS tumors, including neurofibromas, multiple meningiomas, bilateral vestibular schwannomas, optic nerve gliomas, and spinal cord tumors. ...

  12. Synthetic Site-Selectively Mono-6-O-Sulfated Heparan Sulfate Dodecasaccharide Shows Anti-Angiogenic Properties In Vitro and Sensitizes Tumors to Cisplatin In Vivo.

    PubMed

    Avizienyte, Egle; Cole, Claire L; Rushton, Graham; Miller, Gavin J; Bugatti, Antonella; Presta, Marco; Gardiner, John M; Jayson, Gordon C

    2016-01-01

    Heparan sulphate (HS), a ubiquitously expressed glycosaminoglycan (GAG), regulates multiple cellular functions by mediating interactions between numerous growth factors and their cell surface cognate receptors. However, the structural specificity of HS in these interactions remains largely undefined. Here, we used completely synthetic, structurally defined, alternating N-sulfated glucosamine (NS) and 2-O-sulfated iduronate (IS) residues to generate dodecasaccharides ([NSIS]6) that contained no, one or six glucosamine 6-O-sulfates (6S). The aim was to address how 6S contributes to the potential of defined HS dodecasaccharides to inhibit the angiogenic growth factors FGF2 and VEGF165, in vitro and in vivo. We show that the addition of a single 6S at the non-reducing end of [NSIS]6, i.e. [NSIS6S]-[NSIS]5, significantly augments the inhibition of FGF2-dependent endothelial cell proliferation, migration and sprouting in vitro when compared to the non-6S variant. In contrast, the fully 6-O-sulfated dodecasaccharide, [NSIS6S]6, is not a potent inhibitor of FGF2. Addition of a single 6S did not significantly improve inhibitory properties of [NSIS]6 when tested against VEGF165-dependent endothelial cell functions.In vivo, [NSIS6S]-[NSIS]5 blocked FGF2-dependent blood vessel formation without affecting tumor growth. Reduction of non-FGF2-dependent ovarian tumor growth occurred when [NSIS6S]-[NSIS]5 was combined with cisplatin. The degree of inhibition by [NSIS6S]-[NSIS]5 in combination with cisplatin in vivo equated with that induced by bevacizumab and sunitinib when administered with cisplatin. Evaluation of post-treatment vasculature revealed that [NSIS6S]-[NSIS]5 treatment had the greatest impact on tumor blood vessel size and lumen formation. Our data for the first time demonstrate that synthetic, structurally defined oligosaccharides have potential to be developed as active anti-angiogenic agents that sensitize tumors to chemotherapeutic agents. PMID:27490176

  13. Synthetic Site-Selectively Mono-6-O-Sulfated Heparan Sulfate Dodecasaccharide Shows Anti-Angiogenic Properties In Vitro and Sensitizes Tumors to Cisplatin In Vivo

    PubMed Central

    Avizienyte, Egle; Cole, Claire L.; Rushton, Graham; Miller, Gavin J.; Bugatti, Antonella; Presta, Marco; Gardiner, John M.; Jayson, Gordon C.

    2016-01-01

    Heparan sulphate (HS), a ubiquitously expressed glycosaminoglycan (GAG), regulates multiple cellular functions by mediating interactions between numerous growth factors and their cell surface cognate receptors. However, the structural specificity of HS in these interactions remains largely undefined. Here, we used completely synthetic, structurally defined, alternating N-sulfated glucosamine (NS) and 2-O-sulfated iduronate (IS) residues to generate dodecasaccharides ([NSIS]6) that contained no, one or six glucosamine 6-O-sulfates (6S). The aim was to address how 6S contributes to the potential of defined HS dodecasaccharides to inhibit the angiogenic growth factors FGF2 and VEGF165, in vitro and in vivo. We show that the addition of a single 6S at the non-reducing end of [NSIS]6, i.e. [NSIS6S]-[NSIS]5, significantly augments the inhibition of FGF2-dependent endothelial cell proliferation, migration and sprouting in vitro when compared to the non-6S variant. In contrast, the fully 6-O-sulfated dodecasaccharide, [NSIS6S]6, is not a potent inhibitor of FGF2. Addition of a single 6S did not significantly improve inhibitory properties of [NSIS]6 when tested against VEGF165-dependent endothelial cell functions.In vivo, [NSIS6S]-[NSIS]5 blocked FGF2-dependent blood vessel formation without affecting tumor growth. Reduction of non-FGF2-dependent ovarian tumor growth occurred when [NSIS6S]-[NSIS]5 was combined with cisplatin. The degree of inhibition by [NSIS6S]-[NSIS]5 in combination with cisplatin in vivo equated with that induced by bevacizumab and sunitinib when administered with cisplatin. Evaluation of post-treatment vasculature revealed that [NSIS6S]-[NSIS]5 treatment had the greatest impact on tumor blood vessel size and lumen formation. Our data for the first time demonstrate that synthetic, structurally defined oligosaccharides have potential to be developed as active anti-angiogenic agents that sensitize tumors to chemotherapeutic agents. PMID:27490176

  14. Middle Stone Age (MSA) site distributions in eastern Africa and their relationship to Quaternary environmental change, refugia and the evolution of Homo sapiens

    NASA Astrophysics Data System (ADS)

    Basell, Laura S.

    2008-12-01

    This paper considers the evolution of Homo sapiens in eastern Africa in relation to refugia and bottlenecks around ˜200 ka BP, at a macro scale. Middle Stone Age (MSA) lithics, site distributions and locations are analysed in relation to palaeovegetation maps of the last glacial/interglacial cycle, which are used as a proxy for earlier climate cycles. A "push and pull" model is then postulated for the spread of Homo sapiens out of refugia in eastern Africa, involving both volcanism (push) and habitat availability (pull). A date within OIS 5 is suggested for this expansion to other parts of the continent, and potentially further afield, contrary to a frequently proposed expansion within OIS 3.

  15. Brain Tumors

    MedlinePlus

    A brain tumor is a growth of abnormal cells in the tissues of the brain. Brain tumors can be benign, with no cancer cells, ... cancer cells that grow quickly. Some are primary brain tumors, which start in the brain. Others are ...

  16. Urogenital tumors

    SciTech Connect

    Weller, R.E.

    1994-03-01

    An overview is provided for veterinary care of urogenital tumors in companion animals, especially the dog. Neoplasms discussed include tumors of the kidney, urinary bladder, prostate, testis, ovary, vagina, vulva and the canine transmissible venereal tumor. Topics addressed include description, diagnosis and treatment.

  17. Quantification of climate and vegetation from Southern African Middle Stone Age sites - an application using Late Pleistocene plant material from Sibudu, South Africa

    NASA Astrophysics Data System (ADS)

    Bruch, A. A.; Sievers, C.; Wadley, L.

    2012-04-01

    The isolated geographical situation of South Africa makes the unraveling of various parameters that influence its regional climate in time challenging. If the South African climate does not exhibit a linear correlation with global archives as suggested by some authors then the contribution of independent local data that provides direct information on the environment at a certain place and time is crucial. Fossil plant remains provide valuable information on past environmental conditions. Although few paleobotanical data are available from Southern Africa, some sites reveal rich and diverse fossil floras, most notably, Sibudu Cave, KwaZulu-Natal, South Africa, with its numerous fruits, seeds, pollen and charcoal flora. Such plant remains not only provide information on past vegetation, but also serve as a sound base for paleoclimate quantification with the Coexistence Approach (CA). Sibudu Cave has pulses of Middle Stone Age occupation separated by hiatuses that are as long as 10 ka. Pre-Still Bay, Still Bay, Howiesons Poort, post-Howiesons Poort and late and final Middle Stone Age industries are present. Variations in vegetation and the animals preyed on through time suggest that subtle environmental changes could have occurred during MIS4 and MIS3 in the Sibudu area. Whilst always semi-forested, the region may have comprised a mosaic of uneven and changeable patches of coastal forest and savanna. These in turn might have influenced the numbers of forest versus plains animals in the area. Cultural factors could also have played a part in the faunal variability observed in Sibudu. Preliminary analyses of Sibudu Cave material confirm the potential of the CA for its application on Late Pleistocene African floras. In the future, comparison with other contemporaneous sites will help quantify spatial differences in the climate of the Late Pleistocene in South Africa, and may answer if environmental changes effected the cultural development from Still Bay to late MSA

  18. Going the distance: Mapping mobility in the Kalahari Desert during the Middle Stone Age through multi-site geochemical provenancing of silcrete artefacts.

    PubMed

    Nash, David J; Coulson, Sheila; Staurset, Sigrid; Ullyott, J Stewart; Babutsi, Mosarwa; Smith, Martin P

    2016-07-01

    This study utilises geochemical provenancing of silcrete raw materials, in combination with chaîne opératoire analyses, to explore lithic procurement and behavioural patterns in the northern Kalahari Desert during the Middle Stone Age (MSA). New data from the sites of Rhino Cave, Corner Cave, and ≠Gi in northwest Botswana, combined with earlier results from White Paintings Shelter, reveal that the long distance transport of silcrete for stone tool manufacture was a repeated and extensively used behaviour in this region. Silcrete was imported over distances of up to 295 km to all four sites, from locations along the Boteti River and around Lake Ngami. Significantly, closer known sources of silcrete of equivalent quality were largely bypassed. Silcrete artefacts were transported at various stages of production (as partially and fully prepared cores, blanks, and finished tools) and, with the exception of ≠Gi, in large volumes. The import occurred despite the abundance of locally available raw materials, which were also used to manufacture the same tool types. On the basis of regional palaeoenvironmental data, the timing of the majority of silcrete import from the Boteti River and Lake Ngami is constrained to regionally drier periods of the MSA. The results of our investigation challenge key assumptions underlying predictive models of human mobility that use distance-decay curves and drop-off rates. Middle Stone Age peoples in the Kalahari appear to have been more mobile than anticipated, and repeatedly made costly choices with regard to both raw material selection and items to be transported. We conclude that (i) base transport cost has been overemphasised as a restrictive factor in predictive models, and (ii) factors such as source availability and preference, raw material quality, and potential sociocultural influences significantly shaped prehistoric landscape use choices. PMID:27343775

  19. Clinical epidemiology for childhood primary central nervous system tumors.

    PubMed

    Bauchet, Luc; Rigau, Valérie; Mathieu-Daudé, Hélène; Fabbro-Peray, Pascale; Palenzuela, Gilles; Figarella-Branger, Dominique; Moritz, Jorge; Puget, Stéphanie; Bauchet, Fabienne; Pallusseau, Lorelei; Duffau, Hugues; Coubes, Philippe; Trétarre, Brigitte; Labrousse, François; Dhellemmes, Patrick

    2009-03-01

    This work was conducted by the French Brain Tumor Data Bank (FBTDB) and aims to prospectively record all primary central nervous system tumors (PCNST), in France, for which histological diagnosis is available. Results concerning children are presented. This study analyzes the childhood cases (0-19 years) of newly diagnosed and histologically confirmed PCNST (during the years 2004-2006) which have been recorded by the FBTDB. All French neuropathology and neurosurgery departments participated in this program. Neurosurgeons and neuropathologists completed a data file containing socio-demographic, clinical, radiologic and anatomopathologic information. The Tumor Registry from Herault was authorized to compile the data files with personal identifiers. About 1,017 cases (533 boys and 484 girls) of newly diagnosed childhood PCNST have been recorded (gliomas: 52%, all other neuroepithelial tumors: 31%, craniopharyngioma: 5%, germ cell tumors, meningioma and neurinoma: approximately 3% each, all histological subtypes have been detailed). Tumor resections were performed in 83.3%, and biopsies in 16.7%. The distributions by histology, cryopreservation of the samples, age, sex, tumor site and surgery have been detailed. To our knowledge, this work is the first databank in Europe dedicated to PCNST that includes the collection of clinical, radiological and histological data (including cryopreservation of the specimen). The long term goals of the FBTDB are to create a national registry and a network to perform epidemiological studies, to implement clinical and basic research protocols, and to evaluate and harmonize the healthcare of children and adult patients affected by PCNST. PMID:19020806

  20. Adenomatoid odontogenic tumor, an uncommon tumor

    PubMed Central

    Vasudevan, K.; Kumar, Senthil; Vijayasamundeeswari; Vigneswari, Srivel

    2012-01-01

    Here we report a case of adenomatoid odontogenic tumor (AOT) in the maxilla in a young girl aged 14 years and its surgical management. We also review the literature and variations in the nomenclature and classifications of this interesting tumor. The review of literature gives an interesting picture regarding terminologies in the past and dilemma in classifying this tumor. The introduction of the name adenomatoid odontogenic tumour has resulted in the simpler and fruitful surgical management like enucleation and curettage with no reports of recurrences. In the past, similar lesion with the terminology like adeno ameloblastoma has resulted in unnecessary mutilating surgery. The conflicting views whether the lesion is being neoplasm or an anomalous hamartomatous growth is also being discussed. PMID:22919236

  1. Lipoprotein(A) with An Intact Lysine Binding Site Protects the Retina From an Age-Related Macular Degeneration Phenotype in Mice (An American Ophthalmological Society Thesis)

    PubMed Central

    Handa, James T.; Tagami, Mizuki; Ebrahimi, Katayoon; Leibundgut, Gregor; Janiak, Anna; Witztum, Joseph L.; Tsimikas, Sotirios

    2015-01-01

    Purpose: To test the hypothesis that the accumulation of oxidized phospholipids (OxPL) in the macula is toxic to the retina unless neutralized by a variety of mechanisms, including binding by lipoprotein(a) [Lp(a)], which is composed of apolipoprotein(a) [apo(a)] and apolipoprotein B-100 (apoB). Methods: Human maculas and eyes from two Lp(a) transgenic murine models were subjected to morphologic, ultrastructural, and immunohistochemical analysis. “Wild-type Lp(a)” mice, which express human apoB-100 and apo(a) that contains oxidized phospholipid, and “mutant LBS− Lp(a)” mice with a defective apo(a) lysine binding site (LBS) for oxidized phospholipid binding, were fed a chow or high-fat diet for 2 to 12 months. Oxidized phospholipid–containing lipoproteins were detected by immunoreactivity to E06, a murine monoclonal antibody binding to the phosphocholine headgroup of oxidized, but not native, phospholipids. Results: Oxidized phospholipids, apo(a), and apoB accumulate in maculas, including drusen, of age-related macular degeneration (AMD) samples and age-matched controls. Lp(a) mice fed a high-fat diet developed age-related changes. However, mutant LBS− Lp(a) mice fed a high-fat diet developed retinal pigment epithelial cell degeneration and drusen. These changes were associated with increased OxPL, decreased antioxidant defenses, increased complement, and decreased complement regulators. Conclusions: Human maculas accumulate Lp(a) and OxPL. Mutant LBS− Lp(a) mice, lacking the ability to bind E06-detectable oxidized phospholipid, develop AMD-like changes. The ability of Lp(a) to bind E06-detectable OxPL may play a protective role in AMD. PMID:26538774

  2. Epilepsy and brain tumors.

    PubMed

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

    2016-01-01

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

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

    PubMed

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

    2012-01-01

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

  4. Relative radiosensitivity of bone tumor induction among beagles as a function of age at injection of {sup 239}Pu or {sup 226}Ra

    SciTech Connect

    Lloyd, R.D.; Taylor, G.N.; Jee, W.S.S.; Miller, S.C.

    1999-01-01

    A comparison was made of the response to induction of skeletal malignancy from exposure of beagles to monomeric {sup 239}Pu or to {sup 226}Ra as juveniles (3 mo of age), young adults (1.5 y of age), or mature adults (5 y of age). This indicated that of these age groups, animals injected as young adults are most sensitive per Gy of average skeletal dose evaluated at 1 y before death. Dogs exposed either as juveniles or as mature adults appeared to be less sensitive. Relative radiosensitivities (RRS) of juvenile and mature beagles ranged between about 0.3 and 0.7 that of dogs injected as young adults. Mean values of RRS for both radionuclides were about 0.5, but RRS values derived from dogs given monomeric {sup 239}Pu appeared to be most reliable and were 0.27 {+-} 0.09 for dogs injected as juveniles and 0.41 {+-} 0.13 for animals exposed as mature adults.

  5. Young T Cells Age During a Redirected Anti-Tumor Attack: Chimeric Antigen Receptor-Provided Dual Costimulation is Half the Battle

    PubMed Central

    Hombach, Andreas A.; Abken, Hinrich

    2013-01-01

    Adoptive therapy with chimeric antigen receptor (CAR)-redirected T cells showed spectacular efficacy in the treatment of leukemia in recent early phase trials. Patient’s T cells were ex vivo genetically engineered with a CAR, amplified and re-administered to the patient. While T cells mediating the primary response were predominantly of young effector and central memory phenotype, repetitive antigen engagement irreversible triggers T cell maturation leaving late memory cells with the KLRG1+ CD57+ CD7− CCR7− phenotype in the long-term. These cells preferentially accumulate in the periphery, are hypo-responsive upon TCR engagement and prone to activation-induced cell death. A recent report indicates that those T cells can be rescued by CAR provided CD28 and OX40 (CD134) stimulation. We discuss the strategy with respect to prolong the anti-tumor response and to improve the over-all efficacy of adoptive cell therapy. PMID:23761793

  6. Young T Cells Age During a Redirected Anti-Tumor Attack: Chimeric Antigen Receptor-Provided Dual Costimulation is Half the Battle.

    PubMed

    Hombach, Andreas A; Abken, Hinrich

    2013-01-01

    Adoptive therapy with chimeric antigen receptor (CAR)-redirected T cells showed spectacular efficacy in the treatment of leukemia in recent early phase trials. Patient's T cells were ex vivo genetically engineered with a CAR, amplified and re-administered to the patient. While T cells mediating the primary response were predominantly of young effector and central memory phenotype, repetitive antigen engagement irreversible triggers T cell maturation leaving late memory cells with the KLRG1(+) CD57(+) CD7(-) CCR7(-) phenotype in the long-term. These cells preferentially accumulate in the periphery, are hypo-responsive upon TCR engagement and prone to activation-induced cell death. A recent report indicates that those T cells can be rescued by CAR provided CD28 and OX40 (CD134) stimulation. We discuss the strategy with respect to prolong the anti-tumor response and to improve the over-all efficacy of adoptive cell therapy. PMID:23761793

  7. Beta-2 Microglobulin Tumor Marker

    MedlinePlus

    ... limited. Home Visit Global Sites Search Help? Beta-2 Microglobulin Tumor Marker Share this page: Was this page helpful? Also known as: B2M; B 2 M; β2-Microglobulin; Thymotaxin Formal name: Beta 2 ...

  8. Long-term psychological effects in children treated for intracranial tumors

    SciTech Connect

    Jannoun, L.; Bloom, H.J. )

    1990-04-01

    The results are reported of the psychological assessment of 62 children who presented with primary intracranial tumors and who received radiotherapy at the Royal Marsden Hospital between 1963 and 1973. Evaluations were carried out 3-20 years after treatment. All patients were free from progressive tumor at testing. The average IQ of the total series was within the normal range (Full-Scale IQ 92) but 23% of the patients were functioning at an educationally subnormal level of intelligence (IQ less than 80). Sex, tumor type, tumor location and the radiotherapy volume and site of maximum dose were not found to have a significant effect on intellectual outcome. A significant correlation was found between intelligence and age at the time of treatment. Children who received treatment under the age of 5 years were more adversely affected (average IQ 72) than those who were aged 6-10 (average IQ 93) and those aged 11-15 years (average IQ 107). The incidence of neurological abnormalities and physical disability was significantly greater among patients with supratentorial tumors (72% of cases), compared with patients with infratentorial lesions (44% of cases). The results were discussed in terms of the management of young patients with intracranial tumors.

  9. OM/OC Ratio and Specific Attenuation Coefficient in Ambient Particulate Matter at a Rural Site in Southern Ontario: Implications for Aerosol Aging and Emission Sources

    NASA Astrophysics Data System (ADS)

    Chan, T. W.; Huang, L.; Leaitch, R.; Sharma, S.; Brook, J.; Slowik, J.; Abbatt, J.

    2008-05-01

    Carbonaceous species (organic carbon (OC) and elemental carbon (EC)) contribute a large portion of atmospheric fine particle mass and influence air quality, human health, and climate forcing. However, their emission sources and atmospheric aging processes are not well understood. The OM/OC ratio, defined as the organic mass per unit OC mass, is useful to understand the degree of oxidation of aerosol particles in atmospheric processes. We define the modified BC/EC (mod BC/EC) ratio as the ratio of the non-scattering corrected absorption coefficient per unit mass of EC. The mod BC/EC ratio has a similar meaning as the site specific attenuation coefficient, which is an important parameter used to convert light absorption measurements to black carbon mass. The mod BC/EC ratio can vary due to light scattering effect on absorption measurements, in which the oxygenated organics may play a role. The pyrolysis organic carbon (POC) is defined as the carbon mass fraction obtained at T= 870°C under a pure helium environment using the thermal separation method [Huang et al., 2006]. Since POC mass is generally proportional to the amount of oxygenated OC, studying the relationships among OC, EC, POC, as well as OM/OC and mod BC/EC ratios may help us understand the mechanisms of aerosol aging from different emission sources. Two 1-month field studies were conducted at a rural site in southern Ontario (NW of Toronto) during fall 2005 and spring 2007. Quartz filter samples were collected and analyzed for OC, POC, and EC concentrations using a thermal/optical method [Huang et al., 2006]. Together with the total organic matter measured by an Aerodyne Aerosol Mass Spectrometer (AMS) and the absorption coefficient obtained from a Particle Soot Absorption Photometer (PSAP), the OM/OC and mod BC/EC ratios for ambient aerosols were obtained. Our results show that when air mass was mainly from south, OC, POC, and EC were relatively high, with average ratios of OC/EC, OM/OC, and POC/EC as 1

  10. Prognosis and Survival in Patients With Gastrointestinal Tract Carcinoid Tumors

    PubMed Central

    Shebani, Khaled O.; Souba, Wiley W.; Finkelstein, Dianne M.; Stark, Paul C.; Elgadi, Khaled M.; Tanabe, Kenneth K.; Ott, Mark J.

    1999-01-01

    Objective To determine the impact of clinical presentation variables on the management and survival of patients with gastrointestinal (GI) tract carcinoid tumors. Methods A 20-year (1975–1995) retrospective analysis of 150 patients with GI tract carcinoid tumors at the Massachusetts General Hospital was conducted. Median follow-up was 66 months (range 1–378). Survival estimates for prognostic factors were calculated using Kaplan-Meier product limit estimators, with death from carcinoid as the outcome. Univariate analyses for each factor were obtained using a log-rank test, and multivariate survival analysis was performed. Results All but two patients underwent surgical intervention with the intent to cure (90%) or debulk the tumor (9%). Mean age at presentation was 55 ± 18 years (range 11–90). There was a slight female/male predominance (80:70). Symptoms were nonspecific; the most common were abdominal pain (40%), nausea and vomiting (29%), weight loss (19%), and GI blood loss (15%). Incidental carcinoids, discovered at the time of another procedure, occurred in 40% of patients and were noted at multiple sites throughout the GI tract. The distribution of tumors was ileojejunum (37%), appendix (31%), colon (13%), rectum (12%), stomach (4%), duodenum (1.3%), and Meckel’s diverticulum (1.3%). Of the 27 patients with documented liver metastases, carcinoid syndrome developed in only 13 patients (48%), manifested by watery diarrhea (100%), upper body flushing (70%), asthma (38%), and tricuspid regurgitation (23%). All 13 patients with carcinoid syndrome had elevated levels of 5-HIAA, but the absolute levels did not correlate with the severity of symptoms. An additional 11 patients, 3 without liver metastases, had elevated levels of 5-HIAA without any evidence of carcinoid syndrome. Multicentric carcinoid tumors occurred in 15 patients (10%), and all but one of these tumors were centered around the ileocecal valve. There was no difference in the incidence of

  11. Rhabdoid tumor predisposition syndrome.

    PubMed

    Sredni, Simone T; Tomita, Tadanori

    2015-01-01

    Rhabdoid tumors (RT), or malignant rhabdoid tumors, are among the most aggressive and lethal forms of human cancer. They can arise in any location in the body but are most commonly observed in the brain, where they are called atypical teratoid/rhabdoid tumors (AT/RT), and in the kidneys, where they are called rhabdoid tumors of the kidney. The vast majority of rhabdoid tumors present with a loss of function in the SMARCB1 gene, also known as INI1, BAF47, and hSNF5, a core member of the SWI/SNF chromatin-remodeling complex. Recently, mutations in a 2nd locus of the SWI/SNF complex, the SMARCA4 gene, also known as BRG1, were found in rhabdoid tumors with retention of SMARCB1 expression. Familial cases may occur in a condition known as rhabdoid tumor predisposition syndrome (RTPS). In RTPS, germline inactivation of 1 allele of a gene occurs. When the mutation occurs in the SMARCB1 gene, the syndrome is called RTPS1, and when the mutation occurs in the SMARCA4 gene it is called RTPS2. Children presenting with RTPS tend to develop tumors at a younger age, but the impact that germline mutation has on survival remains unclear. Adults who carry the mutation tend to develop multiple schwannomas. The diagnosis of RTPS should be considered in patients with RT, especially if they have multiple primary tumors, and/or in individuals with a family history of RT. Because germline mutations result in an increased risk of carriers developing RT, genetic counseling for families with this condition is recommended. PMID:25494491

  12. Application of hydrogeology and groundwater-age estimates to assess the travel time of groundwater at the site of a landfill to the Mahomet Aquifer, near Clinton, Illinois

    USGS Publications Warehouse

    Kay, Robert T.; Buszka, Paul M.

    2016-01-01

    The U.S. Geological Survey used interpretations of hydrogeologic conditions and tritium-based groundwater age estimates to assess the travel time of groundwater at a landfill site near Clinton, Illinois (the “Clinton site”) where a chemical waste unit (CWU) was proposed to be within the Clinton landfill unit #3 (CLU#3). Glacial deposits beneath the CWU consist predominantly of low-permeability silt- and clay-rich till interspersed with thin (typically less than 2 feet in thickness) layers of more permeable deposits, including the Upper and Lower Radnor Till Sands and the Organic Soil unit. These glacial deposits are about 170 feet thick and overlie the Mahomet Sand Member of the Banner Formation. The Mahomet aquifer is composed of the Mahomet Sand Member and is used for water supply in much of east-central Illinois.Eight tritium analyses of water from seven wells were used to evaluate the overall age of recharge to aquifers beneath the Clinton site. Groundwater samples were collected from six monitoring wells on or adjacent to the CLU#3 that were open to glacial deposits above the Mahomet aquifer (the upper and lower parts of the Radnor Till Member and the Organic Soil unit) and one proximal production well (approximately 0.5 miles from the CLU#3) that is screened in the Mahomet aquifer. The tritium-based age estimates were computed with a simplifying, piston-flow assumption: that groundwater moves in discrete packets to the sampled interval by advection, without hydrodynamic dispersion or mixing.Tritium concentrations indicate a recharge age of at least 59 years (pre-1953 recharge) for water sampled from deposits below the upper part of the Radnor Till Member at the CLU#3, with older water expected at progressively greater depth in the tills. The largest tritium concentration from a well sampled by this study (well G53S; 0.32 ± 0.10 tritium units) was in groundwater from a sand deposit in the upper part of the Radnor Till Member; the shallowest permeable unit

  13. Geographic distribution, age pattern and sites of lesions in a cohort of Buruli ulcer patients from the Mapé Basin of Cameroon.

    PubMed

    Bratschi, Martin W; Bolz, Miriam; Minyem, Jacques C; Grize, Leticia; Wantong, Fidèle G; Kerber, Sarah; Njih Tabah, Earnest; Ruf, Marie-Thérèse; Mou, Ferdinand; Noumen, Djeunga; Um Boock, Alphonse; Pluschke, Gerd

    2013-01-01

    Buruli ulcer (BU), a neglected tropical disease of the skin, caused by Mycobacterium ulcerans, occurs most frequently in children in West Africa. Risk factors for BU include proximity to slow flowing water, poor wound care and not wearing protective clothing. Man-made alterations of the environment have been suggested to lead to increased BU incidence. M. ulcerans DNA has been detected in the environment, water bugs and recently also in mosquitoes. Despite these findings, the mode of transmission of BU remains poorly understood and both transmission by insects or direct inoculation from contaminated environment have been suggested. Here, we investigated the BU epidemiology in the Mapé basin of Cameroon where the damming of the Mapé River since 1988 is believed to have increased the incidence of BU. Through a house-by-house survey in spring 2010, which also examined the local population for leprosy and yaws, and continued surveillance thereafter, we identified, till June 2012, altogether 88 RT-PCR positive cases of BU. We found that the age adjusted cumulative incidence of BU was highest in young teenagers and in individuals above the age of 50 and that very young children (<5) were underrepresented among cases. BU lesions clustered around the ankles and at the back of the elbows. This pattern neither matches any of the published mosquito biting site patterns, nor the published distribution of small skin injuries in children, where lesions on the knees are much more frequent. The option of multiple modes of transmission should thus be considered. Analyzing the geographic distribution of cases in the Mapé Dam area revealed a closer association with the Mbam River than with the artificial lake. PMID:23785529

  14. Geographic Distribution, Age Pattern and Sites of Lesions in a Cohort of Buruli Ulcer Patients from the Mapé Basin of Cameroon

    PubMed Central

    Bratschi, Martin W.; Bolz, Miriam; Minyem, Jacques C.; Grize, Leticia; Wantong, Fidèle G.; Kerber, Sarah; Njih Tabah, Earnest; Ruf, Marie-Thérèse; Mou, Ferdinand; Noumen, Djeunga; Um Boock, Alphonse; Pluschke, Gerd

    2013-01-01

    Buruli ulcer (BU), a neglected tropical disease of the skin, caused by Mycobacterium ulcerans, occurs most frequently in children in West Africa. Risk factors for BU include proximity to slow flowing water, poor wound care and not wearing protective clothing. Man-made alterations of the environment have been suggested to lead to increased BU incidence. M. ulcerans DNA has been detected in the environment, water bugs and recently also in mosquitoes. Despite these findings, the mode of transmission of BU remains poorly understood and both transmission by insects or direct inoculation from contaminated environment have been suggested. Here, we investigated the BU epidemiology in the Mapé basin of Cameroon where the damming of the Mapé River since 1988 is believed to have increased the incidence of BU. Through a house-by-house survey in spring 2010, which also examined the local population for leprosy and yaws, and continued surveillance thereafter, we identified, till June 2012, altogether 88 RT-PCR positive cases of BU. We found that the age adjusted cumulative incidence of BU was highest in young teenagers and in individuals above the age of 50 and that very young children (<5) were underrepresented among cases. BU lesions clustered around the ankles and at the back of the elbows. This pattern neither matches any of the published mosquito biting site patterns, nor the published distribution of small skin injuries in children, where lesions on the knees are much more frequent. The option of multiple modes of transmission should thus be considered. Analyzing the geographic distribution of cases in the Mapé Dam area revealed a closer association with the Mbam River than with the artificial lake. PMID:23785529

  15. [Imaging of childhood brain tumors].

    PubMed

    Couanet, D; Adamsbaum, C

    2006-06-01

    Brain tumors represent around a quarter of all solid tumors observed in the pediatric population. Infratentorial tumors are the most frequent, mostly encountered between 4 and 11 years of age. Early imaging is important because initial symptoms can be misinterpreted as statural and pubertal disorders or pseudoabdominal symptoms with apathy and vomiting in infants. Because signal abnormalities on MRI are most often not specific, it is essential to take into account the clinical and topographic characteristics of the lesion to establish an appropriate differential diagnosis. The main patterns of brain tumors observed in pediatrics are presented. Brain metastases are very unusual in children, in contrast to lepto-meningeal metastasis. PMID:16778744

  16. Age distribution of Ocean Drill sites across the Central Walvis Ridge indicates plate boundary control of plume volcanism in the South Atlantic

    NASA Astrophysics Data System (ADS)

    O'Connor, John M.; Jokat, Wilfried

    2015-08-01

    The Tristan-Gough hotspot trail on the African plate consists of the Walvis Ridge and a younger province of seamounts and islands. In order to determine the relative motion between the African plate and the Tristan-Gough hotspot it is essential to resolve changes in the age and morphology of the Walvis Ridge. A significant problem is, however, to establish how the vigor and flow of hotspot material to the mid-ocean ridge constructed the Walvis Ridge. We have addressed this issue by measuring an 40Ar/39Ar stratigraphy at three sites across the central Walvis Ridge sampled by Ocean Drilling (DSDP Leg 74). The age-distance relation of volcanism, together with geophysical, geochemical and paleodepth information, suggests collectively that hotspot volcanism was occurring locally c. 72 Ma on an elevated segment of the mid-ocean ridge located close to the Tristan-Gough hotspot. As the mid-ocean ridge migrated away from the hotspot (c. 36 km/Ma) between c. 72 Ma and 68 Ma, hotspot material continued flowing to the mid-ocean ridge and the Walvis Ridge shoaled rapidly (c. 500 m/Ma) to the west, on seafloor that might have been subsiding at a rate consistent with normal crustal cooling. This apparent correlation points to the possibility of an inverse relation between the volume flux of hotspot volcanism and the distance between the mid-ocean ridge and the Tristan-Gough hotspot. We infer that since c. 93 Ma the geometry and motion of the mid-ocean ridge determined where the hotspot material that built the Walvis Ridge was channeled to the plate surface. Furthermore, interplay between hotspot flow, and the changing geometry of the mid-ocean ridge as it migrated relative to the Tristan-Gough hotspot, might explain the age and morphology of the Walvis Ridge. Our finding provides further evidence that the distribution of hotspot volcanism in the southeast Atlantic expresses interaction between deep mantle (plume) and shallow plate tectonic and asthenosphere processes.

  17. Prenatal Organochlorine and Methylmercury Exposure and Memory and Learning in School-Age Children in Communities Near the New Bedford Harbor Superfund Site, Massachusetts

    PubMed Central

    Orenstein, Sara T.C.; Thurston, Sally W.; Bellinger, David C.; Schwartz, Joel D.; Amarasiriwardena, Chitra J.; Altshul, Larisa M.

    2014-01-01

    organochlorine and methylmercury exposure and memory and learning in school-age children in communities near the New Bedford Harbor Superfund Site, Massachusetts. Environ Health Perspect 122:1253–1259; http://dx.doi.org/10.1289/ehp.1307804 PMID:25062363

  18. Demographic and histopathologic profile of pediatric brain tumors: A hospital-based study

    PubMed Central

    Shah, Harshil C.; Ubhale, Bhushan P.; Shah, Jaimin K.

    2015-01-01

    Background: Very few hospital-based or population-based studies are published in the context to the epidemiologic profile of pediatric brain tumors (PBTs) in India and Indian subcontinent. Aim: To study the demographic and histopathologic profile of PBTs according to World Health Organization 2007 classification in a single tertiary health care center in India. Materials and Methods: Data regarding age, gender, topography, and histopathology of 76 pediatric patients (0–19 years) with brain tumors operated over a period of 24 months (January-2012 to December-2013) was collected retrospectively and analyzed using EpiInfo 7. Chi-square test and test of proportions (Z-test) were used wherever necessary. Results: PBTs were more common in males (55.3%) as compared to females (44.7%) with male to female ratio of 1.23:1. Mean age was 10.69 years. Frequency of tumors was higher in childhood age group (65.8%) when compared to adolescent age group (34.2%). The most common anatomical site was cerebellum (39.5%), followed by hemispheres (22.4%). Supratentorial tumors (52.6%) were predominant than infratentorial tumors (47.4%). Astrocytomas (40.8%) and embryonal tumors (29.0%) were the most common histological types almost contributing more than 2/3rd of all tumors. Craniopharyngiomas (11.8%) and ependymomas (6.6%) were the third and fourth most common tumors, respectively. Conclusion: Astrocytomas and medulloblastomas are the most common tumors among children and adolescents in our region, which needs special attention from the neurosurgical department of our institute. Demographic and histopathologic profile of cohort in the present study do not differ substantially from that found in other hospital-based and population-based studies except for slight higher frequency of craniopharyngiomas. PMID:26942148

  19. Calcifying Fibrous Tumor

    PubMed Central

    Chorti, Angeliki; Papavramidis, Theodossis S.; Michalopoulos, Antonios

    2016-01-01

    Abstract Calcifying fibrous tumor (CFT) is a benign lesion characterized by its specific histological findings and is found as solitary or multiple lesions in several locations of the human body. The aim of the present systematic review is to give a detailed account of all reported cases of CFT in the literature and to analyze the available data, to completely characterize the entity from epidemiological, medical, and surgical aspects. A bibliographic research was performed from 1988 until 2015. A database with the patients’ characteristics was made, including sex, age, location of the tumor, symptoms, symptoms duration, size of the tumor, diagnostic methods, treatment, metastasis, and follow-up. A total of 104 articles were identified, reporting 157 cases of CFT. Mean age of patients was 33.58 years and the ratio between men and women was 1:1.27. The most common locations of CFT were stomach (18%), small intestine (8.7%), pleura (9.9%), mesentery (5%), and peritoneum (6.8%). Mean diameter of the tumor was estimated 4.6 cm. The correlations proceeded showed that as age increases, size decreases (P = 0.001) and that the tumor is larger in females (P = 0.027). Kruskal-Wallis test showed that the larger tumors appear in the neck and adrenal gland (P = 0.001). The percentage of asymptomatic patients was 30.57%. Computed tomography and biopsy were the most common tests for the diagnosis of CFT. Open surgical procedure was performed in the majority of cases. The median hospitalization was 6.06 days and the mean follow-up period was 29.97 months. Recurrences were mentioned in 10 of 96 patients with available data. No deaths owing to CFT were mentioned in the literature. CFT should be included in the differential diagnosis of enlarging mass revealed by clinical or imaging examination either incidentally or after specific acute or chronic symptomatology. PMID:27196478

  20. Imaging findings of various talus bone tumors-clinico-radiologic features of talus bone tumors.

    PubMed

    Jeon, Ji Young; Chung, Hye Won; Kwon, Jong Won; Hong, Sung Hwan; Lee, Guen Young; Ryu, Kyung Nam

    2016-01-01

    Osseous neoplasms of the foot are uncommon, accounting for only 3.3% of all primary bone tumors. Bone tumors of the talus are even rarer, and there are not many publications that comprehensively evaluate the imaging findings of talus tumors. The purpose of this article is to review the benign and malignant bone tumors affecting this uncommon site and to describe the clinical and radiologic features of each tumor. PMID:27317211

  1. Pindborg tumor

    PubMed Central

    Caliaperoumal, Santhosh Kumar; Gowri, S.; Dinakar, J.

    2016-01-01

    Calcifying epithelial odontogenic tumor (CEOT), also known as Pindborg tumor, is a rare odontogenic epithelial neoplasm. So far, nearly 200 cases have been reported in the literature. We are reporting a case of CEOT in a 42-year-old male patient with painless bony swelling in the mandible. The clinical, radiographic, and histopathologic features are discussed with relevant references. PMID:27041911

  2. Latexin exhibits tumor-suppressor potential in pancreatic ductal adenocarcinoma

    PubMed Central

    XUE, ZHANXIONG; ZHOU, YUHUI; WANG, CHENG; ZHENG, JIHANG; ZHANG, PU; ZHOU, LINGLING; WU, LIANG; SHAN, YUNFENG; YE, MENGSI; HE, YUN; CAI, ZHENZHAI

    2016-01-01

    Recent studies suggest that latexin (Lxn) expression is involved in stem cell regulation and that it plays significant roles in tumor cell migration and invasion. The clinicopathological significance of Lxn expression and its possible correlation with CD133 expression in pancreatic ductal adenocarcinoma (PDAC) is currently unknown. In the present study, immunohistochemical analysis was performed to determine Lxn and CD133 expression in 43 PDAC patient samples and in 32 corresponding adjacent non-cancerous samples. The results were analyzed and compared with patient age, gender, tumor site and size, histological grade, clinical stage and overall mean survival time. Lxn expression was clearly decreased in the PDAC tissues compared with that in the adjacent non-cancerous tissues, while CD133 expression was increased. Low Lxn expression in the PDAC tissues was significantly correlated with tumor size (P=0.002), histological grade (P=0.000), metastasis (P=0.007) and clinical stage (P=0.018), but not with age (P=0.451), gender (P=0.395) or tumor site (P=0.697). Kaplan-Meier survival analysis revealed that low Lxn expression was significantly correlated with reduced overall survival time (P=0.000). Furthermore, Lxn expression was found to be inversely correlated with CD133 expression (r=−0.485, P=0.001). Furthermore, CD133-positive MIA PaCa-2 pancreatic tumor cells were sorted by magnetic-activated cell sorting (MACS), and those that overexpressed Lxn exhibited a significantly higher rate of apoptosis and lower proliferative activity. Our findings suggest that Lxn may function as a tumor suppressor that targets CD133-positive pancreatic cancer cells. PMID:26530530

  3. Technical Note: Intrafractional changes in time lag relationship between anterior–posterior external and superior–inferior internal motion signals in abdominal tumor sites

    SciTech Connect

    Regmi, Rajesh; Lovelock, D. Michael; Zhang, Pengpeng; Pham, Hai; Xiong, Jianping; Yorke, Ellen D.; Mageras, Gig S.; Goodman, Karyn A.; Wu, Abraham J.

    2015-06-15

    Purpose: To investigate constancy, within a treatment session, of the time lag relationship between implanted markers in abdominal tumors and an external motion surrogate. Methods: Six gastroesophageal junction and three pancreatic cancer patients (IRB-approved protocol) received two cone-beam CTs (CBCT), one before and one after treatment. Time between scans was less than 30 min. Each patient had at least one implanted fiducial marker near the tumor. In all scans, abdominal displacement (Varian RPM) was recorded as the external motion signal. Purpose-built software tracked fiducials, representing internal signal, in CBCT projection images. Time lag between superior–inferior (SI) internal and anterior–posterior external signals was found by maximizing the correlation coefficient in each breathing cycle and averaging over all cycles. Time-lag-induced discrepancy between internal SI position and that predicted from the external signal (external prediction error) was also calculated. Results: Mean ± standard deviation time lag, over all scans and patients, was 0.10 ± 0.07 s (range 0.01–0.36 s). External signal lagged the internal in 17/18 scans. Change in time lag between pre- and post-treatment CBCT was 0.06 ± 0.07 s (range 0.01–0.22 s), corresponding to 3.1% ± 3.7% (range 0.6%–10.8%) of gate width (range 1.6–3.1 s). In only one patient, change in time lag exceeded 10% of the gate width. External prediction error over all scans of all patients varied from 0.1 ± 0.1 to 1.6 ± 0.4 mm. Conclusions: Time lag between internal motion along SI and external signals is small compared to the treatment gate width of abdominal patients examined in this study. Change in time lag within a treatment session, inferred from pre- to post-treatment measurements is also small, suggesting that a single measurement of time lag at the session start is adequate. These findings require confirmation in a larger number of patients.

  4. Technical Note: Intrafractional changes in time lag relationship between anterior–posterior external and superior–inferior internal motion signals in abdominal tumor sites

    PubMed Central

    Regmi, Rajesh; Lovelock, D. Michael; Zhang, Pengpeng; Pham, Hai; Xiong, Jianping; Yorke, Ellen D.; Goodman, Karyn A.; Wu, Abraham J.; Mageras, Gig S.

    2015-01-01

    Purpose: To investigate constancy, within a treatment session, of the time lag relationship between implanted markers in abdominal tumors and an external motion surrogate. Methods: Six gastroesophageal junction and three pancreatic cancer patients (IRB-approved protocol) received two cone-beam CTs (CBCT), one before and one after treatment. Time between scans was less than 30 min. Each patient had at least one implanted fiducial marker near the tumor. In all scans, abdominal displacement (Varian RPM) was recorded as the external motion signal. Purpose-built software tracked fiducials, representing internal signal, in CBCT projection images. Time lag between superior–inferior (SI) internal and anterior–posterior external signals was found by maximizing the correlation coefficient in each breathing cycle and averaging over all cycles. Time-lag-induced discrepancy between internal SI position and that predicted from the external signal (external prediction error) was also calculated. Results: Mean ± standard deviation time lag, over all scans and patients, was 0.10 ± 0.07 s (range 0.01–0.36 s). External signal lagged the internal in 17/18 scans. Change in time lag between pre- and post-treatment CBCT was 0.06 ± 0.07 s (range 0.01–0.22 s), corresponding to 3.1% ± 3.7% (range 0.6%–10.8%) of gate width (range 1.6–3.1 s). In only one patient, change in time lag exceeded 10% of the gate width. External prediction error over all scans of all patients varied from 0.1 ± 0.1 to 1.6 ± 0.4 mm. Conclusions: Time lag between internal motion along SI and external signals is small compared to the treatment gate width of abdominal patients examined in this study. Change in time lag within a treatment session, inferred from pre- to post-treatment measurements is also small, suggesting that a single measurement of time lag at the session start is adequate. These findings require confirmation in a larger number of patients. PMID:26127033

  5. Morphological spectrum of peripheral nerve sheath tumors: An insight into World Health Organization 2013 classification

    PubMed Central

    Chikkannaiah, Panduranga; Boovalli, Mythri M.; Nathiyal, Velusamy; Venkataramappa, Srinivasamurthy

    2016-01-01

    Introduction: Peripheral nerve sheath tumors (PNSTs) are neuroectodermal in origin. Now these tumors are classified under World Health Organization (WHO) classification of tumors of soft tissue and bone 2013. Objective: To study the morphological spectrum of PNST and to study the secondary degenerative changes associated with it. Materials and Methods: This study was conducted from January 2010 to June 2015. The gross details of tumor and patient's demographic profiles were reviewed. The hematoxylin and eosin stained slides were reassessed and the lesions were categorized and classified as per the WHO 2013 classification. The tumors were also assessed for secondary degenerative changes. Results: Our study comprised 143 cases of PNST. Age of the patients ranged from 5 to 75 years. 21–30 years is the most common age of occurrence with head and neck being the most common site. The PNSTs observed in the present study were neurofibroma (NF) (61.5%), schwannoma (36%), malignant PNST (2%), and granular cell tumor (0.5%). Nearly 10% of NF fulfilled the criteria for neurofibromatosis 1 (NF1). Rare tumors such as plexiform schwannoma and granular cell tumor were also observed. Malignant tumors were larger in dimension than benign. Myxoid, cystic, and hyaline changes were commonly associated with benign tumors while necrosis, hemorrhage, and mitotic activity were seen with malignant tumors. Conclusion: This series highlights the pathological variants of PNST along with their morphological changes and NF1 association. It is essential to be familiar with all these variants of PNST for accurate diagnosis as they have varied biological behavior. PMID:27365950

  6. Assessment of the fish tumor beneficial use impairment in brown bullhead (Ameiurus nebulosus) at selected Great Lakes Areas of Concern

    USGS Publications Warehouse

    Blazer, Vicki; Mazik, Patricia M.; Iwanowicz, Luke R.; Braham, Ryan P.; Hahn, Cassidy M.; Walsh, Heather L.; Sperry, Adam J.

    2014-01-01

    A total of 878 adult Brown Bullhead were collected at 11 sites within the Lake Erie and Lake Ontario drainages from 2011 to 2013. The sites included seven Areas of Concern (AOC; 670 individuals), one delisted AOC (50 individuals) and three non-AOC sites (158 individuals) used as reference sites. These fish were used to assess the “fish tumor or other deformities” beneficial use impairment. Fish were anesthetized, weighed, measured and any external abnormalities documented and removed. Abnormal orocutaneous and barbel tissue, as well as five to eight pieces of liver, were preserved for histopathological analyses. Otoliths were removed and used for age analyses. Visible external abnormalities included reddened (raised or eroded), melanistic areas and raised growths on lips, body surface, fins and barbels. Microscopically, these raised growths included papilloma, squamous cell carcinoma, osteoma and osteosarcoma. Proliferative lesions of the liver included bile duct hyperplasia, foci of cellular alteration, bile duct (cholangioma, cholangiocarcinoma) and hepatocellular (adenoma, hepatic cell carcinoma) neoplasia. The two reference sites (Long Point Inner Bay, Conneaut Creek), at which 30 or more bullhead were collected had a skin tumor prevalence of 10% or less and liver tumor prevalence of 4% or less. Presque Isle Bay, recently delisted, had a similar liver tumor prevalence (4%) and slightly higher prevalence (12%) of skin tumors. The prevalence of skin neoplasms was 15% or less at sites in the Black River, Cuyahoga River and Maumee AOCs, while more than 20% of the bullheads from the Rochester Embayment, Niagara River, Detroit River and Ashtabula River AOCs had skin tumors. The prevalence of liver tumors was greater than 4% at all AOC sites except the Old Channel site at the Cuyahoga River AOC, Wolf Creek within the Maumee AOC and the upper and lower sites within the Niagara River AOC.

  7. [Tumors and tumor-like diseases of the carpal bones].

    PubMed

    Baron, J; Scharizer, E

    1987-07-01

    This presentation concerns the findings in 105 tumors or tumor-like lesions in the bones of the carpus. These tumors generally produce complaints which are uncharacteristic and they are quite difficult to recognize on X-ray. Due to this difficulty, there may be many different therapies before the correct final diagnosis is confirmed. These tumors are usually found in the scaphoid, capitate, lunate, or hamate. Of the 105 tumors, 45.7% were osteoid osteoma, which has an incidence of only 11.33% of all bone tumors in the body as a whole. Of the remaining tumors, 15.24% were diagnoses to be intraosseous ganglia (= tumorlike lesions). Lesser percentages were giant-cell tumors, osteochondromas, chondromas. One intraosseous lipoma was found and this had never before been reported. The majority of the patients were between twenty and thirty years of age. With surgical removal, complaints are generally reduced. Dramatic relief from pain is reported by patients when an osteoid osteoma is removed. The most important deduction from these findings is that tumors in the carpus are not as rare as once assumed. The possibility of bone tumors should be considered in patients with intractable pain in the carpus. PMID:3623270

  8. Macrophage Diversity Enhances Tumor Progression and Metastasis

    PubMed Central

    Qian, Binzhi; Pollard, Jeffrey W.

    2016-01-01

    There is persuasive clinical and experimental evidence that macrophages promote cancer initiation and malignant progression. During tumor initiation they create an inflammatory environment that is mutagenic and which promotes growth. As tumors progress to malignancy, macrophages stimulate angiogenesis, enhance tumor cell migration, invasion, and suppress anti-tumor immunity. At metastatic sites macrophages prepare the target tissue for arrival of tumor cells and then a different subpopulation of macrophages promotes tumor cell extravasation, survival, and subsequent growth. Specialized subpopulations of macrophages may represent important new therapeutic targets. PMID:20371344

  9. A novel protein kinase D phosphorylation site in the tumor suppressor Rab interactor 1 is critical for coordination of cell migration

    PubMed Central

    Ziegler, Susanne; Eiseler, Tim; Scholz, Rolf-Peter; Beck, Alexander; Link, Gisela; Hausser, Angelika

    2011-01-01

    The multifunctional signal adapter protein Ras and Rab interactor 1 (RIN1) is a Ras effector protein involved in the regulation of epithelial cell processes such as cell migration and endocytosis. RIN1 signals via two downstream pathways, namely the activation of Rab5 and Abl family kinases. Protein kinase D (PKD) phosphorylates RIN1 at serine 351 in vitro, thereby regulating interaction with 14–3-3 proteins. Here, we report the identification of serine 292 in RIN1 as an in vivo PKD phosphorylation site. PKD-mediated phosphorylation at this site was confirmed with a phospho-specific antibody and by mass spectrometry. We demonstrate that phosphorylation at serine 292 controls RIN1-mediated inhibition of cell migration by modulating the activation of Abl kinases. We further provide evidence that RIN1 in vivo phosphorylation at serine 351 occurs independently of PKD. Collectively, our data identify a novel PKD signaling pathway through RIN1 and Abl kinases that is involved in the regulation of actin remodeling and cell migration. PMID:21209314

  10. Vascular Tumors

    PubMed Central

    Sepulveda, Abel; Buchanan, Edward P.

    2014-01-01

    Vascular anomalies are divided into two main groups: tumors and malformations. Vascular tumors are a large and complex group of lesions, especially for clinicians with none or little experience in this field. In the past, these lesions caused a great deal of confusion because many appear analogous to the naked eye. Thankfully, recent advances in diagnostic techniques have helped the medical community to enhance our comprehension, accurately label, diagnose, and treat these lesions. In this article, we will review the most frequent vascular tumors and provide the reader with the tools to properly label, diagnose, and manage these complex lesions. PMID:25045329

  11. 78 FR 52984 - Stone Age Interiors, Inc.; d/b/a Colorado Springs Marble and Granite Including On-Site Leased...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-08-27

    ... Employment and Training Administration Stone Age Interiors, Inc.; d/b/a Colorado Springs Marble and Granite... former workers of Stone Age Interiors, Inc., d/b/a Colorado Springs Marble and Granite, Colorado Springs... investigation, I determine that workers of Stone Age Interiors, Inc., d/b/a Colorado Springs Marble and...

  12. Hypothalamic tumor

    MedlinePlus

    ... in the brain to reduce spinal fluid pressure. Risks of radiation therapy include damage to healthy brain cells when tumor cells are destroyed. Common side effects from chemotherapy include loss of appetite, nausea and vomiting, and fatigue.

  13. Brain Tumors

    MedlinePlus

    ... brain. Brain tumors can be benign, with no cancer cells, or malignant, with cancer cells that grow quickly. Some are primary brain ... targeted therapy. Targeted therapy uses substances that attack cancer cells without harming normal cells. Many people get ...

  14. Wilms Tumor

    MedlinePlus

    ... diagnosis, and the condition, or histology , of the cancer cells when observed under a microscope. "Favorable" histology is associated with a good chance of a cure; tumors with "unfavorable" histology are more aggressive and ...

  15. Tumor Markers

    MedlinePlus

    ... types: Germ cell tumors, lymphoma, leukemia, melanoma, and neuroblastoma Tissue analyzed: Blood How used: To assess stage, ... NSE) Cancer types: Small cell lung cancer and neuroblastoma Tissue analyzed: Blood How used: To help in ...

  16. Wilms tumor

    MedlinePlus

    ... this tumor in most children is unknown. A missing iris of the eye (aniridia) is a birth ... Nausea Swelling in the abdomen (abdominal hernia or mass) Vomiting Exams and Tests The doctor or nurse ...

  17. Synergistic Induction of Endothelin-1 by Tumor Necrosis Factor α and Interferon γ Is due to Enhanced NF-κB Binding and Histone Acetylation at Specific κB Sites

    PubMed Central

    Wort, Stephen J.; Ito, Misako; Chou, Pai-Chien; Mc Master, Shaun K.; Badiger, Rekha; Jazrawi, Elen; de Souza, Patricia; Evans, Timothy W.; Mitchell, Jane A.; Pinhu, Liao; Ito, Kaz; Adcock, Ian M.

    2009-01-01

    Endothelin-1 (ET-1) is a potent vasoconstrictor and co-mitogen for vascular smooth muscle and is implicated in pulmonary vascular remodeling and the development of pulmonary arterial hypertension. Vascular smooth muscle is an important source of ET-1. Here we demonstrate synergistic induction of preproET-1 message RNA and release of mature peptide by a combination of tumor necrosis factor α (TNFα) and interferon γ (IFNγ) in primary human pulmonary artery smooth muscle cells. This induction was prevented by pretreatment with the histone acetyltransferase inhibitor anacardic acid. TNFα induced a rapid and prolonged pattern of nuclear factor (NF)-κB p65 subunit activation and binding to the native preproET-1 promoter. In contrast, IFNγ induced a delayed activation of interferon regulatory factor-1 without any effect on NF-κB p65 nuclear localization or consensus DNA binding. However, we found cooperative p65 binding and histone H4 acetylation at distinct κB sites in the preproET-1 promoter after stimulation with both TNFα and IFNγ. This was associated with enhanced recruitment of RNA polymerase II to the ATG start site and read-through of the ET-1 coding region. Understanding such mechanisms is crucial in determining the key control points in ET-1 release. This has particular relevance to developing novel treatments targeted at the inflammatory component of pulmonary vascular remodeling. PMID:19592490

  18. Brain tumors in infants

    PubMed Central

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

    2015-01-01

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

  19. Neuroimaging of spine tumors.

    PubMed

    Pinter, Nandor K; Pfiffner, Thomas J; Mechtler, Laszlo L

    2016-01-01

    Intramedullary, intradural/extramedullary, and extradural spine tumors comprise a wide range of neoplasms with an even wider range of clinical symptoms and prognostic features. Magnetic resonance imaging (MRI), commonly used to evaluate the spine in patients presenting with pain, can further characterize lesions that may be encountered on other imaging studies, such as bone scintigraphy or computed tomography (CT). The advantage of the MRI is its multiplane capabilities, superior contrast agent resolution, and flexible protocols that play an important role in assessing tumor location, extent in directing biopsy, in planning proper therapy, and in evaluating therapeutic results. A multimodality approach can be used to fully characterize the lesion and the combination of information obtained from the different modalities usually narrows the diagnostic possibilities significantly. The diagnosis of spinal tumors is based on patient age, topographic features of the tumor, and lesion pattern, as seen at CT and MRI. The shift to high-end imaging incorporating diffusion-weighted imaging, diffusion tensor imaging, magnetic resonance spectroscopy, whole-body short tau inversion recovery, positron emission tomography, intraoperative and high-field MRI as part of the mainstream clinical imaging protocol has provided neurologists, neuro-oncologists, and neurosurgeons a window of opportunity to assess the biologic behavior of spine neoplasms. This chapter reviews neuroimaging of spine tumors, primary and secondary, discussing routine and newer modalities that can reduce the significant morbidity associated with these neoplasms. PMID:27430436

  20. Sleep and Aging: Insomnia

    MedlinePlus

    ... this page please turn Javascript on. Sleep and Aging Insomnia Insomnia is the most common sleep complaint ... us | contact us | site map National Institute on Aging | U.S. National Library of Medicine | National Institutes of ...

  1. A rare case of extraskeletal Ewing's sarcoma/primitive neuroectodermal tumor developing in maxillary sinus of an old patient.

    PubMed

    Kulkarni, Maithili Mandar; Khandeparkar, Siddhi Gaurish Sinai; Joshi, Avinash R; Barpande, Chitrangi

    2016-01-01

    Ewing's sarcoma/primitive neuroectodermal tumor (ES/PNET) family of tumors is an uncommon group of malignant neoplasms that may present in both skeletal and extraskeletal sites. PNET outside the central nervous system is called peripheral PNET (pPNET) developing from migrating embryonal cells of the neural crest. Very few cases of pPNET of the maxilla are reported in English literature. These tumors may be difficult to diagnose due to their primitive morphology. These tumors occur predominantly in infancy or early childhood. The occurrence of extraskeletal ES/PNET in the maxillary sinus in an old age is very rare. We report a case of extraskeletal ES/PNET developing in maxillary sinus in a 60-year-old woman. The ES/PNET should be included in the differential diagnosis of a small round cell tumor and immunohistochemical analysis with a panel of immunomarkers should be done for correct diagnosis and proper treatment. PMID:27601837

  2. A rare case of extraskeletal Ewing's sarcoma/primitive neuroectodermal tumor developing in maxillary sinus of an old patient

    PubMed Central

    Kulkarni, Maithili Mandar; Khandeparkar, Siddhi Gaurish Sinai; Joshi, Avinash R; Barpande, Chitrangi

    2016-01-01

    Ewing's sarcoma/primitive neuroectodermal tumor (ES/PNET) family of tumors is an uncommon group of malignant neoplasms that may present in both skeletal and extraskeletal sites. PNET outside the central nervous system is called peripheral PNET (pPNET) developing from migrating embryonal cells of the neural crest. Very few cases of pPNET of the maxilla are reported in English literature. These tumors may be difficult to diagnose due to their primitive morphology. These tumors occur predominantly in infancy or early childhood. The occurrence of extraskeletal ES/PNET in the maxillary sinus in an old age is very rare. We report a case of extraskeletal ES/PNET developing in maxillary sinus in a 60-year-old woman. The ES/PNET should be included in the differential diagnosis of a small round cell tumor and immunohistochemical analysis with a panel of immunomarkers should be done for correct diagnosis and proper treatment. PMID:27601837

  3. Role of tumor associated macrophages in tumor angiogenesis and lymphangiogenesis

    PubMed Central

    Riabov, Vladimir; Gudima, Alexandru; Wang, Nan; Mickley, Amanda; Orekhov, Alexander; Kzhyshkowska, Julia

    2014-01-01

    Tumor angiogenesis is an essential process for supplying rapidly growing malignant tissues with essential nutrients and oxygen. An angiogenic switch allows tumor cells to survive and grow, and provides them access to vasculature resulting in metastatic disease. Monocyte-derived macrophages recruited and reprogrammed by tumor cells serve as a major source of angiogenic factors boosting the angiogenic switch. Tumor endothelium releases angiopoietin-2 and further facilitates recruitment of TIE2 receptor expressing monocytes (TEM) into tumor sites. Tumor-associated macrophages (TAM) sense hypoxia in avascular areas of tumors, and react by production of angiogenic factors such as VEGFA. VEGFA stimulates chemotaxis of endothelial cells (EC) and macrophages. In some tumors, TAM appeared to be a major source of MMP9. Elevated expression of MMP9 by TAM mediates extracellular matrix (ECM) degradation and the release of bioactive VEGFA. Other angiogenic factors released by TAM include basic fibroblast growth factor (bFGF), thymidine phosphorylase (TP), urokinase-type plasminogen activator (uPA), and adrenomedullin (ADM). The same factors used by macrophages for the induction of angiogenesis [like vascular endothelial growth factor A (VEGF-A) and MMP9] support lymphangiogenesis. TAM can express LYVE-1, one of the established markers of lymphatic endothelium. TAM support tumor lymphangiogenesis not only by secretion of pro-lymphangiogenic factors but also by trans-differentiation into lymphatic EC. New pro-angiogenic factor YKL-40 belongs to a family of mammalian chitinase-like proteins (CLP) that act as cytokines or growth factors. Human CLP family comprises YKL-40, YKL-39, and SI-CLP. Production of all three CLP in macrophages is antagonistically regulated by cytokines. It was recently established that YKL-40 induces angiogenesis in vitro and in animal tumor models. YKL-40-neutralizing monoclonal antibody blocks tumor angiogenesis and progression. The role of YKL-39 and SI

  4. [Craniosinusonasal tumors].

    PubMed

    Blagoveshchenskaia, N S; Egorova, V K

    1997-01-01

    Tumors extending into the nasal cavity, cranium, and paranasal sinuses have a number of distinctive features to take into consideration. Among them are the communication with an open air, high incidence of associated intracranial infections, specific complications (i.e. suppurative sinusitis, polyps, mucocele, pneumocephalus, nasal CSF leak). The features mentioned make these lesions unique. 50 consecutive patients underwent treatment in Burdenko Neurosurgical Institute. The diagnosis was confirmed either by CT, MRI, or at operation. Rhinological and otoneurological signs were also subjected to analysis. Most frequently these tumors (the majority of which were meningiomas (n = 34) extended into the nasal cavity (40 patients) and paranasal sinuses (n = 50). It was noted that the clinical signs vary depending on the histological type of tumor, its location and direction of growth (i.e. medial or lateral). Medially growing tumors usually involved 2-4 sinuses, while laterally growing tumors involved only one sinus. Among the symptoms, disturbances of smell, conductive hearing impairment, deformation of both the soft and hard palate, slowing of the experimental nystagmus due to disturbed extraocular movements. Some light is shed on the differential diagnosis, indications for various surgical approaches (transcranial, transnasal, and facial). The results of surgical treatment and postoperative complications are presented in the paper. The diagnosis and treatment of such patients require an interdisciplinary approach while would involve a team of a neurosurgeon, neuroradiologist, otoneurologist, and a neuro-ophthalmologist. PMID:9424946

  5. Tumor-associated macrophages: from mechanisms to therapy

    PubMed Central

    Noy, Roy; Pollard, Jeffrey W.

    2014-01-01

    The tumor microenvironment is a complex ecology of cells that evolves with and provides support to tumor cells during the transition to malignancy. Among the innate and adaptive immune cells recruited to the tumor site, macrophages are particularly abundant and are present at all stages of tumor progression. Clinical studies and experimental mouse models indicate these macrophages generally play a pro-tumoral role. In the primary tumor, macrophage can stimulate angiogenesis and enhance tumor cell invasion, motility and intravasation. During metastasis, macrophages prime the pre-metastatic site and promote tumor cell extravasation, survival and persistent growth. Macrophages are also immunosuppressive preventing tumor cell attack by natural killer and T cells during tumor progression and after recovery from chemo- or immuno-therapy. Therapeutic success in targeting these pro-tumoral roles in pre-clinical models and in early clinical trials suggests that macrophages are attractive targets as part of combination therapy in cancer treatment. PMID:25035953

  6. 78 FR 37586 - Stone Age Interiors, Inc., D/B/A Colorado Springs Marble and Granite, Including On-Site Leased...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-06-21

    ... Determination was published in the Federal Register on May 15, 2013 (78 FR 28628-28630). Workers at the subject... Employment and Training Administration Stone Age Interiors, Inc., D/B/A Colorado Springs Marble and Granite... former workers of Stone Age Interiors, Inc., d/b/a Colorado Springs Marble and Granite, Colorado...

  7. [Thymic tumors].

    PubMed

    Le Péchoux, C; Mahé, M; Bretel, J-J; Roberti, E; Ruffié, P

    2005-11-01

    Thymomas and thymic carcinomas are rare and slow-growing tumors, which develop within the anterior mediastinum. Thymomas are often associated with autoimmune disorders and most particularly myasthenia gravis. The treatment of choice remains a complete surgical resection. Postoperative radiotherapy is often combined in case of invasive thymoma invading into adjacent organs. Postoperative radiotherapy in stage II with invasion into capsule has been more controversial lately. In inoperable locally advanced, or metastatic thymic tumors, neoadjuvant cisplatin-based followed by surgery and radiotherapy has given interesting results in the past years. PMID:16168694

  8. Ovarian tumors of the hen.

    PubMed Central

    Fredrickson, T N

    1987-01-01

    Present available information regarding ovarian tumors in hens is incomplete in most aspects, and this lack of knowledge hampers use of hens as models for study of ovarian cancer. A study of 466 hens ranging from 2 to 7 years of age and covering a period of more than 3 years has provided much needed information relative to reproductive tract neoplasia. On the basis of this study, it is apparent that hens have a high rate of ovarian tumors, but that such tumors are uncommon in hens less than 2 years of age. Adenocarcinomas with a high degree of morphologic variability are the most common ovarian tumors in hens. Hormonal imbalance does not appear to be a factor in the development of these adenocarcinomas. Steroidogenic and morphologically distinctive granulosa cell tumors originating from follicles in atrophic ovaries represent another common ovarian tumor type. Unique to the hen are oviductal adenocarcinomas. These tumors arise from the albumin-secreting glands of the oviduct, occur with relatively high frequency, and must be differentiated from ovarian adenocarcinomas. Images PLATE 1. PLATE 2. PLATE 3. PLATE 4. PLATE 5. PLATE 6. PLATE 7. PLATE 8. PLATE 9. PLATE 10. PLATE 11. PLATE 12. PLATE 13. PLATE 14. PLATE 15. PLATE 16. PLATE 17. PLATE 18. PLATE 19. PLATE 20. PLATE 21. PLATE 22. PLATE 23. PLATE 24. PLATE 25. PMID:3665870

  9. Superior sulcus tumors (Pancoast tumors)

    PubMed Central

    Battistella, Lucia; Mammana, Marco; Calabrese, Francesca; Rea, Federico

    2016-01-01

    Superior Sulcus Tumors, frequently termed as Pancoast tumors, are a wide range of tumors invading the apical chest wall. Due to its localization in the apex of the lung, with the potential invasion of the lower part of the brachial plexus, first ribs, vertebrae, subclavian vessels or stellate ganglion, the superior sulcus tumors cause characteristic symptoms, like arm or shoulder pain or Horner’s syndrome. The management of superior sulcus tumors has dramatically evolved over the past 50 years. Originally deemed universally fatal, in 1956, Shaw and Paulson introduced a new treatment paradigm with combined radiotherapy and surgery ensuring 5-year survival of approximately 30%. During the 1990s, following the need to improve systemic as well as local control, a trimodality approach including induction concurrent chemoradiotherapy followed by surgical resection was introduced, reaching 5-year survival rates up to 44% and becoming the standard of care. Many efforts have been persecuted, also, to obtain higher complete resection rates using appropriate surgical approaches and involving multidisciplinary team including spine surgeon or vascular surgeon. Other potential treatment options are under consideration like prophylactic cranial irradiation or the addition of other chemotherapy agents or biologic agents to the trimodality approach. PMID:27429965

  10. Superior sulcus tumors (Pancoast tumors).

    PubMed

    Marulli, Giuseppe; Battistella, Lucia; Mammana, Marco; Calabrese, Francesca; Rea, Federico

    2016-06-01

    Superior Sulcus Tumors, frequently termed as Pancoast tumors, are a wide range of tumors invading the apical chest wall. Due to its localization in the apex of the lung, with the potential invasion of the lower part of the brachial plexus, first ribs, vertebrae, subclavian vessels or stellate ganglion, the superior sulcus tumors cause characteristic symptoms, like arm or shoulder pain or Horner's syndrome. The management of superior sulcus tumors has dramatically evolved over the past 50 years. Originally deemed universally fatal, in 1956, Shaw and Paulson introduced a new treatment paradigm with combined radiotherapy and surgery ensuring 5-year survival of approximately 30%. During the 1990s, following the need to improve systemic as well as local control, a trimodality approach including induction concurrent chemoradiotherapy followed by surgical resection was introduced, reaching 5-year survival rates up to 44% and becoming the standard of care. Many efforts have been persecuted, also, to obtain higher complete resection rates using appropriate surgical approaches and involving multidisciplinary team including spine surgeon or vascular surgeon. Other potential treatment options are under consideration like prophylactic cranial irradiation or the addition of other chemotherapy agents or biologic agents to the trimodality approach. PMID:27429965

  11. Locoregional Tumor Progression After Radiation Therapy Influences Overall Survival in Pediatric Patients With Neuroblastoma

    SciTech Connect

    Pai Panandiker, Atmaram S.; McGregor, Lisa; Krasin, Matthew J.; Wu Shengjie; Xiong Xiaoping; Merchant, Thomas E.

    2010-03-15

    Purpose: There is renewed attention to primary site irradiation and local control for patients with high-risk neuroblastoma (NB). We conducted a retrospective review to identify factors that might predict for locoregional tumor control and its impact on overall survival. Methods and Materials: Between July 2000 through August 2006, a total of 44 pediatric patients with NB received radiation therapy (RT) with curative intent using computed tomography (CT)-based treatment planning. The median age was 3.4 years and the median cumulative dose was 23.4 Gy. Overall survival and locoregional tumor control were measured from the start of RT to the date of death or event as determined by CT/magnetic resonance imaging/meta-iodobenzylguanidine. The influence of age at irradiation, gender, race, cumulative radiation dose, International Neuroblastoma Staging System stage, treatment protocol and resection status was determined with respect to locoregional tumor control. Results: With a median follow-up of 34 months +- 21 months, locoregional tumor progression was observed in 11 (25%) and was evenly divided between primary site and adjacent nodal/visceral site failure. The influence of locoregional control reached borderline statistical significance (p = 0.06). Age (p = 0.5), dose (p = 0.6), resection status (p = 0.7), and International Neuroblastoma Staging System stage (p = 0.08) did not influence overall survival. Conclusions: Overall survival in high-risk neuroblastoma is influenced by locoregional tumor control. Despite CT-based planning, progression in adjacent nodal/visceral sites appears to be common; this requires further investigation regarding target volume definitions, dose, and the effects of systemic therapy.

  12. Biology and Treatment of Rhabdoid Tumor.

    PubMed

    Geller, James I; Roth, Jacquelyn J; Biegel, Jaclyn A

    2015-01-01

    Rhabdoid tumor is a rare, highly aggressive malignancy that primarily affects infants and young children. These tumors typically arise in the brain and kidney, although extrarenal, non-central nervous system tumors in almost all soft-tissue sites have been described. SMARCB1 is a member of the SWI/SNF chromatin-remodeling complex and functions as a tumor suppressor in the vast majority of rhabdoid tumors. Patients with germline mutations or deletions affecting SMARCB1 are predisposed to the development of rhabdoid tumors, as well as the genetic disorder schwannomatosis. The current hypothesis is that rhabdoid tumors are driven by epigenetic dysregulation, as opposed to the alteration of a specific biologic pathway. The strategies for novel therapeutic approaches based on what is currently known about rhabdoid tumor biology are presented. PMID:26349416

  13. Expression of Advanced Glycation End-Products on Sun-Exposed and Non-Exposed Cutaneous Sites during the Ageing Process in Humans

    PubMed Central

    Crisan, Maria; Taulescu, Marian; Crisan, Diana; Cosgarea, Rodica; Parvu, Alina; Cãtoi, Cornel; Drugan, Tudor

    2013-01-01

    The glycation process is involved in both the intrinsic (individual, genetic) and extrinsic (ultraviolet light, polution and lifestyle) aging processes, and can be quantified at the epidermal or dermal level by histological, immunohistochemical (IHC), or imagistic methods. Our study is focused on a histological and immunohistological comparison of sun-protected regions versus sun-exposed regions from different age groups of skin phototype III subjects, related to the aging process. Skin samples collected from non-protected and UV protected regions of four experimental groups with different ages, were studied using histology and IHC methods for AGE-CML [N(epsilon)-(carboxymethyl)lysine]. A semi-quantitative assessment of the CML expression in the microvascular endothelium and dermal fibroblasts was performed. The Pearson one-way ANOVA was used to compare data between the groups. In the dermis of sun-exposed skin, the number and the intensity of CML positive cells in both fibroblasts and endothelial cells (p<0.05) was higher compared to sun-protected skin, and was significantly increased in older patients. The sun-exposed areas had a more than 10% higher AGE-CML score than the protected areas. No statistically significant correlation was observed between the histological score and the IHC expression of CML. We concluded that in healthy integument, the accumulation of final glycation products increases with age and is amplified by ultraviolet exposure. The study provides new knowledge on differences of AGE-CML between age groups and protected and unprotected areas and emphasizes that endothelium and perivascular area are most affected, justifying combined topical and systemic therapies. PMID:24116020

  14. Expression of advanced glycation end-products on sun-exposed and non-exposed cutaneous sites during the ageing process in humans.

    PubMed

    Crisan, Maria; Taulescu, Marian; Crisan, Diana; Cosgarea, Rodica; Parvu, Alina; Cãtoi, Cornel; Drugan, Tudor

    2013-01-01

    The glycation process is involved in both the intrinsic (individual, genetic) and extrinsic (ultraviolet light, polution and lifestyle) aging processes, and can be quantified at the epidermal or dermal level by histological, immunohistochemical (IHC), or imagistic methods. Our study is focused on a histological and immunohistological comparison of sun-protected regions versus sun-exposed regions from different age groups of skin phototype III subjects, related to the aging process. Skin samples collected from non-protected and UV protected regions of four experimental groups with different ages, were studied using histology and IHC methods for AGE-CML [N(epsilon)-(carboxymethyl)lysine]. A semi-quantitative assessment of the CML expression in the microvascular endothelium and dermal fibroblasts was performed. The Pearson one-way ANOVA was used to compare data between the groups. In the dermis of sun-exposed skin, the number and the intensity of CML positive cells in both fibroblasts and endothelial cells (p<0.05) was higher compared to sun-protected skin, and was significantly increased in older patients. The sun-exposed areas had a more than 10% higher AGE-CML score than the protected areas. No statistically significant correlation was observed between the histological score and the IHC expression of CML. We concluded that in healthy integument, the accumulation of final glycation products increases with age and is amplified by ultraviolet exposure. The study provides new knowledge on differences of AGE-CML between age groups and protected and unprotected areas and emphasizes that endothelium and perivascular area are most affected, justifying combined topical and systemic therapies. PMID:24116020

  15. Pituitary Tumors

    MedlinePlus

    ... org Tel: 773-577-8750; 800-886-2282 Fax: 847-827-9918 National Brain Tumor Society 55Chapel ... http://www.braintumor.org Tel: 866-455-3214 Fax: 617-924-9998 Pituitary Network Association P.O. ...

  16. Plutonium aging

    SciTech Connect

    Olivas, J.D.

    1999-03-01

    The author describes the plutonium aging program at the Los Alamos National Laboratory. The aging of plutonium components in the US nuclear weapons stockpile has become a concern due to several events: the end of the cold war, the cessation of full scale underground nuclear testing as a result of the Comprehensive Test Ban Treaty (CTBT) and the closure of the Rocky Flats Plant--the site where the plutonium components were manufactured. As a result, service lifetimes for nuclear weapons have been lengthened. Dr. Olivas will present a brief primer on the metallurgy of plutonium, and will then describe the technical approach to ascertaining the long-term changes that may be attributable to self-radiation damage. Facilities and experimental techniques which are in use to study aging will be described. Some preliminary results will also be presented.

  17. Revised Risk Classification for Pediatric Extracranial Germ Cell Tumors Based on 25 Years of Clinical Trial Data From the United Kingdom and United States

    PubMed Central

    Frazier, A. Lindsay; Hale, Juliet P.; Rodriguez-Galindo, Carlos; Dang, Ha; Olson, Thomas; Murray, Matthew J.; Amatruda, James F.; Thornton, Claire; Arul, G. Suren; Billmire, Deborah; Shaikh, Furqan; Pashankar, Farzana; Stoneham, Sara; Krailo, Mark; Nicholson, James C.

    2015-01-01

    Purpose To risk stratify malignant extracranial pediatric germ cell tumors (GCTs). Patients and Methods Data from seven GCT trials conducted by the Children's Oncology Group (United States) or the Children's Cancer and Leukemia Group (United Kingdom) between 1985 and 2009 were merged to create a data set of patients with stage II to IV disease treated with platinum-based therapy. A parametric cure model was used to evaluate the prognostic importance of age, tumor site, stage, histology, tumor markers, and treatment regimen and estimate the percentage of patients who achieved long-term disease-free (LTDF) survival in each subgroup of the final model. Validation of the model was conducted using the bootstrap method. Results In multivariable analysis of 519 patients with GCTs, stage IV disease (P = .001), age ≥ 11 years (P < .001), and tumor site (P < .001) were significant predictors of worse LTDF survival. Elevated alpha-fetoprotein (AFP) ≥ 10,000 ng/mL was associated with worse outcome, whereas pure yolk sac tumor (YST) was associated with better outcome, although neither met criteria for statistical significance. The analysis identified a group of patients age > 11 years with either stage III to IV extragonadal tumors or stage IV ovarian tumors with predicted LTDF survival < 70%. A bootstrap procedure showed retention of age, tumor site, and stage in > 94%, AFP in 12%, and YST in 27% of the replications. Conclusion Clinical trial data from two large national pediatric clinical trial organizations have produced a new evidence-based risk stratification of malignant pediatric GCTs that identifies a poor-risk group warranting intensified therapy. PMID:25452439

  18. Gastrointestinal Stromal Tumors: A Case Report

    PubMed Central

    Sashidharan, Palankezhe; Matele, Apoorva; Matele, Usha; Al Felahi, Nowfel; Kassem, Khalid F.

    2014-01-01

    Advances in the identification of gastrointestinal stromal tumors, its molecular and immunohiostochemical basis, and its management have been a watershed in the treatment of gastrointestinal tumors. This paradigm shift occurred over the last two decades and gastrointestinal stromal tumors have now come to be understood as rare gastrointestinal tract tumors with predictable behavior and outcome, replacing the older terminologies like leiomyoma, schwannoma or leiomyosarcoma. This report presents a case of gastric gastrointestinal stromal tumor operated recently in a 47-year-old female patient and the outcome, as well as literature review of the pathological identification, sites of origin, and factors predicting its behavior, prognosis and treatment. PMID:24715944

  19. [Mediastinal germ cell tumors].

    PubMed

    Bremmer, F; Ströbel, P

    2016-09-01

    The mediastinum is among the most frequent anatomic region in which germ cell tumors (GCT) arise, second only to the gonads. Mediastinal GCT (mGCT) account for 16 % of all mediastinal neoplasms. Although the morphology and (according to all available data) the molecular genetics of mediastinal and gonadal GCT are identical, a number of unique aspects exist. There is a highly relevant bi-modal age distribution. In pre-pubertal children of both sexes, mGCT consist exclusively of teratomas and yolk sac tumors. The prognosis is generally favorable with modern treatment. In post-pubertal adults, virtually all patients with malignant mGCT are males; the prognosis is more guarded and depends (among other factors) on the histological GCT components and is similar to GCT in other organs. So-called somatic type malignancies (i. e. clonally related, non-germ cell neoplasias arising in a GCT) are much more frequent in mGCT than in other organs, and the association between mediastinal yolk sac tumors and hematological malignancies, such as myelodysplasias and leukemias, is unique to mediastinal tumors. The prognosis of GCT with somatic type malignancies is generally dismal. PMID:27491549

  20. Phyllodes tumor of the breast

    PubMed Central

    Herazo, Fernando; Gil, Monica; Echeverri, Carolina; Ángel, Gonzalo; Borrero, Mauricio; Madrid, Jorge; Jaramillo, Ricardo

    2015-01-01

    Introduction: Breast Phyllodes tumors are rare breast tumors present in less than 1% of new cases of breast cancer, usually occurring among middle-aged women (40-50 yrs). Objective: This study shows diagnostic experience, surgical management and follows up of patients with this disease during a period of ten years in a oncology referral center. Methods: Retrospectively, breast cancer registries at the institution were reviewed, identifying 77 patients with Phyllodes tumors between 2002 and 2012, who had been operated on at the Instituto de Cancerología - Clínica Las Américas, in Medellín (Colombia). Clinical and histopathological data belonging to these cases was captured and analyzed and descriptive statistics were used. Results: The follow up median was 22.5 months (IQR: 10.5-60.0), average age was 47.2 yrs (SD: 12.4), mean tumor size was 3.6 cm (SD: 4.6), 88.3% of the patients (68 cases) presented negative margins and none of them received adjuvant chemotherapy. Of the patients with Phyllodes tumors; 33.8% had benign, 31.2% had borderline and 35.0% had malignant tumor. Disease-free survival was 85.8% and overall survival was 94.5%. Discussion: Reported data in this article is in accordance with what has been reported in worldwide literature. In our cohort even the high mean size of the tumors, the risk of local relapse and metastatic disease is low than previously reported in literature. Trials with longer follow up and molecular trials in Phyllodes tumors are necessary to understand the behavior of these tumors in Hispanics population. PMID:26600624

  1. Age Offsets of the Matuyama-Brunhes Polarity Transition in Records From the Atlantic: Lock-in Depth Variations or Site Dependent Field Behavior?

    NASA Astrophysics Data System (ADS)

    Clement, B. M.; Acton, G.; Lund, S.; Okada, M.; Williams, T.

    2004-12-01

    A number of high -resolution Matuyama-Brunhes transitions have recently been obtained from deep-sea sediments in the Atlantic Ocean. Three of these transition records were obtained from sites on the Blake-Bahama Outer Ridge and the Bermuda Rise as part of depth transect drilled during ODP Leg 172. The polarity transition records from these sites are remarkably similar, both during the reversal and in excursions that occurred prior to the reversal. Previous work has shown that in this region initial magnetic susceptibility records provide a useful proxy for marine isotopic stages. However, using the shipboard susceptibility records as a correlation tool, it becomes apparent that while the transition records exhibit very similar features, these features are offset relative to the susceptibility records at ODP Sites 1060, 1061 and 1063. The distance between Sites 1060 and 1061 is insignificant on a geomagnetic scale, implying that the differences are not likely due to time transgressive field behavior. Instead, the offset of the magnetization record relative to the susceptibility record may result from a difference in the lock-in depths at these sites. A possible explanation is that the different water depths at the sites affect the amount of organic matter that is oxidized before reaching the sea-floor. This in turn would lead to different depths of the redox boundaries within the sediment column. If the remanence lock-in zone is related to processes associated with the redox boundary, the difference in water depths may explain the offsets. To test this hypothesis, we compare the other Matuyama-Brunhes records from the Atlantic with the positions of the reversal relative to the marine isotopic stages, including the record from Site 1083, which was recorded in anoxic sediments.

  2. Akt and Hippo Pathways in Ewing's Sarcoma Tumors and Their Prognostic Significance

    PubMed Central

    Ahmed, Atif A.; Abedalthagafi, Malak; Anwar, Ahmed E.; Bui, Marilyn M.

    2015-01-01

    Background: Ewing's sarcoma tumor is an aggressive malignancy of bone and soft tissue in children and young adults. Despite advances in modern therapy, metastasis occurs and results in high mortality. Intracellular molecules Yap, Akt, mTOR, and Erk are signaling pathway members that regulate the proliferation of tumor cells. Objective and Methods: We studied the immunohistochemical expression of these proteins in 36 tumor samples from adult and pediatric patients with Ewing's sarcoma tumors. Patients' age, sex, tumor site, tumor size, clinical stage and survival (overall and disease-free survival) were collected. Tissue microarrays slides were stained with antibodies against Yap, Akt, mTOR, and Erk proteins. Results: Tumors exhibited variable expression of Yap, Akt, mTOR, and Erk (from negative, low to high), with high levels of expression present in 31%, 53%, 77% and 0% respectively. Immunohistochemical expression of Akt was associated with worse overall and disease-free survival (p<0.05). The other biomarkers did not demonstrate any difference in survival between low versus high expression. Conclusion: Although Yap, Akt, mTOR, and Erk protein are all expressed in Ewing's sarcoma by immunohistochemistry, only Akt expression is associated with worse prognosis. Larger studies are needed to verify these results and plan targeted therapy, particularly against Akt. PMID:26366214

  3. Pediatric and Adolescent Extracranial Germ Cell Tumors: The Road to Collaboration

    PubMed Central

    Olson, Thomas A.; Murray, Matthew J.; Rodriguez-Galindo, Carlos; Nicholson, James C.; Billmire, Deborah F.; Krailo, Mark D.; Dang, Ha M.; Amatruda, James F.; Thornton, Claire M.; Arul, G. Suren; Stoneham, Sara J.; Pashankar, Farzana; Stark, Daniel; Shaikh, Furqan; Gershenson, David M.; Covens, Allan; Hurteau, Jean; Stenning, Sally P.; Feldman, Darren R.; Grimison, Peter S.; Huddart, Robert A.; Sweeney, Christopher; Powles, Thomas; Lopes, Luiz Fernando; dos Santos Agular, Simone; Chinnaswamy, Girish; Khaleel, Sahar; Abouelnaga, Sherif; Hale, Juliet P.; Frazier, A. Lindsay

    2015-01-01

    During the past 35 years, survival rates for children with extracranial malignant germ cell tumors (GCTs) have increased significantly. Success has been achieved primarily through the application of platinum-based chemotherapy regimens; however, clinical challenges in GCTs remain. Excellent outcomes are not distributed uniformly across the heterogeneous distribution of age, histologic features, and primary tumor site. Despite good outcomes overall, the likelihood of a cure for certain sites and histologic conditions is less than 50%. In addition, there are considerable long-term treatment-related effects for survivors. Even modest cisplatin dosing can cause significant long-term morbidities. A particular challenge in designing new therapies for GCT is that a variety of specialists use different risk stratifications, staging systems, and treatment approaches for three distinct age groups (childhood, adolescence, and young adulthood). Traditionally, pediatric cancer patients younger than 15 years have been treated by pediatric oncologists in collaboration with their surgical specialty colleagues. Adolescents and young adults with GCTs often are treated by medical oncologists, urologists, or gynecologic oncologists. The therapeutic dilemma for all is how to best define disease risk so that therapy and toxicity can be appropriately reduced for some patients and intensified for others. Further clinical and biologic insights can only be achieved through collaborations that do not set limitations by age, sex, and primary tumor site. Therefore, international collaborations, spanning different cooperative groups and disciplines, have been developed to address these challenges. PMID:26304902

  4. Pediatric and Adolescent Extracranial Germ Cell Tumors: The Road to Collaboration.

    PubMed

    Olson, Thomas A; Murray, Matthew J; Rodriguez-Galindo, Carlos; Nicholson, James C; Billmire, Deborah F; Krailo, Mark D; Dang, Ha M; Amatruda, James F; Thornton, Claire M; Arul, G Suren; Stoneham, Sara J; Pashankar, Farzana; Stark, Daniel; Shaikh, Furqan; Gershenson, David M; Covens, Allan; Hurteau, Jean; Stenning, Sally P; Feldman, Darren R; Grimison, Peter S; Huddart, Robert A; Sweeney, Christopher; Powles, Thomas; Lopes, Luiz Fernando; dos Santos Agular, Simone; Chinnaswamy, Girish; Khaleel, Sahar; Abouelnaga, Sherif; Hale, Juliet P; Frazier, A Lindsay

    2015-09-20

    During the past 35 years, survival rates for children with extracranial malignant germ cell tumors (GCTs) have increased significantly. Success has been achieved primarily through the application of platinum-based chemotherapy regimens; however, clinical challenges in GCTs remain. Excellent outcomes are not distributed uniformly across the heterogeneous distribution of age, histologic features, and primary tumor site. Despite good outcomes overall, the likelihood of a cure for certain sites and histologic conditions is less than 50%. In addition, there are considerable long-term treatment-related effects for survivors. Even modest cisplatin dosing can cause significant long-term morbidities. A particular challenge in designing new therapies for GCT is that a variety of specialists use different risk stratifications, staging systems, and treatment approaches for three distinct age groups (childhood, adolescence, and young adulthood). Traditionally, pediatric cancer patients younger than 15 years have been treated by pediatric oncologists in collaboration with their surgical specialty colleagues. Adolescents and young adults with GCTs often are treated by medical oncologists, urologists, or gynecologic oncologists. The therapeutic dilemma for all is how to best define disease risk so that therapy and toxicity can be appropriately reduced for some patients and intensified for others. Further clinical and biologic insights can only be achieved through collaborations that do not set limitations by age, sex, and primary tumor site. Therefore, international collaborations, spanning different cooperative groups and disciplines, have been developed to address these challenges. PMID:26304902

  5. Understanding Brain Tumors

    MedlinePlus

    ... to Know About Brain Tumors . What is a Brain Tumor? A brain tumor is an abnormal growth
 ... Tumors” from Frankly Speaking Frankly Speaking About Cancer: Brain Tumors Download the full book Questions to ask ...

  6. Brain tumor - children

    MedlinePlus

    ... children; Neuroglioma - children; Oligodendroglioma - children; Meningioma - children; Cancer - brain tumor (children) ... The cause of primary brain tumors is unknown. Primary brain tumors may ... (spread to nearby areas) Cancerous (malignant) Brain tumors ...

  7. Brain tumor - primary - adults

    MedlinePlus

    ... Vestibular schwannoma (acoustic neuroma) - adults; Meningioma - adults; Cancer - brain tumor (adults) ... Primary brain tumors include any tumor that starts in the brain. Primary brain tumors can start from brain cells, ...

  8. Brain Tumor Diagnosis

    MedlinePlus

    ... Types of Brain Scans X-rays Laboratory Tests DNA Profiling Biopsy Procedure Malignant and Benign Brain Tumors Tumor ... Types of Brain Scans X-rays Laboratory Tests DNA Profiling Biopsy Procedure Malignant and Benign Brain Tumors Tumor ...

  9. Metastatic brain tumor

    MedlinePlus

    Brain tumor - metastatic (secondary); Cancer - brain tumor (metastatic) ... For many people with metastatic brain tumors, the cancer is not curable. It will eventually spread to other areas of the body. Prognosis depends on the type of tumor ...

  10. Identification of the in vivo truncation sites at the C-terminal region of alpha-A crystallin from aged bovine and human lens

    NASA Technical Reports Server (NTRS)

    Takemoto, L. J.; Spooner, B. S. (Principal Investigator)

    1995-01-01

    Total alpha-A crystallin was purified from young versus old lens, followed by digestion with cyanogen bromide. Laser desorption mass spectrometry of the C-terminal fragment demonstrated age-dependent loss of one and five amino acids from the C-terminus of alpha-A crystallin from both bovine and human lens. These results demonstrate specific peptide bonds of alpha-A crystallin are cleaved during the aging process of the normal lens. The C-terminal region is cleaved in two places between the two hydroxyl-containing amino acids present in the sequence -P-S(T)-S-.

  11. Granular Cell Tumor: An Uncommon Benign Neoplasm

    PubMed Central

    Gayen, Tirthankar; Das, Anupam; Shome, Kaushik; Bandyopadhyay, Debabrata; Das, Dipti; Saha, Abanti

    2015-01-01

    Granular cell tumor is a distinctly rare neoplasm of neural sheath origin. It mainly presents as a solitary asymptomatic swelling in the oral cavity, skin, and rarely internal organs in the middle age. Histopathology is characteristic, showing polyhedral cells containing numerous fine eosinophilic granules with indistinct cell margins. We present a case of granular cell tumor on the back of a 48-year-old woman which was painful, mimicking an adnexal tumor. PMID:26120181

  12. Asymptomatic Glomus Tumor of the Mediastinum

    PubMed Central

    Kanakis, Meletios; Rapti, Nikoletta; Chorti, Maria; Lioulias, Achilleas

    2015-01-01

    Glomus tumors are rare benign neoplasms that predominate in limbs. Infrequently, they can occur in a wide anatomic distribution, to include sites not known to contain glomus cells. Although glomus tumors are usually small, pain and tenderness are common clinical symptoms. We report the case of a 69-year-old man with an asymptomatic large mediastinal glomus tumor, who underwent surgical resection. PMID:26442165

  13. Malignant phylloides tumor in pregnancy.

    PubMed

    Blaker, Kristen M; Sahoo, Sunati; Schweichler, Maria R; Chagpar, Anees B

    2010-03-01

    Malignant phylloides tumors are exceedingly rare with few cases being reported in pregnancy. We describe the first case ever reported of a malignant phylloides tumor presenting in the first trimester of pregnancy and provide insight into the complexities of management as well as a review of the known literature. An extensive PubMed literature search for "cystosarcoma," "phylloides," and "pregnancy" was performed. References of each citation were reviewed. Only six previous cases of phylloides tumor in pregnancy were found, none of which were in the first trimester. Medical records of a patient presenting to our institution at 9 weeks gestation with a malignant phylloides tumor were reviewed. We further provide a review of the current literature of the management of phylloides tumor in pregnancy. A 27-year-old white G2P0SA1 woman with no family history of breast cancer presented with a right breast mass at her first prenatal examination at 9 weeks of pregnancy. Ultrasound confirmed a solid mass measuring 24 mm. Core needle biopsy demonstrated a malignant phylloides tumor. She previously had a fibroadenoma removed from the same breast 7 years previously. The current tumor was excised to clear margins. Histopathological examination revealed a 4-cm fibroepithelial tumor with marked stromal cellularity and a high mitotic count (five to seven mitoses/high-power field), confirming the diagnosis of malignant phylloides tumor. The patient continued her pregnancy without complications. Six other cases of phylloides tumor presenting in pregnancy have been reported in the literature, one of which had bilateral disease. Of these, the average patient age was 32 years (range, 28 to 35 years). The majority of these patients presented in their third trimester (mean, 29 weeks; range, 20 to 36 weeks) and often had large tumors (mean, 15 cm; range, 5 to 21 cm). Four of the seven tumors (57%) required a mastectomy. Previous cases have shown phylloides tumors to present in the third

  14. Brain Tumor Symptoms

    MedlinePlus

    ... Types of Tumors Risk Factors Brain Tumor Statistics Brain Tumor Dictionary Webinars Anytime Learning About Us Our Founders Board of Directors Staff ... Types of Tumors Risk Factors Brain Tumor Statistics Brain Tumor Dictionary Webinars Anytime Learning Donate to the ABTA Help advance the understanding ...

  15. Meningeal Solitary Fibrous Tumors with Delayed Extracranial Metastasis

    PubMed Central

    Han, Nayoung; Kim, Hannah; Min, Soo Kee; Paek, Sun-Ha; Park, Chul-Kee; Choi, Seung-Hong; Chae, U-Ri; Park, Sung-Hye

    2016-01-01

    Background: The term solitary fibrous tumor (SFT) is preferred over meningeal hemangiopericytoma (HPC), because NAB2-STAT6 gene fusion has been observed in both intracranial and extracranial HPCs. HPCs are now considered cellular variants of SFTs. Methods: This study analyzes 19 patients with STAT6-confirmed SFTs, who were followed for over 11 years in a single institution. Ten patients (10/19, 56.2%) had extracranial metastases (metastatic group), while the remainder (9/19) did not (non-metastatic group). These two groups were compared clinicopathologically. Results: In the metastatic group, the primary metastatic sites were the lungs (n = 6), bone (n = 4), and liver (n = 3). There was a mean lag time of 14.2 years between the diagnosis of the initial meningeal tumor to that of systemic metastasis. The median age at initial tumor onset was 37.1 years in the metastatic group and 52.5 in the non-metastatic group. The 10-year survival rates of the metastatic- and non-metastatic groups were 100% and 33%, respectively. The significant prognostic factors for poor outcomes on univariate analysis included advanced age (≥45 years) and large initial tumor size (≥5 cm). In contrast, the patients with higher tumor grade, high mitotic rate (≥5/10 high-power fields), high Ki-67 index (≥5%), and the presence of necrosis or CD34 positivity showed tendency of poor prognosis but these parameters were not statistically significant poor prognostic markers. Conclusions: Among patients with SFTs, younger patients (<45 years) experienced longer survival times and paradoxically had more frequent extracranial metastases after long latent periods than did older patients. Therefore, young patients with SFTs require careful surveillance and follow-up for early detection of systemic metastases. PMID:26657311

  16. [Synchronous tumors of the gastrointestinal tract].

    PubMed

    Pătraşcu, Tr; Doran, H; Catrina, E; Mihalache, O; Degeratu, D; Predescu, G

    2010-01-01

    The term "synchronous tumors" is reserved for simultaneous evolution of two or more tumors with distinct sites, in which the possibility that one tumor is a metastasis of the other has been excluded. In medical practice, the involvement of two different cavitary organs of the gastrointestinal tract is very rare. We present two clinical cases of synchronous tumors: one of a malignant degeneration of a colonic polyp, associated to a jejunal tumor; the other of a patient with a gastric adenocarcinoma, who also had a bulky rectal villous tumor. We tried to find out the etiology of the tumors and the frequency of these associations, mentioned in medical literature. Immunohistochemistry investigations, genetic analysis and familial screening must complete an individualized medical approach in which the surgical technique must be adequate for each case. PMID:20405687

  17. How Are Gastrointestinal Stromal Tumors Staged?

    MedlinePlus

    ... spread to nearby lymph nodes (any N). The cancer has spread to distant sites, such as the liver or the lungs (M1). The tumor can have any mitotic rate. Resectable versus unresectable tumors The AJCC staging system provides a detailed summary of how far ...

  18. Aging and Cancer Vaccines

    PubMed Central

    Gravekamp, Claudia; Chandra, Dinesh

    2014-01-01

    Cancer vaccination is less effective at old than at young age, due to T cell unresponsiveness. This is caused by age-related changes of the immune system. Major immune defects at older age are lack of naïve T cells, impaired activation pathways of T cells and antigen-presenting cells (APC), and age-related changes in the tumor microenvironment (TME). Also innate immune responses are affected by aging, but this seems less abundant than adaptive immune responses. In this review we compared various cancer vaccine studies at young and old age, demonstrating the importance of both innate and adaptive immune responses for cancer immunotherapy. Moreover, we found suggestive evidence that innate immune responses could help improve adaptive immune responses through cancer vaccination in old age. PMID:24579737

  19. [Desmoid tumors].

    PubMed

    Montagliani, L; Duverger, V

    2008-01-01

    Desmoid tumors are a rare form of malignancy with a great propensity for local extension and recurrence. They typically occur in the abdominal wall or within the abdomen but also may occur extra-abdominally. Most cases are sporadic but traumatic, hormonal, and genetic etiologies have been implicated. The only curative treatment is wide surgical excision, but the risk of local recurrence is high. Several adjuvant or complementary treatments have been proposed and the results show promise; the authors review all these therapies. PMID:18438278

  20. Intensity-Modulated Arc Therapy for Pediatric Posterior Fossa Tumors

    SciTech Connect

    Beltran, Chris; Gray, Jonathan; Merchant, Thomas E.

    2012-02-01

    Purpose: To compare intensity-modulated arc therapy (IMAT) to noncoplanar intensity-modulated radiation therapy (IMRT) in the treatment of pediatric posterior fossa tumors. Methods and Materials: Nine pediatric patients with posterior fossa tumors, mean age 9 years (range, 6-15 years), treated using IMRT were chosen for this comparative planning study because of their tumor location. Each patient's treatment was replanned to receive 54 Gy to the planning target volume (PTV) using five different methods: eight-field noncoplanar IMRT, single coplanar IMAT, double coplanar IMAT, single noncoplanar IMAT, and double noncoplanar IMAT. For each method, the dose to 95% of the PTV was held constant, and the doses to surrounding critical structures were minimized. The different plans were compared based on conformity, total linear accelerator dose monitor units, and dose to surrounding normal tissues, including the entire body, whole brain, temporal lobes, brainstem, and cochleae. Results: The doses to the target and critical structures for the various IMAT methods were not statistically different in comparison with the noncoplanar IMRT plan, with the following exceptions: the cochlear doses were higher and whole brain dose was lower for coplanar IMAT plans; the cochleae and temporal lobe doses were lower and conformity increased for noncoplanar IMAT plans. The advantage of the noncoplanar IMAT plan was enhanced by doubling the treatment arc. Conclusion: Noncoplanar IMAT results in superior treatment plans when compared to noncoplanar IMRT for the treatment of posterior fossa tumors. IMAT should be considered alongside IMRT when treatment of this site is indicated.

  1. Primary hepatic carcinoid tumor in children.

    PubMed

    Foley, David S; Sunil, Indira; Debski, Robert; Ignacio, Romeo C; Nagaraj, Hirkati S

    2008-11-01

    Primary carcinoid tumors of the liver are rare, with fewer than 60 cases currently reported in the English literature. We present the evaluation and management of a solid hepatic tumor in a 14-year-old boy. Intraoperative biopsy was indeterminant for malignant potential, and the patient underwent complete resection by left hepatic lobectomy. Final histopathologic evaluation of the mass revealed a carcinoid tumor. Extensive endoscopic and radiologic workup revealed no other primary source. The patient recovered well from surgery and is currently free of disease 32 months after initial resection. Review of the literature suggests that primary hepatic carcinoid tumors are particularly rare in children. As the liver is frequently a site for carcinoid metastasis from the gastrointestinal tract, any patient with a suspected primary hepatic carcinoid tumor must undergo an extensive search for an extrahepatic primary site. These tumors are typically indolent but may metastasize. In addition, medical therapy is of limited benefit in reducing tumor bulk. The mainstay for treatment of primary hepatic carcinoid tumors is surgical resection, and these tumors carry a more favorable prognosis than other primary hepatic malignancies and metastatic carcinoid. Follow-up is long-term, as these tumors can recur many years after initial resection. PMID:18970916

  2. Solid Tumor Therapy Using a Cannon and Pawn Combination Strategy.

    PubMed

    Song, Wantong; Tang, Zhaohui; Zhang, Dawei; Wen, Xue; Lv, Shixian; Liu, Zhilin; Deng, Mingxiao; Chen, Xuesi

    2016-01-01

    Nanocarrier-based anti-tumor drugs hold great promise for reducing side effects and improving tumor-site drug retention in the treatment of solid tumors. However, therapeutic outcomes are still limited, primarily due to a lack of drug penetration within most tumor tissues. Herein, we propose a strategy using a nanocarrier-based combination of vascular disrupting agents (VDAs) and cytotoxic drugs for solid tumor therapy. Specifically, combretastatin A-4 (CA4) serves as a "cannon" by eradicating tumor cells at a distance from blood vessels; concomitantly, doxorubicin (DOX) serves as a "pawn" by killing tumor cells in close proximity to blood vessels. This "cannon and pawn" combination strategy acts without a need to penetrate every tumor cell and is expected to eliminate all tumor cells in a solid tumor. In a murine C26 colon tumor model, this strategy proved effective in eradicating greater than 94% of tumor cells and efficiently inhibited tumor growth with a weekly injection. In large solid tumor models (C26 and 4T1 tumors with volumes of approximately 250 mm(3)), this strategy also proved effective for inhibiting tumor growth. These results showing remarkable inhibition of tumor growth provide a valuable therapeutic choice for solid tumor therapy. PMID:27217835

  3. Solid Tumor Therapy Using a Cannon and Pawn Combination Strategy

    PubMed Central

    Song, Wantong; Tang, Zhaohui; Zhang, Dawei; Wen, Xue; Lv, Shixian; Liu, Zhilin; Deng, Mingxiao; Chen, Xuesi

    2016-01-01

    Nanocarrier-based anti-tumor drugs hold great promise for reducing side effects and improving tumor-site drug retention in the treatment of solid tumors. However, therapeutic outcomes are still limited, primarily due to a lack of drug penetration within most tumor tissues. Herein, we propose a strategy using a nanocarrier-based combination of vascular disrupting agents (VDAs) and cytotoxic drugs for solid tumor therapy. Specifically, combretastatin A-4 (CA4) serves as a “cannon” by eradicating tumor cells at a distance from blood vessels; concomitantly, doxorubicin (DOX) serves as a “pawn” by killing tumor cells in close proximity to blood vessels. This “cannon and pawn” combination strategy acts without a need to penetrate every tumor cell and is expected to eliminate all tumor cells in a solid tumor. In a murine C26 colon tumor model, this strategy proved effective in eradicating greater than 94% of tumor cells and efficiently inhibited tumor growth with a weekly injection. In large solid tumor models (C26 and 4T1 tumors with volumes of approximately 250 mm3), this strategy also proved effective for inhibiting tumor growth. These results showing remarkable inhibition of tumor growth provide a valuable therapeutic choice for solid tumor therapy. PMID:27217835

  4. Clinical Outcomes of Surgically Managed Spontaneous Tumors in 114 Client-owned Dogs

    PubMed Central

    Choi, Ji-Won; Yoon, Hun-Young

    2016-01-01

    Medical records of 139 tumors from 114 dogs that underwent surgery from May 2010 through March 2015 were retrospectively reviewed. Among 114 dogs, females (64.9%) were significantly more common than males (35.1%) (p<0.05). Dogs aged 6 to 10 years were more presented than non-tumor patients, however, there was no significant difference. The mean age (±SD) was 10.3±3.0 years. Although we found no significant difference of breed predisposition, the most common breed was Maltese (19.3%), followed by Shih-Tzu (14.0%), and Yorkshire terrier (13.2%). Proportional morbidity ratios (PMRs) of mammary gland, oral cavity, and skin tumors were high in Poodles, Yorkshire terriers, and Golden retrievers, respectively. Mammary gland (36.0%) was the most common site, followed by skin and soft tissues (12.2%), oral cavity (10.8%), and digestive organs (8.6%), but there was no significant difference. The objectives of surgery were curative surgery (86.2%), biopsy (4.9%), and palliative surgery (6.5%). In this study, 123 of 139 tumors had histopathological diagnoses. Adenocarcinoma was the most common type (n=24), followed by adenoma (n=17), soft tissue sarcoma (n=13), benign mixed tumor (n=5), and others (n=64). Recurrence or suspected metastasis was identified in 26 dogs. Median survival times of malignant mammary gland tumors, skin and subcutaneous tumors, and splenic tumors were 1,563.0±1,201.7, 469, and 128 days, respectively. PMID:27162528

  5. Spectrum of Sinonasal Tumors: A 10-year Experience at a Tertiary Care Hospital in North India

    PubMed Central

    Shirazi, Nadia; Bist, Sampan S.; Selvi, Thamarai N.; Harsh, Meena

    2015-01-01

    Objective Sinonasal tumors are a highly heterogeneous group of tumors that account for less than 1% of all cancers. Precise diagnosis is essential because the natural history, treatment, and prognosis vary for different neoplasms. We reviewed 610 cases of sinonasal lesions to understand this entity better. Methods A total of 610 sinonasal biopsies/specimens were received over a period of 10 years (2004–14). All the samples were processed and stained with hematoxylin and eosin. Special staining for microorganisms and immunohistochemistry were performed where indicated. Results Benign lesions were 72% with nasal polyp being the most common. Malignant lesions made up 21.2% of lesions with nasopharyngeal carcinoma being the most common while 7.7% cases were inflammatory/non-neoplastic. The most common cause for this was fungal sinusitis. The maxillary sinus was the most frequently involved site in all the lesions (62%). The average age of presentation was 40 years old, and the male to female ratio was 3:1 in those with benign tumors. The average age of presentation in the malignant and inflammatory group were 45 and 43 years, respectively, with an almost equal sex ratio in both categories. Computed tomography and magnetic resonance imaging scans were done in virtually all cases to assess the extent of the tumor as well as bony destruction. Local recurrence was the most frequent cause of treatment failure. Conclusion Tumors of the nasal cavity are often grouped with those in the paranasal sinuses. Benign tumors constituted approximately 75% of tumors in our hospital. Squamous cell carcinoma was the most common malignancy of this region. These tumors need to be studied closely and accurately because their proximity to vital structures pose significant challenges for their treatment and may be the source of significant patient morbidity. PMID:26674709

  6. Skeletal sequelae of radiation therapy for malignant childhood tumors

    SciTech Connect

    Butler, M.S.; Robertson, W.W. Jr.; Rate, W.; D'Angio, G.J.; Drummond, D.S. )

    1990-02-01

    One hundred forty-three patients who received radiation therapy for childhood tumors, and survived to the age of skeletal maturity, were studied by retrospective review of oncology records and roentgenograms. Diagnoses for the patients were the following: Hodgkin's lymphoma (44), Wilms's tumor (30), acute lymphocytic leukemia (26), non-Hodgkin's lymphoma (18), Ewing's sarcoma (nine), rhabdomyosarcoma (six), neuroblastoma (six), and others (four). Age at the follow-up examination averaged 18 years (range, 14-28 years). Average length of follow-up study was 9.9 years (range, two to 18 years). Asymmetry of the chest and ribs was seen in 51 (36%) of these children. Fifty (35%) had scoliosis; 14 had kyphosis. In two children, the scoliosis was treated with a brace, while one developed significant kyphosing scoliosis after laminectomy and had spinal fusion. Twenty-three (16%) patients complained of significant pain at the radiation sites. Twelve of the patients developed leg-length inequality; eight of those were symptomatic. Three patients developed second primary tumors. Currently, the incidence of significant skeletal sequelae is lower and the manifestations are less severe than reported in the years from 1940 to 1970. The reduction in skeletal complications may be attributed to shielding of growth centers, symmetric field selection, decreased total radiation doses, and sequence changes in chemotherapy.

  7. [Analysis of Single Particle Aging and Mixing State at an Agriculture Site (Quzhou) in the North China Plain in Summer Using a Single Particle Aerosol Mass Spectrometer].

    PubMed

    Huang, Zi-long; Zeng, Li-mm; Dong, I-Iua-Bin; Li, Mei; Zhu, Tong

    2016-04-15

    To characterize the size distribution and chemical ompsitins f abiet prtices t a agicuturesit intheNorh o Chinese Plain, a single particle aerosol mass spectrometer (SPAMS) was deployed from June 30 to July 8, 2013. A total of 230,152 particles in the size range of 0.2-2.0 pm were chemically analyzed with both positive and negative ion spectra. The results revealed that aerosol could he classified into eight dominant groups, including elemental carbon (EC, 55.5%), organic carbon (OC, 10.7%), alkalis (Na-K, 17.4%), other metals (1.7%), Fe-rich (6.3%), Pb-rich (3.1%), dust (4.8%), and other (0.8%). The observed eight types of particles contained secondary components such as 46NO2-, 62NO3-, 96SO3-, 96SO4-, 97HSO4-, showing that they probably went through different aging processes. The analysis of particle size distribution showed that 700-800 nm was the peak value of all particles, and that dust and Fe particles were mainly in the coarse size range. EC particles subtype group research revealed EC particles tended to be aging with the above mentioned secondary ions and eventually led to a particle type conversion from EC to the less aging ECN and the more serious aging ECS, the diurnal variation of which was obviously negatively correlated, and there was a possibility of forming OC/EC mixture with the adsorption of secondary organic matter on EC surface. PMID:27548937

  8. Carcinogenesis and aging

    SciTech Connect

    Anisimov, V.N.

    1983-01-01

    A suggested mechanism of carcinogenesis is presented. This scheme takes into account the effect of carcinogens at different integration levels: subcellular, tissue, and organism. Any of these levels may be age dependent. Age-associated changes in the activity of enzymes responsible for activation and inactivation of carcinogens, and variations in concentrations of lipids and proteins contributing to the transport of carcinogenic agents into cells, may play an important role in the modifying effect of age on carcinogenesis. The effects of age-associated changes in DNA repair need clarification. However, they are thought to exert a permissive influence on the age-associated rise in tumor incidence. It seems that proliferative activity of target tissues is the important modifying factor of carcinogenesis. Age-related changes of regulation at tissue and organism levels are also powerful factors in carcinogenesis modification. Age-dependent changes in the neuroendocrine system provide conditions for metabolic immunodepression and promotion of carcinogenesis. On the other hand, carcinogens per se (especially chemical and radiological) may intensify aging processes in the organism. Normalization, by drugs, of age-associated shifts requiring synthetic and energetic changes of a transformed tumor cells, and of immunological shifts, may exert both antitumor and geroprotective effects.

  9. Pío del Río Ortega: A Pioneer in the Pathology of Central Nervous System Tumors

    PubMed Central

    Ramon y Cajal Agüeras, Santiago

    2016-01-01

    The last 140 years have seen considerable advances in knowledge of central nervous system tumors. However, the main tumor types had already been described during the early years of the twentieth century. The studies of Dr. Pío del Río Hortega have been ones of the most exhaustive histology and cytology-based studies of nervous system tumors. Río Hortega's work was performed using silver staining methods, which require a high level of practical skill and were therefore difficult to standardize. His technical aptitude and interest in nervous system tumors played a key role in the establishment of his classification, which was based on cell lineage and embryonic development. Río Hortega's approach was controversial when he proposed it. Current classifications are not only based on cell type and embryonic lineage, as well as on clinical characteristics, anatomical site, and age. PMID:26973470

  10. [Succinate dehydrogenase-deficient tumors--a novel mechanism of tumor formation].

    PubMed

    Miettinen, Markku

    2015-01-01

    Succinate dehydrogenase (SDH) is a heterotetrameric enzyme complex participating in the Krebs cycle and electron transfer of oxidative phosphorylation. These tumors, discovered during the past 15 years, often occur in young patients and include 15% of paragangliomas, 7% of gastric gastrointestinal stromal tumors (GISTs), and <1% of renal cell carcinomas and pituitary adenomas. SDH-deficient tumors have lost SDH complex activity via bi-allelic genomic losses or epigenetic silencing. This deficiency is oncogenic, activating pseudohypoxia signaling. SDH deficiency has to be suspected in the above-cited tumor types presenting at a young age. Immunohistochemical testing of tumor tissue for SDHB loss is diagnostic. PMID:26749909

  11. Familial pituitary tumors.

    PubMed

    Alband, Neda; Korbonits, Márta

    2014-01-01

    Pituitary adenomas are benign intracranial neoplasms that present a major clinical concern due to hormone overproduction and/or tumor mass effects. The majority of pituitary adenomas occur sporadically; however, familial cases are increasingly being recognized, such as multiple endocrine neoplasia type 1 (MEN1), Carney complex (CNC), and familial isolated pituitary adenoma (FIPA). Familial pituitary tumors appear to differ from their sporadic counterparts both in their genetic basis and in clinical characteristics. Evidence suggests that, especially in MEN1 and FIPA, tumors are more aggressive and affect patients at a younger age, therefore justifying the importance of early diagnosis, while in Carney complex pituitary hyperplasia is common. The genetic alterations responsible for the formation of familial pituitary syndromes include the MEN1 gene, responsible for about 80% of MEN1 cases, the regulatory subunit of the protein kinase A, PRKAR1A, responsible for about 70% of Carney complex cases, and AIP, the gene coding the aryl hydrocarbon receptor interacting protein, responsible for about 20% of FIPA cases. Rarely other genes have also been found responsible for familial pituitary adenoma cases. McCune-Albright syndrome (MAS) also has a genetic origin due to mosaic mutations in the G protein-coupled α subunit coded by the GNAS1 gene. In this chapter, we summarize the genetic and clinical characteristics of these familial pituitary syndromes and MAS. PMID:25248598

  12. Preliminary data from IODP Site U1338 of the Pacific Equatorial Age Transect (PEAT IODP Expedition 320/321): a study on the interaction between paleoenvironment and evolution of selected calcareous nannofossil taxa

    NASA Astrophysics Data System (ADS)

    Raffi, I.; Ciummelli, M.; Backman, J.; Iodp Expedition 320/321 Shipboard Scientific Party

    2010-12-01

    A continuous Cenozoic sediment record of the paleoequatorial Pacific ocean was recovered during IODP Expedition 320/321 (March-June 2009). The Pacific Equatorial Age Transect (PEAT) includes eight sites (U1331 to U1338), cored above the paleo-position of the equator at successive crustal ages on the Pacific plate, with records from the sediment surface to basement, with basalt aged between 53 to 18 Ma. The present study is focused on IODP Site 1338 that collected a 3-18 Ma segment of the PEAT equatorial megasplice. Although the target equatorial interval of Site 1338 was the middle and late Miocene, ~415 m of a complete sedimentary succession from Pleistocene to lower Miocene was recovered. Sediments are nannofossil ooze and chalk with varying concentrations (often relatively high abundances) of biosiliceous components, and show decimeter to meter lithological cycles that possibly reflect changes in production, dissolution, photic zone paleoecology. Ongoing analysis on nannofossil assemblages and selected taxa are providing distribution and abundance data that, combined with geochemical proxies, will unravel the biotic response to different climatic and oceanographic conditions. Biometric analysis and quantitative abundance analysis are used for providing a clear taxonomy of an important Neogene component of the nannofossil assemblages, the genus Discoaster, and for delineating in detail the evolutionary trends within the taxon. Moreover, we will try to relate the evolutionary signal observed in Discoaster lineage to the environmental evolution, namely to significant events such as the carbonate crash (Vincent and Berger, 1985; Lyle, et al., in prep.), the fluctuation and shallowing of the Calcite Compensation Depth (CCD) (Lyle, 2003), and deposition of diatom enriched intervals (Kemp and Baldauf, 1993).

  13. Relative paleointensity (RPI) and oxygen isotope stratigraphy at IODP Site U1308: North Atlantic RPI stack for 1.2-2.2 Ma (NARPI-2200) and age of the Olduvai Subchron

    NASA Astrophysics Data System (ADS)

    Channell, J. E. T.; Hodell, D. A.; Curtis, J. H.

    2016-01-01

    Integrated Ocean Drilling Program (IODP) Site U1308 (49°53‧N, 24°14‧W; water depth 3871 m) provides a record of relative paleointensity (RPI) and benthic stable isotope stratigraphy back to 3.2 Ma. The record since 1.5 Ma was published previously, and here we present the interval from 1.5 Ma to 3.2 Ma (Early Pleistocene-Late Pliocene). The benthic oxygen isotope record in this interval is correlated to Marine Isotope Stage (MIS) 51 to KM2, with an apparent hiatus that removed part of the interval spanning MIS 104-G2 (2.6-2.65 Ma), at the Gauss-Matuyama boundary. The mean sedimentation rate for the 1.5-3.2 Ma period is 8.5 cm/kyr. The age model was built by correlation of the benthic oxygen isotope record to a global stack (LR04). Apart from the expected polarity reversals, three magnetic excursions are recorded: Punaruu in MIS 31/32 at 1092 ka, Gilsa in MIS 54/55 at 1584 ka, and a newly recognized excursion labeled Porcupine (after the nearby Porcupine Abyssal Plain) in MIS G6/G7 at 2737 ka. The ages of polarity reversals at Site U1308, on the LR04 time scale, are consistent with the current geomagnetic polarity timescale (GPTS) with the exception of the base of the Olduvai Subchron that occurred in MIS 73, corresponding to 1925 ka on the LR04 time scale, 25 kyr younger than in the current GPTS. The RPI record at Site U1308 is calibrated using the oxygen isotope age model, and combined with four other North Atlantic records to obtain a North Atlantic RPI stack for 1.2-2.2 Ma (NARPI-2200) that is compared with published RPI stacks: Epapis, Sint-2000 and PADM2M. For 2.2-3.2 Ma, the Site U1308 RPI record is compared with a RPI record from North Atlantic IODP Site U1314, and with the Pacific Epapis stack. The mean sedimentation rates of the North Atlantic sites in NARPI-2200 are greater (by about an order of magnitude) than most of the records incorporated in other stacks. The comparison of Epapis and NARPI-2200 yields an apparent lag for NARPI-2200 relative to

  14. Germ Cell Tumors in Adolescents and Young Adults.

    PubMed

    Calaminus, Gabriele; Joffe, Jonathan

    2016-01-01

    Germ cell tumors (GCTs) represent a group of biologically complex malignancies that affect patients at different sites within the body and at different ages. The varying nature of these tumors reflects their cell of origin which is the primordial germ cell, which normally gives rise to ovarian and testicular egg and sperm producing cells. These cells retain an ability to give rise to all types of human tissues, and this is illustrated by the different kinds of GCTs that occur. In adolescent and young adult (AYA) patients, GCTs predominantly present as testicular, ovarian or mediastinal primary GCTs, and represent some of the most complex therapeutic challenges within any AYA practice. The varying types of GCTs, defined by primary site and/or age at presentation, can look very similar microscopically. However, there is growing evidence that they may have different molecular characteristics, different biology and different requirements for curative treatments. Whilst in adult testicular GCTs there is evidence for an environmental cause during fetal development and a genetic component, these causative factors are much less well understood in other GCTs. GCTs are some of the most curable cancers in adults, but some patients exhibit resistance to standard treatments. Because of this, today's clinical research is directed at understanding how to best utilize toxic therapies and promote healthy survivorship. This chapter explores the biology, behavior and treatment of GCTs and discusses how the AYA group of GCTs may hold some of the keys to understanding fundamental unanswered questions of biological variance and curability in GCTs. PMID:27595361

  15. [Clinical features of accessory parotid gland tumors].

    PubMed

    Iguchi, Hiroyoshi; Wada, Tadashi; Yamamoto, Hidefumi; Yamada, Kei; Matsushita, Naoki; Okamoto, Sachimi; Teranishi, Yuichi; Koda, Yuki; Kosugi, Yuki; Yamane, Hideo

    2013-12-01

    Accessory parotid gland tumors are relatively rare; hence, adequately detailed clinical analyses of these tumors are difficult to perform at a single institution. In this report, we describe the findings for 65 patients [29 men, 36 women; median age, 51 (9-81) years] with accessory parotid gland tumors, consisting of 4 cases documented by us and 61 cases previously reported by other Japanese authors. Approximately 50% of the patients were treated in an otolaryngology department, while the remaining patients were treated in plastic surgery, oral surgery, or dermatology departments. In 4 patients, the results of preoperative fine-needle aspiration cytology indicated that the tumor was benign; however, the postoperative histopathology results revealed malignant tumors. The frequencies of malignant and benign tumors were 44.6% (n = 29) and 55.4% (n = 36), respectively. Mucoepidermoid carcinoma and pleomorphic adenoma were the most frequent types of malignant and benign accessory parotid gland tumors, respectively. Among the various surgical methods that were used, such as direct cheek and intraoral incisions, a standard parotidectomy incision was the most preferred treatment approach for these tumors. Recently, an endoscopic approach has also been found to yield satisfactory results. An optimal approach should be selected after evaluating the advantages and disadvantages of these methods. No definite guidelines are available regarding the choice of elective neck dissection and postoperative radiation therapy for malignant accessory parotid gland tumors. Although tumor resection (plus elective neck dissection) and postoperative radiation therapy have been frequently performed for various kinds of malignant accessory parotid gland tumors to date, additional studies are needed regarding the criteria for selecting elective neck dissection and postoperative radiation therapy. Since the malignancy rate for accessory parotid gland tumors is higher than that for parotid gland

  16. A small molecule focal adhesion kinase (FAK) inhibitor, targeting Y397 site: 1-(2-hydroxyethyl)-3, 5, 7-triaza-1-azoniatricyclo [3.3.1.1(3,7)]decane; bromide effectively inhibits FAK autophosphorylation activity and decreases cancer cell viability, clonogenicity and tumor growth in vivo.

    PubMed

    Golubovskaya, Vita M; Figel, Sheila; Ho, Baotran T; Johnson, Christopher P; Yemma, Michael; Huang, Grace; Zheng, Min; Nyberg, Carl; Magis, Andrew; Ostrov, David A; Gelman, Irwin H; Cance, William G

    2012-05-01

    Focal adhesion kinase (FAK) is a protein tyrosine kinase that is overexpressed in most solid types of tumors and plays an important role in the survival signaling. Recently, we have developed a novel computer modeling combined with a functional assay approach to target the main autophosphorylation site of FAK (Y397). Using these approaches, we identified 1-(2-hydroxyethyl)-3, 5, 7-triaza-1-azoniatricyclo [3.3.1.1(3,7)]decane; bromide, called Y11, a small molecule inhibitor targeting Y397 site of FAK. Y11 significantly and specifically decreased FAK autophosphorylation, directly bound to the N-terminal domain of FAK. In addition, Y11 decreased Y397-FAK autophosphorylation, inhibited viability and clonogenicity of colon SW620 and breast BT474 cancer cells and increased detachment and apoptosis in vitro. Moreover, Y11 significantly decreased tumor growth in the colon cancer cell mouse xenograft model. Finally, tumors from the Y11-treated mice demonstrated decreased Y397-FAK autophosphorylation and activation of poly (ADP ribose) polymerase and caspase-3. Thus, targeting the major autophosphorylation site of FAK with Y11 inhibitor is critical for development of cancer therapeutics and carcinogenesis field. PMID:22402131

  17. Solitary Fibrous Tumor of the Orbit: A Case Report and Review of the Literature.

    PubMed

    Genc, Ali; Toktas, Zafer; Azman, Coruh; Bozkurt, Suheyla Uyar; Kilic, Turker

    2015-01-01

    Solitary fibrous tumor (SFT) is a rare, benign, spindle cell tumor that is most commonly found in the visceral pleura. The orbit is one of the most common extrapleural sites of occurrence. Though they can be seen in any age, they typically present in adults with proptosis as the prominent symptom. They show no significant gender predominance. Orbital solitary fibrous tumors routinely exhibit a benign course, but malignant forms with an increased propensity for local recurrence have been reported. Histopathologically, they share similar features with hemangiopericytoma, which is much more common. The diagnosis of SFT depends on the diffuse and intense positivity of CD34 staining by immunohistochemistry (14). Here, we report a case of SFT, which presented with proptosis and double vision on lateral gaze. We describe the clinical, radiographic, histopathological, and immunohistochemical findings. We also provide a discussion on its origin and differential diagnosis in the light of relevant literature. PMID:26617156

  18. Immunosuppressive cells in tumor immune escape and metastasis.

    PubMed

    Liu, Yang; Cao, Xuetao

    2016-05-01

    Tumor immune escape and the initiation of metastasis are critical steps in malignant progression of tumors and have been implicated in the failure of some clinical cancer immunotherapy. Tumors develop numerous strategies to escape immune surveillance or metastasize: Tumors not only modulate the recruitment and expansion of immunosuppressive cell populations to develop the tumor microenvironment or pre-metastatic niche but also switch the phenotype and function of normal immune cells from a potentially tumor-reactive state to a tumor-promoting state. Immunosuppressive cells facilitate tumor immune escape by inhibiting antitumor immune responses and furthermore promote tumor metastasis by inducing immunosuppression, promoting tumor cell invasion and intravasation, establishing a pre-metastatic niche, facilitating epithelial-mesenchymal transition, and inducing angiogenesis at primary tumor or metastatic sites. Numerous translational studies indicate that it is possible to inhibit tumor immune escape and prevent tumor metastasis by blocking immunosuppressive cells and eliminating immunosuppressive mechanisms that are induced by either immunosuppressive cells or tumor cells. Furthermore, many clinical trials targeting immunosuppressive cells have also achieved good outcome. In this review, we focus on the underlying mechanisms of immunosuppressive cells in promoting tumor immune escape and metastasis, discuss our current understanding of the interactions between immunosuppressive cells and tumor cells in the tumor microenvironment, and suggest future research directions as well as potential clinical strategies in cancer immunotherapy. PMID:26689709

  19. WWOX: a fragile tumor suppressor

    PubMed Central

    Schrock, Morgan S.; Huebner, Kay

    2015-01-01

    WWOX, the WW domain-containing oxidoreductase gene at chromosome region 16q23.3-q24.1, spanning chromosomal fragile site FRA16D, encodes the 46 kDa Wwox protein. WWOX is a tumor suppressor that is lost or reduced in expression in a wide variety of cancers, including breast, prostate, ovarian, and lung. The function of WWOX as a tumor suppressor implies that it serves an essential function in the prevention of carcinogenesis. Indeed, in vitro studies show that Wwox protein interacts with many binding partners to regulate cellular apoptosis, proliferation and/or maturation. It has been reported that newborn Wwox knockout mice exhibit nascent osteosarcomas while Wwox+/- mice exhibit increased incidence of spontaneous and induced tumors. Furthermore, absence or reduction of Wwox expression in mouse xenograft models results in increased tumorigenesis, which can be rescued by Wwox re-expression, though there is not universal agreement among investigators regarding the role of Wwox loss in these experimental models. Despite this proposed tumor suppressor function, the overlap of WWOX with FRA16D sensitizes the gene to protein-inactivating deletions caused by replication stress. The high frequency of deletions within the WWOX locus in cancers of various types, without the hallmark protein inactivation-associated mutations of ‘classical’ tumor suppressors, has led to the proposal that WWOX deletions in cancers are passenger events that occur in early cancer progenitor cells due to fragility of the genetic locus, rather than driver events which provide the cancer cell a selective advantage. Recently, a proposed epigenetic cause of chromosomal fragility has suggested a novel mechanism for early fragile site instability and has implications regarding the involvement of tumor suppressor genes at CFSs in cancer. In this review, we provide an overview of the evidence for WWOX as a tumor suppressor gene and put this into the context of fragility associated with the FRA16D

  20. Glomus Tumor of the Hand

    PubMed Central

    Lee, Won; Kwon, Soon Beom; Eo, Su Rak; Kwon, Chan

    2015-01-01

    Background Glomus tumors were first described by Wood in 1812 as painful subcutaneous tubercles. It is an uncommon benign neoplasm involving the glomus body, an apparatus that involves in thermoregulation of cutaneous microvasculature. Glomus tumor constitutes 1%-5% of all hand tumors. It usually occurs at the subungual region and more commonly in aged women. Its classical clinical triad consists of pain, tenderness and temperature intolerance, especially cold sensitivity. This study reviews 15 cases of glomus tumor which were analyzed according to its anatomic location, surgical approach and histologic findings. Methods Fifteen patients with subungual glomus tumors of the hand operated on between January 2006 and March 2013, were retrospectively reviewed. Patients were evaluated preoperatively with standard physical examination including ice cube test and Love's test. Diagnostic imaging consisted of ultrasonography, computed tomography, and magnetic resonance imaging. All procedures were performed with tourniquet control under local anesthesia. Eleven patients underwent excision using the transungual approach, 3 patients using the volar approach and 1 patient using the lateral subperiosteal approach. Results Total of 15 cases were reviewed. 11 tumors were located in the nail bed, 3 in the volar pulp and 1 in the radial aspect of the finger tip. After complete excision, patients remained asymptomatic in the immediate postoperative period. In the long term follow up, patients exhibited excellent cosmetic results with no recurrence. Conclusions Accurate diagnosis should be made by physical, radiologic and pathologic examinations. Preoperative localization and complete extirpation is essential in preventing recurrence and subsequent nail deformity. PMID:26015884

  1. Concomitant Double Tumors of Myxopapillary Ependymoma Presented at Cauda Equina-Filum Terminale in Adult Patient.

    PubMed

    Yener, Ulaş; Güdük, Mustafa; Ekşi, Murat Şakir; Aytar, Murat Hamit; Sav, Aydın; Özgen, Serdar

    2016-03-01

    A 32-year-old man presented with gradually increasing bilateral buttock pain. He had intermittent claudication. Multiple, homogenously enhanced intradural extramedullary lesions at L2-L3 and L5-S1 levels were observed on magnetic resonance imaging. The tumors were debulked and were removed in piecemeal pattern until they had completely been resected. Histopathological examination of the surgical specimens confirmed that both tumors were myxopapillary ependymomas (MPE). MPE presenting as concomitant double tumor at conus-cauda-filum level are very rare. This kind of presentation could not be directly considered as dissemination, since both tumors were in the site of classical origin of MPE. Ten cases of double spinal MPEs have been reported to date. Including the present case, analysis of the 11 patients revealed some facts. There is a male predominance, which is opposite to the ependymomas that are commonly observed in females. Median age at presentation is 15 years. Most pronounced symptom is low back pain that sometimes radiates to lower extremities. Surgical approach was aimed in all tumors, which could be succeeded in all tumors except one. Adjuvant radiation therapy was applied in 5 patients. No recurrences have been reported after surgery or surgery + radiotherapy regimens. PMID:27123029

  2. Concomitant Double Tumors of Myxopapillary Ependymoma Presented at Cauda Equina-Filum Terminale in Adult Patient

    PubMed Central

    Güdük, Mustafa; Ekşi, Murat Şakir; Aytar, Murat Hamit; Sav, Aydın; Özgen, Serdar

    2016-01-01

    A 32-year-old man presented with gradually increasing bilateral buttock pain. He had intermittent claudication. Multiple, homogenously enhanced intradural extramedullary lesions at L2-L3 and L5-S1 levels were observed on magnetic resonance imaging. The tumors were debulked and were removed in piecemeal pattern until they had completely been resected. Histopathological examination of the surgical specimens confirmed that both tumors were myxopapillary ependymomas (MPE). MPE presenting as concomitant double tumor at conus-cauda-filum level are very rare. This kind of presentation could not be directly considered as dissemination, since both tumors were in the site of classical origin of MPE. Ten cases of double spinal MPEs have been reported to date. Including the present case, analysis of the 11 patients revealed some facts. There is a male predominance, which is opposite to the ependymomas that are commonly observed in females. Median age at presentation is 15 years. Most pronounced symptom is low back pain that sometimes radiates to lower extremities. Surgical approach was aimed in all tumors, which could be succeeded in all tumors except one. Adjuvant radiation therapy was applied in 5 patients. No recurrences have been reported after surgery or surgery + radiotherapy regimens. PMID:27123029

  3. Risk of extrathyroid tumors following radiation treatment in infancy for thymic enlargement

    SciTech Connect

    Hildreth, N.G.; Shore, R.E.; Hempelmann, L.M.; Rosenstein, M.

    1985-06-01

    Two thousand eight hundred and fifty-six individuals who received X-ray treatments in infancy for an enlarged thymus gland and their 5053 nonirradiated siblings have been followed prospectively since 1953 to evaluate the risk of radiation-induced neoplastic disease. Based on the cumulative experience of five surveys of this cohort, the irradiated group has a statistically significant increased risk for both benign and malignant extrathyroid tumors, the age-adjusted relative risks being 2.0 and 2.2, respectively. Benign tumors of the bone, nervous system, salivary gland, skin, and breast (females only) and malignant tumors of the skin and breast (females only) account for the excess incidence of extrathyroid tumors among the thymic-irradiated individuals. Although a radiation-induced excess of extrathyroid tumors was suggested in an earlier survey of this cohort, small numbers restricted attribution of this excess to specific sites. The implications of these findings are discussed. Thyroid tumors are addressed in a separate paper.

  4. Spontaneous and radiation-induced renal tumors in the Eker rat model of dominantly inherited cancer.

    PubMed Central

    Hino, O; Klein-Szanto, A J; Freed, J J; Testa, J R; Brown, D Q; Vilensky, M; Yeung, R S; Tartof, K D; Knudson, A G

    1993-01-01

    Hereditary renal carcinoma (RC) in the rat, originally reported by R. Eker in 1954, is an example of a Mendelian dominant predisposition to a specific cancer in an experimental animal. At the histologic level, RCs develop through multiple stages from early preneoplastic lesions (e.g., atypical tubules) to adenomas in virtually all heterozygotes by the age of 1 year. The homozygous mutant condition is lethal at approximately 10 days of fetal life. Ionizing radiation induces additional tumors in a linear dose-response relationship, suggesting that in heterozygotes two events (one inherited, one somatic) are necessary to produce tumors, and that the predisposing gene is a tumor suppressor gene. No genetic linkage has yet been found between the Eker mutation and rat DNA sequences homologous to those in human chromosome 3p, the presumed site of the putative tumor suppressor gene responsible for human RC. Nonrandom loss of rat chromosome 5 in RC-derived cell lines is sometimes associated with homozygous deletion of the interferon gene loci at rat chromosome bands 5q31-q33. Since this locus is not linked with the predisposing inherited gene in the Eker rat, it probably represents a second tumor suppressor gene involved in tumor progression. Images PMID:8419937

  5. Adolescent and Pediatric Brain Tumors

    MedlinePlus

    ... abta.org Donate Now Menu Adolescent & Pediatric Brain Tumors Brain Tumors In Children Pediatric Brain Tumor Diagnosis Family ... or Complete our contact form Adolescent & Pediatric Brain Tumors Brain Tumors In Children Pediatric Brain Tumor Diagnosis Family ...

  6. Interleukin 2 expression by tumor cells alters both the immune response and the tumor microenvironment.

    PubMed

    Lee, J; Fenton, B M; Koch, C J; Frelinger, J G; Lord, E M

    1998-04-01

    Microenvironmental conditions within solid tumors can have marked effects on the growth of the tumors and their response to therapies. The disorganized growth of tumors and their attendant vascular systems tends to result in areas of the tumors that are deficient in oxygen (hypoxic). Cells within these hypoxic areas are more resistant to conventional therapies such as radiation and chemotherapy. Here, we examine the hypoxic state of EMT6 mouse mammary tumors and the location of host cells within the different areas of the tumors to determine whether such microenvironmental conditions might also affect their ability to be recognized by the immune system. Hypoxia within tumors was quantified by flow cytometry and visualized by immunohistochemistry using a monoclonal antibody (ELK3-51) against cellular adducts of 2-(2-nitro-1H-imidazol-1-yl)-N-(2,2,3,3,3-pentafluoropropyl)acetam ide (EF5), a nitroimidazole compound that binds selectively to hypoxic cells. Thy-1+ cells, quantified using a monoclonal antibody, were found only in the well-oxygenated areas. The location of these Thy-1+ cells was also examined in EMT6 tumors that had been transfected with the gene for interleukin-2 (IL-2) because these tumors contain greatly increased numbers of host cells. Surprisingly, we found that IL-2-transfected tumors had significantly decreased hypoxia compared to parental tumors. Furthermore, using the fluorescent dye Hoechst 33342, an in vivo marker of perfused vessels, combined with immunochemical staining of PECAM-1 (CD31) as a marker of tumor vasculature, we found increased vascularization in the IL-2-transfected tumors. Thus, expression of IL-2 at the site of tumor growth may enhance tumor immunity not only by inducing the generation of tumor-reactive CTLs but also by allowing increased infiltration of activated T cells into the tumors. PMID:9537251

  7. Tumor-Associated Endothelial Cells Promote Tumor Metastasis by Chaperoning Circulating Tumor Cells and Protecting Them from Anoikis.

    PubMed

    Yadav, Arti; Kumar, Bhavna; Yu, Jun-Ge; Old, Matthew; Teknos, Theodoros N; Kumar, Pawan

    2015-01-01

    Tumor metastasis is a highly inefficient biological process as millions of tumor cells are released in circulation each day and only a few of them are able to successfully form distal metastatic nodules. This could be due to the fact that most of the epithelial origin cancer cells are anchorage-dependent and undergo rapid anoikis in harsh circulating conditions. A number of studies have shown that in addition to tumor cells, activated endothelial cells are also released into the blood circulation from the primary tumors. However, the precise role of these activated circulating endothelial cells (CECs) in tumor metastasis process is not known. Therefore, we performed a series of experiments to examine if CECs promoted tumor metastasis by chaperoning the tumor cells to distal sites. Our results demonstrate that blood samples from head and neck cancer patients contain significantly higher Bcl-2-positive CECs as compared to healthy volunteers. Technically, it is challenging to know the origin of CECs in patient blood samples, therefore we used an orthotopic SCID mouse model and co-implanted GFP-labeled endothelial cells along with tumor cells. Our results suggest that activated CECs (Bcl-2-positive) were released from primary tumors and they co-migrated with tumor cells to distal sites. Bcl-2 overexpression in endothelial cells (EC-Bcl-2) significantly enhanced adhesion molecule expression and tumor cell binding that was predominantly mediated by E-selectin. In addition, tumor cells bound to EC-Bcl-2 showed a significantly higher anoikis resistance via the activation of Src-FAK pathway. In our in vivo experiments, we observed significantly higher lung metastasis when tumor cells were co-injected with EC-Bcl-2 as compared to EC-VC. E-selectin knockdown in EC-Bcl-2 cells or FAK/FUT3 knockdown in tumor cells significantly reversed EC-Bcl-2-mediated tumor metastasis. Taken together, our results suggest a novel role for CECs in protecting the tumor cells in circulation and

  8. Mucinous borderline ovarian tumor with ascites.

    PubMed

    Batool, Tahira; Ullah, Nasreen Rehmat

    2014-11-01

    Borderline mucinous tumors are epithelial ovarian tumors with low rate of growth and low potential to invade or metastasize and associated with significantly better prognosis and excellent disease-free survival after surgical removal than other epithelial ovarian cancers. The accepted initial treatment is surgical removal of the tumor. Fertility-sparing surgery may suffice in young patients with tumors confined to the ovary. Radical surgery is recommended in patients with advanced disease and advanced age. Long-term surveillance is recommended to document and treat late recurrences. We report a case of a 59 years old postmenopausal patient with complex ovarian mucinous tumor and gross ascites; she had received three lines of chemotherapeutic agents pre-operatively, without any favorable outcome. Then, she went for staging laparotomy and histopathology showed borderline ovarian mucinous tumor required no further treatment and is fine till date. PMID:25518783

  9. Primary bone tumors of the spine.

    PubMed

    Cañete, A Navas; Bloem, H L; Kroon, H M

    2016-04-01

    Primary bone tumors of the spine are less common than metastases or multiple myeloma. Based on the patient's age and the radiologic pattern and topography of the tumor, a very approximate differential diagnosis can be established for an osseous vertebral lesion. This article shows the radiologic manifestations of the principal primary bone tumors of the spine from a practical point of view, based on our personal experience and a review of the literature. If bone metastases, multiple myeloma, lymphomas, hemangiomas, and enostoses are excluded, only eight types of tumors account for 80% of all vertebral tumors. These are chordomas, osteoblastomas, chondrosarcomas, giant-cell tumors, osteoid osteomas, Ewing's sarcomas, osteosarcomas, and aneurysmal bone cysts. PMID:26917429

  10. Rare Presentation of Supratentorial Primitive Neuroectodermal Tumors Mimicking Bifocal Germ Cell Tumors: 2 Case Reports.

    PubMed

    Phuakpet, Kamon; Larouche, Valerie; Hawkins, Cynthia; Huang, Annie; Tabori, Uri; Bartels, Ute K; Bouffet, Eric

    2016-03-01

    Bifocal pineal and suprasellar tumors have only been described in the context of germ cell tumors in the pediatric age group. We report 2 patients with radiologic findings of bifocal pineal and suprasellar lesions, with a histologic diagnosis of supratentorial primitive neuroectodermal tumor. The absence of diabetes insipidus and other endocrine abnormalities was noteworthy in both cases. This observation challenges previous reports on the pathognomonic value of this clinico-radiologic entity. PMID:26241725

  11. Self-Instructional Manual for Tumor Registrars: Book 3, Tumor Registrar Vocabulary - The Composition of Medical Terms.

    ERIC Educational Resources Information Center

    Shambaugh, Evelyn M., Ed.

    Book 3 of the self-instructional manual for tumor registrars deals with tumor registrar vocabulary. It is designed to teach tumor registrars to recognize diagnostic terms versus treatment terms, terms that refer to anatomical sites, terms that refer to patient symptoms. The first three parts of the book are concerned with word roots, prefixes and…

  12. Laparoscopic excision of abdominal wall desmoid tumor.

    PubMed

    Meshikhes, Abdul-Wahed; Al-Zahrani, Hana; Ewies, Tarek

    2016-02-01

    Open surgical resection is the mainstay treatment for desmoid tumors. Laparoscopic resection is rarely used and not well described in the literature. We report a case of a single, 35-year-old woman who presented with palpable abdominal wall desmoid tumor. The patient had had laparoscopic cholecystectomy 2 years earlier, and the tumor was at the insertion site of the right upper quadrant trocar. The diagnosis was made by a Tru-Cut biopsy at another institution, after the lesion had increased in size and caused increased discomfort. The patient underwent successful laparoscopic resection of the tumor. This report aimed to promote laparoscopic resection of abdominal wall desmoid tumors, whenever feasible, and describe the laparoscopic technique. We believe this is the second case of laparoscopic excision of desmoid tumor reported in the English-language literature. PMID:26781534

  13. Neuroendocrine Tumor: Statistics

    MedlinePlus

    ... Tumor > Neuroendocrine Tumor - Statistics Request Permissions Neuroendocrine Tumor - Statistics Approved by the Cancer.Net Editorial Board , 04/ ... the body. It is important to remember that statistics on how many people survive this type of ...

  14. Overview of Heart Tumors

    MedlinePlus

    ... the heart. Most heart tumors are metastatic cancer. Did You Know... Noncancerous tumors can be as deadly ... slow the tumor's growth. Resources In This Article Did You Know 1 Did You Know... Table 2 ...

  15. Brain Tumors (For Parents)

    MedlinePlus

    ... Story" 5 Things to Know About Zika & Pregnancy Brain Tumors KidsHealth > For Parents > Brain Tumors Print A ... radiation therapy or chemotherapy, or both. Types of Brain Tumors There are many different types of brain ...

  16. Childhood Brain Tumors

    MedlinePlus

    Brain tumors are abnormal growths inside the skull. They are among the most common types of childhood ... still be serious. Malignant tumors are cancerous. Childhood brain and spinal cord tumors can cause headaches and ...

  17. Pathology of eyelid tumors.

    PubMed

    Pe'er, Jacob

    2016-03-01

    The eyelids are composed of four layers: skin and subcutaneous tissue including its adnexa, striated muscle, tarsus with the meibomian glands, and the palpebral conjunctiva. Benign and malignant tumors can arise from each of the eyelid layers. Most eyelid tumors are of cutaneous origin, mostly epidermal, which can be divided into epithelial and melanocytic tumors. Benign epithelial lesions, cystic lesions, and benign melanocytic lesions are very common. The most common malignant eyelid tumors are basal cell carcinoma in Caucasians and sebaceous gland carcinoma in Asians. Adnexal and stromal tumors are less frequent. The present review describes the more important eyelid tumors according to the following groups: Benign and malignant epithelial tumors, benign and malignant melanocytic tumors, benign and malignant adnexal tumors, stromal eyelid tumors, lymphoproliferative and metastatic tumors, other rare eyelid tumors, and inflammatory and infections lesions that simulate neoplasms. PMID:27146927

  18. Pathology of eyelid tumors

    PubMed Central

    Pe’er, Jacob

    2016-01-01

    The eyelids are composed of four layers: skin and subcutaneous tissue including its adnexa, striated muscle, tarsus with the meibomian glands, and the palpebral conjunctiva. Benign and malignant tumors can arise from each of the eyelid layers. Most eyelid tumors are of cutaneous origin, mostly epidermal, which can be divided into epithelial and melanocytic tumors. Benign epithelial lesions, cystic lesions, and benign melanocytic lesions are very common. The most common malignant eyelid tumors are basal cell carcinoma in Caucasians and sebaceous gland carcinoma in Asians. Adnexal and stromal tumors are less frequent. The present review describes the more important eyelid tumors according to the following groups: Benign and malignant epithelial tumors, benign and malignant melanocytic tumors, benign and malignant adnexal tumors, stromal eyelid tumors, lymphoproliferative and metastatic tumors, other rare eyelid tumors, and inflammatory and infections lesions that simulate neoplasms. PMID:27146927

  19. Tumors and Pregnancy

    MedlinePlus

    Tumors during pregnancy are rare, but they can happen. Tumors can be either benign or malignant. Benign tumors aren't cancer. Malignant ones are. The most common cancers in pregnancy are breast cancer, cervical cancer, lymphoma, and melanoma. ...

  20. Pancreatic islet cell tumor

    MedlinePlus

    Islet cell tumors; Islet of Langerhans tumor; Neuroendocrine tumors ... In the healthy pancreas, cells called islet cells produce hormones that regulate a several bodily functions. These include blood sugar level and the production of ...

  1. Childhood Brain Tumors

    MedlinePlus

    ... They are among the most common types of childhood cancers. Some are benign tumors, which aren't ... can still be serious. Malignant tumors are cancerous. Childhood brain and spinal cord tumors can cause headaches ...

  2. Surgical treatment of cardiac tumors: a 5-year experience from a single cardiac center

    PubMed Central

    Yin, Liang; He, Dengke; Shen, Hua; Ling, Xinyu; Li, Wei; Xue, Qian

    2016-01-01

    Background Cardiac tumors are rare but manifested with various clinical presentations and often cause unexpected symptoms or sudden death. The objective is to review the clinical presentation, histopathological spectrum, mortality and follow-up data of patients with cardiac tumors following surgery treatment over a period of 5 years. Methods We retrospectively collected the medical records of all patients diagnosed of cardiac tumors in the period between January 2008 and December 2013 at the cardiac center of our university. Clinical histories, perioperative data, surgical findings, efficacy and follow-up data were reviewed in our study. Patients were divided into two groups according to site distribution of the tumors in the heart. Results A total of 131 patients underwent surgical treatment of cardiac tumors were enrolled in this study, with a mean age of 51.39±16.37. The result of analysis showed that 79.47% (n=104) of the primary intracardiac tumors were benign, while primary malignant neoplasms accounted for 16.03% (n=21) of all patients, with the remainder (n=6, 4.6%) metastatic tumors transferred from other organs. Among all patients there were 2 in-hospital deaths and the survival rate in all patients at 1-year, 3-year and 5-year follow up was 83.20%, 78.62% and 66.41% respectively. Both patients with tumors in the left and right heart had similar basic characteristics except sex gender (P=0.002), BSA (P=0.045) and weight (P=0.033). Compared with patients with tumors in the right heart, patients with tumors in the left heart had significant higher CPB time (P<0.001), cross clamp time (P<0.001) and time of mechanical ventilation (P<0.001), and they also had longer ICU stay (P<0.001) but not total hospital stay (P=0.434). Conclusions Surgical resection represents an effective protocol in treating cardiac tumors. Data in our study of cardiac tumors on frequency and allocation were consistent with previous reports which may provide useful clinical evidence on

  3. Tumor cells as cellular vehicles to deliver gene therapies to metastatic tumors.

    PubMed

    García-Castro, Javier; Martínez-Palacio, Jesús; Lillo, Rosa; García-Sánchez, Félix; Alemany, Ramón; Madero, Luis; Bueren, Juan A; Ramírez, Manuel

    2005-04-01

    A long-pursued goal in cancer treatment is to deliver a therapy specifically to metastases. As a result of the disseminated nature of the metastatic disease, carrying the therapeutic agent to the sites of tumor growth represents a major step for success. We hypothesized that tumor cells injected intravenously (i.v.) into an animal with metastases would respond to many of the factors driving the metastatic process, and would target metastases. Using a model of spontaneous metastases, we report here that i.v. injected tumor cells localized on metastatic lesions. Based on this fact, we used genetically transduced tumor cells for tumor targeting of anticancer agents such as a suicide gene or an oncolytic virus, with evident antitumoral effect and negligible systemic toxicity. Therefore, autologous tumor cells may be used as cellular vehicles for systemic delivery of anticancer therapies to metastatic tumors. PMID:15650763

  4. Intra-Site Variability in the Still Bay Fauna at Blombos Cave: Implications for Explanatory Models of the Middle Stone Age Cultural and Technological Evolution.

    PubMed

    Discamps, Emmanuel; Henshilwood, Christopher Stuart

    2015-01-01

    To explain cultural and technological innovations in the Middle Stone Age (MSA) of southern Africa, scholars invoke several factors. A major question in this research theme is whether MSA technocomplexes are adapted to a particular set of environmental conditions and subsistence strategies or, on the contrary, to a wide range of different foraging behaviours. While faunal studies provide key information for addressing these factors, most analyses do not assess intra-technocomplex variability of faunal exploitation (i.e. variability within MSA phases). In this study, we assess the spatial variability of the Still Bay fauna in one phase (M1) of the Blombos Cave sequence. Analyses of taxonomic composition, taphonomic alterations and combustion patterns reveal important faunal variability both across space (lateral variation in the post-depositional history of the deposits, spatial organisation of combustion features) and over time (fine-scale diachronic changes throughout a single phase). Our results show how grouping material prior to zooarchaeological interpretations (e.g. by layer or phase) can induce a loss of information. Finally, we discuss how multiple independent subdivisions of archaeological sequences can improve our understanding of both the timing of different changes (for example in technology, culture, subsistence, environment) and how they may be inter-related. PMID:26658195

  5. Intra-Site Variability in the Still Bay Fauna at Blombos Cave: Implications for Explanatory Models of the Middle Stone Age Cultural and Technological Evolution

    PubMed Central

    Discamps, Emmanuel; Henshilwood, Christopher Stuart

    2015-01-01

    To explain cultural and technological innovations in the Middle Stone Age (MSA) of southern Africa, scholars invoke several factors. A major question in this research theme is whether MSA technocomplexes are adapted to a particular set of environmental conditions and subsistence strategies or, on the contrary, to a wide range of different foraging behaviours. While faunal studies provide key information for addressing these factors, most analyses do not assess intra-technocomplex variability of faunal exploitation (i.e. variability within MSA phases). In this study, we assess the spatial variability of the Still Bay fauna in one phase (M1) of the Blombos Cave sequence. Analyses of taxonomic composition, taphonomic alterations and combustion patterns reveal important faunal variability both across space (lateral variation in the post-depositional history of the deposits, spatial organisation of combustion features) and over time (fine-scale diachronic changes throughout a single phase). Our results show how grouping material prior to zooarchaeological interpretations (e.g. by layer or phase) can induce a loss of information. Finally, we discuss how multiple independent subdivisions of archaeological sequences can improve our understanding of both the timing of different changes (for example in technology, culture, subsistence, environment) and how they may be inter-related. PMID:26658195

  6. Final Report, 2011-2014. Forecasting Carbon Storage as Eastern Forests Age. Joining Experimental and Modeling Approaches at the UMBS AmeriFlux Site

    SciTech Connect

    Curtis, Peter; Bohrer, Gil; Gough, Christopher; Nadelhoffer, Knute

    2015-03-12

    At the University of Michigan Biological Station (UMBS) AmeriFlux sites (US-UMB and US-UMd), long-term C cycling measurements and a novel ecosystem-scale experiment are revealing physical, biological, and ecological mechanisms driving long-term trajectories of C cycling, providing new data for improving modeling forecasts of C storage in eastern forests. Our findings provide support for previously untested hypotheses that stand-level structural and biological properties constrain long-term trajectories of C storage, and that remotely sensed canopy structural parameters can substantially improve model forecasts of forest C storage. Through the Forest Accelerated Succession ExperimenT (FASET), we are directly testing the hypothesis that forest C storage will increase due to increasing structural and biological complexity of the emerging tree communities. Support from this project, 2011-2014, enabled us to incorporate novel physical and ecological mechanisms into ecological, meteorological, and hydrological models to improve forecasts of future forest C storage in response to disturbance, succession, and current and long-term climate variation

  7. Carotid body tumor: a 25-year experience.

    PubMed

    Metheetrairut, Choakchai; Chotikavanich, Chanticha; Keskool, Phawin; Suphaphongs, Nit

    2016-08-01

    Carotid body tumor is an uncommon hypervascular benign tumor in the head and neck region. It usually presents as a slow growing mass at the carotid bifurcation. Because of the high rate of neurovascular complications, resection of this tumor is considered challenging for otolaryngologists. Between 1988 and 2013, 40 carotid body tumors from 38 patients were diagnosed and underwent resection at Siriraj Hospital (25 female and 13 male patients). Their age ranged from 15 to 59 years. Seven patients had bilateral tumors simultaneously whereas six cases had familial history of carotid body tumor. Carotid angiography was performed in 29 cases; other additional diagnostic studies included CT scan, MRI, and MRA to detect the widening of carotid bifurcation, its extension, and multifocal tumors. All diagnosed tumors were successfully removed. However, internal carotid artery and carotid bifurcation were injured in 11 cases (27.5 %). Shamblin class III and previous biopsy history were considered risk factors for vascular injury. Postoperative cranial nerves deficit was found in 20 % of the cases and CNS complication occurred in two patients (5 %). There was no surgical mortality. Additionally, upon the mean follow-up period of 36 months, no recurrence or malignant transformation was detected in this study. Multidisciplinary approach, early tumor detection, meticulous preoperative evaluation, and modern vascular surgical technique are the key success factors for tumor removal. PMID:26233244

  8. Vulvar and vaginal tumors in the dog: a retrospective study.

    PubMed

    Thacher, C; Bradley, R L

    1983-09-15

    Vulvar or vaginal neoplasia was diagnosed in 99 dogs. The most common clinical sign was vulvar discharge or the sudden appearance of a protruding mass from the vulva. Most of the dogs were old (average age, 10.8 years) and sexually intact. Of the 99 tumors, 72 were benign, 17 were malignant, and 10 were transmissible venereal tumors. Except for the transmissible venereal tumors, most tumors were of smooth muscle or fibrous tissue origin (leiomyoma, fibroma, and leiomyosarcoma). In the dogs with benign tumors, surgical excision of the tumor combined with ovariohysterectomy was effective in preventing recurrence of disease. PMID:6629979

  9. [Synovial tumors and tumor-like lesions].

    PubMed

    Doepfer, A-K; Meurer, A

    2015-10-01

    Synovial tumors comprise a variety of lesions, including those with benign and aggressive neoplastic changes as well as inflammatory causes. In this article we focus on neoplastic tumors. Synovial tumors with other etiologies, such as sarcoidosis, granuloma, synovitis, or gouty arthritis, are not dealt with here. Through a precise differentiation between these disease entities can an optimization of treatment be achieved. PMID:26370407

  10. Primary malignant chest wall tumors: analysis of 40 patients

    PubMed Central

    2014-01-01

    Background Primary chest wall tumors originate from different constructions of thoracic wall. We report our multidisciplinary experience on primary thoracic tumor resection and thoracic reconstruction, the need to additional therapy and evaluating prognostic factors affecting survival. Methods We performed a retrospective review of our prospectively maintained database of 40 patients treated for malignant primary chest wall tumor from 1989 to 2009. Patients were evaluated in terms of age, sex, clinical presentation, type of imaging, tissue diagnosis methods, pathology, surgical technique, early complications, hospital mortality, prevalence of recurrence and distant metastases, additional treatment, 3 years survival and factors affecting survival. Results Male/Female (F/M) = 1, with median age of 43.72 years. Mass was the most common symptoms and the soft tissue sarcoma was the most common pathology. Resection without reconstruction was performed in 5 patients and Thirty-five patients (87.5%) had extensive resection and reconstruction with rotatory muscular flap, prosthetic mesh and/or cement. Overall, 12.5% (5/40) of patients received neoadjuvant therapy and 75% (30/40) of patients were treated with adjuvant therapy. The 3-year survival rate was 65%. Recurrences occurred in 24 patients (60%), 14 developed local recurrences, and 10 developed distant metastases. The primary treatment modality for both local and distant recurrences was surgical resection; among them, 10 underwent repeated resection, 9 adjuvant therapy and 5 were treated with lung metastasectomy. The most common site of distant metastasis was lung (n = 7). Factors that affected survival were type of pathology and evidence of distant metastasis. Conclusion Surgery with wide margin is the safe and good technique for treatment of primary chest wall tumors with acceptable morbidity and mortality. PMID:24947314

  11. Age-associated impairment of antitumor immunity in carcinoma-bearing mice and restoration by oral administration of Lentinula edodes mycelia extract.

    PubMed

    Ishikawa, Satoru; Matsui, Yasunori; Wachi, Satoshi; Yamaguchi, Hiroshi; Harashima, Nanae; Harada, Mamoru

    2016-08-01

    Because cancer is associated with aging, immunological features in the aged should be considered in anticancer immunotherapy. In this study, we investigated antitumor immunity in aged mice using a CT26 colon carcinoma model. The tumor growth of CT26 was accelerated in aged mice compared with that in young mice, but this difference was not observed in nude mice. The serum levels of IL-6 and TNF-α were higher in aged mice than those in young mice, irrespective of the CT26-bearing state. The in vitro induction of CT26-specific CTLs from aged mice that were vaccinated with doxorubicin (DTX)-treated CT26 cells was impaired. In vivo neutralization of IL-6, but not TNF-α, showed a tendency to restore the in vitro induction of CT26-specific CTLs from vaccinated aged mice. Analyses on tumor-infiltrating immune cells as early as day 5 after CT26 inoculation revealed that monocytic and granulocytic MDSCs preferentially infiltrated into tumor sites in aged mice compared with young mice. Alternatively, oral administration of Lentinula edodes mycelia (L.E.M.) extract, which has the potential to suppress inflammation in tumor-bearing hosts, decreased the serum levels of IL-6 in aged mice. When administration of L.E.M. extract was started 1 week earlier, CT26 growth was retarded in aged mice and the in vivo priming of tumor-specific CTLs was improved in CT26-vaccinated aged mice. These results indicate early infiltration of MDSCs is related to impaired immunity of aged hosts and that oral administration of L.E.M. extract can mitigate the impairment. PMID:27312060

  12. Human tumor clonogenic assay for carcinoma of the lung. II. Factors that influence colony formation in soft agar.

    PubMed

    Kanzawa, F; Matsushima, Y; Hamburger, A W; Ishihara, J; Sasaki, Y; Shimizu, E; Eguchi, K; Shinkai, T; Saijo, N; Miyazawa, N

    1987-01-01

    The human tumor clonogenic assay (HTCA) has potential value for studies of both the chemosensitivity and biology of human tumors. However, many technical problems including low plating efficiencies and the preparation of sufficient numbers of viable cells remain. In this study, an improved method for disaggregation of solid tumors increased the yield of single cells. Consequently, more than 10 anticancer drugs could be tested in 94 of 168 specimens (56%). Removal of peripheral blood lymphocytes from cell suspensions derived from effusions also improved colony formation. Adequate growth for sensitivity testing (greater than 30 colonies/plate) was obtained in 122 cases (73%), inadequate growth for drug evaluation (5-29 colonies/plate) in 29 cases (17%), and no colony formation (less than 5 colonies/plate) in 17 cases (10%) of the 168 viable samples. The cloning efficiencies of cells derived from primary tumors (median 0.015%) were higher than those of cells derived from metastatic tumors (0.012%), and they varied with the location of the metastatic site. Cloning efficiencies varied markedly from specimen to specimen, and were unaffected by tumor histology, grade of differentiation, patient age, stage of disease, or prior chemotherapy. The HTCA is promising as a potential tool for studying the biology of tumors. PMID:3601316

  13. Detection of Circulating Tumor Cells by Fluorescent Immunohistochemistry in Patients with Esophageal Squamous Cell Carcinoma: Potential Clinical Applications.

    PubMed

    Li, Shu-Ping; Guan, Quan-Lin; Zhao, Da; Pei, Guang-Jun; Su, Hong-Xin; Du, Lan-Ning; He, Jin-Xiang; Liu, Zhao-Chen

    2016-01-01

    BACKGROUND Circulating tumor cells (CTCs) are tumor cells that leave the primary tumor site and enter the bloodstream, where they can spread to other organs; they are very important in the diagnosis, treatment, and prognosis of malignant tumors. However, few studies have investigated CTCs in esophageal squamous cell carcinoma (ESCC). The aim of this study was to investigate the CTCs in blood of ESCC patients and its potential relevance to clinicopathological features and prognosis. MATERIAL AND METHODS CTCs were acquired by a negative enrichment method that used magnetic activated cell sorting (MACSTM). Fluorescent immunohistochemistry (IHC) was used to identify the CTCs. Then, the positive CTC patients with ESCC were analyzed, after which the relationship between CTCs and clinicopathologic features was evaluated. RESULTS In the present study, 62 out of 140 (44.3%) patients with ESCC were positive for CTCs. The positive rate of CTCs was significantly related with stage of ESCC patients (P=0.013). However, there was no relationship between CTC status and age, sex, smoking tumor history, tumor location, differentiation of tumor, lymphatic invasion, or lymph venous invasion (P>0.05). Kaplan-Meier analysis showed that patients positive for CTCs had significantly shorter survival time than patients negative for CTCs. Multivariate analysis demonstrated that stage and CTC status were significant prognostic factors for patients with ESCC. CONCLUSIONS CTCs positivity is an independent prognostic biomarker that indicates a worse prognosis for patients with ESCC. PMID:27184872

  14. Role of Radiotherapy in the Management of Desmoid Tumors

    SciTech Connect

    Gluck, Iris; Griffith, Kent A.; Biermann, J. Sybil; Feng, Felix Y.; Lucas, David R.; Ben-Josef, Edgar

    2011-07-01

    Purpose: To identify high-risk patients with desmoid tumors who could benefit from postoperative radiotherapy (RT) and to determine the efficacy of postoperative and definitive RT. Materials and Methods: Retrospective analysis of clinical data for all patients with desmoid tumors who underwent definitive local therapy at the University of Michigan from 1984 through 2008. Estimates for local control were calculated using the product-limit method of Kaplan and Meier, and associations with patient, tumor, and RT characteristics were explored using Cox proportional hazard regression. Results: Treatment for 95 patients who qualified for the study included surgery, RT, or both in 54, 13, and 28 cases, respectively. With a median follow-up of 38 months, the actuarial 3-year local control (95% confidence interval [CI]) was not significantly different (p = 0.3) among the three treatment groups: 84.6% (70.2-92.4), 92.3% (56.6-98.9), and 69.0% (43.1-84.9), respectively. Tumor site in the head/neck (p = 0.03) and history of previous surgical therapy (p = 0.01) were associated with increased recurrence risk (HR = 2.8, 95% CI 1.1-7.4, and HR = 3.2, 95% CI = 1.3-7.8), whereas gender, age, use of RT, and positive margins were not (p > 0.2). Conclusions: Our findings suggest equivalent local control rates after surgery, RT, or a combination of both. Although history of previous surgical therapy or site of origin in the head/neck region were found to be associated with increased risk of recurrence after local therapy, there was no clear association between surgical margin status and local control.

  15. Inflammatory Myofibroblastic Tumor Mimicking Apical Periodontitis.

    PubMed

    Adachi, Makoto; Kiho, Kazuki; Sekine, Genta; Ohta, Takahisa; Matsubara, Makoto; Yoshida, Takakazu; Katsumata, Akitoshi; Tanuma, Jun-ichi; Sumitomo, Shinichiro

    2015-12-01

    Inflammatory myofibroblastic tumors (IMTs) are rare. IMTs of the head and neck occur in all age groups, from neonates to old age, with the highest incidence occurring in childhood and early adulthood. An IMT has been defined as a histologically distinctive lesion of uncertain behavior. This article describes an unusual case of IMT mimicking apical periodontitis in the mandible of a 42-year-old man. At first presentation, the patient showed spontaneous pain and percussion pain at teeth #28 to 30, which continued after initial endodontic treatment. Panoramic radiography revealed a radiolucent lesion at the site. Cone-beam computed tomographic imaging showed osteolytic lesions, suggesting an aggressive neoplasm requiring incisional biopsy. Histopathological examination indicated an IMT. The lesion was removed en bloc under general anesthesia, and the patient manifested no clinical evidence of recurrence for 24 months. Lesions of nonendodontic origin should be included in the differential diagnosis of apical periodontitis. Every available diagnostic tool should be used to confirm the diagnosis. Cone-beam computed tomographic imaging is very helpful for differential diagnosis in IMTs mimicking apical periodontitis. PMID:26602450

  16. Tumor-host interactions in the gallbladder suppress distal angiogenesis and tumor growth: involvement of transforming growth factor beta1.

    PubMed

    Gohongi, T; Fukumura, D; Boucher, Y; Yun, C O; Soff, G A; Compton, C; Todoroki, T; Jain, R K

    1999-10-01

    Angiogenesis inhibitors produced by a primary tumor can create a systemic anti-angiogenic environment and maintain metastatic tumor cells in a state of dormancy. We show here that the gallbladder microenvironment modulates the production of transforming growth factor (TGF)-beta1, a multifunctional cytokine that functions as an endogenous anti-angiogenic and anti-tumor factor in a cranial window preparation. We found that a wide variety of human gallbladder tumors express TGF-beta1 irrespective of histologic type. We implanted a gel impregnated with basic fibroblast growth factor or Mz-ChA-2 tumor in the cranial windows of mice without tumors or mice with subcutaneous or gallbladder tumors to study angiogenesis and tumor growth at a secondary site. Angiogenesis, leukocyte-endothelial interaction in vessels and tumor growth in the cranial window were substantially inhibited in mice with gallbladder tumors. The concentration of TGF-beta1 in the plasma of mice with gallbladder tumors was 300% higher than that in the plasma of mice without tumors or with subcutaneous tumors. In contrast, there was no difference in the plasma levels of other anti- and pro-angiogenic factors. Treatment with neutralizing antibody against TGF-beta1 reversed both angiogenesis suppression and inhibition of leukocyte rolling induced by gallbladder tumors. TGF-beta1 also inhibited Mz-ChA-2 tumor cell proliferation. Our results indicate that the production of anti-angiogenesis/proliferation factors is regulated by tumor-host interactions. PMID:10502827

  17. Using polarization-sensitive optical coherence tomography to identify tumor stromal fibrosis and increase tumor biopsy yield (Conference Presentation)

    NASA Astrophysics Data System (ADS)

    Hariri, Lida P.; Adams, David C.; Miller, Alyssa J.; Mino-Kenudson, Mari; Suter, Melissa J.

    2016-03-01

    Tissue biopsy is the principal method used to diagnose tumors in a variety of organ systems. It is essential to maximize tumor yield in biopsy specimens for both clinical diagnostic and research purposes. This is particularly important in tumors where additional tissue is needed for molecular analysis to identify patients who would benefit from mutation-specific targeted therapy, such as in lung carcinomas. Inadvertent sampling of fibrotic stroma within tumor nodules contaminates biopsies, decreases tumor yield, and can impede diagnosis. The ability to assess tumor composition and guide biopsy site selection in real time is likely to improve diagnostic yield. Polarization sensitive OCT (PS-OCT) measures birefringence in organized tissues, such as collagen, and could be used to distinguish tumor from fibrosis. In this study, PS-OCT was obtained in 65 lung nodule samples from surgical resection specimens containing varying ratios of tumor and fibrosis. PS-OCT was obtained with either a custom-built helical scanning catheter (0.8 or 1.6mm in diameter) or a dual-axis bench top scanner. Strong birefringence was observed in nodules containing dense fibrosis, with no birefringence in adjacent regions of tumor. Tumors admixed with early, loosely-organized collagen demonstrated mild-to-moderate birefringence, and tumors with little collagen content showed little to no birefringent signal. PS-OCT provides significant insights into tumor nodule composition, and has potential to differentiate tumor from stromal fibrosis during biopsy site selection to increase diagnostic tumor yield.

  18. Aging Brain, Aging Mind.

    ERIC Educational Resources Information Center

    Selkoe, Dennis J.

    1992-01-01

    Discusses the aging process related to physical changes of the human neural structure involved in learning, memory, and reasoning. Presents evidence that indicates such alterations do not necessarily signal the decline in cognitive function. Vignettes provide images of brain structures involved in learning, memory, and reasoning; hippocampal…

  19. Effects of Aging Quartz Sand and Hanford Site Sediment with Sodium Hydroxide on Radionuclide Sorption Coefficients and Sediment Physical and Hydrologic Properties: Final Report for Subtask 2a

    SciTech Connect

    DI Kaplan; JC Ritter; KE Parker

    1998-12-04

    Column and batch experiments were conducted in fiscal year 1998 at Pacific Northwest National Laboratory to evaluate the effect of varying concentrations of NaOH on the sorptive, physical, and hydraulic properties of two media, a quartz sand and a composite subsurface sediment from the 200-East Area of the Hanford Site. The NaOH solutions were used as a simplified effluent from a low-activity glass waste form. These experiments were conducted over a limited (O-to 10-month) contact time, with respect to the 10,000-to 100,000-year scenarios described in the Immobilized Low-Activity Waste- Performance Assessment (ILAW-PA). Wheq these two solids were put in contact with the NaOH solutions, dissolution was evident by a substantial increase in dissolved Si concentrations in the leachates. Incremental increases in NaOH con- centrations, resulted in corresponding increases in Si concentrations. A number of physical and hydraulic properties also changed as the NaOH concentrations were changed. It was observed that quartz sand was less reactive than the composite sediment. Further, moisture- retention measurements were made on the quartz sand and composite sedimen$ which showed that the NaOH-treated solids retained more water than the non-NaOH-treated solids. Because the other chemical, physical, and hydraulic measurements did not change dramatically after the high-NaOH treatments, the greater moisture retention of the high-NaOH treatments was attributed to a "salt effect" and not to the formation of small particles during the dissolution (weathering). The distribution coefficients (IQ) for Cs and Sr were measured on the NaOH-treated sediments, with decreases from -3,000 to 1,000 and 1,300 to 300 mL/g noted, respectively, at the 0.01-to 1.O-M NaOH levels. There was no apparent trend for the Sr & values with contact time. The lack of such a trend sug- gests that dissolution of sediment particles is not controlling the drop in IQ rather, it is the competition of the added Na

  20. Chemokines and the microenvironment in neuroectodermal tumor-host interaction

    PubMed Central

    Somasundaram, Rajasekharan; Herlyn, Dorothee

    2009-01-01

    Chemokines and chemokine receptors play an important role in immune homeostasis and surveillance. Altered or defective expression of chemokines and/or chemokine receptors could lead to a disease state including autoimmune disorder or cancer. Tumors from glioblastoma, melanoma, and neuroblastoma secrete high levels of chemokines that can promote tumor growth and progression or induce stromal cells present in the tumor microenvironment to produce cytokines or chemokines which, in turn, can regulate angiogenesis, tumor growth, and metastasis. On the other hand, chemokines secreted by tumor or stromal cells can also attract leukocytes such as dendritic cells, macrophages, neutrophils, and lymphocytes which may downmodulate tumor growth. New therapies that are aimed at limiting tumor growth and progression by attracting immune effector cells to the tumor site with chemokines may hold the key to the successful treatment of cancer, although this approach may be hampered by possible tumor growth-stimulating effects of chemokines. PMID:19049876

  1. Immunological Consequences of Epithelial-Mesenchymal Transition in Tumor Progression.

    PubMed

    Chockley, Peter J; Keshamouni, Venkateshwar G

    2016-08-01

    Microenvironments that tumor cells encounter are different during the stages of cancer progression-primary tumor, metastasis, and at the metastatic site. This suggests potential differences in immune surveillance of primary tumor and metastasis. Epithelial-mesenchymal transition (EMT) is a key reversible process in which cancer cells transition into highly motile and invasive cells for dissemination. Only a tiny proportion successfully metastasize, supporting the notion of metastasis-specific immune surveillance. EMT involves extensive molecular reprogramming of cells conferring many clinically relevant features to cancer cells and affects tumor cell interactions within the tumor microenvironment. We review the impact of tumor immune infiltrates on tumor cell EMT and the consequences of EMT in shaping the immune microenvironment of tumors. The usefulness of EMT as a model to investigate metastasis-specific immune surveillance mechanisms are also explored. Finally, we discuss potential implications of EMT for tumor immunogenicity, as well as current immunotherapies and future strategies. PMID:27431984

  2. Phyllodes Tumor of the Breast

    SciTech Connect

    Belkacemi, Yazid Bousquet, Guilhem; Marsiglia, Hugo; Ray-Coquard, Isabelle; Magne, Nicolas; Malard, Yann; Lacroix, Magalie; Gutierrez, Cristina; Senkus, Elzbieta; Christie, David; Drumea, Karen; Lagneau, Edouard; Kadish, Sidney P.; Scandolaro, Luciano; Azria, David; Ozsahin, Mahmut

    2008-02-01

    Purpose: To better identify prognostic factors for local control and survival, as well as the role of different therapeutic options, for phyllodes tumors, a rare fibroepithelial neoplasm of the breast. Methods and Materials: Data from 443 women treated between 1971 and 2003 were collected from the Rare Cancer Network. The median age was 40 years (range, 12-87 years). Tumors were benign in 284 cases (64%), borderline in 80 cases (18%), and malignant in 79 cases (18%). Surgery consisted of breast-conserving surgery (BCS) in 377 cases (85%) and total mastectomy (TM) in 66 cases (15%). Thirty-nine patients (9%) received adjuvant radiotherapy (RT). Results: After a median follow-up of 106 months, local recurrence (LR) and distant metastases rates were 19% and 3.4%, respectively. In the malignant and borderline group (n = 159), RT significantly decreased LR (p = 0.02), and TM had better results than BCS (p = 0.0019). Multivariate analysis revealed benign histology, negative margins, and no residual disease (no RD) after initial treatment and RT delivery as independent favorable prognostic factors for local control; benign histology and low number of mitosis for disease-free survival; and pathologic tumor size tumor necrosis for overall survival. In the malignant and borderline subgroup multivariate analysis TM was the only favorable independent prognostic factor for disease-free survival. Conclusions: This study showed that phyllodes tumor patients with no RD after treatment have better local control. Benign tumors have a good prognosis after surgery alone. In borderline and malignant tumors, TM had better results than BCS. Thus, in these forms adjuvant RT should be considered according to histologic criteria.

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

    PubMed

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

    2009-01-01

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

  4. Natural history of tumor growth and immune modulation in common spontaneous murine mammary tumor models

    PubMed Central

    Gad, Ekram; Rastetter, Lauren; Slota, Meredith; Koehnlein, Marlese; Treuting, Piper M.; Dang, Yushe; Stanton, Sasha; Disis, Mary L.

    2014-01-01

    Purpose Recent studies in patients with breast cancer suggest the immune microenvironment influences response to therapy. We aimed to evaluate the relationship between growth rates of tumors in common spontaneous mammary tumor models and immune biomarkers evaluated in the tumor and blood. Methods TgMMTV-neu and C3(1)-Tag transgenic mice were followed longitudinally from birth, and MPA-DMBA treated mice from the time of carcinogen administration, for the development of mammary tumors. Tumor infiltrating CD4+ and CD8+ T-cells, FOXP3+ T-regulatory cells, and myeloid derived suppressor cells were assessed by flow cytometry. Serum cytokines were evaluated in subsets of mice. Fine needle aspirates of tumors were collected and RNA isolated to determine levels of immune and proliferation markers. Results Age of tumor onset and kinetics of tumor growth were significantly different among the models. Mammary tumors from TgMMTV-neu contained a lower CD8/CD4 ratio than other models (p<0.05). MPA-DMBA induced tumors contained a higher percentage of FOXP3+ CD4+ T-cells (p<0.01) and MDSC (p<0.001) as compared to the other models. Individuals with significantly slower tumor growth demonstrated higher levels of Type I serum cytokines prior to the development of lesions as compared to those with rapid tumor growth. Moreover, the tumors of animals with more rapid tumor growth demonstrated a significant increase in expression of genes associated with Type II immunity than those with slower progressing tumors. Conclusions These data provide a foundation for the development of in vivo models to explore the relationship between endogenous immunity and response to standard therapies for breast cancer. PMID:25395320

  5. Adrenal Gland Tumor

    MedlinePlus

    ... here Home > Types of Cancer > Adrenal Gland Tumor Adrenal Gland Tumor This is Cancer.Net’s Guide to Adrenal Gland Tumor. Use the menu below to choose ... social workers, and patient advocates. Cancer.Net Guide Adrenal Gland Tumor Introduction Statistics Risk Factors Symptoms and ...

  6. Pediatric Odontogenic Tumors.

    PubMed

    Abrahams, Joshua M; McClure, Shawn A

    2016-02-01

    Pediatric odontogenic tumors are rare, and are often associated with impacted teeth. Although they can develop anywhere in the jaws, odontogenic tumors mainly occur in the posterior mandible. This article discusses the diagnosis and treatment of the most common pediatric odontogenic tumors, such as ameloblastoma, keratocystic odontogenic tumor, odontoma, and cementoblastoma. PMID:26614700

  7. Malignant perivascular epithelioid cell tumor of the gallbladder: a case report and review of literature.

    PubMed

    Zhao, Liena; Anders, Karl H

    2014-09-01

    Perivascular epithelioid cell tumors are rare mesenchymal neoplasms composed of histologically and immunohistochemically distinctive perivascular epithelioid cells. The perivascular epithelioid cell tumor family includes angiomyolipoma, clear cell sugar tumor of the lung, lymphangioleiomyomatosis, clear cell myomelanocytic tumor of the falciform ligament/ligamentum teres, and rare clear cell tumors of other anatomic sites. Perivascular epithelioid cell tumors have been reported previously in various sites, but to our knowledge not in the gallbladder. We report here, for the first time, a malignant perivascular epithelioid cell tumor arising in the gallbladder. PMID:25171708

  8. Mesenchymal Stem Cell-Mediated Effects of Tumor Support or Suppression

    PubMed Central

    Rhee, Ki-Jong; Lee, Jong In; Eom, Young Woo

    2015-01-01

    Mesenchymal stem cells (MSCs) can exhibit a marked tropism towards site of tumors. Many studies have reported that tumor progression and metastasis increase by MSCs. In contrast, other studies have shown that MSCs suppress growth of tumors. MSCs contribute to tumor growth promotion by several mechanisms: (1) transition to tumor-associated fibroblasts; (2) suppression of immune response; (3) promotion of angiogenesis; (4) stimulation of epithelial-mesenchymal transition (EMT); (5) contribution to the tumor microenvironment; (6) inhibition of tumor cell apoptosis; and (7) promotion of tumor metastasis. In contrast to the tumor-promoting properties, MSCs inhibit tumor growth by increasing inflammatory infiltration, inhibiting angiogenesis, suppressing Wnt signaling and AKT signaling, and inducing cell cycle arrest and apoptosis. In this review, we will discuss potential mechanisms by which MSC mediates tumor support or suppression and then the possible tumor-specific therapeutic strategies using MSCs as delivery vehicles, based on their homing potential to tumors. PMID:26694366

  9. Tumor heterogeneity and circulating tumor cells.

    PubMed

    Zhang, Chufeng; Guan, Yan; Sun, Yulan; Ai, Dan; Guo, Qisen

    2016-05-01

    In patients with cancer, individualized treatment strategies are generally guided by an analysis of molecular biomarkers. However, genetic instability allows tumor cells to lose monoclonality and acquire genetic heterogeneity, an important characteristic of tumors, during disease progression. Researchers have found that there is tumor heterogeneity between the primary tumor and metastatic lesions, between different metastatic lesions, and even within a single tumor (either primary or metastatic). Tumor heterogeneity is associated with heterogeneous protein functions, which lowers diagnostic precision and consequently becomes an obstacle to determining the appropriate therapeutic strategies for individual cancer patients. With the development of novel testing technologies, an increasing number of studies have attempted to explore tumor heterogeneity by examining circulating tumor cells (CTCs), with the expectation that CTCs may comprehensively represent the full spectrum of mutations and/or protein expression alterations present in the cancer. In addition, this strategy represents a minimally invasive approach compared to traditional tissue biopsies that can be used to dynamically monitor tumor evolution. The present article reviews the potential efficacy of using CTCs to identify both spatial and temporal tumor heterogeneity. This review also highlights current issues in this field and provides an outlook toward future applications of CTCs. PMID:26902424

  10. Pathogenesis of pituitary tumors.

    PubMed

    Yu, Run; Melmed, Shlomo

    2010-01-01

    Pituitary tumors are common and mostly benign neoplasia which cause excess or deficiency of pituitary hormones and compressive damage to adjacent organs. Oncogene activation [e.g. PTTG (pituitary tumor-transforming gene) and HMGA2], tumor suppressor gene inactivation (e.g. MEN1 and PRKAR1A), epigenetic changes (e.g. methylation) and humoral factors (e.g. ectopic production of stimulating hormones) are all possible pituitary tumor initiators; the micro-environment of pituitary tumors including steroid milieu, angiogenesis and abnormal cell adhesion further promote tumor growth. Senescence, a cellular defence mechanism against malignant transformation, may explain the benign nature of at least some pituitary tumors. We suggest that future research on pituitary tumor pathogenesis should incorporate systems approaches, and address regulatory mechanisms for pituitary cell proliferation, development of new animal models of pituitary tumor and isolation of functional human pituitary tumor cell lines. PMID:20541667

  11. PT-12SURGICAL APPROACH FOR THALAMIC TUMORS

    PubMed Central

    Smrcka, Martin; Priban, Vladimír; Brichtova, Eva; Juran, Vilem

    2014-01-01

    INTRODUCTION: Thalamic tumors are relatively rare tumors growing in a highly functional part of brain. They are more frequent in pediatric population. Their surgery is challenging and a high morbidity is possible. Relatively benign nature of many of these tumors means that an attempt for radical resection should frequently be performed. The approach has to be very carefully planned, sometimes with the help of modern diagnostic methods like DTI. The location and projection of the tumor in the thalamus plays an important role in choosing the approach. MATERIAL: We have studied a group of 12 patients with thalamic tumors treated from 2005 - 2012. There were 10 males and 2 females, age ranged from 1 - 64 years (mean 17,5 years). Transcortical approach was used 6x, transcallosal 3x, transsylvian 2x and supracerebellar infratentorial 1x. One patient is being observed only. RESULTS: Gross total resection was achieved in 6 cases, subtotal in 2 and partial in 3. There were 7 pilocytic astrocytomas, one subependymal giant cell astrocytoma, one diffuse astrocytoma G II and two glioblastomas. All patients are still alive with the mean follow-up 4 years. There was no permanent morbidity in this group. CONCLUSION: Thalamic tumors might be safely radically resected if correct approach is used. The choice of approach is based in the projection of the tumor. Smaller tumors which are not close to the thalamic surface might be followed or biopsied if there is a likelihood of its malignant nature. Oncological treatment should be reserved for malignant tumors.

  12. Hypoxia in Microscopic Tumors

    PubMed Central

    Li, Xiao-Feng; O’Donoghue, Joseph A

    2008-01-01

    Tumor hypoxia has been commonly observed in a broad spectrum of primary solid malignancies. Hypoxia is associated with tumor progression, increased aggressiveness, enhanced metastatic potential and poor prognosis. Hypoxic tumor cells are resistant to radiotherapy and some forms of chemotherapy. Using an animal model, we recently showed that microscopic tumors less than 1 mm diameter were severely hypoxic. In this review, models and techniques for the study of hypoxia in microscopic tumors are discussed. PMID:18384940

  13. Targeting of drugs and nanoparticles to tumors

    PubMed Central

    Bhatia, Sangeeta N.; Sailor, Michael J.

    2010-01-01

    The various types of cells that comprise the tumor mass all carry molecular markers that are not expressed or are expressed at much lower levels in normal cells. These differentially expressed molecules can be used as docking sites to concentrate drug conjugates and nanoparticles at tumors. Specific markers in tumor vessels are particularly well suited for targeting because molecules at the surface of blood vessels are readily accessible to circulating compounds. The increased concentration of a drug in the site of disease made possible by targeted delivery can be used to increase efficacy, reduce side effects, or achieve some of both. We review the recent advances in this delivery approach with a focus on the use of molecular markers of tumor vasculature as the primary target and nanoparticles as the delivery vehicle. PMID:20231381

  14. Naturally arising tumors of the inbred WAB/Not rat strain. II. Immunogenicity of transplanted tumors

    SciTech Connect

    Middle, J.G.; Embleton, M.J.

    1981-09-01

    The immunogenicity of 28 transplanted naturally arising tumors of the inbred WAB/Not rat was investigated at early passages in strictly syngeneic, contemporary animals. Included were nephroblastomas, histologically benign and malignant mammary tumors, soft tissue and skin tumors, 1 lymphoid tumor, and 2 gastrointestinal lesions. In no case was evidence of immunogenicity observed when animals were treated with multiple grafts of irradiated (15,000 rad) tissue or by excision of a growing tumor. A few of these tumors were further investigated by other methods of immunization, including injection at various sites of irradiated cells followed by challenge at different sites and multiple injections of mitomycin C- or Formalin-treated cells. Again no evidence of immunogenicity was seen. Attempts to immunize with viable cells mixed with BCG or Corynebacterium parvum failed due to lack of tumor suppression by these agents. Limited concomitant immunity experiments yielded similarly negative results, except in one case of a fibrosarcoma for which a slight reduction in second tumor growth was observed when primary implants were very large. Some alterations in biologic properties during transplant passage and the incidence of postexcision recurrence and metastatic spread of some of the tumors are described.

  15. Rare Tumors in Children: Progress Through Collaboration

    PubMed Central

    Furman, Wayne L.; Schultz, Kris A.; Ferrari, Andrea; Helman, Lee; Krailo, Mark D.

    2015-01-01

    Rare pediatric tumors account for approximately 10% of all childhood cancers, which in themselves are a rare entity. The diverse histologies and clinical behaviors of rare pediatric tumors pose challenges to the investigation of their biologic and clinical features. National and international cooperative groups such as the Rare Tumor Committee of the Children's Oncology Group, Rare Tumors in Pediatric Age Project, and European Cooperative Study Group for Pediatric Rare Tumors have developed several initiatives to advance knowledge about rare pediatric cancers. However, these programs have been only partially effective, necessitating the development of alternative mechanisms to study these challenging diseases. In this article, we review the current national and international collaborative strategies to study rare pediatric cancers and alternative methods under exploration to enhance those efforts, such as independent registries and disease-specific, National Cancer Institute–sponsored clinics. PMID:26304909

  16. Somatotroph pituitary tumors in budgerigars (Melopsittacus undulatus).

    PubMed

    Langohr, I M; Garner, M M; Kiupel, M

    2012-05-01

    A series of 11 pituitary tumors in budgerigars were classified on the basis of their clinical, gross, microscopic, and immunohistochemical characteristics. Affected birds were young to middle-aged. Clinically, neurologic signs--including difficulties flying, ataxia, and blindness--were most commonly reported. Additional clinical signs included weight loss, abnormal feathers or molting, increased respiratory efforts, and exophthalmos. Nine birds were diagnosed with chromophobic pituitary adenomas, and 2 birds had chromophobic pituitary carcinomas. Only 1 tumor was delimited to the pituitary gland; the other 10 variably invaded the brain, skull, and retrobulbar space. Distant metastases were identified in 2 birds. All tumors were immunohistochemically strongly positive for growth hormone, consistent with the diagnosis of somatotroph tumors. The common occurrence and early onset may suggest a genetic predisposition of budgerigars to develop somatotroph pituitary tumors with a high incidence of local invasion and with metastatic potential. PMID:21900544

  17. Urokinase-controlled tumor penetrating peptide.

    PubMed

    Braun, Gary B; Sugahara, Kazuki N; Yu, Olivia M; Kotamraju, Venkata Ramana; Mölder, Tarmo; Lowy, Andrew M; Ruoslahti, Erkki; Teesalu, Tambet

    2016-06-28

    Tumor penetrating peptides contain a cryptic (R/K)XX(R/K) CendR element that must be C-terminally exposed to trigger neuropilin-1 (NRP-1) binding, cellular internalization and malignant tissue penetration. The specific proteases that are involved in processing of tumor penetrating peptides identified using phage display are not known. Here we design de novo a tumor-penetrating peptide based on consensus cleavage motif of urokinase-type plasminogen activator (uPA). We expressed the peptide, uCendR (RPARSGR↓SAGGSVA, ↓ shows cleavage site), on phage or coated it onto silver nanoparticles and showed that it is cleaved by uPA, and that the cleavage triggers binding to recombinant NRP-1 and to NPR-1-expressing cells. Upon systemic administration to mice bearing uPA-overexpressing breast tumors, FAM-labeled uCendR peptide and uCendR-coated nanoparticles preferentially accumulated in tumor tissue. We also show that uCendR phage internalization into cultured cancer cells and its penetration in explants of murine tumors and clinical tumor explants can be potentiated by combining the uCendR peptide with tumor-homing module, CRGDC. Our work demonstrates the feasibility of designing tumor-penetrating peptides that are activated by a specific tumor protease. As upregulation of protease expression is one of the hallmarks of cancer, and numerous tumor proteases have substrate specificities compatible with proteolytic unmasking of cryptic CendR motifs, the strategy described here may provide a generic approach for designing proteolytically-actuated peptides for tumor-penetrative payload delivery. PMID:27106816

  18. Giant-cell tumor: analysis on the importance of early diagnosis and the epidemiological profile☆

    PubMed Central

    de Carvalho Diniz Ferraz, Diego Firmino; Torres dos Santos, César Augusto; Farias Costa, Victor Hugo; Gonçalves Souza, Antônio Marcelo; Gomes Lima, Paulo Rogerio

    2016-01-01

    Objective This study aimed to ascertain the relationship between early diagnosis of giant-cell tumors (GCT) and their prognosis, by correlating the time of symptom onset with the staging of the injury (through the Campanacci classification at the time of diagnosis), and with the type of treatment. The secondary objective of the study was to outline the epidemiological profile of patients with GCT in the region where the data were gathered, and to compare them with data in the literature. Methods The authors present an evaluation on 61 patients diagnosed with bone GCT, with regard to the site of involvement, age, initial symptoms, time of symptom onset, classification and type of treatment, among patients attended between May 1994 and August 2009. Results The threshold indicated as the limit for Campanacci stage I tumors to be the commonest diagnosis, with a 98.2% chance that the treatment would be non-aggressive, was 2 months after symptom onset. This finding was statistically significant (p = 0.017). Every additional month increased the chance that a patient would be diagnosed with an advanced-stage tumor by 10.94%, in relation to the chances of having the other two stages of the tumor. Conclusion The study result not only suggests that the alternative hypothesis that the earlier the diagnosis of GCT is, the less severe the lesion will be, has been confirmed; but also especially predicts the relationship between the time of symptom appearance and the severity of the tumor. PMID:26962501

  19. Autoclaved Tumor Bone for Skeletal Reconstruction in Paediatric Patients: A Low Cost Alternative in Developing Countries

    PubMed Central

    Umer, Masood; Umer, Hafiz Muhammad; Qadir, Irfan; Rashid, Haroon; Awan, Rabia; Askari, Raza; Ashraf, Shamvil

    2013-01-01

    We reviewed in this series forty patients of pediatric age who underwent resection for malignant tumors of musculoskeletal system followed by biological reconstruction. Our surgical procedure for reconstruction included (1) wide en bloc resection of the tumor; (2) curettage of tumor from the resected bone; (3) autoclaving for 8 minutes (4) bone grafting from the fibula (both vascularized and nonvascularized fibular grafts used); (5) reimplantation of the autoclaved bone into the host bone defect and fixation with plates. Functional evaluation was done using MSTS scoring system. At final followup of at least 18 months (mean 29.2 months), 31 patients had recovered without any complications. Thirty-eight patients successfully achieved a solid bony union between the graft and recipient bone. Three patients had surgical site infection. They were managed with wound debridement and flap coverage of the defect. Local recurrence and nonunion occurred in two patients each. One patient underwent disarticulation at hip due to extensive local disease and one died of metastasis. For patients with non-union, revision procedure with bone graft and compression plates was successfully used. The use of autoclaved tumor grafts provides a limb salvage option that is inexpensive and independent of external resources and is a viable option for musculoskeletal tumor management in developing countries. PMID:24455717

  20. Does Radiotherapy for the Primary Tumor Benefit Prostate Cancer Patients with Distant Metastasis at Initial Diagnosis?

    PubMed Central

    Cho, Yeona; Chang, Jee Suk; Rha, Koon Ho; Hong, Sung Joon; Choi, Young Deuk; Ham, Won Sik; Kim, Jun Won; Cho, Jaeho

    2016-01-01

    Purpose/Objectives Treatment of the primary tumor reportedly improves survival in several types of metastatic cancer. We herein evaluated the efficacy and toxicity of radiotherapy for the primary tumor in prostate cancer with metastasis. Materials/Methods The study cohort included 140 men with metastatic prostate cancer at initial diagnosis. Metastatic sites were divided into 4 groups as follows: solitary bone, 2–4 bones, ≥5 bones, and visceral organs. Patient, tumor, and treatment characteristics, and clinical outcomes were compared between patients treated with (prostate radiotherapy [PRT] group) or without radiotherapy to the primary tumor. Results Patients in PRT group presented with a statistically significantly younger age (p = .02), whereas other characteristics showed no significant difference. Overall survival (OS) and biochemical failure-free survival (BCFFS) were improved in PRT patients (3-year OS: 69% vs. 43%, p = 0.004; 3-year BCFFS: 52% vs. 16%, p = 0.002). Multivariate analysis identified PRT as a significant predictor of both OS (hazard ratio [HR] = 0.43, p = 0.015). None of the 38 PRT patients experienced severe (grade ≥3) genitourinary or gastrointestinal toxicity. Conclusions Our data suggest that radiotherapy to the primary tumor was associated with improved OS and BCFFS in metastatic prostate cancer. The results of this study warrant prospective controlled clinical trials of this approach in stage IV prostate cancer patients with limited extent of bone metastasis and good performance status. PMID:26807740

  1. Knee bone tumors: findings on conventional radiology*

    PubMed Central

    Andrade Neto, Francisco; Teixeira, Manuel Joaquim Diógenes; Araújo, Leonardo Heráclio do Carmo; Ponte, Carlos Eduardo Barbosa

    2016-01-01

    The knee is a common site for bone tumors, whether clinically painful or not. Conventional radiology has been established as the first line of investigation in patients with knee pain and can reveal lesions that often generate questions not only for the generalist physician but also for the radiologist or general orthopedist. History, image examination, and histopathological analysis compose the essential tripod of the diagnosis of bone tumors, and conventional radiology is an essential diagnostic tool in patients with knee pain. This pictorial essay proposes to depict the main conventional radiography findings of the most common bone tumors around the knee, including benign and malignant tumors, as well as pseudo-tumors. PMID:27403019

  2. Knee bone tumors: findings on conventional radiology.

    PubMed

    Andrade Neto, Francisco; Teixeira, Manuel Joaquim Diógenes; Araújo, Leonardo Heráclio do Carmo; Ponte, Carlos Eduardo Barbosa

    2016-01-01

    The knee is a common site for bone tumors, whether clinically painful or not. Conventional radiology has been established as the first line of investigation in patients with knee pain and can reveal lesions that often generate questions not only for the generalist physician but also for the radiologist or general orthopedist. History, image examination, and histopathological analysis compose the essential tripod of the diagnosis of bone tumors, and conventional radiology is an essential diagnostic tool in patients with knee pain. This pictorial essay proposes to depict the main conventional radiography findings of the most common bone tumors around the knee, including benign and malignant tumors, as well as pseudo-tumors. PMID:27403019

  3. The Extent of mRNA Editing Is Limited in Chicken Liver and Adipose, but Impacted by Tissular Context, Genotype, Age, and Feeding as Exemplified with a Conserved Edited Site in COG3

    PubMed Central

    Roux, Pierre-François; Frésard, Laure; Boutin, Morgane; Leroux, Sophie; Klopp, Christophe; Djari, Anis; Esquerré, Diane; Martin, Pascal GP; Zerjal, Tatiana; Gourichon, David; Pitel, Frédérique; Lagarrigue, Sandrine

    2015-01-01

    RNA editing is a posttranscriptional process leading to differences between genomic DNA and transcript sequences, potentially enhancing transcriptome diversity. With recent advances in high-throughput sequencing, many efforts have been made to describe mRNA editing at the transcriptome scale, especially in mammals, yielding contradictory conclusions regarding the extent of this phenomenon. We show, by detailed description of the 25 studies focusing so far on mRNA editing at the whole-transcriptome scale, that systematic sequencing artifacts are considered in most studies whereas biological replication is often neglected and multi-alignment not properly evaluated, which ultimately impairs the legitimacy of results. We recently developed a rigorous strategy to identify mRNA editing using mRNA and genomic DNA sequencing, taking into account sequencing and mapping artifacts, and biological replicates. We applied this method to screen for mRNA editing in liver and white adipose tissue from eight chickens and confirm the small extent of mRNA recoding in this species. Among the 25 unique edited sites identified, three events were previously described in mammals, attesting that this phenomenon is conserved throughout evolution. Deeper investigations on five sites revealed the impact of tissular context, genotype, age, feeding conditions, and sex on mRNA editing levels. More specifically, this analysis highlighted that the editing level at the site located on COG3 was strongly regulated by four of these factors. By comprehensively characterizing the mRNA editing landscape in chickens, our results highlight how this phenomenon is limited and suggest regulation of editing levels by various genetic and environmental factors. PMID:26637431

  4. The Extent of mRNA Editing Is Limited in Chicken Liver and Adipose, but Impacted by Tissular Context, Genotype, Age, and Feeding as Exemplified with a Conserved Edited Site in COG3.

    PubMed

    Roux, Pierre-François; Frésard, Laure; Boutin, Morgane; Leroux, Sophie; Klopp, Christophe; Djari, Anis; Esquerré, Diane; Martin, Pascal G P; Zerjal, Tatiana; Gourichon, David; Pitel, Frédérique; Lagarrigue, Sandrine

    2016-02-01

    RNA editing is a posttranscriptional process leading to differences between genomic DNA and transcript sequences, potentially enhancing transcriptome diversity. With recent advances in high-throughput sequencing, many efforts have been made to describe mRNA editing at the transcriptome scale, especially in mammals, yielding contradictory conclusions regarding the extent of this phenomenon. We show, by detailed description of the 25 studies focusing so far on mRNA editing at the whole-transcriptome scale, that systematic sequencing artifacts are considered in most studies whereas biological replication is often neglected and multi-alignment not properly evaluated, which ultimately impairs the legitimacy of results. We recently developed a rigorous strategy to identify mRNA editing using mRNA and genomic DNA sequencing, taking into account sequencing and mapping artifacts, and biological replicates. We applied this method to screen for mRNA editing in liver and white adipose tissue from eight chickens and confirm the small extent of mRNA recoding in this species. Among the 25 unique edited sites identified, three events were previously described in mammals, attesting that this phenomenon is conserved throughout evolution. Deeper investigations on five sites revealed the impact of tissular context, genotype, age, feeding conditions, and sex on mRNA editing levels. More specifically, this analysis highlighted that the editing level at the site located on COG3 was strongly regulated by four of these factors. By comprehensively characterizing the mRNA editing landscape in chickens, our results highlight how this phenomenon is limited and suggest regulation of editing levels by various genetic and environmental factors. PMID:26637431

  5. Plasma content of soluble fas antigen in patients with adrenal tumors and tumor-like pathologies.

    PubMed

    Kushlinskii, N E; Britvin, T A; Polyakova, G A; Abbasova, S G; Baronini, A A; Tishenina, R S; Molchanova, G S; Sel'chuk, V Yu; Pirogov, D A; Bogatyrev, O P; Lipkin, V M; Kalinin, A P

    2002-08-01

    We compared plasma content of soluble Fas antigen (sFas) in 59 patients with tumors and tumor-like pathologies of the adrenal cortex and medulla and 60 healthy donors (control). The incidence and content of sFas in the plasma from patients with adrenal tumors was significantly higher than in healthy donors. A direct correlation was found between sFas content and patient's age. The maximum sFas concentrations were found in patients with pheochromocytoma and aldosterone-producing adenoma. In patients with adrenocortical cancer plasma content of sFas was lower than in patients with tumors of other morphological types. Plasma sFas content in patients with adrenocortical cancer directly correlated with the size of tumors. Our results suggest that sFas plays a role in the pathogenesis of primary adrenal tumors. PMID:12459844

  6. Role of cell type and animal species in tumor metastasis

    NASA Astrophysics Data System (ADS)

    Solban, Nicolas; Georgakoudi, Irene; Rice, William L.; Lin, Charles; Hasan, Tayyaba

    2004-06-01

    Photodynamic therapy (PDT) is now a reasonably well-known therapeutic option and is approved as a first line treatment of age-related macular degeneration (AMD), a non-oncologic condition. For most cancer applications PDT is approved mainly as a palliative or adjunctive treatment often when all other options have failed. As the modality evolves toward becoming a first-line or curative option, long-term effects of processes involved will need to be studied. Cellular and tissue responses to PDT are more complex than responses to the more conventional therapies, perhaps because PDT is inherently a binary (or ternary) therapy. In addition to the nature and localization of the photosensitizer (PS), the timing of illumination after administration, the mode of administration and the PS and light doses, the efficacy and selectivity of responses are also determined by the physiology and geometry of tumors, the inherent survivability of tumor cells (in circulation and other anatomic sites) and cellular and molecular responses to PDT. The overall outcome of photodynamic treatment in the long term is determined by a combination, in varying degrees, of all of the above factors. In order to enhance and broaden the application of PDT to complex anatomical sites, an understanding of these factors would be useful. In the laboratory, the outcome is also dependent on the specific animal models being studied. This manuscript discusses preliminary studies along these lines using a variety of tools and implications, if any, of the results obtained.

  7. Tumor prevalence and biomarkers of exposure in brown bullheads (Ameiurus nebulosus) from the tidal Potomac River, USA, watershed.

    PubMed

    Pinkney, A E; Harshbarger, J C; May, E B; Melancon, M J

    2001-06-01

    Associations between contaminant exposure and liver and skin tumor prevalence were evaluated in brown bullheads (Ameiurus nebulosus) from the tidal Potomac River, USA, watershed. Thirty bullheads (> or = age 3) were collected from Quantico embayment, near a Superfund site that released organochlorine contaminants; Neabsco Creek, a tributary with petroleum inputs from runoff and marinas; and Anacostia River (spring and fall), an urban tributary designated as a Chesapeake Bay region of concern, that was contaminated with polychlorinated biphenyls (PCBs), polycyclic aromatic hydrocarbons (PAHs), and organochlorine pesticides. Fish were collected from the Tuckahoe River, as a reference. Cytochrome P450 activity, bile PAH metabolites, and muscle organochlorine pesticide and PCB concentrations were measured in randomly selected individuals and sediment contaminants were analyzed. We found statistically significant differences in liver tumor prevalences: Anacostia (spring), 50%; Anacostia (fall), 60%; Neabsco, 17%; Quantico, 7%; and Tuckahoe, 10%. Skin tumor prevalences were significantly different: Anacostia (spring), 37%; Anacostia (fall), 10%; Neabsco, 3%; Quantico, 3%; and Tuckahoe, 0%. Tumor prevalence in Anacostia bullheads warrants concern and was similar to those at highly contaminated sites in the Great Lakes. Evidence was found of higher PAH exposure in Anacostia fish but a cause-effect linkage could not be established. Fish tumor surveys, with histopathologic examination of internal and external organs, are recommended for monitoring the status of regions of concern. PMID:11392129

  8. Tumor prevalence and biomarkers of exposure in brown bullheads (Ameiurus nebulosus) from the tidal Potomac River, USA, watershed

    USGS Publications Warehouse

    Pinkney, A.E.; Harshbarger, J.C.; May, E.B.; Melancon, M.J.

    2001-01-01

    Associations between contaminant exposure and liver and skin tumor prevalence were evaluated in brown bullheads (Ameiurus nebulosus) from the tidal Potomac River, USA, watershed. Thirty bullheads (>age 3) were collected from Quantico embayment near a Superfund site that released organochlorine contaminants; Neabsco Creek, a tributary with petroleum inputs from runoff and marinas; and Anacostia River (spring and fall), an urban tributary designated as a Chesapeake Bay region of concern, that was contaminated with polychlorinated biphenyls (PCBs), polycyclic aromatic hydrocarbons (PAHs), and organochlorine pesticides. Fish were collected from the Tuckahoe River, as a reference. Cytochrome P450 activity, bile PAH metabolites, and muscle organochlorine pesticide and PCB concentrations were measured in randomly selected individuals and sediment contaminants were analyzed. We found statistically significant differences in liver tumor prevalences: Anacostia (spring), 50%, Anacostia (fall), 60%, Neabsco, 17%, Quantico, 7%, and Tuckahoe, 10%. Skin tumor prevalences were significantly different: Anacostia (spring), 37%, Anacostia (fall), 10%, Neabsco, 3%, Quantico, 3%, and Tuckahoe, 0%. Tumor prevalences in Anacostia bullheads warrants concern and was similar to those as highly contaminated sites in the Great Lakes. Evidence was found of higher PAH exposure in Anacostia fish but a cause-effect linkage could not be established. Fish tumor surveys, with histopathologic examination of internal and external organs are recommended for monitoring the status of regions of concern.

  9. Radioembolization with yttrium-90 resin microspheres for neuroendocrine tumor liver metastases

    PubMed Central

    Peker, Ahmet; Çiçek, Okan; Soydal, Çiğdem; Küçük, Nuriye Özlem; Bilgiç, Sadık

    2015-01-01

    PURPOSE We aimed to evaluate the effectiveness and safety of radioembolization with yttrium-90 (90Y) microspheres in cases with unresectable neuroendocrine tumor liver metastases (NETLMs). METHODS Thirty patients (mean age, 55 years) underwent resin-based 90Y radioembolization for unresectable NETLM at a single institution between April 2008 and June 2013. Post-treatment tumor response was assessed by cross-sectional imaging using the Response Evaluation Criteria in Solid Tumors (RECIST). Prognostic variables that affected survival were determined. RESULTS The mean follow-up was 23.0±19.4 months and the median overall survival was 39 months (95% CI, 12.6–65.4 months), with one- and two-year survival rates of 71% and 45%, respectively. Imaging follow-up using RECIST at three-month intervals demonstrated partial response in 43%, complete remission in 3%, stable disease in 37%, and progressive disease in 17% of patients. Extent of tumor involvement was found to have a statistically significant influence on overall survival (P = 0.03). The existence of extrahepatic disease at the time of radioembolization, radiographic response, age, and primary neuroendocrine tumor site were not significant prognostic factors. CONCLUSION The current study demonstrates the effectiveness and safety of radioembolization for the treatment of unresectable NETLMs. We identified that the extent of tumor involvement has a significant effect on overall survival. The use of imaging methods reflecting metabolic activity or cellularity such as scintigraphy or diffusion-weighted MRI would be more appropriate, for the response evaluation of liver metastases after radioembolization. PMID:25430526

  10. Lapatinib Plasma and Tumor Concentrations and Effects on HER Receptor Phosphorylation in Tumor

    PubMed Central

    Bacus, Sarah; Blackwell, Kimberly; Smith, Deborah A.; Glenn, Kelli; Cartee, Leanne; Harris, Jennifer; Kimbrough, Carie L.; Gittelman, Mark; Avisar, Eli; Beitsch, Peter; Koch, Kevin M.

    2015-01-01

    Purpose The paradigm shift in cancer treatment from cytotoxic drugs to tumor targeted therapies poses new challenges, including optimization of dose and schedule based on a biologically effective dose, rather than the historical maximum tolerated dose. Optimal dosing is currently determined using concentrations of tyrosine kinase inhibitors in plasma as a surrogate for tumor concentrations. To examine this plasma-tumor relationship, we explored the association between lapatinib levels in tumor and plasma in mice and humans, and those effects on phosphorylation of human epidermal growth factor receptors (HER) in human tumors. Experimental Design Mice bearing BT474 HER2+ human breast cancer xenografts were dosed once or twice daily (BID) with lapatinib. Drug concentrations were measured in blood, tumor, liver, and kidney. In a randomized phase I clinical trial, 28 treatment-naïve female patients with early stage HER2+ breast cancer received lapatinib 1000 or 1500 mg once daily (QD) or 500 mg BID before evaluating steady-state lapatinib levels in plasma and tumor. Results In mice, lapatinib levels were 4-fold higher in tumor than blood with a 4-fold longer half-life. Tumor concentrations exceeded the in vitro IC90 (~ 900 nM or 500 ng/mL) for inhibition of HER2 phosphorylation throughout the 12-hour dosing interval. In patients, tumor levels were 6- and 10-fold higher with QD and BID dosing, respectively, compared to plasma trough levels. The relationship between tumor and plasma concentration was complex, indicating multiple determinants. HER receptor phosphorylation varied depending upon lapatinib tumor concentrations, suggestive of changes in the repertoire of HER homo- and heterodimers. Conclusion Plasma lapatinib concentrations underestimated tumor drug levels, suggesting that optimal dosing should be focused on the site of action to avoid to inappropriate dose escalation. Larger clinical trials are required to determine optimal dose and schedule to achieve tumor

  11. Pathologic aspects of skull base tumors.

    PubMed

    Marszałek, Andrzej; Szylberg, Łukasz; Wiśniewski, Sławomir

    2016-01-01

    Skull base tumors form a highly heterogeneous group. As there are several structures in this anatomical site, a large number of different primary malignancies might develop, as well as a variety of secondary (metastatic) tumors. In this article, the most common malignancies are presented, along with a short histopathologic description. For some entities, an immunohistochemical profile is also given that should be helpful in proper diagnosis. As many pathologic diagnoses nowadays also include genetic studies, the most common genetic abnormalities in skull base tumors are presented. PMID:27330415

  12. Tumor microenvironment and nanotherapeutics

    PubMed Central

    Upreti, Meenakshi; Jyoti, Amar; Sethi, Pallavi

    2014-01-01

    Recent studies delineate a predominant role for the tumor microenvironment in tumor growth and progression. Improved knowledge of cancer biology and investigation of the complex functional interrelation between the cellular and noncellular compartments of the tumor microenvironment have provided an ideal platform for the evolution of novel cancer nanotherapies. In addition, multifunctional “smart” nanoparticles carrying imaging agents and delivering multiple drugs targeted preferentially to the tumor/tumor microenvironment will lead to early diagnosis and better treatment for patients with cancer. The emerging knowledge of the tumor microenvironment has enabled rational designing of nanoparticles for combinatorial treatment strategies that include radiotherapy, antiangiogenesis and chemotherapy. This multimodality approach is thus expected to achieve therapeutic efficacy and enhance the quality of life of cancer patients. This review highlights the unique characteristics of the tumor microenvironment that are exploited by nanotechnology to develop novel drug delivery systems aimed to target the tumor/tumor microenvironment. PMID:24634853

  13. Healthy Aging

    MedlinePlus

    ... About Us Contact Us Text size | Print | Healthy Aging This information in Spanish ( en español ) A healthy ... Aging email updates. Enter email address Submit Healthy Aging news Accessibility | Privacy policy | Disclaimers | FOIA | Link to ...

  14. Healthy Aging

    MedlinePlus

    ... A Change Contrast print sign up Share Healthy Aging This category offers tips on how to stay ... with Smell Problems with Taste Skin Care and Aging Sleep and Aging Taking Medicines Talking with Your ...

  15. Spatiotemporal Patterns of Tumor Occurrence in Children with Intraocular Retinoblastoma

    PubMed Central

    King, Benjamin A.; Parra, Carlos; Li, Yimei; Helton, Kathleen J.; Qaddoumi, Ibrahim; Wilson, Matthew W.; Ogg, Robert J.

    2015-01-01

    Purpose To accurately map the retinal area covered by tumor in a prospectively enrolled cohort of children diagnosed with retinoblastoma. Methods Orbital MRI in 106 consecutive retinoblastoma patients (44 bilateral) was analyzed. For MRI-visible tumors, the polar angle and angle of eccentricity of points defining tumor perimeter on the retina were determined by triangulation from images in three orthogonal planes. The centroid of the mapped area was calculated to approximate tumor origin, and the location and cumulative tumor burden were analyzed in relation to mutation type (germline vs. somatic), tumor area, and patient age at diagnosis. Location of small tumors undetected by MRI was approximated with fundoscopic images. Results Mapping was successful for 129 tumors in 91 eyes from 67 patients (39 bilateral, 43 germline mutation). Cumulative tumor burden was highest within the macula and posterior pole and was asymmetrically higher within the inferonasal periphery. Tumor incidence was lowest in the superotemporal periphery. Tumor location varied with age at diagnosis in a complex pattern. Tumor location was concentrated in the macula and superonasal